Brain ictal state characterisation through multimodal information integration

This Thesis addresses the problem of automated false-positive free detection of epileptic events by the fusion of information extracted from simultaneously recorded electro-encephalographic (EEG) and the electrocardiographic (ECG) time-series. The approach relies on a biomedical case for the coupling of the Brain and Heart systems through the central autonomic network during temporal lobe epileptic events: neurovegetative manifestations associated with temporal lobe epileptic events consist of alterations to the cardiac rhythm. From a neurophysiological perspective, epileptic episodes are characterised by a loss of complexity of the state of the brain. The description of arrhythmias, from a probabilistic perspective, observed during temporal lobe epileptic events and the description of the complexity of the state of the brain, from an information theory perspective, are integrated in a fusion-of-information framework towards temporal lobe epileptic seizure detection. The main contributions of the Thesis include the introduction of a biomedical case for the coupling of the Brain and Heart systems during temporal lobe epileptic seizures, partially reported in the clinical literature; the investigation of measures for the characterisation of ictal events from the EEG time series towards their integration in a fusion-of-knowledge framework; the probabilistic description of arrhythmias observed during temporal lobe epileptic events towards their integration in a fusion-of-knowledge framework; and the investigation of the different levels of the fusion-of-information architecture at which to perform the combination of information extracted from the EEG and ECG time-series. The performance of the method designed in the Thesis for the false-positive free automated detection of epileptic events achieved a false-positives rate of zero on the dataset of long-term recordings used in the Thesis.

Targeted mass spectrometry methods for detecting oxidative post-translational modifications

Oxidative post-translational modifications (oxPTMs) can alter the function of proteins, and are important in the redox regulation of cell behaviour. The most informative technique to detect and locate oxPTMs within proteins is mass spectrometry (MS). However, proteomic MS data are usually searched against theoretical databases using statistical search engines, and the occurrence of unspecified or multiple modifications, or other unexpected features, can lead to failure to detect the modifications and erroneous identifications of oxPTMs. We have developed a new approach for mining data from accurate mass instruments that allows multiple modifications to be examined. Accurate mass extracted ion chromatograms (XIC) for specific reporter ions from peptides containing oxPTMs were generated from standard LC-MSMS data acquired on a rapid-scanning high-resolution mass spectrometer (ABSciex 5600 Triple TOF). The method was tested using proteins from human plasma or isolated LDL. A variety of modifications including chlorotyrosine, nitrotyrosine, kynurenine, oxidation of lysine, and oxidized phospholipid adducts were detected. For example, the use of a reporter ion at 184.074 Da/e, corresponding to phosphocholine, was used to identify for the first time intact oxidized phosphatidylcholine adducts on LDL. In all cases the modifications were confirmed by manual sequencing. ApoB-100 containing oxidized lipid adducts was detected even in healthy human samples, as well as LDL from patients with chronic kidney disease. The accurate mass XIC method gave a lower false positive rate than normal database searching using statistical search engines, and identified more oxidatively modified peptides. A major advantage was that additional modifications could be searched after data collection, and multiple modifications on a single peptide identified. The oxPTMs present on albumin and ApoB-100 have potential as indicators of oxidative damage in ageing or inflammatory diseases.

Handwritten and machine-printed text discrimination using a template matching approach

We propose a novel template matching approach for the discrimination of handwritten and machine-printed text. We first pre-process the scanned document images by performing denoising, circles/lines exclusion and word-block level segmentation. We then align and match characters in a flexible sized gallery with the segmented regions, using parallelised normalised cross-correlation. The experimental results over the Pattern Recognition & Image Analysis Research Lab-Natural History Museum (PRImA-NHM) dataset show remarkably high robustness of the algorithm in classifying cluttered, occluded and noisy samples, in addition to those with significant high missing data. The algorithm, which gives 84.0% classification rate with false positive rate 0.16 over the dataset, does not require training samples and generates compelling results as opposed to the training-based approaches, which have used the same benchmark.

Exchange rate economic exposure and hedging:the significance of currency options

This thesis focuses on the theoretical examination of the exchange rate economic (operating) exposure within the context of the theory of the firm, and proposes some hedging solutions using currency options. The examination of economic exposure is based on such parameters as firms' objectives, industry structure and production cost efficiency. In particular, it examines an hypothetical exporting firm with costs in domestic currency, which faces competition from foreign firms in overseas markets and has a market share expansion objective. Within this framework, the hypothesis is established that economic exposure, portrayed in a diagram connecting export prices and real exchange rates, is asymmetric (i.e. the negative effects depreciation are higher than the positive effects of a currency depreciation). In this case, export business can be seen as a real option, given by exporting firms to overseas customer. Different scenarios about the asymmetry hypothesis can be derived for different assumptions about the determinants of economic exposure. Having established the asymmetry hypothesis, the hedging against this exposure is analysed. The hypothesis is established, that a currency call option should be used in hedging against asymmetric economic exposure. Further, some advanced currency options stategies are discussed, and their use in hedging several scenarios of exposure is indicated, establishing the hypothesis that, the optimal options strategy is a function of the determinants of exposure. Some extensions on the theoretical analysis are examined. These include the hedging of multicurrency exposure using options, and the exposure of a purely domestic firm facing import competition. The empirical work addresses two issues: the empirical validity of the asymmetry hypothesis and the examination of the hedging effectiveness of currency options.

