On-board mass monitoring of heavy vehicles : results of testing program

The Transport Certification Australia on-board mass feasibility project is testing various on-board mass devices in a range of heavy vehicles (HVs). Extensive field tests of on-board mass measurement systems for HVs have been conducted during 2008. These tests were of accuracy, robustness and tamper-evidence of heavy vehicle on-board mass telematics. All the systems tested showed accuracies within approximately +/- 500 kg of gross combination mass or approximately +/- 2% of the attendant weighbridge reading. Analysis of the dynamic data also showed encouraging results and has raised the possibility of use of such dynamic information in tamper evidence in two areas. This analysis was to determine if the use of averaged dynamic data could identify potential tampering or incorrect operating procedures as well as the possibility of dynamic measurements flagging a tamper event by the use of metrics including a tampering index (TIX). Technical and business options to detect tamper events will now be developed during implementation of regulatory OBM system application to Australian heavy vehicles (HVs).

Knowledge transfer in project-based organisations : the need for a unique approach

Effective knowledge transfer between infrastructure projects plays a significant role in organisational success and discovery of new technologies, helping to achieve and maintain competitive advantage and, in effect, sustainable infrastructure development. Knowledge is recognised as an important organisational asset that adds value while being shared. To date, research on knowledge transfer has focused on traditional (functional) types of organisations. However, existing knowledge transfer approaches fail to address the issue of unique characteristics of project-based organisations, and the fact that functional and project-based organisations significantly differ in terms of structure, processes, and characteristics. Therefore, there is a need for a different, separate approach for managing knowledge in the project environment. The aim of this chapter is to highlight this need. An extensive literature review is provided on the areas of project management, knowledge management, and organisational structure; this is further supported by empirical evidence from interviews with project management practitioners. Conducting a ‘cross-field’ literature review provides a better understanding of the knowledge transfer mechanisms and its application to projects, and of the importance of knowledge transfer across projects. This research is crucial to gaining a better understanding of knowledge transfer in the project environment. It stresses that there are dissimilarities between project-based organisations and functional organisations in terms of organisational structure, duration of processes, viewpoint of time, response to change, and mobility of people, and that there is a need for a unique strategic approach in order to achieve effective transfer of knowledge. Furthermore, findings presented in this chapter reveal key elements that play an important role in across project knowledge transfer. These elements include: social communication, lessons learned databases, and project management offices.

