Insights into a multidrug resistant Escherichia coli pathogen of the globally disseminated ST131 lineage : genome analysis and virulence mechanisms

Escherichia coli strains causing urinary tract infection (UTI) are increasingly recognized as belonging to specific clones. E. coli clone O25b:H4-ST131 has recently emerged globally as a leading multi-drug resistant pathogen causing urinary tract and bloodstream infections in hospitals and the community. While most molecular studies to date examine the mechanisms conferring multi-drug resistance in E. coli ST131, relatively little is known about their virulence potential. Here we examined E. coli ST131 clinical isolates from two geographically diverse collections, one representing the major pathogenic lineages causing UTI across the United Kingdom and a second representing UTI isolates from patients presenting at two large hospitals in Australia. We determined a draft genome sequence for one representative isolate, E. coli EC958, which produced CTX-M-15 extended-spectrum β-lactamase, CMY-23 type AmpC cephalosporinase and was resistant to ciprofloxacin. Comparative genome analysis indicated that EC958 encodes virulence genes commonly associated with uropathogenic E. coli (UPEC). The genome sequence of EC958 revealed a transposon insertion in the fimB gene encoding the activator of type 1 fimbriae, an important UPEC bladder colonization factor. We identified the same fimB transposon insertion in 59% of the ST131 UK isolates, as well as 71% of ST131 isolates from Australia, suggesting this mutation is common among E. coli ST131 strains. Insertional inactivation of fimB resulted in a phenotype resembling a slower off-to-on switching for type 1 fimbriae. Type 1 fimbriae expression could still be induced in fimB-null isolates; this correlated strongly with adherence to and invasion of human bladder cells and bladder colonisation in a mouse UTI model. We conclude that E. coli ST131 is a geographically widespread, antibiotic resistant clone that has the capacity to produce numerous virulence factors associated with UTI.

An economic case for providing free access to antiretroviral therapy for HIV-positive people in South Australia

Background As financial constraints can be a barrier to accessing HIV antiretroviral therapy (ART), we argue for the removal of copayment requirements from HIV medications in South Australia. Methods Using a simple mathematical model informed by available behavioural and biological data and reflecting the HIV epidemiology in South Australia, we calculated the expected number of new HIV transmissions caused by persons who are not currently on ART compared with transmissions for people on ART. The extra financial investment required to cover the copayments to prevent an HIV infection was compared with the treatment costs saved due to averting HIV infections. Results It was estimated that one HIV infection is prevented per year for every 31.4 persons (median, 24.0–42.7 interquartile range (IQR)) who receive treatment. By considering the incremental change in costs and outcomes of a change in program from the current status quo, it would cost the health sector $17 860 per infection averted (median, $13 651–24 287 IQR) if ART is provided as a three-dose, three-drug combination without requirements for user-pay copayments. Conclusions The costs of removing copayment fees for ART are less than the costs of treating extra HIV infections that would result under current conditions. Removing the copayment requirement for HIV medication would be cost-effective from a governmental perspective.

How does access to development finance shape our cities?

In market economies the built environment is largely the product of private sector property development. Property development is a high-risk entrepreneurial activity executing expensive projects with long gestation periods in an uncertain environment and into an uncertain future. Risk lies at the core of development: the developer manages the multiple risks of development and it is the capital injection and financing that is placed at risk. From the developer's perspective the search for development capital is a quest: to access more finance, over a longer term, with fewer conditions and at lower rates. From the supply angle, capital of various sources - banks, insurance companies, superannuation funds, accumulated firm profits, retail investors and private equity - is always seeking above market returns for limited risk. Property development presents one potentially lucrative, but risky, investment opportunity. Competition for returns on capital produces a continual dynamic evolution of methods for funding property developments. And thus the relationship between capital and development and the outcomes for the built environment are in a restless continual evolution. Little is documented about the ways development is financed in Australia and even less of the consequences for cities. Using publicly available data sources and examples of different development financing from Australian practice, this paper argues that different methods of financing development have different outcomes and consequences for the built environment. This paper also presents an agenda for further research into these themes.

Resolving the conflicts of sustainable world heritage landscapes in cities : fully open or limited access for visitors?

