Polycaprolactone-based scaffold plus recombinant human bone morphogenetic protein (rhBMP-2) in an ovine model of anterior spinal fusion

Synthetic scaffolds combined with growth factors have the potential to replace allograft or autograft as a graft material for spinal interbody fusion. Such tissue engineering approaches may be useful in Adolescent Idiopathic Scoliosis (AIS) surgery, however there are no studies to date examining the use of such biodegradable implants in combination with biologics in a thoracic spine model. This in vivo study examines the use of biodegradable polycaprolactone (PCL) based scaffolds with rhBMP-2 as a bone graft substitute in a sheep thoracic fusion model, where an anterior approach is used to simulate minimally invasive surgical deformity correction in the setting of AIS.

Bayesian experimental design for models with intractable likelihoods

In this paper we present a methodology for designing experiments for efficiently estimating the parameters of models with computationally intractable likelihoods. The approach combines a commonly used methodology for robust experimental design, based on Markov chain Monte Carlo sampling, with approximate Bayesian computation (ABC) to ensure that no likelihood evaluations are required. The utility function considered for precise parameter estimation is based upon the precision of the ABC posterior distribution, which we form efficiently via the ABC rejection algorithm based on pre-computed model simulations. Our focus is on stochastic models and, in particular, we investigate the methodology for Markov process models of epidemics and macroparasite population evolution. The macroparasite example involves a multivariate process and we assess the loss of information from not observing all variables.

Compass points : the locations, landscapes and coordinates of identities in contemporary performance making : proceedings of the Australasian Association for Theatre, Drama & Performance Studies (ADSA) Conference 2012

Compass Points: The Locations, Landscapes and Coordinates of Identities' the Australasian Association for Theatre, Drama and Performance Studies (ADSA) Conference 2012 was held at Queensland University of Technology, July 3-6 2012. The Conference was sponsored by the Australasian Association for Theatre, Drama and Performance Studies (ADSA), Queensland University of Technology (QUT), Ian Potter Foundation, Arts Queensland, La Boite Theatre Company and Queensland Theatre Company. The papers selected for this collection represent a small sample of the scope, depth and diversity of scholarship presented at the conference - they cover a range of genres, cultures and contexts in contemporary performance making from autobiography, to playwrighting, to public space performance and beyond. The papers collected have been peer-reviewed to Australia’s Department of Education, Science and Training (DEST) standards - each has been subject to two blind reviews, followed by acceptance, rejection or revision, and editing of accepted papers - by colleagues from Australasia and overseas. The review process for the conference publication was separate from the review process for acceptance of abstracts for the actual conference presentations. The conference convenors, Bree Hadley and Caroline Heim, edited the collection, and would like to thank all those who gave their time to advise on the peer review process and act as reviewers - Tom Burvill, Christine Comans, Sean Edgecomb, Angela Campbell, Natalie Lazaroo, Jo Loth, Meg Mumford, Ulrike Garde, Laura Ginters, Andre Bastian, Sam Trubridge, Delyse Ryan, Georgia Seffrin, Gillian Arrighi, Rand Hazou, Rob Pensalfini, Sue Fenty-Studham, Mark Radvan, Rob Conkie, Kris Plummer, Lisa Warrington, Kate Flaherty, Bryoni Tresize, Janys Hayes, Lisa Warrington, Teresa Izzard, Kim Durban, Veronica Kelly, Adrian Keirnander, James Davenport, Julie Robson and others. We, and the authors, appreciate the rigour and care with which peers have approached the scholarship presented here. This collection was published in final form on July 3rd 2012, the first day of the ADSA Conference 2012.

Cartilage regeneration using zonal chondrocyte subpopulations : a promising approach or an overcomplicated strategy?

