A variety of pathologies exist which increase the likelihood of bone fracture. Present methods for determining the fracture risk of a specific patient are based exclusively on the amount of bone present. While the quantity of bone tissue is correlated with strength, it neglects to account for bone’s intricate microarchitecture. To assess the effect of bone quality on strength, a methodology was developed for the structural analysis of cancellous bone biopsies. Thirty biopsies were selected from a pre-existing biopsy bank, and scanned using a SCANCO µCT-40 at a resolution of 30 microns. Cortical bone was removed from the resulting three-dimensional geometry, and the remaining cancellous bone was meshed with solid tetrahedral elements. A linear static uniaxial compression test was performed using ANSYS v14.0 to determine the apparent-level Young’s modulus. The maximum von Mises stress was also investigated, but showed poor convergence with increased mesh density. Consistent with the methodology of Pistoia et al., the failure load was assumed to occur when 2% of the bone volume exceeded 7000 µstrain. The results of the finite element analysis compared favorably with known values for cancellous bone strength.

The behavior of unsaturated soils depends heavily on material properties and soil conditions. In Geotechnical Engineering, compacted soils are frequently used as fill material, and quality control is vital to the construction process. There are few methods available to estimate the parameters associated with unsaturated soils based on field measurements, and a relationship between these factors could reduce testing time and lower construction costs. Undrained triaxial tests were performed on four clays representing a range of material properties in an effort to reach the maximum dry density, which provides the highest bearing capacity. Each clay was compacted at optimum moisture content, as well as wet and dry of optimum. Measurements were taken using the GeoGauge and shear wave velocities. An empirical approach was used to estimate the effect of a density gradient on soil suction. A relationship between the normal stress and matric suction produced a strong trend when plotted against a function of stiffness and the void ratio, which represents a density gradient. Another relationship between the GeoGauge and shear wave stiffness measurements was found, but no relationship with the material properties of the samples was observed, indicating that more in-depth research is needed to find a stronger relationship.

Heart failure is an important medical disease and impacts millions of people throughout the world. In order to treat this problem, biomaterial injectable treatment injected into the myocardium of the failing LV are currently being developed. Through this treatment, the biomaterial material injections can reduce wall stresses during the cardiac remodeling process. By using computational techniques to analyze the effects of a treatment involving the injection of biomaterial material into the LV after MI, the material parameters of the hydrogel injections can be optimized. The results shows that the hydrogel injections could reduce the global average fiber stress and the transmural average stress seen from optimization. These results indicated that the hydrogel injections could influence the stiffness in passive LV tissue, but there is still need for more research on the active part of ventricular contraction. Conclusion: hydrogel injection is a viable way to alter ventricular mechanical properties.

Cell-substrate interactions influence various cellular processes such as morphology, motility, proliferation and differentiation. Actin dynamics within cells have been shown to be influenced by substrate stiffness, as NIH 3T3 fibroblasts grown on stiffer substrates tend to exhibit more prominent actin stress fiber formation. Circular dorsal ruffles (CDRs) are transient actin-rich ring-like structures within cells, induced by various growth factors, such as the platelet-derived growth factor (PDGF). CDRs grow and shrink in size after cells are stimulated with PDGF, eventually disappearing ten of minutes after stimulation. As substrate stiffness affect actin structures and cell motility, and CDRs are actin structures which have been previously linked to cell motility and macropinocytosis, the role of substrate stiffness on the properties of CDRs in NIH 3T3 fibroblasts and how they proceed to affect cell behavior is investigated. Cells were seeded on Poly-dimethylsiloxane (PDMS) substrates of various stiffnesses and stimulated with PDGF to induce CDR formation. It was found that an increase in substrate stiffness increases the lifetime of CDRs, but did not affect their size. A mathematical model of the signaling pathways involved in CDR formation is developed to provide insight into this lifetime and size dependence, and is linked to substrate stiffness via Rac-Rho antagonism. CDR formation did not affect the motility of cells seeded on 10 kPa stiff substrates, but is shown to increase localized lamellipodia formation in the cell via the diffusion of actin from the CDRs to the lamellipodia. To further probe the influence of cell-substrate interactions on cell behavior and actin dynamics, a two dimensional system which introduces a dynamically changing, reversible and localized substrate stiffness environment is constructed. Cells are seeded on top of thin PDMS nano-membranes, and are capable of feeling through the thin layer, experiencing the stiffness of the polyacrylamide substrates below the nano-membrane. The membranes are carefully re-transplanted on top of other polyacrylamide substrates with differing stiffnesses. This reversible dynamic stiffness system is a novel approach which would help in the investigation of the influence of reversible dynamic stiffness environments on cell morphology, motility, proliferation and differentiation in various cells types.

