The Department of Automatic Control and Systems Engineering research reports offer a forum for the research output of the academic staff and research students of the Department at the University of Sheffield. Papers are reviewed for quality and presentation by a departmental editor. However, the contents and opinions expressed remain the responsibility of the authors. Some papers in the series may have been subsequently published elsewhere and you are advised to cite the later published version in these instances. ing a Decision Support System for the Histopathalogical Diagnosis of Chronic Idiopathic Inflammatory Bowel Disease- Comparison of Radial Basis Function Neural Networks and Logistic Regression

The medical problem domain that is investigated i this study is the histopathological diagnosis of chronic idiopathic inflammatory bowel disease (CIBD). CIBD is a generic category that describes diseases of the bowel which are characterised by acute and chronic inflammation and which have no identified aetiological agent (such as an infective agent) The two major diseases within this category are ulcerative colitis (UC) and Crohn's disease. Both diseases are chronic conditions characterised by periods of relapse and remission and may produce life threatening complications such as intestinal perforation, sepsis and carcinoma. Many conditions mimic the clinical symptoms of CIBID (Farmer, 1990: Hamilton 1987: Moxon et al. 1994 Shepherd 1991: Shivananda et al. 1991: Suarwicz et al. 1994) and thus histopathalogical examination of colorectal biopsies is important, both in confirming the diagnosis and in excluding other conditions such as infective colitis..........

Making the Distinction Between Crohn's Disease and Ulcerative Colitis by Histopathological Examination: A Comparison of Human Performance, Logistic Regression and Adaptive Resonance Theory Mapping Neural Networks (ARTMAP)

280 cases of inflammatory bowel disease were examined histopathologically and defined features were observed and recorded using a graphical user interface with digitised reference images. The outcome of each case was determined independent of the histopathological report giving 75 cases of Crohn's disease and 105 cases of ulcerative colitis. The cases were randomised and split into training and test sets, each of 140 cases. All 23 observed features were used as input data for logistic regression and adaptive resonance theory mapping neural networks (ARTMAP). The ARTMAP's were used singularly or as a voting cohort of 11 networks, the majority and unanimous decisions of the cohort were analysed separately. The vigilance parameter for the ARTMAP's was varied from high (0.9) to lower (0.5) to vary the number of clusters in ARTa. The best resukts were produced by logistic regression and the 11 high vigilance ARTMAP's with a sensitivity for Crohn's disease of 60% and a specificity of 80%. This was a significant improvement on the original human diagnoses that gave a sensitivity of 25% and specificity of 60%. Either of these technologies could form the basis of a decision support system in this domain (193

An Automated Pattern Recognition System for the Quantification of Inflammatory Cells in Hepatitis C Infected Liver Biopsies.

Hepatitis C is a common viral infection of the liver. The degree of inflammation associated with the infection is normally estimated manually from a liver biopsy, by considering the quantity and nature of inflammatory cells. This paper presents an automated pattern recognition system for the quantification of inflammatory cells in liver biopsies. Initially, images are corrected for colour variation. Features are then extracted for from colour biopsy images at positions of interest identified by adaptive thresholding and clump decomposition. A sequential floating search method and principal component analysis are used to reduce the dimensionality of the feature vector. Manually annotated training images allow supervised training by providing the class membership for each position of interest. Gaussian parametric and Gaussian mixture model density estimation methods are compared and are used to classify cells as either inflammatory or healthy via Bayes' theorem. The system is optimised using a response surface method, where the response or system performance is derived from the area under the receiver operating characteristic curve. The optimised system is then tested on test images previously ranked by a number of observers with varing levels of pathology experience. The observers results are compared to the automated system using Spearman rank correlation. Results show that this system can rank 15 test images, with varying degrees of inflammation, in strong agreement with five expert pathologists

The clinical and phenotypical assessment of seronegative villous atrophy; a prospective UK centre experience evaluating 200 adult cases over a 15-year period (2000-2015).

BACKGROUND: Seronegative villous atrophy (SNVA) is commonly attributed to coeliac disease (CD). However, there are other causes of SNVA. More recently angiotensin-2-receptor-blockers (A2RBs) have been reported as an association but data on SNVA have been limited to centres evaluating complex case referrals and not SNVA in general. OBJECTIVES: To provide clinical outcomes and associations in a large prospective study overseeing all newcomers with SNVA. DESIGN: Over a 15-year period (2000-2015) we evaluated 200 adult patients with SNVA at a UK centre. A diagnosis of either seronegative CD (SNCD) or seronegative non-CD (SN-non-CD) was reached. Baseline comparisons were made between the groups, with 343 seropositive CD subjects serving as controls. RESULTS: Of the 200 SNVA cases, SNCD represented 31% (n=62) and SN-non-CD 69% (n=138). The human leucocyte antigen (HLA)-DQ2 and/or DQ8 genotype was present in 61%, with a 51% positive predictive value for SNCD. The breakdown of identifiable causes in the SN-non-CD group comprised infections (27%, n=54), inflammatory/immune-mediated disorders (17.5%, n=35) and drugs (6.5%, n=13; two cases related to A2RBs). However, no cause was found in 18% (n=36) and of these 72% (n=26/36) spontaneously normalised duodenal histology while consuming a gluten-enriched diet. Following multivariable logistic regression analysis an independent factor associated with SN-non-CD was non-white ethnicity (OR 10.8, 95% CI 2.2 to 52.8); in fact, 66% of non-whites had GI infections. On immunohistochemistry all groups stained positive for CD8-T-cytotoxic intraepithelial lymphocytes. However, additional CD4-T helper intraepithelial lymphocytes were occasionally seen in SN-non-CD mimicking the changes associated with refractory CD. CONCLUSIONS: Most patients with SNVA do not have CD, in particular those who are not white. Furthermore, a subgroup with no obvious aetiology will show spontaneous histological resolution while consuming gluten. These findings suggest caution in empirically prescribing a gluten-free diet without investigation

Adaptive Resonance Theory: A Foundation for "Apprentice" Systems in Clinical Decision Support?

