Excessive bone formation in a mouse model of ankylosing spondylitis is associated with decreases in Wnt pathway inhibitors

Introduction: Ankylosing spondylitis (AS) is unique in its pathology where inflammation commences at the entheses before progressing to an osteoproliferative phenotype generating excessive bone formation that can result in joint fusion. The underlying mechanisms of this progression are poorly understood. Recent work has suggested that changes in Wnt signalling, a key bone regulatory pathway, may contribute to joint ankylosis in AS. Using the proteoglycan-induced spondylitis (PGISp) mouse model which displays spondylitis and eventual joint fusion following an initial inflammatory stimulus, we have characterised the structural and molecular changes that underlie disease progression. Methods: PGISp mice were characterised 12 weeks after initiation of inflammation using histology, immunohistochemistry (IHC) and expression profiling. Results: Inflammation initiated at the periphery of the intervertebral discs progressing to disc destruction followed by massively excessive cartilage and bone matrix formation, as demonstrated by toluidine blue staining and IHC for collagen type I and osteocalcin, leading to syndesmophyte formation. Expression levels of DKK1 and SOST, Wnt signalling inhibitors highly expressed in joints, were reduced by 49% and 63% respectively in the spine PGISp compared with control mice (P < 0.05) with SOST inhibition confirmed by IHC. Microarray profiling showed genes involved in inflammation and immune-regulation were altered. Further, a number of genes specifically involved in bone regulation including other members of the Wnt pathway were also dysregulated. Conclusions: This study implicates the Wnt pathway as a likely mediator of the mechanism by which inflammation induces bony ankylosis in spondyloarthritis, raising the potential that therapies targeting this pathway may be effective in preventing this process.

Fracture healing via periosteal callus formation requires macrophages for both initiation and progression of early endochondral ossification

The distribution, phenotype, and requirement of macrophages for fracture-associated inflammation and/or early anabolic progression during endochondral callus formation were investigated. A murine femoral fracture model [internally fixed using a flexible plate (MouseFix)] was used to facilitate reproducible fracture reduction. IHC demonstrated that inflammatory macrophages (F4/80+Mac-2+) were localized with initiating chondrification centers and persisted within granulation tissue at the expanding soft callus front. They were also associated with key events during soft-to-hard callus transition. Resident macrophages (F4/80+Mac-2neg), including osteal macrophages, predominated in the maturing hard callus. Macrophage Fas-induced apoptosis transgenic mice were used to induce macrophage depletion in vivo in the femoral fracture model. Callus formation was completely abolished when macrophage depletion was initiated at the time of surgery and was significantly reduced when depletion was delayed to coincide with initiation of early anabolic phase. Treatment initiating 5 days after fracture with the pro-macrophage cytokine colony stimulating factor-1 significantly enhanced soft callus formation. The data support that inflammatory macrophages were required for initiation of fracture repair, whereas both inflammatory and resident macrophages promoted anabolic mechanisms during endochondral callus formation. Overall, macrophages make substantive and prolonged contributions to fracture healing and can be targeted as a therapeutic approach for enhancing repair mechanisms. Thus, macrophages represent a viable target for the development of pro-anabolic fracture treatments with a potentially broad therapeutic window...

Predictive models for water sources with high susceptibility for bromine-containing disinfection by-product formation: Implications for water treatment

This study examines a matrix of synthetic water samples designed to include conditions that favour brominated disinfection by-product (Br-DBP) formation, in order to provide predictive models suitable for high Br-DBP forming waters such as salinity-impacted waters. Br-DBPs are known to be more toxic than their chlorinated analogues, in general, and their formation may be favoured by routine water treatment practices such as coagulation/flocculation under specific conditions; therefore, circumstances surrounding their formation must be understood. The chosen factors were bromide concentration, mineral alkalinity, bromide to dissolved organic carbon (Br/DOC) ratio and Suwannee River natural organic matter concentration. The relationships between these parameters and DBP formation were evaluated by response surface modelling of data generated using a face-centred central composite experimental design. Predictive models for ten brominated and/or chlorinated DBPs are presented, as well as models for total trihalomethanes (tTHMs) and total dihaloacetonitriles (tDHANs), and bromide substitution factors for the THMs and DHANs classes. The relationships described revealed that increasing alkalinity and increasing Br/DOC ratio were associated with increasing bromination of THMs and DHANs, suggesting that DOC lowering treatment methods that do not also remove bromide such as enhanced coagulation may create optimal conditions for Br-DBP formation in waters in which bromide is present.

