Mechanical tension as a driver of connective tissue growth in vitro

We propose the progressive mechanical expansion of cell-derived tissue analogues as a novel, growth-based approach to in vitro tissue engineering. The prevailing approach to producing tissue in vitro is to culture cells in an exogenous “scaffold” that provides a basic structure and mechanical support. This necessarily pre-defines the final size of the implantable material, and specific signals must be provided to stimulate appropriate cell growth, differentiation and matrix formation. In contrast, surgical skin expansion, driven by increments of stretch, produces increasing quantities of tissue without trauma or inflammation. This suggests that connective tissue cells have the innate ability to produce growth in response to elevated tension. We posit that this capacity is maintained in vitro, and that order-of-magnitude growth may be similarly attained in self-assembling cultures of cells and their own extracellular matrix. The hypothesis that growth of connective tissue analogues can be induced by mechanical expansion in vitro may be divided into three components: (1) tension stimulates cell proliferation and extracellular matrix synthesis; (2) the corresponding volume increase will relax the tension imparted by a fixed displacement; (3) the repeated application of static stretch will produce sustained growth and a tissue structure adapted to the tensile loading. Connective tissues exist in a state of residual tension, which is actively maintained by resident cells such as fibroblasts. Studies in vitro and in vivo have demonstrated that cellular survival, reproduction, and matrix synthesis and degradation are regulated by the mechanical environment. Order-of-magnitude increases in both bone and skin volume have been achieved clinically through staged expansion protocols, demonstrating that tension-driven growth can be sustained over prolonged periods. Furthermore, cell-derived tissue analogues have demonstrated mechanically advantageous structural adaptation in response to applied loading. Together, these data suggest that a program of incremental stretch constitutes an appealing way to replicate tissue growth in cell culture, by harnessing the constituent cells’ innate mechanical responsiveness. In addition to offering a platform to study the growth and structural adaptation of connective tissues, tension-driven growth presents a novel approach to in vitro tissue engineering. Because the supporting structure is secreted and organised by the cells themselves, growth is not restricted by a “scaffold” of fixed size. This also minimises potential adverse reactions to exogenous materials upon implantation. Most importantly, we posit that the growth induced by progressive stretch will allow substantial volumes of connective tissue to be produced from relatively small initial cell numbers.

An overview of Australian intrans*igence : a systemic Pandora’s Box

Despite the fact that Australia is a socially progressive country and boasts one of the largest Gender Dysphoria Clinics in the Southern Hemisphere, delivering services for almost four decades, Australian Governments fail to arrive at any consensus on the legal and human rights approaches to Trans*people. The subsequent lack of recognition does little more than increase the levels of frustration of and the continued discrimination to Trans*people, including adverse mental health problems, in this country. The purpose of this presentation is to provide an overview of the Australian systems that govern Trans*people and to identify how Trans*identities are manipulated in our Federal system of government; a system which offers little to protect the human rights of Trans*people. In order to contextualise the Australian situation, I commence with a brief description on the layers of government which will include how Australian Trans*people are currently protected under the law in those jurisdictions. I then present some of the impracticalities endured by the transitioning individual (single or married) including change of documentation and legal gender status before, during and after surgical transition for both those born on and off shore. This presentation will also include discussion of legislation that has been described by Trans*advocates as “Gesture”, “Cart before the Horse” and “Harmful”. I will conclude with a way forward by suggesting the development of a coordinated all of government approach in consultation with key stakeholders for “Trans* Friendly Legislation” to improve the human and legal rights, and ultimately the health and wellbeing of Australian Trans*identities.

Blast response and safety evaluation of a composite column for use as key element in structural systems

This paper presents the blast response, damage mechanism and evaluation of residual load capacity of a concrete–steel composite (CSC) column using dynamic computer simulation techniques. This study is an integral part of a comprehensive research program which investigated the vulnerability of structural framing systems to catastrophic and progressive collapse under blast loading and is intended to provide design information on blast mitigation and safety evaluation of load bearing vulnerable columns that are key elements in a building. The performance of the CSC column is compared with that of a reinforced concrete (RC) column with the same dimensions and steel ratio. Results demonstrate the superior performance of the CSC column, compared to the RC column in terms of residual load carrying capacity, and its potential for use as a key element in structural systems. The procedure and results presented herein can be used in the design and safety evaluation of key elements of multi-storey buildings for mitigating the impact of blast loads.

