Revisiting Irish poetic modernisms

This thesis discusses Irish Modernist poetry written between 1905 and 1970, specifically the poetry of Joseph Campbell (1879-1944), Thomas MacGreevy (1893-1967), Denis Devlin (1908-1959) and Brian Coffey (1905-1995). All four poets have been largely neglected in criticism until a growth of interest encouraged by Michael Smith and Trevor Joyce’s New Writers’ Press during the 1970s. J.C.C. Mays, Stan Smith, Susan Schreibman, Terence Brown, Patricia Coughlan and Alex Davis published subsequent critical support during the ‘80s and ‘90s. My research aims to highlight poetry previously omitted from the canon of Irish literature, those with connections to British or continental European literary movements as well as poetry by women writers and writers from the North. Part of this exploration of Irish Poetic Modernisms involves an investigation of intersections between poetic modernisms and Irish war poetry and of depictions of Irish masculinity in the poetry of Devlin and Coffey. My discussion of Campbell’s poetry focuses on links between the early regional modernism of his poetry and later Irish modernist poetry, including his participation in the Ulster Literary Theatre, with the Literary Revival community in Dublin and his association with the proto-Imagist movement in London. My examination of connections between Irish war poetry and Irish modernism allows me to discuss the writing of several underrecognized Irish poets who are contemporaries and near contemporaries of the main subjects of my thesis. Thomas MacGreevy’s poetry is the most clear case study of the links between Irish modernist poetry and poetry about Ireland’s participation in the Great War. MacGreevy’s writing reveals his multiple allegiances: he both elegizes and challenges the increasing cultural inhibitions of Free State Ireland. Denis Devlin’s poetic portrayals of Ireland reveal his rejection both of the Literary Revival’s fascination with Celticism and of Dublin’s literary community while upholding tradition poetic gender roles. My research explores representations of masculinity and Irish politics, including heroic masculine imagery, in the long poems of Devlin and Coffey. My discussion of Brian Coffey considers the importance of the figure of the “poet as maker” to his writing and his relationship with Ireland during his long writing career. I also consider his role as the editor and executor of Devlin’s literary estate and the impact that had on both the latter’s posthumous reputation and Coffey’s later writing.

Wearable wireless inertial measurement for sports applications

A wearable WIMU (Wireless Inertial Measurement Unit) [1] system for sports applications based on Tyndall's 25mm mote technology [2] has been developed to identify tennis performance determining factors, giving coaches & players improved feedback [3, 4]. Multiple WIMUs transmit player motion data to a PC/laptop via a receiver unit. Internally the WIMUs consist of: an IMU layer with MEMS based sensors; a microcontroller/transceiver layer; and an interconnect layer with supplemental 70g accelerometers and a lithium-ion battery. Packaging consists of a robust ABS plastic case with internal padding, a power switch, battery charging port and status LED with Velcro-elastic straps that are used to attach the device to the player. This offers protection from impact, sweat, and movement of sensors which could cause degradation in device performance. In addition, an important requirement for this device is that it needs to be lightweight and comfortable to wear. Calibration ensures that misalignment of the accelerometer and magnetometer axes are accounted for, allowing more accurate measurements to be made.

Monitoring the vegetation start of season (SOS) across the island of Ireland using the MERIS global vegetation index

