Simulation-based Bayesian inference for epidemic models

This is the author pre-print version. The final version is available from the publisher via the DOI in this record.A powerful and flexible method for fitting dynamic models to missing and censored data is to use the Bayesian paradigm via data-augmented Markov chain Monte Carlo (DA-MCMC). This samples from the joint posterior for the parameters and missing data, but requires high memory overheads for large-scale systems. In addition, designing efficient proposal distributions for the missing data is typically challenging. Pseudo-marginal methods instead integrate across the missing data using a Monte Carlo estimate for the likelihood, generated from multiple independent simulations from the model. These techniques can avoid the high memory requirements of DA-MCMC, and under certain conditions produce the exact marginal posterior distribution for parameters. A novel method is presented for implementing importance sampling for dynamic epidemic models, by conditioning the simulations on sets of validity criteria (based on the model structure) as well as the observed data. The flexibility of these techniques is illustrated using both removal time and final size data from an outbreak of smallpox. It is shown that these approaches can circumvent the need for reversible-jump MCMC, and can allow inference in situations where DA-MCMC is impossible due to computationally infeasible likelihoods. © 2013 Elsevier B.V. All rights reserved.T. J. M. was in part supported by Department for the Environment, Food and Rural Affairs/Higher Education Funding Council of England, grant number VT0105 and BBSRC grant (BB/I012192/1). J. V. R was in part supported by Australian Research Council’s Discovery Projects funding scheme (project number DP110102893). R. D. was in part supported by Natural Sciences and Engineering Research Council (NSERC) of Canada’s Discovery Grants Program. A. R. C. was in part supported by National Medical Research Council (NMRC/HINIR/005/2009) and NUS Initiative to Improve Health in Asia. The authors would like to thank Andrew Conlan and Theo Kypraios for useful discussions

Paleoclimate histories improve access and sustainability in index insurance programs

Proxy-based climate reconstructions can extend instrumental records by hundreds of years, providing a wealth of climate information at high temporal resolution. To date, however, their usefulness for informing climate risk and variability in policy and social applications has been understudied. Here, we apply tree-ring based reconstructions of drought for the last 700 years in a climate index insurance framework to show that additional information from long climate reconstructions significantly improves our understanding of the underlying climate distributions and variability. We further show that this added information can be used to better characterize risk to insurance providers, in many cases providing meaningful reductions in long-term contract costs to farmers in stand-alone policies. The impact of uncertainty on insurance premiums can also be reduced when insurers diversify portfolios, and the availability of long-term climate information from tree rings across a broad geographic range provides an opportunity to characterize spatial correlation in climate risk across geographic regions. Our results are robust to the range of climate variability experienced over the last 400 years and in model simulations of the twenty-first century, even within the context of changing baselines due to low frequency variability and secular climate trends. These results demonstrate the utility of longer-term climate histories in index insurance applications. Furthermore, they make the case from a climate-variability perspective for the continued importance of such approaches to improving the instrumental climate record, even into a non-stationary climate future

Paleoclimate histories improve access and sustainability in index insurance programs

Proxy-based climate reconstructions can extend instrumental records by hundreds of years, providing a wealth of climate information at high temporal resolution. To date, however, their usefulness for informing climate risk and variability in policy and social applications has been understudied. Here, we apply tree-ring based reconstructions of drought for the last 700 years in a climate index insurance framework to show that additional information from long climate reconstructions significantly improves our understanding of the underlying climate distributions and variability. We further show that this added information can be used to better characterize risk to insurance providers, in many cases providing meaningful reductions in long-term contract costs to farmers in stand-alone policies. The impact of uncertainty on insurance premiums can also be reduced when insurers diversify portfolios, and the availability of long-term climate information from tree rings across a broad geographic range provides an opportunity to characterize spatial correlation in climate risk across geographic regions. Our results are robust to the range of climate variability experienced over the last 400 years and in model simulations of the twenty-first century, even within the context of changing baselines due to low frequency variability and secular climate trends. These results demonstrate the utility of longer-term climate histories in index insurance applications. Furthermore, they make the case from a climate-variability perspective for the continued importance of such approaches to improving the instrumental climate record, even into a non-stationary climate future

