Respiratory Syncytial Virus

RSV infection has an estimated global incidence of 33 million cases in children <5 years of age, with 10% requiring hospital admission and up to 199 000 dying of the disease. There is growing evidence that severe infantile RSV bronchiolitis, a condition characterised by an inflammatory reaction to the virus, is associated with later childhood wheeze in some vulnerable children; however, a direct causal relationship with asthma has not yet been established. RSV infection is also increasingly recognised as a cause of morbidity and mortality in those with underlying airway disease, the immunocompromised and frail elderly persons. Novel molecular-based diagnostic tools are becoming established, but treatment remains largely supportive, with palivizumab the only licensed agent currently available for passive prophylaxis of selected pre-term infants. While effective treatments remain elusive, there is optimism about the testing of novel antiviral drugs and the development of vaccines that may induce long-lasting immunity without the risk of disease augmentation

Towards the paperless office : an introduction to electronic structured document interchange : a thesis submitted to the Faculty of Technology in candidacy for the degree of Master of Technology (Computing), Department of Production Technology

Floppy disk is unreadable.Despite the advances in computing technology and office automation, and forecasts of the paperless office having become a reality by now, there remains the fact that very few companies would face less paper today than they did five years ago. Offices today are still deluged with paper because current office automation technology has failed to address one aspect of paperwork common in the office environment: the electronic equivalent to structured internal paper-based documents. Electronic structured document interchange (ESDI) has been proposed as the last remaining technology in providing the complete infrastructure for the "paperless office." Complementing current electronic office system technology, including imaging technologies, electronic mail, and electronic data interchange, ESDI was designed to provide the electronic equivalent to structured internal paper-based documents. Electronic structured document interchange is the intra-company computer-to-computer processing of business transactions in a format that allows the receiver to process the transaction by traditional business practices. Fundamentally, ESDI is a data processing concept that spans a single business enterprise, providing the complete electronic equivalent to the handling and processing of internal paper-based documents. The rationale being to take advantage of the benefits of electronic processing and delivery, while retaining traditional business practices. In some respects, ESDI systems have the potential to improve business practices by providing capabilities that are simply not possible with traditional paper-based systems. This emerging technology, the justification for such a technology, and features of the technology, including details of the administrative ESDI system implemented at Massey University, are discussed

Crystal structure of geranylgeranyl pyrophosphate synthase (CrtE) involved in cyanobacterial terpenoid biosynthesis

Cyanobacteria are photosynthetic prokaryotes that perform oxygenic photosynthesis. Due to their ability to use the photon energy of sunlight to fix carbon dioxide into biomass, cyanobacteria are promising hosts for the sustainable production of terpenoids, also known as isoprenoids, a diverse class of natural products with potential as advanced biofuels and high-value chemicals. However, the cyanobacterial enzymes involved in the biosynthesis of the terpene precursors needed to make more complicated terpenoids are poorly characterized. Here we show that the predicted type II prenyltransferase CrtE encoded by the model cyanobacterium Synechococcus sp. PCC 7002 is homodimeric and able to synthesize C20-geranylgeranyl pyrophosphate (GGPP) from C5-isopentenyl pyrophosphate (IPP) and C5-dimethylallyl pyrophosphate (DMAPP). The crystal structure of CrtE solved to a resolution of 2.7 Å revealed a strong structural similarity to the large subunit of the heterodimeric geranylgeranyl pyrophosphate synthase 1 from Arabidopsis thaliana with each subunit containing 14 helices. Using mutagenesis, we confirmed that the fourth and fifth amino acids (Met-87 and Ser-88) before the first conserved aspartate-rich motif (FARM) play important roles in controlling chain elongation. While the WT enzyme specifically produced GGPP, variants M87F and S88Y could only generate C15-farnesyl pyrophosphate (FPP), indicating that residues with large side chains obstruct product elongation. In contrast, replacement of M87 with the smaller Ala residue allowed the formation of the longer C25-geranylfarnesyl pyrophosphate (GFPP) product. Overall, our results provide new structural and functional information on the cyanobacterial CrtE enzyme that could lead to the development of improved cyanobacterial platforms for terpenoid production

