An investigation of the natural history of early cervical human papillomavirus infection and its relationship to the acquisition of epithelial abnormalities of the cervix

Cervical human papillomavirus (HPV) infection is a very common sexually transmitted disease which is now considered to be a necessary, but not sufficient, cause of cervical cancer. It has been suggested that the association between HPV infection and cervical neoplasia can be exploited to improve the efficiency and effectiveness of primary- and secondary-prevention programmes for cervical cancer. However, whether this aspiration can be realized in practice requires a greater understanding of the natural history of early cervical HPV infection and its role in the acquisition of epithelial abnormalities of the cervix. In this thesis, a longitudinal study of young women who had recently embarked on sexual activity has provided sequential observations on the natural history of cervical HPV infection. This thesis addresses four aspects of this natural history: the association between HPV infection and the proximity of first sexual intercourse to menarche; the association between smoking, cervical HPV infection and high-grade cervical disease; the validation of a neutralising antibody assay and its use in defining the kinetics of the humoral immune response to cervical HPV16 and HPV18 infections; and the analysis of measurements of the viral load of HPV16 and HPV18, and their association with epithelial abnormalities of the cervi

Nucleation, Growth And Transformations In Dna Linked Colloidal Assemblies

The use of short, synthetic DNA strands to mediate self-assembly of a collection of colloidal particles into ordered structures is now quite well established experimentally. However, it is increasingly apparent that DNA-linked colloidal assemblies (DLCA) are subject to many of the processing challenges relevant to atomic materials, including kinetic barriers related to nucleation and growth, defect formation, and even diffusionless transformations between different crystal symmetries. Understanding, and ultimately controlling, these phenomena will be required to truly utilize this technology to make new materials. Here, I describe a series of computational studies—based on a complementary suite of tools that includes Brownian dynamics, free energy calculations, vibrational mode theory, and hydrodynamic drag analysis—that address several issues related to the nucleation, growth, and stability of DNA-linked colloidal assemblies. The primary focus is on understanding the nature of the apparently enormous number of diffusionless solid-solid phase transformations that occur in crystallites assembled from DNA-functionalized colloidal particles. We find that the ubiquitous nature of these transformations is largely due to the short-ranged nature of DNA mediated interactions, which produces a panoply of zero-energy barrier pathways (or zero frequency vibrational modes) in a number of crystalline configurations. Furthermore, it is shown that hydrodynamic drag forces play a key role in biasing the transformations towards specific pathways, leading to unexpected order in the final arrangements. Additional studies also highlight how heterogeneity in the surface density of DNA strands grafted onto the particles may be used to improve nucleation and growth behavior, which is generally difficult in systems near the ‘sticky-sphere’ limit in which the interaction range is short relative to the particle size. In the final chapter of the thesis, a general and powerful technique is presented for extracting particle-particle interactions directly from particle trajectory data

Cardiac myoglobin deficit has evolved repeatedly in teleost fishes

Peer reviewedPublisher PD

On the influence of time-dependent behaviour of elastomeric wave energy harvesting membranes using experimental and numerical modelling techniques

The transient response of elastomeric polymers is dependent on polymer composition, temperature and the loading history. In particular, hysteresis, dissipation and creep are significant in the choice of material for elastomer membrane wave energy converters. Natural rubber is a good candidate when looking for material for a wave energy harvester since it has an excellent stretchability, is almost resistant to the environment in which the harvester will be used and has good fatigue properties. The mechanical behaviour of the natural rubber used in this work has been deeply characterised: the material resulted to have a very little hysteretical behaviour (that is a very low energy dissipation during stretching) but also to show a strain-dependency, stress softening, and relaxation at constant stretch. Low dissipation represents the best case scenario for energy harvesting; in reality reinforcement of the material is required which adds to the dissipative behaviour. Afterwards, an extended finite strain viscoelastic constitutive model is proposed that is calibrated analytically to the experimental data to identify the relevant material parameters resulting in non-linear viscosity functions in the evolution equations of the constitutive model. The model was able to capture the minimal dissipation behaviour with good degrees of accuracy. Results are shown for a flexible membrane wave energy converter under creep and cyclic loading. A parametric study is made comparing the experimentally characterised polymer with different amounts of viscous dissipation. The response of the wave energy converter shows that even minimal amounts of dissipation manifests itself into changes in the pressure–volume function and reduction in energy capture through hysteresis. The new material model shows, for the first time, that the control of internal pressure in wave energy membranes must take into account transient material effects

