Accommodating the diverse cultural needs of cancer patients and their families in palliative care

Cultural issues have become an increasingly important consideration in healthcare. Such cultural issues, however, are underresearched in Australia, especially in palliative care. This study has sought to address this gap, exploring the social construction of cultural issues in palliative care by oncology nurses. A grounded theory approach was used. Semistructured interviews with 7 Australian oncology nurses provided the data for the study. The core category emerging from the study was that of accommodating cultural needs whereby to meet patients' specific cultural requirements, nurses actively found ways to accommodate the needs of patients and their families. This process often included compromise and negotiation whereby limits were set. In addition, the use of cross-cultural communication strategies emerged from the data as an important feature of cultural care. A series of subcategories were also identified as factors that could influence the process by which nurses would accommodate cultural needs.

Repositioning an ethic of sustainability in early childhood education, with Reconciliation as central

In this chapter I raise questions about the current scope and purpose of early childhood education for sustainability (ECEfS) and the ways ECEfS is enacted in practice. This is to highlight why social, political and economic areas of concern should be central in ECEfS alongside an environmental focus. Specifically, this chapter establishes the place of Reconciliation in ECEfS because it is one of the most pressing ethical, social, political and economic issues on the Australian landscape. To reposition an ethic of sustainability is to broaden the scope and purpose of sustainability work so that particular regard is given to the place of Reconciliation in ECEfS. An ethic of sustainability is also concerned with the responsibility of non-Indigenous educators to take ownership of Reconciliation work in education curricula and contexts.

Ultimate shear strength of LiteSteel beams

This paper presents the details of an investigation on the shear behaviour of a recently developed, cold-formed steel beam known as LiteSteel Beam (LSB).The LSB section has a unique shape of a channel beam with two rectangular hollow flanges and is produced by a patented manufacturing process involving simultaneous cold-forming and dual electric resistance welding. In the present investigation, a series of numerical analyses based on three-dimensional finite element modeling and an experimental study were carried out to investigate the shear behaviour of 10 different LSB sections. It was found that the current design rules in cold-formed steel structures design codes are very conservative for the shear design of LiteSteel beams. Significant improvements to web shear buckling occurred due to the presence of rectangular hollow flanges while considerable post-buckling strength was also observed. Therefore the design rules were further modified to include the available post-buckling strength. Suitable design rules were also developed under the direct strength method format. This paper presents the details of this investigation and the results including the final design rules for the shear capacity of LSBs. It also presents new shear strength formulae for lipped channel beams based on the current design equations for shear strength given in AISI (2007) using the same approach used for LSBs.

Personal epistemology in pre-service teachers : belief changes throughout a teacher education course

Classrooms of the 21st century are complex systems. They support diverse learners from varied contexts and function in a “messy” bricolage of policy contexts. This complexity is also evident in the nature of teaching and learning deployed in these classrooms. There is also, in current contexts, a general expectation that teachers will support students to construct, rather than simply receive knowledge. This process of constructing knowledge requires a focus on critical thinking in complex social and real world contexts (see also Elen & Clarebout, 2001; Yang, Chang & Hsu 2008). Critical thinking, which involves the identification and evaluation of multiple perspectives when making decisions, is a process of knowing – a tool of wisdom (Kuhn & Udell, 2001). Schommer-Aikens, Bird and Bakken (2010) refer to classrooms that encourage critical thinking as “epistemologically based” in which “the teacher encourages his/her students to look for connections among concepts within the text, with their prior knowledge, and with concepts found in the world beyond themselves” (p. 48).

Elastic shear buckling characteristics of LiteSteel Beams

LiteSteel beam (LSB) is a new cold-formed steel hollow flange channel beam. The unique LSB section is produced by a patented manufacturing process involving simultaneous cold-forming and dual electric resistance welding. To date, limited research has been undertaken on the shear buckling behaviour of LSBs with torsionally rigid, rectangular hollow flanges. For the shear design of LSB web panels, their elastic shear buckling strength must be determined accurately including the potential post-buckling strength. Currently the elastic shear buckling coefficients of web panels are determined by assuming conservatively that the web panels are simply supported at the junction between the flange and web elements. Therefore finite element analyses were carried out to investigate the elastic shear buckling behaviour of LSB sections including the effect of true support conditions at the junction between their flange and web elements. An improved equation for the higher elastic shear buckling coefficient of LSBs was developed and included in the shear capacity equations of Australian cold-formed steel codes. Predicted ultimate shear capacity results were compared with available experimental results, both of which showed considerable improvement to the shear capacities of LSBs. A study on the shear flow distribution of LSBs was also undertaken prior to the elastic buckling analysis study. This paper presents the details of this investigation and the results including the shear flow distribution of LSBs. Keywords: LiteSteel beam, Elastic shear buckling, Shear flow, Cold-formed steel structures, Slender web, Hollow flanges.

