The role of BNP testing in heart failure

Brain natriuretic peptide (BNP) levels are simple and objective measures of cardiac function. These measurements can be used to diagnose heart failure, including diastolic dysfunction, and using them has been shown to save money in the emergency department setting. The high negative predictive value of BNP tests is particularly helpful for ruling out heart failure. Treatment with angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, spironolactone, and diuretics reduces BNP levels, suggesting that BNP testing may have a role in monitoring patients with heart failure. However, patients with treated chronic stable heart failure may have levels in the normal range (i.e., BNP less than 100 pg per mL and N-terminal proBNP less than 125 pg per mL in patients younger than 75 years). Increases in BNP levels may be caused by intrinsic cardiac dysfunction or may be secondary to other causes such as pulmonary or renal diseases (e.g., chronic hypoxia). BNP tests are correlated with other measures of cardiac status such as New York Heart Association classification. BNP level is a strong predictor of risk of death and cardiovascular events in patients previously diagnosed with heart failure or cardiac dysfunction.

The development of a testing procedure for dry friction brakes

A description of the background to testing friction materials for automotive brakes explains the need for a rapid, inexpensive means of assessing their behaviour in a way which is both accurate and meaningful. Various methods of controlling inertia dynamometers to simulate road vehicles are rejected in favour of programming by means of a commercially available XY plotter. Investigation of brake service conditions is used to set up test schedules, and a dynamometer programming unit built to enable service conditions on vehicles to be simulated on a full scale dynamometer. A technique is developed by which accelerated testing can be achieved without operating under overload conditions, saving time and cost without sacrificing validity. The development of programming by XY plotter is described, with a method of operating one XY plotter to programme the machine, monitor its own behaviour, and plot its own results in logical sequence. Commissioning trials are described and the generation of reproducible results in frictional behaviour and material durability is discussed. Teclmiques are developed to cross check the operation of the machine in retrospect, and retrospectively correct results in the event of malfunctions. Sensitivity errors in the measuring circuits are displayed between calibrations, whilst leaving the recorded results almost unaffected by error. Typical results of brake lining tests are used to demonstrate the range of performance parameters which can be studied by use of the machine. Successful test investigations completed on the machine are reported, including comments on behaviour of cast iron drums and discs. The machine shows that materials can repeat their complex friction/ temperature/speed/pressure relationships at a reproducibility of the order of +-0.003u and +~ 0.0002 in. thickness loss during wear tests. Discussion of practical and academic implications completes the report with recommendations for further work in both fields.

Development of a co-culture model of the human lungs for toxicity testing and identification of biomarkers of inhalation toxicity

The airway epithelium is the first point of contact in the lung for inhaled material, including infectious pathogens and particulate matter, and protects against toxicity from these substances by trapping and clearance via the mucociliary escalator, presence of a protective barrier with tight junctions and initiation of a local inflammatory response. The inflammatory response involves recruitment of phagocytic cells to neutralise and remove and invading materials and is oftern modelled using rodents. However, development of valid in vitro airway epithelial models is of great importance due to the restrictions on animal studies for cosmetic compound testing implicit in the 7th amendment to the European Union Cosmetics Directive. Further, rodent innate immune responses have fundamental differences to human. Pulmonary endothelial cells and leukocytes are also involved in the innate response initiated during pulmonary inflammation. Co-culture models of the airways, in particular where epithelial cells are cultured at air liquid interface with the presence of tight junctions and differentiated mucociliary cells, offer a solution to this problem. Ideally validated models will allow for detection of early biomarkers of response to exposure and investigation into inflammatory response during exposure. This thesis describes the approaches taken towards developing an in vitro epithelial/endothelial cell model of the human airways and identification biomarkers of response to exposure to xenobiotics. The model comprised normal human primary microvascular endothelial cells and the bronchial epithelial cell line BEAS-2B or normal human bronchial epithelial cells. BEAS-2B were chosen as their characterisation at air liquid interface is limited but they are robust in culture, thereby predicted to provide a more reliable test system. Proteomics analysis was undertaken on challenged cells to investigate biomarkers of exposure. BEAS-2B morphology was characterised at air liquid interface compared with normal human bronchial epithelial cells. The results indicate that BEAS-2B cells at an air liquid interface form tight junctions as shown by expression of the tight junction protein zonula occludens-1. To this author’s knowledge this is the first time this result has been reported. The inflammatory response of BEAS-2B (measured as secretion of the inflammatory mediators interleukin-8 and -6) air liquid interface mono-cultures to Escherichia coli lipopolysaccharide or particulate matter (fine and ultrafine titanium dioxide) was comparable to published data for epithelial cells. Cells were also exposed to polymers of “commercial interest” which were in the nanoparticle range (and referred to particles hereafter). BEAS-2B mono-cultures showed an increased secretion of inflammatory mediators after challenge. Inclusion of microvascular endothelial cells resulted in protection against LPS- and particle- induced epithelial toxicity, measured as cell viability and inflammatory response, indicating the importance of co-cultures for investigations into toxicity. Two-dimensional proteomic analysis of lysates from particle-challenged cells failed to identify biomarkers of toxicity due to assay interference and experimental variability. Separately, decreased plasma concentrations of serine protease inhibitors, and the negative acute phase proteins transthyretin, histidine-rich glycoprotein and alpha2-HS glycoprotein were identified as potential biomarkers of methyl methacrylate/ethyl methacrylate/butylacrylate treatment in rats.

