Comparative proteomics of excretory-secretory proteins released by the liver fluke Fasciola hepatica in sheep host bile and during in vitro culture ex host

Russell M. Morphew, Hazel A. Wright, E. James LaCourse, Debra J. Woods and Peter M. Brophy (2007). Comparative proteomics of excretory-secretory proteins released by the liver fluke Fasciola hepatica in sheep host bile and during in vitro culture ex host. Molecular and Cellular Proteomics, 6 (6), 963-972. Sponsorship: BBSRC / EU RAE2008

INVESTIGATION OF OCEAN ACOUSTICS USING AUTONOMOUS INSTRUMENTATION TO QUANTIFY THE WATER-SEDIMENT BOUNDARY PROPERTIES

Sound propagation in shallow water is characterized by interaction with the oceans surface, volume, and bottom. In many coastal margin regions, including the Eastern U.S. continental shelf and the coastal seas of China, the bottom is composed of a depositional sandy-silty top layer. Previous measurements of narrow and broadband sound transmission at frequencies from 100 Hz to 1 kHz in these regions are consistent with waveguide calculations based on depth and frequency dependent sound speed, attenuation and density profiles. Theoretical predictions for the frequency dependence of attenuation vary from quadratic for the porous media model of M.A. Biot to linear for various competing models. Results from experiments performed under known conditions with sandy bottoms, however, have agreed with attenuation proportional to f1.84, which is slightly less than the theoretical value of f2 [Zhou and Zhang, J. Acoust. Soc. Am. 117, 2494]. This dissertation presents a reexamination of the fundamental considerations in the Biot derivation and leads to a simplification of the theory that can be coupled with site-specific, depth dependent attenuation and sound speed profiles to explain the observed frequency dependence. Long-range sound transmission measurements in a known waveguide can be used to estimate the site-specific sediment attenuation properties, but the costs and time associated with such at-sea experiments using traditional measurement techniques can be prohibitive. Here a new measurement tool consisting of an autonomous underwater vehicle and a small, low noise, towed hydrophone array was developed and used to obtain accurate long-range sound transmission measurements efficiently and cost effectively. To demonstrate this capability and to determine the modal and intrinsic attenuation characteristics, experiments were conducted in a carefully surveyed area in Nantucket Sound. A best-fit comparison between measured results and calculated results, while varying attenuation parameters, revealed the estimated power law exponent to be 1.87 between 220.5 and 1228 Hz. These results demonstrate the utility of this new cost effective and accurate measurement system. The sound transmission results, when compared with calculations based on the modified Biot theory, are shown to explain the observed frequency dependence.

A FLOW-THROUGH ACOUSTIC WAVEGUIDE FOR TWO-PHASE BUBBLY FLOW VOID FRACTION MEASUREMENT

In the Spallation Neutron Source (SNS) facility at Oak Ridge National Laboratory (ORNL), the deposition of a high-energy proton beam into the liquid mercury target forms bubbles whose asymmetric collapse cause Cavitation Damage Erosion (CDE) to the container walls, thereby reducing its usable lifetime. One proposed solution for mitigation of this damage is to inject a population of microbubbles into the mercury, yielding a compliant and attenuative medium that will reduce the resulting cavitation damage. This potential solution presents the task of creating a diagnostic tool to monitor bubble population in the mercury flow in order to correlate void fraction and damage. Details of an acoustic waveguide for the eventual measurement of two-phase mercury-helium flow void fraction are discussed. The assembly’s waveguide is a vertically oriented stainless steel cylinder with 5.08cm ID, 1.27cm wall thickness and 40cm length. For water experiments, a 2.54cm thick stainless steel plate at the bottom supports the fluid, provides an acoustically rigid boundary condition, and is the mounting point for a hydrophone. A port near the bottom is the inlet for the fluid of interest. A spillover reservoir welded to the upper portion of the main tube allows for a flow-through design, yielding a pressure release top boundary condition for the waveguide. A cover on the reservoir supports an electrodynamic shaker that is driven by linear frequency sweeps to excite the tube. The hydrophone captures the frequency response of the waveguide. The sound speed of the flowing medium is calculated, assuming a linear dependence of axial mode number on modal frequency (plane wave). Assuming that the medium has an effective-mixture sound speed, and that it contains bubbles which are much smaller than the resonance radii at the highest frequency of interest (Wood’s limit), the void fraction of the flow is calculated. Results for water and bubbly water of varying void fraction are presented, and serve to demonstrate the accuracy and precision of the apparatus.