An identification of factors influencing police workplace motivation

Police work tasks are diverse and require the ability to take command, demonstrate leadership, make serious decisions and be self directed (Beck, 1999; Brunetto & Farr-Wharton, 2002; Howard, Donofrio & Boles, 2002). This work is usually performed in pairs or sometimes by an officer working alone. Operational police work is seldom performed under the watchful eyes of a supervisor and a great amount of reliance is placed on the high levels of motivation and professionalism of individual officers. Research has shown that highly motivated workers produce better outcomes (Whisenand & Rush, 1998; Herzberg, 2003). It is therefore important that Queensland police officers are highly motivated to provide a quality service to the Queensland community. This research aims to identify factors which motivate Queensland police to perform quality work. Researchers acknowledge that there is a lack of research and knowledge in regard to the factors which motivate police (Beck, 1999; Bragg, 1998; Howard, Donofrio & Boles, 2002; McHugh & Verner, 1998). The motivational factors were identified in regard to the demographic variables of; age, sex, rank, tenure and education. The model for this research is Herzberg’s two-factor theory of workplace motivation (1959). Herzberg found that there are two broad types of workplace motivational factors; those driven by a need to prevent loss or harm and those driven by a need to gain personal satisfaction or achievement. His study identified 16 basic sub-factors that operate in the workplace. The research utilised a questionnaire instrument based on the sub-factors identified by Herzberg (1959). The questionnaire format consists of an initial section which sought demographic information about the participant and is followed by 51 Likert scale questions. The instrument is an expanded version of an instrument previously used in doctoral studies to identify sources of police motivation (Holden, 1980; Chiou, 2004). The questionnaire was forwarded to approximately 960 police in the Brisbane, Metropolitan North Region. The data were analysed using Factor Analysis, MANOVAs, ANOVAs and multiple regression analysis to identify the key sources of police motivation and to determine the relationships between demographic variables such as: age, rank, educational level, tenure, generation cohort and motivational factors. A total of 484 officers responded to the questionnaire from the sample population of 960. Factor analysis revealed five broad Prime Motivational Factors that motivate police in their work. The Prime Motivational Factors are: Feeling Valued, Achievement, Workplace Relationships, the Work Itself and Pay and Conditions. The factor Feeling Valued highlighted the importance of positive supportive leaders in motivating officers. Many officers commented that supervisors who only provided negative feedback diminished their sense of feeling valued and were a key source of de-motivation. Officers also frequently commented that they were motivated by operational police work itself whilst demonstrating a strong sense of identity with their team and colleagues. The study showed a general need for acceptance by peers and an idealistic motivation to assist members of the community in need and protect victims of crime. Generational cohorts were not found to exert a significant influence on police motivation. The demographic variable with the single greatest influence on police motivation was tenure. Motivation levels were found to drop dramatically during the first two years of an officer’s service and generally not improve significantly until near retirement age. The findings of this research provide the foundation of a number of recommendations in regard to police retirement, training and work allocation that are aimed to improve police motivation levels. The five Prime Motivational Factor model developed in this study is recommended for use as a planning tool by police leaders to improve motivational and job-satisfaction components of police Service policies. The findings of this study also provide a better understanding of the current sources of police motivation. They are expected to have valuable application for Queensland police human resource management when considering policies and procedures in the areas of motivation, stress reduction and attracting suitable staff to specific areas of responsibility.

Impacts of vessel capacity reduction programs on the efficiency in fisheries. The case of Australia's multispecies in northern prawn fishery

Capacity reduction programs in the form of buybacks or decommissioning programs have had relatively widespread application in fisheries in the US, Europe and Australia. A common criticism of such programs is that they remove the least efficient vessels first, resulting in an increase in average efficiency of the remaining fleet. The effective fishing power of the fleet, therefore, does not decrease in proportion to the number of vessels removed. Further, reduced crowding may increase efficiency of the remaining vessels. In this paper, the effects of a buyback program on average technical efficiency in Australia’s Northern Prawn Fishery are examined using a multi-output distance function approach with an explicit inefficiency model. The results indicate that average efficiency of the remaining vessels was greater than that of the removed vessels, and that average efficiency of remaining vessels also increased as a result of reduced crowding.

On democracy

If one clear argument emerged from my doctoral thesis in political science, it is that there is no agreement as to what democracy is. There are over 40 different varieties of democracy ranging from those in the mainstream with subtle or minute differences to those playing by themselves in the corner. And many of these various types of democracy are very well argued, empirically supported, and highly relevant to certain polities. The irony is that the thing which all of these democratic varieties or the ‘basic democracy’ that all other forms of democracy stem from, is elusive. There is no international agreement in the literature or in political practice as to what ‘basic democracy’ is and that is problematic as many of us use the word ‘democracy’ every day and it is a concept of tremendous importance internationally. I am still uncertain as to why this problem has not been resolved before by far greater minds than my own, and it may have something to do with the recent growth in democratic theory this past decade and the innovative areas of thought my thesis required, but I think I’ve got the answer. By listing each type of democracy and filling the column next to this list with the literature associated with these various styles of democracy, I amassed a large and comprehensive body of textual data. My research intended to find out what these various styles of democracy had in common and to create a taxonomy (like the ‘tree of life’ in biology) of democracy to attempt at showing how various styles of democracy have ‘evolved’ over the past 5000 years.ii I then ran a word frequency analysis program or a piece of software that counts the 100 most commonly used words in the texts. This is where my logic came in as I had to make sense of these words. How did they answer what the most fundamental commonalities are between 40 different styles of democracy? I used a grounded theory analysis which required that I argue my way through these words to form a ‘theory’ or plausible explanation as to why these particular words and not others are the important ones for answering the question. It came down to the argument that all 40 styles of democracy analysed have the following in common 1) A concept of a citizenry. 2) A concept of sovereignty. 3) A concept of equality. 4) A concept of law. 5) A concept of communication. 6) And a concept of selecting officials. Thus, democracy is a defined citizenry with its own concept of sovereignty which it exercises through the institutions which support the citizenry’s understandings of equality, law, communication, and the selection of officials. Once any of these 6 concepts are defined in a particular way it creates a style of democracy. From this, we can also see that there can be more than one style of democracy active in a particular government as a citizenry is composed of many different aggregates with their own understandings of the six concepts.

