Gonadotropin-induced ovarian cancer cell migration and proliferation require extracellular signal-regulated kinase 1/2 activation regulated by calcium and protein kinase Cδ

The gonadotropin hypothesis proposes that elevated serum gonadotropin levels may increase the risk of epithelial ovarian cancer (EOC). We have studied the effect of treating EOC cell lines (OV207 and OVCAR-3) with FSH or LH. Both gonadotropins activated the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and increased cell migration that was inhibited by the MAPK 1 inhibitor PD98059. Both extra- and intracellular calcium ion signalling were implicated in gonadotropin-induced ERK1/2 activation as treatment with either the calcium chelator EGTA or an inhibitor of intracellular calcium release, dantrolene, inhibited gonadotropin-induced ERK1/2 activation. Verapamil was also inhibitory, indicating that gonadotropins activate calcium influx via L-type voltage-dependent calcium channels. The cAMP/protein kinase A (PKA) pathway was not involved in the mediation of gonadotropin action in these cells as gonadotropins did not increase intracellular cAMP formation and inhibition of PKA did not affect gonadotropin-induced phosphorylation of ERK1/2. Activation of ERK1/2 was inhibited by the protein kinase C (PKC) inhibitor GF 109203X as well as by the PKCδ inhibitor rottlerin, and downregulation of PKCδ was inhibited by small interfering RNA (siRNA), highlighting the importance of PKCδ in the gonadotropin signalling cascade. Furthermore, in addition to inhibition by PD98059, gonadotropin-induced ovarian cancer cell migration was also inhibited by verapamil, GF 109203X and rottlerin. Similarly, gonadotropin-induced proliferation was inhibited by PD98059, verapamil, GF 109203X and PKCδ siRNA. Taken together, these results demonstrate that gonadotropins induce both ovarian cancer cell migration and proliferation by activation of ERK1/2 signalling in a calcium- and PKCδ-dependent manner.

A continuous time model for election timing

We consider a continuous time model for election timing in a Majoritarian Parliamentary System where the government maintains a constitutional right to call an early election. Our model is based on the two-party-preferred data that measure the popularity of the government and the opposition over time. We describe the poll process by a Stochastic Differential Equation (SDE) and use a martingale approach to derive a Partial Differential Equation (PDE) for the government’s expected remaining life in office. A comparison is made between a three-year and a four-year maximum term and we also provide the exercise boundary for calling an election. Impacts on changes in parameters in the SDE, the probability of winning the election and maximum terms on the call exercise boundaries are discussed and analysed. An application of our model to the Australian Federal Election for House of Representatives is also given.

Assessing population limits : a carrying capacity approach to planning

While purporting to enhance Australia’s sustainability, the federal government’s Population Strategy rejects the assessment of the limiting factors to future population growth, thus avoiding urgent threshold issues such as resource depletion and environmental destruction. A more forward-thinking and whole-system perspective would assess and incorporate critical biophysical limits into governance processes with suitable prioritisation. It would encourage communities to examine their individual and collective responsibilities in the context of these limits in order to most equitably optimise outcomes; and it would employ both a resource-based examination of minimum population requirements, and an impact-based assessment of maximum thresholds. This carrying capacity approach to planning could help guide society towards a more sustainable future.

Elections 2.0 : reflections on the 2010 federal election and the future of Australian electoral law

This article analyses the 2010 federal election and the impact the internet and social media had on electoral law, and what this may mean for electoral law in the future. Four electoral law issues arising out of the 2010 election as a result of the internet are considered, including online enrolment, regulation of online advertising and comment, fundraising and the role of lobby groups, especially when it comes to crowdsourcing court challenges. Finally, the article offers some suggestions as to how the parliament and the courts should respond to these challenges.

