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Search Results: 1 - 10 of 195762 matches for " Ian G. Barr "
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Rapid Detection and Subtyping of Human Influenza A Viruses and Reassortants by Pyrosequencing
Yi-Mo Deng, Natalie Caldwell, Ian G. Barr
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023400
Abstract: Background Given the continuing co-circulation of the 2009 H1N1 pandemic influenza A viruses with seasonal H3N2 viruses, rapid and reliable detection of newly emerging influenza reassortant viruses is important to enhance our influenza surveillance. Methodology/Principal Findings A novel pyrosequencing assay was developed for the rapid identification and subtyping of potential human influenza A virus reassortants based on all eight gene segments of the virus. Except for HA and NA genes, one universal set of primers was used to amplify and subtype each of the six internal genes. With this method, all eight gene segments of 57 laboratory isolates and 17 original specimens of seasonal H1N1, H3N2 and 2009 H1N1 pandemic viruses were correctly matched with their corresponding subtypes. In addition, this method was shown to be capable of detecting reassortant viruses by correctly identifying the source of all 8 gene segments from three vaccine production reassortant viruses and three H1N2 viruses. Conclusions/Significance In summary, this pyrosequencing assay is a sensitive and specific procedure for screening large numbers of viruses for reassortment events amongst the commonly circulating human influenza A viruses, which is more rapid and cheaper than using conventional sequencing approaches.
A Working Classification of Retraction for the Whole Tympanic Membrane  [PDF]
G. D. Barr
International Journal of Otolaryngology and Head & Neck Surgery (IJOHNS) , 2013, DOI: 10.4236/ijohns.2013.24031
Abstract:

Objective: To formulate a reliable classification of tympanic membrane retraction which is easy to use but capable of detecting small differences in retraction. Study Design: Prospective study. Methods: The classification was developed from observations dividing the drum into 3 areas: the pars tensa anterior to the malleus, type I, posterior to the malleus (subdivided into upper and lower) type II, and attic type III. The subclassification on paper is more complicated but using a database it is easy to use. The classification is automatically calculated by the database which can also be converted to numerical form. The classification also allows documentation of active disease in retractions. Photographs of seven retracted ear drums were incorporated into the database and ten otolaryngologists asked to classify them. Five were asked to reclassify the retractions in the same way after 3 months. Results: Intra class correlation was significantly high (>0.9) for pars tensa, attic, and for bony erosion. Cronbach’s alpha values were also high (>0.9) in all groups. Retest values were evaluated with Wilcoxon’s signed rank sum test establishing that there was no significant difference in results. Conclusion: The classification shows reliabiliy and validity allowing detection of small changes in tympanic membrane retraction especially affecting the pars tensa but allows classification of the whole tympanic membrane.

Innate Immunity and the Inter-exposure Interval Determine the Dynamics of Secondary Influenza Virus Infection and Explain Observed Viral Hierarchies
Pengxing Cao?,Ada W. C. Yan?,Jane M. Heffernan?,Stephen Petrie?,Robert G. Moss?,Louise A. Carolan?,Teagan A. Guarnaccia?,Anne Kelso?,Ian G. Barr,Jodie McVernon
PLOS Computational Biology , 2015, DOI: 10.1371/journal.pcbi.1004334
Abstract: Influenza is an infectious disease that primarily attacks the respiratory system. Innate immunity provides both a very early defense to influenza virus invasion and an effective control of viral growth. Previous modelling studies of virus–innate immune response interactions have focused on infection with a single virus and, while improving our understanding of viral and immune dynamics, have been unable to effectively evaluate the relative feasibility of different hypothesised mechanisms of antiviral immunity. In recent experiments, we have applied consecutive exposures to different virus strains in a ferret model, and demonstrated that viruses differed in their ability to induce a state of temporary immunity or viral interference capable of modifying the infection kinetics of the subsequent exposure. These results imply that virus-induced early immune responses may be responsible for the observed viral hierarchy. Here we introduce and analyse a family of within-host models of re-infection viral kinetics which allow for different viruses to stimulate the innate immune response to different degrees. The proposed models differ in their hypothesised mechanisms of action of the non-specific innate immune response. We compare these alternative models in terms of their abilities to reproduce the re-exposure data. Our results show that 1) a model with viral control mediated solely by a virus-resistant state, as commonly considered in the literature, is not able to reproduce the observed viral hierarchy; 2) the synchronised and desynchronised behaviour of consecutive virus infections is highly dependent upon the interval between primary virus and challenge virus exposures and is consistent with virus-dependent stimulation of the innate immune response. Our study provides the first mechanistic explanation for the recently observed influenza viral hierarchies and demonstrates the importance of understanding the host response to multi-strain viral infections. Re-exposure experiments provide a new paradigm in which to study the immune response to influenza and its role in viral control.