Tendering ethics : a study of collusive tendering from a marketing perspective

This thesis provides a behavioural perspective to the problem of collusive tendering in the construction market by examining the decision making factors of individuals potentially involved in such agreements using marketing ethics theory and techniques. The findings of a cross disciplinary literature review were synthesised into a model of factors theoretically expected to determine the individual's behavioural intent towards a set of collusive tendering agreements and the means of reaching them. The factors were grouped as internal cognitive (the individuals' value systems) and affective (demographic and psychographic characteristics) as well as external environmental (legal, industrial and organisational codes and norms) and situational (company, market and economic conditions). The model was tested using empirical data collected through a questionnaire survey of estimators employed in the largest Australian construction firms. All forms of explicit collusive tendering agreements were considered as having a prohibitive moral content by the majority of respondents who also clearly differentiated between agreements and discussions of contract terms (which they found to be a moral concern but not prohibitive) or of prices. The comparisons between those of the respondents that would never participate in a collusive agreement and the potential offenders clearly showed two distinctly different groups. The law abiding estimators are less reliant on situational factors, happier and more comfortable in their work environments and they live according to personal value and belief systems. The potential offenders on the other hand are mistrustful of colleagues, feel their values are not respected, put company priorities above principles and none of them is religious or a member of a professional body. The research results indicate that Australian estimators are, overall law abiding and principled and accept the existing codification of collusion as morally defensible and binding. Professional bodies' and organisational codes of conduct as well as personal value and belief systems that guide one's own conduct appear to be deterrents to collusive tendering intent and so are moral comfort and work satisfaction. These observations are potential indicators of areas where intervention and behaviour modification can increase individuals' resistance to collusion.

Shear behaviour and design of LiteSteel beams

OneSteel Australian Tube Mills has recently developed a new hollow flange channel cold-formed section, known as the LiteSteel Beam (LSB). The innovative LSB sections have the beneficial characteristics of torsionally rigid closed rectangular flanges combined with economical fabrication processes from a single strip of high strength steel. They combine the stability of hot-rolled steel sections with the high strength to weight ratio of conventional cold-formed steel sections. The LSB sections are commonly used as flexural members in residential, industrial and commercial buildings. In order to ensure safe and efficient designs of LSBs, many research studies have been undertaken on the flexural behaviour of LSBs. However, no research has been undertaken on the shear behaviour of LSBs. Therefore this thesis investigated the ultimate shear strength behaviour of LSBs with and without web openings including their elastic buckling and post-buckling characteristics using both experimental and finite element analyses, and developed accurate shear design rules. Currently the elastic shear buckling coefficients of web panels are determined by assuming conservatively that the web panels are simply supported at the junction between the web and flange elements. Therefore finite element analyses were conducted first to investigate the elastic shear buckling behaviour of LSBs to determine the true support condition at the junction between their web and flange elements. An equation for the higher elastic shear buckling coefficient of LSBs was developed and included in the shear capacity equations in the cold-formed steel structures code, AS/NZS 4600. Predicted shear capacities from the modified equations and the available experimental results demonstrated the improvements to the shear capacities of LSBs due to the presence of higher level of fixity at the LSB flange to web juncture. A detailed study into the shear flow distribution of LSB was also undertaken prior to the elastic buckling analysis study. The experimental study of ten LSB sections included 42 shear tests of LSBs with aspect ratios of 1.0 and 1.5 that were loaded at midspan until failure. Both single and back to back LSB arrangements were used. Test specimens were chosen such that all three types of shear failure (shear yielding, inelastic and elastic shear buckling) occurred in the tests. Experimental results showed that the current cold-formed steel design rules are very conservative for the shear design of LSBs. Significant improvements to web shear buckling occurred due to the presence of rectangular hollow flanges while considerable post-buckling strength was also observed. Experimental results were presented and compared with corresponding predictions from the current design rules. Appropriate improvements have been proposed for the shear strength of LSBs based on AISI (2007) design equations and test results. Suitable design rules were also developed under the direct strength method (DSM) format. This thesis also includes the shear test results of cold-formed lipped channel beams from LaBoube and Yu (1978a), and the new design rules developed based on them using the same approach used with LSBs. Finite element models of LSBs in shear were also developed to investigate the ultimate shear strength behaviour of LSBs including their elastic and post-buckling characteristics. They were validated by comparing their results with experimental test results. Details of the finite element models of LSBs, the nonlinear analysis results and their comparisons with experimental results are presented in this thesis. Finite element analysis results showed that the current cold-formed steel design rules are very conservative for the shear design of LSBs. They also confirmed other experimental findings relating to elastic and post-buckling shear strength of LSBs. A detailed parametric study based on validated experimental finite element model was undertaken to develop an extensive shear strength data base and was then used to confirm the accuracy of the new shear strength equations proposed in this thesis. Experimental and numerical studies were also undertaken to investigate the shear behaviour of LSBs with web openings. Twenty six shear tests were first undertaken using a three point loading arrangement. It was found that AS/NZS 4600 and Shan et al.'s (1997) design equations are conservative for the shear design of LSBs with web openings while McMahon et al.'s (2008) design equation are unconservative. Experimental finite element models of LSBs with web openings were then developed and validated by comparing their results with experimental test results. The developed nonlinear finite element model was found to predict the shear capacity of LSBs with web opening with very good accuracy. Improved design equations have been proposed for the shear capacity of LSBs with web openings based on both experimental and FEA parametric study results. This thesis presents the details of experimental and numerical studies of the shear behaviour and strength of LSBs with and without web openings and the results including the developed accurate design rules.

