The molecular mechanisms utilised by mesenchymal stem cells in migration to acute myocardial infarction

Heart damage caused by acute myocardial infarction (AMI) is a leading cause of death and disability in Australia. Novel therapies are still required for the treatment of this condition due to the poor reparative ability of the heart. As such, cellular therapies that assist in the recovery of heart muscle are of great current interest. Culture expanded mesenchymal stem cells (MSC) represent a stem and progenitor cell population that has been shown to promote tissue recovery in pre-clinical studies of AMI. For MSC-based therapies in the clinic, an intravenous route of administration would ideally be used due to the low cost, ease of delivery and relative safety. The study of MSC migration is therefore clinically relevant for a minimally invasive cell therapy to promote regeneration of damaged tissue. C57BL/6, UBI-GFP-BL/6 and CD44-/-/GFP+/+ mice were utilised to investigate mMSC migration. To assist in murine models of MSC migration, a novel method was used for the isolation of murine MSC (mMSC). These mMSC were then expanded in culture and putative mMSC were positive for Sca-1, CD90.2, and CD44 and were negative for CD45 and CD11b. Furthermore, mMSC from C57BL/6 and UBI-GFP-BL/6 mice were shown to differentiate into cells of the mesodermal lineage. Cells from CD44-/-/GFP+/+ mice were positive for Sca-1 and CD90.2, and negative for CD44, CD45 and CD11b however, these cells were unable to differentiate into adipocytes and chondrocytes and express lineage specific genes, PLIN and ACAN. Analysis of mMSC chemokine receptor (CR) expression showed that although mMSC do express chemokine receptors, (including those specific for chemokines released after AMI), these were low or undetectable by mRNA. However, protein expression could be detected, which was predominantly cytoplasmic. It was further shown that in both healthy (unperturbed) and inflamed tissues, mMSC had very little specific migration and engraftment after intravenous injection. To determine if poor mMSC migration was due to the inability of mMSC to respond to chemotactic stimuli, chemokine expression in bone marrow, skin injury and hearts (healthy and after AMI) was analysed at various time points by quantitative real-time PCR (qRT PCR). Many chemokines were up-regulated after skin biopsy and AMI, but the highest acute levels were found for CXCL12 and CCL7. Due to their high expression in infarcted hearts, the chemokines CXCL12 and CCL7 were tested for their effect on mMSC migration. Despite CR expression at both protein and mRNA levels, migration in response to CXCL12 and CCL7 was low in mMSC cultured on Nunclon plastic. A novel tissue culture plastic technology (UpCellTM) was then used that allowed gentle non-enzymatic dissociation of mMSC, thus preserving surface expression of the CRs. Despite this the in vitro data indicated that CXCL12 fails to induce significant migration ability of mMSC, while CCL7 induces significant, but low-level migration. We speculated this may be because of low levels of surface expression of chemokine receptors. In a strategy to increase cell surface expression of mMSC chemokine receptors and enhance their in vitro and in vivo migration capacity, mMSC were pre-treated with pro-inflammatory cytokines. Increased levels of both mRNA and surface protein expression were found for CRs by pre-treating mMSC with pro-inflammatory cytokines including TNF-á, IFN-ã, IL-1á and IL-6. Furthermore, the chemotactic response of mMSC to CXCL12 and CCL7 was significantly higher with these pretreated cells. Finally, the effectiveness of this type of cell manipulation was demonstrated in vivo, where mMSC pre-treated with TNF-á and IFN-ã showed significantly increased migration in skin injury and AMI models. Therefore this thesis has demonstrated, using in vitro and in vivo models, the potential for prior manipulation of MSC as a possible means for increasing the utility of intravenously delivery for MSC-based cellular therapies.