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Fusion Research Cente

3D UK? 3D History and the Absent British Pioneers

The recent television ‘rediscovery’ of a small cohort of 1950s British 3D films (and the producers who made them) has offered a new route into considering how the historical stories told about 3D film have focused almost exclusively on the American experience, eliding other national contexts. This article challenges both the partiality of existing academic histories of 3D, and the specific popular media narratives that have been constructed around the British 3D pioneers. Offering a rebuttal of those narratives and an expansion of them based around primary archival research, the article considers how the British 3D company Stereo Techniques created a different business and production model based around non-fiction short 3D films that stand in contrast to the accepted view of 3D as an American feature film novelty. Through an exploration of the depiction (and absence) of these 3D pioneers from existing media histories, the article argues for a revision to both 3D studies and British cinema history

Comprehensive translational assessment of human-induced pluripotent stem cell derived cardiomyocytes for evaluating drug-induced arrhythmias

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) hold promise for assessment of drug-induced arrhythmias and are being considered for use under the comprehensive in vitro proarrhythmia assay (CiPA). We studied the effects of 26 drugs and 3 drug combinations on 2 commercially available iPSC-CM types using high-throughput voltage-sensitive dye and microelectrode-array assays being studied for the CiPA initiative and compared the results with clinical QT prolongation and torsade de pointes (TdP) risk. Concentration-dependent analysis comparing iPSC-CMs to clinical trial results demonstrated good correlation between drug-induced rate-corrected action potential duration and field potential duration (APDc and FPDc) prolongation and clinical trial QTc prolongation. Of 20 drugs studied that exhibit clinical QTc prolongation, 17 caused APDc prolongation (16 in Cor.4U and 13 in iCell cardiomyocytes) and 16 caused FPDc prolongation (16 in Cor.4U and 10 in iCell cardiomyocytes). Of 14 drugs that cause TdP, arrhythmias occurred with 10 drugs. Lack of arrhythmic beating in iPSC-CMs for the four remaining drugs could be due to differences in relative levels of expression of individual ion channels. iPSC-CMs responded consistently to human ether-a-go-go potassium channel blocking drugs (APD prolongation and arrhythmias) and calcium channel blocking drugs (APD shortening and prevention of arrhythmias), with a more variable response to late sodium current blocking drugs. Current results confirm the potential of iPSC-CMs for proarrhythmia prediction under CiPA, where iPSC-CM results would serve as a check to ion channel and in silico modeling prediction of proarrhythmic risk. A multi-site validation study is warranted

Direct access:how is it working?

AimThe aim of this study was to identify and survey dental hygienists and therapists working in direct access practices in the UK, obtain their views on its benefits and disadvantages, establish which treatments they provided, and what barriers they had encountered.MethodThe study used a purposive sample of GDC-registered hygienists and therapists working in practices offering direct access, identified through a ‘Google’ search. An online survey was set up through the University of Edinburgh, and no-responses followed up by post.ResultsThe initial search identified 243 individuals working in direct access practices. Where a practice listed more than one hygienist/therapist, one was randomly selected. This gave a total of 179 potential respondents. Eighty six responses were received, representing a response rate of 48%. A large majority of respondents (58, 73%) were favourable in their view of the GDC decision to allow direct access, and most thought advantages outnumbered disadvantages for patients, hygienists, therapists and dentists. There were no statistically significant differences in views between hygienists and therapists. Although direct access patients formed a small minority of their caseload for most respondents, it is estimated that on average respondents saw approximately 13 per month. Treatment was mainly restricted to periodontal work, irrespective of whether the respondent was singly or dually qualified. One third of respondents reported encountering barriers to successful practice, including issues relating to teamwork and dentists’ unfavourable attitudes. However, almost two thirds(64%) felt that direct access had enhanced their job satisfaction, and 45% felt their clinical skills had increased.DiscussionComments were mainly positive, but sometimes raised worrying issues, for example in respect to training, lack of dental nurse support and the limited availability of periodontal treatment under NHS regulations

