Examining lipid metabolism of colorectal adenomas and carcinomas using Rapid Evaporative Ionisation Mass Spectrometry (REIMS)

Background There is an unmet need for real-time intraoperative colorectal tissue recognition, which would promote personalised oncologic decision making. Rapid Evaporative Ionization Mass Spectrometry (REIMS) analyses the composition of cellular lipids through the aerosol generated from electrosurgical instruments, providing a novel diagnostic platform and surgeon feedback. Thesis Hypothesis Colorectal lipid metabolism and cellular lipid composition are associated with the phenotype of colorectal adenomas and carcinomas, which can be leveraged for tissue recognition in vivo. Methods This thesis contains three work packages. First, a method for REIMS spectral quality control was developed based on a human dataset and analysis of a porcine model assessed the spectral impact of technical and environmental factors. Second, an ex vivo spectral reference database was constructed from analysis of human colorectal tissues, assessing the ability of REIMS for tissue recognition. Finally, REIMS was translated into the operating theatre, for proof-of-principle application of during transanal minimally invasive surgery (TAMIS). Results Sensitivity analyses revealed seven minimum quality criteria for REIMS spectra to be included in all future statistical analyses, with quality also impacted by low diathermy power, coagulation mode and tissue contamination. Based on tissue of 161 patients, REIMS could differentiate colorectal normal, adenoma and cancer tissue with 91.1% accuracy, and disease from normal with 93.5% accuracy. REIMS could risk-stratify adenomas by predicting grade of dysplasia, however not histological features of poor prognosis in cancers. 61 pertinent lipid metabolites were structurally identified. REIMS was coupled to TAMIS in seven patients. Optimisation of the workflow successfully increased signal intensity, with tissue recognition showing high accuracy in vivo and identification of a cancer-involved margin. Discussion This thesis demonstrates that REIMS can be optimised and applied for accurate real-time colorectal tissue recognition based on cellular lipid composition. This can be translated in vivo, with promising results during first-in-man mass spectrometry-coupled TAMIS.Open Acces

Evaluating observer agreement of scoring systems for foot integrity and footrot lesions in sheep

Background: A scoring scale with five ordinal categories is used for visual diagnosis of footrot in sheep and to study its epidemiology and control. More recently a 4 point ordinal scale has been used by researchers to score foot integrity (wall and sole horn damage) in sheep. There is no information on observer agreement using either of these scales. Observer agreement for ordinal scores is usually estimated by single measure values such as weighted kappa or Kendall’s coefficient of concordance which provide no information where the disagreement lies. Modeling techniques such as latent class models provide information on both observer bias and whether observers have different thresholds at which they change the score given. In this paper we use weighted kappa and located latent class modeling to explore observer agreement when scoring footrot lesions (using photographs and videos) and foot integrity (using post mortem specimens) in sheep. We used 3 observers and 80 photographs and videos and 80 feet respectively. Results: Both footrot and foot integrity scoring scales were more consistent within observers than between. The weighted kappa values between observers for both footrot and integrity scoring scales ranged from moderate to substantial. There was disagreement between observers with both observer bias and different thresholds between score values. The between observer thresholds were different for scores 1 and 2 for footrot (using photographs and videos) and for all scores for integrity (both walls and soles). The within observer agreement was higher with weighted kappa values ranging from substantial to almost perfect. Within observer thresholds were also more consistent than between observer thresholds. Scoring using photographs was less variable than scoring using video clips or feet. Conclusions: Latent class modeling is a useful method for exploring components of disagreement within and between observers and this information could be used when developing a scoring system to improve reliability

Counterparty Credit Limits: An Effective Tool for Mitigating Counterparty Risk?

A counterparty credit limit (CCL) is a limit imposed by a financial institution to cap its maximum possible exposure to a specified counterparty. Although CCLs are designed to help institutions mitigate counterparty risk by selective diversification of their exposures, their implementation restricts the liquidity that institutions can access in an otherwise centralized pool. We address the question of how this mechanism impacts trade prices and volatility, both empirically and via a new model of trading with CCLs. We find empirically that CCLs cause little impact on trade. However, our model highlights that in extreme situations, CCLs could serve to destabilize prices and thereby influence systemic risk

A four year longitudinal sero-epidemiological study of bovine herpesvirus type-1 (BHV-1) in adult cattle in 107 unvaccinated herds in south west England

Background: Bovine herpesvirus type-1 (BHV-1) is an important pathogen of cattle that presents with a variety of clinical signs, including the upper respiratory tract infection infectious bovine rhinotracheitis (IBR). A seroepidemiological study of BHV-1 antibodies was conducted in England from 2002 – 2004: 29,782 blood samples were taken from 15,736 cattle from 114 herds which were visited on up to three occasions. Antibody concentration was measured using a commercial ELISA. Farm management information was collected using an interview questionnaire, and herd size and cattle movements were obtained from the cattle tuberculosis testing database and the British Cattle Movement Service. Hierarchical statistical models were used to investigate associations between cattle and herd variables and the continuous outcome percentage positive (PP) values from the ELISA test in unvaccinated herds. Results: There were 7 vaccinated herds, all with at least one seropositive bovine. In unvaccinated herds 83.2% had at least one BHV-1 seropositive bovine, and the mean cattle and herd BHV-1 seroprevalence were 42.5% and 43.1% respectively. There were positive associations between PP value, age, herd size, presence of dairy cattle. Adult cattle in herds with grower cattle had lower PP values than those in herds without grower cattle. Purchased cattle had significantly lower PP values than homebred cattle, whereas cattle in herds that were totally restocked after the foot-and-mouth epidemic in 2001 had significantly higher PP values than those in continuously stocked herds. Samples taken in spring and summer had significantly lower PP values than those taken in winter, whereas those taken in autumn had significantly higher PP values than those taken in winter. The risks estimated from a logistic regression model with a binary outcome (seropositive yes/no) were similar. Conclusion: The prevalence of BHV-1 seropositivity in cattle and herds has increased since the 1970s. Although the study population prevalence of BHV-1 was temporally stable during study period, the associations between serological status and cattle age, herd size, herd type, presence of young stock and restocked versus continuously stocked herds indicate that there is heterogeneity between herds and so potential for further spread of BHV-1 within and between herds