Fitness outcomes from a randomised controlled trial of exercise training for men with prostate cancer: the ENGAGE study

Purpose The main purpose of this study was to investigate the effects of a 12-week, clinician-referred, community-based exercise training program with supervised and unsupervised sessions for men with prostate cancer. The secondary purpose was to determine whether androgen deprivation therapy (ADT) modified responses to exercise training.Methods Secondary analysis was undertaken on data from a multicentre cluster randomised controlled trial in which 15 clinicians were randomly assigned to refer eligible patients to an exercise training intervention (n&thinsp;=&thinsp;8) or to provide usual care (n&thinsp;=&thinsp;7). Data from 119 patients (intervention n&thinsp;=&thinsp;53, control n&thinsp;=&thinsp;66) were available for this analysis. Outcome measures included fitness and physical function, anthropometrics, resting heart rate, and blood pressure.Results Compared to the control condition, men in the intervention significantly improved their 6-min walk distance (Mdiff&thinsp;=&thinsp;49.98 m, padj&thinsp;=&thinsp;0.001), leg strength (Mdiff&thinsp;=&thinsp;21.82 kg, padj&thinsp;=&thinsp;0.001), chest strength (Mdiff&thinsp;=&thinsp;6.91 kg, padj&thinsp;=&thinsp;0.001), 30-s sit-to-stand result (Mdiff&thinsp;=&thinsp;3.38 reps, padj&thinsp;=&thinsp;0.001), and reach distance (Mdiff&thinsp;=&thinsp;4.8 cm, padj&thinsp;=&thinsp;0.024). A significant difference (unadjusted for multiplicity) in favour of men in the intervention was also found for resting heart rate (Mdiff&thinsp;=&thinsp;&minus;3.76 beats/min, p&thinsp;=&thinsp;0.034). ADT did not modify responses to exercise training.Conclusions Men with prostate cancer who act upon clinician referrals to community-based exercise training programs can improve their strength, physical functioning, and, potentially, cardiovascular health, irrespective of whether or not they are treated with ADT.Implications for Cancer Survivors Clinicians should inform men with prostate cancer about the benefits of exercise and refer them to appropriately qualified exercise practitioners and suitable community-based programs

Predictors of adherence to a 12-week exercise program among men treated for prostate cancer: ENGAGE study

Understanding the factors that influence adherence to exercise programs is necessary to develop effective interventions for people with cancer. We examined the predictors of adherence to a supervised exercise program for participants in the ENGAGE study – a cluster randomized controlled trial that assessed the efficacy of a clinician-referred 12-week exercise program among men treated for prostate cancer. Demographic, clinical, behavioral, and psychosocial data from 52 participants in the intervention group were collected at baseline through self-report and medical records. Adherence to the supervised exercise program was assessed through objective attendance records. Adherence to the supervised exercise program was 80.3%. In the univariate analyses, cancer-specific quality of life subscales (role functioning r = 0.37, P = 0.01; sexual activity r = 0.26, P = 0.06; fatigue r = −0.26, P = 0.06, and hormonal symptoms r = −0.31, P = 0.03) and education (d = −0.60, P = 0.011) were associated with adherence. In the subsequent multivariate analysis, role functioning (B = 0.309, P = 0.019) and hormonal symptoms (B = −0.483, P = 0.054) independently predicted adherence. Men who experienced more severe hormonal symptoms had lower levels of adherence to the exercise program. Those who experienced more positive perceptions of their ability to perform daily tasks and leisure activities had higher levels of adherence to the exercise program. Hormonal symptoms and role functioning need to be considered when conducting exercise programs for men who have been treated for prostate cancer

Trauma as counter-revolutionary colonisation: narratives from (post)revolutionary Egypt

