Standardized Patient Methodology to Assess Refractive Error Reproducibility

Purpose. Standardized patient (SP) methodology is the gold standard for evaluating clinical practice. This approach was used to investigate the content of typical optometric eyecare in England and the reproducibility of refractive error measurement using prescriptions obtained by three SPs. Methods. The three SPs were independently examined by three to four expert optometric clinicians to obtain “benchmark” estimates of refractive error. One hundred two community optometrists consented to be visited by three SPs who were trained to provide accurate responses during the examinations. The spectacle prescriptions obtained by the SPs were analyzed for spherical equivalent refraction, spherical power and cylindrical power using astigmatic decomposition. Results. The spherical equivalent refractions were found to be within ±0.25 D of the benchmark on average 81% of the time and within ±0.50 D 97% of the time. The spherical power was within ±0.25 D 90% of the time and within ±0.50 D 98% of the time. The cylindrical power agreed within ±0.25 D 93% of the time and within ±0.50 D 100% of the time. Based on reproducibility limits data obtained for all six eyes, any two optometrists would differ in their estimation of spherical equivalent refraction by no more than 0.75 D in 95% of repeated measures. The astigmatic data (C0 and C45) show that optometrists will differ in their estimation of the C0 component by between 0.25 and 0.61 D and for the C45 component by between 0.22 and 0.47 D in 95% of repeated measures. Conclusions. The agreement between our data and the results of other similar studies support the conclusions that subjective refractive findings are reproducible to approximately ±0.75 D when performed by multiple optometrists in patients of different age groups and levels of ametropia. SPs are an effective way of measuring reproducibility of refractive error and should be considered for further comparative analysis in different age groups and different levels of ametropia

Assessing the impact of multi-channel BLE beacons on fingerprint-based positioning

Bluetooth Low Energy (BLE) beacons are attractive for indoor location due to their ease of deployment, wide support on consumer devices and low cost. Co-ordinate location can be estimated using radio fingerprinting techniques applied to Received Signal Strength (RSS) values from BLE beacons. Earlier work on BLE fingerprinting has noted that the separate BLE advertising channels can exhibit different RSS values, although modern consumer devices do not provide channel information and therefore report a composite RSS with artificially inflated variance that can lead to reduced positioning accuracy. In this work we quantify how often this channel dispersion occurs in typical environments, what the extent of the dispersion is, and what impact it has on positioning. Furthermore we explore how to obtain channel information when using today's consumer devices. We find that the dispersion is both common and significant and leads to significantly reduced positioning accuracy; in our experiments only 10% of composite variances were within 1 dBm of an individual channel's variance, and 40% of composite variances were at least 4 dBm greater. We also show that the behaviour of the channels is sufficiently distinct that a fingerprinting scheme that uses a signal map for each achieves significantly increased positioning accuracy (up to 3 m)

Aprepitant for cough in lung cancer: a randomised placebo-controlled trial and mechanistic insights

RATIONALE: Effective cough treatments are a significant unmet need in lung cancer patients. Aprepitant is a licensed treatment for nausea and vomiting, which blocks substance P activation of Neurokinin 1 (NK-1) receptors, a mechanism also implicated in cough. OBJECTIVE: To assess aprepitant in lung cancer patients with cough and evaluate mechanisms in vagal nerve tissue. METHODS: Randomised double-blind crossover trial of lung cancer patients with bothersome cough. They received three days of aprepitant or matched placebo; following a three day wash out, patients crossed to the alternative treatment. The primary endpoint was awake cough frequency measured at screening and day 3 of each treatment; secondary endpoints included patient-reported outcomes. In vitro, the depolarization of isolated guinea pig and human vagus nerve sections in grease gap recording chambers, indicative of sensory nerve activation, was measured to evaluate mechanism. MEASUREMENTS AND MAIN RESULTS: Twenty lung cancer patients enrolled, mean age 66years (±7.7), 60% female, 80% non-small cell cancer, 50% advanced stage and 55% WHO performance status 1. Cough frequency improved with aprepitant, reducing by 22.2%(95%CI 2.8-37.7%) over placebo whilst awake (p=0.03), 30.3%(95%CI 12.7-44.3) over 24hours (p=0.002) and 59.8%(95%CI 15.1-86.0) during sleep (p=0.081). Patient-reported outcomes all significantly improved. Substance P depolarised both guinea pig and human vagus nerve. Aprepitant significantly inhibited substance P induced depolarisation by 78% in guinea pig (p=0.0145) and 94% in human vagus (p=0.0145). DISCUSSION: Substance P activation of NK-1 receptors appears to be an important mechanism driving cough in lung cancer, and NK-1 antagonists show promise as anti-tussive therapies. Clinical trial registration available at www.http://www.isrctn.com/, ID: ISRCTN16200035