Making media participatory: Digital storytelling

From journalism to social media, the practices of our professional storytellers continue to evolve and change along with our storytelling institutions and their functions. Comprehending these developments is a key problem of contemporary media and cultural studies. Are the politics of representation giving way to a new progressive politics of self-representation and direct participation? Or, instead, are these new genres of self-representation part of a more general demotic turn in the function of contemporary media? Do media merely mediate or amplify cultural identities, or is media functionality becoming, closer to that of a translator or even an author of identities? How can we know if the changing actor-networks of storytelling contribute to a wider democratisation, a reshaping of the hierarchies of voice and agency? This chapter considers the place of one specific critical participatory media production practice known as 'digital storytelling’ in addressing these larger questions of socio-cultural change.

Antifeminist backlash and critical criminology

The backlash against feminist criminology is intertwined with broader resistance to feminism and other progressive social movements. Carol Smart noted in 1979 that changes in women's social or economic status have long been perceived as threats to the patriarchal gender order and are therefore "viewed with considerable misgiving, whilst any reinforcement of the value of women's traditional, domestic role has been perceived as a stand against further social decline and disorder" (Smart, 1979, p. 50). The contemporary backlash exists at the nexus of economic and ideological retrenchment seeking to enforce the hegemony of neoliberal conceptions of justice as formal equality. Critical criminology is linked to the backlash against feminism in two key ways. First, critical criminology is an important location for the study of antifeminism and its implications. Second, criminologists who study women or gender have frequently been attacked by antifeminist scholars and commentators.

The impacts of FOREX fluctuations on construction business performance : an organisational capabilities perspective

Construction projects are a high risk business activity. When undertaking projects in an international context, it is further complicated by the risk of fluctuations in the foreign exchange rates (FOREX). Construction business performance is affected by these fluctuations. They affect progress and cause delays, which in turn create problems for subcontractors, namely cost overruns, disputes, arbitration, total abandonment and litigation. FOREX fluctuations also cause the price of raw materials to increase, leading the cost overruns. Managing FOREX risk is critical and past research have focused on the need for adequate insurance, careful planning and management, and foreign exchange futures hedging to overcome issues that have been caused by the FOREX risk. Analysis of FOREX risk in international construction business usually focused only on issues at the project level. There is currently lack of understanding of Organisational Capabilities (OC) to manage the impacts of FOREX risk, which when examined, are seen in isolation. This paper attempts to bridge the gap by discussing the impacts of FOREX fluctuations on the international construction business. The focus is on the OC perspective and the need to develop OC framework to mitigate the risk in sustaining construction business performance.

Intrinsics and dynamics of fat grafts : an in vitro study

Background Despite a revived interest in fat grafting procedures, clinicians still fail to demonstrate clearly the in vivo behavior of fat grafts as a dynamic tissue substitute. However, the basic principles in cellular biology teach us that cells can survive and develop, provided that a structural matrix exists that directs their behavior. The purpose of this in vitro study was to analyze that behavior of crude fat grafts, cultured on a three-dimensional laminin-rich matrix. Methods Nonprocessed, human fat biopsy specimens (approximately 1 mm) were inoculated on Matrigel-coated wells to which culture medium was added. The control group consisted of fat biopsy specimens embedded in medium alone. The cellular proliferation pattern was followed over 6 weeks. Additional cultures of primary generated cellular spheroids were performed and eventually subjected to adipogenic differentiation media. Results A progressive outgrowth of fibroblast-like cells from the core fat biopsy specimen was observed in both groups. Within the Matrigel group, an interconnecting three-dimensional network of spindle-shaped cells was established. This new cell colony reproduced spheroids that functioned again as solitary sources of cellular proliferation. Addition of differentiation media resulted in lipid droplet deposition in the majority of generated cells, indicating the initial steps of adipogenic differentiation. Conclusions The authors noticed that crude, nonprocessed fat biopsy specimens do have considerable potential for future tissue engineering-based applications, provided that the basic principles of developmental, cellular biology are respected. Spontaneous in vitro expansion of the stromal cells present in fat grafts within autologous and injectable matrices could create "off-the-shelf" therapies for reconstructive procedures.