Scaling acoustic data analysis through collaboration and automation

Monitoring and assessing environmental health is becoming increasingly important as human activity and climate change place greater pressure on global biodiversity. Acoustic sensors provide the ability to collect data passively, objectively and continuously across large areas for extended periods of time. While these factors make acoustic sensors attractive as autonomous data collectors, there are significant issues associated with large-scale data manipulation and analysis. We present our current research into techniques for analysing large volumes of acoustic data effectively and efficiently. We provide an overview of a novel online acoustic environmental workbench and discuss a number of approaches to scaling analysis of acoustic data; collaboration, manual, automatic and human-in-the loop analysis.

Space : Irrealis objects and their role in a new political economy

In this paper, I show how new spaces are being prefigured for colonisation in the language of contemporary technology policy. Drawing on a corpus of 1.3 million words collected from technology policy centres throughout the world, I show the role of policy language in creating the foundations of an emergent form of political economy. The analysis is informed by principles from critical discourse analysis (CDA) and classical political economy. It foregrounds a functional aspect of language called process metaphor to show how aspects of human activity are prefigured for mass commodification by the manipulation of irrealis spaces. I also show how the fundamental element of any new political economy, the property element, is being largely ignored. The potential creation of a global space as concrete as landed property – electromagnetic spectrum – has significant ramifications for the future of social relations in any global “knowledge economy”.

Influence of culture conditions on the molecular signature of mesenchymal stem cells