Environmental stress cracking (ESC) is one of the main, and probably the most common, failure mechanisms involved in polymer fractures. This type of failure is critically important as it occurs suddenly, without any visible pre-fracture deformation. Such failure can be catastrophic and costly in cases where structural integrity is required. In polyethylene (PE), ESC occurs through a slow crack growth mechanism. Cracks initiate from stress-concentrated imperfections, propagate through the bulk of PE, and ultimately result in a brittle fracture. In order to predict the environmental stress cracking resistance (ESCR) of PE, it is necessary to fully understand the molecular structure of the resin. In this thesis, attempts were made to find relationships between molecular structure characteristics and material responses, mainly inter-lamellar entanglements and strain hardening behaviour of PE resins, through mechanical and rheological experiments. Inter-lamellar entanglements are believed to be the main factor controlling slow crack growth of PE. Extent of entanglements and entanglement efficiency were investigated by monitoring the strain hardening behaviour of PE resins in the solid state through a uniaxial tensile test, and in the melt state, through extensional rheometry. ESCR is usually assessed by unreliable and time consuming testing methods such as the notch constant load test (NCLT) on notched PE specimens in the presence of an aggressive fluid and elevated temperatures. In this thesis, a practical, yet reliable, tensile test was developed for the evaluation and prediction of ESCR. The developed test offers a more reliable and consistent ESCR picture without the drawbacks of the subjective notching process and presence of aggressive fluids. Through this test, a factor called ???corrected hardening stiffness (cHS)??? was developed, which can easily be used for a relative ranking of ESCR of different PE resins. Studies were next extended to the melt state via shear and extensional rheometry. Through studies in the shear mode, a molecular weight-normalized average characteristic relaxation time (??N) was found to be efficient in predicting the extent of chain entanglements in resins. This provided a potential melt indicator for a relative measure of ESCR, for linear low density polyethylene (LLDPE), with different short chain branching levels. Extensional studies were conducted to evaluate the strain hardening behaviour in the melt state. An inverse correlation was obtained between ESCR and the melt strain hardening coefficient (MSHC), found from Sentmanat Extensional Rheometry (SER). This indicated an inverse relationship between ESCR and chain extensibility in the melt. In addition, a new factor called ???melt hardening stiffness (mHS)??? was developed from the slope of a stress-strain line, obtained from SER. This factor, analogous to cHS, can be used for a practical and reliable ranking of ESCR of PEs. ESCR is usually associated with classical crystalline phase property indicators, such as crystallinity and lamella thickness. In this thesis, the effect of processing and post processing temperature on the extent of inter-lamellar entanglements were investigated, evaluated, and correlated to ESCR. Also, analysis of the lamella surface area (LSA) was pursued since LSA reflects changes in phase interconnectivity more precisely. The focus of this part of the study was on the effect of temperature on LSA to identify the optimum processing and post-processing conditions which yield a higher LSA. It was reasonable to presume that PE with larger lamella lateral surface areas will have more inter-lamellar entanglements, hence higher ESCR. Finally, a well-controlled ultraviolet (UV) photoinitiated reactive extrusion (REX) process was developed for selective formation of long chain branches in the PE structure. This was conducted to impose restrictions against stretching of the polymer chain, which consequently enhanced ESCR.

