893 resultados para AL-2004-1


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Ecological networks are often represented as utopian webs of green meandering through cities, across states, through regions and even across a country (Erickson, 2006, p.28; Fabos, 2004, p.326; Walmsley, 2006). While this may be an inspiring goal for some in developed countries, the reality may be somewhat different in developing countries. China, in its shift to urbanisation and suburbanisation, is also being persuaded to adjust its planning schemes according to these aspirational representations of green spaces (Yu et al, 2006, p.237; Zhang and Wang, 2006, p.455). The failure of other countries to achieve regional goals of natural and cultural heritage protection on the ground in this way (Peterson et al, 2007; Ryan et al, 2006; von Haaren and Reich, 2006) suggests that there may be flaws in the underpinning concepts that are widely circulated in North American and Western European literature (Jongman et al, 2004; Walmsley, 2006). In China, regional open space networks, regional green infrastructure or regional ecological corridors as we know them in the West, are also likely to be problematic, at least in the foreseeable future. Reasons supporting this view can be drawn from lessons learned from project experience in landscape planning and related fields of study in China and overseas. Implementation of valuable regional green space networks is problematic because: • the concept of region as a spatial unit for planning green space networks is ambiguous and undefinable for practical purposes; • regional green space networks traditionally require top down inter-governmental cooperation and coordination which are generally hampered by inequalities of influence between and within government agencies; • no coordinating body with funding powers exists for regional green space development and infrastructure authorities are still in transition from engineering authorities; • like other infrastructure projects, green space is likely to become a competitive rather than a complementary resource for city governments; • stable long-term management, maintenance and uses of green space networks must fit into a ‘family’ social structure rather than a ‘public good’ social structure, particularly as rural and urban property rights are being re-negotiated with city governments; and • green space provision is a performance indicator of urban improvement in cities within the city hierarchy and remains quantitatively-based (land area, tree number and per capita share) rather than qualitatively-based with local people as the focus.

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When asymptotic series methods are applied in order to solve problems that arise in applied mathematics in the limit that some parameter becomes small, they are unable to demonstrate behaviour that occurs on a scale that is exponentially small compared to the algebraic terms of the asymptotic series. There are many examples of physical systems where behaviour on this scale has important effects and, as such, a range of techniques known as exponential asymptotic techniques were developed that may be used to examinine behaviour on this exponentially small scale. Many problems in applied mathematics may be represented by behaviour within the complex plane, which may subsequently be examined using asymptotic methods. These problems frequently demonstrate behaviour known as Stokes phenomenon, which involves the rapid switches of behaviour on an exponentially small scale in the neighbourhood of some curve known as a Stokes line. Exponential asymptotic techniques have been applied in order to obtain an expression for this exponentially small switching behaviour in the solutions to orginary and partial differential equations. The problem of potential flow over a submerged obstacle has been previously considered in this manner by Chapman & Vanden-Broeck (2006). By representing the problem in the complex plane and applying an exponential asymptotic technique, they were able to detect the switching, and subsequent behaviour, of exponentially small waves on the free surface of the flow in the limit of small Froude number, specifically considering the case of flow over a step with one Stokes line present in the complex plane. We consider an extension of this work to flow configurations with multiple Stokes lines, such as flow over an inclined step, or flow over a bump or trench. The resultant expressions are analysed, and demonstrate interesting implications, such as the presence of exponentially sub-subdominant intermediate waves and the possibility of trapped surface waves for flow over a bump or trench. We then consider the effect of multiple Stokes lines in higher order equations, particu- larly investigating the behaviour of higher-order Stokes lines in the solutions to partial differential equations. These higher-order Stokes lines switch off the ordinary Stokes lines themselves, adding a layer of complexity to the overall Stokes structure of the solution. Specifically, we consider the different approaches taken by Howls et al. (2004) and Chap- man & Mortimer (2005) in applying exponential asymptotic techniques to determine the higher-order Stokes phenomenon behaviour in the solution to a particular partial differ- ential equation.

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My research investigates why nouns are learned disproportionately more frequently than other kinds of words during early language acquisition (Gentner, 1982; Gleitman, et al., 2004). This question must be considered in the context of cognitive development in general. Infants have two major streams of environmental information to make meaningful: perceptual and linguistic. Perceptual information flows in from the senses and is processed into symbolic representations by the primitive language of thought (Fodor, 1975). These symbolic representations are then linked to linguistic input to enable language comprehension and ultimately production. Yet, how exactly does perceptual information become conceptualized? Although this question is difficult, there has been progress. One way that children might have an easier job is if they have structures that simplify the data. Thus, if particular sorts of perceptual information could be separated from the mass of input, then it would be easier for children to refer to those specific things when learning words (Spelke, 1990; Pylyshyn, 2003). It would be easier still, if linguistic input was segmented in predictable ways (Gentner, 1982; Gleitman, et al., 2004) Unfortunately the frequency of patterns in lexical or grammatical input cannot explain the cross-cultural and cross-linguistic tendency to favor nouns over verbs and predicates. There are three examples of this failure: 1) a wide variety of nouns are uttered less frequently than a smaller number of verbs and yet are learnt far more easily (Gentner, 1982); 2) word order and morphological transparency offer no insight when you contrast the sentence structures and word inflections of different languages (Slobin, 1973) and 3) particular language teaching behaviors (e.g. pointing at objects and repeating names for them) have little impact on children's tendency to prefer concrete nouns in their first fifty words (Newport, et al., 1977). Although the linguistic solution appears problematic, there has been increasing evidence that the early visual system does indeed segment perceptual information in specific ways before the conscious mind begins to intervene (Pylyshyn, 2003). I argue that nouns are easier to learn because their referents directly connect with innate features of the perceptual faculty. This hypothesis stems from work done on visual indexes by Zenon Pylyshyn (2001, 2003). Pylyshyn argues that the early visual system (the architecture of the "vision module") segments perceptual data into pre-conceptual proto-objects called FINSTs. FINSTs typically correspond to physical things such as Spelke objects (Spelke, 1990). Hence, before conceptualization, visual objects are picked out by the perceptual system demonstratively, like a finger pointing indicating ‘this’ or ‘that’. I suggest that this primitive system of demonstration elaborates on Gareth Evan's (1982) theory of nonconceptual content. Nouns are learnt first because their referents attract demonstrative visual indexes. This theory also explains why infants less often name stationary objects such as plate or table, but do name things that attract the focal attention of the early visual system, i.e., small objects that move, such as ‘dog’ or ‘ball’. This view leaves open the question how blind children learn words for visible objects and why children learn category nouns (e.g. 'dog'), rather than proper nouns (e.g. 'Fido') or higher taxonomic distinctions (e.g. 'animal').