Functional status, postural stability and falls among older adults with glaucoma

Visual impairment is an important contributing factor in falls among older adults, which is one of the leading causes of injury and injury-related death in this population. Visual impairment is also associated with greater disability among older adults, including poorer health-related quality of life, increased frailty and reduced postural stability. The majority of this evidence, however, is based on measures of central visual function, rather than peripheral visual function. As such, there is comparatively limited research on the associations between peripheral visual function, disability and falls, and even fewer studies involving older adults with specific diseases which affect peripheral visual function, the most common of which is glaucoma. Glaucoma is one of the leading causes of irreversible vision loss among older adults, affecting around 3 per cent of adults aged over 60 years. The condition is characterised by retinal nerve fibre loss, primarily affecting peripheral visual function. Importantly, the number of older adults with glaucomatous visual impairment is projected to increase as the ageing population grows. The first component of the thesis examined the cross-sectional association between glaucomatous visual impairment and health-related quality of life (Study 1a), functional status (Study 1b) and postural stability (Study 1c) among older adults. A cohort of 74 community-dwelling adults with glaucoma (mean age 74.2 ± 5.9 years) was recruited and completed a baseline assessment. A number of visual function measures was assessed, including central visual function (visual acuity and contrast sensitivity), motion sensitivity, retinal nerve fibre analysis and monocular and binocular visual field measures (monocular 24-2 and binocular integrated visual fields (IVF): IVF-60 and IVF-120). The analyses focused on the associations between the outcomes measures and severity and location of visual field loss, as this is the primary visual function affected by glaucoma. In Study 1a, we examined the association between visual field loss and health-related quality of life, measured by the Short Form 36-item Health Survey (SF-36). Greater binocular visual field loss, on both IVF measures, was associated with lower SF-36 physical component scores, adjusted for age and gender (Pearson's r =|0.32| to |0.36|, p<0.001). Furthermore, inferior visual field loss was more strongly associated with the SF-36 physical component than superior field loss. No association was found between visual field loss and SF-36 mental component scores. The association between visual field loss and functional status was examined in Study 1b. Functional status outcomes measures included a physical activity questionnaire (Physical Activity Scale for the Elderly, PASE), performance tests (six-minute walk test, timed up and go test and lower leg strength) and an overall functional status score. Significant, but weak, correlations were found between binocular visual field loss and PASE and overall functional status scores, adjusted for age and gender (Pearson's r =|0.24| to |0.33|, p<0.05). Greater inferior visual field loss, independent of superior visual field loss, was significantly associated with poorer physical performance results and lower overall functional status scores. In Study 1c, we examined the association between visual field loss and postural stability, using a swaymeter device which recorded body movement during four conditions: eyes open and closed, on a firm and foam surface. Greater binocular visual field loss was associated with increased postural sway, both on firm and foam surfaces, independent of age and gender (Pearson’s r =|0.44| to |0.46|, p <0.001). Furthermore, inferior visual field was a stronger contributor to postural stability, more so than the superior visual field, particularly on the foam condition with the eyes open. Greater visual field loss was associated with a reduction in the visual contribution to postural sway, which underlies the observed association with postural sway. The second component of the thesis examined the association between severity and location of visual field loss and falls during a 12-month longitudinal follow-up. The number of falls was assessed prospectively using monthly fall calendars. Of the 71 participants who successfully completed the follow up (mean age 73.9 ± 5.7 years), 44% reported one or more falls, and around 20% reported two or more falls. After adjusting for age and gender, every 10 points missed on the IVF-120 increased the rate of falls by 25% (rate ratio 1.25, 95% confidence interval 1.08 - 1.44) or every 5dB reduction in IVF-60 increased the rate of falls by 47% (rate ratio 1.47, 95% confidence interval 1.16 - 1.87). Inferior visual field loss was a significant predictor of falls, more so than superior field loss, highlighting the importance of the inferior visual field area in safe and efficient navigation. Further analyses indicated that postural stability, more so than functional status, may be a potential mediating factor in the relationship between visual field loss and falls. Future research is required to confirm this causal pathway. In addition, the use of topical beta-blocker medications was not associated with an increased rate of falls in this cohort, compared with the use of other topical anti-glaucoma medications. In summary, greater binocular visual field loss among older adults with glaucoma was associated with poorer health-related quality of life in the physical domain, reduced functional status, greater postural instability and higher rates of falling. When the location of visual field loss was examined, inferior visual field loss was consistently more strongly associated with these outcomes than superior visual field loss. Insights gained from this research improve our understanding of the association between glaucomatous visual field loss and disability, and its link with falls among older adults. The clinical implications of this research include the need to include visual field screening in falls risk assessments among older adults and to raise awareness of these findings to eye care practitioners and adults with glaucoma. The findings also assist in developing further research to examine strategies to reduce disability and prevent falls among older adults with glaucoma to promote healthy ageing and independence for these individuals.

Sustainable urban infrastructure development in south east Asia : evidence from Hong Kong, Kuala Lumpur and Singapore

Many South East Asian cities have experienced substantial physical, economic and social transformations during the past several decades. The rapid pace of globalisation and economic restructuring has resulted in these cities receiving the full impact of urbanisation pressures. In an attempt to ease these pressures, cities such as Singapore, Hong Kong and Kuala Lumpur have advocated growth management approaches focussing especially on urban infrastructure sustainability. These approaches aim to achieve triple bottom line sustainability by balancing economic and social development, and environmental protection. This chapter evaluates three Asia-Pacific city cases, Singapore, Hong Kong and Kuala Lumpur, and assesses their experiences in managing their urban forms and infrastructure whilst promoting sustainable patterns of urban development.