Background Anthropogenic air pollution is a global health problem estimated to contribute to millions of premature deaths. Exposure to biomass smoke is common due to varying sources, such as wildfires, indoor cooking over open fires, and residential heating from wood stoves. In urban environments transportation and industry rely heavily on the combustion of fossil fuels yet environmental policies increasingly support a shift to renewable fuels such as biodiesel. It has not been investigated how either wood smoke or biodiesel exhaust affect human health in general or the cardiovascular system in particular. We hypothesized that wood smoke exposure would induce acute cardiovascular impairment via similar underlying mechanisms as have been established for petrodiesel exhaust exposure. We also hypothesized that replacing petrodiesel with biodiesel, as a blend or pure biodiesel, would generate an exhaust profile with a less harmful effect on the cardiovascular system than petrodiesel exhaust. Methods In four separate studies healthy non-smoking subjects were exposed to different air pollutants in controlled exposure chambers followed by clinical investigations of the cardiovascular system. All studies were performed as randomized controlled trials in a crossover fashion with each individual acting as her own control. In study I healthy volunteers were exposed to wood smoke at a target concentration of particulate matter (PM) 300 µg/m3 for three hours followed by measures of blood pressure, heart rate variability and central arterial stiffness. In study II subjects were exposed to wood smoke at a target concentration of PM 1000 µg/m3 for one hour followed by measures of thrombus formation using the Badimon technique and vasomotor function using forearm venous occlusion plethysmography. In study III subjects were exposed to petrodiesel exhaust and a 30% rapeseed methyl ester (RME30) biodiesel blend for one hour at a target concentration of PM 300 µg/m3. Following exposure, thrombus formation and vasomotor function were assessed as in study II. In study IV subjects were exposed to petrodiesel exhaust at a target concentration of PM 300 μg/m3for one hour and pure rapeseed methyl ester (RME100) exhaust generated at identical running conditions of the engine. Following exposure, thrombus formation and vasomotor function were assessed as in study II and III. Results In study I fourteen subjects (8 males) were exposed to wood smoke at P M 294±36 μg/m3. Compared to filtered air exposure, measures of central arterial stiffness were increased and heart rate variability was decreased following wood smoke exposure. No effect was seen on blood pressure. In study II sixteen males were exposed to wood smoke at PM 899±100 μg/m3. We found no evidence of increased thrombus formation or impaired vasomotor function following wood smoke exposure. In study III sixteen subjects (14 males) were exposed to petrodiesel exhaust (PM 314±27 µg/m3) and RME30 exhaust (PM 309±30 µg/m3). Thrombus formation and vasomotor function were equal following either exposure. In study IV nineteen males were exposed to petrodiesel exhaust (PM 310±34 µg/m3, 1.7±0.3 x105 particles/cm3) and RME100 exhaust (PM 165±16 µg/m3, 2.2±0.1 x105 particles/cm3). As in study III, thrombus formation and vasomotor function were identical following both exposures. Conclusions We have for the first time demonstrated that wood smoke exposure can increase central arterial stiffness and decrease heart rate variability in healthy subjects. We did not, however find evidence of increased thrombus formation and impaired vasomotor function following wood smoke exposure at a higher concentration for a shorter time period. We have, for the first time, demonstrated that exhaust from RME biodiesel induced acute adverse cardiovascular effects of increased thrombus formation and impaired vasomotor function in man. These effects are on par with those seen following exposure to petrodiesel exhaust, despite marked physicochemical differences of the exhaust characteristics.

There are many situations where workers are required to wear personal protective clothing (PPC), to protect against a primary hazard, such as heat or chemicals. But the PPC can also create ergonomic problems and there are important side effects which typically increase with rising protection requirements. The most extensively studied side effect is that of increased heat strain due to reduced heat and vapour transfer from the skin. Less studied is the extra weight, bulk and stiffness of PPC garments which is likely to increase the energy requirements of the worker, reduce the range of movement and lead to impaired performance. Current heat and cold stress standards assume workers are wearing light, vapour permeable clothing. By failing to consider the metabolic effects of actual PPC garments, the standards will underestimate heat production and therefore current standards cannot be accurately applied to workers wearing PPC. Information on the effect of the clothing on the wearer and the interactions between PPC, wearer and environment is limited. Data was collected to quantify the effect of PPC on metabolic load based on the properties of the PPC for the EU THERMPROTECT project (GERD-CT-2002-00846). The main objective of the project was to provide data to allow heat and cold stress assessment standards to be updated so that they need no longer exclude specialised protective clothing. The aim of this thesis was to investigate the effect of PPC and its properties on energy consumption during work. For this purpose, the effects of a range of PPC garments (Chapter 3), weight (Chapter 4), number of layers and material friction (Chapter 5) and wet layers (Chapter 6) on energy consumption whilst walking, stepping and completing an obstacle course were studied. The impact of PPC on range of movement in the lower limbs was also investigated (Chapter 7). The main findings were; a) Increased metabolic cost of 2.4 - 20.9% when walking, stepping and completing an obstacle course in PPC compared to a control condition. b) An average metabolic rate increase of 2.7% per kg increase in clothing weight, with greater increases with clothing that is heavier on the limbs and in work requiring greater ranges of movement. c) 4.5 to 7.9% increase in metabolic cost of walking and completing an obstacle course wearing 4 layers compared to a single layer control condition of the same weight. d) Changes in range of movement in PPC due to individual behavioural adaptations. e) Garment torso bulk is the strongest correlate of an increased metabolic rate when working in PPC (r=0.828, p<0.001). f) Garment leg bulk (r=0.615), lower sleeve weight (r=0.655) and weight of the garment around the crotch (r=0.638) are also all positively correlated with an increased metabolic rate. Total clothing weight and clothing insulation had r values of 0.5 and 0.35 respectively. This thesis has confirmed the major effect of clothing on metabolic rate, and the importance of including this effect in standards and models.