Inter-Seasonal Influenza is Characterized by Extended Virus Transmission and Persistence
Zoe Patterson Ross?,Naomi Komadina?,Yi-Mo Deng?,Natalie Spirason?,Heath A. Kelly?,Sheena G. Sullivan?,Ian G. Barr,Edward C. Holmes
PLOS Pathogens , 2015, DOI: 10.1371/journal.ppat.1004991
Abstract: The factors that determine the characteristic seasonality of influenza remain enigmatic. Current models predict that occurrences of influenza outside the normal surveillance season within a temperate region largely reflect the importation of viruses from the alternate hemisphere or from equatorial regions in Asia. To help reveal the drivers of seasonality we investigated the origins and evolution of influenza viruses sampled during inter-seasonal periods in Australia. To this end we conducted an expansive phylogenetic analysis of 9912, 3804, and 3941 hemagglutinnin (HA) sequences from influenza A/H1N1pdm, A/H3N2, and B, respectively, collected globally during the period 2009-2014. Of the 1475 viruses sampled from Australia, 396 (26.8% of Australian, or 2.2% of global set) were sampled outside the monitored temperate influenza surveillance season (1 May – 31 October). Notably, rather than simply reflecting short-lived importations of virus from global localities with higher influenza prevalence, we documented a variety of more complex inter-seasonal transmission patterns including “stragglers” from the preceding season and “heralds” of the forthcoming season, and which included viruses sampled from clearly temperate regions within Australia. We also provide evidence for the persistence of influenza B virus between epidemic seasons, in which transmission of a viral lineage begins in one season and continues throughout the inter-seasonal period into the following season. Strikingly, a disproportionately high number of inter-seasonal influenza transmission events occurred in tropical and subtropical regions of Australia, providing further evidence that climate plays an important role in shaping patterns of influenza seasonality.
Rapid Detection of the H275Y Oseltamivir Resistance Mutation in Influenza A/H1N1 2009 by Single Base Pair RT-PCR and High-Resolution Melting
Steven Y. C. Tong, Farshid Dakh, Aeron C. Hurt, Yi-Mo Deng, Kevin Freeman, Peter K. Fagan, Ian G. Barr, Philip M. Giffard
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0021446
Abstract: Introduction We aimed to design a real-time reverse-transcriptase-PCR (rRT-PCR), high-resolution melting (HRM) assay to detect the H275Y mutation that confers oseltamivir resistance in influenza A/H1N1 2009 viruses. Findings A novel strategy of amplifying a single base pair, the relevant SNP at position 823 of the neuraminidase gene, was chosen to maintain specificity of the assay. Wildtype and mutant virus were differentiated when using known reference samples of cell-cultured virus. However, when dilutions of these reference samples were assayed, amplification of non-specific primer-dimer was evident and affected the overall melting temperature (Tm) of the amplified products. Due to primer-dimer appearance at >30 cycles we found that if the cycle threshold (CT) for a dilution was >30, the HRM assay did not consistently discriminate mutant from wildtype. Where the CT was <30 we noted an inverse relationship between CT and Tm and fitted quadratic curves allowed the discrimination of wildtype, mutant and 30:70 mutant:wildtype virus mixtures. We compared the CT values for a TaqMan H1N1 09 detection assay with those for the HRM assay using 59 clinical samples and demonstrated that samples with a TaqMan detection assay CT>32.98 would have an H275Y assay CT>30. Analysis of the TaqMan CT values for 609 consecutive clinical samples predicted that 207 (34%) of the samples would result in an HRM assay CT>30 and therefore not be amenable to the HRM assay. Conclusions The use of single base pair PCR and HRM can be useful for specifically interrogating SNPs. When applied to H1N1 09, the constraints this placed on primer design resulted in amplification of primer-dimer products. The impact primer-dimer had on HRM curves was adjusted for by plotting Tm against CT. Although less sensitive than TaqMan assays, the HRM assay can rapidly, and at low cost, screen samples with moderate viral concentrations.
Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model
Teagan Guarnaccia,Louise A. Carolan,Sebastian Maurer-Stroh,Raphael T. C. Lee,Emma Job,Patrick C. Reading,Stephen Petrie,James M. McCaw,Jodie McVernon,Aeron C. Hurt,Anne Kelso,Jennifer Mosse,Ian G. Barr,Karen L. Laurie
PLOS Pathogens , 2013, DOI: 10.1371/journal.ppat.1003354
Abstract: Surveillance data indicate that most circulating A(H1N1)pdm09 influenza viruses have remained antigenically similar since they emerged in humans in 2009. However, antigenic drift is likely to occur in the future in response to increasing population immunity induced by infection or vaccination. In this study, sequential passaging of A(H1N1)pdm09 virus by contact transmission through two independent series of suboptimally vaccinated ferrets resulted in selection of variant viruses with an amino acid substitution (N156K, H1 numbering without signal peptide; N159K, H3 numbering without signal peptide; N173K, H1 numbering from first methionine) in a known antigenic site of the viral HA. The N156K HA variant replicated and transmitted efficiently between na?ve ferrets and outgrew wildtype virus in vivo in ferrets in the presence and absence of immune pressure. In vitro, in a range of cell culture systems, the N156K variant rapidly adapted, acquiring additional mutations in the viral HA that also potentially affected antigenic properties. The N156K escape mutant was antigenically distinct from wildtype virus as shown by binding of HA-specific antibodies. Glycan binding assays demonstrated the N156K escape mutant had altered receptor binding preferences compared to wildtype virus, which was supported by computational modeling predictions. The N156K substitution, and culture adaptations, have been detected in human A(H1N1)pdm09 viruses with N156K preferentially reported in sequences from original clinical samples rather than cultured isolates. This study demonstrates the ability of the A(H1N1)pdm09 virus to undergo rapid antigenic change to evade a low level vaccine response, while remaining fit in a ferret transmission model of immunization and infection. Furthermore, the potential changes in receptor binding properties that accompany antigenic changes highlight the importance of routine characterization of clinical samples in human A(H1N1)pdm09 influenza surveillance.