The inter-relationships between ovarian-independent growth, tumorigenicity, invasiveness and antioestrogen resistance in the malignant progression of human breast cancer

Among the processes contributing to the progressive acquisition of the highly malignant phenotype in breast cancer are ovarian-independent growth, antioestrogen resistance and increased metastatic potential. We have previously observed that increased invasiveness and development of ovarian-independent growth occur independently. In an attempt to define the inter-relationships between these processes further, we have compared the phenotypes of ovarian-independent, invasive and antioestrogen-resistant sublines of the ovarian-dependent human breast cancer cell line MCF-7. Cells acquiring ovarian-independent growth can retain sensitivity to anti-oestrogens. One clone of MCF-7 cells selected for stable antioestrogen resistance has become non-tumorigenic but its invasive potential remains unaltered. Thus, acquisitions of some characteristics of the progressed phenotype can occur independently. This phenomenon of independent parameters in phenotypic progression could partly explain the considerable intra- and intertumour heterogeneity characteristic of breast tumours.

The Healthy Trends of International Relations Research

As the end of the Cold War approached in 1989, Caroline Thomas argued: “It is important that the discipline [International Relations, IR] should address the issue of disease and more broadly, health, not simply to facilitate containment of disease transmission across international borders but also because central notions of justice, equity, efficiency and order are involved” (1989:273).1 Ten years later, Craig Murphy echoed these sentiments. Murphy (2001: 352) proposed that IR had yet to grapple with the political consequences of growing inequality between the world’s rich and poor, and areas such as health—where these inequalities were most stark—should become the field’s core business. How IR’s theories and methods would approach these issues was less clear. Bettcher and Yach (1998) cautioned that IR would be unable to develop progressive research projects that explored global health diplomacy as a global public good without adopting new perspectives and methods. Others warned that the expansion of security studies into areas such as global health would weaken the intellectual coherency of the field (Walt 1991:213). Taking its cue from the recent Ng and Prah Ruger (2011) study, this paper returns to these concerns to briefly explore key trends and potential future concerns of research in IR on health...

A biomechanical analysis of growing rods used in the management of early onset scoliosis

INTRODUCTION Managing spinal deformities in young children is challenging, particularly early onset scoliosis (EOS). Surgical intervention is often required if EOS has been unresponsive to conservative treatment particularly with rapidly progressive curves. An emerging treatment option for EOS is fusionless scoliosis surgery. Similar to bracing, this surgical option potentially harnesses growth, motion and function of the spine along with correcting spinal deformity. Dual growing rods are one such fusionless treatment, which aims to modulate growth of the vertebrae. The aim of this study was to ascertain the extent to which semiconstrained growing rods (Medtronic, Sofamor, Danek, Memphis, TN) with a telescopic sleeve component, reduce rotational constraint on the spine compared with standard "constrained / rigid" rods and hence potentially provide a more physiological mechanical environment for the growing spine. METHODS Six 40-60kg English Large White porcine spines served as a model for the paediatric human spine. Each spine was dissected into a 7 level thoracolumbar multi-segment unit (MSU), removing all non-ligamentous soft tissues and leaving 3cm of ribs either side. Pure nondestructive axial rotation moments of ±4Nm at a constant rotation rate of 8deg.s-1 were applied to the mounted MSU spines using a biaxial Instron testing machine. Displacement of each vertebral level was captured using a 3D motion tracking system (Optotrak 3020, Northern Digital Inc, Waterloo, ON). Each spine was tested in an un-instrumented state first and then with appropriately sized semi-constrained growing rods and rigid rods in alternating sequence. The rods were secured by multi-axial pedicle screws (Medtronic CD Horizon) at levels 2 and 6 of the construct. The range of motion (ROM), neutral zone (NZ) size and stiffness (Nm.deg-1) were calculated from the Instron load-displacement data and intervertebral ROM was calculated through a MATLAB algorithm from Optotrak data. RESULTS Irrespective of the order of testing, rigid rods significantly reduced the total ROM compared with semi-constrained rods (p<0.05) with in a significantly stiffer spine for both left and right axial rotation (p<0.05). Analysing the intervertebral motion within the instrumented levels 2-6, rigid rods showed reduced ROM compared with semi-constrained growing rods and compared with un-instrumented motion segments. CONCLUSION Semi-constrained growing rods maintain similar stiffness in axial rotation to un-instrumented spines, while dual rigid rods significantly reduce axial rotation. Clinically the effect of semi-constrained growing rods as observed in this study is that they would be expected to allow growth via the telescopic rod components while maintaining the axial flexibility of the spine, which may reduce occurrence of the crankshaft phenomenon.

