Full-scale measurement and analysis of train slipstreams and wakes. Part 1: Ensemble averages

This paper describes a series of extensive and unique full-scale measurements of the slipstreams of trains of various types that were carried out as part of the EU-sponsored AeroTRAIN project, together with the analysis of the experimental data. These experiments were carried out with the fundamental aim of seeking to reduce the complexity of the current technical specifications for interoperability (TSI) testing methodology. Experimental sites in Spain and Germany were used, for a range of different train types - high-speed single-unit trains, high-speed double-unit trains, conventional passenger units and locomotive/coach combinations. The data that was obtained was supplemented by other data from previous projects. The analysis primarily involved a study of the ensemble averages of the slipstream velocities, measured both at trackside and above platforms. The differences between the flows around different train types were elucidated, and the effect of platforms on slipstream behaviour described. A brief analysis of the effects of crosswinds on slipstream behaviour was also carried out. Through a detailed analysis of slipstream velocity components, the detailed nature of the flow around the nose and in the near wake of the train was investigated, again revealing differences in flow pattern between different trains. Significant similarity in the far wake flows was revealed. These fundamental results form the basis for the detailed discussion of the proposed TSI methodology that will be presented in Part 2 of this paper. Overall the results enable the nature of the flow field around trains to be understood in far greater detail than before, and also allow the developments of a revised TSI methodology which is more efficient than current practice. © IMechE 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav

Accuracy and feasibility of an android-based digital assessment tool for post stroke visual disorders - The StrokeVision App

Background: Visual impairment affects up to 70% of stroke survivors. We designed an app (StrokeVision) to facilitate screening for common post stroke visual issues (acuity, visual fields and visual inattention). We sought to describe the test-time, feasibility, acceptability and accuracy of our app based digital visual assessments against a) current methods used for bedside screening, and b) gold standard measures. Methods: Patients were prospectively recruited from acute stroke settings. Index tests were app based assessments of fields and inattention performed by a trained researcher. We compared against usual clinical screening practice of visual fields to confrontation including inattention assessment (simultaneous stimuli). We also compared app to gold standard assessments of formal kinetic perimetry (Goldman or Octopus Visual Field Assessment); and pencil and paper based tests of inattention (Albert’s, Star Cancellation, and Line Bisection). Results of inattention and field tests were adjudicated by a specialist Neuro-Ophthalmologist. All assessors were masked to each other’s results. Participants and assessors graded acceptability using a bespoke scale that ranged from 0 (completely unacceptable) to 10 (perfect acceptability). Results: Of 48 stroke survivors recruited, the complete battery of index and reference tests for fields was successfully completed in 45. Similar acceptability scores were observed for app-based (assessor median score 10 [IQR:9-10]; patient 9 [IQR:8-10]) and traditional bedside testing (assessor 10 [IQR:9-10; patient 10 [IQR:9-10]). Median test time was longer for app-based testing (combined time-to-completion of all digital tests 420 seconds [IQR:390-588]) when compared with conventional bedside testing (70 seconds, [IQR:40-70]) but shorter than gold standard testing (1260 seconds, [IQR:1005-1620]). Compared with gold standard assessments, usual screening practice demonstrated 79% sensitivity and 82% specificity for detection of a stroke-related field defect. This compares with 79% sensitivity and 88% specificity for StrokeVision digital assessment. Conclusion: StrokeVision shows promise as a screening tool for visual complications in the acute phase of stroke. The app is at least as good as usual screening and offers other functionality that may make it attractive for use in acute stroke

Can variability in the effect of opioids on refractory breathlessness be explained by genetic factors?