Microscopic cooperative traffic flow: Calibration and simulation based on a next generation simulation dataset

The deployment of new emerging technologies, such as cooperative systems, allows the traffic community to foresee relevant improvements in terms of traffic safety and efficiency. Autonomous vehicles are able to share information about the local traffic state in real time, which could result in a better reaction to the mechanism of traffic jam formation. An upstream single-hop radio broadcast network can improve the perception of each cooperative driver within a specific radio range and hence the traffic stability. The impact of vehicle to vehicle cooperation on the onset of traffic congestion is investigated analytically and through simulation. A next generation simulation field dataset is used to calibrate the full velocity difference car-following model, and the MOBIL lane-changing model is implemented. The robustness of the calibration as well as the heterogeneity of the drivers is discussed. Assuming that congestion can be triggered either by the heterogeneity of drivers' behaviours or abnormal lane-changing behaviours, the calibrated car-following model is used to assess the impact of a microscopic cooperative law on egoistic lane-changing behaviours. The cooperative law can help reduce and delay traffic congestion and can have a positive effect on safety indicators.

Linear and weakly nonlinear stability analyses of cooperative car-following models

Stability analyses have been widely used to better understand the mechanism of traffic jam formation. In this paper, we consider the impact of cooperative systems (a.k.a. connected vehicles) on traffic dynamics and, more precisely, on flow stability. Cooperative systems are emerging technologies enabling communication between vehicles and/or with the infrastructure. In a distributed communication framework, equipped vehicles are able to send and receive information to/from other equipped vehicles. Here, the effects of cooperative traffic are modeled through a general bilateral multianticipative car-following law that improves cooperative drivers' perception of their surrounding traffic conditions within a given communication range. Linear stability analyses are performed for a broad class of car-following models. They point out different stability conditions in both multianticipative and nonmultianticipative situations. To better understand what happens in unstable conditions, information on the shock wave structure is studied in the weakly nonlinear regime by the mean of the reductive perturbation method. The shock wave equation is obtained for generic car-following models by deriving the Korteweg de Vries equations. We then derive traffic-state-dependent conditions for the sign of the solitary wave (soliton) amplitude. This analytical result is verified through simulations. Simulation results confirm the validity of the speed estimate. The variation of the soliton amplitude as a function of the communication range is provided. The performed linear and weakly nonlinear analyses help justify the potential benefits of vehicle-integrated communication systems and provide new insights supporting the future implementation of cooperative systems.

Theorising the impacts of digitally mediated social interaction on diasporic identity formation: A case of Chinese diaspora in Australia

With the scope of Chinese diaspora in Australia, this paper theorises the impacts of digitally mediated social interaction on diasporic identity formation in the new media landscape. People’s identity is the outcome of their social interactions with other individuals. In the new media landscape, digital media technologies are changing the way in which people communicate with others. On one hand, space and time are unprecedentedly compressed by media technologies so people can maintain more frequent and instant connections with others than before. On the other hand, the digital media technologies have constructed a virtual social space that might withdraw people from their physical social interactions. As we witness today, our social interactions are increasing digitally mediated, in the forms of posts and comments in social network sites, as well as the messages in social apps. As to the diasporic groups, this new media landscape is presenting a challenge to their identity formation. They physically live in the host countries but still keep close social and cultural connections with their homelands. Facilitated by digital media technologies, they are facing two platforms in which they can practice different identity performances: one is the digitally mediated social network; the other is the physical social network. In the case of Chinese diaspora, the situation is more complex due to the language factor and media censorship in Mainland China, which will be articulated in the main text. This paper aims to fill a gap between media studies and diaspora research. Most of existing research on the relationship between diasporic identity and media primarily focuses on the development of ethnic media institutions, and the production and consumption of ethnic media in the pre-digital media context. However, the process of globalisation and digital media technologies are increasing the homogeneity and hybridity of media content worldwide. In this new context, attributing the formation of different identities to the consumption of media content is arguable to some extent. Therefore, the overlapped area of new media studies and diaspora research still has space deserves further investigation.