A four year longitudinal sero-epidemiology study of Neospora caninum in adult cattle from 114 cattle herds in south west England : associations with age, herd and dam-offspring pairs

Background: Neosporosis caused by the protozoan parasite Neospora caninum, is an economically important cause of abortion, stillbirth, low milk yield, reduced weight gain and premature culling in cattle. Consequently, a seroepidemiological study of N. caninum antibodies was conducted in England with 29,782 samples of blood taken from 15,736 cattle from 114 herds visited on three occasions at yearly intervals. Herds were categorised into lower (< 10%) and higher (≥ 10%) median herd seroprevalence. Hierarchical models were run to investigate associations between the sample to positive (S/P) ratio and herd and cattle factors. Results: Ninety-four percent of herds had at least one seropositive cow; 12.9% of adult cattle had at least one seropositive test. Approximately 90% of herds were seropositive at all visits; 9 herds (8%) changed serological status between visits. The median N. caninum seroprevalence in positive herds was 10% (range 0.4% to 58.8%). There was a positive association between the serostatus of offspring and dams that were ever seropositive. In the hierarchical model of low seroprevalence herds there was no significant association between S/P ratio and cattle age. There was a significantly lower S/P ratio in cattle in herds that were totally restocked after the foot-and-mouth epidemic of 2001 compared with those from continuously stocked herds and cattle purchased into these herds had a higher S/P ratio than homebred cattle. In the model of high seroprevalence herds the S/P ratio increased with cattle age, but was not associated with restocking or cattle origin. Conclusion: There were no strong temporal changes in herd seroprevalence of N. caninum but 90% of herds had some seropositive cattle over this time period. Vertical transmission from seropositive dams appeared to occur in all herds. In herds with a high seroprevalence the increasing S/P ratio in 2–4 year old cattle is suggestive of exposure to N. caninum: horizontal transmission between adult cattle, infection from a local source or recrudescence and abortions. Between-herd movements of infected cattle enhance the spread of N. caninum, particularly into low seroprevalence herds. Some restocked herds had little exposure to N. caninum, while in others infection had spread in the time since restocking

Reading groups as radical practice

Reading groups represent a common practice both inside and outside the university, and in many cases provide an important space that breaches the divide. Nevertheless, there is relatively little critical reflection on the political significance of reading groups, their practical utility, and the challenges involved. This intervention emerged through an encounter between three UK based academic-activists and sharing our experiences of ‘doing reading groups’ in and around the university

Departmental Survival through Collaborative Industrial Partnership

In this paper/discussion the author\u27s identify how the Industrial and Engineering technology curriculum and program strengthened at Morehead State University. The author\u27s initially review a brief history of the Industrial and Engineering Technology program and how the department survived from closing down to become one of the most successful departments at the university. The author\u27s also describe how the objectives were set and how department worked with the local industrial partners and advisors to set up and help with the curriculum to meet the industrial demands. The objectives were set based on the local educational and industrial demands for the employment, research and educational collaboration with in the university service region, and the Commonwealth. The paper would then conclude that successful industry-education collaboration is characterized by feelings of mutual ownership and commitment among the faculty, students, department advisors, and the local industries. The evidence of the accomplishments between the department and the industry will be discussed using a model of the relationship and analysis of cooperative education and employee evaluation of the students

A framework for the construction of generative models for mesoscale structure in multilayer networks

Multilayer networks allow one to represent diverse and coupled connectivity patterns—such as time-dependence, multiple subsystems, or both—that arise in many applications and which are difficult or awkward to incorporate into standard network representations. In the study of multilayer networks, it is important to investigate mesoscale (i.e., intermediate-scale) structures, such as dense sets of nodes known as communities, to discover network features that are not apparent at the microscale or the macroscale. The ill-defined nature of mesoscale structure and its ubiquity in empirical networks make it crucial to develop generative models that can produce the features that one encounters in empirical networks. Key purposes of such models include generating synthetic networks with empirical properties of interest, benchmarking mesoscale-detection methods and algorithms, and inferring structure in empirical multilayer networks. In this paper, we introduce a framework for the construction of generative models for mesoscale structures in multilayer networks. Our framework provides a standardized set of generative models, together with an associated set of principles from which they are derived, for studies of mesoscale structures in multilayer networks. It unifies and generalizes many existing models for mesoscale structures in fully ordered (e.g., temporal) and unordered (e.g., multiplex) multilayer networks. One can also use it to construct generative models for mesoscale structures in partially ordered multilayer networks (e.g., networks that are both temporal and multiplex). Our framework has the ability to produce many features of empirical multilayer networks, and it explicitly incorporates a user-specified dependency structure between layers. We discuss the parameters and properties of our framework, and we illustrate examples of its use with benchmark models for community-detection methods and algorithms in multilayer networks