Evaluation of an inactivated Ross River virus vaccine in active and passive mouse immunization models and establishment of a correlate of protection

Ross River Virus has caused reported outbreaks of epidemic polyarthritis, a chronic debilitating disease associated with significant long-term morbidity in Australia and the Pacific region since the 1920s. To address this public health concern, a formalin- and UV-inactivated whole virus vaccine grown in animal protein-free cell culture was developed and tested in preclinical studies to evaluate immunogenicity and efficacy in animal models. After active immunizations, the vaccine dose-dependently induced antibodies and protected adult mice from viremia and interferon α/β receptor knock-out (IFN-α/βR(-/-)) mice from death and disease. In passive transfer studies, administration of human vaccinee sera followed by RRV challenge protected adult mice from viremia and young mice from development of arthritic signs similar to human RRV-induced disease. Based on the good correlation between antibody titers in human sera and protection of animals, a correlate of protection was defined. This is of particular importance for the evaluation of the vaccine because of the comparatively low annual incidence of RRV disease, which renders a classical efficacy trial impractical. Antibody-dependent enhancement of infection, did not occur in mice even at low to undetectable concentrations of vaccine-induced antibodies. Also, RRV vaccine-induced antibodies were partially cross-protective against infection with a related alphavirus, Chikungunya virus, and did not enhance infection. Based on these findings, the inactivated RRV vaccine is expected to be efficacious and protect humans from RRV disease

Vapour phase assembly of a halogen bonded complex of an isoindoline nitroxide and 1,2-diiodotetrafluorobenzene

Vapour phase assembly has been used for the first time to prepare co-crystals in which the primary intermolecular interaction is halogen bonding. Co-crystals of the nitroxide 1,1,3,3-tetramethylisoindolin-2-yloxyl (TMIO) and 1,2-diiodotetrafluorobenzene (1,2-DITFB) are readily formed under standard sublimation conditions. Single crystal X-ray diffraction confirmed the structure of a 2:2 cyclic tetramer, (TMIO)2·(1,2-DITFB)2, which exhibits a new halogen bonding motif, with each nitroxide oxygen atom accepting two halogen bonds. Powder X-ray diffraction confirmed the homogeneity of the bulk sample. The crystalline complex was further characterized in the solid state using thermal analysis and vibrational spectroscopy (infrared and Raman). Density functional theory calculations were also used to evaluate the enthalpy of formation, electrostatic potential and unpaired electron density of the complex. These findings illustrate the preparation of co-crystals where solution state methodology is problematic and the potential of this approach for the formation of novel organic spin systems.

A two-metal ion mechanism operates in the hammerhead ribozyme-mediated cleavage of an RNA substrate

Evidence for a two-metal ion mechanism for cleavage of the HH16 hammerhead ribozyme is provided by monitoring the rate of cleavage of the RNA substrate as a function of La3+ concentration in the presence of a constant concentration of Mg2+. We show that a bell-shaped curve of cleavage activation is obtained as La3+ is added in micromolar concentrations in the presence of 8 mM Mg2+, with a maximal rate of cleavage being attained in the presence of 3 microM La3+. These results show that two-metal ion binding sites on the ribozyme regulate the rate of the cleavage reaction and, on the basis of earlier estimates of the Kd values for Mg2+ of 3.5 mM and > 50 mM, that these sites bind La3+ with estimated Kd values of 0.9 and > 37.5 microM, respectively. Furthermore, given the very different effects of these metal ions at the two binding sites, with displacement of Mg2+ by La3+ at the stronger (relative to Mg2+) binding site activating catalysis and displacement of Mg2+ by La3+ at the weaker (relative to Mg2+) (relative to Mg2+) binding site inhibiting catalysis, we show that the metal ions at these two sites play very different roles. We argue that the metal ion at binding site 1 coordinates the attacking 2'-oxygen species in the reaction and lowers the pKa of the attached proton, thereby increasing the concentration of the attacking alkoxide nucleophile in an equilibrium process. In contrast, the role of the metal ion at binding site 2 is to catalyze the reaction by absorbing the negative charge that accumulates at the leaving 5'-oxygen in the transition state. We suggest structural reasons why the Mg(2+)-La3+ ion combination is particularly suited to demonstrating these different roles of the two-metal ions in the ribozyme cleavage reaction.