The impact of brand and product placements in electronic games

In an environment where it has become increasingly difficult to attract consumer attention, marketers have begun to explore alternative forms of marketing communication. One such form that has emerged is product placement, which has more recently appeared in electronic games. Given changes in media consumption and the growth of the games industry, it is not surprising that games are being exploited as a medium for promotional content. Other market developments are also facilitating and encouraging their use, in terms of both the insertion of brand messages into video games and the creation of brand-centred environments, labelled ‘advergames’. However, while there is much speculation concerning the beneficial outcomes for marketers, there remains a lack of academic work in this area and little empirical evidence of the actual effects of this form of promotion on game players. Only a handful of studies are evident in the literature, which have explored the influence of game placements on consumers. The majority have studied their effect on brand awareness, largely demonstrating that players can recall placed brands. Further, most research conducted to date has focused on computer and online games, but consoles represent the dominant platform for play (Taub, 2004). Finally, advergames have largely been neglected, particularly those in a console format. Widening the gap in the literature is the fact that insufficient academic attention has been given to product placement as a marketing communication strategy overall, and to games in general. The unique nature of the strategy also makes it difficult to apply existing literature to this context. To address a significant need for information in both the academic and business domains, the current research investigates the effects of brand and product placements in video games and advergames on consumer attitude to the brand and corporate image. It was conducted in two stages. Stage one represents a pilot study. It explored the effects of use simulated and peripheral placements in video games on players’ and observers’ attitudinal responses, and whether these are influenced by involvement with a product category or skill level in the game. The ability of gamers to recall placed brands was also examined. A laboratory experiment was employed with a small sample of sixty adult subjects drawn from an Australian east-coast university, some of who were exposed to a console video game on a television set. The major finding of study one is that placements in a video game have no effect on gamers’ attitudes, but they are recalled. For stage two of the research, a field experiment was conducted with a large, random sample of 350 student respondents to investigate the effects on players of brand and product placements in handheld video games and advergames. The constructs of brand attitude and corporate image were again tested, along with several potential confounds. Consistent with the pilot, the results demonstrate that product placement in electronic games has no effect on players’ brand attitudes or corporate image, even when allowing for their involvement with the product category, skill level in the game, or skill level in relation to the medium. Age and gender also have no impact. However, the more interactive a player perceives the game to be, the higher their attitude to the placed brand and corporate image of the brand manufacturer. In other words, when controlling for perceived interactivity, players experienced more favourable attitudes, but the effect was so weak it probably lacks practical significance. It is suggested that this result can be explained by the existence of excitation transfer, rather than any processing of placed brands. The current research provides strong, empirical evidence that brand and product placements in games do not produce strong attitudinal responses. It appears that the nature of the game medium, game playing experience and product placement impose constraints on gamer motivation, opportunity and ability to process these messages, thereby precluding their impact on attitude to the brand and corporate image. Since this is the first study to investigate the ability of video game and advergame placements to facilitate these deeper consumer responses, further research across different contexts is warranted. Nevertheless, the findings have important theoretical and managerial implications. This investigation makes a number of valuable contributions. First, it is relevant to current marketing practice and presents findings that can help guide promotional strategy decisions. It also presents a comprehensive review of the games industry and associated activities in the marketplace, relevant for marketing practitioners. Theoretically, it contributes new knowledge concerning product placement, including how it should be defined, its classification within the existing communications framework, its dimensions and effects. This is extended to include brand-centred entertainment. The thesis also presents the most comprehensive analysis available in the literature of how placements appear in games. In the consumer behaviour discipline, the research builds on theory concerning attitude formation, through application of MacInnis and Jaworski’s (1989) Integrative Attitude Formation Model. With regards to the games literature, the thesis provides a structured framework for the comparison of games with different media types; it advances understanding of the game medium, its characteristics and the game playing experience; and provides insight into console and handheld games specifically, as well as interactive environments generally. This study is the first to test the effects of interactivity in a game environment, and presents a modified scale that can be used as part of future research. Methodologically, it addresses the limitations of prior research through execution of a field experiment and observation with a large sample, making this the largest study of product placement in games available in the literature. Finally, the current thesis offers comprehensive recommendations that will provide structure and direction for future study in this important field.