Correcting mean-field approximations for birth-death-movement processes

On the microscale, migration, proliferation and death are crucial in the development, homeostasis and repair of an organism; on the macroscale, such effects are important in the sustainability of a population in its environment. Dependent on the relative rates of migration, proliferation and death, spatial heterogeneity may arise within an initially uniform field; this leads to the formation of spatial correlations and can have a negative impact upon population growth. Usually, such effects are neglected in modeling studies and simple phenomenological descriptions, such as the logistic model, are used to model population growth. In this work we outline some methods for analyzing exclusion processes which include agent proliferation, death and motility in two and three spatial dimensions with spatially homogeneous initial conditions. The mean-field description for these types of processes is of logistic form; we show that, under certain parameter conditions, such systems may display large deviations from the mean field, and suggest computationally tractable methods to correct the logistic-type description.

Regional field measurement of soil moisture content with neutron probe

The neutron logging method has been widely used for field measurement of soil moisture content. This non-destructive method permitted the measurement of in-situ soil moisture content at various depths without the need for burying any sensor. Twenty-three sites located around regional Melbourne have been selected for long term monitoring of soil moisture content using neutron probe. Soil samples collected during the installation are used for site characterisation and neutron probe calibration purposes. A linear relationship is obtained between the corrected neutron probe reading and moisture content for both the individual and combined data from seven sites. It is observed that the liner relationship, developed using combined data, can be used for all sites with an average accuracy of about 80%. Monitoring of the variation of soil moisture content with depth in six months for two sites is presented in this paper.

Educating EFL preservice teachers for teaching astronomy

Malaysia’s Vision 2020 for enhancing its education system includes the development of scientific literacy commencing at the primary school level. This Vision focuses on using English as the Medium of Instruction (EMI) for teaching primary science, as Malaysia has English as a Foreign Language (EFL) in its curriculum. What changes need to occur in preservice teacher education programs for learning about primary science using EMI? This paper investigates the education of Malaysian preservice teachers for learning how to teach one strand in science education (i.e., space, primary astronomy) in an English-language context. Ninety-six second-year preservice teachers from two Malaysian institutes were involved in a 16-week “Earth and Space” course, half the course involved education about primary astronomy. Seventy-five of these preservice teachers provided written responses about the course and their development as potential teachers of primary astronomy using EMI. Preservice teacher assessments and multimedia presentations provided further evidence on learning how to teach primary astronomy. Many of these preservice teachers claimed that learning to teach primary astronomy needs to focus on teaching strategies, content knowledge with easy-to-understand concepts, computer simulations (e.g., Earth Centered Universe, Stellarium, Celestia), other ICT media, and field experiences that use naked-eye observations and telescopes to investigate celestial bodies. Although generally proficient in using ICT, they claimed there were EFL barriers for learning some new terminology. Nevertheless, powerpoints, animations, videos, and simulations were identified as effective ICT tools for providing clear visual representations of abstract concepts and ways to enhance the learning process.

Probiotics and diarrhoea management in enterally tube fed critically ill patients : what is the evidence?

Objective: The aim of this literature review is to identify the role of probiotics in the management of enteral tube feeding (ETF) diarrhoea in critically ill patients.---------- Background: Diarrhoea is a common gastrointestinal problem seen in ETF patients. The incidence of diarrhoea in tube fed patients varies from 2% to 68% across all patients. Despite extensive investigation, the pathogenesis surrounding ETF diarrhoea remains unclear. Evidence to support probiotics to manage ETF diarrhoea in critically ill patients remains sparse.---------- Method: Literature on ETF diarrhoea and probiotics in critically ill, adult patients was reviewed from 1980 to 2010. The Cochrane Library, Pubmed, Science Direct, Medline and the Cumulative Index of Nursing and Allied Health Literature (CINAHL) electronic databases were searched using specific inclusion/exclusion criteria. Key search terms used were: enteral nutrition, diarrhoea, critical illness, probiotics, probiotic species and randomised clinical control trial (RCT).---------- Results: Four RCT papers were identified with two reporting full studies, one reporting a pilot RCT and one conference abstract reporting an RCT pilot study. A trend towards a reduction in diarrhoea incidence was observed in the probiotic groups. However, mortality associated with probiotic use in some severely and critically ill patients must caution the clinician against its use.---------- Conclusion: Evidence to support probiotic use in the management of ETF diarrhoea in critically ill patients remains unclear. This paper argues that probiotics should not be administered to critically ill patients until further research has been conducted to examine the causal relationship between probiotics and mortality, irrespective of the patient's disease state or projected prophylactic benefit of probiotic administration.