The stabilising role of the costovertebral joints and spinous processes on thoracic spine stability

Introduction The importance of in vitro biomechanical testing in today’s understanding of spinal pathology and treatment modalities cannot be stressed enough. Different studies have used differing levels of dissection of their spinal segments for their testing protocols[1, 2]. The aim of this study was to assess the impact of removing the costovertebral joints and partial resection of the spinous process sequentially, on the stiffness of the immature thoracic bovine spinal segment. Materials and Methods Thoracic spines from 6-8 week old calves were used. Each spine was dissected and divided into motion segments with 5cm of attached rib on each side and full spinous processes including levels T4-T11 (n=28). They were potted in polymethylemethacrylate. An Instron Biaxial materials testing machine with a custom made jig was used for testing. The segments were tested in flexion/extension, lateral bending and axial rotation at 37⁰C and 100% humidity, using moment control to a maximum 1.75 Nm with a loading rate of 0.3 Nm per second. They were first tested intact for ten load cycles with data collected from the tenth cycle. Progressive dissection was performed by removing first the attached ribs, followed by the spinous process at its base. Biomechanical testing was carried out after each level of dissection using the same protocol. Statistical analysis of the data was performed using repeated measures ANOVA. Results In combined flexion/extension there was a significant reduction in stiffness of 16% (p=0.002). This was mainly after resection of the ribs (14%, p=0.024) and mainly occurred in flexion where stiffness reduced by 22% (p=0.021). In extension, stiffness dropped by 13% (p=0.133). However there was no further significant change in stiffness on resection of the spinous process (<1%) (p=1.00). In lateral bending there was a significant decrease in stiffness of 13% (p<0.001). This comprised a drop of 11% on resection of the ribs (p=0.009) and a further 8% on resection of the spinous process (p=0.014). There was no difference between left and right bending. In axial rotation there was no significant change in stiffness after each stage of dissection (p=0.253). There was no difference between left and right rotation. Conclusion The costovertebral joints play a significant role in providing stability to the bovine thoracic spine in both flexion/extension and lateral bending, whereas the spinous processes play a minor role. Both elements have little effect on axial rotation stability.

Contemporary public spaces in urban knowledge precincts : observations from Brisbane, Australia

The advanced era of knowledge-based urban development has led to an unprecedented increase in mobility of people and the subsequent growth in the new typology of agglomerated enclaves of knowledge such as urban knowledge precincts. A new role has been assigned to contemporary public spaces of these precincts to attract and retain the mobile knowledge workforce for long by creating a sense of place for them. This paper sheds light over the place making in the globalised knowledge economy world which develops a sense of permanence spatio-temporally to knowledge workers displaying a set of particular characteristics and simultaneously is process-dependent getting developed by the internal and external flows and contributing substantially in the development of the broader context it stands in relation with. The paper highlights the observations from Australia’s new world city Brisbane to outline the application of urban design as a tool to create and sustain this bipartite place making in urban knowledge precincts, which caters diverse range of social, cultural and democratic needs. It seeks to analyse the modified permeable typology of public spaces that makes it more viable and adaptive as per the changing needs of the contemporary globalised or in other words knowledge society. This research has taken an overall process-based approach reflecting how urban design is an assemblage of the encompassing processes that underlay the resultant place making. It explores how the permeable design typology of these contemporary precincts in Brisbane develops a progressive sense of place that makes them stimulating, effervescent and vibrant.