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Autonomous underwater vehicles (AUVs) are increasingly used, both in military and civilian applications. These vehicles are limited mainly by the intelligence we give them and the life of their batteries. Research is active to extend vehicle autonomy in both aspects. Our intent is to give the vehicle the ability to adapt its behavior under different mission scenarios (emergency maneuvers versus long duration monitoring). This involves a search for optimal trajectories minimizing time, energy or a combination of both. Despite some success stories in AUV control, optimal control is still a very underdeveloped area. Adaptive control research has contributed to cost minimization problems, but vehicle design has been the driving force for advancement in optimal control research. We look to advance the development of optimal control theory by expanding the motions along which AUVs travel. Traditionally, AUVs have taken the role of performing the long data gathering mission in the open ocean with little to no interaction with their surroundings, MacIver et al. (2004). The AUV is used to find the shipwreck, and the remotely operated vehicle (ROV) handles the exploration up close. AUV mission profiles of this sort are best suited through the use of a torpedo shaped AUV, Bertram and Alvarez (2006), since straight lines and minimal (0 deg - 30 deg) angular displacements are all that are necessary to perform the transects and grid lines for these applications. However, the torpedo shape AUV lacks the ability to perform low-speed maneuvers in cluttered environments, such as autonomous exploration close to the seabed and around obstacles, MacIver et al. (2004). Thus, we consider an agile vehicle capable of movement in six degrees of freedom without any preference of direction.

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Segmentation of novel or dynamic objects in a scene, often referred to as background sub- traction or foreground segmentation, is critical for robust high level computer vision applica- tions such as object tracking, object classifca- tion and recognition. However, automatic real- time segmentation for robotics still poses chal- lenges including global illumination changes, shadows, inter-re ections, colour similarity of foreground to background, and cluttered back- grounds. This paper introduces depth cues provided by structure from motion (SFM) for interactive segmentation to alleviate some of these challenges. In this paper, two prevailing interactive segmentation algorithms are com- pared; Lazysnapping [Li et al., 2004] and Grab- cut [Rother et al., 2004], both based on graph- cut optimisation [Boykov and Jolly, 2001]. The algorithms are extended to include depth cues rather than colour only as in the original pa- pers. Results show interactive segmentation based on colour and depth cues enhances the performance of segmentation with a lower er- ror with respect to ground truth.

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The Comprehensive Australian Study of Entrepreneurial Emergence (CAUSEE) is a research programme that aims to uncover the factors that initiate, hinder and facilitate the process of emergence of new economic activities and organizations. It is widely acknowledged that entrepreneurship is one of the most important forces shaping changes in a country’s economic landscape (Baumol 1968; Birch 1987; Acs 1999). An understanding of the process by which new economic activity and business entities emerge is vital (Gartner 1993; Sarasvathy 2001). An important development in the study of ‘nascent entrepreneurs’ and ‘firms in gestation’ was the Panel Study of Entrepreneurial Dynamics (PSED) (Gartner et al. 2004) and its extensions in Argentina, Canada, Greece, the Netherlands, Norway and Sweden. Yet while PSED I is an important first step towards systematically studying new venture emergence, it represents just the beginning of a stream of nascent venture studies – most notably PSED II is currently being undertaken in the US (2005– 10) (Reynolds and Curtin 2008).

