Analysis of parameters of haemostasis in pre-eclamptic, normotensive pregnant and non-pregnant women.

Pregnancy is characterized by a state of heightened coagulation, which is exacerbated in pathological conditions such as pre-eclampsia (PET). PET is further associated with abnormal maternal inflammation and increased circulating microparticles (MP); however, a mechanistic link between these pathological features has never been established. It is proposed in this thesis that abnormal maternal inflammation is causally linked to pro-coagulant trophoblast MP shedding via a mechanism mediated by the pro-inflammatory cytokine tumour necrosis factor alpha (TNF), thereby contributing to maternal coagulopathies associated with PET. Using thromboelastography (TEG) and standard laboratory tests, haemostatic function was evaluated in PET and normotensive subjects at delivery and post-partum. Furthermore, the effects of the menstrual cycle and oral contraceptive (OC) use on haemostatic function were assessed in non-pregnant subjects in order to understand their influence on post-partum haemostasis. Plasma TNF and pro-coagulant MP levels were evaluated in the pregnant subjects. Using chorionic villi explants from human term placentas, MPs were quantified after TNF administration. The pro-coagulant potential of placental MPs was evaluated by TEG by spiking whole-blood with medium containing MPs from chorionic villi. TEG identified increased whole-blood coagulability in PET subjects at delivery, demonstrating its increased sensitivity over standard laboratory tests at identifying haemostatic alterations associated with PET. Haemostatic alterations were normalized by six weeks post-partum. TEG also identified cyclic haemostatic variations associated with OC use. Chorionic villi treated with TNF (1 ng/ml) shed significantly more MPs than untreated placentas. MPs from chorionic villi increased the coagulability of whole-blood. Together, results provide evidence supporting the concept that abnormal maternal inflammation is causally linked to the development of maternal coagulopathies in pregnancy complications. Moreover, TEG may be superior to standard laboratory tests in evaluating haemostasis in pregnant and non-pregnant subjects.

Nonlinear soil-structure interaction for buried pressure pipes under differential ground motion

Pipelines extend thousands of kilometers across wide geographic areas as a network to provide essential services for modern life. It is inevitable that pipelines must pass through unfavorable ground conditions, which are susceptible to natural disasters. This thesis investigates the behaviour of buried pressure pipelines experiencing ground distortions induced by normal faulting. A recent large database of physical modelling observations on buried pipes of different stiffness relative to the surrounding soil subjected to normal faults provided a unique opportunity to calibrate numerical tools. Three-dimensional finite element models were developed to enable the complex soil-structure interaction phenomena to be further understood, especially on the subjects of gap formation beneath the pipe and the trench effect associated with the interaction between backfill and native soils. Benchmarked numerical tools were then used to perform parametric analysis regarding project geometry, backfill material, relative pipe-soil stiffness and pipe diameter. Seismic loading produces a soil displacement profile that can be expressed by isoil, the distance between the peak curvature and the point of contraflexure. A simplified design framework based on this length scale (i.e., the Kappa method) was developed, which features estimates of longitudinal bending moments of buried pipes using a characteristic length, ipipe, the distance from peak to zero curvature. Recent studies indicated that empirical soil springs that were calibrated against rigid pipes are not suitable for analyzing flexible pipes, since they lead to excessive conservatism (for design). A large-scale split-box normal fault simulator was therefore assembled to produce experimental data for flexible PVC pipe responses to a normal fault. Digital image correlation (DIC) was employed to analyze the soil displacement field, and both optical fibres and conventional strain gauges were used to measure pipe strains. A refinement to the Kappa method was introduced to enable the calculation of axial strains as a function of pipe elongation induced by flexure and an approximation of the longitudinal ground deformations. A closed-form Winkler solution of flexural response was also derived to account for the distributed normal fault pattern. Finally, these two analytical solutions were evaluated against the pipe responses observed in the large-scale laboratory tests.