Striving to realise the European idea : judging the news media’s accounts of how the Berlin Wall gave impetus to a new order across Europe

The 1990 European Community was taken by surprise, by the urgency of demands from the newly-elected Eastern European governments to become member countries. Those governments were honouring the mass social movement of the streets, the year before, demanding free elections and a liberal economic system associated with “Europe”. The mass movement had actually been accompanied by much activity within institutional politics, in Western Europe, the former “satellite” states, the Soviet Union and the United States, to set up new structures – with German reunification and an expanded EC as the centre-piece. This paper draws on the writer’s doctoral dissertation on mass media in the collapse of the Eastern bloc, focused on the Berlin Wall – documenting both public protests and institutional negotiations. For example the writer as a correspondent in Europe from that time, recounts interventions of the German Chancellor, Helmut Kohl, at a European summit in Paris nine days after the “Wall”, and separate negotiations with the French President, Francois Mitterrand -- on the reunification, and EU monetary union after 1992. Through such processes, the “European idea” would receive fresh impetus, though the EU which eventuated, came with many altered expectations. It is argued here that as a result of the shock of 1989, a “social” Europe can be seen emerging, as a shared experience of daily life -- especially among people born during the last two decades of European consolidation. The paper draws on the author’s major research, in four parts: (1) Field observation from the strategic vantage point of a news correspondent. This includes a treatment of evidence at the time, of the wishes and intentions of the mass public (including the unexpected drive to join the European Community), and those of governments, (e.g. thoughts of a “Tienanmen Square solution” in East Berlin, versus the non-intervention policies of the Soviet leader, Mikhail Gorbachev). (2) A review of coverage of the crisis of 1989 by major news media outlets, treated as a history of the process. (3) As a comparison, and a test of accuracy and analysis; a review of conventional histories of the crisis appearing a decade later.(4) A further review, and test, provided by journalists responsible for the coverage of the time, as reflection on practice – obtained from semi-structured interviews.

Parliamentary committees are important in developing policy: evidence from a Queensland case study

Abstract This paper uses a case study to identify the impact of a Queensland parliamentary committee on policy. In 2003, the Travelsafe Committee undertook two inquiries investigating young driver and rider issues. In 2007, the Queensland Parliament passed legislation that provided the power to make regulations that changed the graduated driver licensing laws in Queensland. The analysis of the second reading speeches for this bill suggests that parliamentary committees can help set the agenda for government policy. The role of the Travelsafe Committee in this process was recognised by both government and non-government members of Parliament and by those that had been, or were currently, members of the committee and by those that had no membership experience of the Travelsafe Committee prior to the debate of the legislation. This paper suggests that in order for committees to successfully participate in policy work they need to have strong ideas, work to a consistently high standard and the chair needs to be dedicated to the work of the committee. This case study indicates the importance of parliamentary committees in the policy work of a parliament.

Falls in Parkinson's disease : kinematic evidence for impaired head and trunk control

Changes in stride characteristics and gait rhythmicity characterize gait in Parkinson's disease and are widely believed to contribute to falls in this population. However, few studies have examined gait in PD patients who fall. This study reports on the complexities of walking in PD patients who reported falling during a 12-month follow-up. Forty-nine patients clinically diagnosed with idiopathic PD and 34 controls had their gait assessed using three-dimensional motion analysis. Of the PD patients, 32 (65%) reported at least one fall during the follow-up compared with 17 (50%) controls. The results showed that PD patients had increased stride timing variability, reduced arm swing and walked with a more stooped posture than controls. Additionally, PD fallers took shorter strides, walked slower, spent more time in double-support, had poorer gait stability ratios and did not project their center of mass as far forward of their base of support when compared with controls. These stride changes were accompanied by a reduced range of angular motion for the hip and knee joints. Relative to walking velocity, PD fallers had increased mediolateral head motion compared with PD nonfallers and controls. Therefore, head motion could exceed “normal” limits, if patients increased their walking speed to match healthy individuals. This could be a limiting factor for improving gait in PD and emphasizes the importance of clinically assessing gait to facilitate the early identification of PD patients with a higher risk of falling.

