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Evaluation of an improved sanitisation regime in farrowing accommodation, with/without the use of a competitive exclusion agent, to increase piglet growth and reduce antimicrobial usage
No full textPlacement of Distributed Services on Vehicle Clusters for Sensing Applications
Full text linkVehicular fog computing (VFC) is an extension of cloud and mobile edge computing aimed
to utilise the rich sensing and processing resources available in vehicles. The emergence
of VFC was motivated by the need to reduce latency in delay-sensitive applications, which
makes it infeasible to deploy applications on the cloud. Thus, there emerged a need to
deploy data processing services close to the source of data generation to reduce response
time and bandwidth usage in uploading collected data to the cloud. Most modern vehicles
in the near future will be equipped with plentiful sensing and processing capacity to make
sophisticated decisions related to autonomous driving. The aim of this study is to utilise
the under-utilised resources on these vehicles to deploy data-intensive, over-the-top services
on a group of closely-moving vehicles. With the emergence of data-driven applications
developed in the process of urban informatization, there is a need to collect and process data
in a resource-efficient manner.
In this work, we consider applications where vehicles gather and process data for surveillance
purposes such as studying the interaction of users with roadside cafes and gas stations
etc. or detecting vulnerable pedestrians to increase commuter safety. Our work introduces
methods and techniques to use the historic mobility pattern of vehicles to address the challenge
of dynamism and instability in the vehicular network. To determine the availability of
these resources, a stochastic mobility model is utilised, to select nodes with similar mobility
patterns. Then a distributed and flexible service model and a mobility-aware infrastructure
model are designed that are compatible with an unstable, non-static network. These distributed
services are scaled in real-time and placed as multiple instances on the selected
vehicular cluster to make the services more robust. The service scaling and placement
problem is modelled as a bi-objective, constrained optimisation problem with the objective of
efficient resource utilisation. To place the service chains efficiently on the vehicular clusters,
a community detection-based cluster selection scheme and graph-based service placement
heuristics are introduced. The feasibility of the study is presented by demonstrating results
from extensive simulations using different resource and mobility profiles of vehicle clusters.
The results of the performance of our service scaling and placement scheme indicate that it
performs better than competing schemes in terms of resource utilisation
Novel Process Strategies for the Stabilization of Biopharmaceuticals for Parenteral Use
Full text linkIn the past two decades, biopharmaceuticals have provided a breakthrough in improving the quality of lives of patients with various cancers, autoimmune and genetic disorders etc. With the growing demand of biopharmaceuticals, the need for reducing manufacturing costs is essential without compromising on the safety, quality, and efficacy of products. Freeze-drying is the primary commercial means of manufacturing solid biopharmaceuticals. However, Freeze-drying is an economically unfriendly means of production with long production cycles and heavy capital investment, resulting in high overall costs. This thesis reviews several alternative drying technologies such as continuous Freeze-drying, Spray-drying, Active-freeze-drying, Spray-freeze-drying, PRINT® Technology etc. that have not yet gained popularity for manufacturing parenteral biopharmaceuticals and focuses on assessing the stability of two proteins i.e., Lysozyme by Freeze-drying and Spray-drying, and a commercial therapeutic enzyme by Active-freeze-drying and Spray-drying. The key findings of this thesis showed that lysozyme was a robust protein, and its efficacy was enhanced in the presence of excipients such as sucrose and trehalose post Freeze-drying and Spray-drying. To substantiate experimental results, molecular dynamics simulations were performed that elucidated a conformation change (without unfolding) may have resulted in increased flexibility of the active sites. Furthermore, Enzyme ‘A’, a commercial therapeutic enzyme, was susceptible to process-induced stress post Active-freeze-drying and Spray-drying, thereby, resulting in increased protein aggregation. However, the inclusion of Arg-HCl in the formulation of Enzyme ‘A’ significantly improved the reconstitution time by 63 % and turbidity by 83 % and promoted the suppression of insoluble aggregates post Spray-drying. In agreement with experimental results, molecular dynamics simulations showed that while Arg-HCl was capable of acting as the main stabilizer, it interacted the most with the positively and negatively charged residues on the surface of Enzyme ‘A’ and also acted as a neutral crowder resulting in reduced protein-protein interactions. The last segment of this thesis thoroughly evaluates and discusses the potential of Multi-Angle Dynamic Light Scattering (MADLS) as a 3-in-1 screening tool for the determination of particle size, product concentration and protein aggregation of three proteins including Bovine Serum Albumin (BSA), a commercial monoclonal antibody (mAb) and a therapeutic enzyme. A good calibration curve with an R2 of > 0.95 was obtained between the particle number concentration by MADLS and protein concentration by UV-Vis spectroscopy for the 3 proteins whereas an excellent quadratic correlation (R2 = 0.9938) was observed between MADLS and SEC for the quantitative estimation of protein aggregation in the enzyme. Therefore, the approach provided using MADLS can be employed as a rapid screening method for the analysis of aberrations in different formulations and products prior to other Quality Control (QC) tests to speed up the batch release process.