Globalization Impacts on Chinese Politics and Urbanization  [PDF]
Jamie P. Halsall, Ian G. Cook
Chinese Studies (ChnStd) , 2013, DOI: 10.4236/chnstd.2013.22012
Abstract: The aim of this paper is to critically explore the complex debates on the contemporary growth of China’s urban economies. It has been well documented that China is the second largest economy in the world and is seen to be a major player in the financial markets. Over the last decade China has experienced a dramatic urban transformation and globalization is a key factor in the change in China from Maoist production cities to Dengist cities of consumption, albeit with a strong export-oriented production element. As this paper will argue, without the impact of Globalization, the recent development of China as a key economic power could not have taken place. The findings of this research revealed however, that the Chinese State has also played a key role, intertwined as it is with the Chinese Communist Party (CCP).
Serological Response in RT-PCR Confirmed H1N1-2009 Influenza A by Hemagglutination Inhibition and Virus Neutralization Assays: An Observational Study
Mark I. Chen,Ian G. Barr,Gerald C. H. Koh,Vernon J. Lee,Caroline P. S. Lee,Robert Shaw,Cui Lin,Jonathan Yap,Alex R. Cook,Boon Huan Tan,Jin Phang Loh,Timothy Barkham,Vincent T. K. Chow,Raymond T. P. Lin,Yee-Sin Leo
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012474
Abstract: We describe the serological response following H1N1-2009 influenza A infections confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR).
Estimating the Fitness Advantage Conferred by Permissive Neuraminidase Mutations in Recent Oseltamivir-Resistant A(H1N1)pdm09 Influenza Viruses
Jeff Butler,Kathryn A. Hooper,Stephen Petrie,Raphael Lee,Sebastian Maurer-Stroh,Lucia Reh,Teagan Guarnaccia,Chantal Baas,Lumin Xue,Sophie Vitesnik,Sook-Kwan Leang,Jodie McVernon,Anne Kelso,Ian G. Barr,James M. McCaw,Jesse D. Bloom,Aeron C. Hurt
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1004065
Abstract: Oseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection. Surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses. Since the emergence of the pandemic 2009 A(H1N1) influenza virus (A(H1N1)pdm09), the proportion of A(H1N1)pdm09 viruses that are oseltamivir resistant (OR) has generally been low. However, a cluster of OR A(H1N1)pdm09 viruses, encoding the neuraminidase (NA) H275Y oseltamivir resistance mutation, was detected in Australia in 2011 amongst community patients that had not been treated with oseltamivir. Here we combine a competitive mixtures ferret model of influenza infection with a mathematical model to assess the fitness, both within and between hosts, of recent OR A(H1N1)pdm09 viruses. In conjunction with data from in vitro analyses of NA expression and activity we demonstrate that contemporary A(H1N1)pdm09 viruses are now more capable of acquiring H275Y without compromising their fitness, than earlier A(H1N1)pdm09 viruses circulating in 2009. Furthermore, using reverse engineered viruses we demonstrate that a pair of permissive secondary NA mutations, V241I and N369K, confers robust fitness on recent H275Y A(H1N1)pdm09 viruses, which correlated with enhanced surface expression and enzymatic activity of the A(H1N1)pdm09 NA protein. These permissive mutations first emerged in 2010 and are now present in almost all circulating A(H1N1)pdm09 viruses. Our findings suggest that recent A(H1N1)pdm09 viruses are now more permissive to the acquisition of H275Y than earlier A(H1N1)pdm09 viruses, increasing the risk that OR A(H1N1)pdm09 will emerge and spread worldwide.
Nuevo registro de Paralomis otsuae Wilson, 1990 (Decapoda, Anomura, Lithodidae) en la costa centro-sur de Chile
Barría,Erwin M; Jara,Carlos G;
Investigaciones marinas , 2005, DOI: 10.4067/S0717-71782005000100009
Abstract: a report is made on the capture of five male specimens of paralomis otsuae wilson on the continental slope off the coast of corral, chile (39o50`s). this finding significatively extends the southern latitudinal geographic range of the species. the specimens measured between 89 and 115 mm in cephalotoracic length excluding the rostral spine, and between 94 and 118 mm in cephalothoracic width excluding the lateral spines. some morphological characteristics and morphometric dimensions were noteworthy. discussion is presented on the significance of the characteristics of this species and its' geographic distribution
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