Contributors to life satisfaction in parents of an adult child with Down syndrome

Aim: This study investigated: (1) concurrent relationships between measures of family life and parental satisfaction with life in parents of an adult with Down syndrome and (2) influence of early family functioning on current parental satisfaction. Method: Sixty-two families were interviewed using a semi-structured interview, and responded to a series of questionnaires related to family functioning when their child with Down syndrome was between 7 and 15 years. Fifteen years later parents were asked to provide data on their current situation, including mental health, and satisfaction and difficulties with respect to care-giving in relation to their adult child. Results: Over half the families provided data to the second phase of the study. Life circumstances were appreciably worse for a small group of families than had been the case 15 years previously; however, these changes were generally unrelated to their parenting role. Overall, parents reported experiencing satisfaction from their care-giving role and did not report high levels of difficulties emanating from this role. Conclusions: Most parents demonstrated good levels of personal functioning, although there was a small group for whom this was not the case. Earlier functioning did not make a strong contribution to current levels of life satisfaction.

The acquisition of an artificial logographic script and bilingual working memory : Evidence for L1-specific orthographic processing skills transfer in Chinese-English bilinguals

Studies of orthographic skills transfer between languages focus mostly on working memory (WM) ability in alphabetic first language (L1) speakers when learning another, often alphabetically congruent, language. We report two studies that, instead, explored the transferability of L1 orthographic processing skills in WM in logographic-L1 and alphabetic-L1 speakers. English-French bilingual and English monolingual (alphabetic-L1) speakers, and Chinese-English (logographic-L1) speakers, learned a set of artificial logographs and associated meanings (Study 1). The logographs were used in WM tasks with and without concurrent articulatory or visuo-spatial suppression. The logographic-L1 bilinguals were markedly less affected by articulatory suppression than alphabetic-L1 monolinguals (who did not differ from their bilingual peers). Bilinguals overall were less affected by spatial interference, reflecting superior phonological processing skills or, conceivably, greater executive control. A comparison of span sizes for meaningful and meaningless logographs (Study 2) replicated these findings. However, the logographic-L1 bilinguals’ spans in L1 were measurably greater than those of their alphabetic-L1 (bilingual and monolingual) peers; a finding unaccounted for by faster articulation rates or differences in general intelligence. The overall pattern of results suggests an advantage (possibly perceptual) for logographic-L1 speakers, over and above the bilingual advantage also seen elsewhere in third language (L3) acquisition.

Reconstructing the event stratigraphy from the complex structural - stratigraphic architecture of an Archaean volcanic – intrusive – sedimentary succession : the Boorara Domain, Eastern Goldfields Superterrane, Western Australia

Two main deformational phases are recognised in the Archaean Boorara Domain of the Kalgoorlie Terrane, Eastern Goldfields Superterrane, Yilgarn Craton, Western Australia, primarily involving southover- north thrust faulting that repeated and thickened the stratigraphy, followed by east northeast – west-southwest shortening that resulted in macroscale folding of the greenstone lithologies. The domain preserves mid-greenschist facies metamorphic grade, with an increase to lower amphibolite metamorphic grade towards the north of the region. As a result of the deformation and metamorphism, individual stratigraphic horizons are difficult to trace continuously throughout the entire domain. Volcanological and sedimentological textures and structures, primary lithological contacts, petrography and geochemistry have been used to correlate lithofacies between faultbounded structural blocks. The correlated stratigraphic sequence for the Boorara Domain comprises quartzo-feldspathic turbidite packages, overlain by high-Mg tholeiitic basalt (lower basalt), coherent and clastic dacite facies, intrusive and extrusive komatiite units, an overlying komatiitic basalt unit (upper basalt), and at the stratigraphic top of the sequence, volcaniclastic quartz-rich turbidites. Reconstruction of the stratigraphy and consideration of emplacement dynamics has allowed reconstruction of the emplacement history and setting of the preserved sequence. This involves a felsic, mafic and ultramafic magmatic system emplaced as high-level intrusions, with localised emergent volcanic centres, into a submarine basin in which active sedimentation was occurring.