Monitoring and regulatory role of the balanced scorecard in controlling organisational identities

This thesis employs the theoretical fusion of disciplinary knowledge, interlacing an analysis from both functional and interpretive frameworks and applies these paradigms to three concepts—organisational identity, the balanced scorecard performance measurement system, and control. As an applied thesis, this study highlights how particular public sector organisations are using a range of multi-disciplinary forms of knowledge constructed for their needs to achieve practical outcomes. Practical evidence of this study is not bound by a single disciplinary field or the concerns raised by academics about the rigorous application of academic knowledge. The study’s value lies in its ability to explore how current communication and accounting knowledge is being used for practical purposes in organisational life. The main focus of this thesis is on identities in an organisational communication context. In exploring the theoretical and practical challenges, the research questions for this thesis were formulated as: 1. Is it possible to effectively control identities in organisations by the use of an integrated performance measurement system—the balanced scorecard—and if so, how? 2. What is the relationship between identities and an integrated performance measurement system—the balanced scorecard—in the identity construction process? Identities in the organisational context have been extensively discussed in graphic design, corporate communication and marketing, strategic management, organisational behaviour, and social psychology literatures. Corporate identity is the self-presentation of the personality of an organisation (Van Riel, 1995; Van Riel & Balmer, 1997), and organisational identity is the statement of central characteristics described by members (Albert & Whetten, 2003). In this study, identity management is positioned as a strategically complex task, embracing not only logo and name, but also multiple dimensions, levels and facets of organisational life. Responding to the collaborative efforts of researchers and practitioners in identity conceptualisation and methodological approaches, this dissertation argues that analysis can be achieved through the use of an integrated framework of identity products, patternings and processes (Cornelissen, Haslam, & Balmer, 2007), transforming conceptualisations of corporate identity, organisational identity and identification studies. Likewise, the performance measurement literature from the accounting field now emphasises the importance of ‘soft’ non-financial measures in gauging performance—potentially allowing the monitoring and regulation of ‘collective’ identities (Cornelissen et al., 2007). The balanced scorecard (BSC) (Kaplan & Norton, 1996a), as the selected integrated performance measurement system, quantifies organisational performance under the four perspectives of finance, customer, internal process, and learning and growth. Broadening the traditional performance measurement boundary, the BSC transforms how organisations perceived themselves (Vaivio, 2007). The rhetorical and communicative value of the BSC has also been emphasised in organisational self-understanding (Malina, Nørreklit, & Selto, 2007; Malmi, 2001; Norreklit, 2000, 2003). Thus, this study establishes a theoretical connection between the controlling effects of the BSC and organisational identity construction. Common to both literatures, the aspects of control became the focus of this dissertation, as ‘the exercise or act of achieving a goal’ (Tompkins & Cheney, 1985, p. 180). This study explores not only traditional technical and bureaucratic control (Edwards, 1981), but also concertive control (Tompkins & Cheney, 1985), shifting the locus of control to employees who make their own decisions towards desired organisational premises (Simon, 1976). The controlling effects on collective identities are explored through the lens of the rhetorical frames mobilised through the power of organisational enthymemes (Tompkins & Cheney, 1985) and identification processes (Ashforth, Harrison, & Corley, 2008). In operationalising the concept of control, two guiding questions were developed to support the research questions: 1.1 How does the use of the balanced scorecard monitor identities in public sector organisations? 