Defective interfering viral particles in acute dengue infections

While much of the genetic variation in RNA viruses arises because of the error-prone nature of their RNA-dependent RNA polymerases, much larger changes may occur as a result of recombination. An extreme example of genetic change is found in defective interfering (DI) viral particles, where large sections of the genome of a parental virus have been deleted and the residual sub-genome fragment is replicated by complementation by co-infecting functional viruses. While most reports of DI particles have referred to studies in vitro, there is some evidence for the presence of DI particles in chronic viral infections in vivo. In this study, short fragments of dengue virus (DENV) RNA containing only key regulatory elements at the 3' and 5' ends of the genome were recovered from the sera of patients infected with any of the four DENV serotypes. Identical RNA fragments were detected in the supernatant from cultures of Aedes mosquito cells that were infected by the addition of sera from dengue patients, suggesting that the sub-genomic RNA might be transmitted between human and mosquito hosts in defective interfering (DI) viral particles. In vitro transcribed sub-genomic RNA corresponding to that detected in vivo could be packaged in virus like particles in the presence of wild type virus and transmitted for at least three passages in cell culture. DENV preparations enriched for these putative DI particles reduced the yield of wild type dengue virus following co-infections of C6-36 cells. This is the first report of DI particles in an acute arboviral infection in nature. The internal genomic deletions described here are the most extensive defects observed in DENV and may be part of a much broader disease attenuating process that is mediated by defective viruses.

Identification of a cryptic Prokaryotic promoter within the cDNA encoding the 5′ End of Dengue Virus RNA Genome

Infectious cDNA clones of RNA viruses are important research tools, but flavivirus cDNA clones have proven difficult to assemble and propagate in bacteria. This has been attributed to genetic instability and/or host cell toxicity, however the mechanism leading to these difficulties has not been fully elucidated. Here we identify and characterize an efficient cryptic bacterial promoter in the cDNA encoding the dengue virus (DENV) 5′ UTR. Following cryptic transcription in E. coli, protein expression initiated at a conserved in-frame AUG that is downstream from the authentic DENV initiation codon, yielding a DENV polyprotein fragment that was truncated at the N-terminus. A more complete understanding of constitutive viral protein expression in E. coli might help explain the cloning and propagation difficulties generally observed with flavivirus cDNA.

Learning and teaching from the edge to centre stage : Critical factors in embedding sustainable university-wide engagement in external awards and grants funding initiatives.

Teaching awards, grants and fellowships are strategies used to recognise outstanding contributions to learning and teaching, encourage innovation, and to shift learning and teaching from the edge to centre stage. Examples range from school, faculty and institutional award and grant schemes to national schemes such as those offered by the Australian Learning and Teaching Council (ALTC), the Carnegie Foundation for the Advancement of Teaching in the United States, and the Fund for the Development of Teaching and Learning in higher education in the United Kingdom. The Queensland University of Technology (QUT) has experienced outstanding success in all areas of the ALTC funding since the inception of the Carrick Institute for Learning and Teaching in 2004. This paper reports on a study of the critical factors that have enabled sustainable and resilient institutional engagement with ALTC programs. As a lens for examining the QUT environment and practices, the study draws upon the five conditions of the framework for effective dissemination of innovation developed by Southwell, Gannaway, Orrell, Chalmers and Abraham (2005, 2010): 1. Effective, multi-level leadership and management 2. Climate of readiness for change 3. Availability of resources 4. Comprehensive systems in institutions and funding bodies 5. Funding design The discussion on the critical factors and practical and strategic lessons learnt for successful university-wide engagement offer insights for university leaders and staff who are responsible for learning and teaching award, grant and associated internal and external funding schemes.

Identification of area-level influences on regions of high cancer incidence in Queensland, Australia : a classification tree approach

Background: Strategies for cancer reduction and management are targeted at both individual and area levels. Area-level strategies require careful understanding of geographic differences in cancer incidence, in particular the association with factors such as socioeconomic status, ethnicity and accessibility. This study aimed to identify the complex interplay of area-level factors associated with high area-specific incidence of Australian priority cancers using a classification and regression tree (CART) approach. Methods: Area-specific smoothed standardised incidence ratios were estimated for priority-area cancers across 478 statistical local areas in Queensland, Australia (1998-2007, n=186,075). For those cancers with significant spatial variation, CART models were used to identify whether area-level accessibility, socioeconomic status and ethnicity were associated with high area-specific incidence. Results: The accessibility of a person’s residence had the most consistent association with the risk of cancer diagnosis across the specific cancers. Many cancers were likely to have high incidence in more urban areas, although male lung cancer and cervical cancer tended to have high incidence in more remote areas. The impact of socioeconomic status and ethnicity on these associations differed by type of cancer. Conclusions: These results highlight the complex interactions between accessibility, socioeconomic status and ethnicity in determining cancer incidence risk.

