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Modulation of BK channels by the novel auxiliary subunit, LINGO2
Full text linkLarge conductance Ca2+ activated K+ (BK) channels are ubiquitously expressed transmembrane proteins that govern smooth muscle and neuronal excitability (Latorre et al., 2010; Τao et al., 2017). They are activated by both Ca2+ and cellular depolarisation. The biophysical and pharmacological properties of the channels can be fine-tuned by their regulatory subunits, β1-4, γ1-4 and LINGO1 (Solaro and Lingle, 1992; Knaus et al., 1994; Xia et al., 1999; Gonzalez-Perez and Lingle, 2019; Dudem et al., 2020). The aims of this thesis were as follows:
1.TocharacterisethebiophysicalpropertiesofBK:LINGO2currents.
2. To investigate the effects of oxidation on BK:LINGO2 currents and determine the residues responsible for these effects.
3.ToidentifytheresiduesintheLINGO2tailresponsibleforinactivation.
4. To study the role of non-conserved and conserved charged residues in the cytosolic tail of LINGO2.
5. To examine the contribution of phenylalanine residues positioned in the transmembrane of LINGO2.
HEK cells were transiently co-transfected with BK, LINGO2 and GFP cDNA
(100 ng:500 ng:150 ng). Inside out patches were studied at 37oC, under voltage clamp, using the patch clamp technique with equimolar K+ pipette solutions. Site-directed mutagenesis were carried out to study the role of specific amino acids located in the transmembrane and cytosolic tail of LINGO2. A docking model of LINGO2 with BK was utilised to identify the potential binding partner for several LINGO2 residues in BK channels. The main findings of this thesis are:
1. LINGO2isanovelauxiliarysubunitofBKchannels.
2. BK:LINGO2 currents can be modulated by redox reactions and oxidation of M603 and M605 in the C-terminus of LINGO2 tail inhibits the inactivation.
3.TheconservednegativelychargedaminoacidsinLINGO2tailcontributetothe voltage-dependent activation in BK:LINGO2 channels.
4.Mutationoffourphenylalanineresidues(F550,F552,F558&F560)toalanine in the TM domain of LINGO2 reduced the negative shift in V1/2, suggesting that these residues are important in mediating the effects of LINGO2 on activation V1/2.
5.TheF552AmutantintheLINGO2TMregionabolishedinactivation,suggesting that this residue plays a critical role in positioning the LINGO2 tail to permit inactivation
A Risk Management Framework for Data Security and Privacy of Wireless Body Area Network based Healthcare Applications
Full text linkWireless Body Area Network (WBAN) based applications are gaining popularity due to recent
advances in sensor technology, integrated circuits, mobile apps and wireless communication.
The literature review conducted as part of this research indicates that the most challenging
issues related to developing a WBAN based healthcare application are energy efficiency,
antenna design, assuring quality of service, and security and privacy. WBAN applications
operate in environments where people may have open internet access, making the application
vulnerable and open to larger attack surfaces. Attacks can affect the performance and
availability of the service, sometimes leading to life-threatening situations or even death.
Through the literature review and an interview with one WBAN development organisation,
this research has identified that assuring security and privacy while collecting, transmitting,
processing, and storing personal health record (PHR) data is a key challenge for developers.
The reasons for this challenge include (i) developers have limited knowledge of marketspecific regulatory requirements and standards, and (ii) there are a vast number of controls
with insufficient implementation detail. The literature review also found no complete solution
exists for assuring data security and privacy while also meeting the regulatory requirements
for WBAN based healthcare applications.
To address these challenges for assuring security and privacy, this research has developed a
data security and privacy risk management (WBANSecRM) framework that will assist the
developer in assuring security and privacy of the data and put them on the path to regulatory
compliance. The framework outlines the process to identify the list of assets, threats, and
vulnerabilities specific to WBAN applications. The framework also consists of a
comprehensive list of controls, along with implementation details to mitigate the threats and
vulnerabilities. The framework has been validated by implementation in an organisation that
develops WBAN applications and was further validated by expert review
Exploring Patterns of Engagement with Digital Health Technologies Amongst Older Adults Living with Multimorbidity
Full text linkMultiple chronic conditions (multimorbidity) are becoming more prevalent amongst ageing populations. Digital health technologies have the potential to assist in the self-management of multimorbidity, supporting monitoring of symptom and well-being parameters, improving a person’s awareness of their health and well-being, supporting a better understanding of the disease(s), encouraging health behaviour change and ultimately resulting in improved health outcomes. However, little research has explored the long-term engagement of older adults with such digital interventions.