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The question of how to implement evidence effectively reveals a deficiency in our knowledge and understanding of the compound factors involved in such a process (Kitson, Rycroft-Malone et al. 2008). Although there is some awareness of the complexities of the process, there has been little exploration of the effectiveness of implementing evidence-based programs in health care. Despite public awareness of the dangers of smoking in pregnancy, and widespread public health measures to prevent smoking-related disease, women still continue to smoke in pregnancy (Ananth, Savitz et al. 1997; Laws and Hilder 2008). Evaluation of public health measures concludes that smoking cessation interventions during pregnancy increase quit rates among pregnant women (Melvin, Dolan-Mullen et al. 2000; Albrecht, Maloni et al. 2004; Lumley, Oliver et al. 2007). Notwithstanding the potential for improvement in health outcomes for pregnant women and their unborn babies, smoking interventions are often conducted poorly or not at all. Although midwives understand why women smoke in pregnancy and parenthood and are aware of the risks of smoking to both the pregnancy and the unborn child, they require specific knowledge and skills in the provision of support and advice on smoking for pregnant women (Bull and Whitehead 2006) . Organisational-change research demonstrates the complexity of the process of planned change in professionalised institutions such as health care (Greenhalgh, Robert et al. 2005). Some innovations and interventions are never accepted, and others are poorly supported (Greenhalgh, Robert et al. 2004). Comprehension of the change process around health promotion is crucial to the implementation of new health promotion interventions within health care (Riley, Taylor et al. 2003). This study utilised a case study approach to explore the process of implementing a smoking cessation training program for midwives in Queensland metropolitan and regional clinical areas, who attended a ‘Train-the-Trainer program’. The study draws on the organisational change work of Greenhalgh et al (2004) as the theoretical framework through which situational and structural factors are explored and examined as they inform the implementation of smoking cessation programs. The research data constituted staged interviews with midwives who instituted training programs for midwives, as well as organisational and policy documentation. Analysis of the data identified some areas that were not fully addressed in the theoretical model; these formed the basis of the Discussion and Implications for Future Research.

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The quality of early life experiences are known to influence a child’s capacities for emotional, social, cognitive and physical competence throughout their life (Peterson, 1996; Zubrick et al., 2008). These early life experiences are directly affected by parenting and family environments. A lack of positive parenting has significant implications both for children, and the broader communities in which they live (Davies & Cummings, 1994; Dryfoos, 1990; Sanders, 1995). Young parents are known to be at risk of experiencing adverse circumstances that affect their ability to provide positive parenting to their children (Milan et al., 2004; Trad, 1995). There is a need to provide parenting support programs to young parents that offer opportunities for them to come together, support each other and learn ways to provide for their children’s developmental needs in a friendly, engaging and non-judgemental environment. This research project examines the effectiveness of a 10 week group music therapy program Sing & Grow as an early parenting intervention for 535 young parents. Sing & Grow is a national early parenting intervention program funded by the Australian Government and delivered by Playgroup Queensland. It is designed and delivered by Registered Music Therapists for families at risk of marginalisation with children aged from birth to three years. The aim of the program is to improve parenting skills and parent-child interactions, and increase social support networks through participation in a group that is strengths-based and structured in a way that lends itself to modelling, peer learning and facilitated learning. During the 10 weeks parents have opportunities to learn practical, hands-on ways to interact and play with their children that are conducive to positive parent-child relationships and ongoing child development. A range of interactive, nurturing, stimulating and developmental music activities provide the framework for parents to interact and play with their children. This research uses data collected through the Sing & Grow National Evaluation Study to examine outcomes for all participants aged 25 years and younger, who attended programs during the Sing & Grow pilot study and main study from mid-2005 to the end of 2007. The research examines the change from pre to post in self-reported parent behaviours, parent mental health and parent social support, and therapist observed parent-child interactions. A range of statistical analyses are used to address each Research Objective for the young parent population, and for subgroups within this population. Research Objective 1 explored the patterns of attendance in the Sing & Grow program for young parents, and for subgroups within this population. Results showed that levels of attendance were lower than expected and influenced by Indigenous status and source of family income. Patterns of attendance showed a decline over time and incomplete data rates were high which may indicate high dropout rates. Research Objective 2 explored perceived satisfaction, benefits and social support links made. Satisfaction levels with the program and staff were very high. Indigenous status was associated with lower levels of reported satisfaction with both the program and staff. Perceived benefits from participation in the program were very high. Employment status was associated with perceived benefits: parents who were not employed were more likely than employed parents to report that their understanding of child development had increased as a result of participation in the program. Social support connections were reported for participants with other professionals, services and parents. In particular, families were more likely to link up with playgroup staff and services. Those parents who attended six or more sessions were significantly more likely to attend a playgroup than those who attended five sessions or less. Social support connections were related to source of family income, level of education, Indigenous status and language background. Research Objective 3 investigated pre to post change on self-report parenting skills and parent mental health. Results indicated that participation in the Sing & Grow program was associated with improvements in parent mental health. No improvements were found for self-reported parenting skills. Research Objective 4 investigated pre to post change in therapist observation measures of parent-child interactions. Results indicated that participation in the Sing & Grow program was associated with large and significant improvements in parent sensitivity to, engagement with and acceptance of the child. There were significant interactions across time (pre to post) for the parent characteristics of Indigenous status, family income and level of education. Research Objective 5 explored the relationship between the number of sessions attended and extent of change on self-report outcomes and therapist observed outcomes, respectively. For each, an overall change score was devised to ascertain those parents who had made any positive changes over time. Results showed that there was no significant relationship between high attendance and positive change in either the self-report or therapist observed behavioural measures. A risk index was also constructed to test for a relationship between the risk status of the parent. Parents with the highest risk status were significantly more likely to attend six or more sessions than other parents, but risk status was not associated with any differences in parent reported outcomes or therapist observations. The results of this research study indicate that Sing & Grow is effective in improving outcomes for young parents’ mental health, parent-child interactions and social support connections. High attendance by families in the highest category for risk factors may indicate that the program is effective at engaging and retaining parents who are most at-risk and therefore traditionally hard to reach. Very high levels of satisfaction and perceived benefits support this. Further research is required to help confirm the promising evidence from the current study that a short term group music therapy program can support young parents and improve their parenting outcomes. In particular, this needs to address the more disappointing outcomes of the current research study to improve attendance and engagement of all young parents in the program and especially the needs of young Indigenous parents.