Policy analysis of disaster health management in China

Humankind has been dealing with all kinds of disasters since the dawn of time. The risk and impact of disasters producing mass casualties worldwide is increasing, due partly to global warming as well as to increased population growth, increased density and the aging population. China, as a country with a large population, vast territory, and complex climatic and geographical conditions, has been plagued by all kinds of disasters. Disaster health management has traditionally been a relatively arcane discipline within public health. However, SARS, Avian Influenza, and earthquakes and floods, along with the need to be better prepared for the Olympic Games in China has brought disasters, their management and their potential for large scale health consequences on populations to the attention of the public, the government and the international community alike. As a result significant improvements were made to the disaster management policy framework, as well as changes to systems and structures to incorporate an improved disaster management focus. This involved the upgrade of the Centres for Disease Control and Prevention (CDC) throughout China to monitor and better control the health consequences particularly of infectious disease outbreaks. However, as can be seen in the Southern China Snow Storm and Wenchuan Earthquake in 2008, there remains a lack of integrated disaster management and efficient medical rescue, which has been costly in terms of economics and health for China. In the context of a very large and complex country, there is a need to better understand whether these changes have resulted in effective management of the health impacts of such incidents. To date, the health consequences of disasters, particularly in China, have not been a major focus of study. The main aim of this study is to analyse and evaluate disaster health management policy in China and in particular, its ability to effectively manage the health consequences of disasters. Flood has been selected for this study as it is a common and significant disaster type in China and throughout the world. This information will then be used to guide conceptual understanding of the health consequences of floods. A secondary aim of the study is to compare disaster health management in China and Australia as these countries differ in their length of experience in having a formalised policy response. The final aim of the study is to determine the extent to which Walt and Gilson’s (1994) model of policy explains how disaster management policy in China was developed and implemented after SARS in 2003 to the present day. This study has utilised a case study methodology. A document analysis and literature search of Chinese and English sources was undertaken to analyse and produce a chronology of disaster health management policy in China. Additionally, three detailed case studies of flood health management in China were undertaken along with three case studies in Australia in order to examine the policy response and any health consequences stemming from the floods. A total of 30 key international disaster health management experts were surveyed to identify fundamental elements and principles of a successful policy framework for disaster health management. Key policy ingredients were identified from the literature, the case-studies and the survey of experts. Walt and Gilson (1994)’s policy model that focuses on the actors, content, context and process of policy was found to be a useful model for analysing disaster health management policy development and implementation in China. This thesis is divided into four parts. Part 1 is a brief overview of the issues and context to set the scene. Part 2 examines the conceptual and operational context including the international literature, government documents and the operational environment for disaster health management in China. Part 3 examines primary sources of information to inform the analysis. This involves two key studies: • A comparative analysis of the management of floods in China and Australia • A survey of international experts in the field of disaster management so as to inform the evaluation of the policy framework in existence in China and the criteria upon which the expression of that policy could be evaluated Part 4 describes the key outcomes of this research which include: • A conceptual framework for describing the health consequences of floods • A conceptual framework for disaster health management • An evaluation of the disaster health management policy and its implementation in China. The research outcomes clearly identified that the most significant improvements are to be derived from improvements in the generic management of disasters, rather than the health aspects alone. Thus, the key findings and recommendations tend to focus on generic issues. The key findings of this research include the following: • The health consequences of floods may be described in terms of time as ‘immediate’, ‘medium term’ and ‘long term’ and also in relation to causation as ‘direct’ and ‘indirect’ consequences of the flood. These two aspects form a matrix which in turn guides management responses. • Disaster health management in China requires a more comprehensive response throughout the cycle of prevention, preparedness, response and recovery but it also requires a more concentrated effort on policy implementation to ensure the translation of the policy framework into effective incident management. • The policy framework in China is largely of international standard with a sound legislative base. In addition the development of the Centres for Disease Control and Prevention has provided the basis for a systematic approach to health consequence management. However, the key weaknesses in the current system include: o The lack of a key central structure to provide the infrastructure with vital support for policy development, implementation and evaluation. o The lack of well-prepared local response teams similar to local government based volunteer groups in Australia. • The system lacks structures to coordinate government action at the local level. The result of this is a poorly coordinated local response and lack of clarity regarding the point at which escalation of the response to higher levels of government is advisable. These result in higher levels of risk and negative health impacts. The key recommendations arising from this study are: 1. Disaster health management policy in China should be enhanced by incorporating disaster management considerations into policy development, and by requiring a disaster management risk analysis and disaster management impact statement for development proposals. 2. China should transform existing organizations to establish a central organisation similar to the Federal Emergency Management Agency (FEMA) in the USA or the Emergency Management Australia (EMA) in Australia. This organization would be responsible for leading nationwide preparedness through planning, standards development, education and incident evaluation and to provide operational support to the national and local government bodies in the event of a major incident. 3. China should review national and local plans to reflect consistency in planning, and to emphasize the advantages of the integrated planning process. 4. Enhance community resilience through community education and the development of a local volunteer organization. China should develop a national strategy which sets direction and standards in regard to education and training, and requires system testing through exercises. Other initiatives may include the development of a local volunteer capability with appropriate training to assist professional response agencies such as police and fire services in a major incident. An existing organisation such as the Communist Party may be an appropriate structure to provide this response in a cost effective manner. 5. Continue development of professional emergency services, particularly ambulance, to ensure an effective infrastructure is in place to support the emergency response in disasters. 6. Funding for disaster health management should be enhanced, not only from government, but also from other sources such as donations and insurance. It is necessary to provide a more transparent mechanism to ensure the funding is disseminated according to the needs of the people affected. 7. Emphasis should be placed on prevention and preparedness, especially on effective disaster warnings. 8. China should develop local disaster health management infrastructure utilising existing resources wherever possible. Strategies for enhancing local infrastructure could include the identification of local resources (including military resources) which could be made available to support disaster responses. It should develop operational procedures to access those resources. Implementation of these recommendations should better position China to reduce the significant health consequences experienced each year from major incidents such as floods and to provide an increased level of confidence to the community about the country’s capacity to manage such events.

