Development and optimisation of photonic crystal based nanosensors

This thesis involved the development of two Biosensors and their associated assays for the detection of diseases, namely IBR and BVD for veterinary use and C1q protein as a biomarker to pancreatic cancer for medical application, using Surface Plasmon Resonance (SPR) and nanoplasmonics. SPR techniques have been used by a number of groups, both in research [1-3] and commercially [4, 5] , as a diagnostic tool for the detection of various biomolecules, especially antibodies [6-8]. The biosensor market is an ever expanding field, with new technology and new companies rapidly emerging on the market, for both human [8] and veterinary applications [9, 10]. In Chapter 2, we discuss the development of a simultaneous IBR and BVD virus assay for the detection of antibodies in bovine serum on an SPR-2 platform. Pancreatic cancer is the most lethal cancer by organ site, partially due to the lack of a reliable molecular signature for diagnostic testing. C1q protein has been recently proposed as a biomarker within a panel for the detection of pancreatic cancer. The third chapter discusses the fabrication, assays and characterisation of nanoplasmonic arrays. We will talk about developing C1q scFv antibody assays, clone screening of the antibodies and subsequently moving the assays onto the nanoplasmonic array platform for static assays, as well as a custom hybrid benchtop system as a diagnostic method for the detection of pancreatic cancer. Finally, in chapter 4, we move on to Guided Mode Resonance (GMR) sensors, as a low-cost option for potential use in Point-of Care diagnostics. C1q and BVD assays used in the prior formats are transferred to this platform, to ascertain its usability as a cost effective, reliable sensor for diagnostic testing. We discuss the fabrication, characterisation and assay development, as well as their use in the benchtop hybrid system.

Landscape and planning: strengthening discussions in the decision-making process

Since the emergence of the European Landscape Convention (ELC) in 2000, the important link between landscape and planning has greatly intensified. Now, more than ever, the fundamental role of the planning system in delivering the ELC’s requirements is recognised. This has been further substantiated within Ireland’s recently published National Landscape Strategy. However it has continually been suggested that decision-making processes need to adapt better to the holistic, valueladen and multidimensional approaches underpinning the ELC. In light of these milestones for the preservation, management and planning of landscape, this research sets out to establish synergies and disparities in the existing relationship between landscape and planning. It investigates detailed evidence of the presence and manifestations of landscape in key processes of day-to-day planning practice in Ireland, from individual planning appeals and ‘special’ cases, to the major strategic instruments that inform the making of landscape policies within development plans. This is set within wider theoretical and policy contexts where the compatibility of landscape and planning is subjected to critical scrutiny and then explored through these practical case studies. Driving this research is the intention to make a case for the planning domain to be an ideal ‘home’ for landscape – in all its deep, multidimensional meaning – and for enhancing landscape arguments and objectives in the face of conflict, competing values and power-plays in the real world. Emerging out of this research is a set of recommendations for how, at a national level, new approaches for decision making for and about landscape can be more effective and meaningful.

A phenomenological study to explore individuals’ experience of depression

Numerous epidemiological findings suggest that we live in an era that can only be described as the “age of melancholy” in that more and more individuals are diagnosed with depression every year. The aim of this study was to gain a phenomenological understanding of how individuals who experienced depression understood and made sense of their experience of depression through a methodology of interpretative phenomenological analysis. In-depth semi-structured interviews explored the lived experience of depression for eight individuals and identified how social discourses contributed to their understanding. Following rigorous analysis of twelve interview transcripts, data was broken down into four recurrent superordinate themes which related directly to how individuals made sense of their experience of depression; The Descent; The Worlds Conversations and Me - Engagement with Social Discourses; Broken Self - Transforming the Self; Embracing myself and my Mind - Transformation of the Self. Further interrogative analysis identified how some social discourses communicated by healthcare professionals, the media and academia, contributed to individuals experiencing an additional layer of distress, namely meta-distress which in essence is distress about distress.

