Sustained release and osteogenic potential of heparan sulfate-doped fibrin glue scaffolds within a rat cranial model

This paper explores the potential therapeutic role of the naturally occurring sugar heparan sulfate (HS) for the augmentation of bone repair. Scaffolds comprising fibrin glue loaded with 5 lg of embryonically derived HS were assessed, firstly as a release-reservoir, and secondly as a scaffold to stimulate bone regeneration in a critical size rat cranial defect. We show HS-loaded scaffolds have a uniform distribution of HS, which was readily released with a typical burst phase, quickly followed by a prolonged delivery lasting several days. Importantly, the released HS contributed to improved wound healing over a 3-month period as determined by microcomputed tomography (lCT) scanning, histology, histomorphometry, and PCR for osteogenic markers. In all cases, only minimal healing was observed after 1 and 3 months in the absence of HS. In contrast, marked healing was observed by 3 months following HS treatment, with nearly full closure of the defect site. PCR analysis showed significant increases in the gene expression of the osteogenic markers Runx2, alkaline phosphatase, and osteopontin in the heparin sulfate group compared with controls. These results further emphasize the important role HS plays in augmenting wound healing, and its successful delivery in a hydrogel provides a novel alternative to autologous bone graft and growth factorbased therapies.

Modeling and exploiting behavior patterns in dynamic environments

This paper presents a new approach to improving the effectiveness of autonomous systems that deal with dynamic environments. The basis of the approach is to find repeating patterns of behavior in the dynamic elements of the system, and then to use predictions of the repeating elements to better plan goal directed behavior. It is a layered approach involving classifying, modeling, predicting and exploiting. Classifying involves using observations to place the moving elements into previously defined classes. Modeling involves recording features of the behavior on a coarse grained grid. Exploitation is achieved by integrating predictions from the model into the behavior selection module to improve the utility of the robot's actions. This is in contrast to typical approaches that use the model to select between different strategies or plays. Three methods of adaptation to the dynamic features of the environment are explored. The effectiveness of each method is determined using statistical tests over a number of repeated experiments. The work is presented in the context of predicting opponent behavior in the highly dynamic and multi-agent robot soccer domain (RoboCup).

Locking away the mysteries of fair basis : Lockwood v Doric in the High Court

This article updates a previous article on the Lockwood v Doric fair basing case in the Full Court of the Federal Court which was recently appealed to the High Court. The High Court's decision provides a new and welcome level of clarity in this difficult area of patent law. With this new clarity we can finally lock away some of the mysteries that have plagued the area for some time. Already, indications are that Lockwood's guidelines are being usefully applied in the Patent Office and Federal Court.

Interaction and mediation in preadmission clinics : implications for the design of a telehealth stethoscope

A telehealth stethoscope would make it possible for doctors to perform physical examinations on patients at great distances. In order to develop a useful and usable telehealth stethoscope we have conducted fieldwork observations of existing anaesthetic preadmission clinics to understand how stethoscopes are currently used. Both face-to-face consultations and videoconference consultations have been studied. Our results indicate that the stethoscope plays a minor role in the consultation and that consultations are mediated by the administrative work that is the reason for the consultation. We suggest that a stethoscope plays an infrastructural role in the consultation. The implications of considering stethoscopes as infrastructure are explored and considered in the context of a future telehealth stethoscope.

Health law : scope, sources and forces

• For the purposes of this chapter, “health law” encapsulates regulation of the medical and health professions, the administration of health services and the maintenance of public health to the extent that it is connected to the provision of health services. • There are diverging views as to whether health law can be regarded as a discrete “area of law”. • Health law draws on other areas of law such as tort law, criminal law and family law. It is also draws upon other disciplines, most notably medical and health ethics. • Social and economic forces have influenced the development and direction of health law, and these forces may become even more influential as the century develops. • The increasingly globalised world has implications for Australia’s health systems and raises questions and creates commitments in respect of the international community. • Technological developments, including in respect of treatment, diagnosis and information management, create ongoing challenges for health law. • Patient rights, human rights and consumerism are increasingly key drivers in the development of health law. • Health law is significant to contemporary Australian society because of the gravity of the topics that fall within its ambit, its social relevance to so many aspects of human existence and endeavour, the important role it plays in protecting the vulnerable, and the extent to which it engages with fundamental principles of justice.