The aim of this PhD project was to analyse how 60 older adults (average age=74 ± 6.4 [65-92 years]) with multimorbidity (two or more of the conditions diabetes, heart failure, heart disease, chronic obstructive pulmonary disorder (COPD)) engaged with digital symptom and well-being monitoring when using the ProACT digital health platform over a period of approximately 12 months. For the purposes of this thesis, only 56 participants' data records were used in the data analysis phase, as four participants had no data records in the dataset. The ProACT platform consisted of a suite of digital devices (for example a blood pressure monitor, blood glucometer, pulse oximeter, weight scales, and activity and sleep tracker) and the ProACT CareApp which participants used to view their data, self-report on other areas of health and well-being not measurable by a digital device (such as breathlessness, mood), set goals and receive education. Three studies were carried out on the resulting quantitative dataset. In the first study, data analysis focused on user retention, frequency of monitoring, intervals in monitoring and patterns of daily engagement. During the second study, principal component analysis and clustering analysis were used to group participants based on their levels of engagement, and the data analysis focused on characteristics such as age, gender and chronic health conditions, engagement outcomes and symptom outcomes of the different clusters that were discovered. In the final study, the weekly submission times for each parameter were used to obtain an engagement score (ES) and this score was compared with the Mobile Device Proficiency Score (MDPS), a measure of an older adult’s technical proficiency with mobile devices. Both cluster analysis and multiple regression were used in this study to explore whether participants’ engagement with digital health technology was related to their mobile device proficiency.
The findings from the studies show that the overall engagement with the ProACT digital health platform was high, with more than 80% of participants using the technology devices for over 200 days. The submission frequency for different symptom parameters (e.g. blood glucose, blood pressure, etc.) was between three and four times per week which was higher than that of self-report (2.24) and weight (2.84). Submissions of activity (6.12) and sleep (5.67) were more frequent. The majority of interactions happened in the morning time. The most common time of submission for symptom parameters was 10 am, whereas 8 am was the most common time for weight measurements. In addition, three clusters were identified: the typical user group (n = 24), the least engaged user group (n = 13), and the highly engaged user group (n = 17) in the second stage of analysis. The findings indicate that gender and the types of chronic conditions do not influence engagement. Whether the same device was used to submit different health and/or well-being parameters; the number of manual operations required to take a reading; and the daily routine of the participants were the three primary factors influencing engagement. Findings also indicate that higher levels of engagement may improve the participants’ outcomes (e.g., reduce symptom exacerbation, and increase physical activity). Finally, results from the third study indicate that engagement with digital health technology has a weak correlation with mobile device proficiency in older adults. Despite participants having low to modest technical proficiency, the majority engaged with the platform for the duration of the trial.