Evaluation of novel Streptococcus pyogenes vaccine candidates incorporating multiple conserved sequences from the C-repeat region of the M-protein

A major challenge for Streptococcus pyogenes vaccine development is the identification of epitopes that confer protection from infection by multiple S. pyogenes M-types. Here we have identified and characterised the distribution of common variant sequences from individual repeat units of the C-repeat region (CRR) of M-proteins representing 77 different M-types. Three polyvalent fusion vaccine candidates (SV1, SV2 and SV3) incorporating the most common variants were subsequently expressed and purified, and demonstrated to be alpha-helical by Circular Dichroism (CD), a secondary conformational characteristic of the CRR in the M-protein. Antibodies raised against each of these constructs recognise M-proteins that vary in their CRR, and bind to the surface of multiple S. pyogenes isolates. Antibodies raised against SV1, containing five variant sequences, also kill heterologous S. pyogenes isolates in in vitro bactericidal assays. Further structural characterisation of this construct demonstrated the conformation of SV1 was stable at different pHs, and thermal unfolding of SV1 a reversible process. Our findings demonstrate that linkage of multiple variant sequences into a single recombinant construct overcomes the need to embed the variant sequences in foreign helix promoting flanking sequences for conformational stability, and demonstrates the viability of the polyvalent candidates as global S. pyogenes vaccine candidates.

Practice and procedure : a recent Court of Appeal case examines the meaning of 'third party payer' in terms of Part 3.4 of the Legal Profession Act 2007.

In Legal Services Commissioner v Wright [2010] QCA 321 the Queensland Court of Appeal allowed an appeal from the first instance decision. The decision involved the construction of “third party payer” in Part 3.4 of the Legal Profession Act 2007 (Qld).

Editorial : Federal developments

On 10 May 2011, Federal Treasurer Wayne Swan MP delivered the Federal Budget for the 2011–2012 financial year. The Budget contains a number of new initiatives, financial redistributions and reductions that relate to Australia's current regulatory framework governing the environment, climate change and renewable energy. These are set out below...

US Federal Government entrepreneurship : new enterprise structures

Purpose: The purpose of this paper is to guide the formation and to determine the structure of new governmental entrepreneurial ventures based on the nature of the public goods and the need for an entrepreneurial orientation. Design/methodology/research: This paper is conceptual and is based on reviews of appropriate organizational structure and entrepreneurship, cases studies, and the authors' experiences. Findings: Public or quasi-public entities may need to change their organizational structure in order to act more entrepreneurially and to be more effective in accomplishing their missions. Propositions are raised to guide the development of new public or private enterprises and provide the basis for future research. Research limitations/implications: This paper is conceptual and needs to be tested empirically. Though other levels of government and countries were included, a major focus is on the US federal government. Originality/value: This is the first published research on the topic of new enterprise government structures based on the nature of the goods and the requisite entrepreneurial orientation. It will help governmental and quasi-governmental organizations in developing efficient and effective organizational structures.