A philosophy of performance, politics and composition

This thesis discusses socio-political issues worldwide through philosophical approaches to performance, politics and composition. My research also discuss sound decisions which I regard to be simultaneously an outlet for personal expression, as well as a practical tool to inspire a socio-political change in society. Although the latter is paramount to the methodology of the project, the sound cannot be regarded in isolation as a “political composition”. It can only become truly functional in a political sense through interaction with other art forms, within the context of a specific place and time. My portfolio for this project is of two socio-political projects which are my chief concern. The first project concerns the Israeli-Palestinian conflict. I named this project PATH. PATH aims to foster and expand peaceful thought between Jewish and Palestinian civilians in Israel-Palestine. Through performance art, PATH spreads a message of acceptance, unity and brotherhood between our peoples. Above all, PATH demands and end to intolerance, hatred and violence among all the inhabitants of the State of Israel. The second project concerns women’s rights globally. I have realised that although we have come a long way in our struggle for rights for women, great challenges remain. There is a need to unite women and men against a form of oppression that discriminates against 50% of the world’s population. I called this project, For Utopia.

Gene delivery for the treatment of prostate cancer

Prostate cancer is one of the most common cancers diagnosed in men. Whilst treatments for early-stage disease are largely effective, current therapies for metastatic prostate cancer, particularly for bone metastasis, offer only a few months increased lifespan at best. Hence new treatments are urgently required. Small interfering RNA (siRNA) has been investigated for the treatment of prostate cancer where it can ‘silence’ specific cancer-related genes. However the clinical application of siRNA-based gene therapy is limited due to the absence of an optimised gene delivery vector. The optimisation of such gene delivery vectors is routinely undertaken in vitro using 2D cell culture on plastic dishes which does not accurately simulate the in vivo bone cancer metastasis microenvironment. The goal of this thesis was to assess the potential of two different targeted delivery vectors (gold or modified β-cyclodextrin derivatives) to facilitate siRNA receptor-mediated uptake into prostate cancer cells. Furthermore, this project aimed to develop a more physiologically relevant 3D in vitro cell culture model, to mimic prostate cancer bone metastasis, which is suitable for evaluating the delivery of nanoparticulate gene therapeutics. In the first instance, cationic derivatives of gold and β-cyclodextrin were synthesized to complex anionic siRNA. The delivery vectors were targeted to prostate cancer cells using the anisamide ligand which has high affinity for the sigma receptor that is overexpressed by prostate cancer cells. The gold nanoparticle demonstrated high levels of uptake into prostate cancer PC3 cells and efficient gene silencing when transfection was performed in serum-free media. However, due to the absence of a poly(ethylene glycol) (PEG) stabilising group, the formulation was unsuitable for use in serum-containing conditions. Conversely, the modified β-cyclodextrin formulation demonstrated enhanced stability in the presence of serum due to the inclusion of a PEG chain onto which the anisamide ligand was conjugated. However, the maximum level of gene silencing efficacy from three different prostate cancer cell lines (DU145, VCaP and PC3 cells) was 30 %, suggesting that further optimisation of the formulation would be required prior to application in vivo. In order to develop a more physiologically-relevant in vitro model of prostate cancer bone metastasis, prostate cancer cells (PC3 and LNCaP cells) were cultured in 3D on collagenbased scaffolds engineered to mimic the bone microenvironment. While the model was suitable for assessing nanoparticle-mediated gene knockdown, prostate cancer cells demonstrated a phenotype with lower invasive potential when grown on the scaffolds relative to standard 2D cell culture. Hence, prostate cancer cells (PC3 and LNCaP cells) were subsequently co-cultured with bone osteoblast cells (hFOB 1.19 cells) to enhance the physiological relevance of the model. Co-cultures secreted elevated levels of the MMP9 enzyme, a marker of prostate cancer metastasis, relative to prostate cancer cell monocultures (2D and 3D) indicating enhanced physiological relevance of the model. Furthermore, the coculture model proved suitable for investigating nanoparticle-mediated gene silencing. In conclusion, the work outlined in this thesis identified two different sigma receptor-targeted gene delivery vectors with potential for the treatment of prostate cancer. In addition, a more physiologically relevant model of prostate cancer bone metastasis was developed with the capacity to help optimise gene delivery vectors for the treatment of prostate cancer.