Overall, some of these alternative drying technologies offer a paradigm shift towards continuous manufacturing and allow controlled dry particle characteristics. The potential impact of these novel technologies can significantly reduce time, energy and costs associated with the manufacturing of biopharmaceuticals. The inclusion of Process Analytical Technology (PAT) and offline characterization techniques (described in Chapter 1), in tandem, provide additional information on the on the Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs) of biopharmaceutical products. Moreover, molecular modelling is a powerful tool that can reveal atomic-scale details to study the mechanisms of interactions of excipients with biologics. These technologies together can be envisaged to increase the manufacturing capacity of biopharmaceuticals at reduced costs as well as open avenues for further research and development
A retrospective case analysis of serious untoward incidents in super catchment mental health services in the HSE South East
Full text linkSerious untoward incidents, occurring in the context of mental health services and mental
disorder, continue to attract widespread concern amongst professionals, policy-makers and
the wider population. Such occurrences can range from the most serious incidence of violence
and self-harm in communities to more minor but often pervasive and distressing incidents of
violence/aggression/self-harm occurring within inpatient or long-term residential health
settings. Mental health services, internationally, have sought to reduce or limit such
occurrences through the implementation of risk management and patient safety strategies.
This study examined serious untoward incidents occurring within mental health services in
the South East of Ireland over an 8 year period. Utilising a database of staff-completed
incident report forms and with access to relevant patient charts, the study examined and
analysed incident types, prevalence, patterns of activity and contributing/contextual factors.
A mixed-method design was utilised, using the established research methods retrospective
chart review and content analysis. A sample of 325 patients charts were examined with
analysis supported by statistical testing.
Violence and aggression was by far the most widely reported incident type, with occurrences
of self-harm mainly limited to acute psychiatric services. Inpatient care was the predominant
location for untoward incidents with a pervasive level of violence and aggression relating to
longer stay and older adult units. Whilst patient factors such as acute mental disorder, history
of trauma and external pressures were recognised as contributory factors in the incident
reports studied, a number of other areas relating to clinician-patient interaction and
organisational/environmental factors were also considered. The potential for conflict or
‘flashpoints’ occurring was a significant finding of the study, particular conflict occurring
amongst patients and violence and aggression in the context of direct clinical care. Issues of
safety, security and risk are considered in relation to the study findings, in addition to an
analysis of the various systems in place governing mental health service provision
EXPLORING THE RELATIONSHIP BETWEEN LEAN LEADERSHIP AND LEAN PRACTICE TO ACHIEVE ORGANISATIONAL LEAN THINKING
Full text linkIt is widely known that the Lean Thinking concept has been a breakthrough business performance enhancer since it was first embraced by the wider global commercial community in the 1990’s. Furthermore, when an organisation is able to embed lean thinking holistically throughout their organisation, the positive results can move beyond profit and actually enrich the lives of all the employees who work within its realm. However, there is also an acknowledgement that lean implementation failures are unacceptably high with as little as one in ten organisations being able to sustain their efforts. This has caused consternation for both lean academic and practitioners alike and as a result not everyone is convinced that attempting to achieve organisational lean thinking is a worthy business endeavour. This has also resulted in significant academic unrest and discussion regarding the claims and assumptions made within the organizational lean thinking literature. The main concern is the lack of knowledge on how organisations successfully implement and embed organizational lean thinking in the long term. The origins of lean literature are rooted in positive ‘feel-good’, practitioner-written vignettes about lean success stories. Even when the discussion is elevated to consider what has been going wrong with lean, it is still limited to positivistic case studies. If and when leadership is discussed as an enabler for sustenance of lean thinking, it tends to focus on listing required leadership traits. There has been little consideration of the complexity of how organisational lean thinking works and the dynamics between lean leadership and lean practice to sustain it. This study has taken an interpretive research approach and utilised a single case-study to explore and fully understand the phenomenon of organisational lean thinking. The findings are rich and have uncovered new knowledge that will help untangle the complexity and provide guidance to lean leaders
Development and Characterisation of Novel Nanoparticle-Loaded Contact Lenses for the Treatment of Posterior Segment Diseases of the Eye
Full text linkTreatment of ocular diseases face challenges such as low drug bioavailability from topical routes and side effects from intravitreal injection (e.g., retinal detachment and infection). The sophisticated ocular anatomy, while protecting the eye, also prevents therapeutic compound from readily reaching the target site. This project aims to address these challenges through the development of a hydrogel soft contact lens (SCL) impregnated with drug:cyclodextrin complex-loaded biodegradable and biocompatible polymeric nanoparticles (NPs) designed for controlled release and enhanced corneal permeation.