Cell based therapies require cells capable of self renewal and differentiation, and a prerequisite is the ability to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies is therefore an integral part of tissue engineering. Bone marrow is the most easily accessible source of mesenchymal stem cells (MSCs), and harbours two distinct populations of adult stem cells; namely hematopoietic stem cells (HSCs) and bone mesenchymal stem cells (BMSCs). Unlike HSCs, there are yet no rigorous criteria for characterizing BMSCs. Changing understanding about the pluripotency of BMSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to BMSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their in vitro study. Also, when BMSCs are cultured in vitro there is a loss of the in vivo microenvironment which results in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage number, characterized by the onset of senescence related changes. Accordingly, establishing protocols for generating large numbers of BMSCs without affecting their differentiation potential is necessary. The principal aims of this thesis were to identify potential molecular factors for characterizing BMSCs from osteoarthritic patients, and also to attempt to establish culture protocols favourable for generating large number of BMSCs, while at the same time retaining their proliferation and differentiation potential. Previously published studies concerning clonal cells have demonstrated that BMSCs are heterogeneous populations of cells at various stages of growth. Some cells are higher in the hierarchy and represent the progenitors, while other cells occupy a lower position in the hierarchy and are therefore more committed to a particular lineage. This feature of BMSCs was made evident by the work of Mareddy et al., which involved generating clonal populations of BMSCs from bone marrow of osteoarthritic patients, by a single cell clonal culture method. Proliferation potential and differentiation capabilities were used to group cells into fast growing and slow growing clones. The study presented here is a continuation of the work of Mareddy et al. and employed immunological and array based techniques to identify the primary molecular factors involved in regulating phenotypic characteristics exhibited by contrasting clonal populations. The subtractive immunization (SI) was used to generate novel antibodies against favourably expressed proteins in the fast growing clonal cell population. The difference between the clonal populations at the transcriptional level was determined using a Stem Cell RT2 Profiler TM PCR Array which focuses on stem cell pathway gene expression. Monoclonal antibodies (mAb) generated by SI were able to effectively highlight differentially expressed antigenic determinants, as was evident by Western blot analysis and confocal microscopy. Co-immunoprecipitation, followed by mass spectroscopy analysis, identified a favourably expressed protein as the cytoskeletal protein vimentin. The stem cell gene array highlighted genes that were highly upregulated in the fast growing clonal cell population. Based on their functions these genes were grouped into growth factors, cell fate determination and maintenance of embryonic and neural stem cell renewal. Furthermore, on a closer analysis it was established that the cytoskeletal protein vimentin and nine out of ten genes identified by gene array were associated with chondrogenesis or cartilage repair, consistent with the potential role played by BMSCs in defect repair and maintaining tissue homeostasis, by modulating the gene expression pattern to compensate for degenerated cartilage in osteoarthritic tissues. The gene array also presented transcripts for embryonic lineage markers such as FOXA2 and Sox2, both of which were significantly over expressed in fast growing clonal populations. A recent groundbreaking study by Yamanaka et al imparted embryonic stem cell (ESCs) -like characteristic to somatic cells in a process termed nuclear reprogramming, by the ectopic expression of the genes Sox2, cMyc and Oct4. The expression of embryonic lineage markers in adult stem cells may be a mechanism by which the favourable behaviour of fast growing clonal cells is determined and suggests a possible active phenomenon of spontaneous reprogramming in fast growing clonal cells. The expression pattern of these critical molecular markers could be indicative of the competence of BMSCs. For this reason, the expression pattern of Sox2, Oct4 and cMyc, at various passages in heterogeneous BMSCs population and tissue derived cells (osteoblasts and chondrocytes), was investigated by a real-time PCR and immunoflourescence staining. A strong nuclear staining was observed for Sox2, Oct4 and cMyc, which gradually weakened accompanied with cytoplasmic translocation after several passage. The mRNA and protein expression of Sox2, Oct4 and cMyc peaked at the third passage for osteoblasts, chondrocytes and third passage for BMSCs, and declined with each subsequent passage, indicating towards a possible mechanism of spontaneous reprogramming. This study proposes that the progressive decline in proliferation potential and multipotentiality associated with increased passaging of BMSCs in vitro might be a consequence of loss of these propluripotency factors. We therefore hypothesise that the expression of these master genes is not an intrinsic cell function, but rather an outcome of interaction of the cells with their microenvironment; this was evident by the fact that when removed from their in vivo microenvironment, BMSCs undergo a rapid loss of stemness after only a few passages. One of the most interesting aspects of this study was the integration of factors in the culture conditions, which to some extent, mimicked the in vivo microenvironmental niche of the BMSCs. A number of studies have successfully established that the cellular niche is not an inert tissue component but is of prime importance. The total sum of stimuli from the microenvironment underpins the complex interplay of regulatory mechanisms which control multiple functions in stem cells most importantly stem cell renewal. Therefore, well characterised factors which affect BMSCs characteristics, such as fibronectin (FN) coating, and morphogens such as FGF2 and BMP4, were incorporated into the cell culture conditions. The experimental set up was designed to provide insight into the expression pattern of the stem cell related transcription factors Sox2, cMyc and Oct4, in BMSCs with respect to passaging and changes in culture conditions. Induction of these pluripotency markers in somatic cells by retroviral transfection has been shown to confer pluripotency and an ESCs like state. Our study demonstrated that all treatments could transiently induce the expression of Sox2, cMyc and Oct4, and favourably affect the proliferation potential of BMSCs. The combined effect of these treatments was able to induce and retain the endogenous nuclear expression of stem cell transcription factors in BMSCs over an extended number of in vitro passages. Our results therefore suggest that the transient induction and manipulation of endogenous expression of transcription factors critical for stemness can be achieved by modulating the culture conditions; the benefit of which is to circumvent the need for genetic manipulations. In summary, this study has explored the role of BMSCs in the diseased state of osteoarthritis, by employing transcriptional profiling along with SI. In particular this study pioneered the use of primary cells for generating novel antibodies by SI. We established that somatic cells and BMSCs have a basal level of expression of pluripotency markers. Furthermore, our study indicates that intrinsic signalling mechanisms of BMSCs are intimately linked with extrinsic cues from the microenvironment and that these signals appear to be critical for retaining the expression of genes to maintain cell stemness in long term in vitro culture. This project provides a basis for developing an “artificial niche” required for reversion of commitment and maintenance of BMSC in their uncommitted homeostatic state.