Physiological investigation of periosteum structure and its application in periosteum tissue engineering

Although many different materials, techniques and methods, including artificial or engineered bone substitutes, have been used to repair various bone defects, the restoration of critical-sized bone defects caused by trauma, surgery or congenital malformation is still a great challenge to orthopedic surgeons. One important fact that has been neglected in the pursuit of resolutions for large bone defect healing is that most physiological bone defect healing needs the periosteum and stripping off the periosteum may result in non-union or non-healed bone defects. Periosteum plays very important roles not only in bone development but also in bone defect healing. The purpose of this project was to construct a functional periosteum in vitro using a single stem cell source and then test its ability to aid the repair of critical-sized bone defect in animal models. This project was designed with three separate but closely-linked parts which in the end led to four independent papers. The first part of this study investigated the structural and cellular features in periostea from diaphyseal and metaphyseal bone surfaces in rats of different ages or with osteoporosis. Histological and immunohistological methods were used in this part of the study. Results revealed that the structure and cell populations in periosteum are both age-related and site-specific. The diaphyseal periosteum showed age-related degeneration, whereas the metaphyseal periosteum is more destructive in older aged rats. The periosteum from osteoporotic bones differs from normal bones both in terms of structure and cell populations. This is especially evident in the cambial layer of the metaphyseal area. Bone resorption appears to be more active in the periosteum from osteoporotic bones, whereas bone formation activity is comparable between the osteoporotic and normal bone. The dysregulation of bone resorption and formation in the periosteum may also be the effect of the interaction between various neural pathways and the cell populations residing within it. One of the most important aspects in periosteum engineering is how to introduce new blood vessels into the engineered periosteum to help form vascularized bone tissues in bone defect areas. The second part of this study was designed to investigate the possibility of differentiating bone marrow stromal cells (BMSCs) into the endothelial cells and using them to construct vascularized periosteum. The endothelial cell differentiation of BMSCs was induced in pro-angiogenic media under both normoxia and CoCl2 (hypoxia-mimicking agent)-induced hypoxia conditions. The VEGF/PEDF expression pattern, endothelial cell specific marker expression, in vitro and in vivo vascularization ability of BMSCs cultured in different situations were assessed. Results revealed that BMSCs most likely cannot be differentiated into endothelial cells through the application of pro-angiogenic growth factors or by culturing under CoCl2-induced hypoxic conditions. However, they may be involved in angiogenesis as regulators under both normoxia and hypoxia conditions. Two major angiogenesis-related growth factors, VEGF (pro-angiogenic) and PEDF (anti-angiogenic) were found to have altered their expressions in accordance with the extracellular environment. BMSCs treated with the hypoxia-mimicking agent CoCl2 expressed more VEGF and less PEDF and enhanced the vascularization of subcutaneous implants in vivo. Based on the findings of the second part, the CoCl2 pre-treated BMSCs were used to construct periosteum, and the in vivo vascularization and osteogenesis of the constructed periosteum were assessed in the third part of this project. The findings of the third part revealed that BMSCs pre-treated with CoCl2 could enhance both ectopic and orthotopic osteogenesis of BMSCs-derived osteoblasts and vascularization at the early osteogenic stage, and the endothelial cells (HUVECs), which were used as positive control, were only capable of promoting osteogenesis after four-weeks. The subcutaneous area of the mouse is most likely inappropriate for assessing new bone formation on collagen scaffolds. This study demonstrated the potential application of CoCl2 pre-treated BMSCs in the tissue engineering not only for periosteum but also bone or other vascularized tissues. In summary, the structure and cell populations in periosteum are age-related, site-specific and closely linked with bone health status. BMSCs as a stem cell source for periosteum engineering are not endothelial cell progenitors but regulators, and CoCl2-treated BMSCs expressed more VEGF and less PEDF. These CoCl2-treated BMSCs enhanced both vascularization and osteogenesis in constructed periosteum transplanted in vivo.