Fiji pre-service primary teachers' understanding of physical science : a cultural perspective

Science and technology are promoted as major contributors to national development. Consequently, improved science education has been placed high on the agenda of tasks to be tackled in many developing countries, although progress has often been limited. In fact there have been claims that the enormous investment in teaching science in developing countries has basically failed, with many reports of how efforts to teach science in developing countries often result in rote learning of strange concepts, mere copying of factual information, and a general lack of understanding on the part of local students. These generalisations can be applied to science education in Fiji. Muralidhar (1989) has described a situation in which upper primary and middle school students in Fiji were given little opportunity to engage in practical work; an extremely didactic form of teacher exposition was the predominant method of instruction during science lessons. He concluded that amongst other things, teachers' limited understanding, particularly of aspects of physical science, resulted in their rigid adherence to the text book or the omission of certain activities or topics. Although many of the problems associated with science education in developing countries have been documented, few attempts have been made to understand how non-Western students might better learn science. This study addresses the issue of Fiji pre-service primary teachers' understanding of a key aspect of physical science, namely, matter and how it changes, and their responses to learning experiences based on a constructivist epistemology. Initial interviews were used to probe pre-service primary teachers' understanding of this domain of science. The data were analysed to identify students' alternative and scientific conceptions. These conceptions were then used to construct Concept Profile Inventories (CPI) which allowed for qualitative comparison of the concepts of the two ethnic groups who took part in the study. This phase of the study also provided some insight into the interaction of scientific information and traditional beliefs in non-Western societies. A quantitative comparison of the groups' conceptions was conducted using a Science Concept Survey instrument developed from the CPis. These data provided considerable insight into the aspects of matter where the pre-service teachers' understanding was particularly weak. On the basis of these preliminary findings, a six-week teaching program aimed at improving the students' understanding of matter was implemented in an experimental design with a group of students. The intervention involved elements of pedagogy such as the use of analogies and concept maps which were novel to most of those who took part. At the conclusion of the teaching programme, the learning outcomes of the experimental group were compared with those of a control group taught in a more traditional manner. These outcomes were assessed quantitatively by means of pre- and post-tests and a delayed post-test, and qualitatively using an interview protocol. The students' views on the various teaching strategies used with the experimental group were also sought. The findings indicate that in the domain of matter little variation exists in the alternative conceptions held by Fijian and Indian students suggesting that cultural influences may be minimal in their construction. Furthermore, the teaching strategies implemented with the experimental group of students, although largely derived from Western research, showed considerable promise in the context of Fiji, where they appeared to be effective in improving the understanding of students from different cultural backgrounds. These outcomes may be of significance to those involved in teacher education and curriculum development in other developing countries.

The mechanism of maturation of insulin-like growth factor-1

This study, to elucidate the role of des(1-3)IGF-I in the maturation of IGF-I,used two strategies. The first was to detect the presence of enzymes in tissues, which would act on IGF-I to produce des(1-3)IGF-I, and the second was to detect the potential products of such enzymic activity, namely Gly-Pro-Glu(GPE), Gly-Pro(GP) and des(l- 3)IGF-I. No neutral tripeptidyl peptidase (TPP II), which would release the tripeptide GPE from IGF-I, was detected in brain, urine nor in red or white blood cells. The TPPlike activity which was detected, was attributed to a combined action of a dipeptidyl peptidase (DPP N) and an aminopeptidase (AP A). A true TPP II was, however, detected in platelets. Two purified TPP II enzymes were investigated but they did not release GPE from IGF-I under a variety of conditions. Consequently, TPP II seemed unlikely to participate in the formation of des(1-3)IGF-I. In contrast, an acidic tripeptidyl peptidase activity (TPP I) was detected in brain and colostrum, the former with a pH optimum of 4.5 and the latter 3.8. It seems likely that such an enzyme would participate in the formation of des( 1-3 )IGF-I in these tissues in vitro, ie. that des(1-3)IGF-I may have been produced as an artifact in the isolation of IGF-I from brain and colostrum in acidic conditions. This contrasts with suggestions of an in vivo role for des(1-3)IGF-I, as reported by others. The activity of a dipeptidyl peptidase N (DPP N) from urine, which should release the dipeptide GP from IGF-I, was assessed under a variety of conditions and with a variety of additives and potential enzyme stimulants, but there was no release of GP. The DPP N also exhibited a transferase activity with synthetic substrates in the presence of dipeptides, at lower concentrations than previously reported for other acceptors or other proteolytic enzymes. In addition, a low concentration of a product,possibly the tetrapeptide Gly-Pro-Gly-Leu, was detected with the action of the enzyme on IGF-I in the presence of the dipeptide Gly-Leu. As part of attempts to detect tissue production of des(1-3)IGF-I, a monoclonal antibody (MAb ), directed towards the GPE- end ofiGF-I was produced by immunisation with a 10-mer covalently attached to a carrier protein. By the use of indirect ELISA and inhibitor studies, the MAb was shown to selectively recognise peptides with anNterminal GPE- sequence, and applied to the indirect detection of des(1-3)IGF-I. The concentration of GPE in brain, measured by mass spectrometry ( MS), was low, and the concentration of total IGF-I (measured by ELISA with a commercial polyclonal antibody [P Ab]) was 40 times higher at 50 nmol/kg. This also, was not consistent with the action of a tripeptidyl peptidase in brain that converted all IGF-I to des(1-3)IGF-I plus GPE. Contrasting ELISA results, using the MAb prepared in this study, suggest an even higher concentration of intact IGF-I of 150 nmollkg. This would argue against the presence of any des( 1-3 )IGF-I in brain, but in turn, this indicates either the presence of other substances containing a GPE amino-terminus or other cross reacting epitope. Although the results of the specificity studies reported in Chapter 5 would make this latter possibility seem unlikely, it cannot be completely excluded. No GP was detected in brain by MS. No GPE was detected in colostrum by capillary electrophoresis (CE) but the interference from extraneous substances reduced the detectability of GPE by CE and this approach would require further, prior, purification and concentration steps. A molecule, with a migration time equal to that of the peptide GP, was detected in colostrum by CE, but the concentration (~ 10 11mo/L) was much higher than the IGF-I concentration measured by radio-immunoassay using a PAb (80 nmol/L) or using a Mab (300-400 nmolL). A DPP IV enzyme was detected in colostrum and this could account for the GP, derived from substrates other than IGF-1. Based on the differential results of the two antibody assays, there was no indication of the presence of des(1-3)IGF-I in brain or colostrum. In the absence of any enzyme activity directed towards the amino terminus of IGF-I and the absence any potential products, IGF-I, therefore, does not appear to "mature" via des(1-3)IGF-I in the brain, nor in the neutral colostrum. In spite of these results which indicate the absence of an enzymic attack on IGF-I and the absence of the expected products in tissues, the possibility that the conversion of IGF-I may occur in neutral conditions in limited amounts, cannot be ruled out. It remains possible that in the extracellular environment of the membrane, a complex interaction of IGF-I, binding protein, aminopeptidase(s) and receptor, produces des(1- 3)IGF-I as a transient product which is bound to the receptor and internalised.

