Simulation using novel equipment designed to explain spirometric abnormalities in respiratory disease enhances learning in higher cognitive domains

Simulation of disorders of respiratory mechanics shown by spirometry provides insight into the pathophysiology of disease but some clinically important disorders have not been simulated and none have been formally evaluated for education. We have designed simple mechanical devices which, along with existing simulators, enable all the main dysfunctions which have diagnostic value in spirometry to be simulated and clearly explained with visual and haptic feedback. We modelled the airways as Starling resistors by a clearly visible mechanical action to simulate intra- and extra-thoracic obstruction. A narrow tube was used to simulate fixed large airway obstruction and inelastic bands to simulate restriction. We hypothesized that using simulators whose action explains disease promotes learning especially in higher domain educational objectives. The main features of obstruction and restriction were correctly simulated. Simulation of variable extra-thoracic obstruction caused blunting and plateauing of inspiratory flow, and simulation of intra-thoracic obstruction caused limitation of expiratory flow with marked dynamic compression. Multiple choice tests were created with questions allocated to lower (remember and understand) or higher cognitive domains (apply, analyse and evaluate). In a cross-over design, overall mean scores increased after 1½ h simulation spirometry (43-68 %, effect size 1.06, P < 0.0001). In higher cognitive domains the mean score was lower before and increased further than lower domains (Δ 30 vs 20 %, higher vs lower effect size 0.22, P < 0.05). In conclusion, the devices successfully simulate various patterns of obstruction and restriction. Using these devices medical students achieved marked enhancement of learning especially in higher cognitive domains.

Untargeted Metabolomic Analysis of Human Plasma Indicates Differentially Affected Polyamine and L-Arginine Metabolism in Mild Cognitive Impairment Subjects Converting to Alzheimer’s Disease

This study combined high resolution mass spectrometry (HRMS), advanced chemometrics and pathway enrichment analysis to analyse the blood metabolome of patients attending the memory clinic: cases of mild cognitive impairment (MCI; n = 16), cases of MCI who upon subsequent follow-up developed Alzheimer's disease (MCI_AD; n = 19), and healthy age-matched controls (Ctrl; n = 37). Plasma was extracted in acetonitrile and applied to an Acquity UPLC HILIC (1.7μm x 2.1 x 100 mm) column coupled to a Xevo G2 QTof mass spectrometer using a previously optimised method. Data comprising 6751 spectral features were used to build an OPLS-DA statistical model capable of accurately distinguishing Ctrl, MCI and MCI_AD. The model accurately distinguished (R2 = 99.1%; Q2 = 97%) those MCI patients who later went on to develop AD. S-plots were used to shortlist ions of interest which were responsible for explaining the maximum amount of variation between patient groups. Metabolite database searching and pathway enrichment analysis indicated disturbances in 22 biochemical pathways, and excitingly it discovered two interlinked areas of metabolism (polyamine metabolism and L-Arginine metabolism) were differentially disrupted in this well-defined clinical cohort. The optimised untargeted HRMS methods described herein not only demonstrate that it is possible to distinguish these pathologies in human blood but also that MCI patients 'at risk' from AD could be predicted up to 2 years earlier than conventional clinical diagnosis. Blood-based metabolite profiling of plasma from memory clinic patients is a novel and feasible approach in improving MCI and AD diagnosis and, refining clinical trials through better patient stratification.

Northern Ireland Representation at Westminster: Constitutional Conundrums and Political Manoeuvres

This article focuses on the issue of Northern Ireland's representation at Westminster. It investigates the political context of the decision to increase Northern Ireland's representation in the house of commons at Westminster from 12 members to 17 in 1978-9. Exploring this episode in more detail, it is argued, provides a more informed overall understanding of the history of devolution in the UK and of the way issues concerning Northern Ireland often overlapped with questions of constitutional change in Scotland and Wales. The article also throws light on the matter of Northern Ireland MPs and their voting rights at Westminster during Northern Ireland's experience of devolution prior to 1972.

Plasma Clusterin Levels and the rs11136000 Genotype in Individuals with Mild Cognitive Impairment and Alzheimer's Disease

Aim: Substantial evidence links atherosclerosis and Alzheimer's disease (AD). Apolipoproteins, such as apolipoprotein E, have a causal relationship with both diseases. The rs11136000 SNP within the CLU gene, which encodes clusterin (apolipoprotein J), is also associated with increased AD risk. The aim of this study was to investigate the relationship between plasma clusterin and the rs11136000 genotype in mild cognitive impairment (MCI) and AD.

Methods: Plasma and DNA samples were collected from control, MCI and AD subjects (n=142, 111, 154, respectively). Plasma clusterin was determined by ELISA and DNA samples were genotyped for rs11136000 by TaqMan assay.

Results: Plasma clusterin levels were higher in MCI and AD subjects vs. controls (222.3 +/- 61.3 and 193.6 +/- 58.2 vs. 178.6 +/- 52.3 mu g/ml, respectively; p

Conclusion: This study examined control, MCI and AD subjects, identifying for the first time that plasma clusterin levels were influenced, not only by the presence of AD, but also the transitional stage of MCI, while rs11136000 genotype only influenced plasma clusterin levels in the control group. The increase in plasma clusterin in MCI and AD subjects may occur in response to the disease process and would be predicted to increase binding capacity for amyloid-beta peptides in plasma, enhancing their removal from the brain.

An analysis of implied volatility jump dynamics: Novel functional data representation in crude oil markets

The predominant fear in capital markets is that of a price spike. Commodity markets differ in that there is a fear of both upward and down jumps, this results in implied volatility curves displaying distinct shapes when compared to equity markets. The use of a novel functional data analysis (FDA) approach, provides a framework to produce and interpret functional objects that characterise the underlying dynamics of oil future options. We use the FDA framework to examine implied volatility, jump risk, and pricing dynamics within crude oil markets. Examining a WTI crude oil sample for the 2007–2013 period, which includes the global financial crisis and the Arab Spring, strong evidence is found of converse jump dynamics during periods of demand and supply side weakness. This is used as a basis for an FDA-derived Merton (1976) jump diffusion optimised delta hedging strategy, which exhibits superior portfolio management results over traditional methods.

Behind the Headlines: Media Representation of Children and Young People in Northern Ireland:Summary of Research Findings

Funded by the Economic and Social Research Council this partnership project between the Childhood, Transition and Social Justice Initiative at Queen’s University and Include Youth focuses on the negative stereotyping of children and young people and the role and responsibilities of the media in the creation and transmission of negative images. Engaging with children, young people, organisations working with children and young people and media representatives, the project uses research evidence to explore negative media representation and its consequences for children’s rights, public reaction and policy initiatives in Northern Ireland. This report represents a summary of the findings of engagement with 141 children and young people. It outlines how they feel they are presented by the media and the impacts of this. It concludes by noting ways forward in challenging negative portrayals.