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.

Improving the economic value of photographic screening for optical coherence tomography-detectable macular oedema:a prospective, multicentre, UK study

Objectives: To determine the best photographic surrogate markers for detecting sight-threatening macular oedema (MO) in people with diabetes attending UK national screening programmes. Design: A multicentre, prospective, observational cohort study of 3170 patients with photographic signs of diabetic retinopathy visible within the macular region [exudates within two disc diameters, microaneurysms/dot haemorrhages (M/DHs) and blot haemorrhages (BHs)] who were recruited from seven study centres. Setting: All patients were recruited and imaged at one of seven study centres in Aberdeen, Birmingham, Dundee, Dunfermline, Edinburgh, Liverpool and Oxford. Participants: Subjects with features of diabetic retinopathy visible within the macular region attending one of seven diabetic retinal screening programmes. Interventions: Alternative referral criteria for suspected MO based on photographic surrogate markers; an optical coherence tomographic examination in addition to the standard digital retinal photograph. Main outcome measures: (1) To determine the best method to detect sight-threatening MO in people with diabetes using photographic surrogate markers. (2) Sensitivity and specificity estimates to assess the costs and consequences of using alternative strategies. (3) Modelled long-term costs and quality-adjusted life-years (QALYs). Results: Prevalence of MO was strongly related to the presence of lesions and was roughly five times higher in subjects with exudates or BHs or more than two M/DHs within one disc diameter. Having worse visual acuity was associated with about a fivefold higher prevalence of MO. Current manual screening grading schemes that ignore visual acuity or the presence of M/DHs could be improved by taking these into account. Health service costs increase substantially with more sensitive/less specific strategies. A fully automated strategy, using the automated detection of patterns of photographic surrogate markers, is superior to all current manual grading schemes for detecting MO in people with diabetes. The addition of optical coherence tomography (OCT) to each strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. Conclusions: Compared with all current manual grading schemes, for the same sensitivity, a fully automated strategy, using the automated detection of patterns of photographic surrogate markers, achieves a higher specificity for detecting MO in people with diabetes, especially if visual acuity is included in the automated strategy. Overall, costs to the health service are likely to increase if more sensitive referral strategies are adopted over more specific screening strategies for MO, for only very small gains in QALYs. The addition of OCT to each screening strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. © Queen's Printer and Controller of HMSO 2013.

The detection of automated perimetric stimuli in ocular disease

Automated perimetry has made viable a rapid threshold examination of the visual field and has reinforced the role of perimetry in the diagnostic procedure. The aim of this study was twofold: to isolate the influence of certain extraneous factors on the sensitivity gradient, since these might limit the early detection and accurate monitoring of visual field loss and to investigate the efficacy of certain novel combinations of stimulus parameters in the detection of early visual field loss. The work was carried out with particular reference to glaucoma and to ocular hypertension. The effects of media opacities on the visual field were assessed by forward intraocular light scatter (n= 15) and were found to mask diffuse glaucomatous visual field loss and underestimate focal loss. Correction of the visual field indices for the effects of forward intraocular light scatter (n= 26) showed the focal losses to be, in reality, unaffected. Measurements of back scatter underestimated forward intraocular light scatter (n= 60) and the resultant depression of the visual field. Perimetric sensitivity improved with patient learning (n= 25) and exhibited eccentricity- and depth-dependency effects whereby improvements in sensitivity were greatest for peripheral areas of the field and for those areas which initially demonstrated the lowest sensitivity. The effects of practice were retained over several months (n= 16). Perimetric sensitivity decreased during prolonged examination due to fatigue effects (n&61 19); these demonstrated a similar eccentricity-dependency, being greatest for eccentricities beyond 30o. Mean sensitivities over the range of adaptation levels employed obeyed the Weber-Fechner law (n= 10) and, as would be expected, were independent of pupil size. No relationship was found between short-term fluctuation and adaptation level. Detection of diffuse glaucomatous visual field loss was facilitated using a size III stimulus of duration 200msec at an adaptation level of 31.5asb, compared with a size III stimulus of duration 100msec at an adaptation level of 4asb (n= 20). In a pilot study (n= 10), temporal summation was found to be higher in glaucomatous patients compared with age-matched controls, although the difference was not statistically significant.