The expression of ADAM-9 and -10 in prostate cancer and their regulation by dihydrotestosterone, insulin-like growth Factor-1 and epidermal growth factor

Prostrate Cancer(PCa)is the most common cause of cancer death amongst Western males. PCa occurs in two distinct stages. In its early stage, growth and development is dependent primarily on male sex hormones (androgens) such as testosterone, although other growth factors have roles maintaining PCa cell survival in this stage. In the later stage of PCa development, growth and.maintenance is independent of androgen stimulation and growth factors including Insulin-like Growth Factor -1 (IGf.:·l) and Epidermal Growth Factor (EGF) are thought to have more crucial roles in cell survival and PCa progression. PCa, in its late stages, is highly aggressive and metastatic, that is, tumorigenic cells migrate from the primary site of the body (prostate) and travel via the systemic and lymphatic circulation, residing and colonising in the bone, lymph node, lung, and in more rare cases, the brain. Metastasis involves both cell migration and tissue degradation activities. The degradation of the extracellular matrix (ECM), the tissue surrounding the organ, is mediated in part by members of a family of 26 proteins called the Matrix Metalloproteases (MMPs), whilst ceil adhesion molecules, of which proteins known as Integrins are included, mediate ce11 migration. A family of proteins known as the ADAMs (A Disintegrin . And Metalloprotease domain) were a recently characterised family at the commencement of this study and now comprise 34 members. Because of their dual nature, possessing an active metaiioprotease domain, homologous to that of the MMPs, and an integrin-binding domain capable of regulating cell-cell and cell-ECM contacts, it was thought likely that members of the ADAMs family may have implications for the progression of aggressive cancers such as those ofthe prostate. This study focussed on two particular ADAMs -9 and -10. ADAM-9 has an active metalloprotease domain, which has been shown to degrade constituents of the ECM, including fibronectin, in vitro. It also has an integrin-binding capacity through association with key integrins involved in PCa progression, such as a6~1. ADAM-10 has no such integrin binding activities, but its bovine orthologue, MADM, is able to degrade coHagen type IV, a major component of basement membranes. It is likely human ADAM-10 has the same activity. It is also known to cleave Ll -a protein involved in cell anchorage activities - and collagen type XVII - which is a principal component of the hemidesmosomes of cellular tight junctions. The cleavage of these proteins enables the cell to be released from the surrounding environment and commence migratory activities, as required in metastasis. Previous studies in this laboratory showed the mRNA expression of the five ADAMs -9,- 10, -11, -15 and -17 in PCa cell lines, characteristic of androgen-dependent and androgen independent disease. These studies were furthered by the characterisation of AD AM-9, -10 and -17 mRNA regulation by Dihydrotestosterone (DHT) in the androgen-responsive cell line (LNCaP). ADAM-9 and -10 mRNA levels were elevated in response to DHT stimulation. Further to these observations, the expression of ADAM-9 and -10 was shown in primary prostate biopsies from patients with PCa. ADAM-1 0 was expressed in the cytoplasm and on the ceH membrane in epithelial and basal cells ofbenign prostate glands, but in high-grade PCa glands, ADAM-I 0 expression was localised to the nucleus and its expression levels appeared to be elevated when compared to low-grade PCa glands. These studies provided a strong background for the hypothesis that ADAM-9 and -10 have key roles in the development ofPCa and provided a basis for further studies.The aims of this study were to: 1) characterise the expression, localisation and levels, of ADAM-9 and -10 mRNA and protein in cell models representing characteristics of normal through androgen-dependent to androgen-independent PCa, as well as to expand the primary PCa biopsy data for ADAM-9 and ADAM-10 to encompass PCa bone metastases 2) establish an in vitro cell system, which could express elevated levels of ADAM-1 0 so that functional cell-based assays such as cell migration, invasion and attachment could be carried out, and 3) to extend the previous hormonal regulation data, to fully characterise the response of ADAM-9 and -10 mRNA and protein levels to DHT, IGF-1, DHT plus IGF-1 and EGF in the hormonal/growth factor responsive cell line LNCaP. For aim 1 (expression of ADAM-9 and -10 mRNA and protein), ADAM-9 and -10 mRNA were characterised by R T -PCR, while their protein products were analysed by Western blot. Both ADAM-9 and -10 mRNA and protein were expressed at readily detectable levels across progressively metastatic PCa cell lines model that represent characteristics of low-grade,. androgen-dependent (LNCaP and C4) to high-grade, androgen-independent (C4-2 and C4-2B) PCa. When the non-tumorigenic prostate cell line RWPE-1 was compared with the metastatic PCa cell line PC-3, differential expression patterns were seen by Western blot analysis. For ADAM-9, the active form was expressed at higher levels in RWPE-1, whilst subcellular fractionation showed that the active form of ADAM-9 was predominantly located in the cell nucleus. For ADAM-I 0, in both of the cell Jines, a nuclear specific isoform of the mature, catalytically active ADAM-I 0 was found. This isoforrn differed by -2 kDa in Mr (smaller) than the cytoplasmic specific isoform. Unprocessed ADAM-I 0 was readily detected in R WPE-1 cell lines but only occasionally detected in PC-3 cell lines. Immunocytochemistry using ADAM-9 and -10 