Irish and Jordanian general student nurses’ attitudes towards people with mental illness (PWMI) and their relationship to cultural and religious beliefs

Background Attitudes held and cultural and religious beliefs of general nursing students towards individuals with mental health problems are key factors that contribute to the quality of care provided. Negative attitudes towards mental illness and to individuals with mental health problems are held by the general public as well as health professionals. Negative attitudes towards people with mental illness have been reported to be associated with low quality of care, poor access to health care services and feelings of exclusion. Furthermore, culture has been reported to play a significant role in shaping people’s attitudes, values, beliefs, and behaviours, but has been poorly investigated. Research has also found that religious beliefs and practices are associated with better recovery for individuals with mental illness and enhanced coping strategies and provide more meaning and purpose to thinking and actions. The literature indicated that both Ireland and Jordan lack baseline data of general nurses’ and general nursing students’ attitudes towards mental illness and associated cultural and religious beliefs. Aims: To measure general nursing students’ attitudes towards individuals with mental illness and their relationships to socio-demographic variables and cultural and religious beliefs. Method: A quantitative descriptive study was conducted (n=470). 185 students in Jordan and 285 students in Ireland participated, with a response rate of 86% and 73%, respectively. Data were collected using the Community Attitudes towards the Mentally Ill instrument and a Cultural and Religious Beliefs Scale to People with Mental Illness constructed by the author. Results: Irish students reported more positive attitudes yet did not have strong cultural and religious beliefs compared to students from Jordan. Country of origin, considering a career in mental health nursing, knowing somebody with mental illness and cultural and religious beliefs were the most significant variables associated with students’ attitudes towards people with mental illness. In addition, students living in urban areas reported more positive attitudes to people with mental illness compared to those living in rural areas.

Investigating metabolomic biomarkers of hypoxic ischaemic encephalopathy

Background An early objective biomarker to predict the severity of hypoxic-ischaemic encephalopathy (HIE) and identify infants suitable for intervention remains elusive. This thesis aims to progress metabolomic markers of HIE through a pipeline of biomarker discovery and validation by employing a novel untargeted mass spectrometry metabolomic method. Methodology Term infants with perinatal asphyxia were recruited, all having umbilical cord blood (UCB) drawn and biobanked within three hours of birth. HIE was defined by Sarnat score at 24hours and continuous multichannel-EEG. Infant neurodevelopment was assessed at 36-42 months using the Bayley Scales of Infant and Toddler Development Ed. III (BSID-III). Untargeted metabolomic analysis of UCB was performed using direct injection FT-ICR mass spectrometry (DI FT-ICR MS). Putative metabolite annotations and lipid classes were assigned and pathway analysis was performed. Results Untargeted metabolomic analysis: Thirty enrolled infants were diagnosed with HIE, including 17 mild, 8 moderate, and 5 severe cases. Pathway analysis revealed that ΔHIE was associated with a 50% and 75% perturbation of tryptophan and pyrimidine metabolism respectively, alongside alterations in amino acid pathways. Significant metabolite alterations were detected from six putatively identified lipid classes including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids and prenol lipids. Outcome prediction: Metabolite model scores significantly correlated with outcome R=0.429 (model A) and R=0.549 (model B) respectively. Model B demonstrates the potential to predict both severe outcome (AUROC of 0.915) and intact survival (AUROC of 0.800). The effect of haemolysis: On average 5% of polar and 1.5% of non-polar features were altered between paired haemolysed and clean samples. However unsupervised multivariate analysis concluded that the preanalytical variability introduced by haemolysis was negligible compared with the inherent biological inter-individual variability. Conclusion This research has employed untargeted metabolomics to identify potential early cord blood biomarkers of HIE and has performed the technical validation of previously proposed markers.

