Identification of a serine protease inhibitor which causes inclusion vacuole reduction and is lethal to Chlamydia trachomatis

The mechanistic details of the pathogenesis of Chlamydia, an obligate intracellular pathogen of global importance, have eluded scientists due to the scarcity of traditional molecular genetic tools to investigate this organism. Here we report a chemical biology strategy that has uncovered the first essential protease for this organism. Identification and application of a unique CtHtrA inhibitor (JO146) to cultures of Chlamydia resulted in a complete loss of viable elementary body formation. JO146 treatment during the replicative phase of development resulted in a loss of Chlamydia cell morphology, diminishing inclusion size, and ultimate loss of inclusions from the host cells. This completely prevented the formation of viable Chlamydia elementary bodies. In addition to its effect on the human C. trachomatis strain, JO146 inhibited the viability of the mouse strain, Chlamydia muridarum, both in vitro and in vivo. Thus, we report a chemical biology approach to establish an essential role for Chlamydia CtHtrA. The function of CtHtrA for Chlamydia appears to be essential for maintenance of cell morphology during replicative the phase and these findings provide proof of concept that proteases can be targetted for anti-microbial therapy for intracellular pathogens.

The health effects of temperature : current estimates, future projections, and adaptation strategies

Climate change is expected to be one of the biggest global health threats in the 21st century. In response to changes in climate and associated extreme events, public health adaptation has become imperative. This thesis examined several key issues in this emerging research field. The thesis aimed to identify the climate-health (particularly temperature-health) relationships, then develop quantitative models that can be used to project future health impacts of climate change, and therefore help formulate adaptation strategies for dealing with climate-related health risks and reducing vulnerability. The research questions addressed by this thesis were: (1) What are the barriers to public health adaptation to climate change? What are the research priorities in this emerging field? (2) What models and frameworks can be used to project future temperature-related mortality under different climate change scenarios? (3) What is the actual burden of temperature-related mortality? What are the impacts of climate change on future burden of disease? and (4) Can we develop public health adaptation strategies to manage the health effects of temperature in response to climate change? Using a literature review, I discussed how public health organisations should implement and manage the process of planned adaptation. This review showed that public health adaptation can operate at two levels: building adaptive capacity and implementing adaptation actions. However, there are constraints and barriers to adaptation arising from uncertainty, cost, technologic limits, institutional arrangements, deficits of social capital, and individual perception of risks. The opportunities for planning and implementing public health adaptation are reliant on effective strategies to overcome likely barriers. I proposed that high priorities should be given to multidisciplinary research on the assessment of potential health effects of climate change, projections of future health impacts under different climate and socio-economic scenarios, identification of health cobenefits of climate change policies, and evaluation of cost-effective public health adaptation options. Heat-related mortality is the most direct and highly-significant potential climate change impact on human health. I thus conducted a systematic review of research and methods for projecting future heat-related mortality under different climate change scenarios. The review showed that climate change is likely to result in a substantial increase in heatrelated mortality. Projecting heat-related mortality requires understanding of historical temperature-mortality relationships, and consideration of future changes in climate, population and acclimatisation. Further research is needed to provide a stronger theoretical framework for mortality projections, including a better understanding of socioeconomic development, adaptation strategies, land-use patterns, air pollution and mortality displacement. Most previous studies were designed to examine temperature-related excess deaths or mortality risks. However, if most temperature-related deaths occur in the very elderly who had only a short life expectancy, then the burden of temperature on mortality would have less public health importance. To guide policy decisions and resource allocation, it is desirable to know the actual burden of temperature-related mortality. To achieve this, I used years of life lost to provide a new measure of health effects of temperature. I conducted a time-series analysis to estimate years of life lost associated with changes in season and temperature in Brisbane, Australia. I also projected the future temperaturerelated years of life lost attributable to climate change. This study showed that the association between temperature and years of life lost was U-shaped, with increased years of life lost on cold and hot days. The temperature-related years of life lost will worsen greatly if future climate change goes beyond a 2 °C increase and without any adaptation to higher temperatures. The excess mortality during prolonged extreme temperatures is often greater than the predicted using smoothed temperature-mortality association. This is because sustained period of extreme temperatures produce an extra effect beyond that predicted by daily temperatures. To better estimate the burden of extreme temperatures, I estimated their effects on years of life lost due to cardiovascular disease using data from Brisbane, Australia. The results showed that the association between daily mean temperature and years of life lost due to cardiovascular disease was U-shaped, with the lowest years of life lost at 24 °C (the 75th percentile of daily mean temperature in Brisbane), rising progressively as temperatures become hotter or colder. There were significant added effects of heat waves, but no added effects of cold spells. Finally, public health adaptation to hot weather is necessary and pressing. I discussed how to manage the health effects of temperature, especially with the context of climate change. Strategies to minimise the health effects of high temperatures and climate change can fall into two categories: reducing the heat exposure and managing the health effects of high temperatures. However, policy decisions need information on specific adaptations, together with their expected costs and benefits. Therefore, more research is needed to evaluate cost-effective adaptation options. In summary, this thesis adds to the large body of literature on the impacts of temperature and climate change on human health. It improves our understanding of the temperaturehealth relationship, and how this relationship will change as temperatures increase. Although the research is limited to one city, which restricts the generalisability of the findings, the methods and approaches developed in this thesis will be useful to other researchers studying temperature-health relationships and climate change impacts. The results may be helpful for decision-makers who develop public health adaptation strategies to minimise the health effects of extreme temperatures and climate change.

