An influenza virus inspired polymer system for the timed release of siRNA

Small interfering RNA silences specific genes by interfering with mRNA translation, and acts to modulate or inhibit specific biological pathways; a therapy that holds great promise in the cure of many diseases. However, the naked small interfering RNA is susceptible to degradation by plasma and tissue nucleases and due to its negative charge unable to cross the cell membrane. Here we report a new polymer carrier designed to mimic the influenza virus escape mechanism from the endosome, followed by a timed release of the small interfering RNA in the cytosol through a self-catalyzed polymer degradation process. Our polymer changes to a negatively charged and non-toxic polymer after the release of small interfering RNA, presenting potential for multiple repeat doses and long-term treatment of diseases.

Examining the effects of an eco-driving system on driver distraction

Driver distraction has recently been defined by Regan as "the diversion of attention away from activities critical for safe driving toward a competing activity, which may result in insufficient or no attention to activities critical for safe driving (Regan, Hallett & Gordon, 2011, p.1780)". One source of distraction is in-vehicle devices, even though they might provide other benefits, e.g. navigation systems. Currently, eco-driving systems have been growing rapidly in popularity. These systems send messages to drivers so that driving performance can be improved in terms of fuel efficiency. However, there remain unanswered questions about whether eco-driving systems endanger drivers by distracting them. In this research, the CARRS-Q advanced driving simulator was used in order to provide safety for participants and meanwhile simulate real world driving. The distraction effects of tasks involving three different in-vehicle systems were investigated: changing a CD, entering a five digit number as a part of navigation task and responding to an eco-driving task. Driving in these scenarios was compared with driving in the absence of these distractions, and while drivers engaged in critical manoeuvres. In order to account for practice effects, the same scenarios were duplicated on a second day. The three in-vehicle systems were not the exact facsimiles of any particular existing system, but were designed to have similar characteristics to those of system available. In general, the results show that drivers’ mental workloads are significantly higher in navigation and CD changing scenarios in comparison to the two other scenarios, which implies that these two tasks impose more visual/manual and cognitive demands. However, eco-driving mental workload is still high enough to be called marginally significant (p ~ .05) across manoeuvres. Similarly, event detection tasks show that drivers miss significantly more events in the navigation and CD changing scenarios in comparison to both the baseline and eco-driving scenario across manoeuvres. Analysis of the practice effect shows that drivers’ baseline scenario and navigation scenario exhibit significantly less demand on the second day. However, the number of missed events across manoeuvres confirmed that drivers can detect significantly more events on the second day for all scenarios. Distraction was also examined separately for five groups of manoeuvres (straight, lane changing, overtaking, braking for intersections and braking for roundabouts), in two locations for each condition. Repeated measures mixed ANOVA results show that reading an eco-driving message can potentially impair driving performance. When comparing the three in–vehicle distractions tested, attending to an eco-driving message is similar in effect to the CD changing task. The navigation task degraded driver performance much more than these other sources of distraction. In lane changing manoeuvres, drivers’ missed response counts degraded when they engaged in reading eco-driving messages at the first location. However, drivers’ event detection abilities deteriorated less at the second lane changing location. In baseline manoeuvres (driving straight), participants’ mean minimum speed degraded more in the CD changing scenario. Drivers’ lateral position shifted more in both CD changing and navigation tasks in comparison with both eco-driving and baseline scenarios, so they were more visually distracting. Participants were better at event detection in baseline manoeuvres in comparison with other manoeuvres. When approaching an intersection, the navigation task caused more events to be missed by participants, whereas eco-driving messages seemed to make drivers less distracted. The eco-driving message scenario was significantly less distracting than the navigation system scenario (fewer missed responses) when participants commenced braking for roundabouts. To sum up, in spite of the finding that two other in-vehicle tasks are more distracting than the eco-driving task, the results indicate that even reading a simple message while driving could potentially lead to missing an important event, especially when executing critical manoeuvres. This suggests that in-vehicle eco-driving systems have the potential to contribute to increased crash risk through distraction. However, there is some evidence of a practice effect which suggests that future research should focus on performance with habitual rather than novel tasks. It is recommended that eco-driving messages be delivered to drivers off-line when possible.