The aim of this study was to develop a methodology, based on satellite remote sensing, to estimate the vegetation Start of Season (SOS) across the whole island of Ireland on an annual basis. This growing body of research is known as Land Surface Phenology (LSP) monitoring. The SOS was estimated for each year from a 7-year time series of 10-day composited, 1.2 km reduced resolution MERIS Global Vegetation Index (MGVI) data from 2003 to 2009, using the time series analysis software, TIMESAT. The selection of a 10-day composite period was guided by in-situ observations of leaf unfolding and cloud cover at representative point locations on the island. The MGVI time series was smoothed and the SOS metric extracted at a point corresponding to 20% of the seasonal MGVI amplitude. The SOS metric was extracted on a per pixel basis and gridded for national scale coverage. There were consistent spatial patterns in the SOS grids which were replicated on an annual basis and were qualitatively linked to variation in landcover. Analysis revealed that three statistically separable groups of CORINE Land Cover (CLC) classes could be derived from differences in the SOS, namely agricultural and forest land cover types, peat bogs, and natural and semi-natural vegetation types. These groups demonstrated that managed vegetation, e.g. pastures has a significantly earlier SOS than in unmanaged vegetation e.g. natural grasslands. There was also interannual spatio-temporal variability in the SOS. Such variability was highlighted in a series of anomaly grids showing variation from the 7-year mean SOS. An initial climate analysis indicated that an anomalously cold winter and spring in 2005/2006, linked to a negative North Atlantic Oscillation index value, delayed the 2006 SOS countrywide, while in other years the SOS anomalies showed more complex variation. A correlation study using air temperature as a climate variable revealed the spatial complexity of the air temperature-SOS relationship across the Republic of Ireland as the timing of maximum correlation varied from November to April depending on location. The SOS was found to occur earlier due to warmer winters in the Southeast while it was later with warmer winters in the Northwest. The inverse pattern emerged in the spatial patterns of the spring correlates. This contrasting pattern would appear to be linked to vegetation management as arable cropping is typically practiced in the southeast while there is mixed agriculture and mostly pastures to the west. Therefore, land use as well as air temperature appears to be an important determinant of national scale patterns in the SOS. The TIMESAT tool formed a crucial component of the estimation of SOS across the country in all seven years as it minimised the negative impact of noise and data dropouts in the MGVI time series by applying a smoothing algorithm. The extracted SOS metric was sensitive to temporal and spatial variation in land surface vegetation seasonality while the spatial patterns in the gridded SOS estimates aligned with those in landcover type. The methodology can be extended for a longer time series of FAPAR as MERIS will be replaced by the ESA Sentinel mission in 2013, while the availability of full resolution (300m) MERIS FAPAR and equivalent sensor products holds the possibility of monitoring finer scale seasonality variation. This study has shown the utility of the SOS metric as an indicator of spatiotemporal variability in vegetation phenology, as well as a correlate of other environmental variables such as air temperature. However, the satellite-based method is not seen as a replacement of ground-based observations, but rather as a complementary approach to studying vegetation phenology at the national scale. In future, the method can be extended to extract other metrics of the seasonal cycle in order to gain a more comprehensive view of seasonal vegetation development.

The Whitby life of Gregory the Great: exegesis and hagiography

The eight-century Whitby Vita Gregorii is one of the earliest examples of Anglo-Saxon hagiography, and is the earliest surviving life of Gregory the Great (590-604). The work has proved itself an anomaly in subject matter, style and approach, not least because of the writer’s apparently arbitrary insertion of an account of the retrieval of the relics of the Anglo-Saxon King Edwin (d.633). There has, however, been relatively little research on the document to date, the most recent concentrating on elements in the Gregorian material in the work. The present thesis adapts a methodology which identifies patristic exegetical themes and techniques in the Vita. That is not only in material originating from the pen of Gregory himself, which is freely quoted and cited by the writer, but also in the narrative episodes concerning the Pope. It also identifies related exegetical themes underlying the narrative of the Anglo-Saxon material in the document, and this suggests that the work is of much greater coherence then has previously been thought. In the course of the thesis some of the Vita Gregorii’s major patristic themes are compared with Bede and other insular writers in the presentation of topics that have been of considerable interest to insular historians in recent years. That is themes including: the conversion and salvation of the English people; the ideal pastor; monastic influence on formation of Episcopal spiritual authority; relations between king and bishop. The thesis also includes a re-evaluation of the possible historical context and purpose of the work, and demonstrates the value of a proper understanding of the Vita’s spiritual nature in order to achieve this. Finally the research is supported by a new structural analysis of the entire Vita Gregorii as an artefact formed within literary traditions.