A temperate former West Antarctic ice sheet suggested by an extensive zone of bed channels

Several recent studies predict that the West Antarctic Ice Sheet will become increasingly unstable under warmer conditions. Insights on such change can be assisted through investigations of the subglacial landscape, which contains imprints of former ice-sheet behavior. Here, we present radio-echo sounding data and satellite imagery revealing a series of ancient large sub-parallel subglacial bed channels preserved in the region between the Möller and Foundation Ice Streams, West Antarctica. We suggest that these newly recognized channels were formed by significant meltwater routed along the icesheet bed. The volume of water required is likely substantial and can most easily be explained by water generated at the ice surface. The Greenland Ice Sheet today exemplifies how significant seasonal surface melt can be transferred to the bed via englacial routing. For West Antarctica, the Pliocene (2.6–5.3 Ma) represents the most recent sustained period when temperatures could have been high enough to generate surface melt comparable to that of present-day Greenland. We propose, therefore, that a temperate ice sheet covered this location during Pliocene warm periods

G-LiHT: Goddard's LiDAR, Hyperspectral and Thermal Airborne Imager

Scientists at NASA's Goddard Space Flight Center have developed an ultra-portable, low-cost, multi-sensor remote sensing system for studying the form and function of terrestrial ecosystems. G-LiHT integrates two LIDARs, a 905 nanometer single beam profiler and 1550 nm scanner, with a narrowband (1.5 nanometers) VNIR imaging spectrometer and a broadband (8-14 micrometers) thermal imager. The small footprint (approximately 12 centimeters) LIDAR data and approximately 1 meter ground resolution imagery are advantageous for high resolution applications such as the delineation of canopy crowns, characterization of canopy gaps, and the identification of sparse, low-stature vegetation, which is difficult to detect from space-based instruments and large-footprint LiDAR. The hyperspectral and thermal imagery can be used to characterize species composition, variations in biophysical variables (e.g., photosynthetic pigments), surface temperature, and responses to environmental stressors (e.g., heat, moisture loss). Additionally, the combination of LIDAR optical, and thermal data from G-LiHT is being used to assess forest health by sensing differences in foliage density, photosynthetic pigments, and transpiration. Low operating costs (approximately $1 ha) have allowed us to evaluate seasonal differences in LiDAR, passive optical and thermal data, which provides insight into year-round observations from space. Canopy characteristics and tree allometry (e.g., crown height:width, canopy:ground reflectance) derived from G-LiHT data are being used to generate realistic scenes for radiative transfer models, which in turn are being used to improve instrument design and ensure continuity between LiDAR instruments. G-LiHT has been installed and tested in aircraft with fuselage viewports and in a custom wing-mounted pod that allows G-LiHT to be flown on any Cessna 206, a common aircraft in use throughout the world. G-LiHT is currently being used for forest biomass and growth estimation in the CONUS and Mexico in support of NASA's Carbon Monitoring System (CMS) and AMIGA-Carb (AMerican Icesat Glas Assessment of Carbon). For NASA's CMS, wall-to-wall G-LiHT data have been acquired over intensive study sites with historic LiDAR datasets, dense inventory data, stem maps and flux tower observations. For AMIGA-Carb, G-LiHT transects have been acquired over ICESat tracks and USDA-FS inventory plots throughout the CONUS, and similar data will be acquired in Mexico during 2013. This talk will highlight recent science results from continental-scale transects landscape-scale deployments of G-LiHT, as well as seasonal forest dynamics from repeat pass G-LiHT acquisitions