Mapping of transcription termination within the S segment of SFTS phlebovirus facilitated the generation of NSs-deletant viruses

SFTS phlebovirus (severe fever with thrombocytopenia syndrome virus; SFTSV) is an emerging tick-borne bunyavirus that was first reported in China in 2009. Here we report the generation of a recombinant SFTSV (rHB29NSsKO) that cannot express the viral non-structural protein (NSs) upon infection of cells in culture. We show that rHB29NSsKO replication kinetics are greater in interferon (IFN)-incompetent cells and that the virus is unable to suppress IFN induced in response to viral replication. The data confirm for the first time in the context of virus infection that NSs acts as a virally encoded IFN antagonist and that NSs is dispensable for virus replication. Using 3’ RACE we mapped the 3’ -end of the N and NSs mRNAs, showing that the mRNAs terminate within the coding region of the opposite open reading frame. We show that the 3’ end of the N mRNA terminates upstream of a 5’ -GCCAGCC-3’ motif present in the viral genomic RNA. With this knowledge, and using virus-like particles, we could demonstrate that the last 36 nt of the NSs ORF were needed to ensure the efficient termination of the N mRNA and were required for recombinant virus rescue. We demonstrate it is possible to recover viruses lacking NSs, expressing just a 12 amino acid NSs peptide or viruses encoding eGFP or a NSs-eGFP fusion protein in the NSs locus. This opens the possibility for further studies of NSs and potentially the design of attenuated viruses for vaccination studies

Issues in evaluating the costs and cost-effectiveness of Cognitive Behavioural Therapy for overweight/obese adolescents, CHERE Working Paper 2009/1

Economic evaluation is the systematic assessment of the costs and consequences of alternative courses of action. In health and healthcare, the results can be used to inform clinicians and policy makers about the relative cost-effectiveness of options under consideration [1]. Many economic evaluations are undertaken alongside randomised controlled trials (RCTs); the advantages of this approach are that i) prospective, accurate data can be collected on costs and effects and ii) appropriate outcome measures for use in economic evaluation can be chosen. The outcome of an economic evaluation is usually described as a ratio of the costs and effects ? often called the incremental cost-effectiveness ratio (ICER). The ICER is determined by calculating the differences in the costs and effects of both intervention and control groups and dividing the former by the latter. In designing an economic evaluation, the important questions to resolve are: which costs should be included and which outcome measures are most appropriate for estimating the cost-effectiveness ratio? In 2005, the Australian Technology Network of Universities funded the Centre for Metabolic Fitness (CMF) through a competitive, peer-reviewed process. The aims of the centre are to develop and evaluate diet and exercise interventions to counteract metabolic syndrome and assess their acceptability by target community groups. Metabolic syndrome is a cluster of metabolically determined risk factors associated with obesity (e.g. hypertension, impaired blood glucose etc). A number of collaborative projects have been developed within the centre, one of which is the CHOOSE HEALTH project. As part of this project, the effectiveness of cognitive behavioural therapy (CBT) as an intervention for overweight or obese adolescents has been trialled at the University of RMIT by Leah Brennan and the University of South Australia by Margarita Tsiros, as part of their post-graduate studies1. Subsequently, it has been decided to add an economic component to this work. Trials of the effectiveness and cost-effectiveness of different means of delivering cognitive behaviourally based weight management programs are planned2. This paper reports the results of investigations into the two questions which need to be addressed prior to undertaking a formal economic evaluation of the CHOOSE HEALTH program: i) what costs should be included and ii) which measures of outcome are suitable for estimating an ICER in this context. The paper is organised in four sections. Following the introduction (section 1) and brief descriptions of the background to and context in which the program was planned (section 2), details of the RMIT trial design and results are provided in section 3. In the final section (section 4), a cost model is presented and the implications of the outcomes used in the initial trials of the effectiveness are discussed in relation to designing a prospective economic evaluation of the CHOOSE HEALTH program.costs, economic evaluation, cognitive behavioural therapy (CBT), adolescent obesity, Australia