© 2015, BMJ Publishing Group. All rights reserved. Objectives: Opioids modulate the perception of breathlessness with a considerable variation in response, with poor correlation between the required opioid dose and symptom severity. The objective of this hypothesis-generating, secondary analysis was to identify candidate single nucleotide polymorphisms (SNP) from those associated with opioid receptors, signalling or pain modulation to identify any related to intensity of breathlessness while on opioids. This can help to inform prospective studies and potentially lead to better tailoring of opioid therapy for refractory breathlessness. Setting: 17 hospice/palliative care services (tertiary services) in 11 European countries. Participants: 2294 people over 18 years of age on regular opioids for pain related to cancer or its treatment. Primary outcome measures: The relationship between morphine dose, breathlessness intensity (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire; EORTCQLQC30 question 8) and 112 candidate SNPs from 25 genes (n=588). Secondary outcome measures: The same measures for people on oxycodone (n=402) or fentanyl (n=429). Results: SNPs not in Hardy-Weinberg equilibrium or with allele frequencies ( < 5%) were removed. Univariate associations between each SNP and breathlessness intensity were determined with Benjamini-Hochberg false discovery rate set at 20%. Multivariable ordinal logistic regression, clustering over country and adjusting for available confounders, was conducted with remaining SNPs. For univariate morphine associations, 1 variant on the 5-hydroxytryptamine type 3B (HTR3B) gene, and 4 on the β-2-arrestin gene (ARRB2) were associated with more intense breathlessness. 1 SNP remained significant in the multivariable model: people with rs7103572 SNP (HTR3B gene; present in 8.4% of the population) were three times more likely to have more intense breathlessness (OR 2.86; 95% CIs 1.46 to 5.62; p=0.002). No associations were seen with fentanyl nor with oxycodone. Conclusions: This large, exploratory study identified 1 biologically plausible SNP that warrants further study in the response of breathlessness to morphine therapy

Synthesis of the oxysterol, 24(S), 25-epoxycholesterol, parallels cholesterol production and may protect against cellular accumulation of newly-synthesized cholesterol

AIM: The effects of 24(S),25-epoxycholesterol (24,25EC) on aspects of cholesterol homeostasis is well-documented. When added to cells, 24,25EC decreases cholesterol synthesis and up-regulates cholesterol efflux genes, including ABCA1. Synthesis of 24,25EC occurs in a shunt of the mevalonate pathway which also produces cholesterol. Therefore, 24,25EC synthesis should be subject to the same negative feedback regulation as cholesterol synthesis. To date, no role has been ascribed to 24,25EC in light of the fact that increased accumulation of cholesterol should decrease formation of this oxysterol through feedback inhibition. This leads to the intriguing paradox: why inhibit production of an apparently important regulator of cholesterol homeostasis when it is needed most? METHODS: We used a combination of pharmacological and genetic approaches in Chinese Hamster Ovary cell-lines to investigate this paradox. Endogenous synthesis of 24,25EC was manipulated using partial inhibition of the enzyme, Oxidosqualene Cyclase. Changes in cholesterol and 24,25EC synthesis were determined using metabolic labelling with [1-(14)C]-acetate, thin-layer chromatography and phosphorimaging. Transcriptional effects mediated via SREBP and LXR were analysed by luciferase reporter assays. RESULTS: We showed that cholesterol addition to cells lead to a rapid and preferential inhibition of 24,25EC synthesis. Addition of 24,25EC resulted in parallel inhibition of 24,25EC and cholesterol synthesis. Furthermore, we used a variety of approaches to examine the relationship between cholesterol and 24,25EC synthesis, including cell-lines with different rates of cholesterol synthesis, varying cholesterol synthetic rates by pre-treatment with a statin, or lipoprotein cholesterol loading of macrophages. In all cases, we showed that 24,25EC synthesis faithfully tracked cholesterol synthesis. Moreover, changes in 24,25EC synthesis exerted downstream effects, reducing SREBP transcriptional activity whilst increasing ABCA1 and LXR transcriptional activity. CONCLUSION: Our results show that 24,25EC synthesis parallels cholesterol synthesis, consistent with this oxysterol functioning as a safety valve to protect against the accumulation of newly-synthesised cholesterol (as opposed to exogenously-derived cholesterol). Considering that 24,25EC is capable of being produced in all cholesterogenic cells, we propose that production of 24,25EC may represent a ubiquitous defence mechanism

Multiparty Electoral Competition in the Netherlands and Germany: A Model Based on Multinomial Probit

A typical assumption of electoral models of party competition is that parties adopt policy positions so as to maximize expected vote share. Here we use Euro-barometer survey data and European elite-study data from 1979 for the Netherlands and Germany to construct a stochastic model of voter response, based on multinomial probit estimation. For each of these countries, we estimate a pure spatial electoral voting model and a joint spatial model. The latter model also includes individual voter and demographic characteristics. The pure spatial models for the two countries quite accurately described the electoral response as a stochastic function of party positions. We use these models to perform a thought experiment so as to estimate the expected vote maximizing party positions. We go on to propose a model of internal party decision-making based both on pre-election electoral estimation and postelection coalition bargaining. This model suggests why the various parties in the period in question did not adopt vote maximizing positions. We argue that maximizing expected vote will not, in general, be a rational party strategy in multiparty political systems which are based on proportional representation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116246/1/pc98.pd