Cartilage defects heal imperfectly and osteoarthritic changes develop frequently as a result. Although the existence of specific behaviours of chondrocytes derived from various depth-related zones in vitro has been known for over 20 years, only a relatively small body of in vitro studies has been performed with zonal chondrocytes and current clinical treatment strategies do not reflect these native depth-dependent (zonal) differences. This is surprising since mimicking the zonal organization of articular cartilage in neo-tissue by the use of zonal chondrocyte subpopulations could enhance the functionality of the graft. Although some research groups including our own have made considerable progress in tailoring culture conditions using specific growth factors and biomechanical loading protocols, we conclude that an optimal regime has not yet been determined. Other unmet challenges include the lack of specific zonal cell sorting protocols and limited amounts of cells harvested per zone. As a result, the engineering of functional tissue has not yet been realized and no long-term in vivo studies using zonal chondrocytes have been described. This paper critically reviews the research performed to date and outlines our view of the potential future significance of zonal chondrocyte populations in regenerative approaches for the treatment of cartilage defects. Secondly, we briefly discuss the capabilities of additive manufacturing technologies that can not only create patient-specific grafts directly from medical imaging data sets but could also more accurately reproduce the complex 3D zonal extracellular matrix architecture using techniques such as hydrogel-based cell printing.

A history of heart interventions moderates the relationship between psychological variables and the presence of chest pain in older women with self-reported coronary heart disease

Objectives: This study examines the hypothesis that a past history of heart interventions will moderate the relationship between psychosocial factors (stressful life events, social support, perceived stress, having a current partner, having a past diagnosis of depression or anxiety over the past 3 years, time pressure, education level, and the mental health index) and the presence of chest pain in a sample of older women. Design: Longitudinal survey over a 3-year period. Methods: The sample was taken from a prospective cohort study of 10,432 women initially aged between 70 and 75 years, who were surveyed in 1996 and then again in 1999. Two groups of women were identified: those reporting to have heart disease but no past history of heart interventions (i.e., coronary artery bypass graft/angioplasty) and those reporting to have heart disease with a past history of heart interventions. Results: Binary logistic regression analysis was used to show that for the women with self-reported coronary heart disease but without a past history of heart intervention, feelings of time pressure as well as the number of stressful life events experienced in the 12 months prior to 1996 were independent risk factors for the presence of chest pain, even after accounting for a range of traditional risk factors. In comparison, for the women with self-reported coronary heart disease who did report a past history of heart interventions, a diagnosis of depression in the previous 3 years was the significant independent risk factor for chest pain even after accounting for traditional risk factors. Conclusion: The results indicate that it is important to consider a history of heart interventions as a moderator of the associations between psychosocial variables and the frequency of chest pain in older women. Statement of Contribution: What is already known on this subject? Psychological factors have been shown to be independent predictors of a range of health outcomes in individuals with coronary heart disease, including the presence of chest pain. Most research has been conducted with men or with small samples of women; however, the evidence does suggest that these relationships exist in women as well as in men. What does this study add? Most studies have looked at overall relationships between psychological variables and health outcomes. The few studies that have looked at moderators have mainly examined gender as a moderator. To our knowledge, this is the first published study to examine a history of heart interventions as a moderator of the relationship between psychological variables and the presence of chest pain.

Extending the explanatory utility of the EPPM beyond fear-based persuasion

In the 20 years since its inception, the EPPM has attracted much empirical support. Currently, and unsurprisingly given that is a model of fear-based persuasion, the EPPM’s explanatory utility has been based only upon fear-based messages. However, an argument is put forth herein, which draws upon existing evidence, that the EPPM may be an efficacious framework for explaining the persuasive process and outcomes of emotion-based messages more broadly when such messages are addressing serious health topics. For the current study, four different types of emotional appeals were purposefully devised and included a fear, an annoyance/agitation, a pride, and a humour-based message. All messages addressed the serious health issue of road safety, and in particular the risky behaviour of speeding. Participants (N = 551) were exposed to only one of the four messages and subsequently provided responses within a survey. A series of 2 (threat: low, high) x 2 (efficacy: low, high) analysis of variance was conducted for each of the appeals based on the EPPM’s message outcomes of acceptance and rejection. Support was found for the EPPM with a number of main effects of threat and efficacy emerging, reflecting that, irrespective of emotional appeal type, high levels of threat and efficacy enhanced message outcomes via maximising acceptance and minimising rejection. Theoretically, the findings provide support for the explanatory utility of the EPPM for emotion-based health messages more broadly. In an applied sense, the findings highlight the value of adopting the EPPM as a framework when devising and evaluating emotion-based health messages for serious health topics.