specific antibodies confirmed nuclear, cytoplasmic and membrane expression of both ADAMs in these two cell lines. To examine the possibility of ADAM-9 and -10 being shed into the extracellular environment, membrane vesicles that are constitutively shed from the cell surface and contain membrane-associated proteins were collected from the media of the prostate cell lines RWPE-1, LNCaP and PC-3. ADAM-9 was readily detectable in RWPE- 1 and LNCaP cell membrane vesicles by Western blot analysis, but not in PC-3 cells, whilst the expression of ADAM-I 0 was detected in shed vesicles from each of these prostate cell lines. By Laser Capture Microdissection (LCM), secretory epithelial cells of primary prostate gland biopsies were isolated from benign and malignant glands. These secretory cells, by Western blot analysis, expressed similar Mr bands for ADAM-9 and -10 that were found in PCa cell lines in vitro, indicating that the nuclear specific isoforrn of ADAM-I 0 was present in PCa primary tumours and may represent the predominantly nuclear form of ADAM-I 0 expression, previously shown in high-grade PCa by immunohistochemistry (IHC). ADAM-9 and -10 were also examined by IHC in bone metastases taken from PCa patients at biopsy. Both ADAMs could be detected at levels similar to those shown for Prostate Specific Antigen (PSA) in these biopsies. Furthermore, both ADAM-9 and -10 were predominantly membrane- bound with occasional nuclear expression. For aim 2, to establish a cell system that over-expressed levels of ADAM-10, two fulllength ADAM-I 0 mammalian expression vectors were constructed; ADAM-I 0 was cloned into pcDNA3.1, which contains a CMV promoter, and into pMEP4, containing an inducible metallothionine promoter, whose activity is stimulated by the addition of CdC}z. The efficiency of these two constructs was tested by way of transient transfection in the PCa cell line PC-3, whilst the pcDNA3.1 construct was also tested in the RWPE-1 prostate cell line. Resultant Western blot analysis for all transient transfection assays showed that levels of ADAM-I 0 were not significantly elevated in any case, when compared to levels of the housekeeping gene ~-Tubulin, despite testing various levels of vector DNA, and, for pMEP4, the induction of the transfected cell system with different degrees of stimulation with CdCh to activate the metallothionine promoter post-transfection. Another study in this laboratory found similar results when the same full length ADAM-10 sequence was cloned into a Green Fluorescent Protein (GFP) expressing vector, as no fluorescence was observed by means of transient tran sfection in the same, and other, PCa cell lines. It was hypothesised that the Kozak sequence included in the full-length construct (human ADAMI 0 naturally occurring sequence) is not strong enough to initiate translation in an artificial system, in cells, which, as described in Aim 1, are already expressing readily detectable levels of endogenous ADAM-10. As a result, time constraints prevented any further progress with Aim 2 and functional studies including cell attachment, invasion and migration were unable to be explored. For Aim 3, to characterise the response of ADAM-9 and -10 mRNA and protein levels to DHT, IGF-1, DHT plus IGF-1 and EGF in LNCaP cells, the levels of ADAM-9 and -10 mRNA were not stimulated by DHT or IGF-I alone, despite our previous observations that initially characterised ADAM-9 and -10 mRNA as being responsive to DHT. However, IGF-1 in synergy with DHT did significantly elevate mRNA levels ofboth ADAMs. In the case of ADAM-9 and -10 protein, the same trends of stimulation as found at the rnRNA level were shown by Western blot analysis when ADAM-9 and -10 signal intensity was normalised with the housekeeping protein ~-Tubulin. For EGF treatment, both ADAM-9 and -10 mRNA and protein levels were significantly elevated, and further investigation vm found this to be the case for each of these ADAMs proteins in the nuclear fractions of LNCaP cells. These studies are the first to describe extensively, the expression and hormonal/growth factor regulation of two members of the ADAMs family ( -9 and -1 0) in PCa. These observations imply that the expression of ADAM-9 and -10 have varied roles in PCa whilst it develops from androgen-sensitive (early stage disease), through to an androgeninsensitive (late-stage), metastatic disease. Further studies are now required to investigate the several key areas of focus that this research has revealed, including: • Investigation of the cellular mechanisms that are involved in actively transporting the ADAMs to the cell's nuclear compartment and the ADAMs functional roles in the cell nucleus. • The construction of a full-length human ADAM-10 mammalian expression construct with the introduction of a new Kozak sequence, that elevates ADAM-I 0 expression in an in vitro cell system are required, so that functional assays such as cell invasion, migration and attachment may be carried out to fmd the functional consequences of ADAM expression on cellular behaviour. • The regulation studies also need to be extended by confirming the preliminary observations that the nuclear levels of ADAMs may also be elevated by hormones and growth factors such as DHT, IGF-1 and EGF, as well as the regulation of levels of plasma membrany vesicle associated ADAM expression. Given the data presented in this study, it is likely the ADAMs have differential roles throughout the development of PCa due to their differential cellular localisation and synergistic growth-factor regulation. These observations, along with those further studies outlined above, are necessary in identifying these specific components ofPCa metastasis to which the ADAMs may contribute.