A proactive response to the mobbing problem : a guide for HR managers

This paper introduces the concept of workplace mobbing as a destructive organizational behaviour of psychological assaults perpetrated against the target causing them harm and loss of employment. The discussion is drawn from a three year Australian study of 212 self identified targets of workplace mobbing behaviours. The behaviours are typically covert with informal networks and friendship loyalties providing effective mechanisms for emotional abuse, including those arising from human resource management practices. This paper discusses the manipulation of informal sources of power, with the use of gossip, rumour, hearsay, and innuendo to discredit and demonise those targeted. The study explores some of the systemic reasons for these behaviours and identifies some of the contributing risk factors and suggests management practices that can minimise the harm caused.

Learning to act in uncertain environments : technical perspective

The problem of decision making in an uncertain environment arises in many diverse contexts: deciding whether to keep a hard drive spinning in a net-book; choosing which advertisement to post to a Web site visitor; choosing how many newspapers to order so as to maximize profits; or choosing a route to recommend to a driver given limited and possibly out-of-date information about traffic conditions. All are sequential decision problems, since earlier decisions affect subsequent performance; all require adaptive approaches, since they involve significant uncertainty. The key issue in effectively solving problems like these is known as the exploration/exploitation trade-off: If I am at a cross-roads, when should I go in the most advantageous direction among those that I have already explored, and when should I strike out in a new direction, in the hopes I will discover something better?

Dynamics of attacker–defender dyads in Association Football : parameters influencing decision-making

Previous work on pattern-forming dynamics of team sports has investigated sub-phases of basketball and rugby union by focussing on one-versus-one (1v1) attacker-defender dyads. This body of work has identified the role of candidate control parameters, interpersonal distance and relative velocity, in predicting the outcomes of team player interactions. These two control parameters have been described as functioning in a nested relationship where relative velocity between players comes to the fore within a critical range of interpersonal distance. The critical influence of constraints on the intentionality of player behaviour has also been identified through the study of 1v1 attacker-defender dyads. This thesis draws from previous work adopting an ecological dynamics approach, which encompasses both Dynamical Systems Theory and Ecological Psychology concepts, to describe attacker-defender interactions in 1v1 dyads in association football. Twelve male youth association football players (average age 15.3 ± 0.5 yrs) performed as both attackers and defenders in 1v1 dyads in three field positions in an experimental manipulation of the proximity to goal and the role of players. Player and ball motion was tracked using TACTO 8.0 software (Fernandes & Caixinha, 2003) to produce two-dimensional (2D) trajectories of players and the ball on the ground. Significant differences were found for player-to-ball interactions depending on proximity to goal manipulations, indicating how key reference points in the environment such as the location of the goal may act as a constraint that shapes decision-making behaviour. Results also revealed that interpersonal distance and relative velocity alone were insufficient for accurately predicting the outcome of a dyad in association football. Instead, combined values of interpersonal distance, ball-to-defender distance, attacker-to-ball distance, attacker-to-ball relative velocity and relative angles were found to indicate the state of dyad outcomes.

Propagation of low power low divergence Gaussian fields in unbiased self-defocusing photorefractive media and their interactions