1.2 How does the use of the balanced scorecard regulate identities in public sector organisations? This study adopts qualitative multiple case studies using ethnographic techniques. Data were gathered from interviews of 41 managers, organisational documents, and participant observation from 2003 to 2008, to inform an understanding of organisational practices and members’ perceptions in the five cases of two public sector organisations in Australia. Drawing on the functional and interpretive paradigms, the effective design and use of the systems, as well as the understanding of shared meanings of identities and identifications are simultaneously recognised. The analytical structure guided by the ‘bracketing’ (Lewis & Grimes, 1999) and ‘interplay’ strategies (Schultz & Hatch, 1996) preserved, connected and contrasted the unique findings from the multi-paradigms. The ‘temporal bracketing’ strategy (Langley, 1999) from the process view supports the comparative exploration of the analysis over the periods under study. The findings suggest that the effective use of the BSC can monitor and regulate identity products, patternings and processes. In monitoring identities, the flexible BSC framework allowed the case study organisations to monitor various aspects of finance, customer, improvement and organisational capability that included identity dimensions. Such inclusion legitimises identity management as organisational performance. In regulating identities, the use of the BSC created a mechanism to form collective identities by articulating various perspectives and causal linkages, and through the cascading and alignment of multiple scorecards. The BSC—directly reflecting organisationally valued premises and legitimised symbols—acted as an identity product of communication, visual symbols and behavioural guidance. The selective promotion of the BSC measures filtered organisational focus to shape unique identity multiplicity and characteristics within the cases. Further, the use of the BSC facilitated the assimilation of multiple identities by controlling the direction and strength of identifications, engaging different groups of members. More specifically, the tight authority of the BSC framework and systems are explained both by technical and bureaucratic controls, while subtle communication of organisational premises and information filtering is achieved through concertive control. This study confirms that these macro top-down controls mediated the sensebreaking and sensegiving process of organisational identification, supporting research by Ashforth, Harrison and Corley (2008). This study pays attention to members’ power of self-regulation, filling minor premises of the derived logic of their organisation through the playing out of organisational enthymemes (Tompkins & Cheney, 1985). Members are then encouraged to make their own decisions towards the organisational premises embedded in the BSC, through the micro bottom-up identification processes including: enacting organisationally valued identities; sensemaking; and the construction of identity narratives aligned with those organisationally valued premises. Within the process, the self-referential effect of communication encouraged members to believe the organisational messages embedded in the BSC in transforming collective and individual identities. Therefore, communication through the use of the BSC continued the self-producing of normative performance mechanisms, established meanings of identities, and enabled members’ self-regulation in identity construction. Further, this research establishes the relationship between identity and the use of the BSC in terms of identity multiplicity and attributes. The BSC framework constrained and enabled case study organisations and members to monitor and regulate identity multiplicity across a number of dimensions, levels and facets. The use of the BSC constantly heightened the identity attributes of distinctiveness, relativity, visibility, fluidity and manageability in identity construction over time. Overall, this research explains the reciprocal controlling relationships of multiple structures in organisations to achieve a goal. It bridges the gap among corporate and organisational identity theories by adopting Cornelissen, Haslam and Balmer’s (2007) integrated identity framework, and reduces the gap in understanding between identity and performance measurement studies. Parallel review of the process of monitoring and regulating identities from both literatures synthesised the theoretical strengths of both to conceptualise and operationalise identities. This study extends the discussion on positioning identity, culture, commitment, and image and reputation measures in integrated performance measurement systems as organisational capital. Further, this study applies understanding of the multiple forms of control (Edwards, 1979; Tompkins & Cheney, 1985), emphasising the power of organisational members in identification processes, using the notion of rhetorical organisational enthymemes. This highlights the value of the collaborative theoretical power of identity, communication and performance measurement frameworks. These case studies provide practical insights about the public sector where existing bureaucracy and desired organisational identity directions are competing within a large organisational setting. Further research on personal identity and simple control in organisations that fully cascade the BSC down to individual members would provide enriched data. The extended application of the conceptual framework to other public and private sector organisations with a longitudinal view will also contribute to further theory building.