Weakly supervised joint sentiment-topic detection from text

Sentiment analysis or opinion mining aims to use automated tools to detect subjective information such as opinions, attitudes, and feelings expressed in text. This paper proposes a novel probabilistic modeling framework called joint sentiment-topic (JST) model based on latent Dirichlet allocation (LDA), which detects sentiment and topic simultaneously from text. A reparameterized version of the JST model called Reverse-JST, obtained by reversing the sequence of sentiment and topic generation in the modeling process, is also studied. Although JST is equivalent to Reverse-JST without a hierarchical prior, extensive experiments show that when sentiment priors are added, JST performs consistently better than Reverse-JST. Besides, unlike supervised approaches to sentiment classification which often fail to produce satisfactory performance when shifting to other domains, the weakly supervised nature of JST makes it highly portable to other domains. This is verified by the experimental results on data sets from five different domains where the JST model even outperforms existing semi-supervised approaches in some of the data sets despite using no labeled documents. Moreover, the topics and topic sentiment detected by JST are indeed coherent and informative. We hypothesize that the JST model can readily meet the demand of large-scale sentiment analysis from the web in an open-ended fashion.

Evaluation of hemifield sector analysis protocol in multifocal visual evoked potential (MFVEP) objective perimetry for the diagnosis and early detection of glaucomatous field defects

Visual field assessment is a core component of glaucoma diagnosis and monitoring, and the Standard Automated Perimetry (SAP) test is considered up until this moment, the gold standard of visual field assessment. Although SAP is a subjective assessment and has many pitfalls, it is being constantly used in the diagnosis of visual field loss in glaucoma. Multifocal visual evoked potential (mfVEP) is a newly introduced method used for visual field assessment objectively. Several analysis protocols have been tested to identify early visual field losses in glaucoma patients using the mfVEP technique, some were successful in detection of field defects, which were comparable to the standard SAP visual field assessment, and others were not very informative and needed more adjustment and research work. In this study, we implemented a novel analysis approach and evaluated its validity and whether it could be used effectively for early detection of visual field defects in glaucoma. OBJECTIVES: The purpose of this study is to examine the effectiveness of a new analysis method in the Multi-Focal Visual Evoked Potential (mfVEP) when it is used for the objective assessment of the visual field in glaucoma patients, compared to the gold standard technique. METHODS: 3 groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes) and glaucoma suspect patients (38 eyes). All subjects had a two standard Humphrey visual field HFA test 24-2 and a single mfVEP test undertaken in one session. Analysis of the mfVEP results was done using the new analysis protocol; the Hemifield Sector Analysis HSA protocol. Analysis of the HFA was done using the standard grading system. RESULTS: Analysis of mfVEP results showed that there was a statistically significant difference between the 3 groups in the mean signal to noise ratio SNR (ANOVA p<0.001 with a 95% CI). The difference between superior and inferior hemispheres in all subjects were all statistically significant in the glaucoma patient group 11/11 sectors (t-test p<0.001), partially significant 5/11 (t-test p<0.01) and no statistical difference between most sectors in normal group (only 1/11 was significant) (t-test p<0.9). sensitivity and specificity of the HAS protocol in detecting glaucoma was 97% and 86% respectively, while for glaucoma suspect were 89% and 79%. DISCUSSION: The results showed that the new analysis protocol was able to confirm already existing field defects detected by standard HFA, was able to differentiate between the 3 study groups with a clear distinction between normal and patients with suspected glaucoma; however the distinction between normal and glaucoma patients was especially clear and significant. CONCLUSION: The new HSA protocol used in the mfVEP testing can be used to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patient. Using this protocol can provide information about focal visual field differences across the horizontal midline, which can be utilized to differentiate between glaucoma and normal subjects. Sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucoma field loss.

Detection of urinary bladder cancer cells using redox ratio and double excitation wavelengths autofluorescence

The optical redox ratio as a measure of cellular metabolism is determined by an altered ratio between endogenous fluorophores NADH and flavin adenine dinucleotide (FAD). Although reported for other cancer sites, differences in optical redox ratio between cancerous and normal urothelial cells have not previously been reported. Here, we report a method for the detection of cellular metabolic states using flow cytometry based on autofluorescence, and a statistically significant increase in the redox ratio of bladder cancer cells compared to healthy controls. Urinary bladder cancer and normal healthy urothelial cell lines were cultured and redox overview was assessed using flow cytometry. Further localisation of fluorescence in the same cells was carried out using confocal microscopy. Multiple experiments show correlation between cell type and redox ratio, clearly differentiating between healthy cells and cancer cells. Based on our preliminary results, therefore, we believe that this data contributes to current understanding of bladder tissue fluorescence and can inform the design of endoscopic probes. This approach also has significant potential as a diagnostic tool for discrimination of cancer cells among shed urothelial cells in voided urine, and could lay the groundwork for an automated system for population screening for bladder cancer.