‘My people right here…’ Indigenous young people, alienation and paint sniffing in inner Brisbane

This paper describes and explains the social worlds of a group of young Murris who are engaged in chroming (paint sniffing) and who sleep rough in inner Brisbane. In particular, the paper considers the ways young Indigenous drug users describe their marginalisation from wider society and its structures of opportunity, but it also includes some reflections from their youth worker and a young man who frequents the young people’s squat. The paper demonstrates the centrality of racism and material disadvantage to the experience of a group of young Aboriginal and Torres Strait Islander sniffers, a perspective largely unreflected in the literature on Indigenous volatile substance misuse. Further, the young people’s ways of interacting with the broader society are described to explain the ways their rejection of mainstream norms form a significant political response to their marginality and reflect, at least in part, the wider Indigenous historical experience. The work draws on theories of alienation and subculture to analyse the young people’s descriptions of their social estrangement and the formation of the ‘paint sniffer group’. It is concluded that paint sniffing among urban Indigenous youth is, at least in part, an obnoxious and encoded distillation of a wider Indigenous rebuttal of broader societal norms, and that the dominant — normalising — modes of treatment risk further alienating an already oppositional group of young people.

Polycaprolactone-based scaffold plus recombinant human bone morphogenic protein rhBMP-2) in a sheep thoracic spine fusion model

Adolescent idiopathic scoliosis is a complex three dimensional deformity affecting 2-3% of the general population. The resulting spinal deformity consists of coronal curvature, hypokyphosis of the thoracic spine and vertebral rotation in the axial plane with posterior elements turned into the curve concavity. The potential for curve progression is heightened during the adolescent growth spurt. Success of scoliosis deformity correction depends on solid bony fusion between adjacent vertebrae after the intervertebral (IV) discs have been surgically cleared and the disc spaces filled with graft material. Recently a bioactive and resorbable scaffold fabricated from medical grade polycaprolactone has been developed for bone regeneration at load bearing sites. Combined with rhBMP-2, this has been shown to be successful in acting as a bone graft substitute in a porcine lumbar interbody fusion model when compared to autologous bone graft alone. The study aimed to establish a large animal thoracic spine interbody fusion model, develop spine biodegradable scaffolds (PCL) in combination with biologics (rhBMP-2) and to establish a platform for research into spine tissue engineering constructs. Preliminary results demonstrate higher grades of radiologically evident bony fusion across all levels when comparing fusion scores between the 3 and 6 month postop groups at the PCL CaP coated scaffold level, which is observed to be a similar grade to autograft, while no fusion is seen at the scaffold only level. Results to date suggest that the combination of rhBMP-2 and scaffold engineering actively promotes bone formation, laying the basis of a viable tissue engineered constructs.

Biomechanical performance of polycaprolactone (PCL)-based scaffold with rhBMP-2 in a sheep thoracic spine fusion model

Adolescent idiopathic scoliosis is a complex three dimensional deformity affecting 2-3% of the general population. Resulting spine deformities include progressive coronal curvature, hypokyphosis, or frank lordosis in the thoracic spine and vertebral rotation in the axial plane with posterior elements turned into the curve concavity. The potential for curve progression is heightened during the adolescent growth spurt. Success of scoliosis deformity correction depends on solid bony fusion between adjacent vertebrae after the intervertebral discs have been surgically cleared and the disc spaces filled with graft material. Problems with bone graft harvest site morbidity as well as limited bone availability have led to the search for bone graft substitutes. Recently, a bioactive and resorbable scaffold fabricated from medical grade polycaprolactone (PCL) has been developed for bone regeneration at load bearing sites. Combined with recombinant human bone morphogenic protein–2 (rhBMP-2), this has been shown to be successful in acting as a bone graft substitute in acting as a bone graft substitute in a porcine lumbar interbody fusion model when compared to autologous bone graft. This in vivo sheep study intends to evaluate the suitability of a custom designed medical grade PCL scaffold in combination with rhBMP-2 as a bone graft substitute in the setting of mini–thoracotomy surgery as a platform for ongoing research to benefit patients with adolescent idiopathic scoliosis.