Adaptive instantaneous frequency estimation: Techniques and algorithms

This thesis deals with the problem of the instantaneous frequency (IF) estimation of sinusoidal signals. This topic plays significant role in signal processing and communications. Depending on the type of the signal, two major approaches are considered. For IF estimation of single-tone or digitally-modulated sinusoidal signals (like frequency shift keying signals) the approach of digital phase-locked loops (DPLLs) is considered, and this is Part-I of this thesis. For FM signals the approach of time-frequency analysis is considered, and this is Part-II of the thesis. In part-I we have utilized sinusoidal DPLLs with non-uniform sampling scheme as this type is widely used in communication systems. The digital tanlock loop (DTL) has introduced significant advantages over other existing DPLLs. In the last 10 years many efforts have been made to improve DTL performance. However, this loop and all of its modifications utilizes Hilbert transformer (HT) to produce a signal-independent 90-degree phase-shifted version of the input signal. Hilbert transformer can be realized approximately using a finite impulse response (FIR) digital filter. This realization introduces further complexity in the loop in addition to approximations and frequency limitations on the input signal. We have tried to avoid practical difficulties associated with the conventional tanlock scheme while keeping its advantages. A time-delay is utilized in the tanlock scheme of DTL to produce a signal-dependent phase shift. This gave rise to the time-delay digital tanlock loop (TDTL). Fixed point theorems are used to analyze the behavior of the new loop. As such TDTL combines the two major approaches in DPLLs: the non-linear approach of sinusoidal DPLL based on fixed point analysis, and the linear tanlock approach based on the arctan phase detection. TDTL preserves the main advantages of the DTL despite its reduced structure. An application of TDTL in FSK demodulation is also considered. This idea of replacing HT by a time-delay may be of interest in other signal processing systems. Hence we have analyzed and compared the behaviors of the HT and the time-delay in the presence of additive Gaussian noise. Based on the above analysis, the behavior of the first and second-order TDTLs has been analyzed in additive Gaussian noise. Since DPLLs need time for locking, they are normally not efficient in tracking the continuously changing frequencies of non-stationary signals, i.e. signals with time-varying spectra. Nonstationary signals are of importance in synthetic and real life applications. An example is the frequency-modulated (FM) signals widely used in communication systems. Part-II of this thesis is dedicated for the IF estimation of non-stationary signals. For such signals the classical spectral techniques break down, due to the time-varying nature of their spectra, and more advanced techniques should be utilized. For the purpose of instantaneous frequency estimation of non-stationary signals there are two major approaches: parametric and non-parametric. We chose the non-parametric approach which is based on time-frequency analysis. This approach is computationally less expensive and more effective in dealing with multicomponent signals, which are the main aim of this part of the thesis. A time-frequency distribution (TFD) of a signal is a two-dimensional transformation of the signal to the time-frequency domain. Multicomponent signals can be identified by multiple energy peaks in the time-frequency domain. Many real life and synthetic signals are of multicomponent nature and there is little in the literature concerning IF estimation of such signals. This is why we have concentrated on multicomponent signals in Part-H. An adaptive algorithm for IF estimation using the quadratic time-frequency distributions has been analyzed. A class of time-frequency distributions that are more suitable for this purpose has been proposed. The kernels of this class are time-only or one-dimensional, rather than the time-lag (two-dimensional) kernels. Hence this class has been named as the T -class. If the parameters of these TFDs are properly chosen, they are more efficient than the existing fixed-kernel TFDs in terms of resolution (energy concentration around the IF) and artifacts reduction. The T-distributions has been used in the IF adaptive algorithm and proved to be efficient in tracking rapidly changing frequencies. They also enables direct amplitude estimation for the components of a multicomponent

