Preliminary validation of a novel high-resolution melt-based typing method based on the multilocus sequence typing scheme of Streptococcus pyogenes

The major limitation of current typing methods for Streptococcus pyogenes, such as emm sequence typing and T typing, is that these are based on regions subject to considerable selective pressure. Multilocus sequence typing (MLST) is a better indicator of the genetic backbone of a strain but is not widely used due to high costs. The objective of this study was to develop a robust and cost-effective alternative to S. pyogenes MLST. A 10-member single nucleotide polymorphism (SNP) set that provides a Simpson’s Index of Diversity (D) of 0.99 with respect to the S. pyogenes MLST database was derived. A typing format involving high-resolution melting (HRM) analysis of small fragments nucleated by each of the resolution-optimized SNPs was developed. The fragments were 59–119 bp in size and, based on differences in G+C content, were predicted to generate three to six resolvable HRM curves. The combination of curves across each of the 10 fragments can be used to generate a melt type (MelT) for each sequence type (ST). The 525 STs currently in the S. pyogenes MLST database are predicted to resolve into 298 distinct MelTs and the method is calculated to provide a D of 0.996 against the MLST database. The MelTs are concordant with the S. pyogenes population structure. To validate the method we examined clinical isolates of S. pyogenes of 70 STs. Curves were generated as predicted by G+C content discriminating the 70 STs into 65 distinct MelTs.

Validating the design science research roadmap : through the lens of "the idealised model for theory development"

Design Science Research (DSR) has emerged as an important approach in Information Systems (IS) research. However, DSR is still in its genesis and has yet to achieve consensus on even the fundamentals, such as what methodology / approach to use for DSR. While there has been much effort to establish DSR methodologies, a complete, holistic and validated approach for the conduct of DSR to guide IS researcher (especially novice researchers) is yet to be established. Alturki et al. (2011) present a DSR ‘Roadmap’, making the claim that it is a complete and comprehensive guide for conducting DSR. This paper aims to further assess this Roadmap, by positioning it against the ‘Idealized Model for Theory Development’ (IM4TD) (Fischer & Gregor 2011). The IM4TD highlights the role of discovery and justification and forms of reasoning to progress in theory development. Fischer and Gregor (2011) have applied IM4TD’s hypothetico-deductive method to analyze DSR methodologies, which is adopted in this study to deductively validate the Alturki et al. (2011) Roadmap. The results suggest that the Roadmap adheres to the IM4TD, is reasonably complete, overcomes most shortcomings identified in other DSR methodologies and also highlights valuable refinements that should be considered within the IM4TD.

Nonprofit organisations face a restructuring state : the case of local social services in the Hunter region of New South Wales

This paper is concerned with certain of the characteristics of local social services, and their role in a restructuring Australian welfare state. I am particularly concerned with the distinctive gender characteristics of these organisations, because in comparison with most other organisations they have a feminised quality. This partly mirrors women's traditional role of undertaking the major part of the caring labour of society. However, simultaneously work in these organisation deviates from more traditional patterns where employed women occupy subordinate positions. In many community organisations, women occupy leadership roles. The analysis here is concerned with the apparently paradoxical nature of these organisations in their capacity to entrench traditional gender roles and to challenge these by allowing women to fill management positions. It is also concerned to examine whether changes that have been occurring in the community services sector over the last two decades are likely to enhance women's general position in the society, or diminish the power exercised by women. The paper draws in a preliminary way on a study of local services in the Hunter Region of NSW undertaken in the latter half of 1992. These preliminary findings are set against the broader picture of developments in the contemporary welfare state.

The iatrogenic reflex and belief that repression can coercively suppress asymmetric coercive violence : does very robust action by the government decrease functional support for insurgents?