Advanced Bioactive Inorganic Materials for Bone Regeneration and Drug Delivery

Bioceramics play an important role in repairing and regenerating bone defects. Annually, more than 500,000 bone graft procedures are performed in the United states and approximately 2.2 million are conducted worldwide. The estimated cost of these procedures approaches $2.5billion per year. Around 60% of the bone graft substitutes available on the market involve bioceramics. It is reported that bioceramics in the world market increase by 9% per year. For this reason, the research of bioceramics has been one of the most active areas during, the past several years. Considering the significant importance of bioceramics, our goal was to compile this book to review the latest research advances in the field of bioceramics. The text also summarizes our work during the past 10 years in an effort to share innovative concepts, design of bioceramisc, and methods for material synthesis and drug delivery. We anticipate that this text will provide some useful information and guidance in the bioceramics field for biomedical engineering researchers and material scientists. Information on novel mesoporous bioactive glasses and silicate-based ceramics for bone regeneration and drug delivery are presented. Mesoporous bioactive glasses have shown multifunctional characteristics of bone regeneration and drug delivery due to their special mesopore structures,whereas silicated-based bioceramics, as typical third-generation biomaterials,possess significant osteostimulation properties. Silica nanospheres with a core-shell structure and specific properties for controllable drug delivery have been carefully reviewed-a variety of advanced synthetic strategies have been developed to construct functional mesoporous silica nanoparticles with a core-shell structure, including hollow, magnetic, or luminescent, and other multifunctional core-shell mesoporous silica nanoparticles. In addition, multifunctional drug delivery systems based on these nanoparticles have been designed and optimized to deliver the drugs into the targeted organs or cells,with a controllable release fashioned by virtue of various internal and external triggers. The novel 3D-printing technique to prepare advanced bioceramic scaffolds for bone tissue engineering applications has been highlighted, including the preparation, mechanical strength, and biological properties of 3D-printed porous scaffolds of calcium phosphate cement and silicate bioceramics. Three-dimensional printing techniques offer improved large-pore structure and mechanical strength. In addition , biomimetic preparation and controllable crystal growth as well as biomineralization of bioceramics are summarized, showing the latest research progress in this area. Finally, inorganic and organic composite materials are reviewed for bone regeneration and gene delivery. Bioactive inorganic and organic composite materials offer unique biological, electrical, and mechanical properties for designing excellent bone regeneration or gene delivery systems. It is our sincere hope that this book will updated the reader as to the research progress of bioceramics and their applications in bone repair and regeneration. It will be the best reward to all the contributors of this book if their efforts herein in some way help reader in any part of their study, research, and career development.

World's pre-eminent powers recent treatment to international law : a paradigm of interest served or harmed

The US's recent rejection of some international laws may have been done to ensure American interests but it may have the opposite effects. While its recent rejection of some international legal arrangements has meant an unpopular opinion of America, its interest has been served.

Narrative review of changing medical and feminist perspectives on menopause : from femininity and ageing to risk and choice

Meanings and descriptions of menopause have shifted focus over the past century and a half; more particularly the past sixty years has seen a shift from descriptions of hormone decline and its relation to ageing, femininity and symptoms of menopause since the 1960's to the possibility for preventive medicine afforded by menopause. Medicine is not a static field in its construction of menopause. It has changed, not least by its engagement (positively or negatively) with critique from both within (epidemiological) and without (feminist and social sciences). In this review we identify three recent changes: (1) Increasing concern with women's decision-making. (2) The emergence from within medicine of the rejection of the use of language which defines menopause as a condition of deficiency. (3) New insights from postmodern and poststructural analyses of menopause that examine the epistemological foundations of medical and feminist concepts of menopause and contest fixed descriptions of the experience of menopause. Key aspects of a ‘medical menopause’ nevertheless remain constant: menopause is a loss of hormones that results in predictable effects and risks and may be ameliorated by hormone replacement therapy. A question therefore emerges about how and to what effect medical practitioners have engaged with critiques of the medical menopause?