Developing the atlas of cancer in Queensland : methodological issues

Background: Achieving health equity has been identified as a major challenge, both internationally and within Australia. Inequalities in cancer outcomes are well documented, and must be quantified before they can be addressed. One method of portraying geographical variation in data uses maps. Recently we have produced thematic maps showing the geographical variation in cancer incidence and survival across Queensland, Australia. This article documents the decisions and rationale used in producing these maps, with the aim to assist others in producing chronic disease atlases. Methods: Bayesian hierarchical models were used to produce the estimates. Justification for the cancers chosen, geographical areas used, modelling method, outcome measures mapped, production of the adjacency matrix, assessment of convergence, sensitivity analyses performed and determination of significant geographical variation is provided. Conclusions: Although careful consideration of many issues is required, chronic disease atlases are a useful tool for assessing and quantifying geographical inequalities. In addition they help focus research efforts to investigate why the observed inequalities exist, which in turn inform advocacy, policy, support and education programs designed to reduce these inequalities.

Nursing Sans Frontieres: A Three Year Case Study of Multi-State Registration of Support Nursing Practice Using Information Technology

Objective: To highlight the registration issues for nurses who wish to practice nationally, particularly those practicing within the telehealth sector. Design: As part of a national clinical research study, applications were made to every state and territory for mutual recognition of nursing registration and fee waiver for telenursing cross boarder practice for a period of three years. These processes are described using a case study approach. Outcome: The aim of this case study was to achieve registration in every state and territory of Australia without paying multiple fees by using mutual recognition provisions and the cross-border fee waiver policy of the nurse regulatory authorities in order to practice telenursing. Results: Mutual recognition and fee waiver for cross-border practice was granted unconditionally in two states: Victoria (Vic) and Tasmania (Tas), and one territory: the Northern Territory (NT). The remainder of the Australian states and territories would only grant temporary registration for the period of the project or not at all, due to policy restrictions or nurse regulatory authority (NRA) Board decisions. As a consequence of gaining fee waiver the annual cost of registration was a maximum of $145 per annum as opposed to the potential $959 for initial registration and $625 for annual renewal. Conclusions: Having eight individual nurses Acts and NRAs for a population of 265,000 nurses would clearly indicate a case for over regulation in this country. The structure of regulation of nursing in Australia is a barrier to the changing and evolving role of nurses in the 21st century and a significant factor when considering workforce planning.

Libya and the international community’s 'responsibility to protect'

The Libyan regime’s attacks on its own civilian population are a test case for the international community’s commitment to the notion of a “responsibility to protect” (R2P). The UN Security Council’s statement on 22 February 2011 explicitly invoked this concept by calling on “the Government of Libya to meet its responsibility to protect its population”. Yet, with Muammar Gaddafi encouraging further violence against protesters and threatening to fight “until the last drop of blood” it seems unlikely that the Security Council’s warning will be heeded. Greater pressure from the international community will be needed to bring an end to the atrocities in Libya. The international response to the Libyan crisis represents an opportunity to translate the theory of R2P into practice.

A large change in temperature between neighbouring days increases the risk of mortality

Background: Previous studies have found high temperatures increase the risk of mortality in summer. However, little is known about whether a sharp decrease or increase in temperature between neighbouring days has any effect on mortality. Method: Poisson regression models were used to estimate the association between temperature change and mortality in summer in Brisbane, Australia during 1996–2004 and Los Angeles, United States during 1987–2000. The temperature change was calculated as the current day’s mean temperature minus the previous day’s mean. Results: In Brisbane, a drop of more than 3 °C in temperature between days was associated with relative risks (RRs) of 1.157 (95% confidence interval (CI): 1.024, 1.307) for total non external mortality (NEM), 1.186 (95%CI: 1.002, 1.405) for NEM in females, and 1.442 (95%CI: 1.099, 1.892) for people aged 65–74 years. An increase of more than 3 °C was associated with RRs of 1.353 (95%CI: 1.033, 1.772) for cardiovascular mortality and 1.667 (95%CI: 1.146, 2.425) for people aged < 65 years. In Los Angeles, only a drop of more than 3 °C was significantly associated with RRs of 1.133 (95%CI: 1.053, 1.219) for total NEM, 1.252 (95%CI: 1.131, 1.386) for cardiovascular mortality, and 1.254 (95%CI: 1.135, 1.385) for people aged ≥75 years. In both cities, there were joint effects of temperature change and mean temperature on NEM. Conclusion : A significant change in temperature of more than 3 °C, whether positive or negative, has an adverse impact on mortality even after controlling for the current temperature.