Rethinking emergency management and climate adaptation policies

Emergency management and climate change adaptation will increasingly challenge all levels of government because of three main factors. First, Australia is extremely vulnerable to the impacts of climate change, particularly through the increasing frequency and/or intensity of disasters such as floods and bushfires. Second, the system of government that divides powers by function and level can often act as a barrier to a well-integrated response. Third, policymaking processes struggle to cope with such complex inter-jurisdictional issues. This paper discusses these factors and explores the nature of the challenge for Australian governments. Investigations into the 2009 Victorian bushfires, the 2011 Perth Hills bushfires, and the 2011 Brisbane floods offer an indication of the challenges ahead and it is argued that there is a need to: improve community engagement and communication; refocus attention on resilience; improve interagency communication and collaboration; and, develop institutional arrangements that support continual improvement and policy learning. These findings offer an opportunity for improving responses as well as a starting point for integrating disaster risk management and climate change adaptation policies. The paper is based on the preliminary findings of an NCCARF funded research project: The Right Tool for the Job – Achieving climate change adaptation outcomes through improved disaster management policies, planning and risk management strategies involving Griffith University and RMIT.

Estimating the burden of malignant neoplasm on village residents in a mountainous area [山区农村居民恶性肿瘤疾病负担的估计]

Objective To make a comprehensive estimation of the burden of malignant neoplasm on village residents in Linqu County by the means of DALY (Disability-adjusted life year). Methods DALYs, YLLs and YLDs were calculated following the procedures developed for the Global Burden of Disease (GBD) study to ensure comparability, based on the cancer registration data of Linqu villages during 1998-2004, in order to measure the burden of various caners. Results All cancers were responsible for 20.00 DALYs for every thousand population in Linqu County (24.82 for men and 14.96 for women). 92.5% of the losses were due to premature death and 7.5% to disability. 31.5% of the DALYs happened among 45-59 age group. The top 10 cancers for DALYs were stomach cancer, lung cancer, liver cancer, oesophagus cancer, leukemia,colon/rectum cancer, brain cancer, pancreas cancer, breast cancer and bone cancer in turn. Only stomach cancer, lung cancer and liver cancer together account for 69.3% of total DALYs due to malignant neoplasm. The burden of malignant neoplasm was on rising recent years. Conclusions The burden of disease of malignant neoplasm is mainly because of premature death. Stomach cancer, lung cancer and liver cancer lead to heavier burden than the global and national levels. Abstract in Chinese 目的 应用伤残调整寿命年(DALY)对临朐县农村恶性肿瘤疾病负担进行评价. 方法 以1998～2004年临朐县农村肿瘤登记资料为基础,利用全球疾病负担研究中使用的专门公式计算恶性肿瘤的YLLs、YLDs和DALYs,以此评价各类恶性肿瘤的疾病负担. 结果 临朐农村每千人每年因恶性肿瘤造成20.0个DALYs损失(男性24.82,女性14.96),其中92.5%为早死所致,7.5%因残疾所致;恶性肿瘤主要导致45～59岁人群的DALYs损失,占31.5%;恶性肿瘤疾病负担前10位依次为胃癌、肺癌、肝癌、食道癌、白血病、肠癌、脑癌、胰腺癌、乳腺癌和骨癌,其中仅胃癌、肺癌和肝癌三大肿瘤DALYs就占全部肿瘤的69.3%;临朐县农村恶性肿瘤疾病负担有进一步上升的趋势. 结论 恶性肿瘤疾病负担主要由早死所致,胃癌、肺癌、肝癌等主要癌症疾病负担高于全球和中国区水平.