Many optical networks are limited in speed and processing capability due to the necessity for the optical signal to be converted to an electrical signal and back again. In addition, electronically manipulated interconnects in an otherwise optical network lead to overly complicated systems. Optical spatial solitons are optical beams that propagate without spatial divergence. They are capable of phase dependent interactions, and have therefore been extensively researched as suitable all optical interconnects for over 20 years. However, they require additional external components, initially high voltage power sources were required, several years later, high power background illumination had replaced the high voltage. However, these additional components have always remained as the greatest hurdle in realising the applications of the interactions of spatial optical solitons as all optical interconnects. Recently however, self-focusing was observed in an otherwise self-defocusing photorefractive crystal. This observation raises the possibility of the formation of soliton-like fields in unbiased self-defocusing media, without the need for an applied electrical field or background illumination. This thesis will present an examination of the possibility of the formation of soliton-like low divergence fields in unbiased self-defocusing photorefractive media. The optimal incident beam and photorefractive media parameters for the formation of these fields will be presented, together with an analytical and numerical study of the effect of these parameters. In addition, preliminary examination of the interactions of two of these fields will be presented. In order to complete an analytical examination of the field propagating through the photorefractive medium, the spatial profile of the beam after propagation through the medium was determined. For a low power solution, it was found that an incident Gaussian field maintains its Gaussian profile as it propagates. This allowed the beam at all times to be described by an individual complex beam parameter, while also allowing simple analytical solutions to the appropriate wave equation. An analytical model was developed to describe the effect of the photorefractive medium on the Gaussian beam. Using this model, expressions for the required intensity dependent change in both the real and imaginary components of the refractive index were found. Numerical investigation showed that under certain conditions, a low powered Gaussian field could propagate in self-defocusing photorefractive media with divergence of approximately 0.1 % per metre. An investigation into the parameters of a Ce:BaTiO3 crystal showed that the intensity dependent absorption is wavelength dependent, and can in fact transition to intensity dependent transparency. Thus, with careful wavelength selection, the required intensity dependent change in both the real and imaginary components of the refractive index for the formation of a low divergence Gaussian field are physically realisable. A theoretical model incorporating the dependence of the change in real and imaginary components of the refractive index on propagation distance was developed. Analytical and numerical results from this model are congruent with the results from the previous model, showing low divergence fields with divergence less than 0.003 % over the propagation length of the photorefractive medium. In addition, this approach also confirmed the previously mentioned self-focusing effect of the self-defocusing media, and provided an analogy to a negative index GRIN lens with an intensity dependent focal length. Experimental results supported the findings of the numerical analysis. Two low divergence fields were found to possess the ability to interact in a Ce:BaTiO3 crystal in a soliton-like fashion. The strength of these interactions was found to be dependent on the degree of divergence of the individual beams. This research found that low-divergence fields are possible in unbiased self-defocusing photorefractive media, and that soliton-like interactions between two of these fields are possible. However, in order for these types of fields to be used in future all optical interconnects, the manipulation of these interactions, together with the ability for these fields to guide a second beam at a different wavelength, must be investigated.

Preparing the actor for performance capture

Notions of capture and manipulation infer the existence of an interface that combines performer with system, an interface that separates (or intervenes in) the space between performance, intention and history. It is precisely the effect and provided opportunity of the intermediary device on the practice and craft of the actor, that is particularly examined in this work. Defining the scope of current practice for the contemporary actor is a key construct of this challenge with the most appropriate definition revolving around the pursuit of providing a required mixture of performance and content for live, mediated, framed and variously captured formats that exist in the present day. One of these particular formats is Performance Capture which this paper interrogate in more detail.

Corporate governance mechanisms and earnings management in transitional countries – evidence from Chinese listed firms