Evaluating the effect of a patient education brochure on patients’ expectations and satisfaction with emergency department service

Introduction: The purpose of this study was to assess the capacity of a written intervention, in this case a patient information brochure, to improve patient satisfaction during an Emergency Department (ED) visit. For the purpose of measuring the effect of the intervention the ED journey was conceptualised as a series of distinct areas of service comprising waiting time, service by the triage nurse, care from doctors and nurses and information giving Background of study: Research into patient satisfaction has become a widespread activity endorsed by both governments and hospital administrations. The literature on ED patient satisfaction has consistently indicated three primary areas of patient dissatisfaction: waiting time, nursing care and communication. Recent developments in the literature on patient satisfaction studies however have highlighted the relationship between patients. expectations of a service encounter and their consequent assessment of the experience as dissatisfying or satisfying. Disconfirmation theory posits that the degree to which expectations are confirmed will affect subsequent levels of satisfaction. The conceptual framework utilised in this study is Coye.s (2004) model of disconfirmation. Coye while reiterating satisfaction is a consequence of the degree expectations are either confirmed or disconfirmed also posits that expectations can be modified by interventions. Coye.s work conceptualises these interventions as intra encounter experiences (cues) which function to adjust expectations. Coye suggests some cues are unintended and may have a negative impact which also reinforces the value of planned cues intended to meet or exceed consumer expectations. Consequently the brochure can be characterized as a potentially positive cue, encouraging the patient to understand processes and to orient them in what can be a confronting environment. Only a limited number of studies have examined the effect of written interventions within an ED. No studies could be located which have tested the effect of ED interventions using a conceptual framework which relates the effect of the degree to which expectations are confirmed or disconfirmed in terms of satisfaction with services. Method: Two studies were conducted. Study One used qualitative methods to explore patients. expectations of the ED from the perspective of both patients and health care professionals. Study One was used in part to direct the development of the intervention (brochure) in Study Two. The brochure was an intervention designed to modify patients. expectations thus increasing their satisfaction with the provision of ED service. As there was no existing tools to measure ED patients. expectations and satisfaction a new tool was also developed based on the findings and the literature of Study One. Study Two used a non-randomised, quasi-experimental approach using a non-equivalent post-test only comparison group design used to investigate the effect of the patient education brochure (Stommel and Wills, 2004). The brochure was disseminated to one of two study groups (the intervention group). The effect of the brochure was assessed by comparing the data obtained from both the intervention and control group. These two groups consisted of 150 participants each. It was expected that any differences in the relevant domains selected for examination would indicate the effect of the brochure both on expectation and potentially satisfaction. Results: Study One revealed several areas of common ground between patients and nurses in terms of relevant content for the written intervention, including the need for information on the triage system and waiting times. Areas of difference were also found with patients emphasizing communication issues, whereas focus group members expressed concern that patients were often unable to assimilate verbal information. The findings suggested the potential utility of written material to reinforce verbal communication particularly in terms of the triage process and other ED protocols. This material was synthesized within the final version of the written intervention. Overall the results of Study Two indicated no significant differences between the two groups. The intervention group did indicate a significant number of participants who viewed the brochure of having changed their expectations. The effect of the brochure may have been obscured by a lack of parity between the two groups as the control group presented with statistically significantly higher levels of acuity and experienced significantly shorter waiting times. In terms of disconfirmation theory this would suggest expectations that had been met or exceeded. The results confirmed the correlation of expectations with satisfaction. Several domains also indicated age as a significant predictor with older patients tending to score higher satisfaction results. Other significant predictors of satisfaction established were waiting time and care from nurses, reinforcing the combination of efficient service and positive interpersonal experiences as being valued by patients. Conclusions: Information presented in written form appears to benefit a significant number of ED users in terms of orientation and explaining systems and procedures. The degree to which these effects may interact with other dimensions of satisfaction however is likely to be limited. Waiting time and interpersonal behaviours from staff also provide influential cues in determining satisfaction. Written material is likely to be one element in a series of coordinated strategies to improve patient satisfaction during periods of peak demand.