Neural Network and Bioinformatic Methods for Predicting HIV-1 Protease Inhibitor Resistance

This article presents a new method for predicting viral resistance to seven protease inhibitors from the HIV-1 genotype, and for identifying the positions in the protease gene at which the specific nature of the mutation affects resistance. The neural network Analog ARTMAP predicts protease inhibitor resistance from viral genotypes. A feature selection method detects genetic positions that contribute to resistance both alone and through interactions with other positions. This method has identified positions 35, 37, 62, and 77, where traditional feature selection methods have not detected a contribution to resistance. At several positions in the protease gene, mutations confer differing degress of resistance, depending on the specific amino acid to which the sequence has mutated. To find these positions, an Amino Acid Space is introduced to represent genes in a vector space that captures the functional similarity between amino acid pairs. Feature selection identifies several new positions, including 36, 37, and 43, with amino acid-specific contributions to resistance. Analog ARTMAP networks applied to inputs that represent specific amino acids at these positions perform better than networks that use only mutation locations.

St. Columba, Silnán, and the 'Male Bovine' (VC 2.17)

At Vita Columbae VC 2.17, Adomnán has severely misunderstood a written source which originally described how Columba ordered one party to a dispute, an alleged maleficus ‘evil-doer’ called Silnán, to milk a sick cow in order to settle the dispute by demonstrating that its contaminated milk was the real, hidden cause of the harm which had occasioned the dispute. Adomnán misread a description of a bos maculosus ‘pock-marked bovine’ to refer to a bos masculus ‘male bovine’, and proceeded to misunderstand the story as the description of some form of contest between Columba and a maleficus ‘sorcerer’.

Dr. Richard Caulfield: antiquarian, scholar and academic librarian

The history of higher learning in Cork can be traced from its late eighteenth-century origins to its present standing within the extended confines of the Neo-Gothic architecture of University College, Cork. This institution, founded in 1845 was the successor and ultimate achievement of its forerunner, the Royal Cork Institution. The opening in 1849 of the college, then known as Queen's College, Cork, brought about a change in the role of the Royal Cork Institution as a centre of education. Its ambition of being the 'Munster College' was subsumed by the Queen's College even though it continued to function as a centre of learning up to the 1805. At this time its co-habitant, the School of Design, received a new wing under the benevolent patronage of William Crawford, and the Royal Cork Institution ceased to exist as the centre for cultural, technical and scientific learning it had set out to be. The building it occupied is today known as the Crawford Municipal Art Gallery.

Building effectiveness communication ratios (BECs): an integrated ‘life-cycle’ methodology for mitigating energy-use in buildings

Current building regulations are generally prescriptive in nature. It is widely accepted in Europe that this form of building regulation is stifling technological innovation and leading to inadequate energy efficiency in the building stock. This has increased the motivation to move design practices towards a more ‘performance-based’ model in order to mitigate inflated levels of energy-use consumed by the building stock. A performance based model assesses the interaction of all building elements and the resulting impact on holistic building energy-use. However, this is a nebulous task due to building energy-use being affected by a myriad of heterogeneous agents. Accordingly, it is imperative that appropriate methods, tools and technologies are employed for energy prediction, measurement and evaluation throughout the project’s life cycle. This research also considers that it is imperative that the data is universally accessible by all stakeholders. The use of a centrally based product model for exchange of building information is explored. This research describes the development and implementation of a new building energy-use performance assessment methodology. Termed the Building Effectiveness Communications ratios (BECs) methodology, this performance-based framework is capable of translating complex definitions of sustainability for energy efficiency and depicting universally understandable views at all stage of the Building Life Cycle (BLC) to the project’s stakeholders. The enabling yardsticks of building energy-use performance, termed Ir and Pr, provide continuous design and operations feedback in order to aid the building’s decision makers. Utilised effectively, the methodology is capable of delivering quality assurance throughout the BLC by providing project teams with quantitative measurement of energy efficiency. Armed with these superior enabling tools for project stakeholder communication, it is envisaged that project teams will be better placed to augment a knowledge base and generate more efficient additions to the building stock.