A new feedback ANC system approach

We propose a new active noise control (ANC) technique. The technique has a feedback structure to have a simple configuration in practical implementation. In this approach, the secondary path is modelled online to ensure convergence of the system as the secondary paths are practically time varying or non-linear. The proposed method consists of two steps: a noise controller which is based on a modified FxLMS algorithm, and a new variable step size (VSS) LMS algorithm which is used to adapt the modelling filter with the secondary path. The proposed algorithm stops injection of the white noise at the optimum point and reactivate the injection during the operation, if needed, to maintain performance of the system. Eliminating continuous injection of the white noise increases the performance of the proposed method significantly and makes it more desirable for practical ANC systems. The computer simulations are presented to show the effectiveness of the proposed method.

Adaption of horses to a novel dynamic feeding system : movement and behavioural responses

Reasons for performing study: Many domestic horses and ponies are sedentary and obese due to confinement to small paddocks and stables and a diet of infrequent, high-energy rations. Severe health consequences can be associated with this altered lifestyle. Objectives: The aims of this study were to investigate the ability of horses to learn to use a dynamic feeder system and determine the movement and behavioural responses of horses to the novel system. Methods: A dynamic feed station was developed to encourage horses to exercise in order to access ad libitum hay. Five pairs of horses (n = 10) were studied using a randomised crossover design with each pair studied in a control paddock containing a standard hay feeder and an experimental paddock containing the novel hay feeder. Horse movement was monitored by a global positioning system (GPS) and horses observed and their ability to learn to use the system and the behavioural responses to its use assessed. Results: With initial human intervention all horses used the novel feeder within 1 h. Some aggressive behaviour was observed between horses not well matched in dominance behaviour. The median distance walked by the horses was less (P = 0.002) during a 4 h period (117 [57–185] m) in the control paddock than in the experimental paddock (630 [509–719] m). Conclusions: The use of an automated feeding system promotes increased activity levels in horses housed in small paddocks, compared with a stationary feeder.

Insulin and the insulin-like growth factor system : a novel theory for hyperinsulinemic laminitis pathogenesis

Research into hyperinsulinemic laminitis has progressed significantly in recent years with the use of the prolonged-euglycemic, hyperinsulinemic clamp (p-EHC). Previous investigations of laminitis pathophysiology have focused on digital vascular dysfunction, inflammation, altered glucose metabolism within the lamellae, and lamellar basement membrane breakdown by metalloproteinases. The etiopathogenesis of laminitis occurring in association with hyperinsulinemia is yet to be fully characterized, but it may not involve these mechanisms. Insulin stimulates cellular proliferation and can also affect other body systems, such as the insulin-like growth factor (IGF) system. Insulin-like growth factor-1 (IGF-1) is structurally homologous to insulin and, like insulin, binds with strong affinity to a specific tyrosine kinase receptor on the cell surface to produce its effects, which include promoting cell proliferation. Receptors for IGF-1 (IGF-1R) are present in the lamellar epidermis. An alternative theory for the pathogenesis of hyperinsulinemic laminitis is that uncontrolled cell proliferation, mediated through both the insulin receptor (InsR) and IGF-1R, leads to lengthening, weakening, and failure of the lamellae. An analysis of the proliferative activity of lamellar epidermal cells during the developmental and acute phases of hyperinsulinemic laminitis, and lamellar gene expression of the InsR and IGF-1R was undertaken.

Women as victims and offenders : incarcerated for murder in the Australian criminal justice system