Daily disposable hydrogel SCLs (nesofilcon A materials) were successfully fabricated at an academic research lab utilising a comparable process to an industrial commercialized lens manufacturing approach. Naringenin (NAR) was chosen as the drug in this study because of its antioxidant and anti-inflammatory activities as an ocular therapeutic. NAR-loaded SCLs exhibited comparable critical lens parameters with >98% optical transparency, >75% water content, a lens diameter of 14.10-14.20 mm and a Young’s modulus of 0.51-0.55 MPa. A controlled daily drug delivery was achieved within the estimated therapeutic range of 17.88 – 54.42 μg NAR/day.
In order to improve ocular bioavailability and permeation of NAR, a NAR:SBE-ß-CD (sulfobutyl ether-β-cyclodextrin) inclusion complex was formed using a freeze-drying monophasic system approach. A notable increase (6480-fold) in NAR aqueous solubility was obtained arising from complexation. In addition, this complex was used in the synthesis of a NAR-loaded chitosan (CS) NP through an ionic gelation process (333.3 ± 26.6 nm, +22.0 ± 4.3 mV, and a PDI of 0.0777 ± 0.0580). NAR-loaded CS NPs had a %encapsulation efficiency of 37.4 ± 4.0%, while providing a sustained drug release for 30 days through a diffusion-controlled mechanism.
These two drug carrier systems were subsequently loaded into the developed SCLs. Based on the characterized physicochemical properties of the loaded SCLs, a ‘soak and release’ approach was determined to be the optimum method. The release mechanism of NAR in complex- and NP-loaded SCLs was governed by both diffusion and swelling, with a drug release rate of 45.95 ± 2.06 and 45.96 ± 5.18 μg NAR/day, respectively.
The results from this research demonstrated that the developed models could act as promising drug delivery systems to provide a more sustained, less invasive, and controlled delivery of a drug or supplement to the eye. Outcomes from this work suggest potential areas for future work that can lead to the commercialization of the studied technologies
Evolving Skill Mix in the Mental Health Services in Ireland
No full textSkill mix is a topic that is widely discussed within health policy literature and government documents in several countries. There is large variation in terms of what is understood by the concept of ‘skill mix’ and there is a paucity of literature that attempts to analyse this concept. A lack of understanding of the concept can lead to highly localised and inconsistent interpretation and implementation of policy recommendations at local level. A better understanding of the concept of ‘skill mix’ and its attributes is required in order to ensure that the potential of skill mix is maximised.
This study aims to explore the concept ‘skill mix’ and its application in workforce planning in the mental health services in Ireland. The research design consisted of a qualitative case study approach. A framework for the conduct of a comparative systematic international policy review was adopted to place policy in Ireland within a wider context. Individual in-depth interviews were used to collect data from those who engage with and influence policy making in the health services in Ireland, to explore how they conceptualise skill mix. Data derived from these interviews were organised using Computer Aided Qualitative Data Analysis Software (CAQDAS), NVivo 12, and a ‘Framework’ approach was used to manage, analyse and identify themes.
Findings from this study indicate that skill mix is a term that is deliberately ill-defined and misunderstood. The findings contribute towards achieving a better understanding of skill mix through the development of a conceptual model of skill mix for use in the mental health services. This is useful in terms of providing a sense of order to the messiness associated with the term due to its many attributes, as well as the other attributes and terms associated with it and the contextual and political factors that influence it. This has important implications for both policy and practice. It will be useful for policy makers to use this conceptual model as a tool to assist them to identify what dimension(s) of skill mix and corresponding attributes are implicated in the provision of a definition of skill mix that corresponds with what the policy is trying to achieve. This will assist policy makers and clinical stakeholders in ensuring a shared understanding of the concept. This is important as the level of understanding of the term may impact on the degree to which recommendations regarding skill mix are taken up by clinical stakeholders, thus influencing whether workforce policy aspirations in relation to this term are realised
Einstein's Oxford Blackboard : A Unique Historical Artefact
Full text linkEinstein's blackboard is a well-known exhibit at the History of Science Museum at Oxford University. However, it is much less well known that the writing on the board provides a neat summary of a work of historic importance, Einstein's 1931 model of the expanding universe. As a visual representation of one of the earliest models of the universe to be proposed in the wake of Hubble's observations of the nebulae, the blackboard provides an intriguing snapshot of a key moment in modern astronomy and cosmology. In addition, one line on the blackboard that is not in Einstein's 1931 paper casts useful light on some anomalies in the calculations of that paper
Enabling the Convergence of Traditional Electrical Regulatory Framework Documents and Smart Grid Functions Using Digitalisation
Full text linkWith concerted efforts by legislators to reduce CO2 emissions, the ways in which we
produce, regulate, and consume power is going through wholesale changes. These changes
will impact the utilities as they are central components in this shift and will be required to
balance ensuring grid stability against allowing distributed energy sources, which are less
stable than traditional generation, to participate in the supply of "green power" to the grid.