Prospects for improving the representation of coastal and shelf seas in global ocean models

Accurately representing coastal and shelf seas in global ocean models represents one of the grand challenges of Earth system science. They are regions of immense societal importance through the goods and services they provide, hazards they pose and their role in global-scale processes and cycles, e.g. carbon fluxes and dense water formation. However, they are poorly represented in the current generation of global ocean models. In this contribution, we aim to briefly characterise the problem, and then to identify the important physical processes, and their scales, needed to address this issue in the context of the options available to resolve these scales globally and the evolving computational landscape. We find barotropic and topographic scales are well resolved by the current state-of-the-art model resolutions, e.g. nominal 1∕12°, and still reasonably well resolved at 1∕4°; here, the focus is on process representation. We identify tides, vertical coordinates, river inflows and mixing schemes as four areas where modelling approaches can readily be transferred from regional to global modelling with substantial benefit. In terms of finer-scale processes, we find that a 1∕12° global model resolves the first baroclinic Rossby radius for only  ∼ 8% of regions  < 500m deep, but this increases to  ∼ 70% for a 1∕72° model, so resolving scales globally requires substantially finer resolution than the current state of the art. We quantify the benefit of improved resolution and process representation using 1∕12° global- and basin-scale northern North Atlantic nucleus for a European model of the ocean (NEMO) simulations; the latter includes tides and a k-ε vertical mixing scheme. These are compared with global stratification observations and 19 models from CMIP5. In terms of correlation and basin-wide rms error, the high-resolution models outperform all these CMIP5 models. The model with tides shows improved seasonal cycles compared to the high-resolution model without tides. The benefits of resolution are particularly apparent in eastern boundary upwelling zones. To explore the balance between the size of a globally refined model and that of multiscale modelling options (e.g. finite element, finite volume or a two-way nesting approach), we consider a simple scale analysis and a conceptual grid refining approach. We put this analysis in the context of evolving computer systems, discussing model turnaround time, scalability and resource costs. Using a simple cost model compared to a reference configuration (taken to be a 1∕4° global model in 2011) and the increasing performance of the UK Research Councils' computer facility, we estimate an unstructured mesh multiscale approach, resolving process scales down to 1.5km, would use a comparable share of the computer resource by 2021, the two-way nested multiscale approach by 2022, and a 1∕72° global model by 2026. However, we also note that a 1∕12° global model would not have a comparable computational cost to a 1° global model in 2017 until 2027. Hence, we conclude that for computationally expensive models (e.g. for oceanographic research or operational oceanography), resolving scales to  ∼ 1.5km would be routinely practical in about a decade given substantial effort on numerical and computational development. For complex Earth system models, this extends to about 2 decades, suggesting the focus here needs to be on improved process parameterisation to meet these challenges

Projected sea level rise and changes in extreme storm surge and wave events during the 21st century in the region of Singapore

Singapore is an island state with considerable population, industries, commerce and transport located in coastal areas at elevations less than 2 m making it vulnerable to sea-level rise. Mitigation against future inundation events requires a quantitative assessment of risk. To address this need, regional projections of changes in (i) long-term mean sea level and (ii) the frequency of extreme storm surge and wave events have been combined to explore potential changes to coastal flood risk over the 21st century. Local changes in time mean sea level were evaluated using the process-based climate model data and methods presented in the IPCC AR5. Regional surge and wave solutions extending from 1980 to 2100 were generated using ~ 12 km resolution surge (Nucleus for European Modelling of the Ocean – NEMO) and wave (WaveWatchIII) models. Ocean simulations were forced by output from a selection of four downscaled (~ 12 km resolution) atmospheric models, forced at the lateral boundaries by global climate model simulations generated for the IPCC AR5. Long-term trends in skew surge and significant wave height were then assessed using a generalised extreme value model, fit to the largest modelled events each year. An additional atmospheric solution downscaled from the ERA-Interim global reanalysis was used to force historical ocean model simulations extending from 1980–2010, enabling a quantitative assessment of model skill. Simulated historical sea surface height and significant wave height time series were compared to tide gauge data and satellite altimetry data respectively. Central estimates of the long-term mean sea level rise at Singapore by 2100 were projected to be 0.52 m (0.74 m) under the RCP 4.5 (8.5) scenarios respectively. Trends in surge and significant wave height 2 year return levels were found to be statistically insignificant and/or physically very small under the more severe RCP8.5 scenario. We conclude that changes to long-term mean sea level constitute the dominant signal of change to the projected inundation risk for Singapore during the 21st century. We note that the largest recorded surge residual in the Singapore Strait of ~ 84 cm lies between the central and upper estimates of sea level rise by 2100, highlighting the vulnerability of the region