Evaluation of hemifield sector analysis protocol in multifocal visual evoked potential objective perimetry for the diagnosis and early detection of glaucomatous field defects

CONCLUSIONS: The new HSA protocol used in the mfVEP testing can be applied to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patients. Using this protocol can provide information about focal visual field differences across the horizontal midline, which can be utilized to differentiate between glaucoma and normal subjects. Sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucoma field loss. PURPOSE: Multifocal visual evoked potential (mfVEP) is a newly introduced method used for objective visual field assessment. Several analysis protocols have been tested to identify early visual field losses in glaucoma patients using the mfVEP technique, some were successful in detection of field defects, which were comparable to the standard automated perimetry (SAP) visual field assessment, and others were not very informative and needed more adjustment and research work. In this study we implemented a novel analysis approach and evaluated its validity and whether it could be used effectively for early detection of visual field defects in glaucoma. METHODS: Three groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes) and glaucoma suspect patients (38 eyes). All subjects had a two standard Humphrey field analyzer (HFA) test 24-2 and a single mfVEP test undertaken in one session. Analysis of the mfVEP results was done using the new analysis protocol; the hemifield sector analysis (HSA) protocol. Analysis of the HFA was done using the standard grading system. RESULTS: Analysis of mfVEP results showed that there was a statistically significant difference between the three groups in the mean signal to noise ratio (ANOVA test, p < 0.001 with a 95% confidence interval). The difference between superior and inferior hemispheres in all subjects were statistically significant in the glaucoma patient group in all 11 sectors (t-test, p < 0.001), partially significant in 5 / 11 (t-test, p < 0.01), and no statistical difference in most sectors of the normal group (1 / 11 sectors was significant, t-test, p < 0.9). Sensitivity and specificity of the HSA protocol in detecting glaucoma was 97% and 86%, respectively, and for glaucoma suspect patients the values were 89% and 79%, respectively.

EPCIS Event-Based traceability in pharmaceutical supply chains via automated generation of linked pedigrees

In this paper we show how event processing over semantically annotated streams of events can be exploited, for implementing tracing and tracking of products in supply chains through the automated generation of linked pedigrees. In our abstraction, events are encoded as spatially and temporally oriented named graphs, while linked pedigrees as RDF datasets are their specific compositions. We propose an algorithm that operates over streams of RDF annotated EPCIS events to generate linked pedigrees. We exemplify our approach using the pharmaceuticals supply chain and show how counterfeit detection is an implicit part of our pedigree generation. Our evaluation results show that for fast moving supply chains, smaller window sizes on event streams provide significantly higher efficiency in the generation of pedigrees as well as enable early counterfeit detection.

The benefit of combining standard automated perimetry and multifocal visual evoked potential hemifield intersector analysis in suspecious glaucomatous visual field defects

Several analysis protocols have been tested to identify early visual field losses in glaucoma patients using the mfVEP technique, some were successful in detection of field defects, which were comparable to the standard SAP visual field assessment, and others were not very informative and needed more adjustment and research work. In this study we implemented a novel analysis approach and evaluated its validity and whether it could be used effectively for early detection of visual field defects in glaucoma. The purpose of this study is to examine the benefit of adding mfVEP hemifield Intersector analysis protocol to the standard HFA test when there is suspicious glaucomatous visual field loss. 3 groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes) and glaucoma suspect patients (38 eyes). All subjects had a two standard Humphrey visual field HFA test 24-2, optical coherence tomography of the optic nerve head, and a single mfVEP test undertaken in one session. Analysis of the mfVEP results was done using the new analysis protocol; the Hemifield Sector Analysis HSA protocol. The retinal nerve fibre (RNFL) thickness was recorded to identify subjects with suspicious RNFL loss. The hemifield Intersector analysis of mfVEP results showed that signal to noise ratio (SNR) difference between superior and inferior hemifields was statistically significant between the 3 groups (ANOVA p<0.001 with a 95% CI). The difference between superior and inferior hemispheres in all subjects were all statistically significant in the glaucoma patient group 11/11 sectors (t-test p<0.001), partially significant 5/11 in glaucoma suspect group (t-test p<0.01) and no statistical difference between most sectors in normal group (only 1/11 was significant) (t-test p<0.9). Sensitivity and specificity of the HSA protocol in detecting glaucoma was 97% and 86% respectively, while for glaucoma suspect were 89% and 79%. The use of SAP and mfVEP results in subjects with suspicious glaucomatous visual field defects, identified by low RNFL thickness, is beneficial in confirming early visual field defects. The new HSA protocol used in the mfVEP testing can be used to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patient. Using this protocol in addition to SAP analysis can provide information about focal visual field differences across the horizontal midline, and confirm suspicious field defects. Sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucoma field loss. The Intersector analysis protocol can detect early field changes not detected by standard HFA test.