Right to the city, desire for the suburb?

The 2000s have been a lively decade for cities. The Worldwatch Institute estimated that 2007 was the first year in human history that more people worldwide lived in cities than the countryside. Globalisation and new digital media technologies have generated the seemingly paradoxical outcome that spatial location came to be more rather than less important, as combinations of firms, industries, cultural activities and creative talents have increasingly clustered around a select node of what have been termed “creative cities,” that are in turn highly networked into global circuits of economic capital, political power and entertainment media. Intellectually, the period has seen what the UCLA geographer Ed Soja refers to as the spatial turn in social theory, where “whatever your interests may be, they can be significantly advanced by adopting a critical spatial perspective”. This is related to the dynamic properties of socially constructed space itself, or what Soja terms “the powerful forces that arise from socially produced spaces such as urban agglomerations and cohesive regional economies,” with the result that “what can be called the stimulus of socio-spatial agglomeration is today being assertively described as the primary cause of economic development, technological innovation, and cultural creativity”

Towards distributed citizen participation : lessons from WikiLeaks and the Queensland Floods

This paper examines the rapid and ad hoc development and interactions of participative citizen communities during acute events, using the examples of the 2011 floods in Queensland, Australia, and the global controversy surrounding Wikileaks and its spokesman, Julian Assange. The self-organising community responses to such events which can be observed in these cases bypass or leapfrog, at least temporarily, most organisational or administrative hurdles which may otherwise frustrate the establishment of online communities; they fast-track the processes of community development and structuration. By understanding them as a form of rapid prototyping, e-democracy initiatives can draw important lessons from observing the community activities around such acute events.

Work-related subjective experiences among community residents with schizophrenia or schizoaffective disorder

Objective: To develop a self-report scale of subjective experiences of illness perceived to impact on employment functioning, as an alternative to a diagnostic perspective, for anticipating the vocational assistance needs of people with schizophrenia or schizoaffective disorders. Method: A repeated measures pilot study (n1 = 26, n2 = 21) of community residents with schizophrenia identified a set of work-related subjective experiences perceived to impact on employment functioning. Items with the best psychometric properties were applied in a 12 month longitudinal survey of urban residents with schizophrenia or schizoaffective disorder (n1 = 104; n2 = 94; n3 = 94). Results: Construct validity, factor structure, responsiveness, internal consistency, stability, and criterion validity investigations produced favourable results. Work-related subjective experiences provide information about the intersection of the person, the disorder, and expectations of employment functioning, which suggest new opportunities for vocational professionals to explore and discuss individual assistance needs. Conclusion: Further psychometric investigations of test-retest reliability, discriminant and predictive validity, and research applications in supported employment and vocational rehabilitation, are recommended. Subject to adequate psychometric properties, the new measure promises to facilitate exploring: individuals' specific subjective experiences; how each is perceived to contribute to employment restrictions; and the corresponding implications for specialized treatment, vocational interventions and workplace accommodations.

Error analysis and attitude observability of a monocular GPS/visual odometry integrated navigation filter

In this paper, we present a method for the recovery of position and absolute attitude (including pitch, roll and yaw) using a novel fusion of monocular Visual Odometry and GPS measurements in a similar manner to a classic loosely-coupled GPS/INS error state navigation filter. The proposed filter does not require additional restrictions or assumptions such as platform-specific dynamics, map-matching, feature-tracking, visual loop-closing, gravity vector or additional sensors such as an IMU or magnetic compass. An observability analysis of the proposed filter is performed, showing that the scale factor, position and attitude errors are fully observable under acceleration that is non-parallel to velocity vector in the navigation frame. The observability properties of the proposed filter are demonstrated using numerical simulations. We conclude the article with an implementation of the proposed filter using real flight data collected from a Cessna 172 equipped with a downwards-looking camera and GPS, showing the feasibility of the algorithm in real-world conditions.