Follow the leader if you can, hedge if you must

Follow-the-Leader (FTL) is an intuitive sequential prediction strategy that guarantees constant regret in the stochastic setting, but has poor performance for worst-case data. Other hedging strategies have better worst-case guarantees but may perform much worse than FTL if the data are not maximally adversarial. We introduce the FlipFlop algorithm, which is the first method that provably combines the best of both worlds. As a stepping stone for our analysis, we develop AdaHedge, which is a new way of dynamically tuning the learning rate in Hedge without using the doubling trick. AdaHedge refines a method by Cesa-Bianchi, Mansour, and Stoltz (2007), yielding improved worst-case guarantees. By interleaving AdaHedge and FTL, FlipFlop achieves regret within a constant factor of the FTL regret, without sacrificing AdaHedge’s worst-case guarantees. AdaHedge and FlipFlop do not need to know the range of the losses in advance; moreover, unlike earlier methods, both have the intuitive property that the issued weights are invariant under rescaling and translation of the losses. The losses are also allowed to be negative, in which case they may be interpreted as gains.

Correlates of foot pain severity in adults with hallux valgus : a cross-sectional study

Background Hallux valgus (HV) is highly prevalent and associated with progressive first metatarsophalangeal joint subluxation and osteoarthritis. The link between structural HV deformity and foot pain is unclear. This study investigated possible explanatory factors surrounding foot pain in HV, including radiographic HV angle and signs of joint degeneration. Methods Participants were 60 adults (53 female) with HV aged 20 to 75 years. Participant demographics and a range of radiographic, clinical and functional measures were considered potential correlates of foot pain. Self-reported foot pain (visual analogue scales and a dichotomous definition) was considered the dependent variable. Multivariate modelling was used to determine which characteristics and measures explained pain, with univariate analyses first used to screen potential variables. Results Approximately 20 to 30% of the variance in foot pain associated with HV could be explained by patient characteristics such as poorer general health status, lower educational attainment and increased occupational physical activity levels, in combination with some dynamic physical characteristics such as hallux plantarflexion weakness and reduced force-time integral under the second metatarsal during gait. Neither increasing lateral deviation of the hallux (HV angle) nor presence of first metatarsophalangeal joint osteoarthritis was associated with foot pain. Conclusions This study shows that passive structural factors, including HV angle, do not appear to be significant correlates of foot pain intensity in HV. Our data demonstrate the importance of considering patient characteristics such as general health and physical activity levels when assessing foot pain associated with HV.

iNOS expression and osteocyte apoptosis in idiopathic, non- traumatic osteonecrosis

Background and purpose Non-traumatic osteonecrosis is a progressive disease with multiple etiologies. It affects younger individuals more and more, often leading to total hip arthroplasty. We investigated whether there is a correlation between inducible nitric oxide synthase (iNOS) expression and osteocyte apoptosis in non-traumatic osteonecrosis. Patients and methods We collected and studied 20 human idiopathic, non-traumatic osteonecrosis femoral heads. Subchondral bone samples in the non-sclerotic region (n = 30), collected from osteoarthritis patients, were used as controls. Spontaneously hypertensive rats were used as a model for osteonecrosis in the study. We used scanning electron microscopy, TUNEL assay, and immunohistochemical staining to study osteocyte changes and apoptosis. Results The morphology of osteocytes in the areas close to the necrotic region changed and the number of apoptotic osteocytes increased in comparison with the same region in control groups. The expression of iNOS and cytochrome C in osteocytes increased while Bax expression was not detectable in osteonecrosis samples. Using spontaneously hypertensive rats, we found a positive correlation between iNOS expression and osteocyte apoptosis in the osteonecrotic region. iNOS inhibitor (aminoguanidine) added to the drinking water for 5 weeks reduced the production of iNOS and osteonecrosis compared to a control group without aminoguanidine. Interpretation Our findings show that increased iNOS expression can lead to osteocyte apopotosis in idiopathic, non-traumatic osteonecrosis and that an iNOS inhibitor may prevent the progression of the disease.