Assessment of flood-related recharge to alluvial aquifers of an irrigated catchment following extended drought conditions using 3D visualisation and environmental tracers, Lockyer Valley, southeast Queensland, Australia.

The Lockyer Valley in southeast Queensland, Australia, hosts an economically significant alluvial aquifer system which has been impacted by prolonged drought conditions (~1997 to ~ 2009). Throughout this time, the system was under continued groundwater extraction, resulting in severe aquifer depletion. By 2008, much of the aquifer was at <30% of storage but some relief occurred with rains in early 2009. However, between December 2010 and January 2011, most of southeast Queensland experienced unprecedented flooding, which generated significant aquifer recharge. In order to understand the spatial and temporal controls of groundwater recharge in the alluvium, a detailed 3D lithological property model of gravels, sands and clays was developed using GOCAD software. The spatial distribution of recharge throughout the catchment was assessed using hydrograph data from about 400 groundwater observation wells screened at the base of the alluvium. Water levels from these bores were integrated into a catchment-wide 3D geological model using the 3D geological modelling software GOCAD; the model highlights the complexity of recharge mechanisms. To support this analysis, groundwater tracers (e.g. major and minor ions, stable isotopes, 3H and 14C) were used as independent verification. The use of these complementary methods has allowed the identification of zones where alluvial recharge primarily occurs from stream water during episodic flood events. However, the study also demonstrates that in some sections of the alluvium, rainfall recharge and discharge from the underlying basement into the alluvium are the primary recharge mechanisms of the alluvium. This is indicated by the absence of any response to the flood, as well as the observed old radiocarbon ages and distinct basement water chemistry signatures at these locations. Within the 3D geological model, integration of water chemistry and time-series displays of water level surfaces before and after the flood suggests that the spatial variations of the flood response in the alluvium are primarily controlled by the valley morphology and lithological variations within the alluvium. The integration of time-series of groundwater level surfaces in the 3D geological model also enables the quantification of the volumetric change of groundwater stored in the unconfined sections of this alluvial aquifer during drought and following flood events. The 3D representation and analysis of hydraulic and recharge information has considerable advantages over the traditional 2D approach. For example, while many studies focus on singular aspects of catchment dynamics and groundwater-surface water interactions, the 3D approach is capable of integrating multiple types of information (topography, geological, hydraulic, water chemistry and spatial) into a single representation which provides valuable insights into the major factors controlling aquifer processes.

Australia's adoption of an international tax regime : to engage or not to engage?

On 1 November 2011 the Minister for Financial Services and Superannuation, the Honourable Bill Shorten MP, announced that Australia would be undertaking a reform of the ‘transfer pricing rules in the income tax law and Australia's future tax treaties to bring them into line with international best practice, improving the integrity and efficiency of the tax system.’ Mr Shorten stated that the reason for the reform was that ‘recent court decisions suggest our existing transfer pricing rules may be interpreted in a way that is out-of-kilter with international norms.’ Further, he stated that ‘the Government has asked the Treasury to review how the transfer pricing rules can be improved, including but not limited to how to be more in line with international best practice.’ He urged all interested parties to participate in this consultation process.