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Blogs and other online platforms for personal writing such as LiveJournal have been of interest to researchers across the social sciences and humanities for a decade now. Although growth in the uptake of blogging has stalled somewhat since the heyday of blogs in the early 2000s, blogging continues to be a major genre of Internet-based communication. Indeed, at the same time that mass participation has moved on to Facebook, Twitter, and other more recent communication phenomena, what has been left behind by the wave of mass adoption is a slightly smaller but all the more solidly established blogosphere of engaged and committed participants. Blogs are now an accepted part of institutional, group, and personal communications strategies (Bruns and Jacobs, 2006); in style and substance, they are situated between the more static information provided by conventional Websites and Webpages and the continuous newsfeeds provided through Facebook and Twitter updates. Blogs provide a vehicle for authors (and their commenters) to think through given topics in the space of a few hundred to a few thousand words – expanding, perhaps, on shorter tweets, and possibly leading to the publication of more fully formed texts elsewhere. Additionally, they are also a very flexible medium: they readily provide the functionality to include images, audio, video, and other additional materials – as well as the fundamental tool of blogging, the hyperlink itself. Indeed, the role of the link in blogs and blog posts should not be underestimated. Whatever the genre and topic that individual bloggers engage in, for the most part blogging is used to provide timely updates and commentary – and it is typical for such material to link both to relevant posts made by other bloggers, and to previous posts by the present author, both to background material which provides readers with further information about the blogger’s current topic, and to news stories and articles which the blogger found interesting or worthy of critique. Especially where bloggers are part of a larger community of authors sharing similar interests or views (and such communities are often indicated by the presence of yet another type of link – in blogrolls, often in a sidebar on the blog site, which list the blogger’s friends or favourites), then, the reciprocal writing and linking of posts often constitutes an asynchronous, distributed conversation that unfolds over the course of days, weeks, and months. Research into blogs is interesting for a variety of reasons, therefore. For one, a qualitative analysis of one or several blogs can reveal the cognitive and communicative processes through which individual bloggers define their online identity, position themselves in relation to fellow bloggers, frame particular themes, topics and stories, and engage with one another’s points of view. It may also shed light on how such processes may differ across different communities of interest, perhaps in correlation with the different societal framing and valorisation of specific areas of interest, with the socioeconomic backgrounds of individual bloggers, or with other external or internal factors. Such qualitative research now looks back on a decade-long history (for key collections, see Gurak, et al., 2004; Bruns and Jacobs, 2006; also see Walker Rettberg, 2008) and has recently shifted also to specifically investigate how blogging practices differ across different cultures (Russell and Echchaibi, 2009). Other studies have also investigated the practices and motivations of bloggers in specific countries from a sociological perspective, through large-scale surveys (e.g. Schmidt, 2009). Blogs have also been directly employed within both K-12 and higher education, across many disciplines, as tools for reflexive learning and discussion (Burgess, 2006).

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Taxonometrical uncertainty is prevalent in the field of locative media, which has been variously referred to as “the geomobile web” (Crawford and Goggin, 2009), “the geoweb” (Lake et al., 2004), “Where 2.0” (O’Reilly, 2008:1), and “DigiPlace” (Zook and Graham, 2007). However, it is not only the rapid development of the technology, or the various academic disciplinary approaches to it, that have resulted in this uncertainty but also the deeply ideological debates and concerns about what locative media should and should not be. The intention of this article is to provide an overview of existing literature and research in this field in order to develop a synthetic overview of the various types of locative media, and the geographies arising from them. Not only will such taxonomy clarify communication about locative media, it will identify for developers, users, policy-makers and scholars the specific contours and affordances of the different types of locative media, as well as the issues associated with them.

