Exploring the cardiovascular disease continuum: blood pressure and target organ damage

Introduction The objectives of this thesis are to: (1) examine how ambulatory blood pressure monitoring (ABPM) refines office blood pressure (BP) measurement; (2) determine if absolute ambulatory BP or dipping status is better associated with target organ damage (TOD); (3) explore the association of isolated nocturnal hypertension (INH) with TOD; and (4) investigate the association of night-time BP with ultrasound markers of cardiovascular damage. Methods Data from the Mitchelstown Cohort Study was analysed to deliver objectives 1 and 2. Objective 3 was addressed by a systematic review and analysis of data from the Mitchelstown Study. A sample of participants from the Mitchelstown Study underwent an echocardiogram for speckle tracking analysis and carotid ultrasound to achieve objective 4. Results ABPM reclassifies hypertension status in approximately a quarter of individuals, with white coat and masked hypertension prevalence rates of 11% and 13% respectively. Night-time systolic BP is better associated with TOD than daytime systolic BP and dipping level. In multi-variable models the odds ratio (OR) for LVH was 1.4 (95% CI 1.1 -1.8) and for albumin:creatinine ratio ≥ 1.1 mg/mmol was 1.5 (95% CI 1.2 – 1.8) for each 10 mmHg rise in night-time systolic BP. The evidence for the association of INH with TOD is inconclusive. Night-time systolic BP is significantly associated with global longitudinal strain (GLS) (beta coefficient 0.85 for every 10 mmHg rise, 95% CI 0.3 – 1.4) and carotid plaques (OR 1.9 for every 10 mmHg rise, 95% CI 1.1 – 3.2) in univariable analysis. The findings persist for GLS in sex and age adjusted models but not in multivariable models. Discussion Hypertension cannot be effectively managed without using ABPM. Night-time systolic BP is better associated with TOD than daytime systolic BP and dipping level, and therefore, may be a better therapeutic target in future studies.

Modular average case analysis: Language implementation and extension

Motivated by accurate average-case analysis, MOdular Quantitative Analysis (MOQA) is developed at the Centre for Efficiency Oriented Languages (CEOL). In essence, MOQA allows the programmer to determine the average running time of a broad class of programmes directly from the code in a (semi-)automated way. The MOQA approach has the property of randomness preservation which means that applying any operation to a random structure, results in an output isomorphic to one or more random structures, which is key to systematic timing. Based on original MOQA research, we discuss the design and implementation of a new domain specific scripting language based on randomness preserving operations and random structures. It is designed to facilitate compositional timing by systematically tracking the distributions of inputs and outputs. The notion of a labelled partial order (LPO) is the basic data type in the language. The programmer uses built-in MOQA operations together with restricted control flow statements to design MOQA programs. This MOQA language is formally specified both syntactically and semantically in this thesis. A practical language interpreter implementation is provided and discussed. By analysing new algorithms and data restructuring operations, we demonstrate the wide applicability of the MOQA approach. Also we extend MOQA theory to a number of other domains besides average-case analysis. We show the strong connection between MOQA and parallel computing, reversible computing and data entropy analysis.

Integrated genetic analysis systems

The overall objective of this thesis is to integrate a number of micro/nanotechnologies into integrated cartridge type systems to implement such biochemical protocols. Instrumentation and systems were developed to interface such cartridge systems: (i) implementing microfluidic handling, (ii) executing thermal control during biochemical protocols and (iii) detection of biomolecules associated with inherited or infectious disease. This system implements biochemical protocols for DNA extraction, amplification and detection. A digital microfluidic chip (ElectroWetting on Dielectric) manipulated droplets of sample and reagent implementing sample preparation protocols. The cartridge system also integrated a planar magnetic microcoil device to generate local magnetic field gradients, manipulating magnetic beads. For hybridisation detection a fluorescence microarray, screening for mutations associated with CFTR gene is printed on a waveguide surface and integrated within the cartridge. A second cartridge system was developed to implement amplification and detection screening for DNA associated with disease-causing pathogens e.g. Escherichia coli. This system incorporates (i) elastomeric pinch valves isolating liquids during biochemical protocols and (ii) a silver nanoparticle microarray for fluorescent signal enhancement, using localized surface plasmon resonance. The microfluidic structures facilitated the sample and reagent to be loaded and moved between chambers with external heaters implementing thermal steps for nucleic acid amplification and detection. In a technique allowing probe DNA to be immobilised within a microfluidic system using (3D) hydrogel structures a prepolymer solution containing probe DNA was formulated and introduced into the microfluidic channel. Photo-polymerisation was undertaken forming 3D hydrogel structures attached to the microfluidic channel surface. The prepolymer material, poly-ethyleneglycol (PEG), was used to form hydrogel structures containing probe DNA. This hydrogel formulation process was fast compared to conventional biomolecule immobilization techniques and was also biocompatible with the immobilised biomolecules, as verified by on-chip hybridisation assays. This process allowed control over hydrogel height growth at the micron scale.

