Antiretroviral therapy and pregnancy outcome in HIV-infected women in the United Kingdom and Ireland

The aim of this thesis is to explore pregnancy and perinatal outcomes in diagnosed HIV-infected women receiving antiretroviral therapy (ART) in the UK (United Kingdom) and Ireland. Population-based surveillance data on HIV-infected pregnant women and their children is collected through the National Study of HIV in Pregnancy and Childhood (NSHPC), which includes information on over 8000 pregnancies delivered between 1990 and 2007. The majority of diagnosed infected women now take highly active antiretroviral therapy (HAART) in pregnancy, which reduces the risk of mother-to-child HIV transmission. However, there have been concerns over the potential for maternal and fetal adverse effects, with conflicting findings from European and American studies regarding the association between HAART and premature delivery. In this thesis, trends over time in the demographic characteristics of HIV-infected pregnant women in the UK and Ireland are described, along with changes in the uptake of interventions for preventing mother-to-child transmission. Transmission rates are explored over a period when HAART was routinely available, and subgroups of women managed in the context of regularly updated national guidelines are compared with respect to their risk of transmission. Multivariable logistic regression models are used to assess the association between type of ART exposure in pregnancy and adverse outcomes including pre-eclampsia, prematurity, stillbirth, neonatal death and congenital abnormality. In addition, using data from the European Collaborative Study and the Pediatric Spectrum of HIV Disease project alongside the UK and Ireland data, the effects of differences in populations and methodologies (study design and analytical approach) on the observed association between HAART and premature delivery are investigated, and a pooled analysis of individual motherchild pairs is carried out. Finally, the risks and benefits of ART in terms of adverse pregnancy outcomes and mother-to-child transmission were jointly modelled using Monte Carlo simulation methods, to produce a risk-benefit ratio

Characterisation of a complex CaZr0.9Ce0.1Ti2O7 glass–ceramic produced by hot isostatic pressing

The behaviour of Ce-containing zirconolites in hot isostatically pressed (HIPed) materials is complex, characterised by redox interactions between the metallic HIP canister that result in reduction of Ce4+ to Ce3+. In this work, a glass–ceramic of composition 70 wt.% CaZr0.9Ce0.1Ti2O7 ceramic in 30 wt.% Na2Al2Si6O16 glass was produced by HIP (approx. 170 cm3 canister) to examine the extent of the material–canister interaction. A complex material with six distinct regions was produced, with the extent of Ce reduction varying depending on the distance from the canister. Notably, the innermost bulk regions (those approximately 7 mm from the canister) contained only Ce4+, demonstrating that a production-scale HIPed glass–ceramic would indeed have a bulk region unaffected by the reducing environment induced by a ferrous HIP canister despite the flow of glass at the HIP temperature. Each of the six regions was characterised by XRD (including Rietveld method refinements), SEM/EDX and linear combination fitting of Ce L3-edge XANES spectra. Regions in the lower part of the canister were found to contain a significantly higher fraction of Ce4+ compared to the upper regions. Though zirconolite-2M was the major crystalline phase observed in all regions, the relative abundances of minor phases (including sphene, baddeleyite, rutile and perovskite) were higher in the outermost regions, which comprised a significantly reduced Ce inventory

Potential and mass-matrix in gauged N=4 supergravity

We discuss the potential and mass-matrix of gauged N=4 matter coupled supergravity for the case of six matter multiplets, extending previous work by considering the dependence on all scalars. We consider all semi-simple gauge groups and analyse the potential and its first and second derivatives in the origin of the scalar manifold. Although we find in a number of cases an extremum with a positive cosmological constant, these are not stable under fluctuations of all scalar fields.Comment: 28 pages, LaTe

Fabrication, defect chemistry and microstructure of Mn-doped UO2

Mn-doped UO2 is under consideration for use as an accident tolerant nuclear fuel. We detail the synthesis of Mn-doped UO2 prepared via a wet co-precipitation method, which was refined to improve the yield of incorporated Mn. To verify the Mn-doped UO2 defect chemistry, X-ray absorption spectroscopy at the Mn K-edge was performed, in addition to X-ray diffraction, Raman spectroscopy and high-energy resolved fluorescence detection X-ray absorption near edge spectroscopy at the U M4-edge. It was established that Mn2+ directly substitutes for U4+ in the UO2 lattice, accompanied by oxygen vacancy (Ov) charge compensation. In contrast to other divalent-element doped UO2 materials, compelling evidence for U5+ in a charge compensating role was not found. This work furthers understanding of the structure and crystal chemistry of Mn-doped UO2, which could show potential advantages as a novel efficient advanced nuclear fuel

Phase evolution in the CaZrTi2O7–Dy2Ti2O7 system : a potential host phase for minor actinide immobilization