World Heritage Landscapes (WHLs) are receiving increased attention from researchers, urban planners, managers, and policy makers and many heritage values and resources are becoming irreversibly lost. This phenomenon is especially prominent for WHLs located in cities, where greater development opportunities are involved. Decision making for sustainable urban landscape planning, conservation and management of WHLs often takes place from an economic perspective, especially in developing countries. This, together with the uncertain source of funding to cover WHL operating and maintenance costs, has resulted in many urban managers seeking private sector funding either in the form of visitor access fees or leasing part of the site for high-rental facilities such as five star hotels, clubs and expensive restaurants. For the former, this can result in low-income urban citizens being unable to afford the access fees and hence contradicting the principle of equal access for all; while, for the latter, the principle of open access for all is equally violated. To resolve this conflict, a game model is developed to determine how urban managers should allocate WHL spaces to maximize the combination of economic, social and ecological benefits and cultural values. A case study is provided of the Hangzhou's West Lake Scenic Area, a WHL located at the centre of Hangzhou city, in which several high-rental facilities have recently been closed down by the local authorities due to charges of elitism and misuse of public funds by government officials. The result shows that the best solution is to lease a small space with high rents and leave the remainder of the site to the public. This solution is likely to be applicable only in cities with a strong economy.

Better health outcomes for people with physical disabilities in China through audits of mobility related access : a research and implementation need

China has 85 million people with disabilities, 30% of whom have a physical disability(1). Up to 2006, overall disability rates increased by 0.5% per year, more for males and in rural areas, and rates of physical disability increased by 11.2% per year(2). With population ageing the proportion of people with disability will increase even faster. In May 2014 the 67th World Health Assembly adopted a resolution endorsing the WHO Global Disability Action Plan 2014–2021. One of its three objectives is “to remove barriers and improve access to health services and programmes”. Access to transport contributes to positive health outcomes both directly and indirectly (e.g. access to economic opportunities, which is associated with better health)(3). However, once people with physical disabilities leave their dwellings they are confronted with physical barriers to their mobility, ranging from the condition/provision of paths to the cost/availability of transport and access to buildings. In addition, their mobility restrictions increase their vulnerability as road users, exposing them to a higher risk of injury through road crashes. QUT's School of Public Health and Social Work (PHSW) and and Centre for Accident Research and Road Safety-Queensland (CARRS-Q) CARRS-Q have been collaborating on development of a combined disability audit and road safety access tool that can identify transport barriers and safety issues along the routes taken by people with disabilities, to enable prioritisation of actions to address these issues. There are also spin-off benefits for other road users from addressing the rising toll of disability through road crashes in China(4). The tool has undergone initial proof-of-concept testing in India and Viet Nam, and is currently being assessed in Cambodia and Laos. Given the rapid development of China, increases in rates of physical disability and the impacts of an ageing population, it is proposed to establish collaborative research through the Australia-China Centre for Public Health to (1) tailor the combined road safety audit and disability access tool for use in China; (2) evaluate its use on a sample of routes; (3) develop plans for changes to the routes in consultation with local authorities; (4) evaluate the effectiveness of implemented changes in terms of access and health. 1. Zheng, Q, et al, 2014. Health and Quality of Life Outcomes, 12:25. 2. Zheng, X, et al, 2011. Bull World Health Org, 89:788–797. 3. Götschi, T & Kahlmeier, S, 2011. Integrated Transport, Health, and Sustainability Assessment (INTHESA): Final Report. Institute of Social and Preventive Medicine, University of Zurich. 4. Lin, T, et al, 2013. J Public Health, 35:541–547.

Creating a legal framework for copyright management of open access within the Australian academic and research sector

This chapter analyses the copyright law framework needed to ensure open access to outputs of the Australian academic and research sector such as journal articles and theses. It overviews the new knowledge landscape, the principles of copyright law, the concept of open access to knowledge, the recently developed open content models of copyright licensing and the challenges faced in providing greater access to knowledge and research outputs.