An analysis on trend of malignancies incidence and mortality in Linqu County, Shandong Province [山东省临朐县恶性肿瘤发病与 死亡趋势分析]

Purpose To investigate the trend of malignancies incidence and mortality in Linqu county, and to provide scientific evidence for the government to design and adjust polices on cancer prevention and control. [Methods] The cancer registration data of new cases from 1995 to 2004 and death cases from 1998 to 2004 were used to analyse the incidence and mortality and the trend in Linqu county. Results Cancer general incidence significantly increased from 1995 to 2004 (P<0.05). The increasing speed incidence in male was faster than that in female. The incidence of lung cancer, colon/rectum cancer and pancreas cancer increased significantly (P<0.05), especially of lung cancer with an acceleration incidence rate of 2.12/100,000 peryear in average. The general mortality increased gradually from 1998 to 2004 with no significance (P>0.05). Both incidence and mortality in population aged 80 or over increased significantly (P<0.05). Conclusion The cancer incidence is rising during recent 10 years , and the prevention and control for lung cancer are getting increasingly important. [目的] 了解临朐县恶性肿瘤发病与死亡趋势,为政府制订和调整防治对策提供科学依据. [方法] 利用临朐县1995～2004年恶性肿瘤发病登记资料和1998～2004年的死亡登记资料,计算各种癌症发病率和死亡率,并做趋势分析. [结果] 1995～2004年临朐县恶性肿瘤总发病率呈明显上升趋势(P＜0.05),男性发病率上升速度高于女性.肺癌、肠癌、胰腺癌发病率上升显著(P＜0.05),以肺癌最为迅速(年均升高2.12/10万).1998～2004年恶性肿瘤总死亡率略有上升,但无显著性(P＞0.05);80岁及以上人群恶性肿瘤发病率与死亡率均呈上升趋势. [结论] 临朐县恶性肿瘤发病率近10年来呈现上升趋势,肺癌防治地位日益突出.

Shifting global power and shifting state power

The adoption of the Declaration on the Rights of Indigenous Peoples (DRIP) by the United Nations General Assembly in September 2007 has been heralded by many as a major breakthrough in the promotion of Indigenous rights under international law. Many however are sceptical as to whether DRIP actually promotes Indigenous rights or rather limits them in ways that serve the interests of nation states thereby diminishing the universality of human rights with respect to Indigenous peoples. This paper will examine how shifts in global power from the United States to the BRIC nations (Brazil, Russia, India and China) are likely to impact on the realisation of the right of self determination for Indigenous peoples. It will start by outlining the right of self determination as articulated in the Declaration, and in particular how the United States and its allies - the CANZUS group (Canada, Australia, New Zealand and United States) - were influential in shaping its form and content. The paper will then assess the extent to which the right to self determination is realised in Australia, the United States and the BRJC nations to provide an indication of the likely future direction of recognition and realisation of Indigenous rights at a global level.

Responses, relationships and responsibility : examining influences on organisational assets during crisis

This thesis explains how an organisation's relationships with its key stakeholders influence the public's view of its responsibility for a crisis event and how this subsequently influences the protective and reparative powers of its crisis response on its reputation and legitimacy. From the results, a continuum of the influencing effect of relationship history was developed which demonstrates the positive and negative frames through which stakeholders view an organisation in crisis and its response. Organisational age and the evaluative character of its relationships with key stakeholders were considered in the experimental design as descriptors of an organisation's relationship history. The findings provide guidance to crisis managers on effective crisis response selection.

The Law of Real Property Mortgages [2nd. Ed.]