The development of a computer model to optimize the performance of a 50kWp photovoltaic system

A computer model has been developed to optimize the performance of a 50kWp photovoltaic system which supplies electrical energy to a dairy farm at Fota Island in Cork Harbour. Optimization of the system involves maximising the efficiency and increasing the performance and reliability of each hardware unit. The model accepts horizontal insolation, ambient temperature, wind speed, wind direction and load demand as inputs. An optimization program uses the computer model to simulate the optimum operating conditions. From this analysis, criteria are established which are used to improve the photovoltaic system operation. This thesis describes the model concepts, the model implementation and the model verification procedures used during development. It also describes the techniques which are used during system optimization. The software, which is written in FORTRAN, is structured in modular units to provide logical and efficient programming. These modular units may also be used in the modelling and optimization of other photovoltaic systems.

The utility of survey and administrative data to generate information for research and outcomes-based oral health services development

The aim of this research, which focused on the Irish adult population, was to generate information for policymakers by applying statistical analyses and current technologies to oral health administrative and survey databases. Objectives included identifying socio-demographic influences on oral health and utilisation of dental services, comparing epidemiologically-estimated dental treatment need with treatment provided, and investigating the potential of a dental administrative database to provide information on utilisation of services and the volume and types of treatment provided over time. Information was extracted from the claims databases for the Dental Treatment Benefit Scheme (DTBS) for employed adults and the Dental Treatment Services Scheme (DTSS) for less-well-off adults, the National Surveys of Adult Oral Health, and the 2007 Survey of Lifestyle Attitudes and Nutrition in Ireland. Factors associated with utilisation and retention of natural teeth were analysed using count data models and logistic regression. The chi-square test and the student’s t-test were used to compare epidemiologically-estimated need in a representative sample of adults with treatment provided. Differences were found in dental care utilisation and tooth retention by Socio-Economic Status. An analysis of the five-year utilisation behaviour of a 2003 cohort of DTBS dental attendees revealed that age and being female were positively associated with visiting annually and number of treatments. Number of adults using the DTBS increased, and mean number of treatments per patient decreased, between 1997 and 2008. As a percentage of overall treatments, restorations, dentures, and extractions decreased, while prophylaxis increased. Differences were found between epidemiologically-estimated treatment need and treatment provided for those using the DTBS and DTSS. This research confirms the utility of survey and administrative data to generate knowledge for policymakers. Public administrative databases have not been designed for research purposes, but they have the potential to provide a wealth of knowledge on treatments provided and utilisation patterns.

Challengers to provisional republicanism: the official republican movement, people’s democracy and the Irish republican socialist party, 1968–98

The Provisional IRA and its political wing Sinn Féin have attracted by far the greatest scholarly interest of all the players in the Northern Irish conflict. This emphasis is perfectly legitimate, given the centrality of the Provos to so many turning-points in the conflict, from the collapse of Stormont in the early 1970s to the hunger strikes of the following decade and the ceasefires which were followed by the Belfast Agreement. My project, however, looks at political groups that at one time or another challenged the Provos for leadership of the militant, anti-state constituency in Northern Ireland (chiefly based in the Catholic working class). Although never as large or influential as the Provisional republicans, groups such as the Official IRA and the Irish Republican Socialist Party sometimes had a discernible impact on the course of events which is overlooked by most studies, and often pioneered ideas and tactics that were later adopted by the Provos themselves. The idea that republicans should embrace political action and work in broad campaigning alliances was promoted by the IRSP and socialist groups such as People’s Democracy before it was taken up by Gerry Adams and his allies, while the Official IRA supported the principle of a settlement based on democratization of the Northern Irish state, which was later accepted by Sinn Féin in the form of the Belfast Agreement. The goal of my research is to provide a novel perspective on the conflict in Northern Ireland, while engaging with theoretical debates about its character.