This study was undertaken in an effort to contribute to the limited knowledge of women who commit murder. Women account for approximately 10% of the total Australian homicides and according to Mouzos (2000), 20% of these female perpetrated homicides result in murder convictions. In her extensive study of female homicide offending in England, Brookman (2005) asserts that nearly two thirds of the victims of women who kill are intimates, to include violent partners and their own children. The other third of the victims consist largely of acquaintances and to lesser degree strangers (Brookman, 2005). This study strives to introduce further knowledge regarding women convicted of murder; the smaller subgroup of female homicide offenders of which less is known. It is comprised of women who killed intimates and non-intimates to include acquaintances. The study engages the narratives of seven women, all of whom were convicted of murder and serving lengthy sentences at the Dame Phyllis Frost Centre, a medium and maximum security prison that is located on the outskirts of Melbourne, Australia. The seven women fall largely outside of the characteristics of female homicide offenders as revealed in the studies from Australia’s National Homicide Monitoring Program (NHMP, 2007), from Canada by Hoffmann, Lavigne, and Dickie (1998) and research from the United States by Scott and Davies (2002). In this study there were no Indigenous women represented. Only one of the women had a previous criminal charge. The women were older on average than the prevailing demographics from western nations. Two of the women had substance abuse and co-occurring mental illness, which reflects a significant lower rate than the literature suggests. This study expands the current understanding of the phenomenon of women who murder. It communicates the narratives of seven women charged and convicted of murder as they attempt to understand their lives and identities. It moves the dialogue beyond the preponderance of feminist criminological research that examines motive and the relationship the woman has with her victim to the social discourses which dominate in her identity formation. This research found that in their attempt to create a favourable identity the women needed to engage with the master script of normative femininity through the feminisation of victimisation, motherhood and domesticity.

Australia's disabling income support system : tracing the history of the Australian disability income support system 1908 to 2007 : disablism, citizenship and the basic income proposal

The present study examined the historical basis of the Australian disability income support system from 1908 to 2007. Although designed as a safety net for people with a disability, the disability income support system within Australia has been highly targeted. The original eligibility criteria of "permanently incapacitated for work", medical criteria and later "partially capacitated for work" potentially contained ideological inferences that permeated across the time period. This represents an important area for study given the potential consequence for disability income support to marginalise people with a disability. Social policy and disability policy theorists, including Saunders (2007, Social Policy Research Centre [SPRC]) and Gibilisco (2003) have provided valuable insight into some of the effects of disability policy and poverty. Yet while these theorists argued for some form of income support they did not propose a specific form of income security for further exploration. Few studies have undertaken a comprehensive review of the history of disability income support within the Australian context. This thesis sought to redress these gaps by examining disability income support policy within Australia. The research design consisted of an in-depth critical historical-comparative policy analysis methodology. The use of critical historical-comparative policy analysis allowed the researcher to trace the construction of disability within the Australian disability income support policy across four major historical epochs. A framework was developed specifically to guide analysis of the data. The critical discourse analysis method helped to understand the underlying ideological dimensions that led to the predominance of one particular approach over another. Given this, the research purpose of the study centred on: i. Tracing the history of the Australian disability income support system. ii. Examining the historical patterns and ideological assumptions over time. iii. Exploring the historical patterns and ideological assumptions underpinning an alternative model (Basic Income) and the extent to which each model promotes the social citizenship of people with a disability. The research commitment to a social-relational ontology and the quest for social change centred on the idea that "there has to be a better way" in the provision of disability income support. This theme of searching for an alternative reality in disability income support policy resonated throughout the thesis. This thesis found that the Australian disability income support system is disabling in nature and generates categories of disability on the basis of ableness. From the study, ableness became a condition for citizenship. This study acknowledged that, in reality, income support provision reflects only one aspect of the disabling nature of society which requires redressing. Although there are inherent tensions in any redistributive strategy, the Basic Income model potentially provides an alternative to the Australian disability income support system, given its grounding in social citizenship. The thesis findings have implications for academics, policy-makers and practitioners in terms of developing better ways to understand disability constructs in disability income support policy. The thesis also makes a contribution in terms of promoting income support policies based on the rights of all people, not just a few.

Theoretical framework for a management decision evaluation system

A theoretical framework for a construction management decision evaluation system for project selection by means of a literature review. The theory is developed by the examination of the major factors concerning the project selection decision from a deterministic viewpoint, where the decision-maker is assumed to possess 'perfect knowledge' of all the aspects involved. Four fundamental project characteristics are identified together with three meaningful outcome variables. The relationship within and between these variables are considered together with some possible solution techniques. The theory is next extended to time-related dynamic aspects of the problem leading to the implications of imperfect knowledge and a non­deterministic model. A solution technique is proposed in which Gottinger's sequential machines are utilised to model the decision process,

