Multi-scale modelling of diffusion magnetic resonance imaging in heterogeneous media

Diffusion magnetic resonance imaging (diffusion MRI) is an imaging technique which is sensitive to the micrometre scale movement of water molecules within a medium. It is routinely used in clinical practice, as well as increasingly in biomedical research as a quantitative tool. However, mathematical relations describing the image signal in a heterogeneous medium are poorly established. There is therefore a need for a better mathematical foundation for diffusion MRI which accounts for the heterogeneous nature of biological tissue, both in terms of molecular transport and magnetic properties. By using a novel distribution function formulation describing diffusion-weighted spin-echo (DW-SE), which is the most common form of diffusion MRI, it is shown that the local modulation wave-vector, known as the q-vector, and the time scale define the operating regime of a DW-SE pulse sequence. Different locations in the q-t parameter space therefore correspond to respective asymptotic models describing DW-SE. The effects of micro-scale magnetic heterogeneities are then analysed using multiple scales. It is found that in the long-time regime of DW-SE, local induced variations in the q-vector are typically of comparable magnitude to the macro-scale applied q-vector, whereas they are negligible in the short-time regime. Therefore, in the subsequent analysis of the long-time regime, the spatial q-vector variation is considered simultaneously with transport heterogeneities. Using multiple scales homogenisation, a multi-compartmental effective medium model has been derived. The effective diffusion tensors can be calculated by solving a cell problem over a periodic cell of the microstructure, however it is shown that the leading order effect of the spatial q-vector variation integrates exactly to zero. Meanwhile, the short-time regime of DW-SE is analysed using a boundary layer model. It is first considered using an unphysical assumption of instantaneous modulation of spins, with results agreeing with literature. Taking advantage of the reduced problem complexity, the effects of realistic gradient pulses are then numerically computed. The image signal is found to vary approximately linearly with the pulse duration of a rectangular pulse, thus leading to a proposed two-point extrapolation method for correction. Meanwhile, for more general irregular pulse shapes, it is found that as long as they are symmetric, they correspond to an equivalent rectangular pulse with easily computable parameters. Finally, for the intermediate-time regime, numerical solutions to the full problem are sought, using simple model geometries and a microscopy-derived realistic microstructure. The results agree with the two derived models at the respective asymptotes, with a transitional region of about a decade in the q-value. Additionally, the transitional region occurs at smaller q-values for isolated intra-cellular spaces compared to the connected extra-cellular space. This finding can inform future experiment design and modelling, particularly in relation to separating and analysing the intra-cellular signal component

Intergenerational Interactions and the Psychological Health of Internet Users in Later Life

Intergenerational interactions have the potential to benefit older adults psychologically and remains an area warranting further investigation. The growing prevalence of internet use and intergenerational programmes has increased the opportunities for accessing intergenerational interactions in the familial and non-familial settings respectively. This thesis sought to elucidate older adults’ experiences of intergenerational interactions in both realms. Part 1 comprises a systematic review considering the impact of internet-mediated familial intergenerational contact on older adults’ psychological health. Based on the 20 included studies, the five broad areas related to remote familial intergenerational contact are: social connections and isolation, broader psychological well-being, sense of self and meaning, emotions and safety. Owing to limitations of the literature and the review, these findings are preliminary and merit further research. Part 2 comprises an empirical qualitative study exploring older internet users’ experiences of non-familial intergenerational interactions and intergenerational programmes, with a focus on their psychological well-being. Semi-structured interviews were conducted and analysed inductively in a process guided by the reflexive thematic analysis approach. Findings illustrated that participants were able to form social connections, reconnect with their younger selves, fulfil their passion for learning, contribute to others and occupy their time meaningfully through intergenerational programmes. Future research should continue to study factors influencing the usefulness of intergenerational programmes for this increasingly heterogeneous population. Part 3 comprises a critical appraisal of issues related to this research process. Reflections about conducting qualitative research and research more generally will be discussed, with an emphasis on subjectivity and practicality

Targeting STAT3 in Cancer with Nucleotide Therapeutics.