Silicon carbide technology for extreme environments

PhD ThesisWith mankind’s ever increasing curiosity to explore the unknown, including a variety of hostile environments where we cannot tread, there exists a need for machines to do work on our behalf. For applications in the most extreme environments and applications silicon based electronics cannot function, and there is a requirement for circuits and sensors to be built from wide band gap materials capable of operation in these domains. This work addresses the initial development of silicon carbide circuits to monitor conditions and transmit information from such hostile environments. The characterisation, simulation and implementation of silicon carbide based circuits utilising proprietary high temperature passives is explored. Silicon carbide is a wide band gap semiconductor material with highly suitable properties for high-power, high frequency and high temperature applications. The bandgap varies depending on polytype, but the most commonly used polytype 4H, has a value of 3.265 eV at room temperature, which reduces as the thermal ionization of electrons from the valence band to the conduction band increases, allowing operation in ambient up to 600°C. Whilst silicon carbide allows for the growth of a native oxide, the quality has limitations and therefore junction field effect transistors (JFETs) have been utilised as the switch in this work. The characteristics of JFET devices are similar to those of early thermionic valve technology and their use in circuits is well known. In conjunction with JFETs, Schottky barrier diodes (SBDs) have been used as both varactors and rectifiers. Simulation models for high temperature components have been created through their characterisation of their electrical parameters at elevated temperatures. The JFETs were characterised at temperatures up to 573K, and values for TO V , β , λ , IS , RS and junction capacitances were extracted and then used to mathematically describe the operation of circuits using SPICE. The transconductance of SiC JFETs at high temperatures has been shown to decrease quadratically indicating a strong dependence upon carrier mobility in the channel. The channel resistance also decreased quadratically as a direct result of both electric field and temperature enhanced trap emission. The JFETs were tested to be operational up to 775K, where they failed due to delamination of an external passivation layer. ii Schottky diodes were characterised up to 573K, across the temperature range and values for ideality factor, capacitance, series resistance and forward voltage drop were extracted to mathematically model the devices. The series resistance of a SiC SBD exhibited a quadratic relationship with temperature indicating that it is dominated by optical phonon scattering of charge carriers. The observed deviation from a temperature independent ideality factor is due to the recombination of carriers in the depletion region affected by both traps and the formation of an interfacial layer at the SiC/metal interface. To compliment the silicon carbide active devices utilised in this work, high temperature passive devices and packaging/circuit boards were developed. Both HfO2 and AlN materials were investigated for use as potential high temperature capacitor dielectrics in metal-insulator-metal (MIM) capacitor structures. The different thicknesses of HfO2 (60nm and 90nm) and 300nm for AlN and the relevance to fabrication techniques are examined and their effective capacitor behaviour at high temperature explored. The HfO2 based capacitor structures exhibited high levels of leakage current at temperatures above 100°C. Along with elevated leakage when subjected to higher electric fields. This current leakage is due to the thin dielectric and high defect density and essentially turns the capacitors into high value resistors in the order of MΩ. This renders the devices unsuitable as capacitors in hostile environments at the scales tested. To address this issue AlN capacitors with a greater dielectric film thickness were fabricated with reduced leakage currents in comparison even at an electric field of 50MV/cm at 600K. The work demonstrated the world’s first high temperature wireless sensor node powered using energy harvesting technology, capable of operation at 573K. The module demonstrated the world’s first amplitude modulation (AM) and frequency modulation (FM) communication techniques at high temperature. It also demonstrated a novel high temperature self oscillating boost converter cable of boosting voltages from a thermoelectric generator also operating at this temperature. The AM oscillator operated at a maximum temperature of 553K and at a frequency of 19.4MHz with a signal amplitude 65dB above background noise. Realised from JFETs and HfO2 capacitors, modulation of the output signal was achieved by varying the load resistance by use of a second SiC JFET. By applying a negative signal voltage of between -2.5 and -3V, a 50% reduction in the signal amplitude and therefore Amplitude Modulation was achieved by modulating the power within the oscillator through the use of this secondary JFET. Temperature drift in the characteristics were also observed, iii with a decrease in oscillation frequency of almost 200 kHz when the temperature changed from 300K to 573K. This decrease is due to the increase in capacitance density of the HfO2 MIM capacitors and increasing junction capacitances of the JFET used as the amplifier within the oscillator circuit. Direct frequency modulation of a SiC Voltage Controlled Oscillator was demonstrated at a temperature of 573K with a oscillation frequency of 17MHz. Realised from an SiC JFET, AlN capacitors and a SiC SBD used as a varactor. It was possible to vary the frequency of oscillations by 100 kHz with an input signal no greater than 1.5V being applied to the SiC SBD. The effects of temperature drift were more dramatic in comparison to the AM circuit at 400 kHz over the entire temperature range, a result of the properties of the AlN film which causes the capacitors to increase in capacitance density by 10%. A novel self oscillating boost converter was commissioned using a counter wound transformer on high temperature ferrite, a SiC JFET and a SiC SBD. Based upon the operation of a free running blocking oscillator, oscillatory behaviour is a result of the electric and magnetic variations in the winding of the transformer and the amplification characteristics of a JFET. It demonstrated the ability to boost an input voltage of 1.3 volts to 3.9 volts at 573K and exhibited an efficiency of 30% at room temperature. The frequency of operation was highly dependent upon the input voltage due to the increased current flow through the primary coil portion of the transformer and the ambient temperature causing an increase in permeability of the ferrite, thus altering the inductance of both primary and secondary windings. However due its simplicity and its ability to boost the input voltage by 250% meant it was capable of powering the transmitters and in conjunction with a Themoelectric Generator so formed the basis for a self powered high temperature silicon carbide sensor node. The demonstration of these high temperature circuits provide the initial stages of being able to produce a high temperature wireless sensor node capable of operation in hostile environments. Utilising the self oscillating boost converter and a high temperature Thermoelectric Generator these prototype circuits were showed the ability to harvest energy from the high temperature ambient and power the silicon carbide circuitry. Along with appropriate sensor technology it demonstrated the feasibility of being able to monitor and transmit information from hazardous locations which is currently unachievable

Energy transitions, sub-national government and regime flexibility : how has devolution in the United Kingdom affected renewable energy development?

We acknowledge the support of the Economic and Social Research Council for funding the research on which this paper was based (Grant Number RES-062-23-2526).Peer reviewedPostprin

Palliative Care as a Human Right

Examines the state of palliative care for AIDS patients worldwide, approaches to palliative care as a human right and a public health issue, legal foundations, challenges to its promotion and provision, and strategies and mechanisms for enhancing access