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Driving and using prescription medicines that have the potential to impair driving is an emerging research area. To date it is characterised by a limited (although growing) number of studies and methodological complexities that make generalisations about impairment due to medications difficult. Consistent evidence has been found for the impairing effects of hypnotics, sedative antidepressants and antihistamines, and narcotic analgesics, although it has been estimated that as many as nine medication classes have the potential to impair driving (Alvarez & del Rio, 2000; Walsh, de Gier, Christopherson, & Verstraete, 2004). There is also evidence for increased negative effects related to concomitant use of other medications and alcohol (Movig et al., 2004; Pringle, Ahern, Heller, Gold, & Brown, 2005). Statistics on the high levels of Australian prescription medication use suggest that consumer awareness of driving impairment due to medicines should be examined. One web-based study has found a low level of awareness, knowledge and risk perceptions among Australian drivers about the impairing effects of various medications on driving (Mallick, Johnston, Goren, & Kennedy, 2007). The lack of awareness and knowledge brings into question the effectiveness of the existing countermeasures. In Australia these consist of the use of ancillary warning labels administered under mandatory regulation and professional guidelines, advice to patients, and the use of Consumer Medicines Information (CMI) with medications that are known to cause impairment. The responsibility for the use of the warnings and related counsel to patients primarily lies with the pharmacist when dispensing relevant medication. A review by the Therapeutic Goods Administration (TGA) noted that in practice, advice to patients may not occur and that CMI is not always available (TGA, 2002). Researchers have also found that patients' recall of verbal counsel is very low (Houts, Bachrach, Witmer, Tringali, Bucher, & Localio, 1998). With healthcare observed as increasingly being provided in outpatient conditions (Davis et al., 2006; Vingilis & MacDonald, 2000), establishing the effectiveness of the warning labels as a countermeasure is especially important. There have been recent international developments in medication categorisation systems and associated medication warning labels. In 2005, France implemented a four-tier medication categorisation and warning system to improve patients' and health professionals' awareness and knowledge of related road safety issues (AFSSAPS, 2005). This warning system uses a pictogram and indicates the level of potential impairment in relation to driving performance through the use of colour and advice on the recommended behaviour to adopt towards driving. The comparable Australian system does not indicate the severity level of potential effects, and does not provide specific guidelines on the attitude or actions that the individual should adopt towards driving. It is reliant upon the patient to be vigilant in self-monitoring effects, to understand the potential ways in which they may be affected and how serious these effects may be, and to adopt the appropriate protective actions. This thesis investigates the responses of a sample of Australian hospital outpatients who receive appropriate labelling and counselling advice about potential driving impairment due to prescribed medicines. It aims to provide baseline data on the understanding and use of relevant medications by a Queensland public hospital outpatient sample recruited through the hospital pharmacy. It includes an exploration and comparison of the effect of the Australian and French medication warning systems on medication user knowledge, attitudes, beliefs and behaviour, and explores whether there are areas in which the Australian system may be improved by including any beneficial elements of the French system. A total of 358 outpatients were surveyed, and a follow-up telephone survey was conducted with a subgroup of consenting participants who were taking at least one medication that required an ancillary warning label about driving impairment. A complementary study of 75 French hospital outpatients was also conducted to further investigate the performance of the warnings. Not surprisingly, medication use among the Australian outpatient sample was high. The ancillary warning labels required to appear on medications that can impair driving were prevalent. A subgroup of participants was identified as being potentially at-risk of driving impaired, based on their reported recent use of medications requiring an ancillary warning label and level of driving activity. The sample reported previous behaviour and held future intentions that were consistent with warning label advice and health protective action. Participants did not express a particular need for being advised by a health professional regarding fitness to drive in relation to their medication. However, it was also apparent from the analysis that the participants would be significantly more likely to follow advice from a doctor than a pharmacist. High levels of knowledge in terms of general principles about effects of alcohol, illicit drugs and combinations of substances, and related health and crash risks were revealed. This may reflect a sample specific effect. Emphasis is placed in the professional guidelines for hospital pharmacists that make it essential that advisory labels are applied to medicines where applicable and that warning advice is given to all patients on medication which may affect driving (SHPA, 2006, p. 221). The research program applied selected theoretical constructs from Schwarzer's (1992) Health Action Process Approach, which has extended constructs from existing health theories such as the Theory of Planned Behavior (Ajzen, 1991) to better account for the intention-behaviour gap often observed when predicting behaviour. This was undertaken to explore the utility of the constructs in understanding and predicting compliance intentions and behaviour with the mandatory medication warning about driving impairment. This investigation revealed that the theoretical constructs related to intention and planning to avoid driving if an effect from the medication was noticed were useful. Not all the theoretical model constructs that had been demonstrated to be significant predictors in previous research on different health behaviours were significant in the present analyses. Positive outcome expectancies from avoiding driving were found to be important influences on forming the intention to avoid driving if an effect due to medication was noticed. In turn, intention was found to be a significant predictor of planning. Other selected theoretical constructs failed to predict compliance with the Australian warning label advice. It is possible that the limited predictive power of a number of constructs including risk perceptions is due to the small sample size obtained at follow up on which the evaluation is based. Alternately, it is possible that the theoretical constructs failed to sufficiently account for issues of particular relevance to the driving situation. The responses of the Australian hospital outpatient sample towards the Australian and French medication warning labels, which differed according to visual characteristics and warning message, were examined. In addition, a complementary study with a sample of French hospital outpatients was undertaken in order to allow general comparisons concerning the performance of the warnings. While a large amount of research exists concerning warning effectiveness, there is little research that has specifically investigated medication warnings relating to driving impairment. General established principles concerning factors that have been demonstrated to enhance warning noticeability and behavioural compliance have been extrapolated and investigated in the present study. The extent to which there is a need for education and improved health messages on this issue was a core issue of investigation in this thesis. Among the Australian sample, the size of the warning label and text, and red colour were the most visually important characteristics. The pictogram used in the French labels was also rated highly, and was salient for a large proportion of the sample. According to the study of French hospital outpatients, the pictogram was perceived to be the most important visual characteristic. Overall, the findings suggest that the Australian approach of using a combination of visual characteristics was important for the majority of the sample but that the use of a pictogram could enhance effects. A high rate of warning recall was found overall and a further important finding was that higher warning label recall was associated with increased number of medication classes taken. These results suggest that increased vigilance and care are associated with the number of medications taken and the associated repetition of the warning message. Significantly higher levels of risk perception were found for the French Level 3 (highest severity) label compared with the comparable mandatory Australian ancillary Label 1 warning. Participants' intentions related to the warning labels indicated that they would be more cautious while taking potentially impairing medication displaying the French Level 3 label compared with the Australian Label 1. These are potentially important findings for the Australian context regarding the current driving impairment warnings about displayed on medication. The findings raise other important implications for the Australian labelling context. An underlying factor may be the differences in the wording of the warning messages that appear on the Australian and French labels. The French label explicitly states "do not drive" while the Australian label states "if affected, do not drive", and the difference in responses may reflect that less severity is perceived where the situation involves the consumer's self-assessment of their impairment. The differences in the assignment of responsibility by the Australian (the consumer assesses and decides) and French (the doctor assesses and decides) approaches for the decision to drive while taking medication raises the core question of who is most able to assess driving impairment due to medication: the consumer, or the health professional? There are pros and cons related to knowledge, expertise and practicalities with either option. However, if the safety of the consumer is the primary aim, then the trend towards stronger risk perceptions and more consistent and cautious behavioural intentions in relation to the French label suggests that this approach may be more beneficial for consumer safety. The observations from the follow-up survey, although based on a small sample size and descriptive in nature, revealed that just over half of the sample recalled seeing a warning label about driving impairment on at least one of their medications. The majority of these respondents reported compliance with the warning advice. However, the results indicated variation in responses concerning alcohol intake and modifying the dose of medication or driving habits so that they could continue to drive, which suggests that the warning advice may not be having the desired impact. The findings of this research have implications for current countermeasures in this area. These have included enhancing the role that prescribing doctors have in providing warnings and advice to patients about the impact that their medication can have on driving, increasing consumer perceptions of the authority of pharmacists on this issue, and the reinforcement of the warning message. More broadly, it is suggested that there would be benefit in a wider dissemination of research-based information on increased crash risk and systematic monitoring and publicity about the representation of medications in crashes resulting in injuries and fatalities. Suggestions for future research concern the continued investigation of the effects of medications and interactions with existing medical conditions and other substances on driving skills, effects of variations in warning label design, individual behaviours and characteristics (particularly among those groups who are dependent upon prescription medication) and validation of consumer self-assessment of impairment.