The architecture of influence: Paul Rudolph's Art and Architecture Building at Yale

Focussing on Paul Rudolph’s Art & Architecture Building at Yale, this thesis demonstrates how the building synthesises the architect’s attitude to architectural education, urbanism and materiality. It tracks the evolution of the building from its origins – which bear a relationship to Rudolph’s pedagogical ideas – to later moments when its occupants and others reacted to it in a series of ways that could never have been foreseen. The A&A became the epicentre of the university’s counter culture movement before it was ravaged by a fire of undetermined origins. Arguably, it represents the last of its kind in American architecture, a turning point at the threshold of postmodernism. Using an archive that was only made available to researchers in 2009, this is the first study to draw extensively on the research files of the late architectural writer and educator, C. Ray Smith. Smith’s 1981 manuscript about the A&A entitled “The Biography of a Building,” was never published. The associated research files and transcripts of discussions with some thirty interviewees, including Rudolph, provide a previously unavailable wealth of information. Following Smith’s methodology, meetings were recorded with those involved in the A&A including, where possible, some of Smith’s original interviewees. When placed within other significant contexts – the physicality of the building itself as well as the literature which surrounds it – these previously untold accounts provide new perspectives and details, which deepen the understanding of the building and its place within architectural discourse. Issues revealed include the importance of the influence of Louis Kahn’s Yale Art Gallery and Yale’s Collegiate Gothic Campus on the building’s design. Following a tumultuous first fifty years, the A&A remains an integral part of the architectural education of Yale students and, furthermore, constitutes an important didactic tool for all students of architecture.

The contribution of warlordism to the disintegration of the western Roman army (c. AD 395-480)

My thesis investigates the dynamics behind the changing nature of the leadership of the western Roman army in the fifth century through the concept of ‘warlordism’. I carried this out by analyzing those cases of insubordination and military unrest in the officer class of the western Roman army, which can be shown to be linked to the slow decline of central authority and the imperial office in the period 395-480. My thesis demonstrates that theories of ‘Warlordism’, as developed in social sciences, can be useful for both the late Imperial west as for other eras of ancient history, such as the late Roman republic. Warlordism was a way of continuing politics, if necessary by military means, when commanders found themselves outside the legitimate framework. Unlike the case of usurpation of the imperial office, when there was little hope of achieving permanent recognition and acceptance, it offered insubordinate officers a chance of returning to the ruling imperial regime depending on circumstances and the success of their resistance. I propose that warlordism functioned as an alternative to usurpation, a tool for military dissidence, fuelled by an economy of violence. Contrary to modern warlordism, the warlordism of the fifth century AD represented a transient phase which no imperial commander was willing to prolong indefinitely. At some stage, given the means, warlords in the western Roman army wanted to become part of the imperial echelon again. Yet these alternative methods of violent opposition, and the acquisition of force through private means, ensured the breakdown of the state’s monopoly on violence and the disintegration of centralized armies. What started as an accidental revolution became a new form of military rule.

The effects of copayment policies on adherence to prescription medicines in publicly insured populations