The objective of this thesis is to investigate whether the corporate governance practices adopted by Chinese listed firms are associated with the quality of earnings information. Based on a review of agency and institutional theory, this study develops hypotheses that predict the monitoring effectiveness of the board and the audit committee. Using a combination of univariate and multivariate analyses, the association between corporate governance mechanisms and earnings management are tested from 2004 to 2008. Through analysing the empirical results, a number of findings are summarised as below. First, board independence is weakened by the introduction of government officials as independent directors on the boards. Government officials acting as independent directors, claim that they meet the definition of independent director set by the regulation. However, they have some connection with the State, which is the controlling shareholder in listed SOEs affiliated companies. Consequently, the effect of the independent director’s expertise in constraining earnings management is mitigated as demonstrated by an insignificant association between board expertise and earnings management. An alternative explanation for the inefficiency of board independence may point to the pre-selection of independent directors by the powerful CEO. It is argued that a CEO can manipulate the board composition and choose the "desirable" independent directors to monitor themselves. Second, a number of internal mechanisms, such as board size, board activities, and the separation of the roles of the CEO and chair are found to be significantly associated with discretionary accruals. This result suggests that there are advantages in having a large and active board in the Chinese setting. This can offset the disadvantages associated with large boards, such as increased bureaucracy, and hence, increase the constraining effects of a large and resourceful board. Third, factor analysis identifies two factors: CEO power and board power. CEO power is the factor which consists of CEO duality and turnover, and board power is composed of board size and board activity. The results of CEO power show that if a Chinese listed company has CEO duality and turnover at the same time, it is more likely to have a high level of earnings management. The significant and negative relationship between board power and accruals indicate that large boards with frequent meetings can be associated with low level of earnings management. Overall, the factor analysis suggests that certain governance mechanisms complement each other to become more efficient monitors of opportunistic earnings management. A combination of board characteristics can increase the negative association with earnings management. Fourth, the insignificant results between audit committees and earnings management in Chinese listed firms suggests that the Chinese regulator should strengthen the audit committee functions. This thesis calls for listed firms to disclose more information on audit committee composition and activities, which can facilitate future research on the Chinese audit committee’s monitoring role. Fifth, the interactive results between State ownership and board characteristics show that dominant State ownership has a moderating effect on board monitoring power as the State totally controls 42% of the issued shares. The high percentage of State ownership makes it difficult for the non-controlling institutional shareholders to challenge the State’s dominant status. As a result, the association between non-controlling institutional ownership and earnings management is insignificant in most situations. Lastly, firms audited by the international Big4 have lower abnormal accruals than firms audited by domestic Chinese audit firms. In addition, the inverse U-shape relationship between audit tenure and earnings quality demonstrates the changing effects of audit quality after a certain period of appointment. Furthermore, this thesis finds that listing in Hong Kong Stock Exchanges can be an alternative governance mechanism to discipline Chinese firms to follow strict Hong Kong listing requirements. Management of Hong Kong listed companies are exposed to the scrutiny of international investors and Hong Kong regulators. This in turn reduces their chances of conducting self-interested earnings manipulation. This study is designed to fill the gap in governance literature in China that is related to earnings management. Previous research on corporate governance mechanisms and earnings management in China is not conclusive. The current research builds on previous literature and provides some meaningful implications for practitioners, regulators, academic, and international investors who have investment interests in a transitional country. The findings of this study contribute to corporate governance and earnings management literature in the context of the transitional economy of China. The use of alternative measures for earnings management yields similar results compared with the accruals models and produces additional findings.

Comparing the medium-term effects of exercise or dietary restriction on appetite regulation and compensatory responses

Previous studies have shown that exercise (Ex) interventions create a stronger coupling between energy intake (EI) and energy expenditure (EE) leading to increased homeostasis of the energy-balance (EB) regulatory system compared to a diet intervention where an un-coupling between EI and EE occurs. The benefits of weight loss from Ex and diet interventions greatly depend on compensatory responses. The present study investigated an 8-week medium-term Ex and diet intervention program (Ex intervention comprised of 500kcal EE five days per week over four weeks at 65-75% maximal heart rate, whereas the diet intervention comprised of a 500kcal decrease in EI five days per week over four weeks) and its effects on compensatory responses and appetite regulation among healthy individuals using a between- and within-subjects design. Effects of an acute dietary manipulation on appetite and compensatory behaviours and whether a diet and/or Ex intervention pre-disposes individuals to disturbances in EB homeostasis were tested. Energy intake at an ad libitum lunch test meal after a breakfast high- and low-energy pre-load (the high energy pre-load contained 556kcal and the low energy pre-load contained 239kcal) were measured at the Baseline (Weeks -4 to 0) and Intervention (Weeks 0 to 4) phases in 13 healthy volunteers (three males and ten females; mean age 35 years [sd + 9] and mean BMI 25 kg/m2 [sd + 3.8]) [participants in each group included Ex=7, diet=5 (one female in the diet group dropped out midway), thus, 12 participants completed the study]. At Weeks -4, 0 and 4, visual analogue scales (VAS) were used to assess hunger and satiety and liking and wanting (L&W) for nutrient and taste preferences using a computer-based system (E-Prime v1.1.4). Ad libitum test meal EI was consistently lower after the HE pre-load compared to the LE pre-load. However, this was not consistent during the diet intervention however. A pre-load x group interaction on ad libitum test meal EI revealed that during the intervention phase the Ex group showed an improved sensitivity to detect the energy content between the two pre-loads and improved compensation for the ad libitum test meal whereas the diet group’s ability to differentiate between the two pre-loads decreased and showed poorer compensation (F[1,10]=2.88, p-value not significant). This study supports previous findings of the effect Ex and diet interventions have on appetite and compensatory responses; Ex increases and diet decreases energy balance sensitivity.