Non-state insurgent actors are too weak to compel powerful adversaries to their will, so they use violence to coerce. A principal objective is to grow and sustain violent resistance to the point that it either militarily challenges the state, or more commonly, generates unacceptable political costs. To survive, insurgents must shift popular support away from the state and to grow they must secure it. State actor policies and actions perceived as illegitimate and oppressive by the insurgent constituency can generate these shifts. A promising insurgent strategy is to attack states in ways that lead angry publics and leaders to discount the historically established risks and take flawed but popular decisions to use repressive measures. Such decisions may be enabled by a visceral belief in the power of coercion and selective use of examples of where robust measures have indeed suppressed resistance. To avoid such counterproductive behaviours the cases of apparent 'successful repression' must be understood. This thesis tests whether robust state action is correlated with reduced support for insurgents, analyses the causal mechanisms of such shifts and examines whether such reduction is because of compulsion or coercion? The approach is founded on prior research by the RAND Corporation which analysed the 30 insurgencies most recently resolved worldwide to determine factors of counterinsurgent success. This new study first re-analyses their data at a finer resolution with new queries that investigate the relationship between repression and insurgent active support. Having determined that, in general, repression does not correlate with decreased insurgent support, this study then analyses two cases in which the data suggests repression seems likely to be reducing insurgent support: the PKK in Turkey and the insurgency against the Vietnamese-sponsored regime after their ousting of the Khmer Rouge. It applies 'structured-focused' case analysis with questions partly built from the insurgency model of Leites and Wolf, who are associated with the advocacy of US robust means in Vietnam. This is thus a test of 'most difficult' cases using a 'least likely' test model. Nevertheless, the findings refute the deterrence argument of 'iron fist' advocates. Robust approaches may physically prevent effective support of insurgents but they do not coercively deter people from being willing to actively support the insurgency.

The persistence of phase-separation in LiFePO4 with two-dimensional Li+ transport : the Cahn-Hilliard-reaction equation and the role of defects

We examine the solution of the two-dimensional Cahn-Hilliard-reaction (CHR) equation in the xy plane as a model of Li+ intercalation into LiFePO4 material. We validate our numerical solution against the solution of the depth-averaged equation, which has been used to model intercalation in the limit of highly orthotropic diffusivity and gradient penalty tensors. We then examine the phase-change behaviour in the full CHR system as these parameters become more isotropic, and find that as the Li+ diffusivity is increased in the x direction, phase separation persists at high currents, even in small crystals with averaged coherency strain included. The resulting voltage curves decrease monotonically, which has previously been considered a hallmark of crystals that fill homogeneously.

Disability and the labour market : an analysis of British males

This paper attempts, using data from the British Labour Force Survey 1996, to examine to what extent differences in labour market outcomes between able-bodied and disabled men may be attributed to differences in endowments of human capital and associated productivity differences. Both labour force participation and selectivity corrected human capital equations are estimated and decomposition techniques applied to them. Using the methodology of Baldwin and Johnson [Baldwin, M., Johnson, W.G., 1994. Labor market discrimination against men with disabilities. Journal of Human Resources, XXIX(1), Winter, 1–19], the employment effects of wage discrimination against the disabled are also estimated. Evidence of both substantial wage and participation rate differences between able-bodied and disabled men are found, which have implications for the operation of the 1995 Disability Discrimination Act.

Evaluation of the GHR car following model for traffic safety studies

Traffic safety studies mandate more than what existing micro-simulation models can offer as they postulate that every driver exhibits a safe behaviour. All the microscopic traffic simulation models are consisting of a car-following model and the Gazis–Herman–Rothery (GHR) car-following model is a widely used model. This paper highlights the limitations of the GHR car-following model capability to model longitudinal driving behaviour for safety study purposes. This study reviews and compares different version of the GHR model. To empower the GHR model on precise metrics reproduction a new set of car-following model parameters is offered to simulate unsafe vehicle conflicts. NGSIM vehicle trajectory data is used to evaluate the new model and short following headways and Time to Collision are employed to assess critical safety events within traffic flow. Risky events are extracted from available NGSIM data to evaluate the modified model against the generic versions of the GHR model. The results from simulation tests illustrate that the proposed model does predict the safety metrics better than the generic GHR model. Additionally it can potentially facilitate assessing and predicting traffic facilities’ safety using microscopic simulation. The new model can predict Near-miss rear-end crashes.

WikiLeaks, journalism and the consequences of chaos

This article considers the impact of the WikiLeaks organisation in relation to debates around the defence of national security and free speech, global media citizenship and the emerging dynamics of the global public sphere. Building on the author’s previous work on political communication, journalism and ‘cultural chaos’, it explores the implications of WikiLeaks for emerging conceptions and definitions of journalism, and for the changing structure of media–politics power relations at the global level, against the background of three trends: democratisation, declining deference and digitalisation.