A study of potential serum markers for a diagnosis of gram-positive and gram-negative bacterial sepsis

Sepsis continues to be a major cause of morbidity and mortality as it can readily lead tosevere sepsis, septic shock, multiple organ failure and death. The onset can be rapid and difficult to define clinically. Despite the numerous candidate markers proposed in the literature, to date a serum marker for sepsis has not been found. The aim of this study was to assay the serum of clinically diagnosed patients with eithera Gram-negative or Gram- positive bacterial sepsis for elevated levels of nine potentialmarkers of sepsis, using commercially produced enzyme linked immunosorbent assays(ELISA). The purpose was to find a test marker for sepsis that would be helpful toclinicians in cases of uncertain sepsis and consequently expose false positive BC'scaused by skin or environmental contaminants. Nine test markers were assayed including IL-6, IL-I 0, ILI2, TNF-α, lipopolysaccharide binding protein, procalcitonin, sE-selectin, sICAM -1 and a potential differential marker for Gram-positive sepsis- anti-lipid S antibody. A total of 445 patients were enrolled into this study from the Queen Elizabeth Hospital and Selly Oak Hospital (Birmingham). The results showed that all the markers were elevated in patients with sepsis and that patients with a Gram-negative sepsis consistently produced higher median/range serum levels than those with a Gram-positive sepsis. No single marker was able to identify all the septic patients. Combining two markers caused the sensitivities and specificities for a diagnosis of sepsis to increase to within a 90% to 100% range. By a process of elimination the markers that survived into the last phase were IL-6 with sICAM -1, and anti-lipid S IgG assays Defining cut-off levels for a diagnosis of sepsis became problematic and a semi-blind trial was devised to test the markers in the absence of both clinical details and positive blood cultures. Patients with pyrexia of unknown origin and negative BC were included in this phase (4). The results showed that IL-6 with sICAM-l are authentic markers of sepsis. There was 82% agreement between the test marker diagnosis and the clinical diagnosis for sepsis in patients with a Gram-positive BC and 78% agreement in cases of Gram-negative Be. In the PUO group the test markers identified 12 cases of sepsis and the clinical diagnosis 15. The markers were shown to differentiate between early sepsis and sepsis, inflammatory responses and infection. Anti-lipid S with IL-6 proved be a sensitive marker for Gram-positive infections/sepsis.

Putting service relations to the test:how can negative consumer reactions of price increases be reduced?

Price increases seem to be an adequate way to improve the earnings of companies. This fact becomes especially crucial because of increased price competition in many markets. Price increases might lead to negative customer reactions, such as a lower perceived utility or a lower loyalty intention. Therefore, the question for managers remains how prices can be increased without losing customers. Results of our experimental study suggest that customers of energy suppliers rate the perceived utility of the offer relatively better when the price increase is combined with an additional modification of the product or accompanied by a new service. It becomes clear that intensifying service relations can offset the negative effects of price increases.

Pulse oximetry screening for congenital heart defects in newborn infants:an evaluation of acceptability to mothers

Background: Introducing neonatal screening procedures may not be readily accepted by parents and may increase anxiety. The acceptability of pulse oximetry screening to parents has not been previously reported. Objective: To assess maternal acceptability of pulse oximetry screening for congenital heart defects and to identify factors predictive of participation in screening. Design and setting: A questionnaire was completed by a cross-sectional sample of mothers whose babies were recruited into the PulseOx Study which investigated the test accuracy of pulse oximetry screening. Participants: A total of 119 mothers of babies with false-positive (FP) results, 15 with true-positive and 679 with true-negative results following screening. Main outcome measures: Questionnaires included measures of satisfaction with screening, anxiety, depression and perceptions of test results. Results: Participants were predominantly satisfied with screening. The anxiety of mothers given FP results was not significantly higher than that of mothers given true-negative results (median score 32.7 vs 30.0, p=0.09). White British/Irish mothers were more likely to participate in screening, with a decline rate of 5%; other ethnic groups were more likely to decline with the largest increase in declining being for Black African mothers (21%, OR 4.6, 95% CI 3.8 to 5.5). White British mothers were also less anxious (p<0.001) and more satisfied (p<0.001) than those of other ethnicities Conclusions: Pulse oximetry screening was acceptable to mothers and FP results were not found to increase anxiety. Factors leading to differences in participation and satisfaction across ethnic groups need to be identified so that staff can support parents appropriately.