Academia and industry are combining resources to tackle this challenge with advances in
power systems electronics methods, applying advanced ICT technologies and testing new
regulatory and market frameworks and models. This is evident in the Electrical Industry
Regulatory Policies or Network Codes, which is a set of agreed rules between the actors that
participate in the supply, distribution, transmission, and regulation of electrical power. In
Ireland, like many other countries, these codes are contained in static documents and consist
of quantifiable constraints, interspersed with text. The only way to verify, update or interpret
the codes is by humans reading and editing them directly. The work in this thesis, using
cloud-based text mining and graph database management, aims to extract the network codes
from the documents and derive a richer representation of the network codes, while
maintaining their providence and structure, consistent with their representation in the
document. This work derived from two overarching scenarios which encompass the research
questions, motivate the research methodology and help explore the potential impact that the
proposed enriched representation might have on the business processes within the electricity
supply industry. These scenarios are derived from real challenges faced in the industry and
were selected because of their practical interest for energy stakeholders but we also consider
the technical and business potential of our proposed extraction and representation
processes
DEVELOPMENT OF RECOMBINANT ENZYMES TOWARDS THE PRODUCTION OF PHARMACEUTICAL INTERMEDIATES USING BIOTRANSFORMATIONS
Full text linkNitrile compounds are versatile and can be converted into amides, amines, imines, oximes, carboxylic acids, esters and alcohols, encompassing a large group of economically important synthetic intermediates. The pharmaceutical industry particularly requires amides and acids for use as intermediates in the manufacture of many drugs and chemicals. The biotransformation of nitriles mediated by microorganisms has therefore attracted considerable attention in academia and industry as a sustainable alternative to the conventional chemical reactions that require drastic conditions of pH, temperature and pressure, use of metal catalysts, high-energy consumption and low selectivity in the process. Certain bacterial cells contain a nitrile-metabolizing gene; when the corresponding enzyme is incubated in a reaction-mixture containing a nitrile, the nitrile-metabolizing enzyme catalyses the conversion of the nitrile to the corresponding amide or acid. The amide or acid may then be extracted from the reaction mixture. This biological conversion is referred to as a biotransformation and is considered “Green Chemistry”. As a result, the search for microorganisms which contain the enzymes responsible for these biotransformations (nitrilases, NHase and amidases) is crucial.
The main goals of this research were to; isolate bacteria with activity towards three pharmaceutically relevant β-hydroxynitriles from environmental samples collected worldwide; develop a high throughput screening strategy for filamentous fungi with potential for nitrile biotransformation; apply functional metagenomics to search for novel nitrile hydrolyzing enzymes using environmental samples collected in Ireland; and to formulate an appropriate production medium using statistical optimization that can substantially increase nitrilase production.
In this study, we have found three promising bacterial isolates which are source of genes for nitrile-degrading enzymes including, Nocardia coeliaca strain DSM, Klebsiella oxytoca strain JCM1665 and R. erythropolis PR4. The three strains presented with enantiomeric excess of >90 % towards 3-hydroxybutyronitrile (3HBN). Of the three promising isolates, one showed exceptional >99.99 ee % towards 3HBN, indicating that the bacterial isolate is highly enantioselective and possibly enantiospecific with 100 % ee of (S)-acid. In contrast, while most industrial nitrilase enzymes are derived from bacterial sources, the potential of filamentous fungi was explored with a view to industrial use. The fungus Fusarium solani strain F3 was isolated and exhibited exceptional enantioselectivity towards 3-phenylpropionitrile with >99.99 % ee and enantioselectivity towards 3-hydroxybutyronitrile with 98.03 %, indicating the presence of a highly enantioselective enzyme using the whole mycelial cells.
Once an enzyme is characterized and chosen for its desired properties, large scale production in heterologous hosts often becomes essential, with growth conditions requiring optimisation even before scale-up can begin. Acknowledging this frequent need, providing an approach that addresses these technical challenges was demonstrated in this work by integrating two science fields: statistics with microbiology laboratory experiments to optimize the fermentation process parameters. Our results showed that an average of 5.54 mmol/L of nitrilase activity was attained using whole cells in the validation experiment under optimized conditions, which was 66 % higher than the prior yield of 3.33 mmol/L