An expert system for the strategic planning of construction projects

This paper describes the instigation and development of an expert system to aid in the strategic planning of construction projects. The paper consists of four parts - the origin of the project, the development of the concepts needed for the proposed system, the building of the system itself, and assessment of its performance. The origin of the project is outlined starting with the Japanese commitment to 5th generation computing together with the increasing local reaction to theory based prescriptive research in the field. The subsequent development of activities via the Alvey Commission and the RICS in conjunction with Salford University are traced culminating in the proposal and execution of the first major expert system to be built for the UK construction industry, subsequently recognised as one of the most successful of the expert system projects commissioned under the Alvey programme

Which procurement system? Towards a universal procurement selection technique

Two approaches are described, which aid the selection of the most appropriate procurement arrangements for a building project. The first is a multi-attribute technique based on the National Economic Development Office procurement path decision chart. A small study is described in which the utility factors involved were weighted by averaging the scores of five 'experts' for three hypothetical building projects. A concordance analysis is used to provide some evidence of any abnormal data sources. When applied to the study data, one of the experts was seen to be atypical. The second approach is by means of discriminant analysis. This was found to provide reasonably consistent predictions through three discriminant functions. The analysis also showed the quality criteria to have no significant impact on the decision process. Both approaches provided identical and intuitively correct answers in the study described. Some concluding remarks are made on the potential of discriminant analysis for future research and development in procurement selection techniques.

A critical assessment of the Australian OHS accreditation system's "Body of Knowledge (BoK)"

In response to an increasing perception of poor OHS consultancy quality amongst the Australian public, regulator and OHS professionals, the Safety Institute Australia (SIA) was tasked by the Victorian government to establish an accreditation process for OHS professionals. The OHS accreditation board decided to base its accreditation on a core "body of knowledge" (BoK), against which applicants are assesssed. While the foundation and structure of the BoK is unclear, the BoK consists of a collection of essays from a variety of invited authors. The BoK comprises about 811 pages in 34 chapters, with significant redundancy and considerable subjective components. The SIA BoK is benchmarked against two international best-practices, the German "Core Definition, Object Catalog and Research Domains of Labour Science (Ergonomics)" (Luzcak, Volpert, Raeithel & Schwier, 1989)(100 pages) and the American "Core Competency Model" for the "Master's Degree in Public Health" (Association of Schools of Public Health, 2006) (21 pages). Both "core definition" and "core competency model" are on a comparative level to the BoK. While the German expert panel consisted of 14 eminent professors, the American panel consisted of 135 members, organized in 6 groups chaired by discipline leading academics. The Australian approach employed a broad approach, where 137 professionals, consultants, emerging academics and academics contributed to 8 workshops. Both the German and the American panels maintained an open communication amongst members and with the discipline community throughout the process, whereas SIA applied an open and directed peer-review process. Moreover, the German process involved an analysis of all congress content and journal publications in the scientific domain in a set timeframe, which were then systematically clustered. These results were further expanded by structured interviews with 38 professors in the discpline, grasping their research and teaching practice. The American workgroup however assumed core scientific areas, underlying the domain. Based upon the a-priori assumption, they then established well defined competencies across all areas using a modified Delphi process. Although the BoK attempts to explore the knowledge in the OHS domain without an imposed structure in a bottom-up approach, it does not result in a structured systematic of the science. We conclude that the outcome of the German, rigorous academic approach, and the US American democratic approach under unambiguous academic leadership both outperform the Australian advocacy group approach. This product was determined for both structure and content of the taxonomy delivered through the processes.

First steps towards modeling a multi-scale Earth system

Recent advances in computational geodynamics are applied to explore the link between Earth’s heat, its chemistry and its mechanical behavior. Computational thermal-mechanical solutions are now allowing us to understand Earth patterns by solving the basic physics of heat transfer. This approach is currently used to solve basic convection patterns of terrestrial planets. Applying the same methodology to smaller scales delivers promising similarities between observed and predicted structures which are often the site of mineral deposits. The new approach involves a fully coupled solution to the energy, momentum and continuity equations of the system at all scales, allowing the prediction of fractures, shear zones and other typical geological patterns out of a randomly perturbed initial state. The results of this approach are linking a global geodynamic mechanical framework over regional-scale mineral deposits down to the underlying micro-scale processes. Ongoing work includes the challenge of incorporating chemistry into the formulation.