Application of an appearance-based intervention to improve sun protection outcomes of outdoor workers in Queensland, Australia

Outdoor workers are exposed to high levels of ultraviolet radiation (UVR) and may thus be at greater risk to experience UVR-related health effects such as skin cancer, sun burn, and cataracts. A number of intervention trials (n=14) have aimed to improve outdoor workers’ work-related sun protection cognitions and behaviours. Only one study however has reported the use of UV-photography as part of a multi-component intervention. This study was performed in the USA and showed long-term (12 months) improvements in work-related sun protection behaviours. Intervention effects of the other studies have varied greatly, depending on the population studied, intervention applied, and measurement of effect. Previous studies have not assessed whether: - Interventions are similarly effective for workers in stringent and less stringent policy organisations; - Policy effect is translated into workers’ leisure time protection; - Implemented interventions are effective in the long-term; - The facial UV-photograph technique is effective in Australian male outdoor workers without a large additional intervention package, and; - Such interventions will also affect workers’ leisure time sun-related cognitions and behaviours. Therefore, the present Protection of Outdoor Workers from Environmental Radiation [POWER]-study aimed to fill these gaps and had the objectives of: a) assessing outdoor workers’ sun-related cognitions and behaviours at work and during leisure time in stringent and less stringent sun protection policy environments; b) assessing the effect of an appearance-based intervention on workers’ risk perceptions, intentions and behaviours over time; c) assessing whether the intervention was equally effective within the two policy settings; and d) assessing the immediate post-intervention effect. Effectiveness was described in terms of changes in sun-related risk perceptions and intentions (as these factors were shown to be main precursors of behaviour change in many health promotion theories) and behaviour. The study purposefully selected and recruited two organisations with a large outdoor worker contingent in Queensland, Australia within a 40 kilometre radius of Brisbane. The two organisations differed in the stringency of implementation and reinforcement of their organisational sun protection policy. Data were collected from 154 male predominantly Australian born outdoor workers with an average age of 37 years and predominantly medium to fair skin (83%). Sun-related cognitions and behaviours of workers were assessed using self-report questionnaires at baseline and six to twelve months later. Variation in follow-up time was due to a time difference in the recruitment of the two organisations. Participants within each organisation were assigned to an intervention or control group. The intervention group participants received a one-off personalised Skin Cancer Risk Assessment Tool [SCRAT]-letter and a facial UV-photograph with detailed verbal information. This was followed by an immediate post-intervention questionnaire within three months of the start of the study. The control group only received the baseline and follow-up questionnaire. Data were analysed using a variety of techniques including: descriptive analyses, parametric and non-parametric tests, and generalised estimating equations. A 15% proportional difference observed was deemed of clinical significance, with the addition of reported statistical significance (p<0.05) where applicable. Objective 1: Assess and compare the current sun-related risk perceptions, intentions, behaviours, and policy awareness of outdoor workers in stringent and less stringent sun protection policy settings. Workers within the two organisations (stringent n=89 and less stringent n=65) were similar in their knowledge about skin cancer, self efficacy, attitudes, and social norms regarding sun protection at work and during leisure time. Participants were predominantly in favour of sun protection. Results highlighted that compared to workers in a less stringent policy organisation working for an organisation with stringent sun protection policies and practices resulted in more desirable sun protection intentions (less willing to tan p=0.03) ; actual behaviours at work (sufficient use of upper and lower body protection, headgear, and sunglasses (p<0.001 for all comparisons), and greater policy awareness (awareness of repercussions if Personal Protective Equipment (PPE) was not used, p<0.001)). However the effect of the work-related sun protection policy was found not to extend to leisure time sun protection. Objective 2: Compare changes in sun-related risk perceptions, intentions, and behaviours between the intervention and control group. The effect of the intervention was minimal and mainly resulted in a clinically significant reduction in work-related self-perceived risk of developing skin cancer in the intervention compared to the control group (16% and 32% for intervention and control group, respectively estimated their risk higher compared to other outdoor workers: , p=0.11). No other clinical significant effects were observed at 12 months follow-up. Objective 3: Assess whether the intervention was equally effective in the stringent sun protection policy organisation and the less stringent sun protection policy organisation. The appearance-based intervention resulted in a clinically significant improvement in the stringent policy intervention group participants’ intention to protect from the sun at work (workplace*time interaction, p=0.01). In