An empirical examination of risk equalisation in a regulated community rated health insurance market

Despite universal access entitlements to the public healthcare system in Ireland, over half the population is covered by voluntary private health insurance. The market operates on the basis of community rating, open enrolment and lifetime cover. A set of minimum benefits also exists, and two risk equalisation schemes have been put in place but neither was implemented. These schemes have proved highly controversial. To date, the debate has primarily consisted of qualitative arguments. This study adds a quantitative element by analysing a number of pertinent issues. A model of a community rated insurance market is developed, which shows that community rating can only be maintained in a competitive market if all insurers in the market have the same risk profile as the market overall. This has relevance to the Irish market in the aftermath of a Supreme Court decision to set aside risk equalisation. Two reasons why insurers’ risk profiles might differ are adverse selection and risk selection. Evidence is found of the existence of both forms of selection in the Irish market. A move from single rate community rating to lifetime community rating in Australia had significant consequences for take-up rates and the age profile of the insured population. A similar move has been proposed in Ireland. It is found that, although this might improve the stability of community rating in the short term, it would not negate the need for risk equalisation. If community rating were to collapse then risk rating might result. A comparison of the Irish, Australian and UK health insurance markets suggests that community rating encourages higher take-up among older consumers than risk rating. Analysis of Irish hospital discharge figures suggests that this yields significant savings for the Irish public healthcare system. This thesis has implications for government policy towards private health insurance in Ireland.

Politically motivated former prisoner groups: community activism and conflict transformation

Aims and objectives: This study represents the first sustained quantitative and qualitative attempt to involve both Republicans and Loyalists in an investigation of the impact of imprisonment and the role of politically motivated former prisoners in the process of conflict transformation in Northern Ireland. The overall aim of the project is to examine the ways in which groups of former prisoners are involved in peace-building and conflict transformation work and to evaluate the constraints and impediments placed upon their activities by the effects of the imprisonment process, politically motivated release and residual criminalisation. In pursuing the evaluation of the role of politically motivated former prisoners working within and without their own communities, the research has six specific objectives: To trace the evolution and development of former prisoner groups; To evaluate the impacts of imprisonment and release on the personal lives of former prisoners; To assess the constraints imposed on former prisoners as agents of change by the residual criminalisation arising from their status; To determine the potential of the former prisoner community in challenging intra-community tensions and evaluate their potential and actual contribution to conflict transformation at the inter-community level; To compare and contrast the effectiveness of Loyalist and Republican former prisoners as agents of change within their own communities; To explore the notion of former prisoners as agents of social and communal transformation within broader political processes through grounding the knowledge and practical experience of the former prisoner community within the broader conceptual context of conflict transformation.

Spatial and energetic mode dynamics of cold atomic systems

In this thesis we relate the formal description of various cold atomic systems in the energy eigenbasis, to the observable spatial mode dynamics. Herein the `spatial mode dynamics' refers to the direction of photon emission following the spontaneous emission of an excited fermion in the presence of a same species and spin ideal anisotropic Fermi sea in its internal ground state. Due to the Pauli principle, the presence of the ground state Fermi sea renders the phase space, anisotropic and only partially accessible, thereby a ecting the direction of photon emission following spontaneous emission. The spatial and energetic mode dynamics also refers to the quantum `tunneling' interaction between localised spatial modes, synonymous with double well type potentials. Here we relate the dynamics of the wavefunction in both the energetic and spatial representations. Using this approach we approximate the relationship between the spatial and energetic representations of a wavefunction spanning three spatial and energetic modes. This is extended to a process known as Spatial Adiabatic Passage, which is a technique to transport matter waves between localised spatial modes. This approach allows us to interpret the transport of matter waves as a signature of a geometric phase acquired by the one of the internal energy eigenstates of the system during the cyclical evolution. We further show that this geometric phase may be used to create spatial mode qubit and qutrit states.

Wavelength division multiplexing at 2μm

This paper shows, for the first time, the implementation of a WDM subsystem at the 2μm wavelength window with mixed formats. Three wavelength channels were directly modulated withBPSK Fast-OFDM at 5Gbit/s per channel, with a fourth channel NRZ-OOK externally modulated at8.5Gbit/s giving a total capacity in excess of 20 Gbit/s.

Enhancing the health-status of processed meats through ingredient manipulation and its effects on sensory and physiochemical product attributes

An important component of this Ph.D. thesis was to determine the European consumers’ views on processed meats and bioactive compounds. Thus a survey gathered information form over 500 respondents and explored their perceptions on the healthiness and purchase-ability for both traditional and functional processed meats. This study found that the consumer was distrustful towards processed meat, especially high salt and fat content. Consumers were found to be very pro-bioactive compounds in yogurt style products but unsure of their feelings on the idea of them in meat based products, which is likely due to the lack of familiarity to these products. The work in this thesis also centred on the applied acceptable reduction of salt and fat in terms of consumer sensory analysis. The products chosen ranged in the degree of comminution, from a coarse beef patty to a more fine emulsion style breakfast sausage and frankfurter. A full factorial design was implemented which saw the production of twenty beef patties with varying concentrations of fat (30%, 40%, 50%, 60% w/w) and salt (0.5%, 0.75%, 1.0%, 1.25%, 1.5% w/w). Twenty eight sausage were also produced with varying concentrations of fat (22.5%, 27.5%, 32.5%, 37.5% w/w) and salt (0.8%, 1%, 1.2%, 1.4%, 1.6%, 2%, 2.4% w/w). Finally, twenty different frankfurters formulations were produced with varying concentrations of fat (10%, 15%, 20%, 25% w/w) and salt (1%, 1.5%, 2%, 2.5%, 3% w/w). From these products it was found that the most consumer acceptable beef patty was that containing 40% fat with a salt level of 1%. This is a 20% decrease in fat and a 50% decrease in salt levels when compared to commercial patty available in Ireland and the UK. For sausages, salt reduced products were rated by the consumers as paler in colour, more tender and with greater meat flavour than higher salt containing products. The sausages containing 1.4 % and 1.0 % salt were significantly (P<0.01) found to be more acceptable to consumers than other salt levels. Frankfurter salt levels below 1.5% were shown to have a negative effect on consumer acceptability, with 2.5% salt concentration being the most accepted (P<0.001) by consumers. Samples containing less fat and salt were found to be tougher, less juicy and had greater cooking losses. Thus salt perception is very important for consumer acceptability, but fat levels can be potentially reduced without significantly affecting overall acceptability. Overall it can be summarised that the consumer acceptability of salt and fat reduced processed meats depends very much on the product and generalisations cannot be assumed. The study of bio-actives in processed meat products found that the reduced salt/fat patties fortified with CoQ10 were rated as more acceptable than commercially available products for beef patties. The reduced fat and salt, as well as the CoQ10 fortified, sausages were found to compare quite well to their commercial counterparts for overall acceptability, whereas commercial frankfurters were found to be the more favoured in comparison to reduced fat and CoQ10 fortified Frankfurters.

Hardware design of cryptographic accelerators

With the rapid growth of the Internet and digital communications, the volume of sensitive electronic transactions being transferred and stored over and on insecure media has increased dramatically in recent years. The growing demand for cryptographic systems to secure this data, across a multitude of platforms, ranging from large servers to small mobile devices and smart cards, has necessitated research into low cost, flexible and secure solutions. As constraints on architectures such as area, speed and power become key factors in choosing a cryptosystem, methods for speeding up the development and evaluation process are necessary. This thesis investigates flexible hardware architectures for the main components of a cryptographic system. Dedicated hardware accelerators can provide significant performance improvements when compared to implementations on general purpose processors. Each of the designs proposed are analysed in terms of speed, area, power, energy and efficiency. Field Programmable Gate Arrays (FPGAs) are chosen as the development platform due to their fast development time and reconfigurable nature. Firstly, a reconfigurable architecture for performing elliptic curve point scalar multiplication on an FPGA is presented. Elliptic curve cryptography is one such method to secure data, offering similar security levels to traditional systems, such as RSA, but with smaller key sizes, translating into lower memory and bandwidth requirements. The architecture is implemented using different underlying algorithms and coordinates for dedicated Double-and-Add algorithms, twisted Edwards algorithms and SPA secure algorithms, and its power consumption and energy on an FPGA measured. Hardware implementation results for these new algorithms are compared against their software counterparts and the best choices for minimum area-time and area-energy circuits are then identified and examined for larger key and field sizes. Secondly, implementation methods for another component of a cryptographic system, namely hash functions, developed in the recently concluded SHA-3 hash competition are presented. Various designs from the three rounds of the NIST run competition are implemented on FPGA along with an interface to allow fair comparison of the different hash functions when operating in a standardised and constrained environment. Different methods of implementation for the designs and their subsequent performance is examined in terms of throughput, area and energy costs using various constraint metrics. Comparing many different implementation methods and algorithms is nontrivial. Another aim of this thesis is the development of generic interfaces used both to reduce implementation and test time and also to enable fair baseline comparisons of different algorithms when operating in a standardised and constrained environment. Finally, a hardware-software co-design cryptographic architecture is presented. This architecture is capable of supporting multiple types of cryptographic algorithms and is described through an application for performing public key cryptography, namely the Elliptic Curve Digital Signature Algorithm (ECDSA). This architecture makes use of the elliptic curve architecture and the hash functions described previously. These components, along with a random number generator, provide hardware acceleration for a Microblaze based cryptographic system. The trade-off in terms of performance for flexibility is discussed using dedicated software, and hardware-software co-design implementations of the elliptic curve point scalar multiplication block. Results are then presented in terms of the overall cryptographic system.

Integrated spot size converters for InP based photonic systems

The ever increasing demand for broadband communications requires sophisticated devices. Photonic integrated circuits (PICs) are an approach that fulfills those requirements. PICs enable the integration of different optical modules on a single chip. Low loss fiber coupling and simplified packaging are key issues in keeping the price of PICs at a low level. Integrated spot size converters (SSC) offer an opportunity to accomplish this. Design, fabrication and characterization of SSCs based on an asymmetric twin waveguide (ATG) at a wavelength of 1.55 μm are the main elements of this dissertation. It is theoretically and experimentally shown that a passive ATG facilitates a polarization filter mechanism. A reproducible InP process guideline is developed that achieves vertical waveguides with smooth sidewalls. Birefringence and resonant coupling are used in an ATG to enable a polarization filtering and splitting mechanism. For the first time such a filter is experimentally shown. At a wavelength of 1610 nm a power extinction ratio of (1.6 ± 0.2) dB was measured for the TE- polarization in a single approximately 372 μm long TM- pass polarizer. A TE-pass polarizer with a similar length was demonstrated with a TM/TE-power extinction ratio of (0.7 ± 0.2) dB at 1610 nm. The refractive indices of two different InGaAsP compositions, required for a SSC, are measured by the reflection spectroscopy technique. A SSC layout for dielectric-free fabricated compact photodetectors is adjusted to those index values. The development and the results of the final fabrication procedure for the ATG concept are outlined. The etch rate, sidewall roughness and selectivity of a Cl2/CH4/H2 based inductively coupled plasma (ICP) etch are investigated by a design of experiment approach. The passivation effect of CH4 is illustrated for the first time. Conditions are determined for etching smooth and vertical sidewalls up to a depth of 5 μm.

Development of germanium/silicon integration for near infrared detection

Silicon (Si) is the base material for electronic technologies and is emerging as a very attractive platform for photonic integrated circuits (PICs). PICs allow optical systems to be made more compact with higher performance than discrete optical components. Applications for PICs are in the area of fibre-optic communication, biomedical devices, photovoltaics and imaging. Germanium (Ge), due to its suitable bandgap for telecommunications and its compatibility with Si technology is preferred over III-V compounds as an integrated on-chip detector at near infrared wavelengths. There are two main approaches for Ge/Si integration: through epitaxial growth and through direct wafer bonding. The lattice mismatch of ~4.2% between Ge and Si is the main problem of the former technique which leads to a high density of dislocations while the bond strength and conductivity of the interface are the main challenges of the latter. Both result in trap states which are expected to play a critical role. Understanding the physics of the interface is a key contribution of this thesis. This thesis investigates Ge/Si diodes using these two methods. The effects of interface traps on the static and dynamic performance of Ge/Si avalanche photodetectors have been modelled for the first time. The thesis outlines the original process development and characterization of mesa diodes which were fabricated by transferring a ~700 nm thick layer of p-type Ge onto n-type Si using direct wafer bonding and layer exfoliation. The effects of low temperature annealing on the device performance and on the conductivity of the interface have been investigated. It is shown that the diode ideality factor and the series resistance of the device are reduced after annealing. The carrier transport mechanism is shown to be dominated by generation–recombination before annealing and by direct tunnelling in forward bias and band-to-band tunnelling in reverse bias after annealing. The thesis presents a novel technique to realise photodetectors where one of the substrates is thinned by chemical mechanical polishing (CMP) after bonding the Si-Ge wafers. Based on this technique, Ge/Si detectors with remarkably high responsivities, in excess of 3.5 A/W at 1.55 μm at −2 V, under surface normal illumination have been measured. By performing electrical and optical measurements at various temperatures, the carrier transport through the hetero-interface is analysed by monitoring the Ge band bending from which a detailed band structure of the Ge/Si interface is proposed for the first time. The above unity responsivity of the detectors was explained by light induced potential barrier lowering at the interface. To our knowledge this is the first report of light-gated responsivity for vertically illuminated Ge/Si photodiodes. The wafer bonding approach followed by layer exfoliation or by CMP is a low temperature wafer scale process. In principle, the technique could be extended to other materials such as Ge on GaAs, or Ge on SOI. The unique results reported here are compatible with surface normal illumination and are capable of being integrated with CMOS electronics and readout units in the form of 2D arrays of detectors. One potential future application is a low-cost Si process-compatible near infrared camera.

Empirical analysis and improved modelling of natural gas demand in Ireland

Countries across the world are being challenged to decarbonise their energy systems in response to diminishing fossil fuel reserves, rising GHG emissions and the dangerous threat of climate change. There has been a renewed interest in energy efficiency, renewable energy and low carbon energy as policy‐makers seek to identify and put in place the most robust sustainable energy system that can address this challenge. This thesis seeks to improve the evidence base underpinning energy policy decisions in Ireland with a particular focus on natural gas, which in 2011 grew to have a 30% share of Ireland’s TPER. Natural gas is used in all sectors of the Irish economy and is seen by many as a transition fuel to a low-carbon energy system; it is also a uniquely excellent source of data for many aspects of energy consumption. A detailed decomposition analysis of natural gas consumption in the residential sector quantifies many of the structural drives of change, with activity (R2 = 0.97) and intensity (R2 = 0.69) being the best explainers of changing gas demand. The 2002 residential building regulations are subject to an ex-post evaluation, which using empirical data finds a 44 ±9.5% shortfall in expected energy savings as well as a 13±1.6% level of non-compliance. A detailed energy demand model of the entire Irish energy system is presented together with scenario analysis of a large number of energy efficiency policies, which show an aggregate reduction in TFC of 8.9% compared to a reference scenario. The role for natural gas as a transition fuel over a long time horizon (2005-2050) is analysed using an energy systems model and a decomposition analysis, which shows the contribution of fuel switching to natural gas to be worth 12 percentage points of an overall 80% reduction in CO2 emissions. Finally, an analysis of the potential for CCS in Ireland finds gas CCS to be more robust than coal CCS for changes in fuel prices, capital costs and emissions reduction and the cost optimal location for a gas CCS plant in Ireland is found to be in Cork with sequestration in the depleted gas field of Kinsale.