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Since the identification of the gene family of kallikrein related peptidases (KLKs), their function has been robustly studied at the biochemical level. In vitro biochemical studies have shown that KLK proteases are involved in a number of extracellular processes that initiate intracellular signaling pathways by hydrolysis, as reviewed in Chapters 8, 9, and 15, Volume 1. These events have been associated with more invasive phenotypes of ovarian, prostate, and other cancers. Concomitantly, aberrant expression of KLKs has been associated with poor prognosis of patients with ovarian and prostate cancer (Borgoño and Diamandis, 2004; Clements et al., 2004; Yousef and Diamandis, 2009), with prostate-specific antigen (PSA, KLK3) being a long standing, clinically employed biomarker for prostate cancer (Lilja et al., 2008). Data generated from patient samples in clinical studies, alongwith biochemical activity, suggests that KLKs function in the development and progression of these diseases. To bridge the gap between their function at the molecular level and the clinical need for efficacious treatment and prognostic biomarkers, functional assessment at the in vitro cellular level, using various culture models, is increasing, particularly in a three-dimensional (3D) context (Abbott, 2003; Bissell and Radisky, 2001; Pampaloni et al., 2007; Yamada and Cukierman, 2007).

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Asthma is an incapacitating disease of the respiratory system, which causes extensive morbidity and mortality worldwide. Asthma affects more than 300 million people globally(Masoli et al. 2004). In Australia, it affects 10.2% of the population (Masoli et al. 2004) and causes 60,000 people to be hospitalised annually. Health care expenditure due to asthma in Australia was $606 million in 2004–2005. There are four primary biological factors that function in the initiation and exacerbation of asthma. Airway inflammation is important as it is often the first response to an airway insult, initiating the three other components: bronchoconstriction, mucus hyper-secretion and hyper-reactivity. The mediators involved in asthma are still not well understood, and current anti-inflammatory corticosteroid treatments are not effective with all asthmatics. As there is currently no cure for asthma, and airway inflammation is the primary component of the disease, it is important that we understand and investigate the mediators of airway inflammation to look for a potential cure and to produce better therapeutics to treat the inflammation. Trefoil factors (TFFs) and secretoglobins (SCGBs) are small secreted proteins involved in the mediation of inflammation and epithelial restitution. TFFs are pro-inflammatory and SCGBs anti-inflammatory by nature. The hypothesis of this study is that in response to induced acute airway inflammation, the expression of TFF1 and TFF3 will increase and expression of SCGB1A1 and SCGB3A2 will decrease in non-asthmatics (N-A), asthmatics medicating with bronchodilators (A-BD) and asthmatics medicating with corticosteroids (A-ST). When comparing the three groups, we expect to see higher expression of the TFFs in the A-BD group compared to the N-A and A-ST groups, indicating that inflammation is mediated by TFFs in asthma and that corticosteroid medication controls their expression as part of the control of inflammation. We expect to see the opposite with SCGBs, with a greater decrease in the A-BD group compared to the other two groups, suggesting that the A-BD group has the least anti-inflammatory activity in response to inflammatory insult. Epigenetic modification plays a role in the regulation of genes that initiate disease states such as inflammatory conditions and cancers. Histone acetylation is one such modification, which involves the acetylation of histones in chromatin by histone acetyltransferases (HATs). This increases the transcription of genes involved with inflammation or enrols histone deacetylases (HDACs) to down-regulate the transcription of inflammatory genes. These HATs and HDACs work in a homeostatic fashion; however, in the event of inflammation, increased HAT activity can stimulate further inflammation, which is believed to be the mechanism involved in some inflammatory diseases. This study hypothesises that in response to inflammation, the expression of HDACs (HDAC1-5) will decrease and the expression of HATs (NCOA1-3, HAT-1 and CREBBP) will increase in all groups. When comparing the expression between the groups, it was expected that a greater decrease in HDACs and a greater increase in HATs will be seen in the A-BD group compared to the other two groups. This would identify histone acetylation as a mechanism involved in the inflammatory condition of asthma and indicate that corticosteroids may treat the inflammation in asthma at least in part by controlling histone acetylation. The aim of the project was to compare the expression of inflammatory genes TFF1, TFF3, SCGB1A1 and SCGB3A2, as well as to compare the gene expression of HDAC1-5, NCOA1-3, HAT-1 and CREBBP within and between N-A (n=15), A-BD (n=15) and A-ST (n=15) groups in response to inflammation. This was performed by collecting airway cells and proteins by sputum induction in three sessions. The sessions were coordinated into an initial baseline collection (SI-1), followed by a second session at least one week later (SI-2) and a third session, six hours after SI-2 to collect a sample containing the resultant acute inflammation caused in SI-2 (SI-3). Analysis of the SI-1 and SI-2 samples in all three groups had high amounts of variability between samples. The samples were taken at least one weak apart and the environmental stimuli on each participant outside of the testing sessions could not be controlled. For this reason, the SI-1 samples were not used for analysis; instead SI-2 and SI-3 samples were compared as they were same-day collections, reducing the probability of differences being due to anything other than the sputum induction. The gene expressions of the TFFs, SCGBs, HDACs and HATs were analysed using real-time PCR. Western blot analysis was performed to analyse the protein