Impact of epigallocatechin-3-gallate (EGCG), a broad-spectrum anti-inflammatory, in controlling intestinal factors contributing to inflammatory bowel disease.

This dissertation explores the role of epigallocatechin-3-gallate (EGCG), as a potential treatment for patients with inflammatory bowel disease (IBD). IBD is a common disorder that causes a great deal of suffering. Our understanding of the etiologies, pathogenic mechanisms, and treatment targets continues to evolve. Many new therapeutic targets are making their way through the pharmaceutical pipelines. However, not all patients benefit from these therapies. EGCG has long been studied as an anti-cancer agent. Most of our understanding of this compound comes from the oncologic literature. As the pathways of oncology and inflammation converge, new lessons can be taken from the cross discipline. EGCG’s effects on intracellular signaling bridges cancer to inflammation. Many of the same cytokines, chemokines, and molecular signals influencing cancer cells to grow also stimulate immune cells. Chapter 3 first explores the role of EGCG as both a preventative as well as a therapeutic agent and its effect on the dextran sulfate sodium (DSS) mouse model of colitis. The influence of EGCG on immune cell function is then explored in chapter 4. One novel approach in chapter 4 has to do with a focus on intestinal epithelial cells as agents of an immune response, and how EGCG impacts their function in that role. Chapter 5 explores the impact of EGCG on bolstering barrier function, as this is an important aspect of inflammatory bowel disease that is often neglected when considering new approaches to treating IBD. Finally, chapter 6 ends this dissertation with the first clinical trial in the world’s literature to evaluate EGCG as a therapeutic for IBD

Revamped fly‐over for accurate colon visualisation in virtual colonoscopy

This study revisits a visualisation technique for virtual colonoscopy, known as virtual fly‐over (FO). The method views the entire colon anatomy from above the centreline. It assigns two cameras located on opposite sides of the centreline, each of which is responsible for viewing one half of the colon. This approach has several advantages over related colon visualisation methods with regards to visibility coverage and polyp detection rate. However, the traditional FO implementation created a few drawbacks that hinder complete visualisation. For example, it could overlook polyps located on the line between the two halves, and it has no data‐specific initialisation for cutting planes. The authors enhance the FO method in a number of respects in this study: resolve the cutting issue and improve the virtual camera setup in order to better visualise both the colon surface's hidden structures and polyps that are difficult to locate. Quantitative validation of the revamped FO on 30 actual clinical datasets with complicated shapes and large volumes demonstrated that the average surface visualisation rate is equal to 99.5 ± 0.2%. Also, true and synthetic polyps with various shapes and sizes were used to clinically validate the proposed method. Detection rate is up to 100% on the tested sets

Rethinking the risk matrix

So far risk has been mostly defined as the expected value of a loss, mathematically PL (being P the probability of an adverse event and L the loss incurred as a consequence of the adverse event). The so called risk matrix follows from such definition. This definition of risk is justified in a long term “managerial” perspective, in which it is conceivable to distribute the effects of an adverse event on a large number of subjects or a large number of recurrences. In other words, this definition is mostly justified on frequentist terms. Moreover, according to this definition, in two extreme situations (high-probability/low-consequence and low-probability/high-consequence), the estimated risk is low. This logic is against the principles of sustainability and continuous improvement, which should impose instead both a continuous search for lower probabilities of adverse events (higher and higher reliability) and a continuous search for lower impact of adverse events (in accordance with the fail-safe principle). In this work a different definition of risk is proposed, which stems from the idea of safeguard: (1Risk)=(1P)(1L). According to this definition, the risk levels can be considered low only when both the probability of the adverse event and the loss are small. Such perspective, in which the calculation of safeguard is privileged to the calculation of risk, would possibly avoid exposing the Society to catastrophic consequences, sometimes due to wrong or oversimplified use of probabilistic models. Therefore, it can be seen as the citizen’s perspective to the definition of risk