Saviour Siblings and the Regulation of Assisted Reproductive Technology: Harm, Ethics and Law

Advances in the field of Assisted Reproductive Technology (ART) have been revolutionary. This book focuses on the use of ARTs in the context of families who seek to conceive a matching sibling donor as a source of tissue to treat an existing sick child. Such children have been referred to as ‘saviour siblings’. Considering the legal and regulatory frameworks that impact on the accessibility of this technology in Australia and the UK, the work analyses the ethical and moral issues that arise from the use of the technology for this specific purpose. The author claims the only justification for limiting a family’s reproductive liberty in this context is where the exercise of reproductive decision-making results in harm to others. It is argued that the harm principle is the underlying feature of legislative action in Western democratic society, and as such, this principle provides the grounds upon which a strong and persuasive argument is made for a less-restrictive regulatory approach in the context of ‘saviour siblings’.

Creating a global law graduate: The need, benefits and practical approaches to internationalise the curriculum

The increasingly integrated world has facilitated important international and trans-border trends, such as a progressively connected global economy, a significant growth in transnational business transactions and an increase in global regulation of global issues. Such globalisation has had a transformational impact on the legal profession in a number of ways. These include the need to provide advice on issues or transactions that have a transnational or international element; the increasing globalisation of large law firms; and the delivery of offshore services by legal service providers. This means that not only do law graduates need to be prepared to practice in an increasingly globalised economy and legal profession, there will also be new career opportunities available to them which require understanding of international law, for example in emerging international institutions and non-government organisations. Accordingly there is a need to ensure that law students develop the knowledge and skills they will require to succeed in a globalised legal profession. That is, there is a need to internationalise the law curriculum. This paper provides an insight into the recent progression of law schools in internationalising the law curriculum and provides practical avenues and strategies for the increased integration of international law, foreign law and a comparative perspective into core subjects which will develop the graduates’ knowledge and skills in international and foreign law, in order to enhance their ability to succeed as legal professionals in a globalised world.

Osteoclast formation from circulating precursors in osteoporosis

Objective: An imbalance between bone formation and bone resorption is thought to underlie the pathogenesis of reduced bone mass in osteoporosis. Bone resorption is carried out by osteoclasts, which are formed from marrow-derived cells that circulate in the monocyte fraction. Ihe aim of this study was to determine the role of osteoclast formation in the pathogenesis of bone loss in osteoporosis. Methods: The proportion of circulating osteoclast precursors and their relative sensitivity to the osteoclastogenic effects of M-CSF, 1,25(OH)2D3 and RANKL were assessed in primary osteoporosis patients and normal controls. Results: Although there was no difference in the number of circulating osteoclast precursors in osteoporosis patients and normal controls, osteoclasts formed from osteoporosis patients exhibited substantially increased resorptive activity relative to normal controls. Although no increased sensitivity to the osteoclastogenic effects of 1,25(OH)2D3 or M-CSF was noted, increased bone resorption was found in osteoporosis peripheral blood mononuclear cell (PBMC) cultures to which these factors were added. Conclusion: Our findings suggest that osteoclast functional activity rather than formation is increased in primary involutional osteoporosis and that dexamethasone acts to increase osteoclast formation.

Australian Media Law [5th Edition]

Australian Media Law details and explains the complex case law, legislation and regulations governing media practice in areas as diverse as journalism, advertising, multimedia and broadcasting. It examines the issues affecting traditional forms of media such as television, radio, film and newspapers as well as for recent forms such as the internet, online forums and digital technology, in a clear and accessible format. New additions to the fifth edition include: - the implications of new anti-terrorism legislation for journalists; - developments in privacy law, including Law Reform recommendations for a statutory cause of action to protect personal privacy in Australia and the expanding privacy jurisprudence in the United Kingdom and New Zealand; - liability for defamation of internet search engines and service providers; - the High Court decision in Roadshow v iiNet and the position of internet service providers in relation to copyright infringement via their services; - new suppression order regimes; - statutory reforms providing journalists with a rebuttable presumption of non-disclosure when called upon to reveal their sources in a court of law; - recent developments regarding whether journalists can use electronic devices to collect and disseminate information about court proceedings; - contempt committed by jurors via social media; and an examination of recent decisions on defamation, confidentiality, vilification, copyright and contempt.