concentrations of the TFFs and SCGBs in secreted fractions of the sputum collection. Both the secreted and intracellular protein fractions collected from the sputum inductions for pre- and post-inflammation (SI-2, SI-3) samples of the N-A and A-BD groups were analysed using a proteomic method called iTRAQ. This allowed the comparison of the change in protein expression as a result of airway inflammation in each group. This technique was used as a discovery method to identify novel proteins that are modulated by induced acute airway inflammation. Any proteins of interest would then be further validated and used for future research. Inflammation was achieved in the SI-3 samples of the N-A group with a 21% unit increase in % neutrophils compared to SI-2 (p=0.01). The N-A group had a marked 5.5-fold decrease in HDAC1 gene expression in SI-3 compared to SI-2 (p=0.03). No differences were seen in any of the TFFs, SCGBs or any of the rest of the HDACs and HATs. Western blot data did not display any significant changes in the protein levels of the TFFs and SCGBs analysed. However, non-significant analysis of the data displayed increases in TFF1 and TFF3, and decreases in SCGB1A1 and SCGB3A2 for the majority of SI-3 samples compared to SI-2. The A-BD group also presented a marked increase in neutrophils in the SI-3 samples compared to SI-2 (27% unit increase, p=0.04). The A-BD group had a significant increase in TFF3 and SCGB1A1 gene expression concomitant with induced acute airway inflammation. A 7.3-fold increase in TFF3 (p=0.05) in SI-3 indicated that TFF3 is linked to inflammation in asthmatics. A 2.8-fold increase in SCGB1A1 (p=0.03) indicated that this gene is also up-regulated, suggesting that this SCGB is expressed to try to combat induced acute airway inflammation. No significant changes were seen in any of the other genes analysed. Western blot data did not display any significant changes in the protein levels of the TFFs and SCGBs analysed. However, non-significant analysis of the data displayed an increase in TFF1 and TFF3, and a decrease in SCGB1A1 and SCGB3A2 in SI-3, similar to that seen in the N-A group. The A-ST group was different from the A-BD group, characterised by the use of inhaled corticosteroid medication to treat asthma symptoms. Inhaled corticosteroids are known to treat asthma symptoms through the control of inflammation. Therefore, it was expected that corticosteroid medication would also control the expression of TFFs, SCGBs, HATs and HDACs. Gene expression results only identified a 7.6-fold decrease in HDAC2 expression in SI-3 (p=0.001), which is proposed to be due to the up-regulation of HDAC2 protein that is known to be a function of corticosteroid use. Western blot data did not display any significant changes in the protein levels of the TFFs and SCGBs analysed. The gene expression in SI-2 and SI-3 in each group was compared. When comparing the A-BD group to the N-A group, a 9-fold increase in TFF3 (p=0.008) and a 34-fold increase in SCGB1A1 (p=0.03) were seen in the SI-3 samples. Comparisons of the A-ST group to the N-A group had an increased expression in SI-2 samples for HDAC5 (3.6-fold, p=0.04), NCOA2 (8.5-fold, p=0.04), NCOA3 (17-fold, p=0.01), HAT-1 (36-fold, p=0.003) and CREBBP (13-fold, p=0.001). The SI-3 samples in the A-ST group compared to the N-A group had increased expression for HDAC1 (6.4-fold, p=0.04), HDAC5 (5.2-fold, p=0.008), NCOA2 (9.6-fold, p=0.03), NCOA3 (16-fold, p=0.06), HAT-1 (41-fold, p<0.001) and CREBBP (31-fold, p=0.001). Comparisons of the A-ST group to the A-BD group had SI-2 increases in HDAC1 (3.8-fold, p=0.03), NCOA3 (4.5-fold, p=0.03), HAT-1 (5.3-fold, p=0.01) and CREBBP (23-fold, p=0.001), while SI-3 comparisons saw a decrease in HDAC2 (41-fold, p=0.008) and increases in HAT-1 (4.3-fold, p=0.003) and CREBBP (40-fold, p=0.001). Results showed that TFF3 and SCGB1A1 expression is higher in asthmatics than non-asthmatics and that histone acetylation is more active in the A-ST group than either the N-A or A-BD group, which suggests that histone acetylation activity may be positively correlated with asthma severity. The iTRAQ proteomic analysis of the secreted protein samples identified the SCGB1A1 protein and found it to be decreased in both the N-A and A-BD groups post-inflammation, but significantly so only in the A-BD group. Although no significant results were obtained from the western blot data, both groups displayed a decrease in SCGB1A1 concentration in SI-3 samples, suggesting a correlation with the proteomic data. Only 31 peptides were identified from the secreted samples. The intracellular iTRAQ analysis successfully identified 664 peptides, eight of which had differential expression in association with induced acute airway inflammation. Significant increases were seen in the A-BD group in SI-3 compared to SI-2 than in the N-A group in chloride intracellular channel protein 1, keratin-19, eosinophil cationic protein, calnexin, peroxiredoxin-5, and ATP-synthase delta subunit, while decreases were seen in cystatin-A and mucin-5AC. The iTRAQ analysis was only a discovery measure and further validation must be performed. In summary, the expression of TFFs and SCGBs differed between non-asthmatics and asthmatics. It is clear that TFF3 is active in the airway inflammation associated with asthma as indicated by an increase associated with inflammation in the A-BD group compared to the N-A group. Results for HDAC and HAT genes showed high HAT expression in the A-ST group compared to the N-A and A-BD groups, suggesting that histone acetyltransferases may be responsible for the characteristic unregulated inflammatory symptoms of asthmatics taking corticosteroids. Interestingly, corticosteroid medication did not seem to silence the expression of the analysed HAT genes, which indicates that corticosteroids may not control inflammation by direct regulation of HATs, but instead by competition, most probably with HDAC2 protein. As a discovery tool, iTRAQ is a potent method to both identify and compare the concentration of proteins between samples. The method is a powerful first step into the identification of novel proteins that are regulated in response to different treatments.