Experimental evaluation of the culture performance of three exotic and a ‘local’ Giant Freshwater Prawn (Macrobrachium rosenbergii, De Man 1879) culture strain in Fiji

Giant freshwater prawn (GFP; Macrobrachium rosenbergii) aquaculture has expanded rapidly since 1990. Most local culture industries, however, have developed in an unsystematic way. Fiji has a small culture industry producing the ‘Anuenue’ strain; however, performance of this strain has never been systematically evaluated. Recently, some Fijian farmers have reported declines in stock productivity. The current project evaluated the relative performance of three exotic strains with different genetic backgrounds from Malaysia, Indonesia and Vietnam, against the ‘local’ strain in Fiji in a 4 × 3 replicated pond trial experiment. A total of 5827 prawns were harvested after 143 days growout. Individual growth rate and relative survival of the Fiji strain were not statistically different from any of the introduced strains, but Vietnam strain was superior to that of the Malaysia strain. Genetic diversity showed significant differences in variability among strains, with the Malaysian strain displaying the lowest genetic diversity. Indonesia strain showed that females were reaching maturation earlier than other strains and were smaller in size. This study suggests that Malaysian and Indonesian strains would constitute a poor choice for Fiji, whereas the Vietnam strain consistently performed well on all criteria measured. High variation among replicate ponds within strains unfortunately confounded among-strain variation.

Sensitivity to the MEK inhibitor E6201 in melanoma cells is associated with mutant BRAF and wildtype PTEN status

BACKGROUND: Melanoma is the most lethal form of skin cancer, but recent advances in molecularly targeted agents against the Ras/Raf/MAPK pathway demonstrate promise as effective therapies. Despite these advances, resistance remains an issue, as illustrated recently by the clinical experience with vemurafenib. Such acquired resistance appears to be the result of parallel pathway activation, such as PI3K, to overcome single-agent inhibition. In this report, we describe the cytotoxicity and anti-tumour activity of the novel MEK inhibitor, E6201, in a broad panel of melanoma cell lines (n = 31) of known mutational profile in vitro and in vivo. We further test the effectiveness of combining E6201 with an inhibitor of PI3K (LY294002) in overcoming resistance in these cell lines. RESULTS: The majority of melanoma cell lines were either sensitive (IC50 < 500 nM, 24/31) or hypersensitive (IC50 < 100 nM, 18/31) to E6201. This sensitivity correlated with wildtype PTEN and mutant BRAF status, whereas mutant RAS and PI3K pathway activation were associated with resistance. Although MEK inhibitors predominantly exert a cytostatic effect, E6201 elicited a potent cytocidal effect on most of the sensitive lines studied, as evidenced by Annexin positivity and cell death ELISA. Conversely, E6201 did not induce cell death in the two resistant melanoma cell lines tested. E6201 inhibited xenograft tumour growth in all four melanoma cell lines studied to varying degrees, but a more pronounced anti-tumour effect was observed for cell lines that previously demonstrated a cytocidal response in vitro. In vitro combination studies of E6201 and LY294002 showed synergism in all six melanoma cell lines tested, as defined by a mean combination index < 1. CONCLUSIONS: Our data demonstrate that E6201 elicits a predominantly cytocidal effect in vitro and in vivo in melanoma cells of diverse mutational background. Resistance to E6201 was associated with disruption of PTEN and activation of downstream PI3K signalling. In keeping with these data we demonstrate that co-inhibition of MAPK and PI3K is effective in overcoming resistance inherent in melanoma.

Cameron's hot air. Pollution, fraud and the politics of carbon emissions

It is widely recognised that exposure to air pollutants affect pulmonary and lung dysfunction as well as a range of neurological and vascular disorders. The rapid increase of worldwide carbon emissions continues to compromise environmental sustainability whilst contributing to premature death. Moreover, the harms caused by air pollution have a more pernicious reach, such as being the major source of climate change and ‘natural disasters’, which reportedly kills millions of people each year (World Health Organization, 2012). The opening quotations tell a story of the UK government's complacency towards the devastation of toxic and contaminating air emissions. The above headlines greeted the British public earlier this year after its government was taken to the Court of Appeal for an appalling air pollution record that continues to cause the premature deaths of 30,000 British people each year at a health cost estimated at £20 billion per annum. This combined with pending legal proceedings against the UK government for air pollution violations by the European Commission, point to a Cameron government that prioritises hot air and profit margins over human lives. The UK's legal air pollution regimes are an industry dominated process that relies on negotiation and partnership between regulators and polluters. The entire model seeks to assist business compliance rather than punish corporate offenders. There is no language of ‘crime’ in relation to UK air pollution violations but rather a discourse of ‘exceedence’ (Walters, 2010). It is a regulatory system not premised on the ‘polluter pay’ principle but instead the ‘polluter profit’ principle.

