Molecular evolutionary dynamics of Ross River virus and implications for vaccine efficacy

Ross River virus (RRV) is a mosquito-borne member of the genus Alphavirus that causes epidemic polyarthritis in humans, costing the Australian health system at least US$10 million annually. Recent progress in RRV vaccine development requires accurate assessment of RRV genetic diversity and evolution, particularly as they may affect the utility of future vaccination. In this study, we provide novel RRV genome sequences and investigate the evolutionary dynamics of RRV from time-structured E2 gene datasets. Our analysis indicates that, although RRV evolves at a similar rate to other alphaviruses (mean evolutionary rate of approx. 8x10(-4) nucleotide substitutions per site year(-1)), the relative genetic diversity of RRV has been continuously low through time, possibly as a result of purifying selection imposed by replication in a wide range of natural host and vector species. Together, these findings suggest that vaccination against RRV is unlikely to result in the rapid antigenic evolution that could compromise the future efficacy of current RRV vaccines.

Mental harm, rescuers and the Civil Liability Act 2002 (NSW)

At common law, a duty of care may be owed to a claimant who suffers nervous shock or pure mental harm due to witnessing, or hearing about, physical injury caused to another due to a defendant’s negligence. “Pure mental harm” is the ‘impairment of a person’s mental condition’ that is not suffered as a consequence of any other kind of personal injury to them. However, as many accidents have the potential to create a wide circle of mental suffering to bystanders, family members or others not physically injured themselves, it has traditionally been ‘thought impolitic that everybody so affected should be able to recover damages from the tortfeasor.’ ‘To allow such extended recovery would stretch liability too far.’ Nevertheless, whilst adopting a restrictive approach to liability, the common law courts have recognised that a defendant might owe a duty in relation to the pure mental harm suffered by one who foreseeably attends an accident scene to rescue another from a situation created by the defendant’s negligence.

Standardisation and patent ambush : potential liability under Australian competition law

This article examines the problem of patent ambush in standard setting, where patent owners are sometimes able to capture industry standards in order to secure monopoly power and windfall profits. Because standardisation generally introduces high switching costs, patent ambush can impose significant costs on downstream manufacturers and consumers and drastically reduce the efficiency gains of standardisation.This article considers how Australian competition law is likely to apply to patent ambush both in the development of a standard (through misrepresenting the existence of an essential patent) and after a standard is implemented (through refusing to license an essential patented technology either at all or on reasonable and non-discriminatory (RAND) terms). This article suggests that non-disclosure of patent interests is unlikely to restrained by Part IV of the Trade Practices Act (TPA), and refusals to license are only likely to be restrained if the refusal involves leveraging or exclusive dealing. By contrast, Standard Setting Organisations (SSOs) which seek to limit this behaviour through private ordering may face considerable scrutiny under the new cartel provisions of the TPA. This article concludes that SSOs may be best advised to implement administrative measures to prevent patent hold-up, such as reviewing which patents are essential for the implementation of a standard, asking patent holders to make their licence conditions public to promote transparency, and establishing forums where patent licensees can complain about licence terms that they consider to be unreasonable or discriminatory. Additionally, the ACCC may play a role in authorising SSO policies that could otherwise breach the new cartel provisions, but which have the practical effect of promoting competition in the standards setting environment.

Self-defence against terrorism in the post 9/11 world

In 1986 the then United States Secretary of State George Shultz asserted that: It is absurd to argue that international law prohibits us from capturing terrorists in international waters or airspace; from attacking them on the soil of other nations, even for the purpose of rescuing hostages; or from using force against states that support, train and harbor terrorists or guerrillas. At that time the United States’ claim of a right to use military force in self-defence against terrorism2 received little support from other states.3 The predominant view then was that terrorist attacks committed by private or non-state actors were a form of criminal activity to be combated through domestic and international criminal justice mechanisms. The notion that such terrorist acts should be treated as ‘armed attacks’ triggering a victim state’s right of self-defence was not accepted by the majority of states. To suggest, as Shultz had done, that a state not directly responsible for terrorist acts could have its territorial integrity violated by military action targeting terrorists located within that state, was a controversial proposition in 1986. However, some fifteen years later, when the United States and a coalition of allies launched a military campaign in Afghanistan following the 11 September 2001 (hereafter ‘9/11’) terrorist attacks, there was virtually unanimous international support for the use of force.

Open content licensing of public sector information and the risk of tortious liability for Australian Governments

There has been an increasing interest by governments worldwide in the potential benefits of open access to public sector information (PSI). However, an important question remains: can a government incur tortious liability for incorrect information released online under an open content licence? This paper argues that the release of PSI online for free under an open content licence, specifically a Creative Commons licence, is within the bounds of an acceptable level of risk to government, especially where users are informed of the limitations of the data and appropriate information management policies and principles are in place to ensure accountability for data quality and accuracy.

