758 research outputs found
Influenza B viruses in swine: virus tropism in swine respiratory organ explant cultures
Poster Session: Virology and Viral ReceptorsBackground: Swine has been considered an animal reservoir of pandemic influenza A virus (IAV), for
example, the 2009 H1N1 pandemic virus, swine is acting as a “mixing vessel” for the reassortment of
swine, human and avian IAVs. Certain influenza B virus (IBV) strains were also found to be readily
infecting piglets as early as in 1969. However, tissue tropism of IBV in swine is understudied, at least
in 2000s, mainly due to the misconception that IBV causes milder disease than IAV. IBV has in fact
circulated in many parts of the world causing regular seasonal epidemics in humans with mortality
rates sometimes higher than that in IAV seasons. Here, our research group hypothesizes that swine
could be a neglected host of IBV, apart from human and seal, due to the previous infectivity of IBV in
this animal, as well as the fact that swine has close contact with human and possesses a similar sialic
acid (influenza virus receptor) distribution profile as the human respiratory tract. We aim to examine
the characteristics of IBV tissue tropism using swine tracheal and lung explant models, and risk
assess swine susceptibility to a panel of IBV strains from both Yamagata and Victoria lineages of
different years. Materials and Methods: The tracheal and lung explants were prepared from fresh
swine respiratory organs from approximately 6-month-old pigs, and cultured with maximal similarity to
the in vivo conditions. A panel of IBV strains, from both Yamagata and Victoria lineages and from
different years, were used to infect the tissue explants at 37oC or 39oC according to the original
physiological temperature of the tissue. The virus replication efficiencies were evaluated through
viral titration and immunohistochemistry of the collected supernatant and formalin-fixed tissue
explants respectively at 1, 24, 48 and 72 h postinfection. Seasonal IAVs (H1N1 - A/OK/447/08
and H3N2 - A/OK/370/05) were used as controls. Results: Most of the tested IBVs showed
productive replication in the swine lung explants. Swine tracheal explants, on the other hand,
supported the replication of limited IBV strains. Most of these IBVs belong to the Victoria lineage,
which spread across the years from 2005 to 2011. IBVs that could replicate in swine lung explants
reached their maxima at 48 hpi or sometimes later. This is comparatively slower than the
replication rates of seasonal IAVs (H1N1 & H3N2) used in the study, which usually showed
significant increase at 24 hpi with still increasing virus yields at 48 hpi in some cases. However, the
overall increase in titres between the IBVs and seasonal IAVs were similar. In swine tracheal
explants, both IBVs and seasonal IAVs showed limited replications with similar trends of having
maxima being reached at 24 hpi. Conclusions: The successful replication of IBVs in swine explants
cultures indicates the possible susceptibility of swine to IBV and provides the essential basis for
further investigation on the likelihood for swine to be an animal reservoir of the virus, as well as the
threat it may pose to humans. Continuous studies on the replication kinetics of a greater number of
IBVs in swine explant cultures across a wider range of years, countries and lineages will probably be
our future target.published_or_final_versio
Aflatoxin regulations and global pistachio trade: Insights from social network analysis
Aflatoxins, carcinogenic toxins produced by Aspergillus fungi, contaminate maize, peanuts, and tree nuts in many regions of the world. Pistachios are the main source of human dietary aflatoxins from tree nuts worldwide. Over 120 countries have regulations for maximum allowable aflatoxin levels in food commodities. We developed social network models to analyze the association between nations' aflatoxin regulations and global trade patterns of pistachios from 1996-2010. The main pistachio producing countries are Iran and the United States (US), which together contribute to nearly 75% of the total global pistachio market. Over this time period, during which many nations developed or changed their aflatoxin regulations in pistachios, global pistachio trade patterns changed; with the US increasingly exporting to countries with stricter aflatoxin standards. The US pistachio crop has had consistently lower levels of aflatoxin than the Iranian crop over this same time period. As similar trading patterns have also been documented in maize, public health may be affected if countries without aflatoxin regulations, or with more relaxed regulations, continually import crops with higher aflatoxin contamination. Unlike the previous studies on maize, this analysis includes a dynamic element, examining how trade patterns change over time with introduction or adjustment of aflatoxin regulations. © 2014 Bui-Klimke et al
Deep Gaussian processes for regression using approximate expectation propagation
Deep Gaussian processes (DGPs) are multi-layer hierarchical generalisations
of Gaussian processes (GPs) and are formally equivalent to neural networks with
multiple, infinitely wide hidden layers. DGPs are nonparametric probabilistic
models and as such are arguably more flexible, have a greater capacity to
generalise, and provide better calibrated uncertainty estimates than
alternative deep models. This paper develops a new approximate Bayesian
learning scheme that enables DGPs to be applied to a range of medium to large
scale regression problems for the first time. The new method uses an
approximate Expectation Propagation procedure and a novel and efficient
extension of the probabilistic backpropagation algorithm for learning. We
