423 research outputs found

    Displacement based multiple wedge slope stability analysis

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    Thermal imaging assessment of drystone retaining walls:some case studies

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    Drystone retaining walls form an essential part of the infrastructure in hilly and mountainous regions around the world, by providing platforms for roads, buildings and for agricultural terraces. Research carried out in England and in France has led to a good understanding of their behaviour, but it is difficult to determine the details of the construction of individual walls without dismantling them – so it can be hard to tell if apparent defects and deformations are a threat to stability. Replacing every apparently defective or deformed wall would be a waste of resources, yet dismantling a wall would obviously be completely disruptive to its function. Invasive investigation, such as drilling, could easily cause damage to the wall structure and destabilise the wall. There is therefore a pressing need for non-intrusive methods of investigation that can reveal critical aspects of a wall’s construction. Thermal imaging can reveal important information about aspects of a wall’s construction that are critical to its stability. This paper presents case studies and numerical modelling that have contributed to the development of this technique, and demonstrate its potential

    Validation and assessment of variant calling pipelines for next-generation sequencing

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    Background: The processing and analysis of the large scale data generated by next-generation sequencing (NGS) experiments is challenging and is a burgeoning area of new methods development. Several new bioinformatics tools have been developed for calling sequence variants from NGS data. Here, we validate the variant calling of these tools and compare their relative accuracy to determine which data processing pipeline is optimal. Results: We developed a unified pipeline for processing NGS data that encompasses four modules: mapping, filtering, realignment and recalibration, and variant calling. We processed 130 subjects from an ongoing whole exome sequencing study through this pipeline. To evaluate the accuracy of each module, we conducted a series of comparisons between the single nucleotide variant (SNV) calls from the NGS data and either gold-standard Sanger sequencing on a total of 700 variants or array genotyping data on a total of 9,935 single-nucleotide polymorphisms. A head to head comparison showed that Genome Analysis Toolkit (GATK) provided more accurate calls than SAMtools (positive predictive value of 92.55% vs. 80.35%, respectively). Realignment of mapped reads and recalibration of base quality scores before SNV calling proved to be crucial to accurate variant calling. GATK HaplotypeCaller algorithm for variant calling outperformed the UnifiedGenotype algorithm. We also showed a relationship between mapping quality, read depth and allele balance, and SNV call accuracy. However, if best practices are used in data processing, then additional filtering based on these metrics provides little gains and accuracies of >99% are achievable. Conclusions: Our findings will help to determine the best approach for processing NGS data to confidently call variants for downstream analyses. To enable others to implement and replicate our results, all of our codes are freely available at http://metamoodics.org/wes

    Thermal imaging assessment of drystone retaining walls:some case studies

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    Drystone retaining walls form an essential part of the infrastructure in hilly and mountainous regions around the world, by providing platforms for roads, buildings and for agricultural terraces. Research carried out in England and in France has led to a good understanding of their behaviour, but it is difficult to determine the details of the construction of individual walls without dismantling them – so it can be hard to tell if apparent defects and deformations are a threat to stability. Replacing every apparently defective or deformed wall would be a waste of resources, yet dismantling a wall would obviously be completely disruptive to its function. Invasive investigation, such as drilling, could easily cause damage to the wall structure and destabilise the wall. There is therefore a pressing need for non-intrusive methods of investigation that can reveal critical aspects of a wall’s construction. Thermal imaging can reveal important information about aspects of a wall’s construction that are critical to its stability. This paper presents case studies and numerical modelling that have contributed to the development of this technique, and demonstrate its potential. </jats:p

    Drystone retaining walls: ductile engineering structures with tensile strength

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    Belgium Herbarium image of Meise Botanic Garden

    The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial

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    Background: Despite improving evidence-based practice following clinical guidelines to optimise drug therapy, Type 2 diabetes (T2DM) still exerts a devastating toll from vascular complications and premature death. Biochemical remission of T2DM has been demonstrated with weight loss around 15kg following bariatric surgery and in several small studies of non-surgical energy-restriction treatments. The non-surgical Counterweight-Plus programme, running in Primary Care where obesity and T2DM are routinely managed, produces &gt;15 kg weight loss in 33 % of all enrolled patients. The Diabetes UK-funded Counterpoint study suggested that this should be sufficient to reverse T2DM by removing ectopic fat in liver and pancreas, restoring first-phase insulin secretion. The Diabetes Remission Clinical Trial (DiRECT) was designed to determine whether a structured, intensive, weight management programme, delivered in a routine Primary Care setting, is a viable treatment for achieving durable normoglycaemia. Other aims are to understand the mechanistic basis of remission and to identify psychological predictors of response. Methods/Design: Cluster-randomised design with GP practice as the unit of randomisation: 280 participants from around 30 practices in Scotland and England will be allocated either to continue usual guideline-based care or to add the Counterweight-Plus weight management programme, which includes primary care nurse or dietitian delivery of 12-20weeks low calorie diet replacement, food reintroduction, and long-term weight loss maintenance. Main inclusion criteria: men and women aged 20-65years, all ethnicities, T2DM 0-6years duration, BMI 27-45 kg/m2. Tyneside participants will undergo Magnetic Resonance (MR) studies of pancreatic and hepatic fat, and metabolic studies to determine mechanisms underlying T2DM remission. Co-primary endpoints: weight reduction ≥ 15 kg and HbA1c &lt;48 mmol/mol at one year. Further follow-up at 2 years. Discussion: This study will establish whether a structured weight management programme, delivered in Primary Care by practice nurses or dietitians, is a viable treatment to achieve T2DM remission. Results, available from 2018 onwards, will inform future service strategy

    Behaviour of drystone retaining structures

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    Limit-equilibrium assessment of drystone retaining structures.

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    A Hybrid Likelihood Model for Sequence-Based Disease Association Studies

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    In the past few years, case-control studies of common diseases have shifted their focus from single genes to whole exomes. New sequencing technologies now routinely detect hundreds of thousands of sequence variants in a single study, many of which are rare or even novel. The limitation of classical single-marker association analysis for rare variants has been a challenge in such studies. A new generation of statistical methods for case-control association studies has been developed to meet this challenge. A common approach to association analysis of rare variants is the burden-style collapsing methods to combine rare variant data within individuals across or within genes. Here, we propose a new hybrid likelihood model that combines a burden test with a test of the position distribution of variants. In extensive simulations and on empirical data from the Dallas Heart Study, the new model demonstrates consistently good power, in particular when applied to a gene set (e.g., multiple candidate genes with shared biological function or pathway), when rare variants cluster in key functional regions of a gene, and when protective variants are present. When applied to data from an ongoing sequencing study of bipolar disorder (191 cases, 107 controls), the model identifies seven gene sets with nominal p-values<0.05, of which one MAPK signaling pathway (KEGG) reaches trend-level significance after correcting for multiple testing. © 2013 Chen et al
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