Marginalising the mainstream : a signed performance of The Miracle Worker places deaf issues centre-stage

William Gibson’s The Miracle Worker was staged at the Brisbane Powerhouse June 2009 by Crossbow Productions. In this adaption, people with hearing impairment were privileged through the use of shadow-signing, unscripted signing and the appropriation of signing as a theatrical language in itself. 250 people living with hearing impairment attended the production, 70 had never attended a theatrical event before. During the post-performance discussions hearing audience members expressed feelings of displacement through experiencing the culture of the deaf society and not grasping some of the ideas. This paper argues that this inversion enhanced meaning making for all and illustrates a way forward to encourage the signing of more theatrical events.

The naked audience : audience performance at a recent staging of Gibson’s "the Miracle Worker"

Contemporary mainstream theatre audiences observe etiquette strictures that regulate behaviour. As Baz Kershaw argues, “the idea of the passive audience for performance has been associated usually with mainstream theatre.” This paper explores a mainstream event where the extant contract of audience silence was replaced with a raw, emotional audience response that continued into the post-performance discussion. William Gibson’s The Miracle Worker was performed by Crossbow Productions at the Brisbane Powerhouse to an audience made up of mainstream theatre patrons and people living with hearing and visual impairment. Various elements such as shadow signing and tactile tours worked metatheatrically and self-referentially to heighten audience awareness. During the performances the verbal and non-verbal responses of the audience were so pervasive that the audience became not only co-creators of the performance text but performers of a rich audience text that had a dramatic impact on the theatrical experience for audience and actors alike. During the post-performance discussion the audience performers spilled onto the stage interacting with the actors, extending the pleasure of the experience. This paper discusses how in privileging the audience as co-creators and performers, the chasm between stage and audience was bridged. The audiences’ performance changed, enriched and created new meanings for each performance.

In vivo knockdown of the androgen receptor results in growth inhibition and regression of well-established, castration-resistant prostate tumours

Purpose: Progression to the castration-resistant state is the incurable and lethal end stage of prostate cancer, and there is strong evidence that androgen receptor (AR) still plays a central role in this process. We hypothesize that knocking down AR will have a major effect on inhibiting growth of castration-resistant tumors. Experimental Design: Castration-resistant C4-2 human prostate cancer cells stably expressing a tetracycline-inducible AR-targeted short hairpin RNA (shRNA) were generated to directly test the effects of AR knockdown in C4-2 human prostate cancer cells and tumors. Results:In vitro expression of AR shRNA resulted in decreased levels of AR mRNA and protein, decreased expression of prostate-specific antigen (PSA), reduced activation of the PSA-luciferase reporter, and growth inhibition of C4-2 cells. Gene microarray analyses revealed that AR knockdown under hormone-deprived conditions resulted in activation of genes involved in apoptosis, cell cycle regulation, protein synthesis, and tumorigenesis. To ensure that tumors were truly castration-resistant in vivo, inducible AR shRNA expressing C4-2 tumors were grown in castrated mice to an average volume of 450 mm3. In all of the animals, serum PSA decreased, and in 50% of them, there was complete tumor regression and disappearance of serum PSA. Conclusions: Whereas castration is ineffective in castration-resistant prostate tumors, knockdown of AR can decrease serum PSA, inhibit tumor growth, and frequently cause tumor regression. This study is the first direct evidence that knockdown of AR is a viable therapeutic strategy for treatment of prostate tumors that have already progressed to the castration-resistant state.

The miracle worker

Helen Keller’s fight to speak, to understand, to love aided by her teacher Annie Sullivan was nothing short of a miracle. This is her story. Crossbow Productions staged six performances of The Miracle Worker at the Brisbane Powerhouse in June 2009 to raise awareness of people living with disabilities. The play was shadow signed for the hearing impaired and tactile tours of the set were held before each performance for the vision impaired. Over 200 hearing and vision impaired attended and 70 of these had never been to the theatre before. I’m deaf and we should be able to go to anything, and you’ve done that for us. As a blind person, I got a great deal from it. I found it extremely moving. There should be a thousand or so in the audience rather than a hundred so that everyone can experience it.