Shaping strategic action through the rhetorical construction and exploitation of ambiguity

This paper extends existing understandings of how actors' constructions of ambiguity shape the emergent process of strategic action. We theoretically elaborate the role of rhetoric in exploiting strategic ambiguity, based on analysis of a longitudinal case study of an internationalization strategy within a business school. Our data show that actors use rhetoric to construct three types of strategic ambiguity: protective ambiguity that appeals to common values in order to protect particular interests, invitational ambiguity that appeals to common values in order to invite participation in particular actions, and adaptive ambiguity that enables the temporary adoption of specific values in order to appeal to a particular audience at one point in time. These rhetorical constructions of ambiguity follow a processual pattern that shapes the emergent process of strategic action. Our findings show that (1) the strategic actions that emerge are shaped by the way actors construct and exploit ambiguity, (2) the ambiguity intrinsic to the action is analytically distinct from ambiguity that is constructed and exploited by actors, and (3) ambiguity construction shifts over time to accommodate the emerging pattern of actions.

Can psychometric testing be used to explain, predict and measure behavioural competences and the funding resource orchestration of the entrepreneur?

Financing is a critical entrepreneurial activity (Shane et al. 2003) and within the study of entrepreneurship, behaviour has been identified as an area requiring further exploration (Bird et al. 2012). Since 2008 supply side conditions for SMEs have been severe and increasingly entrepreneurs have to bundle or ‘orchestrate’ funding from a variety of sources in order to successfully finance the firm (Wright and Stigliani 2013: p.15). This longitudinal study uses psychometric testing to measure the behavioural competences of a panel of sixty entrepreneurs in the Creative Industries sector. Interviews were conducted over a 3 year period to identify finance finding behaviour. The research takes a pragmatic realism perspective to examine process and the different behavioural competences of entrepreneurs. The predictive qualities of this behaviour are explored in a funding context. The research confirmed a strong behavioural characteristic as validated through interviews and psychometric testing, was an orientation towards engagement and working with other organisations. In a funding context, this manifested itself in entrepreneurs using networks, seeking advice and sharing equity to fund growth. These co-operative, collaborative characteristics are different to the classic image of the entrepreneur as a risk-taker or extrovert. Leadership and achievement orientation were amongst the lowest scores. Three distinctive groups were identified and also shown by subsequent analysis to be a positive contribution to how entrepreneurial behavioural competences can be considered. Belonging to one of these three clusters is a strong predictive indicator of entrepreneurial behaviour – in this context, how entrepreneurs access finance. These Clusters were also proven to have different characteristics in relation to funding outcomes. The study seeks to make a contribution through the development of a methodology for entrepreneurs, policy makers and financial institutions to identify competencies in finding finance and overcome problems in information asymmetry.

The evolution, development and exploitation of SIALON materials

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Student perceptions of the school physical fitness testing program: The Fitnessgram