Transport energy demand: techno-economic modelling and scenarios for Irish climate policy

The case for energy policy modelling is strong in Ireland, where stringent EU climate targets are projected to be overshot by 2015. Policy targets aiming to deliver greenhouse gas and renewable energy targets have been made, but it is unclear what savings are to be achieved and from which sectors. Concurrently, the growth of personal mobility has caused an astonishing increase in CO2 emissions from private cars in Ireland, a 37% rise between 2000 and 2008, and while there have been improvements in the efficiency of car technology, there was no decrease in the energy intensity of the car fleet in the same period. This thesis increases the capacity for evidenced-based policymaking in Ireland by developing techno-economic transport energy models and using them to analyse historical trends and to project possible future scenarios. A central focus of this thesis is to understand the effect of the car fleet‘s evolving technical characteristics on energy demand. A car stock model is developed to analyse this question from three angles: Firstly, analysis of car registration and activity data between 2000 and 2008 examines the trends which brought about the surge in energy demand. Secondly, the car stock is modelled into the future and is used to populate a baseline “no new policy” scenario, looking at the impact of recent (2008-2011) policy and purchasing developments on projected energy demand and emissions. Thirdly, a range of technology efficiency, fuel switching and behavioural scenarios are developed up to 2025 in order to indicate the emissions abatement and renewable energy penetration potential from alternative policy packages. In particular, an ambitious car fleet electrification target for Ireland is examined. The car stock model‘s functionality is extended by linking it with other models: LEAP-Ireland, a bottom-up energy demand model for all energy sectors in the country; Irish TIMES, a linear optimisation energy system model; and COPERT, a pollution model. The methodology is also adapted to analyse trends in freight energy demand in a similar way. Finally, this thesis addresses the gap in the representation of travel behaviour in linear energy systems models. A novel methodology is developed and case studies for Ireland and California are presented using the TIMES model. Transport Energy

Early biomarkers to predict grade of encephalopathy following hypoxic ischaemic injury

The standard early markers for identifying and grading HIE severity, are not sufficient to ensure all children who would benefit from treatment are identified in a timely fashion. The aim of this thesis was to explore potential early biomarkers of HIE. Methods: To achieve this a cohort of infants with perinatal depression was prospectively recruited. All infants had cord blood samples drawn and biobanked, and were assessed with standardised neurological examination, and early continuous multi-channel EEG. Cord samples from a control cohort of healthy infants were used for comparison. Biomarkers studied included; multiple inflammatory proteins using multiplex assay; the metabolomics profile using LC/MS; and the miRNA profile using microarray. Results: Eighty five infants with perinatal depression were recruited. Analysis of inflammatory proteins consisted of exploratory analysis of 37 analytes conducted in a sub-population, followed by validation of all significantly altered analytes in the remaining population. IL-6 and IL-6 differed significantly in infants with a moderate/severely abnormal vs. a normal-mildly abnormal EEG in both cohorts (Exploratory: p=0.016, p=0.005: Validation: p=0.024, p=0.039; respectively). Metabolomic analysis demonstrated a perturbation in 29 metabolites. A Cross- validated Partial Least Square Discriminant Analysis model was developed, which accurately predicted HIE with an AUC of 0.92 (95% CI: 0.84-0.97). Analysis of the miRNA profile found 70 miRNA significantly altered between moderate/severely encephalopathic infants and controls. miRNA target prediction databases identified potential targets for the altered miRNA in pathways involved in cellular metabolism, cell cycle and apoptosis, cell signaling, and the inflammatory cascade. Conclusion: This thesis has demonstrated that the recruitment of a large cohortof asphyxiated infants, with cord blood carefully biobanked, and detailed early neurophysiological and clinical assessment recorded, is feasible. Additionally the results described, provide potential alternate and novel blood based biomarkers for the identification and assessment of HIE.