The role of cognitive and visual abilities as predictors in the Multifactorial Model of Driving Safety

Objective The current study evaluated part of the Multifactorial Model of Driving Safety to elucidate the relative importance of cognitive function and a limited range of standard measures of visual function in relation to the Capacity to Drive Safely. Capacity to Drive Safely was operationalized using three validated screening measures for older drivers. These included an adaptation of the well validated Useful Field of View (UFOV) and two newer measures, namely a Hazard Perception Test (HPT), and a Hazard Change Detection Task (HCDT). Method Community dwelling drivers (n = 297) aged 65–96 were assessed using a battery of measures of cognitive and visual function. Results Factor analysis of these predictor variables yielded factors including Executive/Speed, Vision (measured by visual acuity and contrast sensitivity), Spatial, Visual Closure, and Working Memory. Cognitive and Vision factors explained 83–95% of age-related variance in the Capacity to Drive Safely. Spatial and Working Memory were associated with UFOV, HPT and HCDT, Executive/Speed was associated with UFOV and HCDT and Vision was associated with HPT. Conclusion The Capacity to Drive Safely declines with chronological age, and this decline is associated with age-related declines in several higher order cognitive abilities involving manipulation and storage of visuospatial information under speeded conditions. There are also age-independent effects of cognitive function and vision that determine driving safety.

