The amniotic fluid

No Abstract

Efficient "black-box" multigrid solvers for convection-dominated problems

The main objective of this project is to develop a "black-box" multigrid preconditioner for the iterative solution of finite element discretisations of the convection-diffusion equation with dominant convection. This equation can be considered a stand alone scalar problem or as part of a more complex system of partial differential equations, such as the Navier-Stokes equations. The project will focus on the stand alone scalar problem. Multigrid is considered an optimal preconditioner for scalar elliptic problems. This strategy can also be used for convection-diffusion problems, however an appropriate robust smoother needs to be developed to achieve mesh-independent convergence. The focus of the thesis is on the development of such a smoother. In this context a novel smoother is developed referred to as truncated incomplete factorisation (tILU) smoother. In terms of computational complexity and memory requirements, the smoother is considerably less expensive than the standard ILU(0) smoother. At the same time, it exhibits the same robustness as ILU(0) with respect to the problem and discretisation parameters. The new smoother significantly outperforms the standard damped Jacobi smoother and is a competitor to the Gauss-Seidel smoother (and in a number of important cases tILU outperforms the Gauss-Seidel smoother). The new smoother depends on a single parameter (the truncation ratio). The project obtains a default value for this parameter and demonstrated the robust performance of the smoother on a broad range of problems. Therefore, the new smoothing method can be regarded as "black-box". Furthermore, the new smoother does not require any particular ordering of the nodes, which is a prerequisite for many robust smoothers developed for convection-dominated convection-diffusion problems. To test the effectiveness of the preconditioning methodology, we consider a number of model problems (in both 2D and 3D) including uniform and complex (recirculating) convection fields discretised by uniform, stretched and adaptively refined grids. The new multigrid preconditioner within block preconditioning of the Navier-Stokes equations was also tested. The numerical results gained during the investigation confirm that tILU is a scalable, robust smoother for both geometric and algebraic multigrid. Also, comprehensive tests show that the tILU smoother is a competitive method.EThOS - Electronic Theses Online ServiceEPSRCGBUnited Kingdo

Pathogenic copy number variants and SCN1A mutations in patients with intellectual disability and childhood-onset epilepsy

Background Copy number variants (CNVs) have been linked to neurodevelopmental disorders such as intellectual disability (ID), autism, epilepsy and psychiatric disease. There are few studies of CNVs in patients with both ID and epilepsy. Methods We evaluated the range of rare CNVs found in 80 Welsh patients with ID or developmental delay (DD), and childhood-onset epilepsy. We performed molecular cytogenetic testing by single nucleotide polymorphism array or microarray-based comparative genome hybridisation. Results 8.8 % (7/80) of the patients had at least one rare CNVs that was considered to be pathogenic or likely pathogenic. The CNVs involved known disease genes (EHMT1, MBD5 and SCN1A) and imbalances in genomic regions associated with neurodevelopmental disorders (16p11.2, 16p13.11 and 2q13). Prompted by the observation of two deletions disrupting SCN1A we undertook further testing of this gene in selected patients. This led to the identification of four pathogenic SCN1A mutations in our cohort. Conclusions We identified five rare de novo deletions and confirmed the clinical utility of array analysis in patients with ID/DD and childhood-onset epilepsy. This report adds to our clinical understanding of these rare genomic disorders and highlights SCN1A mutations as a cause of ID and epilepsy, which can easily be overlooked in adults

Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn’s disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource

Objective: Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn’s disease (CD), including their impact on need for surgery. Design: Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines. Results: Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015). Conclusion: Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD

Contemporary Management of Locally Advanced and Recurrent Rectal Cancer: Views from the PelvEx Collaborative

Pelvic exenteration is a complex operation performed for locally advanced and recurrent pelvic cancers. The goal of surgery is to achieve clear margins, therefore identifying adjacent or involved organs, bone, muscle, nerves and/or vascular structures that may need resection. While these extensive resections are potentially curative, they can be associated with substantial morbidity. Recently, there has been a move to centralize care to specialized units, as this facilitates better multi-disciplinary care input. Advancements in pelvic oncology and surgical innovation have redefined the boundaries of pelvic exenterative surgery. Combined with improved neoadjuvant therapies, advances in diagnostics, and better reconstructive techniques have provided quicker recovery and better quality of life outcomes, with improved survival This article provides highlights of the current management of advanced pelvic cancers in terms of surgical strategy and potential future developments