evaluate the new method for non-linear regression on eleven real-world
datasets, showing that it always outperforms GP regression and is almost always
better than state-of-the-art deterministic and sampling-based approximate
inference methods for Bayesian neural networks. As a by-product, this work
provides a comprehensive analysis of six approximate Bayesian methods for
training neural networks
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Black-Box α-divergence minimization
Black-box alpha (BB-α) is a new approximate inference method based on the minimization of α-divergences. BB-α scales to large datasets because it can be implemented using stochastic gradient descent. BB-α can be applied to complex probabilistic models with little effort since it only requires as input the likelihood function and its gradients. These gradients can be easily obtained using automatic differentiation. By changing the divergence parameter α, the method is able to interpolate between variational Bayes (VB) (α → 0) and an algorithm similar to expectation propagation (EP) (α = 1). Experiments on probit regression and neural network regression and classification problems show that BB-a with non-standard settings of α, such as α = 0.5, usually produces better predictions than with α → 0 (VB) or α = 1 (EP).JMHL acknowledges support from the Rafael del Pino Foundation. YL thanks the Schlumberger Foundation Faculty for the Future fellowship on supporting her PhD study. MR acknowledges support from UK Engineering and Physical Sciences Research Council (EPSRC) grant EP/L016516/1 for the University of Cambridge Centre for Doctoral Training, the Cambridge Centre for Analysis. TDB thanks Google for funding his European Doctoral Fellowship. DHL acknowledge support from Plan National I+D+i, Grant TIN2013-42351-P and TIN2015- 70308-REDT, and from Comunidad de Madrid, Grant S2013/ICE-2845 CASI-CAM-CM. RET thanks EPSRC grant #EP/L000776/1 and #EP/M026957/1
Evaluation of the human adaptation of influenza A/H7N9 virus in PB2 protein using human and swine respiratory tract explant cultures
Novel avian H7N9 virus emerged in China in 2013 resulting in a case fatality rate of around 39% and continues to pose zoonotic and pandemic risk. Amino acid substitutions in PB2 protein were shown to influence the pathogenicity and transmissibility of H7N9 following experimental infection of ferrets and mice. In this study, we evaluated the role of amino acid substitution PB2-627K or compensatory changes at PB2-591K and PB2-701N, on the tropism and replication competence of H7N9 viruses for human and swine respiratory tracts using ex vivo organ explant cultures. Recombinant viruses of A/Shanghai/2/2013 (rgH7N9) and its mutants with PB2-K627E, PB2-K627E + Q591K and PB2-K627E + D701N were generated by plasmid-based reverse genetics. PB2-E627K was essential for efficient replication of rgH7N9 in ex vivo cultures of human and swine respiratory tracts. Mutant rgPB2-K627E + D701N replicated better than rgPB2-K627E in human lung but not as well as rgH7N9 virus. The rgPB2-K627E mutant failed to replicate in human type I-like pneumocytes (ATI) and peripheral blood monocyte-derived macrophages (PMϕ) at 37 °C while the compensatory mutant rgPB2-K627E + Q591K and rgPB2-K627E + D701N had partly restored replication competence in PMϕ. Our results demonstrate that PB2-E627K was important for efficient replication of influenza H7N9 in both human and swine respiratory tracts.published_or_final_versio
Statistical Basis for Predicting Technological Progress
Forecasting technological progress is of great interest to engineers, policy
makers, and private investors. Several models have been proposed for predicting
technological improvement, but how well do these models perform? An early
hypothesis made by Theodore Wright in 1936 is that cost decreases as a power
law of cumulative production. An alternative hypothesis is Moore's law, which
can be generalized to say that technologies improve exponentially with time.
Other alternatives were proposed by Goddard, Sinclair et al., and Nordhaus.
These hypotheses have not previously been rigorously tested. Using a new
database on the cost and production of 62 different technologies, which is the
most expansive of its kind, we test the ability of six different postulated
laws to predict future costs. Our approach involves hindcasting and developing
a statistical model to rank the performance of the postulated laws. Wright's
law produces the best forecasts, but Moore's law is not far behind. We discover
a previously unobserved regularity that production tends to increase
exponentially. A combination of an exponential decrease in cost and an
exponential increase in production would make Moore's law and Wright's law
indistinguishable, as originally pointed out by Sahal. We show for the first
time that these regularities are observed in data to such a degree that the
performance of these two laws is nearly tied. Our results show that
technological progress is forecastable, with the square root of the logarithmic
error growing linearly with the forecasting horizon at a typical rate of 2.5%
per year. These results have implications for theories of technological change,
and assessments of candidate technologies and policies for climate change
mitigation
Initiation of Psychotropic Medication after Partner Bereavement: A Matched Cohort Study
Background
Recent changes to diagnostic criteria for depression in DSM-5 remove the bereavement exclusion, allowing earlier diagnosis following bereavement. Evaluation of the potential effect of this change requires an understanding of existing psychotropic medication prescribing by non-specialists after bereavement.