addition to a reduction in their willingness to tan both at work (will tan at baseline: 17% and 61%, p=0.06, at follow-up: 54% and 33%, p=0.07, stringent and less stringent policy intervention group respectively. The workplace*time interaction was significant p<0.001) and during leisure time (will tan at baseline: 42% and 78%, p=0.01, at follow-up: 50% and 63%, p=0.43, stringent and less stringent policy intervention group respectively. The workplace*time interaction was significant p=0.01) over the course of the study compared to the less stringent policy intervention group. However, no changes in actual sun protection behaviours were found. Objective 4: Examine the effect of the intervention on level of alarm and concern regarding the health of the skin as well as sun protection behaviours in both organisations. The immediate post-intervention results showed that the stringent policy organisation participants indicated to be less alarmed (p=0.04) and concerned (p<0.01) about the health of their skin and less likely to show the facial UV-photograph to others (family p=0.03) compared to the less stringent policy participants. A clinically significantly larger proportion of participants from the stringent policy organisation reported they worried more about skin cancer (65%) and skin freckling (43%) compared to those in the less stringent policy organisation (46%,and 23% respectively , after seeing the UV-photograph). In summary the results of this study suggest that the having a stringent work-related sun protection policy was significantly related to for work-time sun protection practices, but did not extend to leisure time sun protection. This could reflect the insufficient level of sun protection found in the general Australian population during leisure time. Alternatively, reactance caused by being restricted in personal decisions through work-time policy could have contributed to lower leisure time sun protection. Finally, other factors could have also contributed to the less than optimal leisure time sun protection behaviours reported, such as unmeasured personal or cultural barriers. All these factors combined may have lead to reduced willingness to take proper preventive action during leisure time exposure. The intervention did not result in any measurable difference between the intervention and control groups in sun protection behaviours in this population, potentially due to the long lag time between the implementation of the intervention and assessment at 12-months follow-up. In addition, high levels of sun protection behaviours were found at baseline (ceiling effect) which left little room for improvement. Further, this study did not assess sunscreen use, which was the predominant behaviour assessed in previous effective appearance-based interventions trials. Additionally, previous trials were mainly conducted in female populations, whilst the POWER-study’s population was all male. The observed immediate post-intervention result could be due to more emphasis being placed on sun protection and risks related to sun exposure in the stringent policy organisation. Therefore participants from the stringent policy organisation could have been more aware of harmful effects of UVR and hence, by knowing that they usually protect adequately, not be as alarmed or concerned as the participants from the less stringent policy organisation. In conclusion, a facial UV-photograph and SCRAT-letter information alone may not achieve large changes in sun-related cognitions and behaviour, especially of assessed 6-12 months after the intervention was implemented and in workers who are already quite well protected. Differences found between workers in the present study appear to be more attributable to organisational policy. However, against a background of organisational policy, this intervention may be a useful addition to sun-related workplace health and safety programs. The study findings have been interpreted while respecting a number of limitations. These have included non-random allocation of participants due to pre-organised allocation of participants to study group in one organisation and difficulty in separating participants from either study group. Due to the transient nature of the outdoor worker population, only 105 of 154 workers available at baseline could be reached for follow-up. (attrition rate=32%). In addition the discrepancy in the time to follow-up assessment between the two organisations was a limitation of the current study. Given the caveats of this research, the following recommendations were made for future research: - Consensus should be reached to define "outdoor worker" in terms of time spent outside at work as well as in the way sun protection behaviours are measured and reported. - Future studies should implement and assess the value of the facial UV-photographs in a wide range of outdoor worker organisations and countries. - More timely and frequent follow-up assessments should be implemented in intervention studies to determine the intervention effect and to identify the best timing of booster sessions to optimise results. - Future research should continue to aim to target outdoor workers’ leisure time cognitions and behaviours and improve these if possible. Overall, policy appears to be an important factor in workers’ compliance with work-time use of sun protection. Given the evidence generated by this research, organisations employing outdoor workers should consider stringent implementation and reinforcement of a sun protection policy. Finally, more research is needed to improve ways to generate desirable behaviour in this population during leisure time.

