Precision Monitoring for Disease Progression in Patients with Multiple Sclerosis: A Deep Learning Approach

Artificial intelligence has tremendous potential in a range of clinical applications. Leveraging recent advances in deep learning, the works in this thesis has generated a range of technologies for patients with Multiple Sclerosis (MS) that facilitate precision monitoring using routine MRI and clinical assessments; and contribute to realising the goal of personalised disease management. MS is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterised by focal demyelinating plaques in the brain and spinal cord; and progressive neurodegeneration. Despite success in cohort studies and clinical trials, the measurement of disease activity using conventional imaging biomarkers in real-world clinical practice is limited to qualitative assessment of lesion activity, which is time consuming and prone to human error. Quantitative measures, such as T2 lesion load, volumetric assessment of lesion activity and brain atrophy, are constrained by challenges associated with handling real-world data variances. In this thesis, DeepBVC was developed for robust brain atrophy assessment through imaging synthesis, while a lesion segmentation model was developed using a novel federated learning framework, Fed-CoT, to leverage large data collaborations. With existing quantitative brain structural analyses, this work has developed an effective deep learning analysis pipeline, which delivers a fully automated suite of MS-specific clinical imaging biomarkers to facilitate the precision monitoring of patients with MS and response to disease modifying therapy. The framework for individualised MRI-guided management in this thesis was complemented by a disease prognosis model, based on a Large Language Model, providing insights into the risks of clinical worsening over the subsequent 3 years. The value and performance of the MS biomarkers in this thesis are underpinned by extensive validation in real-world, multi-centre data from more than 1030 patients

Microstructure and morphological characterization of lead-contaminated clay with nanoscale zero-valent iron (nZVI) treatment

The increasing use of nanoscale zero-valent iron (nZVI) for soil and groundwater remediation has raised concerns about its potential effect on soil properties. Numerous laboratory and field studies have demonstrated its excellent capability to immobilize contaminants and enhance contaminated soil. However, a few studies have shed light on the changes in the microstructure and morphology of the soil due to nZVI treatment. This study explores the variation in particle morphology and microstructure in nZVI-treated soil. A series of microscale experiments, including field emission scanning electron microscopy (FESEM), particle size analysis, mercury injection porosimetry (MIP), optical microscopic analysis, and particle shape tests, were conducted on nZVI-treated samples. The dosages of nZVI used were 0%, 0.2%, 1%, 5%, and 10% of the contaminated soil. Morphological characterization suggested that the addition of nZVI resulted in the occurrence of larger-sized particles, on-particle branched structures, finer pore size distribution, aggregation, and a flocculent network in the soil structure. The aggregated and bonded soil particles via nZVI could be one of the mechanisms for its variation in geotechnical characteristics. The findings of this study may improve our understanding of soil improvement using nZVI treatment

A Practical Response Adaptive Block Randomization Design with Analytic Type I Error Protection

Response adaptive randomization is appealing in confirmatory adaptive clinical trials from statistical, ethical, and pragmatic perspectives, in the sense that subjects are more likely to be randomized to better performing treatment groups based on accumulating data. The Doubly Adaptive Biased Coin Design (DBCD) is a popular solution due to its asymptotic normal property of final allocations, which further justifies its asymptotic type I error rate control. As an alternative, we propose a Response Adaptive Block Randomization (RABR) design with pre-specified randomization ratios for the control and high-performing groups to robustly achieve desired final sample size per group under different underlying responses, which is usually required in industry-sponsored clinical studies. We show that the usual test statistic has a controlled type I error rate. Our simulations further highlight the advantages of the proposed design over the DBCD in terms of consistently achieving final sample allocations and of power performance. We further apply this design to a Phase III study evaluating the efficacy of two dosing regimens of adjunctive everolimus in treating tuberous sclerosis complex but with no previous dose-finding studies in this indication