The purpose of this study was to determine fifth grade students' perceptions of the Fitnessgram physical fitness testing program. This study examined if the Fitnessgram physical fitness testing experience promotes an understanding of the health-related fitness components and examined the relationship between individual fitness test scores and time spent participating in out-of-school physical activity. Lastly, students' thoughts and feelings concerning the Fitnessgram experience were examined. ^ The primary participant population for the study was 110 fifth grade students at Redland Elementary School, a Miami-Dade County Public School (M-DCPS). Data were collected over the course of 5 months. Multiple sources of data allowed for triangulation. Data sources included Fitnessgram test scores, questionnaires, document analysis, and in-depth interviews. ^ Interview data were analyzed qualitatively for common broad themes, which were identified and defined. Document analysis included analyzing student fitness test scores and student questionnaire data. This information was analyzed to determine if the Fitnessgram test scores have an impact on student views about the school fitness-testing program. Data were statistically analyzed using analysis of frequency, crosstabulations (Bryman & Duncan, 1997), and Somers'd Correlation (Bryman & Duncan, 1997). The results of the analysis of data on student knowledge of the physical fitness components tested by each Fitnessgram test revealed students do not understand the health-related fitness components. ^ The results of determining a relationship between individuals' fitness test scores and time spent in out-of-school physical activity revealed a significant positive relationship for 2 of the 6 Fitnessgram tests. ^ The results of examining students' thoughts and feelings about each Fitnessgram test focused around 2 broad themes: (a) these children do not mind the physical fitness testing and (b) how they felt about the experience was directly related to how they thought they had performed. ^ If the goal of physical fitness was only to get children fit, this test may be appropriate. However, the ultimate goal of physical fitness is to encourage students to live active and healthy lifestyles. Findings suggest the Fitnessgram as implemented by M-DCPS may not be the most suitable measurement instrument when assessing attitudinal changes that affect a healthy lifelong lifestyle. ^

Development and testing of the Elderly Social Vulnerability Index (ESVI): A composite indicator to measure social vulnerability in the Jamaican elderly population

Over the last two decades social vulnerability has emerged as a major area of study, with increasing attention to the study of vulnerable populations. Generally, the elderly are among the most vulnerable members of any society, and widespread population aging has led to greater focus on elderly vulnerability. However, the absence of a valid and practical measure constrains the ability of policy-makers to address this issue in a comprehensive way. This study developed a composite indicator, The Elderly Social Vulnerability Index (ESVI), and used it to undertake a comparative analysis of the availability of support for elderly Jamaicans based on their access to human, material and social resources. The results of the ESVI indicated that while the elderly are more vulnerable overall, certain segments of the population appear to be at greater risk. Females had consistently lower scores than males, and the oldest-old had the highest scores of all groups of older persons. Vulnerability scores also varied according to place of residence, with more rural parishes having higher scores than their urban counterparts. These findings support the political economy framework which locates disadvantage in old age within political and ideological structures. The findings also point to the pervasiveness and persistence of gender inequality as argued by feminist theories of aging. Based on the results of the study it is clear that there is a need for policies that target specific population segments, in addition to universal policies that could make the experience of old age less challenging for the majority of older persons. Overall, the ESVI has displayed usefulness as a tool for theoretical analysis and demonstrated its potential as a policy instrument to assist decision-makers in determining where to target their efforts as they seek to address the issue of social vulnerability in old age. Data for this study came from the 2001 population and housing census of Jamaica, with multiple imputation for missing data. The index was derived from the linear aggregation of three equally weighted domains, comprised of eleven unweighted indicators which were normalized using z-scores. Indicators were selected based on theoretical relevance and data availability.

Effectiveness of the cognitive interview in a multiple-testing situation

The present study assessed the effectiveness of the Cognitive Interview (CI) in a multiple-testing situation. One-hundred and eighty-two undergraduate psychology students viewed a short film clip depicting an automobile accident. Subsequently, the subjects were interviewed twice using either the CI or standard interviewing technique. In both instances, subjects who received the CI recalled more accurate information (m=32.30 at Time 1 and m=30.51 at Time 2) than subjects who received the standard interview (m=18.14 at Time 1 and m=18.38 at Time 2). There was no effect of type of interview at Time 1 on amount recalled at Time 2. This research has implications not only for judicial fact-finders, but also for further researchers interested in the CI procedure.

22 years of Predictive Testing for Huntington’s Disease : The Experience of the UK Huntington’s Prediction Consortium

Peer reviewed

22 years of Predictive Testing for Huntington’s Disease : The Experience of the UK Huntington’s Prediction Consortium

Corrigendum European Journal of Human Genetics (2016) 24, 1515; doi:10.1038/ejhg.2016.81 22 Years of predictive testing for Huntington’s disease: the experience of the UK Huntington’s Prediction Consortium Sheharyar S Baig, Mark Strong, Elisabeth Rosser, Nicola V Taverner, Ruth Glew, Zosia Miedzybrodzka, Angus Clarke, David Craufurd, UK Huntington's Disease Prediction Consortium and Oliver W Quarrell Correction to: European Journal of Human Genetics advance online publication, 11 May 2016; doi: 10.1038/ejhg.2016.36 Post online publication the authors realised that they had made an error: The sentence on page 2: 'In the first 5-year period........but this changed significantly in the last 5-year period with 51% positive and 49% negative (χ2=20.6, P<0.0001)' should read: 'In the first 5-year period........but this changed significantly in the last 5-year period with 49% positive and 51% negative (χ2=20.6, P<0.0001)'.