Examining the effects of an eco-driving message on driver distraction

This paper examines the effects of an eco-driving message on driver distraction. Two in-vehicle distracter tasks were compared with an eco-driving task and a baseline task in an advanced driving simulator. N = 22 subjects were asked to perform an eco-driving, CD changing, and a navigation task while engaged in critical manoeuvres during which they were expected to respond to a peripheral detection task (PDT) with total duration of 3.5 h. The study involved two sessions over two consecutive days. The results show that drivers’ mental workloads are significantly higher during navigation and CD changing tasks in comparison to the two other scenarios. However, eco-driving mental workload is still marginally significant (p ∼ .05) across different manoeuvres. Similarly, event detection tasks show that drivers miss significantly more events in the navigation and CD changing scenarios in comparison to both the baseline and eco-driving scenario. Analysis of the practice effect shows that drivers’ baseline scenario and navigation scenario exhibit significantly less demand on the second day. Drivers also can detect significantly more events on the second day for all scenarios. The authors conclude that even reading a simple message while driving could potentially lead to missing an important event, especially when executing critical manoeuvres. However, there is some evidence of a practice effect which suggests that future research should focus on performance with habitual rather than novel tasks. It is recommended that sending text as an eco-driving message analogous to the study circumstances should not be delivered to drivers on-line when vehicle is in motion.

Sharing environmental data : the role of an information policy framework and copyright licensing

Advances in information and communication technologies have brought about an information revolution, leading to fundamental changes in the way that information is collected or generated, shared and distributed. The importance of establishing systems in which research findings can be readily made available to and used by other researchers has long been recognized in international scientific collaborations. If the data access principles adopted by international scientific collaborations are to be effectively implemented they must be supported by the national policies and laws in place in the countries in which participating researchers are operating.

Controlled emergency landing of an unpowered unmanned aerial system

The ability to perform autonomous emergency (forced) landings is one of the key technology enablers identified for UAS. This paper presents the flight test results of forced landings involving a UAS, in a controlled environment, and which was conducted to ascertain the performances of previously developed (and published) path planning and guidance algorithms. These novel 3-D nonlinear algorithms have been designed to control the vehicle in both the lateral and longitudinal planes of motion. These algorithms have hitherto been verified in simulation. A modified Boomerang 60 RC aircraft is used as the flight test platform, with associated onboard and ground support equipment sourced Off-the-Shelf or developed in-house at the Australian Research Centre for Aerospace Automation (ARCAA). HITL simulations were conducted prior to the flight tests and displayed good landing performance, however, due to certain identified interfacing errors, the flight results differed from that obtained in simulation. This paper details the lessons learnt and presents a plausible solution for the way forward.

A randomised controlled trial of an enhanced interdisciplinary community based group program for people with Parkinson’s disease: study rationale and protocol

Parkinson’s disease (PD) is a progressive, chronic neurodegenerative disorder for which there is no known cure. Physical exercise programs may be used to assist with the physical management of PD. Several studies have demonstrated that community based physical therapy programs are effective in reducing physical aspects of disability among people with PD. While multidisciplinary therapy interventions may have the potential to reduce disability and improve the quality of life of people with PD, there is very limited clinical trial evidence to support or refute the use of a community based multidisciplinary or interdisciplinary programs for people with PD. A two group randomized trial is being undertaken within a community rehabilitation service in Brisbane, Australia. Community dwelling adults with a diagnosis of Idiopathic Parkinson’s disease are being recruited. Eligible participants are randomly allocated to a standard exercise rehabilitation group program or an intervention group which incorporates physical, cognitive and speech activities in a multi-tasking framework. Outcomes will be measured at 6-week intervals for a period of six months. Primary outcome measures are the Montreal Cognitive Assessment (MoCA) and the Timed Up and Go (TUG) cognitive test. Secondary outcomes include changes in health related quality of life, communication, social participation, mobility, strength and balance, and carer burden measures. This study will determine the immediate and long-term effectiveness of a unique multifocal, interdisciplinary, dual-tasking approach to the management of PD as compared to an exercise only program. We anticipate that the results of this study will have implications for the development of cost effective evidence based best practice for the treatment of people with PD living in the community.