Signal transducer and activator of transcription 3 (STAT3) plays a critical role in promoting the proliferation and survival of tumor cells. As a ubiquitously-expressed transcription factor, STAT3 has commonly been considered an "undruggable" target for therapy; thus, much research has focused on targeting upstream pathways to reduce the expression or phosphorylation/activation of STAT3 in tumor cells. Recently, however, novel approaches have been developed to directly inhibit STAT3 in human cancers, in the hope of reducing the survival and proliferation of tumor cells. Several of these agents are nucleic acid-based, including the antisense molecule AZD9150, CpG-coupled STAT3 siRNA, G-quartet oligodeoxynucleotides (GQ-ODNs), and STAT3 decoys. While the AZD9150 and CpG-STAT3 siRNA interfere with STAT3 expression, STAT3 decoys and GQ-ODNs target constitutively activated STAT3 and modulate its ability to bind to target genes. Both STAT3 decoy and AZD9150 have advanced to clinical testing in humans. Here we will review the current understanding of the structures, mechanisms, and potential clinical utilities of the nucleic acid-based STAT3 inhibitors

Effects of the plate slenderness ratio on built-up back-to-back channels stub columns

The purpose of this paper is to investigate the influence of plate slenderness ratio on the compression capacity and the performance of cold-formed steel built-up back-to-back C-channels sections. For stub columns, the overall slenderness ratio (KL/r) of the column has little effect on the load carrying capacity of the section. However, the plate element slenderness plays a major role in determining the performance of stub columns. The plate element slenderness for web or flanges needs to be less than the yield slenderness limit to be fully effective. Otherwise, only proportion of the web or flanges can be considered as effective. The study of the effects of plate element slenderness was carried out on the cold formed steel built-up columns fabricated by connecting two lipped C-channel columns back-to-back using self-drilling screws. Experimental results are compared with the calculated design results from the NAS specifications. Finite element model was created using commercial software LUSAS v14.4 to simulate the deformation curves and also to predict the load carrying capacities. Finite element results are validated by the test results. This study on the stub column shows that the plate element slenderness plays an important role in determining the compressive capacity and behavior of the stub column

Magnetic-based purification system with simultaneous sample washing and concentration

Simultaneous washing and concentration of magnetic microparticles was demonstrated using a rotational magnetic system under a continuous-flow condition. The rotation of periodically arranged permanent magnets close to a fluidic channel carrying a suspension of magnetic particles allows the trapping and releasing of particles along the fluidic channel in a periodic manner. Each trapping and releasing event resembles one washing cycle in conventional biological assays. Concentration efficiencies of 99.75 ± 0.083% at a flow rate of 200µl/min and 88.10 ± 3.17% at a flow rate of 1,000µl/min and a purification efficiency of 99.10 ± 4.3% at a flow rate of 900µl/min were achieve

Load Carrying Capacity of High Strength Cold-Formed Steel Built-Up Box Sections

This paper presents an experimental study of the cold-formed steel built-up box sections in compression. The built-up box sections are formed by two identical simple C-lipped channels connected at their flanges with self-drilling screws. The specimens were compressed between fixed end conditions for stub columns and also for intermediate columns. The column test strengths were compared with the theoretical design strengths, which were calculated using the Effective Width Method (EWM) and also the Direct Strength Method (DSM). Three analytical models were proposed for the compressive strength prediction of the built-up box section. Results from the study show that Effective Width Method predicts the compressive strength of built-up box sections better than Direct Strength Method. Proposed analytical model 1 results for stub columns and model 2 results for intermediate columns correlates well with the experimental results

Compression Test on Cold-Formed Steel Built-up Back-to-Back Channels Stub Columns

Built-up sections are used to resist load induced in a structure when a single section is not sufficient to carry the design load for example roof trusses. In current North American Specification, the provision has been substantially taken from research in hot-rolled built-up members connected with bolts or welds [1]. The aim of this paper is to investigate on built-up back-to-back channels stub columns experimentally and theoretically using Effective Width Method and Direct Strength Method. Compression test was performed on 5 lipped channel and 5 back-to-back channels stub columns fabricated from cold-formed steel sheets of 1.2mm thicknesses. The test results indicated that local buckling is the dominant failure modes of stub columns. Therefore, Effective Width Method predicts the capacity of stub columns compared to Direct Strength Method. When compared to the average test results, results based on EWM are 5% higher while results based on DSM are 12% higher for stub column

Convulsions and Shigellosis

The records of 97 children with culture-proven Shigellosis were reviewed in order to assess the frequency and risk factors of convulsions associated with this infection. Thirteen (13.4%) had convulsions, three of whom had additional features suggestive of encephalopathy. Clinical and laboratory data were compared between patients with and without convulsions to define the risk factors for the development of seizures. A high peak temperature and high band forms in excess of 10% of the differential white cell count were significant risk factors. Age, sex, family history of febrile seizure or epilepsy, and the Shigella strain were not significant risk factors.published_or_final_versio