Subsidence Mechanisms of Sedimentary Basins Developed over Accretionary Crust

This thesis uses forward modelling to investigate the formation of intercratonic basins upon accretionary crust. It began from the hypothesis that accretionary crust forms with a near normal thickness crust, but a thin lithosphere inherited from the terranes that compose it. After the accretion process has ceased the lithosphere stabilises and begins to cool, causing it to grow thicker and this in turn drives subsidence of the accretionary crust. A 1-D finite difference computer code was developed to model conductive heat flow through a column of cooling lithosphere and asthenosphere. To test the hypothesis, the subsidence produced by the modelling of this process was compared to the observed subsidence from backstripping numerous basins situated on accretionary crust The model produced a good fit to the subsidence in a detailed case study of two of the Palaeozoic basins in North Africa. The study was then extended to test the applicability of to accretionary crust globally. It found that while using measured values of the crust and lithospheric thickness for each region the model produced subsidence curves that matched the observed subsidence in each basin. It makes a more coherent argument for the formation of these basins that is able to explain a wider variety of features than other proposed subsidence mechanisms such as slow stretching or dynamic topography. These results suggest that such subsidence is an inherent property of accretionary crust which could influence the evolution of the continental crust over long time periods. The model was used to investigate the subsidence of the West Siberian Basin and found the subsidence patterns to be consistent with the decay of a plume head which thinned the lithosphere. This subsidence patterns indicate the plume material thinned the lithosphere over an area of 2.5 million km2 resulting in uplift before it cooled and subsided

Research activity and the association with mortality.

INTRODUCTION: The aims of this study were to describe the key features of acute NHS Trusts with different levels of research activity and to investigate associations between research activity and clinical outcomes. METHODS: National Institute for Health Research (NIHR) Comprehensive Clinical Research Network (CCRN) funding and number of patients recruited to NIHR Clinical Research Network (CRN) portfolio studies for each NHS Trusts were used as markers of research activity. Patient-level data for adult non-elective admissions were extracted from the English Hospital Episode Statistics (2005-10). Risk-adjusted mortality associations between Trust structures, research activity and, clinical outcomes were investigated. RESULTS: Low mortality Trusts received greater levels of funding and recruited more patients adjusted for size of Trust (n = 35, 2,349 £/bed [95% CI 1,855-2,843], 5.9 patients/bed [2.7-9.0]) than Trusts with expected (n = 63, 1,110 £/bed, [864-1,357] p<0.0001, 2.6 patients/bed [1.7-3.5] p<0.0169) or, high (n = 42, 930 £/bed [683-1,177] p = 0.0001, 1.8 patients/bed [1.4-2.1] p<0.0005) mortality rates. The most research active Trusts were those with more doctors, nurses, critical care beds, operating theatres and, made greater use of radiology. Multifactorial analysis demonstrated better survival in the top funding and patient recruitment tertiles (lowest vs. highest (odds ratio & 95% CI: funding 1.050 [1.033-1.068] p<0.0001, recruitment 1.069 [1.052-1.086] p<0.0001), middle vs. highest (funding 1.040 [1.024-1.055] p<0.0001, recruitment 1.085 [1.070-1.100] p<0.0001). CONCLUSIONS: Research active Trusts appear to have key differences in composition than less research active Trusts. Research active Trusts had lower risk-adjusted mortality for acute admissions, which persisted after adjustment for staffing and other structural factors

Myosin-I nomenclature

We suggest that the vertebrate myosin-I field adopt a common nomenclature system based on the names adopted by the Human Genome Organization (HUGO). At present, the myosin-I nomenclature is very confusing; not only are several systems in use, but several different genes have been given the same name. Despite their faults, we believe that the names adopted by the HUGO nomenclature group for genome annotation are the best compromise, and we recommend universal adoption

A community-based intervention (Young SMILES) to improve the health-related quality of life of children and young people of parents with serious mental illness: randomised feasibility protocol

Children and young people of parents with mental illness (COPMI) are at risk of poor mental, physical and emotional health, which can persist into adulthood. They also experience poorer social outcomes and wellbeing as well as poorer quality of life than their peers with ‘healthy’ parents. The needs of COPMI are likely to be significant; however, their prevalence is unknown, although estimates suggest over 60% of adults with a serious mental illness have children. Many receive little or no support and remain ‘hidden’, stigmatised or do not regard themselves as ‘in need’. Recent UK policies have identified supporting COPMI as a key priority, but this alone is insufficient and healthrelated quality of life has been neglected as an outcome

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin