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The aim of this research is to understand the line of development of airport design and consider whether airport architecture is inherently transient and doomed to obsolescence. Little has been written about the multidisciplinary nature of airport design and why, when, where and how new airport concepts have evolved so this is the contribution of this thesis. Airport design is different from other forms of architecture and engineering by virtue of the sheer scale of the development which is more akin to city planning. Because it is on a city scale it requires the input of many disciplines with different philosophies. This thesis analyses the role of architectural philosophies such as Futurism in capturing the spirit of flight and facilitating growth and change, the engineering approach to safety and operational robustness, the planning focus on connectivity and the environmentalist's concern with sustainability. The primary influences on the evolution of airport design, such as airline growth, aircraft characteristics, safety and security and commercial viability are considered, together with how technological advances in communication, mechanisation, automation and digitisation have helped airports avoid obsolescence. The evolution of design response has been looked at through several lenses: the architect concerned with the layout and form of the terminal, the engineer focusing on the design of the airfield, the planner developing the airport as an interchange, and the environmentalist making airport development sustainable. There are case studies to show which concepts have been flexible enough to accommodate growth and change. It concludes that the evolution of airport design can best be categorised in a series of stages each of some two decades. Pioneering Era 1920 to 1940 Evolutionary Phase 1940 to 1960 Jet Age 1960 to 1980 Transfer Interchange 1980 to 2000 Mega Hub 2000 to 2020 This research considers which airports have been adaptable, survived best and avoided obsolescence. The thesis concludes that airport master plan and terminal concepts have largely evolved in response to increasing traffic volumes, and that those that have proved most durable and avoided obsolescence are those that have planned for growth and change from the outset.

Carbon dioxide enhanced oil recovery (CO2EOR) is a proven and available technology used to produce incremental oil from depleted fields. Although this technology has been used successfully onshore in North America and Europe, projects have maximised oil recovery and not CO2 storage. While the majority of onshore CO2EOR projects to date have used CO2 from natural sources, CO2EOR is now more and more being considered as a storage option for captured anthropogenic CO2. In the North Sea the lack of low cost CO2, in large volumes, has meant that no EOR projects have utilised CO2 as an injection fluid. However CO2EOR has the highest potential of all EOR techniques to maximise recovery from depleted UK oil fields. With the prospect of Carbon Capture and Storage (CCS) capturing large tonnages of CO2 from point source emission sites, the feasibility of CO2EOR deployment in the North Sea is high. This thesis primarily aims to address a number of discrete issues which assess the effectiveness of CO2EOR to both produce oil and store CO2. Given the fundamental shift in approach proposed in North Sea CO2EOR projects, the carbon balance of such projects is examined. Using a life cycle accounting approach on a theoretical North Sea field, we examine whether offshore CO2EOR can store more CO2 than onshore projects traditionally have, and whether CO2 storage can offset additional emissions produced through offshore operations and incremental oil production. Using two design scenarios which optimise oil production and CO2 storage, we find that that net GHG emissions were negative in both ‘oil optimised’ and ‘CO2 storage optimised’. However when emissions from transporting, refining and combusting the produced crude oil are incorporated into the life cycle calculations the ‘oil optimised scenario’ became a net emitter of GHG and highlights the importance of continuing CO2 import and injection after oil production has been maximised at a field. This is something that has not traditionally occurred. After assessing rates of flaring and venting of produced associated gas at UK oil fields it is found that the flaring or venting of reproduced CH4 and CO2 has a large control on emissions. Much like currently operating UK oil fields the rates of flaring and venting has a control on the carbon intensity of oil produced. Here values for the carbon intensity of oil produced through CO2EOR are presented. Carbon intensity values are found to be similar to levels of current UK oil production and significantly lower than other unconventional sources. As well as assessing the climate benefits of CO2EOR, a new assessment of CO2EOR potential in Residual Oil Zones (ROZ) is also made. ROZ resource, which is thought to add significant potential to both the oil reserves and CO2 storage potential in some US basins, is here identified in the North Sea for the first time. Based on the foundation of North Sea hydrodynamics study, this thesis identifies the Pierce field as a candidate ROZ field where hydrodynamic tilting of the oil water contact has naturally occurred leaving a zone of residual oil. To test the feasibility of CO2EOR in such a zone a methodology is presented and applied. Notably the study highlights that in this case study recoverable reserves from the ROZ may approach 20% of total field recoverable reserves and have the capability to store up to 11Mt of CO2. While highlighting the CO2EOR potential in the ROZ the thesis discusses the importance in expanding the analysis to quantify its importance on a basin scale. Discussion is also made on whether new resource identification is necessary in a mature basin like the North Sea. With CO2EOR being considered as a feasible option for storing captured anthropogenic CO2, it is important to assess the security of storage in CO2EOR. Using real geochemical and production data from a pilot CO2EOR development in Western Canada two approaches are used to assess the partitioning of CO2 between reservoir fluids through time. Using a number of correlations it is found that CO2 dissolution in oil is up to 7 times greater than in reservoir brine when saturations between the two fluids are equal. It is found that after two years of CO2 injection solubility trapping accounts for 26% of injected CO2. The finding that significantly more dissolution occurs in oil rather than brine indicates that CO2 storage in EOR is safer than in brine storage. However a number of factors such as the increase in oil/CO2 mobility due to CO2 injection is also discussed. The overall conclusion from the work is that CO2EOR in the North Sea has the potential to be an effective way of producing oil and storing CO2 in the North Sea. A number of design, operational and accounting factors are however essential to operate an exemplar CO2EOR project where low carbon intensity oil can be produced from a mature basin while storing large tonnages of captured anthropogenic CO2.

Background: Maternal common mental disorder (CMD), characterised by depression, anxiety and somatic symptoms of distress, is known to be an important health problem in low-and-middle-income countries, but had not been investigated in Malawi, Africa. In preliminary work, we adapted a CMD screening measure and showed that post-partum CMD was common and associated with child stunting. In the research presented here, we expanded the investigation of CMD in Malawi to include pregnant women and mothers of children with severe acute malnutrition (SAM). Using validated measures, we aimed to estimate the prevalence of antenatal CMD/depression and investigate its relationship to social support and intimate partner violence. Secondly, we sought to explore women’s lived experiences of the perinatal period. Finally, we investigated CMD amongst mothers of children admitted with SAM and other life-threatening illness and, in the former, we tested the hypothesis that maternal CMD would be associated with impaired child recovery. Method: In an antenatal clinic-based study, we validated and compared Chichewa and Chiyao versions of the Self Reporting Questionnaire (SRQ) and Edinburgh Postnatal Depression Scale (EPDS) using major depressive episode (MDE) as the criterion diagnosis. We adapted and validated the Multi-dimensional Scale of Perceived Social Support (MSPSS). We measured the prevalence of antenatal MDE and identified associated factors. We conducted focus group discussions with women and enquired about perinatal stressors and supports. We administered the SRQ to mothers of children with SAM during admission to a nutritional rehabilitation unit (NRU) and at 1-month post-discharge, and investigated whether CMD was a risk factor for lower child weight gain at follow-up. In a subsequent study, we compared levels of CMD symptoms between mothers of children admitted to a NRU, a high dependency unit and an oncology ward. Results: We found that the adapted EPDS and SRQ were both valid screening instruments for antenatal CMD/depression. The weighted prevalence of antenatal MDE was 10.7% (95% CI 6.9% - 14.5%). The adapted MSPSS showed adequate test characteristics and differentiated between sources of social support. MDE was associated with lack of support by a significant other; intimate partner violence moderated this association. We found that women in rural Malawi recognised depressive and anxious states in the perinatal period and identified lack of partner support as a key stressor. During admission with a severely malnourished child to a NRU, mothers had very high SRQ scores that greatly reduced post-discharge. There was no association between SRQ score and child weight gain at follow-up. We found no higher level of CMD symptoms amongst mothers of children admitted for treatment of SAM compared with those admitted to other wards. Conclusions: We demonstrated that measures of antenatal CMD and perceived social support can be adapted for use in Malawi. We found that maternal CMD is common and associated with lack of social support, intimate partner violence and child illness. We did not find evidence for a specific association between maternal CMD and child SAM but further prospective studies are required. Our findings suggest that treatment of CMD in mothers in Malawi will require attention to social support and partner behaviour.

As the number of cores in manycore systems grows exponentially, the number of failures is also predicted to grow exponentially. Hence massively parallel computations must be able to tolerate faults. Moreover new approaches to language design and system architecture are needed to address the resilience of massively parallel heterogeneous architectures. Symbolic computation has underpinned key advances in Mathematics and Computer Science, for example in number theory, cryptography, and coding theory. Computer algebra software systems facilitate symbolic mathematics. Developing these at scale has its own distinctive set of challenges, as symbolic algorithms tend to employ complex irregular data and control structures. SymGridParII is a middleware for parallel symbolic computing on massively parallel High Performance Computing platforms. A key element of SymGridParII is a domain specific language (DSL) called Haskell Distributed Parallel Haskell (HdpH). It is explicitly designed for scalable distributed-memory parallelism, and employs work stealing to load balance dynamically generated irregular task sizes. To investigate providing scalable fault tolerant symbolic computation we design, implement and evaluate a reliable version of HdpH, HdpH-RS. Its reliable scheduler detects and handles faults, using task replication as a key recovery strategy. The scheduler supports load balancing with a fault tolerant work stealing protocol. The reliable scheduler is invoked with two fault tolerance primitives for implicit and explicit work placement, and 10 fault tolerant parallel skeletons that encapsulate common parallel programming patterns. The user is oblivious to many failures, they are instead handled by the scheduler. An operational semantics describes small-step reductions on states. A simple abstract machine for scheduling transitions and task evaluation is presented. It defines the semantics of supervised futures, and the transition rules for recovering tasks in the presence of failure. The transition rules are demonstrated with a fault-free execution, and three executions that recover from faults. The fault tolerant work stealing has been abstracted in to a Promela model. The SPIN model checker is used to exhaustively search the intersection of states in this automaton to validate a key resiliency property of the protocol. It asserts that an initially empty supervised future on the supervisor node will eventually be full in the presence of all possible combinations of failures. The performance of HdpH-RS is measured using five benchmarks. Supervised scheduling achieves a speedup of 757 with explicit task placement and 340 with lazy work stealing when executing Summatory Liouville up to 1400 cores of a HPC architecture. Moreover, supervision overheads are consistently low scaling up to 1400 cores. Low recovery overheads are observed in the presence of frequent failure when lazy on-demand work stealing is used. A Chaos Monkey mechanism has been developed for stress testing resiliency with random failure combinations. All unit tests pass in the presence of random failure, terminating with the expected results.

The objectives of this study were identification and verification of key processes that could be used by higher education quality administrators to implement continuous improvement programs and benchmarking processes. East Tennessee State University's Continuous Improvement Key Process Relationship Matrix was used as the basis of a 44-item questionnaire sent to a sample of 49 higher education institutions; 26 replies (53 percent) were received. Responses were tabulated for 10 key processes and 34 associated performance measures. Key processes were: (1) teaching/learning; (2) enrollment management; (3) cultural environment; (4) strategic planning; (5) resource acquisition and development; (6) institutional management and governance; (7) research activity; (8) community outreach; (9) learning environment; and (10) communicating the institutional image. Of the key processes, the study found teaching/learning and enrollment management to have the highest agreement rate. Student retention data and exit examinations were identified as appropriate teaching and learning benchmarking measures; while retention data, student enrollment, and student satisfaction were cited as appropriate benchmarking measures for enrollment management. Twenty-one data tables summarize responses. The four appendixes include: the East Tennessee State University matrix; a copy of the letter of transmittal use; the questionnaire; and a directory of respondents. (Contains 40 references.) (CH)

The precise neurochemical effects of antidepressants that underlie their efficacy remain unclear. Many antidepressants modulate noradrenaline transmission in vivo. However, the selective serotonin reuptake inhibitors (SSRIs) and NK1 receptor antagonists target 5-HT and substance P transmission, respectively. Whether effects on noradrenaline neurones contribute to the efficacy of these drugs has been largely neglected. This study investigates modulation of central NA transmission by an SSRI (fluoxetine) in rats and by NK1 receptor ablation in mice. NK1 'knockout' mice are used as a model for lifelong inhibition of the NK1 receptor. Changes in noradrenaline transmission were determined using in vivo microdialysis to sample the extracellular noradrenaline concentration (efflux). Noradrenaline-related behavioural effects of these treatments were determined using a modified light/dark exploration test. Systemic fluoxetine increased noradrenaline efflux in two brain regions (frontal cortex and hypothalamus). The effect was inconsistent, echoing the 5-HT response to SSRIs. Fluoxetine reduced noradrenaline efflux after partial lesioning of noradrenergic axon terminals (by DSP-4), suggesting an inhibitory action upstream of these terminals. Locally infused (retrodialysis) fluoxetine augmented noradrenaline efflux in the terminal field. Whereas 50uM fluoxetine elevated efflux in both regions, 5uM infusion increased efflux in the frontal cortex only. This effect was 5-HT-dependent (i.e. 5-HT synthesis inhibition with pCPA blocked the response). However, this increase was not secondary to inhibition of 5-HT reuptake (since the more potent and selective SSRI, citalopram, did not change noradrenaline efflux). Thus, fluoxetine has opposing effects on noradrenaline efflux, probably at cell bodies and terminals. The balance of processes could underlie its variable effects. Fluoxetine reduced locomotor activity of DSP-4-pretreated rats in the novel compartment of the exploration box, suggesting a noradrenaline-related effect on behaviour. A 5-HT-related effect of fluoxetine was also found (reduced locomotor activity in the dark compartment), since this was abolished by pCPA.

The deterioration of cellulose nitrate artefacts in museum and art collections is a complex problem facing conservators and conservation scientists. This study has looked at several aspects of the degradation by analysing artefacts and model samples. Initial work concentrated on a survey of a collection of artefacts, many of which showed active degradation, by visual inspection and FTTR spectroscopy. A more thorough analysis of the artefacts was carried out, using ion chromatography, xray fluorescence spectroscopy and atomic absorption spectroscopy, to identify compositional differences between samples, which may relate to degradation. The results of these studies suggested that residual sulphate in the plastics is a cause of increased degradation. The presence of oxalate in degraded artefacts also indicated that chain scission is occurring during deterioration. Later work using gel permeation chromatography confirmed this. Work has also involved the use of accelerated ageing tests to study the effect of sulphate in the degradation and also the influence of inorganic fillers, iron and humidity. It has been concluded that the degradation of cellulose nitrate artefacts is dependent on the presence of sulphate and humidity. The process is diffusion controlled which indicates that loss of plasticiser is a vital factor. This work also suggests simple procedures that can be used to assess an artefact's stability.

This study was concerned with the symbolic costs and benefits associated with different stages of volunteering, from the perspective of 222 participants engaged in three types of community enterprise activity across Scotland. Costs and benefits were set within a social exchange/incentive framework based on the approach of Clark and Wilson (1961). The study was mainly cross-sectional in design and involved a survey-based approach using a structured questionnaire. A related but separate longitudinal component was based on a standard measure of perceived control. The latter was used to explore the issue of empowerment amongst volunteers in general and in a follow up of 26 volunteers. The results generally showed that homogeneity does not rule across or within groups of volunteers. Community enterprise volunteers represented a distinct socio-economic grouping compared to UK populations and associated participation with a range of both costs and benefits. While volunteers were like UK groups and initially participated for mainly purposive reasons, the reasons for continuing participation and remaining involved, despite the associated costs, were instrumental and largely concerned with maintaining organisational achievement. Additionally, while people associated volunteering with a variety of benefits, those relating to perceived control and empowerment were minimal. There was no significant longitudinal evidence established for the latter construct. In contrast to benefits, while initial costs were largely opportunity related, the main costs of continued and retained participation concerned relationships with members, other volunteers and local people. Although there was significant inter-model variation in the reasons for participation at different stages, socio-demographic and organisational variables had a minimal role as moderator variables. The results were discussed in terms of previous research findings and their implications for future research.

Palaeocene Montrose Group sandstones form a regionally extensive sequence of stacked sandbodies within the Central North Sea. The diagenetic sequence has been characterised as chlorite; micro-dolomite; pyrite; early carbonate concretions; dissolution of feldspars; steady precipitation of kaolinite during burial; quartz overgrowths increasing during deep burial; late calcite concretions; illite. Epigenetic chlorite, and pyrite precipitated within depositional marine porefluids (a180 -0.9%oSMOW). During the late Palaeocene-early Eocene, shortly after deposition of the Montrose Group, a dramatic sea-level fall and eastward delta progradation of the Moray group resulted in the regional meteoric flushing of the Montrose Group sands. This flushing is recorded in the isotopic signatures of early carbonate concretions, which indicate that aquifer waters had light meteoric a 180 values. Many of these concretions precipitated from bacterially-mediated reactions. This included fermentation and shallow anaerobic oxidation of hydrocarbons migrating 3km vertically from the underlying Kimmeridge Clay. Examination of 115 well logs shows that locations of vertical migration were structurally controlled, above faulted graben edges, or above thick shales along graben axes. Strontium ratios indicate that dissolution of detrital calcite supplied the calcium. Kaolinite volumes are usually 2-4%; anomalously high volumes of kaolinite (up to 12%) are found close to deltaic palaeo-shorelines and may represent precipitation during vigorous meteoric flushing of the sandstones. Kaolinite isotopic compositions throughout the Central North Sea indicate that precipitation took place within mixed meteoric-marine pore fluids, whilst surrounding marine shales compacted into a meteoric aquifer, over a temperature range of 30-8S·C. Deuterium values are unusually depleted -53 to -76, and suggest a combination of meteoric water and organic interaction. Quartz cement appears to be generally depth-controlled and forms about 4% at 8,SOOft burial. There is also a possibility of 8% quartz overgrowth adjacent to salt diapirs. Secondary porosity does not vary much with depth, always being 2-4%. This· indicates that any increase in porosity due to dissolution of feldspars has been thwarted by continued compaction and no net increase of porosity has occurred. During precipitation of late calcite concretions, pore-water a 180 was isotopically marine and C supplied by decarboxylation. This indicates that porewaters had become dominated by the introduction of evolved-marine compactional waters from overlying Palaeogene mudrocks. Late carbonate concretions contain up to 10% M nCO 3 and are enriched in radiogenic 87 Sr compared to Palaeocene shell ratios. This trend is similar to that noted in cements from the underlying Chalk. It is possible that strontium-rich fluids may have been transferred vertically into the Palaeocene from the deeper-buried Jurassic sequence. Porosity-depth profiles from conventional core analysis data in 42 wells show porosities of 22-36%, with permeabilities of 40-3,000mD at 5,700-9,200ft. The dominant controls are depositional facies, and compaction. Dewatering structures can reduce vertical permeability by lOx. Authigenic chlorite maintains high porosities, but with permeability reduced by lOx. Vertical gradients of porosity and of permeability with depth exhibit "bow curves", which· decrease at the top and base of each channel sand unit. Shorter core lengths give systematically higher rates of porosity decline, due to insufficient sampling of depositionally thick channels, whereas cores longer than 30m give gradients of 5-13%.km- 1. Porosity varies regionally, but no regional variation of decline-gradient was found.

The application of ultrasound to the oxidative dimerisation of pivalic acid to tetramethyladipic acid (TMAA; 2,2,4,4-tetramethylhexa-1,6- dioic acid) using Fenton's reagent is described. Various parameters of the reaction were investigated (gas, equivalents of reagents, temperature, and sonication) and their effect on the yield of TMAA is discussed. Separation of the reaction mixture into TMAA (dimer) and the trimers and tetramers was achieved. The reaction conditions were optimised using experimental design, and statistical analysis illustrates the significant factors that affect the yield. Optimal reaction conditions for the production of TMAA were found to be 0.17 equivalents of Fenton's reagent, high dilution no ultrasound, under nitrogen. Alternative sources of hydroxyl radicals in organic solvents were also investigated The production of 3-bromothiophene (3BT) from the rearrangement of 2,5 -dibromothiophene and reduction of 2,3,5-tribromothiophene was investigated. Ultrasound, reaction time and temperature all have an effect on the yield and selectivity in the synthesis of 3BT. Ultrasound was found to have a modest effect on the yield of 2-methoxythiophene from 2-bromthiophene using sodium methoxide with several catalyst systems (Cu, CuO, CuO/KI, CuO/KI/Copper acetyl acetonate). 2-Bromothiophene was used as a substrate in attempted Wurtz-type coupling reaction conditions. These reactions produced complex mixtures of bromothiophenes via halogen rearrangements. The silylation of bromothiophenes was successfully achieved using several bromothiophene substrates under quiet and sonicated conditions with various reaction times and equivalents of reagents. A calorimetry study on the acoustic output of the ultrasonic probe provided data at different temperatures, depths, solvents, and power settings. The resultant data was in strong agreement with previously published work.

Short-chain, fatty acids (chain length 6-9) were found to be inhibitory to lettuce seed germination. This inhibition was affected by the imbibition temperature in a particular manner. When the G50 dose of each short-chain fatty acid was calculated, the G50 dose being that dose which reduced germination to 50% of the corresponding control, and plotted against temperature they were found to be linearly relented. As the imbibition temperature increased, the dose required to reduce germination to 50% of the control was reduced, Nonanoic acid was the most effective in reducing lettuce seed germination of the fatty acids tested, while hexanoic acid was the least so. All four lines were found to extrapolate to zero dose around 36.5°C. This temperature corresponds to that which has been reported as being a thermal block to germination (Dunlap and Morgan, 1976).

This dissertation explores and reflects on the professional practice of the author and a group of five experts through case studies. Incorporating interviews, observations, reflective journals, video footage, and a choral project, this research aims to explore how five expert choral conductors work in the rehearsal setting. Rehearsal techniques are as diverse as the individuals who practise them. Yet, even though conductors have their differences, the varied outcomes can still be judged as satisfactory. These techniques are not necessarily skills that have been taught in an undergraduate conducting class. Conducting courses and textbooks focus on beat patterns and other skills that must be mastered by the novice and which, in turn, lend themselves more readily to assessment. However, the running of a rehearsal is a complex mixture of musicianship and teaching skills that are continually developed over a lifetime of practice. The following questions emerge: how, then, do highly successful conductors work in rehearsal? What do they consider to be important parts of their own practice? What skills and attributes are crucial for successful ensemble leadership? For this research, five expert choral conductors were observed on site in multiple rehearsals and in working with a variety of vocal ensembles. They also participated in a wide-ranging, semistructured interview that further explored their approaches to conducting, repertoire selection, planning, personal philosophy, and reflections on their craft. The author used the data generated from the case studies and through a survey of core literature to experiment with their own practice during a 12-week rehearsal period that culminated in a performance of Haydn’s Missa in angustiis. The research project revealed that, while each case study conductor had an individualistic approach to their rehearsal delivery, five main characteristics appeared to be common amongst them all: they recognised the conductor’s role as a teacher; they were interested in working towards a sound ideal; they believed in their responsibility to develop skills; they included performance opportunities in the rehearsal setting; and they emphasised the importance of building community. As a result, these concepts formed the foundation of the author’s work with their own ensemble. These findings have implications for the author’s own practice as well as broader implications for other conductors and the training of student conductors. The results appear to advocate a more holistic approach to conducting and conductor training as well as the importance of developing community within the avocational choir.

Voltage gated ion channels underlie the electrical activity of cells. Here I present three data chapters addressing a central question, where does voltage gated ion channel activity occur in neurons? The voltage-gated sodium channel Nav1.7 plays a key role in action potential propagation of C-fiber nociceptors and is an established molecular target for pain therapy. In chapter 2 of this thesis, I find that non-peptidergic nociceptors expressed detectable Nav1.7 protein. I identify that application of a designed peptide, PTx2-3127, inhibits NaV1.7 currents and reduces the number of action potentials fired in mouse non-peptidergic nociceptors. These results providing a mechanism for analgesic activity of the designed peptide. The two members of the Kv2 family of voltage-gated potassium channels Kv2.1 and Kv2.2 play important roles in brain neurons to mediate action potential firing and to organize specialized membrane contact sites. However, little is known about the cellular expression and subcellular localization of Kv2.1 and Kv2.2 in somatosensory neurons. In chapter 3 of this thesis, I use a panel of Kv2.1 and Kv2.2 specific antibodies and a set of genetically modified mouse lines to define the cellular expression and subcellular localization of Kv2.1 and Kv2.2 protein in dorsal root ganglion (DRG) neurons. I find that Kv2 channels have enriched subcellular localization at the plasma membrane distinct from other ion channel proteins in the DRG. While most DRG neurons co-express Kv2.1 and Kv2.2, distinct neuron subpopulations show preferential expression of one or the other. I show that proprioceptors express Kv2.2 robustly but have little detectable Kv2.1. In contrast to Kv2.1, higher levels of Kv2.2 were observed in DRG neurons relative to spinal cord neurons. Kv2.1 expression decreases in older mice while Kv2.2 does not. I show that while both Kv2.1 and Kv2.2 are localized to the soma and stem axon of DRG neurons, Kv2.2 is distinct in being found at juxtaparanodes and paranodes of myelinated DRG neuron axons. Both Kv2 subtypes adopt clustered subcellular patterns in DRG neurons that are similar but distinct from those in central neurons. I find that the overall patterns of Kv2 channel protein expression and subcellular localization are similar between mouse and human DRG neurons. A primary goal of molecular physiology is to understand how conformational changes of proteins affect the function of cells, tissues, and organisms. In chapter 4 of this thesis, I describe an imaging method for measuring the conformational changes of the voltage sensors of endogenous ion channel proteins within live tissue, without genetic modification. GxTX-594 was synthesized from a variant of the peptidyl tarantula toxin guangxitoxin-1E and conjugated to a fluorophore optimal for two-photon excitation imaging through light-scattering tissue. GxTX-594 targets the voltage sensors of Kv2 proteins, which form potassium channels and plasma membrane-endoplasmic reticulum junctions. GxTX-594 dynamically labels Kv2 proteins on cell surfaces in response to voltage stimulation. I found puncta of GxTX-594 on hippocampal CA1 neurons that responded to voltage stimulation and retain a voltage response roughly similar to heterologously expressed Kv2.1 protein. These findings show that EVAP imaging methods enable the identification of conformational changes of endogenous Kv2 voltage sensors in tissue.Together the chapters of this thesis investigate the intersection of localization and activity of voltage gated ion channel subtypes. The work presented here identifies where functional Nav1.7 and Kv2 channels are and how the channels are uniquely positioned in specific anatomical contexts.

The systems of criminal justice and higher education are two major institutions that have profound effects on American social life. Since their inception, both institutions have served as powerful socioeconomic sorting mechanisms. As both institutions have expanded, they have played increasingly important roles in social mobility, socioeconomic status, and life opportunities. Criminal records are a pervasive, acutely restrictive feature of American social life, perpetuating cycles of crime, inequality, and lost opportunity, especially for low-income people and people of color. Higher education has long been considered a key to unlocking social mobility and developing social cohesion in American society, and a potentially compelling mechanism for facilitating desistance. College attendance and completion are associated with lower rates of unemployment and higher relative earnings. Through college, students can access valued opportunities, develop human capital, and foster civic membership. Yet, most colleges require applicants to disclose detailed criminal history information as part of the application process, and some evidence suggests that applicants are being rejected on the basis of their records. Thus, the benefits of higher education may not accrue for students with criminal records. The increasing scrutiny of criminal records in college admissions is especially consequential for groups most subject to the criminal legal system, particularly young Black males. Considering the historic underrepresentation of Black Americans in higher education and overrepresentation in justice-involved populations, criminal history disclosure requirements could raise additional barriers to racial progress, student learning, and citizenship. Drawing on original data sources, including a national audit of college admissions, I find that criminal record screening in college admissions raises substantial hurdles and barriers on the path to college for students with criminal records, demonstrating how records overwhelms potential life course opportunities, hardens inequality, and redefines social membership.

Empirical studies of the well-documented deleterious psychological effects of rigid conformity to traditional masculine norms suggest that many men experience, express and respond to negative affect through a syndrome that combines internalizing depression with externalizing symptoms such as substance use, impulsivity, anger/irritation and risk-taking. These symptoms are not captured by the largely internalizing criteria (e.g. low mood, anhedonia, fatigue) indexed in current depression criteria. Researchers examining men’s externalizing depression have used the Male Depression Risk Scale (MDRS-22; Rice, Fallon, Aucote, & Möller-Leimkühler, 2013), a brief, psychometrically sound self-report instrument, with largely homogeneous Canadian and Australian samples. The current study extends research on men’s externalizing depression to more diverse US populations by evaluating the measurement invariance of the MDRS-22 across Black/African American men (AA) and White/European American men (EA), and applying latent profile similarity analysis (Morin, Meyer, Creusier, & Biétry, 2016) to identify MDRS-22 subpopulations in each sample. Participants were US adult men (AA n = 324, EA n = 319) recruited using Amazon Mechanical Turk. Results supported scalar invariance for the MDRS-22 and indicated the existence of three latent MDRS-22 profiles. While most men were characterized as asymptomatic, two additional profiles, an elevated mixed internalizing/externalizing pattern and a high externalizing pattern were also noted in both groups. EA men were differentiated only by high drug use scores, with the remainder of their externalizing symptoms following a pattern that more resembled the mixed elevated subgroup. High-profile AA men exhibited a range of heightened externalizing symptoms. Results suggest that AA and EA men experience, express and respond to elevated levels of depression in heterogenous ways.

Background: It is well established that people with severe mental illness (SMI; schizophreniform and bipolar disorders) have a significantly shorter life expectancy, and their risks of type 2 diabetes mellitus (T2DM) are also higher than expected. Relatively little research has evaluated outcomes of T2DM or its management in people with SMI, still less in a UK context. However, novel data resources, particularly linkages across healthcare sectors present opportunities to increase the evidence base. Methods: A series of analyses were carried out based around SMI cases defined through the Clinical Record Interactive Search (CRIS) platform at the South London and Maudsley NHS Foundation Trust (SLAM) representing mental healthcare use in four boroughs of southeast London. For the first study, a natural language processing (NLP) application was developed to improve ascertainment of recorded HbA1c levels, and the frequency of recorded levels was investigated in patients following newly diagnosed SMI, comparing this according to demographic and clinical factors. The second study developed this further by investigating HbA1c recording in a series of cross-sectional samples of patients with SMI, additionally considering those with or without a recorded diabetes diagnosis. The third study used a linkage between CRIS and Lambeth DataNet (LDN) data from all primary care services in one of SLAM's catchment boroughs. Drawing information from all LDN patients with T2DM, those with new SMI diagnoses were compared to matched controls in relation to measures of diabetes care, glycaemic control, and outcomes. Associations with adverse outcomes were investigated further in relation to ethnicity and diagnostic subtype within the SMI cohort. The fourth study used a linkage between CRIS and national Hospital Episode Statistics (HES) data. In patients with pre-existing SMI, those with newly recorded diabetes were ascertained and compared with matched controls in relation to hospitalisations for cardiovascular disorders and mortality. These associations and additional hospitalisations for diabetes-related adverse outcomes were investigated further in relation to ethnicity and diagnostic subtype within those with comorbid SMI and diabetes. Results: Study 1: Of 21,462 patients with SMI, HbA1c level was only recorded in 32.2%. Recording was higher in non-white ethnic groups, younger age groups, men, and those with schizophreniform (compared to bipolar) diagnoses. When recorded, mean HbA1c was higher in older age groups, men, non-white ethnic groups, and those with schizophreniform disorders. Study 2: In the primary sample of 5046 patients with SMI in mid-2015, HbA1c levels were recorded in 22.8%, again associated with younger age, non-white ethnicity, and schizophreniform diagnoses. A relatively high proportion of the sample (8.8%) had recorded diabetes. Study 3: In a cohort of 693 cases with SMI and T2DM compared to 3366 controls, age-adjusted all-cause mortality was increased 4.5-fold; however, of a range of outcomes investigated, only reduced likelihood of a foot examination and reduced likelihood of retinal screening were statistically significant. Study 4: In 6107 cases with SMI and recorded diabetes compared to 12,407 controls, diabetes comorbidity was associated with indicators of more severe SMI and a higher risk of hospitalisations for cardiovascular disease or amputations, but not with higher age-adjusted mortality. Conclusions: Comorbidity of SMI and diabetes was associated with adverse outcomes, although longer follow-up periods may be required to capture some inequalities. Suboptimal monitoring of dysglycaemia in mental health services and suboptimal healthcare receipt in primary care would be obvious targets for future interventions.

Graphene is one of the most promising new materials for signicant advancementin electronics, sensing, and energy storage technologies. However producing largequantities of graphene has been a major obstacle towards making graphene baseddevices practical. A new derivative of graphene known as holey graphene, which isjust graphene with nanometer sized holes distributed on it, is much simpler to producein large quantities and also has many advantages over pristine graphene. In this workwe use MD simulations to create periodic holey graphene sheets with holes of varyinggeometry and size and measure the Young's modulus over a range of temperaturesfrom 100-1000 K. The Young's modulus is determined by applying a uni-axial strainalong the armchair and zigzag directions of the graphene lattice and calculating theresulting average stress. For both the armchair and zigzag directions strain wasapplied in increments of 0.1% out to a maximum strain of 1%. The Young's modulusas a function of density was used to identify the scaling coefficients for different holegeometries.

Background: Dementia poses significant challenges for economies and health services worldwide; people with dementia are more likely to require an acute hospital admission and experience poorer in-hospital outcomes than age-matched controls without dementia. Reducing avoidable hospitalisations in people with dementia is a global healthcare priority, and within the UK specifically, there is an increasing focus on improving interventions and causes of hospitalisation which may be prevented by optimised primary care i.e., hospitalisations related to ambulatory care sensitive conditions (ACSC) in this population. Despite this, there is a lack of literature in the UK context describing the risk of ACSC-related hospitalisations and differences in the management or control of ACSCs in the primary care setting in those with dementia. This topic is of particular importance since it is expected that hospitalisations will put an increasing strain on health and social care infrastructures due to the projected increase in the number of cases of dementia over the next few decades. Further, in the absence of effective disease modifying therapies for the treatment of dementia, it is expected that a greater proportion of cases will comprise of those with more advanced dementia, yet there remains limited literature describing associations between the extent of cognitive impairment and the risk of hospitalisations or differences in the primary care management of ACSCs. This evidence could be used to help pre-empt future care needs and identify opportunities to tailor care in order to reduce the risk of ACSCrelated hospitalisations. This thesis seeks to explore the relationship between the extent of cognitive impairment amongst individuals with a confirmed dementia diagnosis and i.) hospitalisations (allcause and ACSC-related) and ii.) management of type 2 diabetes, as an example of an ACSC, within primary care. Methods: Individuals with a confirmed diagnosis of dementia were identified from the Clinical Record Interactive Search (CRIS), a de-identified electronic patient records data resource within the South London and Maudsley (SLaM) NHS Trust. Data relating to acute hospitalisations and encounters within primary care were obtained from existing linkages between CRIS and Hospital Episode Statistics (HES), and between CRIS and Lambeth DataNet (LDN) respectively. The general methods applied to these data sets are outlined in Chapter 4, and more specifically in the subsequent chapters, as follows. Chapter 5 uses age and sex standardised admissions ratios to determine whether individuals with dementia have a greater risk of hospitalisation relative to individuals residing in the same catchment area. Common causes of hospitalisation in those with dementia, and differences in the risk of hospitalisation by dementia severity are explored. Chapters 6 and 7 evaluate associations between ACSC-related admissions by stage of dementia. Hospital admissions in people with dementia within 6 months of a randomly selected date of cognitive function assessment are analysed; the subset of hospitalisations deemed to be ACSC-related are identified using published approaches. Chapter 6 uses data-driven approaches to explore whether stage of dementia can be inferred from hospitalisation patterns. Stage of dementia is first evaluated as a binary variable (mild and moderate-severe) using a logistic regression, then, in an attempt to improve model fit, as an ordinal variable (mild, moderate, severe) using a generalised ordinal logistic regression. To address a specific gap in the literature, Chapter 7 describes ACSC-related admissions amongst individuals with dementia and investigates differences by stage of dementia using a generalised ordinal logistic regression. Finally, Chapter 8 uses the CRIS-LDN linkage to evaluate the management of type 2 diabetesas an example of an ACSC within the primary care setting in individuals with dementia and a matched group of individuals without dementia. Comparisons are made for HbA1c trajectories (multilevel linear mixed-effects models), markers of diabetes-related management (logistic regression), mortality (Cox regression) and healthcare utilisation (multilevel mixed-effects binomial regression) based on presence of dementia, or on its severity at dementia diagnosis. Results: Hospitalisation amongst individuals with newly diagnosed dementia was common, with around half of patients having at least one admission in the 12-month period from first diagnosis. Compared to the catchment population, individuals with newly diagnosed dementia had a higher risk of hospitalisation. Among the common causes of hospitalisation in those with dementia, most were more common in those with more advanced dementia. Similarly, ACSC-related admissions were common in people with dementia, accounting for around 40% of those hospitalised particularly in those with greater cognitive impairment. However, there was no evidence that stage of dementia could be inferred from hospitalisation patterns. In the analysis of management of T2D in primary care, marked differences in the monitoring, management and control of diabetes were observed in people with dementia. HbA1c trajectories differed by dementia status; HbA1c increased over time for mild dementia and non-dementia, but the increase was greater in the mild dementia group. For those with moderate-severe dementia, HbA1c decreased over time. Despite individuals with dementia having increased healthcare utilisation around the time of dementia diagnosis, they were less likely to have received routine diabetes-related management. Patients with dementia had a higher prevalence of macrovascular complications and diabetes foot morbidity at dementia diagnosis and a higher mortality risk than those without dementia; these relationships were most marked in those with moderate-severe dementia. Conclusions: This thesis evaluated ACSCs from different perspectives, namely through primary care management of diabetes as an example of an ACSC and hospitalisations for ACSCs. By using linked clinical datasets, it was possible to address some of the evidence gaps highlighted in the literature. The findings indicate potential areas of suboptimal care amongst the population with dementia and prompts the need for further research. The observed differences in the management and control of T2D in those with dementia, relative to a matched comparator group, particularly those with more advanced dementia, suggests that care in this population could be tailored. Whether these differences explain the higher rates of hospitalisation and ACSC-related hospitalisation reported here and in the published literature could be the subject of future research. Although the population studied is not representative of the UK population, these results may be generalisable to the broader population, given that standardised care frameworks exist within the UK, and healthcare is universal and free at the point of delivery.

Background: Previous research suggests that depression is associated with lower educational attainment. However, many studies rely on questionnaire measures of depression symptoms rather than indicators of clinical depression diagnosis, and there is mixed evidence on effect modifiers of this association. Additionally, compulsory education in England spans ages 5 to 16 years, over which time attainment can change substantially, but there is little understanding of how depression is associated with such changes in attainment over time. Aims: In this thesis, I aimed to fill these gaps in the literature, by providing a robust estimate of the association between a clinical diagnosis of depression and subsequent attainment, understanding the role of effect modifiers, and exploring the association between depression and longitudinal trajectories of attainment over time. Methods: To investigate these issues, I leveraged routinely collected administrative data from an existing data linkage between the National Pupil Database (NPD) and the South London and Maudsley NHS Foundation Trust (SLaM) Clinical Record Interactive Search (CRIS). CRIS extracts data from SLaM electronic health records and removes personal identifiers, so that the resulting pseudonymised data can be safely accessed by researchers. The NPD contains pupil- and school-level data for all pupils in England's state schools. As a result of this linkage, I had access to educational records data for 276,655 pupils, some of whom had been referred to SLaM Child and Adolescent Mental Health Services (CAMHS). In a series of retrospective cohort studies, I used various statistical techniques including regression modelling, mixed modelling, and structural equation modelling to explore associations between receiving a depression diagnosis from SLaM CAMHS and performance on statutory tests in School Years 2, 6 and 11. Results: My findings supported an association between receiving a depression diagnosis and lower subsequent educational attainment in Year 11, and this relationship was not modified by gender, ethnicity, or socioeconomic status. I also found that among pupils who received a depression diagnosis before age 18 years, attainment showed a pattern of stability between Years 2 and 6 followed by a substantial decline in Year 11, relative to a local reference population. Again, this pattern was consistent across multiple different sociodemographic groups. Finally, I found that in a community sample, pupils' attainment could be broadly summarised as following one of five trajectories: average/high-stable (the predominant trajectory), low-improving, average modest declining, average-steep declining, and low-stable. Again, pupils who received a depression diagnosis before age 18 years were more likely to occupy either the modestly declining or steeply declining trajectory. Furthermore, the risk associated with belonging to the steeply declining trajectory was greater than the risk associated with belonging to the modestly declining trajectory. Conclusion: This thesis addresses key gaps in the literature relating to depression and educational attainment, an important and topical area in light of the significant policy attention that school-based mental health is currently attracting. It also demonstrates how a large and novel administrative data linkage can be effectively used for conducting longitudinal and cross-disciplinary research. These findings highlight the importance of providing effective mental health and educational support to children and adolescents with depression.

This thesis examines the longitudinal changes in cognition for patients with schizophrenia using free text from medical records. To this end, we introduce a unified framework to extract, annotate, classify and analyse cognitive impairments from unstructured text, evaluate symptom trajectories and measure their association with socio-demographic factors and clinical outcomes. The framework was further extended to any type of symptom that can be defined using a list of keywords, and allows easy implementation and deployment within the Clinical Record Interactive Search (CRIS) system, which provides researchers with regulated and secure access to anonymised information from clinical records. A standardized approach to extract and annotate portions of unstructured text relevant to cognitive impairments was developed in conjunction with clinicians and researchers. This annotated dataset was then used to train text classification algorithms, in order to separate affirmed versus irrelevant or negated mentions of cognitive symptoms. An extensive comparative study, looking at existing text classification methods within the biomedical as well as general domains was conducted on both public and internal datasets. The results showed that transformer-based approaches, which are the current state of the art for many natural language processing tasks, outperform other methods in terms of accuracy, ease of implementation and scalability, particularly when trained on a combination of general and medical data. This text classification model was subsequently used to derive cognitive score time series from the free text of medical records. This "digital signature" of cognitive changes was in turn validated against scores obtained from clinically administered tests, confirming the accuracy and reliability of the model. Symptom trajectories were then evaluated using mixed linear models, again comparing the results obtained with the transformer model against standardized instruments. Both approaches demonstrated similar rates of change, indicating a gradual cognitive decline with age, which is attenuated by certain socio-demographic factors such as education, employment or marital status. The transformer-based model highlighted a strong association between education and cognition, showing that certain cognitive impairments, specifically attention and social cognition, were more likely to be reported early for patients with a higher education level. The relationship between cognition and clinical outcomes was also analysed, indicating that cognitive problems are correlated with adverse outcomes. This supports the findings in the literature that these symptoms account for much of the disability associated with schizophrenia. Finally, the text classification framework was tested and generalized to cover other symptoms and patient groups, allowing the development of a standardized set of tools that were then deployed within health research settings. This formed the basis for other research, notably COVID-related projects, which involved extracting mentions of anxiety and violent behaviour from the free text of clinical records, paving the way to further clinical applications. The contribution of this research is both methodological and practical. The use of a novel symptom extraction, classification and analysis framework demonstrates that cognitive impairments can be reliably harvested from the free text of medical records using deep learning models. The framework shows that these impairments are common in patients with schizophrenia and are correlated with adverse clinical outcomes. It provides a scalable and adaptable means of conducting research using large, unstructured datasets, typical of the vast amount of data routinely collected in clinical records. Such automated tools can be utilized to detect early impairments, screen individuals and identify those who would benefit from more comprehensive assessments, and ultimately support real-time clinical decision making.

Abstract: Bitumen and heavy oil comprise a significant percentage of proven oil reserves globally. The environmental impacts of producing these resources with current technologies is a concern for environmentalists, oil producing companies, resource rich jurisdictions and society at large. Dilution of the viscous oil with solvents could permit the production of these reserves with lower greenhouse gas emissions than is achieved using current thermal methods where viscosity is reduced by heating. Solvent injection has yet to be implemented as the production method of choice and this suggests that there is significant residual technological uncertainty. Two orders of magnitude disagreements between predicted production rates, based largely on analogies with thermal production methods, and rates extrapolated from laboratory and pilot plant experimental results contribute to this uncertainty, and underscore fundamental and process knowledge gaps between laboratory experiments and field application. This thesis addresses a number of potential impacts of adding solvents to bitumen production processes, whether pilot plants or operating facilities that have been under represented in the publically available literature to date. The addition of solvents to the production environment changes fluid properties beyond the desired viscosity reduction. Changes in fluid density and interfacial tension impact the force balance in reservoirs and laboratory apparatus. External factors such as ambient vibration can also affect production outcomes. The impacts of properties and external environmental conditions are addressed in this work through the systematic application of dimensionless group comparisons and scaling analysis benchmarked with experiments. The change in density of the hydrocarbon with the addition of solvent relative to connate water density is addressed. Conditions where the hydrocarbon phase density changes from more to less dense than that of water are identified. Implications for the production of bitumen are discussed. The impacts of vibration are addressed. An experimental apparatus is described and the predominance of impacts arising from bubble formation and movement in vibrating unconsolidated porous media systems are illustrated using Ultra Violet (UV) fluorescent imaging. The apparatus, experimental outcomes and scaling analysis are expected to apply to diverse processes from packed catalyst beds in process reactors to geologic carbon dioxide sequestration in addition to bitumen and heavy oil production. Dimensionless group analysis is used to compare and contrast solvent and thermal production environments. Bond number value differences suggest that interfacial tension plays a larger role in solvent assisted production environments than previously recognized. This insight, along with support from Prandtl and Schmidt number values, support a new but as yet unproven discrete flow mechanism “sloughing at the bitumen solvent interface” that controls the kinetics of solvent assisted bitumen production. Outcomes from this work are relevant to industrial and academic researchers alike in the target application. They will influence experimental design, apparatus construction and operation, and hypothesis testing as researchers attempt to reduce environmental impacts of heavy hydrocarbon and bitumen production. Impacts in related fields involving complex fluid motion in porous media are also anticipated. The ongoing relevance and importance of scaling laws and dimensional analysis is underscored.

Aim: To ascertain the association between antidepressant and suicidal ideation, self-harm, suicide attempt or death by suicide (ideation and death by suicide) and self-harm) within a secondary psychiatric healthcare setting. Methods: A mental healthcare database with appended text-mined data was used for analyses (including validation exercises and an exploratory study). A retrospective cohort study was carried out, in patients who received a diagnosis of depression during their first referral to psychiatric care services, in a series of studies aimed at understanding factors influencing antidepressant use, factors associated with new instances of suicidal ideation, self-harm, suicide attempt or death by suicide, identifying common antidepressant treatments and assessing the role of antidepressants in future instances of recorded suicidal ideation, self-harm, suicide attempt or death by suicide. Main analysis: Sensitivity and specificity tests were conducted to evaluate text-mining applications. Logistic regression analyses were conducted to determine factors associated with antidepressant treatment and suicidal ideation, self-harm, suicide attempt or death by suicide. Cox regression analyses were conducted to longitudinally assess associations between antidepressants with future recorded suicidal ideation, self-harm, suicide attempt or death by suicide. Results: For the text-mining applications, I found a precision of 91.7% and 82.8% for identifying suicide ideation and suicide attempt, respectively. The study ascertaining factors associated with antidepressant treatment found indications of comorbidity were associated with newer antidepressant use (e.g. SNRIs or mirtazapine). Different depressive symptom clusters were associated differently with antidepressant treatment use, suggesting clinicianpatient communication. In addition, in patients older than 25 years, past suicide attempts were associated with increased use of fluoxetine relative to sertraline. The prevalence of new suicidal ideation, self-harm and deaths by suicide were observed in 8.76%, 1.67% and 0.24% of the cohort, respectively. All three clusters of depressive symptoms - affective, somatic and cognitive - were associated with increased risk of suicidal ideation, self-harm, suicide attempt or death by suicide, compared to their patients who did not experience these symptoms. In terms of the longitudinal association of specific antidepressant treatment with suicidal ideation, self-harm, suicide attempt or death by suicide, results were found to be in line with current literature but also novel: i) There was no association of most of the specified antidepressants with suicidal ideation, self-harm, suicide attempt or death by suicide in young or older adults; ii) however, results suggest that compared to citalopram, mirtazapine and sertraline may be associated with increased risk of suicidal ideation in young people (HR 5.99; 95% CI 1.30 - 27.70; p-value 0.021 and 4.66; 1.52 - 14.24; 0.007, respectively), who experience cognitive symptoms (i.e. helplessness, worthlessness and hopelessness) during antidepressant treatment, iii) whereas mirtazapine (0.46; 0.22 - 0.95; 0.04) or dual combinations of antidepressant treatment (0.40; 0.18 - 0.90; 0.025) is protectively associated with ideation in adults, who experience cognitive symptoms, iv) contrastingly compared to citalopram, mirtazapine may increase the risk of self-harm in adults (23.7; 1.42 - 394.8; 0.02) who experience cognitive symptoms while and v) collectively, the results suggest a general role for mirtazapine increasing the risk of ideation compared to citalopram in adults, in the presence of certain symptoms. Hence, no direct evidence was found between antidepressants and suicidal ideation, self-harm, suicide attempt or death by suicide however there may be an indirect role via depressive symptoms. Conclusions: The current study is one of the first studies to use a naturalistic clinical psychiatric database in research studying the potential role of antidepressants in treatmentemergent suicidal ideation, self-harm, suicide attempt or death by suicide (suicidal ideation, self-harm and death by suicide) (See Chapter 2 and 7). The study calls for attention on patient symptom profiles over the course of mirtazapine treatment in secondary mental healthcare (Chapter 8). The limitations faced in this study (Chapter 5 and 6) requires all conclusions to be interpreted with caution and primarily calls for further studies to validate the current findings in particular dictated by substantial qualitative work given the inconsistencies in clinical text (Chapter 9).

Demand for wireless connectivity is exponentially increasing. Allocated bands in the Radio Frequency (RF) spectrum are commonly presented as being nearly at capacity but in reality, they are often under-utilised. New shared spectrum regulations, combined with Dynamic Spectrum Access (DSA) technologies and Software Defined Radio (SRD) allow third parties to access vacant spectrum that has been traditionally licensed to broadcasters and mobile network operators. Regulators and research institutions worldwide are actively exploring the sharing of finite spectral resources, driving a wireless revolution that will bring lower cost and ubiquitous connectivity. This thesis presents and validates a disruptive new spectrum sharing technique that facilitates access to the significant amount of vacant spectrum in the band traditionally used for analogue FM Radio broadcasting (88-108 MHz), providing a potential communications solution for load balancing and demand side management in smart grid networks. In this work, a novel, real-time DSA-enabled radio transmitter is designed, implemented, and targeted to programmable 'ZynqSDR' hardware, and investigations are carried out to determine whether it is capable of coexisting with incumbent FM Radio stations. The transmitter uses the Frequency Spread Filter Bank Multicarrier (FS-FBMC) modulation scheme - which has low levels of Out-Of-Band (OOB) leakage - and a non-contiguous subchannel mask, which can automatically reconfigure itself in real time to change the spectral characteristics of the output signal. It was developed using low level Digital Signal Processing (DSP) components from within MATLAB and Simulink. The FBMC Secondary User (SU) radio was shown to cause minimal interference to FM Radio stations when 'transmitting' at low broadcast powers (e.g. 20 dBm) and using a 200 kHz guardband, indicating that an SU such as the one proposed in this thesis would be capable of legally coexisting with (and transmit alongside) incumbent FM Radio signals; provided radio spectrum regulations were modified to permit legal operation.

The purpose of this study was to investigate the relationship between TeacherInsight™ (TI) scores and student performance as measured by student academic change scores on the Texas Assessment of Knowledge and Skills (TAKS) test. School district administrators, particularly district personnel administrators, are continually faced with the task of screening and hiring potential teacher applicants who are expected to influence student achievement outcomes directly. Efforts to make the screening, selection, and hiring process more efficient and effective have led to the use of certain teacher prescreening selection instruments that provide a research-based assessment of teachers’ affective attributes, which purportedly predicts teacher effectiveness. This study addressed this concern using a teacher screening and selection tool, the TI, design by the Gallup Organization. According to the Gallup Organization, the TI is a predictor of teacher affective attributes or talents. The state of Texas uses a student evaluation process called the TAKS to measure student academic gains in certain subject areas. This study examined the relationship between the TI and teacher effectiveness as measured by student academic TAKS change scores in mathematics in fourth and fifth grade. I used data obtained from a single school district in north central Texas. The specific targeted population consisted of 874 students enrolled in mathematics and 44 fourth- and fifth-grade teachers hired over a 3-year period (20082011). I applied a quantitative causal-comparative research design. Descriptive statistics for all variables were presented and bivariate relationships between continuous variables were examined. A two-level linear regression model was used to predict student performance on state-mandated assessments using teachers’ TI scores while controlling for relevant covariates. The statistical significance level throughout the study was set at α = .05. A major finding of this study revealed that teachers’ TI scores were not significant predictors of student achievement in the final model (p = .351). Moreover, the final model did not have significant predictive power when compared to the null model. The findings suggest that other factors not recorded in this dataset may influence student academic performance. Only student gender was a significant predictor of TAKS scores. However, the effect size indicated that student gender accounted for less than 1% of the variance in student achievement (R2 = .003). The findings of this study indicate that the TI alone should not be used as the sole instrument in predicting the quality and potential influence a teacher candidate will have on student performance on state-mandated assessments, and the selected school district should consider re-evaluating its use of the screening instrument for selecting teachers. Recommendations based on the results of the study are discussed and areas for future research are provided.

This dissertation describes investigations of fully turbulent decelerating hydraulically roughbed flow over gravel and the development of technology to measure turbulence and associated sediment transport in streams. Theory is developed for predicting velocity distributions in simple uniform flow using the asymptotic invariance principle and tested using laboratory and field collected data. A mixed scale is developed that accounts for bed derived turbulent structures throughout the flows depth and is used to parameterize the external boundary’s effect on the flow for the logarithmic and outer layers. The asymptotic invariance principle and similarity analysis is conducted for the equations of motion in the outer region of decelerating flow over gravel to define equilibrium conditions for this class of flows with the velocity scale is the freestream velocity. The combination of time series and time averaged statistical analysis of turbulent flow is used to elucidate the structure of flow under decelerating conditions. Time averaged statistical measures of turbulence confirm results of others for higher Froude number approaching transcritical and time series analysis shows the effects of decelerating flow on turbulence to be frequency dependent. Wireless velocity sensors were developed and found capable of measuring time averaged velocity and able to resolve macroturbulence from time series data. A semi-theoretical model of elastic deformation of cantilever beams under hydraulic forcing was coupled with circuit theory to develop a calibration procedure for the VBS that requires only three measurement points, one of which is at zero velocity. Light based sensors are developed to estimate light attenuation in water for ecological research or estimating sediment concentration in water. A semi-theoretical scaling of light attenuation and sediment properties was developed which predicts light attenuation from sediment properties. The combination of new theory on open channel velocity, turbulent structure and field sensors for measuring turbulence and sediment offers the possibility to extend our laboratory knowledge to realistic flow situations.

This thesis is an exploration of a problem that exists between cutting edge Natural Language Processing (NLP) methodologies and their real world exploitation in clinical research. I detail the development and validation of a range of NLP methodologies on clinical records, with a specific focus on the case of the symptomatology of Serious Mental Illness (SMI). This publication based thesis covers five main themes: Pre-work to describe the eld of NLP within the context of clinical data. The proposition, development and evaluation of the TextHunter desktop application, a suite of high-throughput tools to overcome bottlenecks in the development of NLP applications. The application of the tools to the novel domain of SMI symptomatology, enabling the development of language models for 46 symptom concepts with a median F1 score of 0.87, and enabling the pro ling of symptom distribution amongst 7 962 patients, based on discharge summaries. A knowledge discovery project using artificial neural networks and clustering techniques, to identify real world patterns of symptom depiction in clinical free text. Here, I demonstrate a granularity and diversity of vocabulary beyond what is described in standard clinical terminologies. A commentary on the realities of text analytics in the NHS, and the development of a software architecture 'CogStack' to address these. This culminated in the establishment of the Clinical Analytics Platform at King's College Hospital.

As the requirement for wireless telecommunications services continues to grow, it has become increasingly important to ensure that the Radio Frequency (RF) spectrum is managed efficiently. As a result of the current spectrum allocation policy, it has been found that portions of RF spectrum belonging to licensed users are often severely underutilised, at particular times and geographical locations. Awareness of this problem has led to the development of Dynamic Spectrum Access (DSA) and Cognitive Radio (CR) as possible solutions. In one variation of the shared-use model for DSA, it is proposed that the inefficient use of licensed spectrum could be overcome by enabling unlicensed users to opportunistically access the spectrum when the licensed user is not transmitting. In order for an unlicensed device to make decisions, it must be aware of its own RF environment and, therefore, it has been proposed that DSA could been abled using CR. One approach that has be identified to allow the CR to gain information about its operating environment is spectrum sensing. An interesting solution that has been identified for spectrum sensing is cyclostationary detection. This property refers to the inherent periodic nature of the second order statistics of many communications signals. One of the most common modulation formats in use today is Orthogonal Frequency Division Multiplexing (OFDM), which exhibits cyclostationarity due to the addition of a Cyclic Prefix (CP). This thesis examines several statistical tests for cyclostationarity in OFDM signals that may be used for spectrum sensing in DSA and CR. In particular, focus is placed on statistical tests that rely on estimation of the Cyclic Autocorrelation Function (CAF). Based on splitting the CAF into two complex component functions, several new statistical tests are introduced and are shown to lead to an improvement in detection performance when compared to the existing algorithms. The performance of each new algorithm is assessed in Additive White Gaussian Noise (AWGN), impulsive noise and when subjected to impairments such as multipath fading and Carrier Frequency Offset (CFO). Finally, each algorithm is targeted for Field Programmable Gate Array (FPGA) implementation using a Xilinx 7 series device. In order to keep resource costs to a minimum, it is suggested that the new algorithms are implemented on the FPGA using hardware sharing, and a simple mathematical re-arrangement of certain tests statistics is proposed to circumvent a costly division operation.

The Multi-Agency Radiological Site Survey Investigation Manual (MARSSIM) is a regulatory guidance document regarding compliance evaluation of radiologically contaminated soils and buildings (USNRC, 2000). Compliance is determined by comparing radiological measurements to established limits using a combination of hypothesis testing and scanning measurements. Scanning allows investigators to identify localized pockets of contamination missed during sampling and allows investigators to assess radiological exposure at different spatial scales. Scale is important in radiological dose assessment as regulatory limits can vary with the size of the contaminated area and sites are often evaluated at more than one scale (USNRC, 2000). Unfortunately, scanning is not possible in the subsurface and direct application of MARSSIM breaks down. This dissertation develops a subsurface decision framework called the Geospatial Extension to MARSSIM (GEM) to provide multi-scale subsurface decision support in the absence of scanning technologies. Based on geostatistical simulations of radiological activity, the GEM recasts the decision rule as a multi-scale, geospatial decision rule called the regulatory limit rule (RLR). The RLR requires simultaneous compliance with all scales and depths of interest at every location throughout the site. The RLR is accompanied by a compliance test called the stochastic conceptual site model (SCSM). For those sites that fail compliance, a remedial design strategy is developed called the Multi-scale Remedial Design Model (MrDM) that spatially indicates volumes requiring remedial action. The MrDM is accompanied by a sample design strategy known as the Multi-scale Remedial Sample Design Model (MrsDM) that refines this remedial action volume through careful placement of new sample locations. Finally, a new sample design called “check and cover” is presented that can support early sampling efforts by directly using prior knowledge about where contamination may exist. This dissertation demonstrates how these tools are used within an environmental investigation and situates the GEM within existing regulatory methods with an emphasis on the Environmental Protection Agency’s Triad method which recognizes and encourages the use of advanced decision methods. The GEM is implemented within the Spatial Analysis and Decision Assistance (SADA) software and applied to a hypothetical radiologically contaminated site.

Tall fescue [Schedonorus arundinaceus (Schreb.) Dumort.] is an important forage crop in the United States and covers over 14 million ha. The presence of Neotyphodium coenophialum, an endophytic fungus in tall fescue, is associated with several disorders in grazing livestock, but also increased persistence of tall fescue. These disorders, commonly called fescue toxicosis, are responsible for large economic losses in the beef cattle industry each year. This research examined the effect of three fescue types [endophyte-infected Kentucky 31 tall fescue (E+), endophyte-free Kentucky 31 tall fescue (E-), non-ergot alkaloid-producing endophyte Q4508-AR542 tall fescue (Q)], and Lakota prairie grass (L; Bromus catharticus Vahl.) on animal response, alkaloid appearance, DMI, and copper status. Ergovaline (EV) is the most abundant ergot alkaloid in tall fescue and has previously been considered the causative toxin in fescue toxicosis. More recently it is simpler ergot alkaloids, such as lysergic acid amide (LSA) have been implicated. The objective of the first project was to evaluate animal performance and alkaloid (EV and LSA) appearance in forage and ruminal fluid of steers grazing E-, Q, E+, and L. Average daily gains were greater (P < 0.05) on E-, Q and L compared to E+, and there was a trend (P = 0.11) for gains on E- to be higher than with Q. The seasonal appearance of LSA in ruminal fluid was similar to the seasonal pattern of alkaloids in E+ forage. Ergovaline was not detectable in ruminal fluid of steers grazing E+. Alkaloids were not detectable in forage or ruminal fluid of steers grazing E-, Q, or L. The appearance of LSA in ruminal fluid of steers grazing E+ suggests that this alkaloid may contribute to fescue toxicosis. Low DMI of animals grazing E+ tall fescue is considered a key factor in decreased animal performance compared to other fescue types. The objective of the second project was to evaluate DMI of steers grazing E-, E+, Q, and L pastures using the alkane technique. Dry matter intake of steers grazing E- was greater (P < 0.001) than Q, E+, and L and DMI of steers grazing Q and E+ were similar (P > 0.10) in 2004. In 2005, DMI did not differ (P = 0.23) among fescue types. These results suggest that decreased DMI effects ADG of steers grazing E+ compared to those grazing E-, and lower DMI of Q suggests that the fescue variety Q4508 may not be the optimal variety for the incorporation on non-ergot alkaloid-producing endophytes. Reactive oxygen metabolites such as superoxide (O₂⁻) are produced by both endogenous and exogenous sources and an accumulation of these compounds can result in oxidative stress. Copper/zinc superoxide dismutase (SOD) is a Cu-based antioxidant metalloprotein that acts as a defense against oxidative stress by the scavenging of O₂⁻. Neotyphodium-infected tall fescue is typically lower in Cu which could potentially increase oxidative stress of animals grazing this forage. Therefore the objective of the third project was to investigate the Cu and SOD status of steers grazing E-, E+, Q, and L forages. Copper levels of all forages were below the dietary requirement (10μg Cu/g DM) of growing cattle. In 2004, steers grazing E+ exhibited lower (P 0.10) among treatments. Copper intake of steers grazing E+ tall fescue was sufficient to maintain, but not replenish liver Cu, and SOD status did not appear compromised by grazing E+ at these Cu levels.