Simultaneous stabilization of Pb and improvement of soil strength using nZVI

This study demonstrates the feasibility of nanoscale Zero-Valent Iron (nZVI) for simultaneous stabilization of Pb and improvement of soil strength via batch experiments. The soil samples were prepared using slurry and pre-consolidation method at nZVI doses of 0.2%, 1%, 5%, and 10% (by dry weight). The physicochemical and geotechnical properties of Pb-contaminated soil treated by nZVI were analyzed. The results indicate that the contamination of Pb(II) resulted in a notable reduction in the undrained shear strength of soil from 16.85 kPa to 7.25 kPa. As expected, the Pb in exchangeable and carbonate-bound fractions decreased significantly with the increasing doses of nZVI. Meanwhile, the undrained shear strength of Pb-contaminated soil enhanced substantially as the increase of nZVI, from 25.83 kPa (0.2% nZVI treatment) to 69.33 kPa (10% nZVI treatment). An abundance of bubbles, generated from the oxidation of nZVI, was recorded. The mechanisms for simultaneous stabilization of Pb and soil improvement primarily include: 1) the precipitation and transformation of Pb-/Fe-hydrated oxides on the soil particles and their induced bounding effects; 2) the increased drainage capability of soil as the occupation of nZVI aggregates and bubbles in the macropores space and 3) the lower soil density derived from the increase in microbubbles retained in the soil. This study is provided to facilitate the application of nZVI in the redevelopment of contaminated soil

Study on properties of Al film on CFRP after cryogenic-thermal cycling

AbstractAl film on CFRP has been tested by cryogenic-thermal cycling according to the especial condition of space. Properties of aluminum film have been characterized by electron pull apparatus, XRD and SEM. The result shows that the adhesion of Al film increases slowly at early stage of cryogenic-thermal cycling. When the times of cryogenic-thermal cycling exceed 50, the adhesion of Al film becomes stability, and then the adhesion of Al film decrease slowly when cycling times from 100 to 600. After 600 times, the adhesion of Al film becomes stability again. The microcrack appears on the surface of Al film after 50 times, and the amounts of microcrack increase and microcrack is coarsening versus times of cryogenic-thermal cycling. The structure of Al film is changing slowly during cryogenic-thermal cycling

Genetic differentiation in Japanese flounder in the Yellow Sea and East China Sea by amplified fragment length polymorphism (AFLP) and mitochondrial DNA markers

The population structure of Japanese flounder (Paralichthys olivaceus) in the Yellow and East China Seas were analyzed using amplified fragment length polymorphism (AFLP) and cytochrome c oxidase subunit I (COI) gene sequencing. A total of 390 reproducible bands were generated by 10 AFLP primer combinations in two populations collected from the coasts of Qingdao (located at the Yellow Sea) and Zhoushan (located at the East China Sea). The percentage of polymorphic loci (P), Nei’s genetic diversity (H) and Shannon’s information index (I) values were higher in the Qingdao population (P = 72.85%, H = 0.243 and I = 0.364) than those in the Zhoushan population (P = 56.35%, H = 0.189 and I = 0.284). The genetic diversity reduction in the Zhoushan population may be attributed to fishing pressure and habitat loss in this area. Based on the COI sequencing analysis, a total of 25 polymorphic sites were examined, and 15 haplotypes were identified in the two populations. The haplotype diversity (h) and nucleotide diversity (π) values in the Qingdao population were 0.746 ± 0.0728 and 0.00334 ± 0.00103, respectively. The corresponding values in the Zhoushan population were 0.712 ± 0.0470 and 0.00318 ± 0.00049. Both the AFLP and mtDNA data revealed significant genetic differentiation between the two populations. The present study discussed the factors that may result in genetic differentiation between the populations in the Yellow and East China Seas.Keywords: Japanese flounder, amplified fragment length polymorphism (AFLP), cytochrome c oxidase subunit I (COI) gene, genetic diversity, population structur

Capturing a Metastable Silver(I) Compound of Pyrazine-2,3-dicarboxylic Acid

A metastable 3D supramolecular compound [Ag(NH3)(2)]-[Ag-3(pzdca)(2)(NH3)(4)] (H(2)pzdca = pyrazine-2,3-dicarboxylic acid) (1) has been synthesized and characterized crystallographically. This study offers important information to in-depth understanding of the self-assembly process involving Ag-1 under ammoniacal conditions and conforms that [Ag(NH3)(2)](+)-containing compounds are the intermediates during synthesis of some Ag-1 coordination polymers.National Natural Science Foundation of China [20721001]; MSTC [2007CB815301]; National Science Fund of China for Fostering Talents in Basic Science [J0630429