Investigations of suction caissons in dense sand

Offshore structures are used in a variety of applications ranging from the traditional oil and gas extraction facilities to emerging renewable energy concepts. These structures must be secured to the seabed in an efficient and cost effective manner. A novel approach is to use shallow inverted buckets as foundations, installed by suction, in place of the more usual piles. These foundations lead to cost savings through reduction in materials and in time required for installation. It is necessary to determine how these foundations perform under typical offshore loading conditions so that design calculations may be developed. This thesis presents experimental data from a comprehensive series of investigations aimed at determining the important mechanisms to consider in the design of these shallow foundations for dense sand. Initially the long term loading behaviour (e.g. wind and current) was investigated by conducting three degree of freedom loading {V:M/2R:H} tests on a foundation embedded in dry sand. The results were interpreted through existing work-hardening plasticity theories. The analysis of the data has suggested a number of improved modelling features. Cyclic and transient tests, representing wave loading, were carried out on a foundation embedded in an oil saturated sand. The novel feature of the cyclic loading was that a 'pseudo-random' load history (based on the 'NewWave' theory) was used to represent realistic loading paths. Of particular interest was the tensile load capacity of the foundation. The results observed suggested that for tensile loading serviceability requirements rather than capacity may govern design. Under combined-load cyclic conditions the results indicated that conventional plasticity theory would not provide a sufficient description of response. A new theory, termed 'continuous hyperplasticity' was used, reproducing the results with impressive accuracy. Surprisingly, under the conditions investigated, loading rate was found to have a negligible effect on response

Investigations of suction caissons in dense sand

Offshore structures are used in a variety of applications ranging from the traditional oil and gas extraction facilities to emerging renewable energy concepts. These structures must be secured to the seabed in an efficient and cost effective manner. A novel approach is to use shallow inverted buckets as foundations, installed by suction, in place of the more usual piles. These foundations lead to cost savings through reduction in materials and in time required for installation. It is necessary to determine how these foundations perform under typical offshore loading conditions so that design calculations may be developed. This thesis presents experimental data from a comprehensive series of investigations aimed at determining the important mechanisms to consider in the design of these shallow foundations for dense sand. Initially the long term loading behaviour (e.g. wind and current) was investigated by conducting three degree of freedom loading {V:M/2R:H} tests on a foundation embedded in dry sand. The results were interpreted through existing work-hardening plasticity theories. The analysis of the data has suggested a number of improved modelling features. Cyclic and transient tests, representing wave loading, were carried out on a foundation embedded in an oil saturated sand. The novel feature of the cyclic loading was that a 'pseudo-random' load history (based on the 'NewWave' theory) was used to represent realistic loading paths. Of particular interest was the tensile load capacity of the foundation. The results observed suggested that for tensile loading serviceability requirements rather than capacity may govern design. Under combined-load cyclic conditions the results indicated that conventional plasticity theory would not provide a sufficient description of response. A new theory, termed 'continuous hyperplasticity' was used, reproducing the results with impressive accuracy. Surprisingly, under the conditions investigated, loading rate was found to have a negligible effect on response

Improving the design of piles driven in chalk through the ALPACA research project

Chalk is present under large areas of NW Europe as a low-density, porous, weak carbonate rock. Large numbers of offshore wind turbines, bridges and port facilities rely on piles driven in chalk. Current European practice assumes ultimate shaft resistances that appear low in comparison with the Chalk’s unconfined compression strength and CPT cone resistance ranges and can impact very significantly on project economics. Little guidance is available on pile driveability, set-up or lateral resistance in chalk, or on how piles driven in chalk can sustain axial or lateral cyclic loading. This paper describes the ALPACA (Axial-Lateral Pile Analysis for Chalk Applying multi-scale field and laboratory testing) project funded by EPSRC and Industry that is developing new design guidance through comprehensive field testing at a well-characterised low-to-medium density test site, supported by analysis of other tests. Field experiments on 36 driven piles, sixteen of which employ high resolution fibre-optic strain gauges, is supported by advanced laboratory and in situ testing, as well as theoretical analysis. The field work commenced in October 2017 and was largely complete in May 2019

PI3K/mTOR signaling in mesothelioma patients treated with induction chemotherapy followed by extrapleural pneumonectomy

INTRODUCTION: The prognostic significance of activity biomarkers within the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway was assessed in two independent cohorts of malignant pleural mesothelioma (MPM) patients uniformly treated with a multimodal approach. We specifically assessed expression signatures in a unique set of pre- and postchemotherapy tumor samples. METHODS: Biomarker expression was assessed in samples of two independent cohorts of 107 (cohort 1) and 46 (cohort 2) MPM cases uniformly treated with platinum-based induction chemotherapy followed by extrapleural pneumonectomy from two different institutions, assembled on tissue microarrays. Expression levels of phosphatase and tensin homologue (PTEN), phospho-mTOR, and p-S6 in addition to marker of proliferation (Ki-67) and apoptosis (cleaved caspase-3) were evaluated by immunohistochemistry and correlated with overall survival (OAS) and progression-free survival (PFS). To assess PTEN genomic status, fluorescence in situ hybridization was performed. RESULTS: Survival analysis showed that high p-S6 and Ki-67 expression in samples of treatment naïve patients of cohort 1 was associated with shorter PFS (p = 0.02 and p = 0.04, respectively). High Ki-67 expression after chemotherapy remained associated with shorter PFS (p = 0.03) and OAS (p = 0.02). Paired comparison of marker expression in samples before and after induction chemotherapy of cohort 1 revealed that decreased cytoplasmic PTEN and increased phospho-mTOR expression was associated with a worse OAS (p = 0.04 and p = 0.03, respectively). CONCLUSIONS: These novel data reveal a prognostic significance of expression changes of PI3K/mTOR pathway components during induction chemotherapy if confirmed in other patient cohorts and support the growing evidence to target the PI3K/mTOR pathway in the treatment of MPM

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used