Making space for knowledge generation and place for knowledge communities : an analysis of the Australian practice

In the era of global knowledge economy, urban regions—seeking to increase their competitive edge, become destinations for talent and investment, and provide prosperity and quality of life to their inhabitants—have little chance achieving their development goals without forming effective knowledge-based urban development strategies. This paper aims to shed light on the planning and development processes of the knowledge-based urban development phenomenon with respect to the construction of knowledge community precincts aimed at making space for knowledge generation and place for knowledge communities. Following to a thorough review of the literature on knowledge-based urban development and strategic asset-based planning, the paper undertakes policy and best practice analyses to learn from the planning and development processes of internationally renowned knowledge community precincts—from Copenhagen, Eindhoven and Singapore. In the light of the analyses findings, this paper scrutinises major Australian knowledge community precinct initiatives—from Sydney, Melbourne and Brisbane—to better understand the dynamics of national practices, and benchmark them against the international best practice cases. The paper concludes with a discussion on the study findings and recommendations for successfully establishing space and place for both knowledge economy and society in Australian cities.

The backfilled GEI : a cross-capture modality gait feature for frontal and side-view gait recognition

In this paper, we propose a novel direction for gait recognition research by proposing a new capture-modality independent, appearance-based feature which we call the Back-filled Gait Energy Image (BGEI). It can can be constructed from both frontal depth images, as well as the more commonly used side-view silhouettes, allowing the feature to be applied across these two differing capturing systems using the same enrolled database. To evaluate this new feature, a frontally captured depth-based gait dataset was created containing 37 unique subjects, a subset of which also contained sequences captured from the side. The results demonstrate that the BGEI can effectively be used to identify subjects through their gait across these two differing input devices, achieving rank-1 match rate of 100%, in our experiments. We also compare the BGEI against the GEI and GEV in their respective domains, using the CASIA dataset and our depth dataset, showing that it compares favourably against them. The experiments conducted were performed using a sparse representation based classifier with a locally discriminating input feature space, which show significant improvement in performance over other classifiers used in gait recognition literature, achieving state of the art results with the GEI on the CASIA dataset.

Submission to the ALRC copyright exceptions review issues paper

Australia should introduce a transformative use exception. Transformative use is an important part of the copyright balance: it provides a mechanism through which to balance the rights of past authors against the interests of future authors. In the interests of promoting creativity and innovation, the impact of copyright law on the ability of Australians to create new works should be minimised. The scope of a transformative use exception should be based primarily on demonstrable harm to the direct licensing interests of copyright owners – the core of copyright. Importantly, however, there are unresolved questions about fairness that need to be more clearly addressed before the appropriate scope of a transformative use exception can be determined. This submission does not directly address the desirability of introducing a broader fair use right. It is likely that an open ended fair use exception is required to provide a more adequate balance between copyright owners and non-transformative users of copyright. If a broad fair use style exception is introduced, it would likely be desirable to include transformative uses within that exception. This submission, however, takes the more limited position that regardless of whether a fair use exception is introduced, an exception that permits unlicensed transformative uses is required in Australian copyright law.

Legal issues in the design and implementation of environmental offset and environmental trading frameworks

The Queensland Government released its new Environmental Offset Policy in July 2008. This policy creates a set of overarching principles which are to be incorporated into existing environmental offset policy. This article is the final article in a set of three interrelated articles discussing the operation and implementation of environmental offsets in Queensland. The first article discusses the Environmental Offsets Discussion Paper and the existing environmental offset requirements. No significant changes have been made to these existing offset requirements under the new Environmental Offset Policy. This article also touches briefly on the legal issues associated with design and implementation of environmental offset and trading frameworks. The second article considered the compatibility of different land tenure arrangements in Queensland against the requirements for the creation and trade of environmental offsets. The third article being the present article, discusses the application of the new Environmental Offset Policy while also analysing the legal issues associated with environmental offsets in further detail.