Transcutaneous immunization with novel lipid-based adjuvants induces protection against gastric Helicobacter pylori infection

The development of vaccines to combat pathogens that infect across mucosal surfaces has been a major goal of vaccine research. Successful mucosal vaccination requires the co-administration of adjuvants that can overcome the state of immune tolerance normally associated with mucosal application of proteins. In the case of oral immunization, delivery systems are also required to protect vaccine antigens against destruction by gastric pH and digestive enzymes. Furthermore, adjuvants used for mucosal delivery must be free of neurotoxic effects like those induced by the commonly used experimental mucosal adjuvant cholera toxin. Maintenance of the "cold chain" is also essential for the effectiveness of any vaccine and adjuvants/delivery systems that enhance the stability of a vaccine would offer a significant advantage. Needle-free methods of vaccination that induce protective immunity at multiple mucosal surfaces are also desirable for rapid vaccination of large populations. In the present study we show that transcutaneous immunization (TCI) using Lipid C, a novel lipid-based matrix originally developed for oral immunization, containing soluble Helicobacter sonicate significantly reduces the gastric bacterial burden in mice following gastric challenge with live Helicobacter pylori. Protection is associated with the production of splenic gamma interferon and gastric IgA and was achieved without the co-administration of potent and potentially toxic adjuvants, although protection was further enhanced by inclusion of CpG-ODN and cholera toxin in the lipid delivery system.

Defending web services against denial of service attacks using client puzzles

The interoperable and loosely-coupled web services architecture, while beneficial, can be resource-intensive, and is thus susceptible to denial of service (DoS) attacks in which an attacker can use a relatively insignificant amount of resources to exhaust the computational resources of a web service. We investigate the effectiveness of defending web services from DoS attacks using client puzzles, a cryptographic countermeasure which provides a form of gradual authentication by requiring the client to solve some computationally difficult problems before access is granted. In particular, we describe a mechanism for integrating a hash-based puzzle into existing web services frameworks and analyze the effectiveness of the countermeasure using a variety of scenarios on a network testbed. Client puzzles are an effective defence against flooding attacks. They can also mitigate certain types of semantic-based attacks, although they may not be the optimal solution.

Community-based protest against construction projects : a case study of movement continuity

Community-based activism against proposed construction projects is growing. Many protests are poorly managed and escalate into long-term and sometimes acrimonious disputes which damage communities, firms and the construction industry as a whole. Using a thematic storytelling approach which draws on ethnographic method, within a single case study framework, new insights into the social forces that shape and sustain community-based protest against construction projects are provided. A conceptual model of protest movement continuity is presented which highlights the factors that sustain protest continuity over time. The model illustrates how social contagion leads to common community perceptions of development risk and opportunity, to a positive internalization of collective values and identity, to a strategic utilization of social capital and an awareness of the need to manage the emotional dynamics of protest through mechanisms such as symbolic artefacts.

Partial protection against chlamydial reproductive tract infection by a recombinant major outer membrane protein/CpG/cholera toxin intranasal vaccine in the guinea pig Chlamydia cavaie model

Chlamydia trachomatis is a major cause of sexually transmitted diseases worldwide. There currently is no vaccine to protect against chlamydial infection of the female reproductive tract. Vaccine development has predominantly involved using the murine model, however infection of female guinea pigs with Chlamydia caviae more closely resembles chlamydial infection of the human female reproductive tract, and presents a better model to assess potential human chlamydial vaccines. We immunised female guinea pigs intranasally with recombinant major outer membrane protein (r-MOMP) combined with CpG-10109 and cholera toxin adjuvants. Both systemic and mucosal immune responses were elicited in immunised animals. MOMP-specific IgG and IgA were present in the vaginal mucosae, and high levels of MOMP-specific IgG were detected in the serum of immunised animals. Antibodies from the vaginal mucosae were also shown to be capable of neutralising C. caviae in vitro. Following immunisation, animals were challenged intravaginally with a live C. caviae infection of 102 inclusion forming units. We observed a decrease in duration of infection and a significant (p<0.025) reduction in infection load in r-MOMP immunised animals, compared to animals immunised with adjuvant only. Importantly, we also observed a marked reduction in upper reproductive tract (URT) pathology in r-MOMP immunised animals. Intranasal immunisation of female guinea pigs with r-MOMP was able to provide partial protection against C. caviae infection, not only by reducing chlamydial burden but also URT pathology. This data demonstrates the value of using the guinea pig model to evaluate potential chlamydial vaccines for protection against infection and disease pathology caused by C. trachomatis in the female reproductive tract.