Auditors and regulatory work (1987-2013): from reporting accountants' to skilled persons' reports in the UK

Purpose – The purpose of this paper is to investigate the jurisdictional expansion of audit into the area of UK financial regulation. The paper draws on the analytical framework of new audit spaces (Andon et al., 2014, 2015), which built on the concept of regulatory space (Hancher and Moran, 1989), and characterises this new audit space as regulatory work. Design/methodology/approach – Through an intensive reading of a variety of publicly available documentary sources, the paper investigates the role of auditors and accountants in the reporting accountants’ and skilled persons’ regimes in the UK under the Banking Act 1987 and the Financial Services and Markets Act 2000. Findings – The paper identifies a new audit space characterised as regulatory work, which is made up of three distinct phases (and suggests the recent emergence of a fourth phase), and considers the extent to which these phases of regulatory work share common themes across new audit spaces identified by Andon et al. (2015) as independence, reporting, accreditation and mediating. Originality/value – The paper identifies a further jurisdictional expansion of audit into a new audit space, characterised as regulatory wor

The uncertainties associated with sediment fingerprinting suspended and recently deposited fluvial sediment in the Nene river basin

The use of tracers within a sediment fingerprinting framework has become a commonly used technique for investigating the sources of fine sediment. However, uncertainties associated with tracer behaviour have been cited as major potential limitations to sediment fingerprinting methodologies. This paper aims to determine the differences between fingerprinting results derived using different groups of tracer properties and to determine the role of organic matter content, particle size, and within-source variability in tracer concentrations on the observed differences. A mean difference of 24.1% between the predicted contributions of sediment originating from channel banks was found when using different tracer groups. Mean differences between tracer group predictions were lower, at between 8% and 11%, when fingerprinting contributions from urban street dusts. Organic matter content and / or particle size showed little indication that they caused differences between tracer group predictions. The within-source variability in tracer concentrations and small contrasts between the tracer concentrations of different source groups were identified as probable causes of inherent uncertainty in the fingerprinting predictions. We determined that the ratio of the percentage difference between median tracer concentrations in the source groups and the average within-source tracer concentration coefficient of variation could indicate the likely uncertainty in model predictions prior to tracer use

Extreme load analysis of flexible wave energy converters utilising nonlocal continuum damage mechanics

In recent years, there has been a notable increase in interest towards Flexible Wave Energy Converters (FlexWECs). These flexible energy harvesters solve structural design challenges faced by rigid-body WECs by responding to external loading by changing shapes. Typically, the structures are made from rubber-like materials which pose few challenges from a material modelling point of view. Firstly, the material is in the finite strain regime requiring a hyperelastic modelling approach, but more critically the material response is expected to change during the operational lifetime. There is softening from both time-dependent viscoelasticity and micro-void growth caused by fatigue loading. The goal of this paper is to understand the latter mechanism and how it manifests within a membrane. To account for this damage accumulation, the gradient-enhanced nonlocal damage model is coupled to a hyperelastic Neo-Hookean constitutive law. The framework has been implemented in the commercial finite element software ABAQUS by exploiting its fully coupled thermo-mechanical formulation. A parametric study is performed on two FlexWEC archetypes: a submerged pressure differential and a floating bulge wave attenuator. The performance evaluation of these devices is carried out by analysing the evolution of the pressure–volume relation and pressure-stretch relation, respectively. The results show that the nonlocal aspects of damage in the pressure differential FlexWECs are small due to membrane action, but the saturation of damage does affect the pressure–volume function of each membrane. However, in the case of attenuator, the damage regularisation plays a crucial role in its behaviour due to the steep stress gradient from the crest of the wave. The outcomes from these analyses suggest FlexWEC design is advantageous from a fatigue loading perspective as it always reaches an equilibrium state which minimises the stress-differential, reducing the likelihood of localised crack growth