High-order adaptive time stepping for vesicle suspensions with viscosity contrast

We construct a high-order adaptive time stepping scheme for vesicle suspensions with viscosity contrast. The high-order accuracy is achieved using a spectral deferred correction (SDC) method, and adaptivity is achieved by estimating the local truncation error with the numerical error of physically constant values. Numerical examples demonstrate that our method can handle suspensions with vesicles that are tumbling, tank-treading, or both. Moreover, we demonstrate that a user-prescribed tolerance can be automatically achieved for simulations with long time horizons

Lung cancer screening participation: attitudinal, socioeconomic and smoking-related factors

Socioeconomic and smoking-related biases in participation threaten the equity and effectiveness of any future UK lung cancer screening programme. This thesis used a mixed methods approach to investigate psychosocial and cognitive factors that might contribute to these biases, with the aim of identifying possible targets for intervention in screening communication strategies. This informed the design of screening invitation materials aimed at engaging low socioeconomic position (SEP) smokers with a screening offer, which were tested using a randomised controlled pilot trial. The findings of these studies suggest that the introduction of a lung cancer screening programme would be acceptable to older English adults. However, while there was high willingness to be screened (>91%), this was not matched by high uptake of screening in the pilot trial (55%). Chapters 4 to 7 showed that negative beliefs about outcomes and early detection for lung cancer were prevalent among participants recruited from low SEP communities, and associated with current smoking status. Compared with their non-smoking counterparts, smokers more commonly expressed fatalistic beliefs about risk, survival and treatment for lung cancer (including early stage disease), worried about lung cancer and the outcome of screening, and perceived smoking and lung cancer to be stigmatised. Intervention screening invitation materials were designed to improve uptake by minimising these factors but an early interim analysis of the pilot trial testing these materials showed no effect on uptake of lung cancer screening appointments (n=241; final target N=2000). Lower SEP smokers’ more negative expectations of risk, stigma, treatment and outcomes for lung cancer, particularly for older high risk adults, appear to undermine the salience and perceived personal benefit of lung cancer screening. Further work needs to be done to explore whether interventions can effectively modify these perceptions to improve engagement with screening among the very group most likely to benefit

And She Went to College... A Short, Short Story

After Sue Jane strapped the last strap on her shiny new black trunk, she plopped down on it with a sigh--college tomorrow and a new world

The role of small open reading frames in myocardial fibrosis and genetic disease

Regions of RNA, previously annotated as noncoding, are increasingly proving to be actively translated. These can hold functional importance when they are translated, either through their production of bioactive micropeptides, or modifying ribosome dynamics during the translation of downstream coding sequences. In this thesis, I will first explore the potential of long noncoding RNAs to produce micropeptides that are functionally relevant in myocardial fibrosis. By analysis of the transcriptome and translatome of activated cardiac fibroblasts, several lncRNAs, differentially expressed in the fibrotic response, were identified as harbouring translated regions. I will use a combination of approaches including knockdown and overexpression to show that LINC01013 is associated with fibroblast activation by TGFB1, is profibrotic, and encodes a novel profibrotic micropeptide. Secondly, I will characterise upstream open reading frames (uORFs) that were similarly identified as having evidence of translation, within the 5’ ‘untranslated’ region (UTR) of genes known to be involved in fibrosis. Specifically, I will show that uORFs of interleukin-11 and platelet-derived growth factor-D are regulatory of translation of the canonical coding sequence. Lastly, I will leverage genomic analysis to functionally characterise genetic variants identified in the 5’ UTR of patients with genetic disease, but with normal candidate coding sequences. In particular, I will investigate variants in myocyte enhancer factor-2C and neurofibromin-2 which create or modify uORFs in the 5’ UTR. I will demonstrate that these have a negative effect on translation of the main coding sequence, thereby providing a novel mechanistic explanation for haploinsufficiency in these patients. Overall, this thesis underscores the emerging importance of translation of regions previously annotated as noncoding, in both health and disease.Open Acces