The idea of an "apprentice" system in contrast to an expert system, is introduced, as one which continues, perpetually, to refine its knowledge-base. Neural networks appear to offer the necessary learning ability for this task, and the Adaptive Resonance Theory family is particularly suited to on-line (casual) learning. The ability of these networks accurately to represent decision problems and to disclose their acquired knowledge is discussed, and their practical application is assessed. Two problems of medical decision making are considered using the approach. The first is the early diagnosis of myocardial infarction from clinical and electrocardiographic data gathered at presentation. The second is the cytopathological diagnosis of breast lesions from fine needle aspirate samples. In both cases good performance is obtained along with sets of "if-then" rules which are in accordance with medical opinion. In the first case, examples of on-line learning are given and the system is seen to be behaving as expected, with performance improving with increasing sample size

Orientations of the lamellar phase of block copolymer melts under oscillatory shear flow

We develop a theory to describe the reorientation phenomena in the lamellar phase of block copolymer melt under reciprocating shear flow. We show that similar to the steady-shear, the oscillating flow anisotropically suppresses fluctuations and gives rise to the parallel-perpendicular orientation transition. The experimentally observed high-frequency reverse transition is explained in terms of interaction between the melt and the shear-cell walls.Comment: RevTex, 3 pages, 1 figure, submitted to PR

A BCL2 promoter polymorphism rs2279115 is not associated with BCL2 protein expression or patient survival in breast cancer patients

The B-cell CLL/lymphoma 2 (BCL2) gene family encodes pro- and anti-apoptotic proteins that are critical regulators of programmed cell death. Higher levels of BCL2 expression in breast tumours have been shown to be an independent prognostic factor for improved survival from breast cancer. The promoter single nucleotide polymorphism (SNP) rs2279115 has been associated with both BCL2 expression and patient survival. The aim of this study was to attempt to replicate these observations in a cohort of 1015 UK women with breast cancer, and to compare genotype frequencies in cases and controls. In this study, 1015 breast cancer cases and 1034 control subjects were genotyped for the rs2279115 SNP by 5’ nuclease PCR. Paraffin embedded tumour tissue for 342 case subjects was assembled into tissue microarrays, and the level of expression of BCL2 was established by immunohistochemistry. Kaplan Meier survival curves and Cox Proportional Hazards models were used to examine the effect of genotype on patient survival. The effect of SNP genotype on tumour BCL2 protein levels and breast cancer susceptibility was assessed by logistic regression. In this study higher BCL2 expression was significantly associated with improved survival from breast cancer (p = 0.015), in keeping with previous reports. The SNP rs2279115 was not found to be associated with tumour expression of BCL2, (p = 0.77), and neither was it associated with case/control status (p = 0.25). There was no significant association between the SNP and overall survival (p = 0.75). In conclusion, we found that higher tumour BCL2 expression is associated with improved survival from breast cancer, in keeping with previous studies. However, in contrast to a previous report, the promoter SNP rs2279115 was not associated with BCL2 expression or overall survival from breast cancer

Inflammation decreases keratin level in ulcerative colitis; inadequate restoration associates with increased risk of colitis-associated cancer

Background Keratins are intermediate filament (IF) proteins, which form part of the epithelial cytoskeleton and which have been implicated pathology of inflammatory bowel diseases (IBD). Methods In this study biopsies were obtained from IBD patients grouped by disease duration and subtype into eight categories based on cancer risk and inflammatory status: quiescent recent onset (<5 years) UC (ROUC); UC with primary sclerosing cholangitis; quiescent long-standing pancolitis (20–40 years) (LSPC); active colitis and non-inflamed proximal colonic mucosa; pancolitis with dysplasia-both dysplastic lesions (DT) and distal rectal mucosa (DR); control group without pathology. Alterations in IF protein composition across the groups were determined by quantitative proteomics. Key protein changes were validated by western immunoblotting and immunohistochemical analysis. Result Acute inflammation resulted in reduced K8, K18, K19 and VIM (all p<0.05) compared to controls and non inflamed mucosa; reduced levels of if– associated proteins were also seen in DT and DR. Increased levels of keratins in LSPC was noted relative to controls or ROUC (K8, K18, K19 and VIM, p<0.05). Multiple K8 forms were noted on immunoblotting, with K8 phosphorylation reduced in progressive disease along with an increase in VIM:K8 ratio. K8 levels and phosphorylation are reduced in acute inflammation but appear restored or elevated in subjects with clinical and endoscopic remission (LSPC) but not apparent in subjects with elevated risk of cancer. Conclusions These data suggest that keratin regulation in remission may influence subsequent cancer risk

From Gapped Excitons to Gapless Triplons in One Dimension

Often, exotic phases appear in the phase diagrams between conventional phases. Their elementary excitations are of particular interest. Here, we consider the example of the ionic Hubbard model in one dimension. This model is a band insulator (BI) for weak interaction and a Mott insulator (MI) for strong interaction. Inbetween, a spontaneously dimerized insulator (SDI) occurs which is governed by energetically low-lying charge and spin degrees of freedom. Applying a systematically controlled version of the continuous unitary transformations (CUTs) we are able to determine the dispersions of the elementary charge and spin excitations and of their most relevant bound states on equal footing. The key idea is to start from an externally dimerized system using the relative weak interdimer coupling as small expansion parameter which finally is set to unity to recover the original model.Comment: 18 pages, 10 figure