Conservatism, disclosure and the cost of equity capital

This study seeks insights into the economic consequences of accounting conservatism by examining the relation between conservatism and cost of equity capital. Appealing to the analytical and empirical literatures, we posit an inverse relation. Importantly, we also posit that the strength of the relation is conditional on the firm’s information environment, being the strongest for firms with high information asymmetry and the weakest (potentially negligible) for firms with low information asymmetry. Based on a sample of US-listed entities, we find, as predicted, an inverse relation between conservatism and the cost of equity capital, but further, that this relation is diminished for firms with low information asymmetry environments. This evidence indicates that there are economic benefits associated with the adoption of conservative reporting practices and leads us to conclude that conservatism has a positive role in accounting principles and practices, despite its increasing rejection by accounting standard setters.

Humanised xenograft models of bone metastasis revisited : novel insights into species-specific mechanisms of cancer cell osteotropism

The determinants and key mechanisms of cancer cell osteotropism have not been identified, mainly due to the lack of reproducible animal models representing the biological, genetic and clinical features seen in humans. An ideal model should be capable of recapitulating as many steps of the metastatic cascade as possible, thus facilitating the development of prognostic markers and novel therapeutic strategies. Most animal models of bone metastasis still have to be derived experimentally as most syngeneic and transgeneic approaches do not provide a robust skeletal phenotype and do not recapitulate the biological processes seen in humans. The xenotransplantation of human cancer cells or tumour tissue into immunocompromised murine hosts provides the possibility to simulate early and late stages of the human disease. Human bone or tissue-engineered human bone constructs can be implanted into the animal to recapitulate more subtle, species-specific aspects of the mutual interaction between human cancer cells and the human bone microenvironment. Moreover, the replication of the entire "organ" bone makes it possible to analyse the interaction between cancer cells and the haematopoietic niche and to confer at least a partial human immunity to the murine host. This process of humanisation is facilitated by novel immunocompromised mouse strains that allow a high engraftment rate of human cells or tissue. These humanised xenograft models provide an important research tool to study human biological processes of bone metastasis.

Establishment and characterisation of an open mini-thoracotomy surgical approach to an ovine thoracic spine fusion model

Background A large animal model is required for assessment of minimally invasive, tissue engineering based approaches to thoracic spine fusion, with relevance to deformity correction surgery for human adolescent idiopathic scoliosis. Here we develop a novel open mini–thoracotomy approach in an ovine model of thoracic interbody fusion which allows assessment of various fusion constructs, with a focus on novel, tissue engineering based interventions. Methods The open mini-thoracotomy surgical approach was developed through a series of mock surgeries, and then applied in a live sheep study. Customized scaffolds were manufactured to conform with intervertebral disc space clearances required of the study. Twelve male Merino sheep aged 4 to 6 years and weighing 35 – 45 kg underwent the abovementioned procedure and were divided into two groups of six sheep at survival timelines of 6 and 12 months. Each sheep underwent a 3-level discectomy (T6/7, T8/9 and T10/11) with randomly allocated implantation of a different graft substitute at each of the three levels; (i) polycaprolactone (PCL) based scaffold plus 0.54μg rhBMP-2, (ii) PCL-based scaffold alone or (iii) autograft. The sheep were closely monitored post- operatively for signs of pain (i.e. gait abnormalities/ teeth gnawing/ social isolation). Fusion assessments were conducted post-sacrifice using Computed Tomography and hard-tissue histology. All scientific work was undertaken in accordance with the study protocol has been approved by the Institute's committee on animal research. Results. All twelve sheep were successfully operated on and reached the allotted survival timelines, thereby demonstrating the feasibility of the surgical procedure and post-operative care. There were no significant complications and during the post-operative period the animals did not exhibit marked signs of distress according to the described assessment criteria. Computed Tomographic scanning demonstrated higher fusion grades in the rhBMP-2 plus PCL-based scaffold group in comparison to either PCL-based scaffold alone or autograft. These results were supported by histological evaluation of the respective groups. Conclusion. This novel open mini-thoracotomy surgical approach to the ovine thoracic spine represents a safe surgical method which can reproducibly form the platform for research into various spine tissue engineered constructs (TEC) and their fusion promoting properties.