This book examines the principles and practice of real estate mortgages in an easily accessible text referenced to all the Australian States. It specifically deals with the major theoretical and practical aspects of the land mortgage, including vitiating factors in formation, mortgagees’ powers and duties and mortgagors’ rights – both statutory and other – as well as assignment, insurance and discharge. It focuses exclusively on real estate mortgages and provides a thorough account of the law through analysis of the plethora of court decisions and statutory provisions in this area. Duncan and Dixon analyse the substance of the mortgage transaction from creation through to rights of enforcement. In its detailed consideration of the rights and obligations of mortgagors and mortgagees, it covers topics such as priorities and tacking, insurance, variation and assignment, rights of discharge, entry into possession, foreclosure and power of sale. In addition, the book contains a separate chapter on factors that may affect the validity and enforcement of a mortgage, together with separate consideration of a mortgagee’s right to enforce a guarantee provided on behalf of a mortgagor, and the rights and liabilities associated with a receivership regime initiated by

Lexis Nexis Questions and Answers : Equity and Trusts [4th Ed.]

"LexisNexis Questions and Answers: Equity and Trusts provides students with a clear and systematic approach to successfully analysing and answering assessment questions on equity and trusts. Each chapter commences with a discussion of key principles and issues including a summary of relevant leading cases and legislation for effective revision. Examples of written questions with fact scenarios follow, each with a suggested answer plan, sample answer and comments on how the answer might be viewed by an examiner. Readers are provided with advice on common errors to avoid when answering questions and practical hints and tips on how to achieve higher marks. Features • Summary of key issues helps students revise key areas before attempting problem questions • Sample questions with model answers assist students with effective exam study preparation"--publisher website

Somatostatin, its receptors and analogs, in lung cancer

Despite developments in diagnosis and treatment, lung cancer is the commonest cause of cancer death in Europe and North America. Due to increasing cigarette consumption, the incidence of the disease and resultant mortality is rising dramatically in women. Novel approaches to the management of lung cancer are urgently required. Somatostatin is a tetradecapeptide first identified in the pituitary and subsequently throughout the body particularly in neuroendocrine cells of the pancreas and gastrointestinal tract and the nervous system. The peptide has numerous functions including inhibition of hormone release, immunomodulation and neurotransmission and is an endogenous inhibitor of cell proliferation and angiogenesis. Somatostatin and its analogs, including octreotide (SMS 201-995), somatuline (BIM 23014) and vapreotide (RC-160), act by binding to specific somatostatin receptors (SSTR) of which there are 5 principal subtypes, SSTR-1-5. Although elevated plasma somatostatin levels may be detected in 14-15% of patients, tumor cell expression appears rare. SSTR may be expressed by lung tumors, particularly small cell lung cancer and bronchial carcinoid disease. [111In]pentetreotide scintigraphy may have a role to play in the localization and staging of lung cancers both before and following treatment, and in detecting relapsed disease. The potential role of radiolabelled somatostatin analogs as radiotherapeutic agents in the management of lung cancer is currently being explored. Somatostatin analog therapy results in significant growth inhibition of both SSTR-positive and SSTR-negative lung tumors in vivo. Recent work indicates that these agents may enhance the efficacy of chemotherapeutic agents in the treatment of solid tumors including lung cancer. Copyright © 2001 S. Karger AG, Basel.

The increasing cost of healthy food

OBJECTIVE: To assess changes in the cost and availability of a standard basket of healthy food items (the Healthy Food Access Basket [HFAB]) in Queensland. METHODS: Analysis of five cross-sectional surveys (1998, 2000, 2001, 2004 and 2006) describes changes over time. Eighty-nine stores in five remoteness categories were surveyed during May 2006. For the first time a sampling framework based on randomisation of towns throughout the state was applied and the survey was conducted by Queensland Treasury. RESULTS: Compared with the costs in major cities, in 2006 the mean cost of the HFAB was $107.81 (24.2%) higher in very remote stores in Queensland, but $145.57 (32.6%) higher in stores more than 2,000 kilometres from Brisbane. Over six years the cost of the HFAB has increased by around 50% ($148.87) across Queensland and, where data was available, by more than the cost of less healthy alternatives. The Consumer Price Index for food in Brisbane increased by 32.5% over the same period. CONCLUSIONS AND IMPLICATIONS: Australians, no matter where they live, need access to affordable, healthy food. Issues of food security in the face of rising food costs are of concern particularly in the current global economic downturn. There is an urgent need to nationally monitor, but also sustainably address the factors affecting the price of healthy foods, particularly for vulnerable groups who suffer a disproportionate burden of poor health.