Biochemistry Instructors’ Views toward Developing and Assessing Visual Literacy in Their Courses

Biochemistry instructors are inundated with various representations from which to choose to depict biochemical phenomena. Because of the immense amount of visual know-how needed to be an expert biochemist in the 21st century, there have been calls for instructors to develop biochemistry students’ visual literacy. However, visual literacy has multiple aspects, and determining which area to develop can be quite daunting. Therefore, the goals of this study were to determine what visual literacy skills biochemistry instructors deem to be most important and how instructors develop and assess visual literacy skills in their biochemistry courses. In order to address these goals, a needs assessment was administered to a national sample of biochemistry faculty at four-year colleges and universities. Based on the results of the survey, a cluster analysis was conducted to group instructors into categories based on how they intended to develop visual literacy in their courses. A misalignment was found between the visual literacy skills that were most important and how instructors developed visual literacy. In addition, the majority of instructors assumed these skills on assessments rather than explicitly testing them. Implications focus on the need for better measures to assess visual literacy skills directly

Direct application of plasmid DNA containing type I interferon transgenes to vaginal mucosa inhibits HSV-2 mediated mortality

The application of naked DNA containing type I interferon (IFN) transgenes is a promising potential therapeutic approach for controlling chronic viral infections. Herein, we detail the application of this approach that has been extensively used to restrain ocular HSV-1 infection, for antagonizing vaginal HSV-2 infection. We show that application of IFN-α1, -α5, and –β transgenes to vaginal mouse lumen 24 hours prior to HSV-2 infection reduces HSV-2 mediated mortality by 2.5 to 3-fold. However, other type I IFN transgenes (IFN- α4, -α5, -α6, and –α9) are non effectual against HSV-2. We further show that the efficacy of IFN-α1 transgene treatment is independent of CD4+ T lymphocytes. However, in mice depleted of CD8+ T lymphocytes, the ability of IFN-α1 transgene treatment to antagonize HSV-2 was lost

Relative vs. absolute wind stress in a circumpolar model of the Southern Ocean

The transfer of momentum between the atmosphere and ocean is dependent upon the velocity difference between the seawater and overlying air. This is commonly known as relative wind, or ocean current interaction, and its direct effect is to damp mesoscale ocean eddies through the imposition of an opposing surface torque. If an ocean model neglects the ocean velocity in its bulk formulae, this can lead to an increase in power input to the ocean and a large increase in Eddy Kinetic Energy (EKE). Other secondary effects that are dependent upon the current system under consideration may also occur. Here we show that the neglect of relative wind leads to an ∼50% increase in surface EKE in a circumpolar model of the Southern Ocean. This acts to increase the southwards eddy heat transport, fluxing more heat into the seasonal ice zone, and subsequently reducing ice cover in all seasons. The net reduction in planetary albedo may be a way for a largescale impact on climate

Challenges in integrative approaches to modelling the marine ecosystems of the North Atlantic: Physics to Fish and Coasts to Ocean

It has long been recognized that there are strong interactions and feedbacks between climate, upper ocean biogeochemistry and marine food webs, and also that food web structure and phytoplankton community distribution are important determinants of variability in carbon production and export from the euphotic zone. Numerical models provide a vital tool to explore these interactions, given their capability to investigate multiple connected components of the system and the sensitivity to multiple drivers, including potential future conditions. A major driver for ecosystem model development is the demand for quantitative tools to support ecosystem-based management initiatives. The purpose of this paper is to review approaches to the modelling of marine ecosystems with a focus on the North Atlantic Ocean and its adjacent shelf seas, and to highlight the challenges they face and suggest ways forward. We consider the state of the art in simulating oceans and shelf sea physics, planktonic and higher trophic level ecosystems, and look towards building an integrative approach with these existing tools. We note how the different approaches have evolved historically and that many of the previous obstacles to harmonisation may no longer be present. We illustrate this with examples from the on-going and planned modelling effort in the Integrative Modelling work package of the EURO-BASIN programme