Talking the talk and walking the walk : how managers can influence the quality of work-life balance in a construction project

Purpose – The construction industry in Australia is characterised by a long work-hours culture, with conditions that make it difficult for staff to balance their work and non-work lives. The objective of this paper is to measure the success of a work-place intervention designed to improve work-life balance (WLB) in an alliance project in the construction industry, and the role the project manager plays in this success. Design/methodology/approach – The paper focuses on an alliance case study. Interviews were conducted at two points in time, several months apart, after the interventions were implemented. Findings – Results showed that staff on the whole were more satisfied with their work experience after the interventions, and indicated the important role that managers' attitudes and behaviours played. Originality/value – Managerial support for work-life initiatives is a critical element in achieving WLB and satisfaction with working arrangements. The fact that the manager “talked the talk and walked the walk” was a major contributing success factor, which has not previously been demonstrated.

Migration of breast cancer cells : understanding the roles of volume exclusion and cell-to-cell adhesion

We study MCF-7 breast cancer cell movement in a transwell apparatus. Various experimental conditions lead to a variety of monotone and nonmonotone responses which are difficult to interpret. We anticipate that the experimental results could be caused by cell-to-cell adhesion or volume exclusion. Without any modeling, it is impossible to understand the relative roles played by these two mechanisms. A lattice-based exclusion process random-walk model incorporating agent-to-agent adhesion is applied to the experimental system. Our combined experimental and modeling approach shows that a low value of cell-to-cell adhesion strength provides the best explanation of the experimental data suggesting that volume exclusion plays a more important role than cell-to-cell adhesion. This combined experimental and modeling study gives insight into the cell-level details and design of transwell assays.

The play's the thing? : Hamlet, Slings & Arrows, and the authority of theatrical consumption

This paper reads season 1 of the critically-acclaimed Canadian television series “Slings & Arrows” (2003). This six-episode series is set in a fictionalised version of the Stratford Festival, and tells the story of a plagued production of Shakespeare’s Hamlet. It follows the play’s rehearsal after the death of the festival’s artistic director; Geoffrey Tennant (himself a plagued Hamlet) takes over the role of director, and must face his past in order to produce a Hamlet that will save the festival, redeem his reputation, and repair his interpersonal relationships. Drawing on popular and theatrical understandings of Shakespeare’s play, the series negotiates tropes of metatheatre, filiality, cultural production and consumption, in order to demonstrate the ongoing relevance and legitimacy of “Shakespeare” in the twenty-first century. The “Slings & Arrows” narrative revolves around the doubled-plot of Hamlet and the experiences of the company mounting Hamlet. In quite obvious ways, the show thus thematises ways in which Shakespeare can be used to read one’s own life and world. In the broader sense, however, the show also offers theatre/performance as a catalyst for affect. In doing so, the show functions as a relatively straight adaptation of Hamlet, and a metatheatrical/metafictional commentary on the functions of Hamlet within contemporary culture. In Shakespeare’s play, the production of “The Mouse-Trap” proves, both to Hamlet and the audience, the legitimacy of the ghost’s claims. Similarly, in “Slings & Arrows”, the successful performance of Hamlet legitimises Geoffrey’s position as artistic director of the festival, and affirms for the viewer the value of Shakespearean production in contemporary culture. In each text, theatre/performance enables and legitimises a son carrying out a dead father’s wishes in order to restore or reproduce socio-cultural order. The metatheatrics of these gestures engage the reader/viewer in a self-reflexive process whereby the ‘value’ of theatre is thematised and performed, and the consumer is positioned as the arbiter and agent of that value: complicit in its production even as they are the site of its consumption.