State-formation, teaching techniques, and globalization as aporia

Eleanor Smith [pseudonym], teacher : I was talking to the kids about MacDonalds*/I forget exactly what the context was*/I said ‘‘ah, the Americans call them French fries, and, you know, MacDonalds is an American chain and they call them French fries because the Americans call them French fries’’, and this little Australian kid in the front row, very Australian child, said to me, ‘‘I call them French fries!’’ . . . Um, a fourth grade boy whom I taught in 1993 at this school, the world basketball championships were on . . . Americans were playing their dream machine and the Boomers were up against them . . . and, ah, this boy was very interested in basketball . . . but it’s not in my blood, not in the way cricket is for example . . . Um, Um, and I said to this fellow, ‘‘um, well’’, I said, ‘‘Australia’s up against Dream Machine tomorrow’’. He [Jason, pseudonym] said, ‘‘Ah, you know, Boomers probably won’t win’’. . . . I said, ‘‘Well that’s sport, mate’’. I said, ‘‘You never know in sport. Australia might win’’. And he looked at me and he said, ‘‘I’m not going for Australia, I’m going for America’’. This is from an Australian boy! And I thought so strong is the hype, so strong is the, is the, power of the media, etc., that this boy is not [pause], I can’t tell you how outraged I was. Here’s me as an Australian and I don’t even support basketball, it’s not even my sport, um, but that he would respond like that because of the power of the American machine that’s converting kids’ minds, the way they think, where they’re putting their loyalties, etc. I was just appalled, but that’s where he was. And when I asked kids for their favourite place, he said Los Angeles.

The Role of the Law in Communicating Patient Safety

This chapter considers the role of the law in communicating patient safety. Downie, Lahey, Ford, et al’s (2006) preventing, knowing and responding theoretical framework is adopted to classify the different elements of patient safety law. Rather than setting out all relevant patient safety laws in detail, this chapter highlights key legal strategies which are employed to: prevent the occurrence of patient safety incidents (preventing); support the discovery and open discussion of patient safety incidents when they do occur (knowing),; and guide responses after they occur (responding) (Downie, Lahey, Ford, et al 2006). The law is increasingly being invoked to facilitate open discussion of and communication surrounding patient safety. After highlighting some legal strategies used to communicate patient safety, two practice examples are presented. The practice examples highlight different aspects of patient safety law and are indicative of communication issues commonly faced in practice. The first practice example focuses on the role of the Ccoroner in communicating patient safety. This example highlights the investigative role of the law in relation to patient safety (knowing). It also showcases the preventing responding and preventing elements in respect of the significant number of communication errors that can occur in a multi-disciplinary, networked health system. The main focus of the second practice example is responding example illustrates how the law responds to health service providers’ and professionals’ miscommunication (and subsequent incidents) during treatment, however it also touches upon knowing and preventing.

Phoenix activity: Regulatory challenges and the law

Remedying the mischief of phoenix activity is of practical importance. The benefits include continued confidence in our economy, law that inspires best practice among directors, and law that is articulated in a manner such that penalties act as a sufficient deterrent and the regulatory system is able to detect offenders and bring them to account. Any further reforms must accommodate and tolerate legal phoenix activity. Phoenix activity pushes tolerance of entrepreneurial activity to its absolute limits. The wisest approach would be to front end the reforms so as to alleviate the considerable detection and enforcement burden upon regulatory bodies. There is little doubt that breach of the existing law is difficult and expensive to detect; and this is a significant burden when regulators have shrinking budgets and are rapidly losing feet on the ground. This front end approach may need to include restrictions on access to limited liability. The more limited liability is misused, the stronger the argument to limit access to limited liability. This paper proposes that such an approach is a legitimate next step for a robust and mature capitalist economy.

Community and the Law: A Critical Reassessment of American Liberalism and Japanese Modernity

"This important book translates seven landmark essays by one of Japan’s most respected and influential legal thinkers. While Takao Tanase concedes that law might not matter as much in Japan as it does in the United States, in a provocative challenge to socio-legal researchers and comparative lawyers, he asks: why should it? The issue, he contends, is not whether law matters to society; it is how society matters to law."--Publisher website