The ghrelin receptor isoforms (GHS-R1a and GHS-R1b) and GPR39 : an investigation into receptor dimerisation

Prostate cancer is the second most common cause of cancer-related deaths in Western males. Current diagnostic, prognostic and treatment approaches are not ideal and advanced metastatic prostate cancer is incurable. There is an urgent need for improved adjunctive therapies and markers for this disease. GPCRs are likely to play a significant role in the initiation and progression of prostate cancer. Over the last decade, it has emerged that G protein coupled receptors (GPCRs) are likely to function as homodimers and heterodimers. Heterodimerisation between GPCRs can result in the formation of novel pharmacological receptors with altered functional outcomes, and a number of GPCR heterodimers have been implicated in the pathogenesis of human disease. Importantly, novel GPCR heterodimers represent potential new targets for the development of more specific therapeutic drugs. Ghrelin is a 28 amino acid peptide hormone which has a unique n-octanoic acid post-translational modification. Ghrelin has a number of important physiological roles, including roles in appetite regulation and the stimulation of growth hormone release. The ghrelin receptor is the growth hormone secretagogue receptor type 1a, GHS-R1a, a seven transmembrane domain GPCR, and GHS-R1b is a C-terminally truncated isoform of the ghrelin receptor, consisting of five transmembrane domains. Growing evidence suggests that ghrelin and the ghrelin receptor isoforms, GHS-R1a and GHS-R1b, may have a role in the progression of a number of cancers, including prostate cancer. Previous studies by our research group have shown that the truncated ghrelin receptor isoform, GHS-R1b, is not expressed in normal prostate, however, it is expressed in prostate cancer. The altered expression of this truncated isoform may reflect a difference between a normal and cancerous state. A number of mutant GPCRs have been shown to regulate the function of their corresponding wild-type receptors. Therefore, we investigated the potential role of interactions between GHS-R1a and GHS-R1b, which are co-expressed in prostate cancer and aimed to investigate the function of this potentially new pharmacological receptor. In 2005, obestatin, a 23 amino acid C-terminally amidated peptide derived from preproghrelin was identified and was described as opposing the stimulating effects of ghrelin on appetite and food intake. GPR39, an orphan GPCR which is closely related to the ghrelin receptor, was identified as the endogenous receptor for obestatin. Recently, however, the ability of obestatin to oppose the effects of ghrelin on appetite and food intake has been questioned, and furthermore, it appears that GPR39 may in fact not be the obestatin receptor. The role of GPR39 in the prostate is of interest, however, as it is a zinc receptor. Zinc has a unique role in the biology of the prostate, where it is normally accumulated at high levels, and zinc accumulation is altered in the development of prostate malignancy. Ghrelin and zinc have important roles in prostate cancer and dimerisation of their receptors may have novel roles in malignant prostate cells. The aim of the current study, therefore, was to demonstrate the formation of GHS-R1a/GHS-R1b and GHS-R1a/GPR39 heterodimers and to investigate potential functions of these heterodimers in prostate cancer cell lines. To demonstrate dimerisation we first employed a classical co-immunoprecipitation technique. Using cells co-overexpressing FLAG- and Myc- tagged GHS-R1a, GHS-R1b and GPR39, we were able to co-immunoprecipitate these receptors. Significantly, however, the receptors formed high molecular weight aggregates. A number of questions have been raised over the propensity of GPCRs to aggregate during co-immunoprecipitation as a result of their hydrophobic nature and this may be misinterpreted as receptor dimerisation. As we observed significant receptor aggregation in this study, we used additional methods to confirm the specificity of these putative GPCR interactions. We used two different resonance energy transfer (RET) methods; bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET), to investigate interactions between the ghrelin receptor isoforms and GPR39. RET is the transfer of energy from a donor fluorophore to an acceptor fluorophore when they are in close proximity, and RET methods are, therefore, applicable to the observation of specific protein-protein interactions. Extensive studies using the second generation bioluminescence resonance energy transfer (BRET2) technology were performed, however, a number of technical limitations were observed. The substrate used during BRET2 studies, coelenterazine 400a, has a low quantum yield and rapid signal decay. This study highlighted the requirement for the expression of donor and acceptor tagged receptors at high levels so that a BRET ratio can be determined. After performing a number of BRET2 experimental controls, our BRET2 data did not fit the predicted results for a specific interaction between these receptors. The interactions that we observed may in fact represent ‘bystander BRET’ resulting from high levels of expression, forcing the donor and acceptor into close proximity. Our FRET studies employed two different FRET techniques, acceptor photobleaching FRET and sensitised emission FRET measured by flow cytometry. We were unable to observe any significant FRET, or FRET values that were likely to result from specific receptor dimerisation between GHS-R1a, GHS-R1b and GPR39. While we were unable to conclusively demonstrate direct dimerisation between GHS-R1a, GHS-R1b and GPR39 using several methods, our findings do not exclude the possibility that these receptors interact. We aimed to investigate if co-expression of combinations of these receptors had functional effects in prostate cancers cells. It has previously been demonstrated that ghrelin stimulates cell proliferation in prostate cancer cell lines, through ERK1/2 activation, and GPR39 can stimulate ERK1/2 signalling in response to zinc treatments. Additionally, both GHS-R1a and GPR39 display a high level of constitutive signalling and these constitutively active receptors can attenuate apoptosis when overexpressed individually in some cell types. We, therefore, investigated ERK1/2 and AKT signalling and cell survival in prostate cancer the potential modulation of these functions by dimerisation between GHS-R1a, GHS-R1b and GPR39. Expression of these receptors in the PC-3 prostate cancer cell line, either alone or in combination, did not alter constitutive ERK1/2 or AKT signalling, basal apoptosis or tunicamycin-stimulated apoptosis, compared to controls. In summary, the potential interactions between the ghrelin receptor isoforms, GHS-R1a and GHS-R1b, and the related zinc receptor, GPR39, and the potential for functional outcomes in prostate cancer were investigated using a number of independent methods. We did not definitively demonstrate the formation of these dimers using a number of state of the art methods to directly demonstrate receptor-receptor interactions. We investigated a number of potential functions of GPR39 and GHS-R1a in the prostate and did not observe altered function in response to co-expression of these receptors. The technical questions raised by this study highlight the requirement for the application of extensive controls when using current methods for the demonstration of GPCR dimerisation. Similar findings in this field reflect the current controversy surrounding the investigation of GPCR dimerisation. Although GHS-R1a/GHS-R1b or GHS-R1a/GPR39 heterodimerisation was not clearly demonstrated, this study provides a basis for future investigations of these receptors in prostate cancer. Additionally, the results presented in this study and growing evidence in the literature highlight the requirement for an extensive understanding of the experimental method and the performance of a range of controls to avoid the spurious interpretation of data gained from artificial expression systems. The future development of more robust techniques for investigating GPCR dimerisation is clearly required and will enable us to elucidate whether GHS-R1a, GHS-R1b and GPR39 form physiologically relevant dimers.