A Jaworskian analysis of four senior class primary teachers endeavouring to teach mathematics from a constructivist-compatible perspective

A constructivist philosophy underlies the Irish primary mathematics curriculum. As constructivism is a theory of learning its implications for teaching need to be addressed. This study explores the experiences of four senior class primary teachers as they endeavour to teach mathematics from a constructivist-compatible perspective with primary school children in Ireland over a school-year period. Such a perspective implies that children should take ownership of their learning while working in groups on tasks which challenge them at their zone of proximal development. The key question on which the research is based is: to what extent will an exposure to constructivism and its implications for the classroom impact on teaching practices within the senior primary mathematics classroom in both the short and longer term? Although several perspectives on constructivism have evolved (von Glaserfeld (1995), Cobb and Yackel (1996), Ernest (1991,1998)), it is the synthesis of the emergent perspective which becomes pivotal to the Irish primary mathematics curriculum. Tracking the development of four primary teachers in a professional learning initiative involving constructivist-compatible approaches necessitated the use of Borko’s (2004) Phase 1 research methodology to account for the evolution in teachers’ understanding of constructivism. Teachers’ and pupils’ viewpoints were recorded using both audio and video technology. Teachers were interviewed at the beginning and end of the project and also one year on to ascertain how their views had evolved. Pupils were interviewed at the end of the project only. The data were analysed from a Jaworskian perspective i.e. using the categories of her Teaching Triad of management of learning, mathematical challenge and sensitivity to students. Management of learning concerns how the teacher organises her classroom to maximise learning opportunities for pupils. Mathematical challenge is reminiscent of the Vygotskian (1978) construct of the zone of proximal development. Sensitivity to students involves a consciousness on the part of the teacher as to how pupils are progressing with a mathematical task and whether or not to intervene to scaffold their learning. Through this analysis a synthesis of the teachers’ interpretations of constructivist philosophy with concomitant implications for theory, policy and practice emerges. The study identifies strategies for teachers wishing to adopt a constructivist-compatible approach to their work. Like O’Shea (2009) it also highlights the likely difficulties to be experienced by such teachers as they move from utilising teacher-dominated methods of teaching mathematics to ones in which pupils have more ownership over their learning.

The structural conversion from α-AgVO3 to β-AgVO3: Ag nanoparticle decorated nanowires with application as cathode materials for Li-ion batteries

The majority of electrode materials in batteries and related electrochemical energy storage devices are fashioned into slurries via the addition of a conductive additive and a binder. However, aggregation of smaller diameter nanoparticles in current generation electrode compositions can result in non-homogeneous active materials. Inconsistent slurry formulation may lead to inconsistent electrical conductivity throughout the material, local variations in electrochemical response, and the overall cell performance. Here we demonstrate the hydrothermal preparation of Ag nanoparticle (NP) decorated α-AgVO3 nanowires (NWs) and their conversion to tunnel structured β-AgVO3 NWs by annealing to form a uniform blend of intercalation materials that are well connected electrically. The synthesis of nanostructures with chemically bound conductive nanoparticles is an elegant means to overcome the intrinsic issues associated with electrode slurry production, as wire-to-wire conductive pathways are formed within the overall electrode active mass of NWs. The conversion from α-AgVO3 to β-AgVO3 is explained in detail through a comprehensive structural characterization. Meticulous EELS analysis of β-AgVO3 NWs offers insight into the true β-AgVO3 structure and how the annealing process facilitates a higher surface coverage of Ag NPs directly from ionic Ag content within the α-AgVO3 NWs. Variations in vanadium oxidation state across the surface of the nanowires indicate that the β-AgVO3 NWs have a core–shell oxidation state structure, and that the vanadium oxidation state under the Ag NP confirms a chemically bound NP from reduction of diffused ionic silver from the α-AgVO3 NWs core material. Electrochemical comparison of α-AgVO3 and β-AgVO3 NWs confirms that β-AgVO3 offers improved electrochemical performance. An ex situ structural characterization of β-AgVO3 NWs after the first galvanostatic discharge and charge offers new insight into the Li+ reaction mechanism for β-AgVO3. Ag+ between the van der Waals layers of the vanadium oxide is reduced during discharge and deposited as metallic Ag, the vacant sites are then occupied by Li+.