In today’s aging population, cerebrovascular health plays a pivotal role in maintaining independence. The identification of early markers of change might help to plan more appropriate preventative and/or therapeutic measures. Recent focus has been placed on the relationship between peripheral vascular characteristics and cerebral hemodynamics. Given the compliant nature of the cerebral circulation, examination of passive properties, including critical closing pressure (CrCP) and resistance area product (RAP), might provide sensitive information about early functional changes. The purpose of this thesis was to provide a comprehensive view of peripheral vascular and cerebrovascular regulation in community-living older adults. In doing so, the thesis covered a spectrum, ranging from an examination of lifestyle factors, including habitual physical activity and sleep quality, to the impact of cerebrovascular health on functional status, characterized by gait speed. Key findings included the observation that while participants showed the ability to regulate cerebral blood flow (CBF) appropriately in most circumstances, the underlying mechanisms used to achieve this regulation was dependent on baseline vascular tone. During sit-to-stand transitions, individuals with lower baseline resistance relied primarily on fluctuations in RAP, which have been suggested to more closely reflect myogenic pathways. In contrast, individuals with elevated resistance had lower baseline CBF and relied relatively more on fluctuations in CrCP during the dynamic transition. The greater reliance on CrCP might indicate that these individuals were required to tap further into reserve pools to avoid hypoperfusion during the transition. Notably, those who exhibited a smaller dynamic RAP response during the posture change also had slower gait speed and higher occurrence of falls over the past year. These results provide evidence that passive cerebrovascular dynamics are sensitive markers linking peripheral and cerebrovascular properties with functional consequences for brain health in the elderly.

In today’s aging population, cerebrovascular health plays a pivotal role in maintaining independence. The identification of early markers of change might help to plan more appropriate preventative and/or therapeutic measures. Recent focus has been placed on the relationship between peripheral vascular characteristics and cerebral hemodynamics. Given the compliant nature of the cerebral circulation, examination of passive properties, including critical closing pressure (CrCP) and resistance area product (RAP), might provide sensitive information about early functional changes. The purpose of this thesis was to provide a comprehensive view of peripheral vascular and cerebrovascular regulation in community-living older adults. In doing so, the thesis covered a spectrum, ranging from an examination of lifestyle factors, including habitual physical activity and sleep quality, to the impact of cerebrovascular health on functional status, characterized by gait speed. Key findings included the observation that while participants showed the ability to regulate cerebral blood flow (CBF) appropriately in most circumstances, the underlying mechanisms used to achieve this regulation was dependent on baseline vascular tone. During sit-to-stand transitions, individuals with lower baseline resistance relied primarily on fluctuations in RAP, which have been suggested to more closely reflect myogenic pathways. In contrast, individuals with elevated resistance had lower baseline CBF and relied relatively more on fluctuations in CrCP during the dynamic transition. The greater reliance on CrCP might indicate that these individuals were required to tap further into reserve pools to avoid hypoperfusion during the transition. Notably, those who exhibited a smaller dynamic RAP response during the posture change also had slower gait speed and higher occurrence of falls over the past year. These results provide evidence that passive cerebrovascular dynamics are sensitive markers linking peripheral and cerebrovascular properties with functional consequences for brain health in the elderly.

Fall-related hip fractures are a substantial public health issue. Unfortunately, little is known about whether the effective stiffness of the pelvis, a critical component governing impact force during lateral falls, differs substantially across different segments of the population. The objective of this thesis was to enhance the knowledge base surrounding pelvis impact dynamics by assessing the influence of gender and body mass index (BMI) on the effective stiffness of the pelvis, and on resulting peak loads applied to the hip, during sideways falls. Towards this end I conducted pelvis release trials (in which the pelvis was suspended and suddenly released onto a force plate) with males and females with low (<22) and high (>28) BMIs. One resonance-based (kvibe), and three force-deflection based (k1st, kcombo 300, and kcombo opt) methods of effective pelvic stiffness estimation were examined. The resulting stiffness estimates, and peak forces sustained during the pelvis release experiments, were compared between each BMI and sex group. The optimized force-deflection stiffness estimation method, kcombo opt provided the strongest fit to the experimental data. Strong main effects of BMI (f (1,13) = 10.87, p = 0.003) and sex (f (1,13) = 5.97, p = 0.022) were found for this stiffness estimation method. Additionally, a significant BMI-sex interaction was observed (f (3,6) = 5.31, p = 0.030), with low BMI males having much higher stiffness estimates than any other group. Normalized peak forces were higher in low BMI participants than in high BMI participants (f(1,13)=24.9, p<0.001). Linear regression demonstrated that peak impact force was positively associated with effective pelvic stiffness (β = 0.550, t(25) = 3.110, p=0.005), height (β = 0.326, t(25) = 2.119, p=0.045) and soft tissue thickness (β = 0.785, t(25) = 4.573, p<0.001). This thesis has demonstrated that body habitus and sex have significant effects on the stiffness of the pelvis during lateral falls. These differences are likely related to a combination of soft tissue and pelvic anatomical differences between BMI and sex groups. Pelvic stiffness, along with other easily collected variables, may be helpful in predicting peak forces resulting from lateral falls in the elderly. Differences in pelvic stiffness estimates between BMI and sex groups, and estimation method, necessitate careful consideration. These data will aid in selecting the most appropriate pelvic stiffness parameters when modeling impact dynamics for higher energy falls.