Cognitive behaviour therapy (CBT) for the treatment of co-occurring depression and substance use : current evidence and directions for future research

Issues and Approach: The high rates of co-occurring depression and substance use, and the negative impact of this on illness course and outcomes have been well established. Despite this, few clinical trials have examined the efficacy of cognitive behaviour therapy (CBT). This paper systematically reviews these clinical trials, with an aim of providing recommendations for how future research can develop a more robust evidence base for the treatment of these common comorbidities. Leading electronic databases, including PubMed (ISI) and PsychINFO (CSA), were searched for peer-reviewed journal articles using CBT for the treatment of co-occurring depression and substance use. Of the 55 articles identified, 12 met inclusion criteria and were included in the review. ---------- Key Findings: There is only a limited evidence for the effectiveness of CBT either alone or in combination with antidepressant medication for the treatment of co-occurring depression and substance use. While there is support for the efficacy of CBT over no treatment control conditions, there is little evidence that CBT is more efficacious than other psychotherapies. There is, however, consistent evidence of improvements in both depression and substance use outcomes, regardless of the type of treatment provided and there is growing evidence that that the effects of CBT are durable and increase over time during follow up. ---------- Conclusions. Rather than declaring the ‘dodo bird verdict’ that CBT and all other psychotherapies are equally efficacious, it would be more beneficial to develop more potent forms of CBT by identifying variables that mediate treatment outcomes.

Double jeopardy : comorbid anxiety and depression in later life

Comorbid depression and anxiety in late life present challenges for geriatric mental health care providers. These challenges include identifying the often complex diagnostic presentations both clinically and in a research context. This potent comorbidity can be conceived as double jeopardy in older adults, further diminishing their quality of life. Geriatric health care providers need to understand psychiatric comorbidity of this type for accurate diagnosis and early referral to specialists, and to coordinate interdisciplinary care. Researchers in the field also need to recognize potential multiple impacts of comorbidities with respect to assessment and treatment domains. This article describes the prevalence of late-life depression and anxiety disorders and reviews studies on this comorbidity in older adults. Risk factors and protective factors for anxiety and depression in later life are reviewed, and information is provided about comparative symptoms, the selection of assessment tools, and challenges to the provision of interdisciplinary, evidence-based care.