Zirconolite is considered to be a suitable wasteform material for the immobilization of Pu and other minor actinide species produced through advanced nuclear separations. Here, we present a comprehensive investigation of Dy3+ incorporation within the self-charge balancing zirconolite Ca1–xZr1–xDy2xTi2O7 solid solution, with the view to simulate trivalent minor actinide immobilization. Compositions in the substitution range 0.10 ≤ x ≤ 1.00 (Δx = 0.10) were fabricated by a conventional mixed oxide synthesis, with a two-step sintering regime at 1400 °C in air for 48 h. Three distinct coexisting phase fields were identified, with single-phase zirconolite-2M identified only for x = 0.10. A structural transformation from zirconolite-2M to zirconolite-4M occurred in the range 0.20 ≤ x ≤ 0.30, while a mixed-phase assemblage of zirconolite-4M and cubic pyrochlore was evident at Dy concentrations 0.40 ≤ x ≤ 0.50. Compositions for which x ≥ 0.60 were consistent with single-phase pyrochlore. The formation of zirconolite-4M and pyrochlore polytype phases, with increasing Dy content, was confirmed by high-resolution transmission electron microscopy, coupled with selected area electron diffraction. Analysis of the Dy L3-edge XANES region confirmed that Dy was present uniformly as Dy3+, remaining analogous to Am3+. Fitting of the EXAFS region was consistent with Dy3+ cations distributed across both Ca2+ and Zr4+ sites in both zirconolite-2M and 4M, in agreement with the targeted self-compensating substitution scheme, whereas Dy3+ was 8-fold coordinated in the pyrochlore structure. The observed phase fields were contextualized within the existing literature, demonstrating that phase transitions in CaZrTi2O7–REE3+Ti2O7 binary solid solutions are fundamentally controlled by the ratio of ionic radius of REE3+ cations

The Strong Energy Condition and the S-Brane Singularity Problem

Recently it has been argued that, because tachyonic matter satisfies the Strong Energy Condition [SEC], there is little hope of avoiding the singularities which plague S-Brane spacetimes. Meanwhile, however, Townsend and Wohlfarth have suggested an ingenious way of circumventing the SEC in such situations, and other suggestions for actually violating it in the S-Brane context have recently been proposed. Of course, the natural context for discussions of [effective or actual] violations of the SEC is the theory of asymptotically deSitter spacetimes, which tend to be less singular than ordinary FRW spacetimes. However, while violating or circumventing the SEC is necessary if singularities are to be avoided, it is not at all clear that it is sufficient. That is, we can ask: would an asymptotically deSitter S-brane spacetime be non-singular? We show that this is difficult to achieve; this result is in the spirit of the recently proved "S-brane singularity theorem". Essentially our results suggest that circumventing or violating the SEC may not suffice to solve the S-Brane singularity problem, though we do propose two ways of avoiding this conclusion.Comment: 13 pages, minor corrections and improvements, references adde

Star Models with Dark Energy

We have constructed star models consisting of four parts: (i) a homogeneous inner core with anisotropic pressure (ii) an infinitesimal thin shell separating the core and the envelope; (iii) an envelope of inhomogeneous density and isotropic pressure; (iv) an infinitesimal thin shell matching the envelope boundary and the exterior Schwarzschild spacetime. We have analyzed all the energy conditions for the core, envelope and the two thin shells. We have found that, in order to have static solutions, at least one of the regions must be constituted by dark energy. The results show that there is no physical reason to have a superior limit for the mass of these objects but for the ratio of mass and radius.Comment: 20 pages, 1 figure, references and some comments added, typos corrected, in press GR

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

Antiretroviral therapy and pregnancy outcome in HIV-infected women in the United Kingdom and Ireland.

The aim of this thesis is to explore pregnancy and perinatal outcomes in diagnosed HIV-infected women receiving antiretroviral therapy (ART) in the UK (United Kingdom) and Ireland. Population-based surveillance data on HIV-infected pregnant women and their children is collected through the National Study of HIV in Pregnancy and Childhood (NSHPC), which includes information on over 8000 pregnancies delivered between 1990 and 2007. The majority of diagnosed infected women now take highly active antiretroviral therapy (HAART) in pregnancy, which reduces the risk of mother-to-child HIV transmission. However, there have been concerns over the potential for maternal and fetal adverse effects, with conflicting findings from European and American studies regarding the association between HAART and premature delivery. In this thesis, trends over time in the demographic characteristics of HIV-infected pregnant women in the UK and Ireland are described, along with changes in the uptake of interventions for preventing mother-to-child transmission. Transmission rates are explored over a period when HAART was routinely available, and subgroups of women managed in the context of regularly updated national guidelines are compared with respect to their risk of transmission. Multivariable logistic regression models are used to assess the association between type of ART exposure in pregnancy and adverse outcomes including pre-eclampsia, prematurity, stillbirth, neonatal death and congenital abnormality. In addition, using data from the European Collaborative Study and the Pediatric Spectrum of HIV Disease project alongside the UK and Ireland data, the effects of differences in populations and methodologies (study design and analytical approach) on the observed association between HAART and premature delivery are investigated, and a pooled analysis of individual motherchild pairs is carried out. Finally, the risks and benefits of ART in terms of adverse pregnancy outcomes and mother-to-child transmission were jointly modelled using Monte Carlo simulation methods, to produce a risk-benefit ratio.

Safety analysis of thorium-based fuels in the General Electric Standard BWR

A denatured (U-233/Th)O/sub 2/ fuel assembly has been designed which is energy equivalent to and hardware interchangeable with a modern boiling water reactor (BWR) reference reload assembly. Relative to the reference UO/sub 2/ fuel, the thorium fuel design shows better performance during normal and transient reactor operation for the BWR/6 product line and will meet or exceed current safety and licensing criteria. Power distributions are flattened and thermal operating margins are increased by reduced steam void reactivity coefficients caused by U-233. However, a (U-233/Th)O/sub 2/-fueled BWR will likely have reduced operating flexibility. A (U-235/Th)O/sub 2/-fueled BWR should perform similar to a UO/sub 2/-fueled BWR under all operating conditions. A (Pu/Th)O/sub 2/-fueled BWR may have reduced thermal margins and similar accident response and be less stable than a UO/sub 2/-fueled BWR. The assessment is based on comparisions of point model and infinite lattice predictions of various nuclear reactivity parameters, including void reactivity coefficients, Doppler reactivity coefficients, and control blade worths