Distance education and the application of academagogy : a case study

The education sector has dramatically changed in the past half decade. In a time of globalisation of education and tightening budgets, various paradigm shifts and challenges have rapidly changed learning and teaching. These include: meeting student expectation for more engaging, more interactive learning experiences, the increased focus to deliver content online, and the complexities of fast-changing technologies. Rising to these challenges and responding to them is a complex and multi-faceted task. This paper discusses educational theories and issues and explores current educational practices in the context of teaching undergraduate students via distance education in the university context. A case study applies a framework drawn from engineering education using the learner-centric concept of academagogy. Results showed that academagogy actively empowers students to build effective learning, and engages facilitators in meaningful teaching and delivery methods.

The effect of retail store managers on aboriginal diet in remote communities

Key nutrient densities of the diet of two remote northern coastal Aboriginal communities were measured using the store-turnover method during the periods that three store managers were responsible for each store respectively. Individual store managers were a greater determinant of nutrient density than the community itself. Furthermore, nutrient densities tended to be highest in both communities when their stores were administered by one particular store manager. The results support the notion that store managers wield considerable power over the food supply of remote Aboriginal communities, and raise questions concerning the ability of Aboriginal community members to influence their own food supplies in retail stores. However, the study also confirms that store managers can be important allies in efforts to improve Aboriginal dietary intake.

Epilogue : Why Study Twitter?

Each of the thirty-one contributions in this volume implicitly spells out its own answer to this question. Surprisingly perhaps even for such a highly interdisciplinary volume as this one, these answers vary considerably in their approaches, their objectives, and their underlying assumptions about the object of study. This diversity of scholarly perspectives on Twitter, barely half a decade since it first emerged as a popular platform, highlights its versatility. Beginning as a side project to a now-forgotten podcasting platform, rising to popularity as a social network service focussed around mundane communication and therefore widely lambasted as a cesspool of vanity and triviality by incredulous journalists (including technology journalists), it was later embraced by those same journalists, governments, and businesses as a crucial source of real-time information on everything from natural disasters to celebrity gossip, and from debates over sexual violence to Vatican politics.

Power profiles of multifocal contact lenses and their interpretation

Purpose Many contact lens (CL) manufacturers produce simultaneous-image lenses in which power varies either smoothly or discontinuously with zonal radius. We present in vitro measurements of some recent CLs and discuss how power profiles might be approximated in terms of nominal distance corrections, near additions, and on-eye visual performance. Methods Fully hydrated soft, simultaneous-image CLs from four manufacturers (Air Optix AQUA, Alcon; PureVision multifocal, Bausch & Lomb; Acuvue OASYS for Presbyopia, Vistakon; Biofinity multifocal- ‘‘D’’ design, Cooper Vision) were measured with a Phase focus Lens Profiler (Phase Focus Ltd., Sheffield,UK) in a wet cell and powerswere corrected to powers in air. All lenses had zero labeled power for distance. Results Sagittal power profiles revealed that the ‘‘low’’ add PureVision and Air Optix lenses exhibit smooth (parabolic) profiles, corresponding to negative spherical aberration. The ‘‘mid’’ and ‘‘high’’ add PureVision and Air Optix lenses have biaspheric designs, leading to different rates of power change for the central and peripheral portions. All OASYS lenses display a series of concentric zones, separated by abrupt discontinuities; individual profiles can be constrained between two parabolically decreasing curves, each giving a valid description of the power changes over alternate annular zones. Biofinity lenses have constant power over the central circular region of radius 1.5 mm, followed by an annular zone where the power increases approximately linearly, the gradient increasing with the add power, and finally an outer zone showing a slow, linear increase in power with a gradient being almost independent of the add power. Conclusions The variation in power across the simultaneous-image lenses produces enhanced depth of focus. The throughfocusnature of the image, which influences the ‘‘best focus’’ (distance correction) and the reading addition, will vary with several factors, including lens centration, the wearer’s pupil diameter, and ocular aberrations, particularly spherical aberration; visual performance with some designs may show greater sensitivity to these factors.