Aims
To describe initiation of psychotropic medication in the first year after partner bereavement.
Methods
In a UK primary care database, we identified 21,122 individuals aged 60 and over with partner bereavement and no psychotropic drug use in the previous year. Prescribing (anxiolytic/hypnotic, antidepressant, antipsychotic) after bereavement was compared to age, sex and practice matched controls.
Results
The risks of receiving a new psychotropic prescription within two and twelve months of bereavement were 9.5% (95% CI 9.1 to 9.9%) and 17.9% (17.3 to 18.4%) respectively; an excess risk of initiation in the first year of 12.4% compared to non-bereaved controls. Anxiolytic/hypnotic and antidepressant initiation rates were highest in the first two months. In this period, the hazard ratio for initiation of anxiolytics/hypnotics was 16.7 (95% CI 14.7 to 18.9) and for antidepressants was 5.6 (4.7 to 6.7) compared to non-bereaved controls. 13.3% of those started on anxiolytics/hypnotics within two months continued to receive this drug class at one year. The marked variation in background family practice prescribing of anxiolytics/hypnotics was the strongest determinant of their initiation in the first two months after bereavement.
Conclusion
Almost one in five older people received a new psychotropic drug prescription in the year after bereavement. The early increase and trend in antidepressant use after bereavement suggests some clinicians did not adhere to the bereavement exclusion, with implications for its recent removal in DSM-5. Family practice variation in use of anxiolytics/hypnotics suggests uncertainty over their role in bereavement with the potential for inappropriate long term use
Variational Analysis Down Under Open Problem Session
© 2018, Springer Science+Business Media, LLC, part of Springer Nature. We state the problems discussed in the open problem session at Variational Analysis Down Under conference held in honour of Prof. Asen Dontchev on 19–21 February 2018 at Federation University Australia
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A new interpretation of total column BrO during Arctic spring
Emission of bromine from sea-salt aerosol, frost flowers, ice leads, and snow results in the nearly complete removal of surface ozone during Arctic spring. Regions of enhanced total column BrO observed by satellites have traditionally been associated with these emissions. However, airborne measurements of BrO and O3 within the convective boundary layer (CBL) during the ARCTAS and ARCPAC field campaigns at times bear little relation to enhanced column BrO. We show that the locations of numerous satellite BrO "hotspots" during Arctic spring are consistent with observations of total column ozone and tropopause height, suggesting a stratospheric origin to these regions of elevated BrO. Tropospheric enhancements of BrO large enough to affect the column abundance are also observed, with important contributions originating from above the CBL. Closure of the budget for total column BrO, albeit with significant uncertainty, is achieved by summing observed tropospheric partial columns with calculated stratospheric partial columns provided that natural, short-lived biogenic bromocarbons supply between 5 and 10 ppt of bromine to the Arctic lowermost stratosphere. Proper understanding of bromine and its effects on atmospheric composition requires accurate treatment of geographic variations in column BrO originating from both the stratosphere and troposphere. Copyright 2010 by the American Geophysical Union
Seizure-Related Gene 6 (Sez-6) in Amacrine Cells of the Rodent Retina and the Consequence of Gene Deletion
Background: Seizure-related gene 6 (Sez-6) is expressed in neurons of the mouse brain, retina and spinal cord. In the cortex, Sez-6 plays a role in specifying dendritic branching patterns and excitatory synapse numbers during development. Methodology/Principal Findings: The distribution pattern of Sez-6 in the retina was studied using a polyclonal antibody that detects the multiple isoforms of Sez-6. Prominent immunostaining was detected in GABAergic, but not in All glycinergic, amacrine cell subpopulations of the rat and mouse retina. Amacrine cell somata displayed a distinct staining pattern with the Sez-6 antibody: a discrete, often roughly triangular-shaped bright spot positioned between the nucleus and the apical dendrite superimposed over weaker general cytoplasmic staining. Displaced amacrines in the ganglion cell layer were also positive for Sez-6 and weaker staining was occasionally observed in neurons with the morphology of alpha ganglion cells. Two distinct Sez-6 positive strata were present in the inner plexiform layer in addition to generalized punctate staining. Certain inner nuclear layer cells, including bipolar cells, stained more weakly and diffusely than amacrine cells, although some bipolar cells exhibited a perinuclear "bright spot" similar to amacrine cells. In order to assess the role of Sez-6 in the retina, we analyzed the morphology of the Sez-6 knockout mouse retina with immunohistochemical markers and compared ganglion cell dendritic arbor patterning in Sez-6 null retinae with controls. The functional importance of Sez-6 was assessed by dark-adapted paired-flash electroretinography (ERG). Conclusions: In summary, we have reported the detailed expression pattern of a novel retinal marker with broad cell specificity, useful for retinal characterization in rodent experimental models. Retinal morphology, ganglion cell dendritic branching and ERG waveforms appeared normal in the Sez-6 knockout mouse suggesting that, in spite of widespread expression of Sez-6, retinal function in the absence of Sez-6 is not affected
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