Background: Individuals with severe mental illness (SMI- schizophrenia, schizoaffective disorder and bipolar disorder) experience higher levels of morbidity and mortality than the general population. An important policy goal is to reduce this gap. Investigating the contributory role of physical illness is of key importance to unpacking the associations between SMI and detrimental outcomes, such as premature mortality and frequent hospital admissions. This thesis builds on recent advances to data extraction technologies to investigate the above. Objectives: • To describe the relative contributions of major disease groups to the gap in life expectancy between individuals with SMI and the general population. • To describe the most common reasons for admission to non-psychiatric hospitals by individuals with SMI and the relative frequencies of these admissions compared to the general population. • As a proof of principle for ascertaining meaningful symptom profiles from routine mental health record text fields, to describe the prospective association between number of recorded negative symptoms and mental healthcare outcomes (admission, duration of admission, and readmission) among individuals with schizophrenia. • To describe the association with mortality and hospitalisation for each of six symptom dimensions (positive, negative, manic, disorganisation, catatonic and depressive) extracted from the clinical records of individuals with SMI. Methods: Information for SMI cohorts were derived from the Clinical Record Interactive Search (CRIS), a de-identified electronic patient records data resource. Data on mortality were extracted using existing linkages between CRIS and death certification (Office for National Statistics). Life expectancy estimates were used to explain the contributions of specific causes of death to the gap. Using Hospital Episode Statistics data, frequencies of and causes for non-psychiatric hospital admissions in SMI were compared to those in the catchment general population. Symptoms within clinical record text fields were ascertained using a range of natural language processing algorithms, and were assessed for their associations with mortality and hospitalisation outcomes. Results: Natural causes accounted for 79.2% of lost life-years in women and 78.6% in men. Deaths from circulatory disorders accounted for more life-years lost in women than men (22.0% versus 17.4%, respectively), as did deaths from cancer (8.1% versus 0%), but the contribution from respiratory disorders was lower in women than men (13.7% versus 16.5%). Commonest discharge diagnosis categories were urinary conditions, digestive conditions, unclassified symptoms, neoplasms, and respiratory conditions. SARs were raised for most major categories, except neoplasms where risk was significantly lower. Hospitalisation risks were specifically higher for poisoning and external causes, injury, endocrine/metabolic conditions, haematological, neurological, dermatological, infectious and non- specific ('Z-code') causes. The five commonest specific ICD-10 diagnoses at discharge were 'chronic renal failure' (N18), a non-specific code (Z04), 'dental caries' (K02), 'other disorders of the urinary system' (N39), and 'pain in throat and chest' (R07), all of which were higher than expected (SARs ranging 1.57-6.66). Proof of concept analyses showed negative symptoms were associated with younger age, male gender and single marital status, and with increased likelihood of hospital admission (OR 1.24, 95% CI 1.10 to 1.39), longer duration of admission (β-coefficient 20.5 days, 95% CI 7.6-33.5), and increased likelihood of readmission following discharge (OR 1.58, 95% CI 1.28 to 1.95). Cox regression analyses detected significant effect of positive (HR 1.08, 95% CI 1.03- 1.16), negative (HR 1.09 95% CI 1.02- 1.16) and catatonic (HR 1.09 95% CI 1.03- 1.16) symptoms on mortality with adjustment of age, sex, employment, marital status and ethnicity. Linear regression analyses detected significant effect of manic (β-coefficient 0.09, 95% CI 0.02- 0.15), catatonic (β-coefficient 0.08, 95% CI 0.02- 0.15) and depressive (β-coefficient 0.14,95% CI 0.08- 0.21) symptoms on admission to non-mental health hospitals. Implications: Clinically, findings from this thesis confirm that SMI has a substantial negative impact on physical health, associated with increased mortality and morbidity. Of clinical relevance, the findings showed differences in burden depending on types of symptoms recorded in health records. From a policy context, the gap in life expectancy and increased non-psychiatric hospitalisation, accounted for by a broad range of causes, need to be addressed systematically. Interventions should focus on a whole system approach to improve health benefits for individuals of SMI.

The purpose of this thesis was to investigate methods of parallelization in the semi-Lagrangian advection scheme. Semi-Lagrangian advection or trans-port (SLT) is a numerical scheme for dealing with advective terms often found in systems of partial differential equations. These advective terms occur in various applications including weather prediction and groundwater contam-ination models. Semi-Lagrangian advection has gained increased attention in the last decade due to its ability to take larger timesteps than Eulerian schemes while maintaining the a regular resolution. Parallelization of the semi-Lagrangian advection scheme has the poten-tial to further increase the efficiency of the scheme by dividing it into smaller independent sub-tasks that can be performed simultaneously on several pro-cessors. Ideally, if the sub-tasks could be evenly assigned to N processors, then the parallel approach should be able to complete the advection N times faster than the sequential method. However, this is usually an unobtainable goal as processor must communicate with each other at certain points in or-der to complete the total task. This is an additional overhead not needed in a sequential setting which reduces the computational speed up to be less than N times faster. Since communication is an important factor in computational efficiency, the communication algorithm used becomes important. Two com-munication algorithms are proposed in this thesis called process migration and data migration. These two approaches are evaluated and compared un-der varying circumstances in order to understand the computational behavior of each. This thesis briefly reviews mathematical transport theory, provides a background for semi-Lagrangian advection, and derives a popular version of SLT known as the three-time-level scheme. Variations of and applications of SLT are discussed. A parallelization of SLT is presented as well as various communication algorithms including data and process migration. Special programming considerations are discussed and a series of tests are conducted on two versions of SLT: the three-time-level and the DN scheme. These tests serve to evaluate the scalability and performance of the parallelization. The performance of the parallelization depended primarily on the magnitude of the velocity field. The larger the magnitude, the greater the communication requirement. In order to better interpret results, most tests were conducted under a constant velocity field. The results of the tests suggest that the latency period (an initialization period before a message is passed) plays a significant role in the parallelization. As a result, under the conditions that were tested, data migration was found to be better for the three-time-level scheme and for the DN scheme until a velocity of about .2. Furthermore, the DN scheme was found to have a computational advantage over the three-time-level scheme using either communication algorithm. These results should not be extended to non-constant velocity as is is illustrated in the final test.

The central question which I address is whether appeal to a hypothetical contract between moral persons is acceptable as a method for justifying basic ethical principles. My first two substantive chapters concern general issues in metaethics, particularly the shortcomings of both st and ard naturalist and noncognitivist theories of evaluative language; some conditions of acceptability for methods of moral justification are proposed and supported as well. Firth's and Hare's methods fail to satisfy these criteria, while Br and t's present approach and Rawls' method of reflective equilibrium largely succeed. Rawls, quite correctly, intends his contract argument to apply only within the framework of this more basic method. Major aspects of Rawls' contract theory are examined at length in Chapter IV. My central concern is with the reasons Rawls gives for regarding his interpretation of the initial contract situation as the "rationally preferred" one. The concepts of impartiality, neutrality, and fairness are discussed at the outset. I then proceed to explain and criticize Rawls' reasons for imposing a "thick veil of ignorance" on the contractors. The argument that natural assets and social contingencies are "morally arbitrary" and hence should not influence the choice of principles of justice is found to be open to serious objection and to rest upon a specific type of egalitarian moral commitment. Rawls' "Kantian" argument is shown to lack sufficient support and to involve an unwarranted exclusion of certain deontological, perfectionist, and other teleological theories from serious consideration. Grice's contract theory, which omits the "veil," is examined in Chapter V, together with his account of prudential reasoning and his argument for a necessary connection between moral obligation and rationality. His type of contract approach is demonstrated to be unworkable due to vague description of the initial situation. Moreover, it has unacceptable implications and cannot serve as an appropriate basis for moral justification in any case. I conclude that the ideal contract method is at best a very conditional procedure of moral justification, far more suitable for some types of moral conceptions than for others. It seems unlikely, furthermore, that achievement of wide reflective equilibrium or "full rationality" in Br and t's sense would result in a consensus favoring any one description of the initial contract situation.

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. Abstract in Penna. state college, Abstracts of doctoral disser-tations, v.3, 1940