We argue that multiple levels of trauma were present in Egypt before, during and after the 2011 revolution. Individual, social and political trauma constitute a triangle of traumatisation which was strategically employed by the Egyptian counter-revolutionary forces – primarily the army and the leadership of the Muslim Brotherhood – to maintain their political and economic power over and above the social, economic and political interests of others. Through the destruction of physical bodies, the fragmentation and polarisation of social relations and the violent closure of the newly emerged political public sphere, these actors actively repressed the potential for creative and revolutionary transformation. To better understand this multi-layered notion of trauma, we turn to Habermas’ ‘colonisation of the lifeworld’ thesis which offers a critical lens through which to examine the wider political and economic structures and context in which trauma occurred as well as its effects on the personal, social and political realms. In doing so, we develop a novel conception of trauma that acknowledges individual, social and political dimensions. We apply this conceptual framing to empirical narratives of trauma in Egypt’s pre- and post-revolutionary phases, thus both developing a non-Western application of Habermas’ framework and revealing ethnographic accounts of the revolution by activists in Cairo

Simulations of atmospheric methane for Cape Grim, Tasmania, to constrain southeastern Australian methane emissions

This study uses two climate models and six scenarios of prescribed methane emissions to compare modelled and observed atmospheric methane between 1994 and 2007, for Cape Grim, Australia (40.7° S, 144.7° E). The model simulations follow the TransCom-CH4 protocol and use the Australian Community Climate and Earth System Simulator (ACCESS) and the CSIRO Conformal-Cubic Atmospheric Model (CCAM). Radon is also simulated and used to reduce the impact of transport differences between the models and observations. Comparisons are made for air samples that have traversed the Australian continent. All six emission scenarios give modelled concentrations that are broadly consistent with those observed. There are three notable mismatches, however. Firstly, scenarios that incorporate interannually varying biomass burning emissions produce anomalously high methane concentrations at Cape Grim at times of large fire events in southeastern Australia, most likely due to the fire methane emissions being unrealistically input into the lowest model level. Secondly, scenarios with wetland methane emissions in the austral winter overestimate methane concentrations at Cape Grim during wintertime while scenarios without winter wetland emissions perform better. Finally, all scenarios fail to represent a~methane source in austral spring implied by the observations. It is possible that the timing of wetland emissions in the scenarios is incorrect with recent satellite measurements suggesting an austral spring (September–October–November), rather than winter, maximum for wetland emissions. © Author(s) 2015

Expression of mammalian GPCRs in C. elegans generates novel behavioural responses to human ligands

BACKGROUND: G-protein-coupled receptors (GPCRs) play a crucial role in many biological processes and represent a major class of drug targets. However, purification of GPCRs for biochemical study is difficult and current methods of studying receptor-ligand interactions involve in vitro systems. Caenorhabditis elegans is a soil-dwelling, bacteria-feeding nematode that uses GPCRs expressed in chemosensory neurons to detect bacteria and environmental compounds, making this an ideal system for studying in vivo GPCR-ligand interactions. We sought to test this by functionally expressing two medically important mammalian GPCRs, somatostatin receptor 2 (Sstr2) and chemokine receptor 5 (CCR5) in the gustatory neurons of C. elegans. RESULTS: Expression of Sstr2 and CCR5 in gustatory neurons allow C. elegans to specifically detect and respond to somatostatin and MIP-1α respectively in a robust avoidance assay. We demonstrate that mammalian heterologous GPCRs can signal via different endogenous G(α )subunits in C. elegans, depending on which cells it is expressed in. Furthermore, pre-exposure of GPCR transgenic animals to its ligand leads to receptor desensitisation and behavioural adaptation to subsequent ligand exposure, providing further evidence of integration of the mammalian GPCRs into the C. elegans sensory signalling machinery. In structure-function studies using a panel of somatostatin-14 analogues, we identified key residues involved in the interaction of somatostatin-14 with Sstr2. CONCLUSION: Our results illustrate a remarkable evolutionary plasticity in interactions between mammalian GPCRs and C. elegans signalling machinery, spanning 800 million years of evolution. This in vivo system, which imparts novel avoidance behaviour on C. elegans, thus provides a simple means of studying and screening interaction of GPCRs with extracellular agonists, antagonists and intracellular binding partners