Talom Rukbo and the Donyipolo Yelam Kebang: restructuring Adi religious practices in Arunachal Pradesh, Northeast India

The purpose of this dissertation is to examine and contextualize the recent changes in the articulation of Donyipolo faith among the indigenous community of the Adi from the 1980s until the present. This is achieved by documenting both ‘non-formalized’ and ‘formalized’ belief and ritual within this Eastern Himalayan community. Since the mid-1980s, the Adi – led by indigenous activist Talom Rukbo and the Donyipolo Yelam Kebang (Donyipolo Faith Council) – have been restructuring Donyipolo to fit the model of more mainstream religions via a series of processes that could be called ‘formalization’ or ‘institutionalization’, a reformation blueprint that has subsequently spread to neighboring ethnic groups. This ethnography, exploring both folk practice and the modern reformation, is rooted in radical empiricism – in this context, meaning to collect data and allow analysis to arise organically. Radical empiricism is employed alongside vernacular theorizing to allow for the acknowledgement of indigenous theory through which we can trace indigenous agencies and the construction of indigenous lifeworlds. Facilitating this space for the acknowledgement of ‘religious re-imaginings’ as a means of cultural preservation – and as a representation of creativity – is significant particularly when viewed in the context of contemporary research on similar movements in Northeast India, which sometimes tends toward the negation of indigenous innovation by representing such religious revivals as conversion tools attributed to the Hindu right. It is hoped that the reader will come away from this dissertation with an understanding of the ‘constellations of faith’ that comprise ‘traditional’ Donyipolo and a comprehension of the innovative institutionalization processes that have shaped the new Adi praxis. Donyipolo should be viewed as a complex, nuanced, and independent indigenous faith, whether in its forms of folk expressions or in its new structure as expressed through the Donyipolo Yelam Kebang.

Development of a novel probe integrated with a micro-structured impedance sensor for the detection of breast cancer

The work described in this thesis focuses on the development of an innovative bioimpedance device for the detection of breast cancer using electrical impedance as the detection method. The ability for clinicians to detect and treat cancerous lesions as early as possible results in improved patient outcomes and can reduce the severity of the treatment the patient has to undergo. Therefore, new technology and devices are continually required to improve the specificity and sensitivity of the accepted detection methods. The gold standard for breast cancer detection is digital x-ray mammography but it has some significant downsides associated with it. The development of an adjunct technology to aid in the detection of breast cancers could represent a significant patient and economic benefit. In this project silicon substrates were pattern with two gold microelectrodes that allowed electrical impedance measurements to be recorded from intact tissue structures. These probes were tested and characterised using a range of in vitro and ex vivo experiments. The end application of this novel sensor device was in a first-in-human clinical trial. The initial results of this study showed that the silicon impedance device was capable of differentiating between normal and abnormal (benign and cancerous) breast tissue. The mean separation between the two tissue types 4,340 Ω with p < 0.001. The cancer type and grade at the site of the probe recordings was confirmed histologically and correlated with the electrical impedance measurements to determine if the different subtypes of cancer could each be differentiated. The results presented in this thesis showed that the novel impedance device demonstrated excellent electrochemical recording potential; was biocompatible with the growth of cultured cell lines and was capable of differentiating between intact biological tissues. The results outlined in this thesis demonstrate the potential feasibility of using electrical impedance for the differentiation of biological tissue samples. The novelty of this thesis is in the development of a new method of tissue determination with an application in breast cancer detection.

Dynamic classifiers for neonatal brain monitoring

Brain injury due to lack of oxygen or impaired blood flow around the time of birth, may cause long term neurological dysfunction or death in severe cases. The treatments need to be initiated as soon as possible and tailored according to the nature of the injury to achieve best outcomes. The Electroencephalogram (EEG) currently provides the best insight into neurological activities. However, its interpretation presents formidable challenge for the neurophsiologists. Moreover, such expertise is not widely available particularly around the clock in a typical busy Neonatal Intensive Care Unit (NICU). Therefore, an automated computerized system for detecting and grading the severity of brain injuries could be of great help for medical staff to diagnose and then initiate on-time treatments. In this study, automated systems for detection of neonatal seizures and grading the severity of Hypoxic-Ischemic Encephalopathy (HIE) using EEG and Heart Rate (HR) signals are presented. It is well known that there is a lot of contextual and temporal information present in the EEG and HR signals if examined at longer time scale. The systems developed in the past, exploited this information either at very early stage of the system without any intelligent block or at very later stage where presence of such information is much reduced. This work has particularly focused on the development of a system that can incorporate the contextual information at the middle (classifier) level. This is achieved by using dynamic classifiers that are able to process the sequences of feature vectors rather than only one feature vector at a time.

'A piece of fine meshwork': the intertwining fiction of Philip Roth and Edna O'Brien

This thesis comprises a comparative analysis of the works the Irish author Edna O’Brien and her contemporary and friend, the Jewish-American author Philip Roth. It investigates the striking biographical, textual and stylistic symmetries between two writers from very different cultures and literary traditions. The thesis begins with the, until now, undetected intertextual nexuses between Roth’s fiction and O’Brien’s. These allusions significantly alter the readings of a number of their novels, while at the same time indicating wider transatlantic frames of reference now apparent in their work. O’Brien has, since the beginning of her career, been in frequent correspondence with all of the pre-eminent Jewish-American authors of her time, and her work conducts a dialogue with key Jewish-American texts. Conversely, Roth’s fiction—like O’Brien’s, obviously indebted to Joyce—has frequently alluded to other seminal Irish authors. The literary and personal relationship of Roth and O’Brien symbolize myriad links between Jewish and Irish literary cultures. In O’Brien’s (and wider Irish) fiction, the Jew is often positioned as an exotic but dangerous “Other”. Equally, throughout the Jewish canon Irish Catholics are frequently employed as foils. Roth and O’Brien investigate difference by depicting relationships that cross these boundaries. Through understanding the complex interrelations at play between the fiction of Roth and O’Brien, and between their work and that of a wider pantheon of Irish and American writers, this thesis will reposition both as transnational authors while developing a culturally sensitive, textually nuanced account of their transatlantic literary relations.

The quality of financial information in the extractive industries: a value relevance analysis

The extractive industry is characterized by high levels of risk and uncertainty. These attributes create challenges when applying traditional accounting concepts (such as the revenue recognition and matching concepts) to the preparation of financial statements in the industry. The International Accounting Standards Board (2010) states that the objective of general purpose financial statements is to provide useful financial information to assist the capital allocation decisions of existing and potential providers of capital. The usefulness of information is defined as being relevant and faithfully represented so as to best aid in the investment decisions of capital providers. Value relevance research utilizes adaptations of the Ohlson (1995) to assess the attribute of value relevance which is one part of the attributes resulting in useful information. This study firstly examines the value relevance of the financial information disclosed in the financial reports of extractive firms. The findings reveal that the value relevance of information disclosed in the financial reports depends on the circumstances of the firm including sector, size and profitability. Traditional accounting concepts such as the matching concept can be ineffective when applied to small firms who are primarily engaged in nonproduction activities that involve significant levels of uncertainty such as exploration activities or the development of sites. Standard setting bodies such as the International Accounting Standards Board and the Financial Accounting Standards Board have addressed the financial reporting challenges in the extractive industry by allowing a significant amount of accounting flexibility in industryspecific accounting standards, particularly in relation to the accounting treatment of exploration and evaluation expenditure. Therefore, secondly this study examines whether the choice of exploration accounting policy has an effect on the value relevance of information disclosed in the financial reports. The findings show that, in general, the Successful Efforts method produces value relevant information in the financial reports of profitable extractive firms. However, specifically in the oil & gas sector, the Full Cost method produces value relevant asset disclosures if the firm is lossmaking. This indicates that investors in production and non-production orientated firms have different information needs and these needs cannot be simultaneously fulfilled by a single accounting policy. In the mining sector, a preference by large profitable mining companies towards a more conservative policy than either the Full Cost or Successful Efforts methods does not result in more value relevant information being disclosed in the financial reports. This finding supports the fact that the qualitative characteristic of prudence is a form of bias which has a downward effect on asset values. The third aspect of this study is an examination of the effect of corporate governance on the value relevance of disclosures made in the financial reports of extractive firms. The findings show that the key factor influencing the value relevance of financial information is the ability of the directors to select accounting policies which reflect the economic substance of the particular circumstances facing the firms in an effective way. Corporate governance is found to have an effect on value relevance, particularly in the oil & gas sector. However, there is no significant difference between the exploration accounting policy choices made by directors of firms with good systems of corporate governance and those with weak systems of corporate governance.