Driving human motor cortical oscillations leads to behaviorally relevant changes in local GABAA inhibition: a tACS-TMS study

Beta and gamma oscillations are the dominant oscillatory activity in the human motor cortex (M1). However, their physiological basis and precise functional significance remain poorly understood. Here, we used transcranial magnetic stimulation (TMS) to examine the physiological basis and behavioral relevance of driving beta and gamma oscillatory activity in the human M1 using transcranial alternating current stimulation (tACS). tACS was applied using a sham-controlled crossover design at individualized intensity for 20 min and TMS was performed at rest (before, during, and after tACS) and during movement preparation (before and after tACS). We demonstrated that driving gamma frequency oscillations using tACS led to a significant, duration-dependent decrease in local resting-state GABAA inhibition, as quantified by short interval intracortical inhibition. The magnitude of this effect was positively correlated with the magnitude of GABAA decrease during movement preparation, when gamma activity in motor circuitry is known to increase. In addition, gamma tACS-induced change in GABAA inhibition was closely related to performance in a motor learning task such that subjects who demonstrated a greater increase in GABAA inhibition also showed faster short-term learning. The findings presented here contribute to our understanding of the neurophysiological basis of motor rhythms and suggest that tACS may have similar physiological effects to endogenously driven local oscillatory activity. Moreover, the ability to modulate local interneuronal circuits by tACS in a behaviorally relevant manner provides a basis for tACS as a putative therapeutic intervention.SIGNIFICANCE STATEMENT Gamma oscillations have a vital role in motor control. Using a combined tACS-TMS approach, we demonstrate that driving gamma frequency oscillations modulates GABAA inhibition in the human motor cortex. Moreover, there is a clear relationship between the change in magnitude of GABAA inhibition induced by tACS and the magnitude of GABAA inhibition observed during task-related synchronization of oscillations in inhibitory interneuronal circuits, supporting the hypothesis that tACS engages endogenous oscillatory circuits. We also show that an individual's physiological response to tACS is closely related to their ability to learn a motor task. These findings contribute to our understanding of the neurophysiological basis of motor rhythms and their behavioral relevance and offer the possibility of developing tACS as a therapeutic tool

Accurate Mental Maps as an Aspect of Local Ecological Knowledge (LEK): A Case Study from Lough Neagh, Northern Ireland

A mental map of the substrate of Lough Neagh, Northern Ireland, compiled from interviews with local fishermen, is compared with maps produced by science-based techniques. The comparison reveals that the mental map is highly accurate. This finding contrasts with the spatial distortion characteristic of the classic mental map. The accuracy of the Lough Neagh map is attributed to the fact that it is a compendium of the knowledge of several generations, rather than an individual perception. Individual distortions are filtered out, and accuracy is promoted by economic self-interest. High accuracy may be characteristic of the mental maps held by artisanal exploiters of natural resources

Climate Science, Development Practice, and Policy Interactions in Dryland Agroecological Systems

The literature on drought, livelihoods, and poverty suggests that dryland residents are especially vulnerable to climate change. However, assessing this vulnerability and sharing lessons between dryland communities on how to reduce vulnerability has proven difficult because of multiple definitions of vulnerability, complexities in quantification, and the temporal and spatial variability inherent in dryland agroecological systems. In this closing editorial, we review how we have addressed these challenges through a series of structured, multiscale, and interdisciplinary vulnerability assessment case studies from drylands in West Africa, southern Africa, Mediterranean Europe, Asia, and Latin America. These case studies adopt a common vulnerability framework but employ different approaches to measuring and assessing vulnerability. By comparing methods and results across these cases, we draw out the following key lessons: (1) Our studies show the utility of using consistent conceptual frameworks for vulnerability assessments even when quite different methodological approaches are taken; (2) Utilizing narratives and scenarios to capture the dynamics of dryland agroecological systems shows that vulnerability to climate change may depend more on access to financial, political, and institutional assets than to exposure to environmental change; (3) Our analysis shows that although the results of quantitative models seem authoritative, they may be treated too literally as predictions of the future by policy makers looking for evidence to support different strategies. In conclusion, we acknowledge there is a healthy tension between bottom-up/ qualitative/place-based approaches and top-down/quantitative/generalizable approaches, and we encourage researchers from different disciplines with different disciplinary languages, to talk, collaborate, and engage effectively with each other and with stakeholders at all levels