Introduction: Copayments for prescriptions are associated with decreased adherence to medicines resulting in increased health service utilisation, morbidity and mortality. In October 2010 a 50c copayment per prescription item was introduced on the General Medical Services (GMS) scheme in Ireland, the national public health insurance programme for low-income and older people. The copayment was increased to €1.50 per prescription item in January 2013. To date, the impact of these copayments on adherence to prescription medicines on the GMS scheme has not been assessed. Given that the GMS population comprises more than 40% of the Irish population, this presents an important public health problem. The aim of this thesis was to assess the impact of two prescription copayments, 50c and €1.50, on adherence to medicines.Methods: In Chapter 2 the published literature was systematically reviewed with meta-analysis to a) develop evidence on cost-sharing for prescriptions and adherence to medicines and b) develop evidence for an alternative policy option; removal of copayments. The core research question of this thesis was addressed by a large before and after longitudinal study, with comparator group, using the national pharmacy claims database. New users of essential and less-essential medicines were included in the study with sample sizes ranging from 7,007 to 136,111 individuals in different medication groups. Segmented regression was used with generalised estimating equations to allow for correlations between repeated monthly measurements of adherence. A qualitative study involving 24 individuals was conducted to assess patient attitudes towards the 50c copayment policy. The qualitative and quantitative findings were integrated in the discussion chapter of the thesis. The vast majority of the literature on this topic area is generated in North America, therefore a test of generalisability was carried out in Chapter 5 by comparing the impact of two similar copayment interventions on adherence, one in the U.S. and one in Ireland. The method used to measure adherence in Chapters 3 and 5 was validated in Chapter 6. Results: The systematic review with meta-analysis demonstrated an 11% (95% CI 1.09 to 1.14) increased odds of non-adherence when publicly insured populations were exposed to copayments. The second systematic review found moderate but variable improvements in adherence after removal/reduction of copayments in a general population. The core paper of this thesis found that both the 50c and €1.50 copayments on the GMS scheme were associated with larger reductions in adherence to less-essential medicines than essential medicines directly after the implementation of policies. An important exception to this pattern was observed; adherence to anti-depressant medications declined by a larger extent than adherence to other essential medicines after both copayments. The cross country comparison indicated that North American evidence on cost-sharing for prescriptions is not automatically generalisable to the Irish setting. Irish patients had greater immediate decreases of -5.3% (95% CI -6.9 to -3.7) and -2.8% (95% CI -4.9 to -0.7) in adherence to anti-hypertensives and anti-hyperlipidaemic medicines, respectively, directly after the policy changes, relative to their U.S. counterparts. In the long term, however, the U.S. and Irish populations had similar behaviours. The concordance study highlighted the possibility of a measurement bias occurring for the measurement of adherence to non-steroidal anti-inflammatory drugs in Chapter 3. Conclusions: This thesis has presented two reviews of international cost-sharing policies, an assessment of the generalisability of international evidence and both qualitative and quantitative examinations of cost-sharing policies for prescription medicines on the GMS scheme in Ireland. It was found that the introduction of a 50c copayment and its subsequent increase to €1.50 on the GMS scheme had a larger impact on adherence to less-essential medicines relative to essential medicines, with the exception of anti-depressant medications. This is in line with policy objectives to reduce moral hazard and is therefore demonstrative of the value of such policies. There are however some caveats. The copayment now stands at €2.50 per prescription item. The impact of this increase in copayment has yet to be assessed which is an obvious point for future research. Careful monitoring for adverse effects in socio-economically disadvantaged groups within the GMS population is also warranted. International evidence can be applied to the Irish setting to aid in future decision making in this area, but not without placing it in the local context first. Patients accepted the introduction of the 50c charge, however did voice concerns over a rising price. The challenge for policymakers is to find the ‘optimal copayment’ – whereby moral hazard is decreased, but access to essential chronic disease medicines that provide advantages at the population level is not deterred. This evidence presented in this thesis will be utilisable for future policy-making in Ireland.

Totality of experience: sound, music and mythology in Gus Van Sant’s “Death Quartet”

Reflecting on Gus Van Sant’s films Gerry (2003) Elephant (2004) and Last Days (2005), the director’s long-term sound-designer Leslie Shatz observed that “You have to get into the totality of the experience and not just the dialogue”. Shatz’s comment expresses something fundamental about the experimental approach to cinema and to soundscapes undertaken by Van Sant in these three films, unofficially known as the “Death Trilogy”. This thesis contends that Van Sant makes deliberate aesthetic choices which do indicate a distinctly “auteurist” leaning. However, I also argue that intertextual elements, prior knowledge, and audience participation in meaningmaking enhance the experience of, and reveal the nuances in, the soundtracks themselves. This thesis aims to contribute to a growing body of work within filmmusic scholarship concerned with resisting a traditional bias in the field: that film music should be understood as a means of characterisation and as emotional signifier. The films of the “Death Quartet”, which includes Paranoid Park (2007), I believe, offer fertile ground on which to explore these new approaches. It is my contention that these films deconstruct the traditional approach to soundtracking and the relationship between soundtrack and character, and that only an approach sensitive to the aesthetic and philosophical functions of music and sound can adequately acknowledge their unique cinematic qualities.