Paediatric Inflammatory Bowel Disease: Epidemiology and Immunopathogenesis

IBD is a chronic inflammatory disorder of the gut where the exact pathogenesis is not fully understood. The thesis makes important contributions to knowledge in this area. It presents previously unavailable information on the incidence of PIBD in NSW from 1968 to 2013. It also presents findings from an investigation of the immunopathogenesis of IBD based on 2 studies of monogenic IBD and lymphocyte immunophenotyping. The incidence of PIBD in NSW in 2013 was estimated to be 5.32 per 100,000 children, which represents a nearly 30-fold increase over the past 5 decades. This finding is consistent with the reported increase in incidence across the world. Novel mutations in the IL-10 receptor gene (c.583T>C and c.1368G>T) that lead to infantile onset IBD were identified. One of the mutations was de novo, prompting the need to consider an IL-10 pathway defect in patients with VEOIBD, even if the parents are non-consanguineous. TRIM22 variant (R442C) was discovered to cause a severe form of VEOIBD associated with granulomatous colitis and fistulising perianal disease. Subsequently, it was shown that TRIM22 regulates NOD2 mediated activation of downstream signalling pathways pertinent to viral and bacterial handling. Through lymphocyte immunophenotyping, it was established that a lack of Treg in numerical terms is unlikely to be the cause of uncontrolled inflammation in IBD. However, failure to induce Treg in inflamed tissue may play a role in the immunopathogenesis of IBD. Age-dependent changes in gut-homing CD4 T-cells were observed and may have clinical implications for the use of vedolizumab in children. Classifications of IBD based on genomics and immunopathogenesis pathways may be more helpful in the future to guide individualised therapy and risk management.

Development of an expert system to minimize energy production cost

In this project, a prototype real-time expert system is developed to monitor the performance of a stream power plants

Noninvasive and point-of-care surface-enhanced Raman scattering (SERS)-based breathalyzer for mass screening of coronavirus disease 2019 (COVID-19) under 5 min

Population-wide surveillance of COVID-19 requires tests to be quick and accurate to minimize community transmissions. The detection of breath volatile organic compounds presents a promising option for COVID-19 surveillance but is currently limited by bulky instrumentation and inflexible analysis protocol. Here, we design a hand-held surface-enhanced Raman scattering-based breathalyzer to identify COVID-19 infected individuals in under 5 min, achieving >95% sensitivity and specificity across 501 participants regardless of their displayed symptoms. Our SERS-based breathalyzer harnesses key variations in vibrational fingerprints arising from interactions between breath metabolites and multiple molecular receptors to establish a robust partial least-squares discriminant analysis model for high throughput classifications. Crucially, spectral regions influencing classification show strong corroboration with reported potential COVID-19 breath biomarkers, both through experiment and in silico. Our strategy strives to spur the development of next-generation, noninvasive human breath diagnostic toolkits tailored for mass screening purposes.Agency for Science, Technology and Research (A*STAR)Nanyang Technological UniversityNational Medical Research Council (NMRC)Submitted/Accepted versionThis research is supported by National Medical Research Council, Singapore under COVID-19 Research Fund (MOH-COVID19RF-0007 and MOH-COVID19RF-0012), A*STAR Singapore, AME Individual Research Grant (A20E5c0082) and Max Planck Institute-Nanyang Technological University Joint Lab. S.X.L and L.B.T.N. acknowledge Nanyang Presidential scholarship support from Nanyang Technological University, Singapore