Performance load testing and structural adequacy evaluation of road bridge decks

Many ageing road bridges, particularly timber bridges, require urgent improvement due to the demand imposed by the recent version of the Australian bridge loading code, AS 5100. As traffic volume plays a key role in the decision of budget allocations for bridge refurbishment/ replacement, many bridges in low volume traffic network remain in poor condition with axle load and/ or speed restrictions, thus disadvantaging many rural communities. This thesis examines an economical and environmentally sensible option of incorporating disused flat rail wagons (FRW) in the construction of bridges in low volume, high axle load road network. The constructability, economy and structural adequacy of the FRW road bridge is reported in the thesis with particular focus of a demonstration bridge commissioned in regional Queensland. The demonstration bridge comprises of a reinforced concrete slab (RCS) pavement resting on two FRWs with custom designed connection brackets at regular intervals along the span of the bridge. The FRW-RC bridge deck assembly is supported on elastomeric rubber pads resting on the abutment. As this type of bridge replacement technology is new and its structural design is not covered in the design standards, the in-service structural performance of the FRW bridge subjected to the high axle loadings prescribed in AS 5100 is examined through performance load testing. Both the static and the moving load tests are carried out using a fully laden commonly available three-axle tandem truck. The bridge deck is extensively strain gauged and displacement at several key locations is measured using linear variable displacement transducers (LVDTs). A high speed camera is used in the performance test and the digital image data are analysed using proprietary software to capture the locations of the wheel positions on the bridge span accurately. The wheel location is thus synchronised with the displacement and strain time series to infer the structural response of the FRW bridge. Field test data are used to calibrate a grillage model, developed for further analysis of the FRW bridge to various sets of high axle loads stipulated in the bridge design standard. Bridge behaviour predicted by the grillage model has exemplified that the live load stresses of the FRW bridge is significantly lower than the yield strength of steel and the deflections are well below the serviceability limit state set out in AS 5100. Based on the results reported in this thesis, it is concluded that the disused FRWs are competent to resist high axle loading prescribed in AS 5100 and are a viable alternative structural solution of bridge deck in the context of the low volume road networks.

Determinants of rapid weight gain during infancy: Baseline results from the NOURISH randomised controlled trial.

Background: Rapid weight gain in infancy is an important predictor of obesity in later childhood. Our aim was to determine which modifiable variables are associated with rapid weight gain in early life. Methods: Subjects were healthy infants enrolled in NOURISH, a randomised, controlled trial evaluating an intervention to promote positive early feeding practices. This analysis used the birth and baseline data for NOURISH. Birthweight was collected from hospital records and infants were also weighed at baseline assessment when they were aged 4-7 months and before randomisation. Infant feeding practices and demographic variables were collected from the mother using a self administered questionnaire. Rapid weight gain was defined as an increase in weight-for-age Z-score (using WHO standards) above 0.67 SD from birth to baseline assessment, which is interpreted clinically as crossing centile lines on a growth chart. Variables associated with rapid weight gain were evaluated using a multivariable logistic regression model. Results: Complete data were available for 612 infants (88% of the total sample recruited) with a mean (SD) age of 4.3 (1.0) months at baseline assessment. After adjusting for mother's age, smoking in pregnancy, BMI, and education and infant birthweight, age, gender and introduction of solid foods, the only two modifiable factors associated with rapid weight gain to attain statistical significance were formula feeding [OR=1.72 (95%CI 1.01-2.94), P= 0.047] and feeding on schedule [OR=2.29 (95%CI 1.14-4.61), P=0.020]. Male gender and lower birthweight were non-modifiable factors associated with rapid weight gain. Conclusions: This analysis supports the contention that there is an association between formula feeding, feeding to schedule and weight gain in the first months of life. Mechanisms may include the actual content of formula milk (e.g. higher protein intake) or differences in feeding styles, such as feeding to schedule, which increase the risk of overfeeding. Trial Registration: Australian Clinical Trials Registry ACTRN12608000056392

Determining indicators of transportation disadvantage for establishing knowledge-based environments

Although, transportation disadvantage or imbalance between travel needs and supply of transportation system is a great harm to knowledge based environments, quantification and objectively measuring the state of transportation disadvantaged remain to be a great challenge for researcher due to its ambiguity. This poses questions of whether the current indicators are accurately linked with transportation disadvantages and the effectiveness of the current policies. Using current indicators of transportation disadvantages, the state of transportation disadvantage is often exaggerated due to limited afford has been put forward to provide clear assessment on the existed relationship between transportation disadvantage indicators with travel performance or capability. This paper proposes a structural equation model of transportation disadvantage using household variables gained from the 2006-2008 South-East Queensland Travel Survey (SEQTS). The underlying relationships between social economics and demographic characteristics of household with travel performance are modelled using a latent variable approach. The final model has been able to fit the data gathered from SEQTS and explained established links between key household factors with travel capability and determined key indicator of travel capability. The model recognises that travel capability is directly influenced by household factors; vehicle ratio, license possession, retirees and pensioners.