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In 1963, the National Institutes of Health (NIH) first issued guidelines for animal housing and husbandry. The most recent 2010 revision emphasizes animal care “in ways judged to be scientifically, technically, and humanely appropriate” (National Institutes of Health, 2010, p. XIII). The goal of these guidelines is to ensure humanitarian treatment of animals and to optimize the quality of research. Although these animal care guidelines cover a substantial amount of information regarding animal housing and husbandry, researchers generally do not report all these variables (see Table ​Table1).1). The importance of housing and husbandry conditions with respect to standardization across different research laboratories has been debated previously (Crabbe et al., 1999; Van Der Staay and Steckler, 2002; Wahlsten et al., 2003; Wolfer et al., 2004; Van Der Staay, 2006; Richter et al., 2010, 2011). This paper focuses on several animal husbandry and housing issues that are particularly relevant to stress responses in rats, including transportation, handling, cage changing, housing conditions, light levels and the light–dark cycle. We argue that these key animal housing and husbandry variables should be reported in greater detail in an effort to raise awareness about extraneous experimental variables, especially those that have the potential to interact with the stress response.

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Black et al. (2004) identified a systematic difference between LA–ICP–MS and TIMS measurements of 206Pb/238U in zircons, which they correlated with the incompatible trace element content of the zircon. We show that the offset between the LA–ICP–MS and TIMS measured 206Pb/238U correlates more strongly with the total radiogenic Pb than with any incompatible trace element. This suggests that the cause of the 206Pb/238U offset is related to differences in the radiation damage (alpha dose) between the reference and unknowns. We test this hypothesis in two ways. First, we show that there is a strong correlation between the difference in the LA–ICP–MS and TIMS measured 206Pb/238U and the difference in the alpha dose received by unknown and reference zircons. The LA–ICP–MS ages for the zircons we have dated can be as much as 5.1% younger than their TIMS age to 2.1% older, depending on whether the unknown or reference received the higher alpha dose. Second, we show that by annealing both reference and unknown zircons at 850 °C for 48 h in air we can eliminate the alpha-dose-induced differences in measured 206Pb/238U. This was achieved by analyzing six reference zircons a minimum of 16 times in two round robin experiments: the first consisting of unannealed zircons and the second of annealed grains. The maximum offset between the LA–ICP–MS and TIMS measured 206Pb/238U for the unannealed zircons was 2.3%, which reduced to 0.5% for the annealed grains, as predicted by within-session precision based on counting statistics. Annealing unknown zircons and references to the same state prior to analysis holds the promise of reducing the 3% external error for the measurement of 206Pb/238U of zircon by LA–ICP–MS, indicated by Klötzli et al. (2009), to better than 1%, but more analyses of annealed zircons by other laboratories are required to evaluate the true potential of the annealing method.