Ocular characteristics of anisometropia

Animal models of refractive error development have demonstrated that visual experience influences ocular growth. In a variety of species, axial anisometropia (i.e. a difference in the length of the two eyes) can be induced through unilateral occlusion, image degradation or optical manipulation. In humans, anisometropia may occur in isolation or in association with amblyopia, strabismus or unilateral pathology. Non-amblyopic myopic anisometropia represents an interesting anomaly of ocular growth, since the two eyes within one visual system have grown to different endpoints. These experiments have investigated a range of biometric, optical and mechanical properties of anisometropic eyes (with and without amblyopia) with the aim of improving our current understanding of asymmetric refractive error development. In the first experiment, the interocular symmetry in 34 non-amblyopic myopic anisometropes (31 Asian, 3 Caucasian) was examined during relaxed accommodation. A high degree of symmetry was observed between the fellow eyes for a range of optical, biometric and biomechanical measurements. When the magnitude of anisometropia exceeded 1.75 D, the more myopic eye was almost always the sighting dominant eye. Further analysis of the optical and biometric properties of the dominant and non-dominant eyes was conducted to determine any related factors but no significant interocular differences were observed with respect to best-corrected visual acuity, corneal or total ocular aberrations during relaxed accommodation. Given the high degree of symmetry observed between the fellow eyes during distance viewing in the first experiment and the strong association previously reported between near work and myopia development, the aim of the second experiment was to investigate the symmetry between the fellow eyes of the same 34 myopic anisometropes following a period of near work. Symmetrical changes in corneal and total ocular aberrations were observed following a short reading task (10 minutes, 2.5 D accommodation demand) which was attributed to the high degree of interocular symmetry for measures of anterior eye morphology, and corneal biomechanics. These changes were related to eyelid shape and position during downward gaze, but gave no clear indication of factors associated with near work that might cause asymmetric eye growth within an individual. Since the influence of near work on eye growth is likely to be most obvious during, rather than following near tasks, in the third experiment the interocular symmetry of the optical and biometric changes was examined during accommodation for 11 myopic anisometropes. The changes in anterior eye biometrics associated with accommodation were again similar between the eyes, resulting in symmetrical changes in the optical characteristics. However, the more myopic eyes exhibited slightly greater amounts of axial elongation during accommodation which may be related to the force exerted by the ciliary muscle. This small asymmetry in axial elongation we observed between the eyes may be due to interocular differences in posterior eye structure, given that the accommodative response was equal between eyes. Using ocular coherence tomography a reduced average choroidal thickness was observed in the more myopic eyes compared to the less myopic eyes of these subjects. The interocular difference in choroidal thickness was correlated with the magnitude of spherical equivalent and axial anisometropia. The symmetry in optics and biometrics between fellow eyes which have undergone significantly different visual development (i.e. anisometropic subjects with amblyopia) is also of interest with respect to refractive error development. In the final experiment the influence of altered visual experience upon corneal and ocular higher-order aberrations was investigated in 21 amblyopic subjects (8 refractive, 11 strabismic and 2 form deprivation). Significant differences in aberrations were observed between the fellow eyes, which varied according to the type of amblyopia. Refractive amblyopes displayed significantly higher levels of 4th order corneal aberrations (spherical aberration and secondary astigmatism) in the amblyopic eye compared to the fellow non-amblyopic eye. Strabismic amblyopes exhibited significantly higher levels of trefoil, a third order aberration, in the amblyopic eye for both corneal and total ocular aberrations. The results of this experiment suggest that asymmetric visual experience during development is associated with asymmetries in higher-order aberrations, proportional to the magnitude of anisometropia and dependent upon the amblyogenic factor. This suggests a direct link between the development of higher-order optical characteristics of the human eye and visual feedback. The results from these experiments have shown that a high degree of symmetry exists between the fellow eyes of non-amblyopic myopic anisometropes for a range of biomechanical, biometric and optical parameters for different levels of accommodation and following near work. While a single specific optical or biomechanical factor that is consistently associated with asymmetric refractive error development has not been identified, the findings from these studies suggest that further research into the association between ocular dominance, choroidal thickness and higher-order aberrations with anisometropia may improve our understanding of refractive error development.

Towards automatic object segmentation with sequential multiple views

Object segmentation is one of the fundamental steps for a number of robotic applications such as manipulation, object detection, and obstacle avoidance. This paper proposes a visual method for incorporating colour and depth information from sequential multiview stereo images to segment objects of interest from complex and cluttered environments. Rather than segmenting objects using information from a single frame in the sequence, we incorporate information from neighbouring views to increase the reliability of the information and improve the overall segmentation result. Specifically, dense depth information of a scene is computed using multiple view stereo. Depths from neighbouring views are reprojected into the reference frame to be segmented compensating for imperfect depth computations for individual frames. The multiple depth layers are then combined with color information from the reference frame to create a Markov random field to model the segmentation problem. Finally, graphcut optimisation is employed to infer pixels belonging to the object to be segmented. The segmentation accuracy is evaluated over images from an outdoor video sequence demonstrating the viability for automatic object segmentation for mobile robots using monocular cameras as a primary sensor.

Experience design and interactive software in music education research

This paper examines the integration of computing technologies into music education research in a way informed by constructivism. In particular, this paper focuses on an approach established by Jeanne Bamberger, which the author also employs, that integrates software design, pedagogical exploration, and the building of music education theory. In this tradition, researchers design software and associated activities to facilitate the interactive manipulation of musical structures and ideas. In short, this approach focuses on designing experiences and tools that support musical thinking and doing. In comparing the work of Jean Bamberger with that of the author, this paper highlights and discusses issues of significance and identifies lessons for future research.