Individuals, Innovation, and the Internet : Why Access is Essential

As each day passes, and as new and better devices and services are developed, more and more government and private services are being moved to an online format. This movement makes access to the internet an essential for 21st Century life. The internet has become so integrated in our lives that many of us cannot imagine how we could operate without it. This omnipresent ‘being’ affects all forms of ‘normal’ social and economic activity and does so in ways that we do not realize. Those with access are able to engage with government, business, and family and friends more easily, which can lead to an improved standard of living. For the disadvantaged, however – those with the desire but without the capacity – a lack of access can be socially isolating. "Between the idea And the reality Between the motion And the act Falls the Shadow – T. S. Elliott. “The Hollow Men” Engagement in the internet economy requires both physical access and the individual to have the necessary finances and skills to make and sustain their use. If governments and the international community want a fully functioning internet economy this requires that all individuals must be operating in it. That not all individuals do so means, very simply, that the internet economy is not fully functioning. The text contextualizes for policy makers and legislatures why it is essential to ensure that individuals have appropriate access to the internet and what can be done to achieve it. The interrelationship/overlap between why access is essential, how it can be achieved and the central role of the individual to the internet economy is explored and translated into the concept of connectedness. From this, solutions for ensuring connectedness for all individuals are developed. It is Dr Cradduck’s hope that in the not too distant future readers will puzzle over why texts such as this needed to be written.

Improving access to housing for low-income communities in Dhaka: From rhetoric to reality in community participation

The research explores how community participation can address affordable housing problems of the poor in Dhaka. The research, based on extensive interviews, community focus groups and household surveys in different Dhaka slums, identifies the limiting factors to promote community participation in affordable housing creation. In Dhaka housing options for poor are currently limited to affordable shelters in informal settlements. Public housing programs have failed to reach the poor and meet affordability levels due to a number of factors including lack of beneficiary participation. Beneficiary participation, though widely recognized for success in housing initiatives, often deteriorates in process of implementation into mere involvement, not reflecting community needs and aspirations and thus failing to meet its core objectives. This research identified the most significant impediments as well as opportunities to advance participation in their own housing provisions in Dhaka city.

Access to the Internet Submission to ALRC IP 46

This submission is directed to issues arising in respect of the need to recognise and support access to the internet for all Australian residents and citizens. As such it addresses the following questions only: Questions 2-1: What general principles or criteria should be applied to help determine whether a law that interferes with freedom of speech is justified? Question 2-2: Which Commonwealth laws unjustifiably interfere with freedom of speech, and why are these laws unjustified?

Liquid Business Process Model Collections

Many organizations realize that increasing amounts of data (“Big Data”) need to be dealt with intelligently in order to compete with other organizations in terms of efficiency, speed and services. The goal is not to collect as much data as possible, but to turn event data into valuable insights that can be used to improve business processes. However, data-oriented analysis approaches fail to relate event data to process models. At the same time, large organizations are generating piles of process models that are disconnected from the real processes and information systems. In this chapter we propose to manage large collections of process models and event data in an integrated manner. Observed and modeled behavior need to be continuously compared and aligned. This results in a “liquid” business process model collection, i.e. a collection of process models that is in sync with the actual organizational behavior. The collection should self-adapt to evolving organizational behavior and incorporate relevant execution data (e.g. process performance and resource utilization) extracted from the logs, thereby allowing insightful reports to be produced from factual organizational data.

Collecting in an urban context: Relationships between collections and space in the home

Collecting has become a popular hobby within Western society, with collectables including anything from ‘bottle tops’ to ‘skyscrapers’. As the nature and size of these collections can impact upon the use of space in the home, the purpose of this study is to explore the relationship between the collections, space in the home and the impacts on others. This qualitative study explores the experiences of 11 Australian collectors, investigating the motivations, practices and adaption techniques used within their urban home environment. The themes of sentimentality, sociability and spatial tensions, including physical, personal and use of space are discussed within the context of their home and family environments. Overall the practice of collecting objects is a complex, varied, sentimental and sociable activity, providing enjoyment, knowledge and friendships. Space can be a central consideration to the practice of collecting as collections shape and are shaped by the available space in a household.

Knowledge unlatched: A global library consortium model for funding open access scholarly books: Full report on the Proof of Concept Pilot 2014

This special issue of Cultural Science Journal is devoted to the report of a groundbreaking experiment in re-coordinating global markets for specialist scholarly books and enabling the knowledge commons: the Knowledge Unlatched proof-of-concept pilot. The pilot took place between January 2012 and September 2014. It involved libraries, publishers, authors, readers and research funders in the process of developing and testing a global library consortium model for supporting Open Access books. The experiment established that authors, librarians, publishers and research funding agencies can work together in powerful new ways to enable open access; that doing so is cost effective; and that a global library consortium model has the potential dramatically to widen access to the knowledge and ideas contained in book-length scholarly works.