The findings highlight the patterns of engagement of older adults with complex chronic diseases with a digital home-based self-management platform and demonstrate the potential of a digital health platform, such as ProACT, to empower older adults with multimorbidity to engage in digital self-management. Based on the findings, a series of recommendations for researchers, designers and developers of digital health technologies are provided. For example, engagement might be enhanced by delivering reminders in the mornings and reducing the number of manual operations required to use monitoring devices. The outcomes of this PhD also have possible implications spanning digital inclusion policies, health outcomes, health systems, cost-effectiveness, and health policy. For example, through the use of digital health technologies, older adults might potentially have better health outcomes, which could ultimately reduce healthcare costs for both patients and healthcare systems
A NEED FOR PIED PIPERS?: MAKING CONNECTIONS IN A COMMUNITY ARTS SONG-MAKING PROJECT
Full text linkMusic and musicking are powerful contributors to a sense and
awareness of place. A community music project in 2021 focused on the small town of Dunleer on the east coast of Ireland. Overshadowed by the larger towns of Dundalk and Drogheda to the north and south respectively, Dunleer has a rich history and many opportunities for the local community to engage in the arts. However, despite much talent, the groups and individuals involved are largely disconnected from and sometimes unaware of each other. This paper considers how a participatory, arts-based virtual project that sought to encourage collaboration through artistic endeavour highlighted the potential for greater collaboration between stakeholders to achieve increased participation in the arts and the local community. Drawing on the author’s perspective as an artist and lead facilitator, it details the process and critiques the role of various stakeholders in the project, incorporating an autoethnographic approach that focuses on the role of third-party facilitators in community music initiatives
Development of BEM-AD model for optimisation of Horizontal Axis Tidal Current Turbine Arrays
Full text linkAdvancement and improvement of new and efficient techniques to meet the ever- increasing energy demand for economic and social development are of significant interest. Renewable energy technologies offer an appealing option to supply this growing electricity demand, while also assisting with the European Union’s policy on sustainability. Ireland has excellent tidal energy resources which can be utilised to meet future energy goals. However, significant research and development is still needed to realise Ireland’s tidal energy potential. tidal current turbines (TCTs) are at an early stage of development, particularly the deployment of devices in arrays, thus more studies and investigations are required on wake interactions between tur- bines to optimise array performance via numerical modelling. Computational Fluid Dynamics (CFD) is a very suitable numerical method to study TCT arrays, but high computational cost is needed to obtain high-accuracy results. For that reason, the development of low computational cost numerical models with suitable accuracy is paramount.
In this work, a numerical model was developed to predict the wake effects of a tidal current turbine for array optimisation with a focus on downstream velocity, turbulence intensity and energetic predictions. The first stage of the work focused on developing and enhancing a single-turbine model by coupling Actuator Disk (AD) theory and Blade Element Momentum (BEM) theory to model turbine wake effects known as BEM-AD model. Variations and hybrid models were developed to further improve prediction of downstream wake effects. In the second stage of the work, a multiple turbine wake interaction study was performed to evaluate hydrodynamically, the array spacing, array arrangement, effects of turbine sizes and the placement of turbines at different depths in the water column. For the third stage of the work, an optimised TCT array model was developed and evaluation was conducted for a range of different domain conditions. Finally, a case study on the Shannon Estuary was conducted to assess the tidal current turbine array model’s energetic performance in a pseudo-transient state
Ensemble modeling of lake evaporation under climate change
Full text linkApproximately 87% of the freshwater on Earth resides in lakes, making them a critical resource for freshwater. Due to the open-water nature of lakes, evaporation is typically the main water loss in most lakes. Therefore, understanding lake evaporation responses to climate change is of paramount importance for the development of mitigation and adaptation strategies. In spite of the complexity of evaporation as a physical process, many studies simulate and quantify lake evaporation using single mechanistic models. The primary objective of this dissertation is to investigate lake evaporation responses to climate change using an ensemble of lake-climate models (i.e., different lake models driven by various climate models) under historic and future climate change scenarios. The dissertation consists of the analyses of local (i.e., lake-specific), regional (i.e., continental), and global lake evaporation simulations over the 20th and 21st centuries (1901-2099) under historic and future scenarios of climate change from the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP) round 2b. Firstly, an evaluation of the differences in lake evaporation estimates among the model ensemble during the historic period was undertaken for a single lake with high socio-economic and political relevance. Furthermore, future lake evaporation projections for this lake are provided by the end of the 21st century. Secondly, the analysis was upscaled to 23 lakes located in Europe, where the association between lake morphometry and evaporation was investigated. Furthermore, historic and future changes in evaporation are reported for these European lakes, along with their implications for water availability. Thirdly, global lake evaporation simulations for 13K ‘representative lakes’ are assessed for historic and future scenarios of climate change. Spatial patterns among the lake-climate model ensemble are evaluated for distinct lake thermal regions. In addition, the associated uncertainties in future evaporation projections and the changes by the end of the century are calculated. Overall, this dissertation highlights the importance of using a multi-model approach for the prediction of lake evaporation responses to global warming and the need to inform the uncertainties associated with evaporation estimation
Assessing environmental distribution and stakeholder awareness of microplastics: A case study in Dundalk Bay
Full text linkMicroplastics have fast become a pollutant of ubiquitous nature in the environment, documented in pristine and remote regions worldwide and recently in humans. While studies on microplastics in marine environments are more established, comparatively understudied is the freshwater environment, with freshwater research generally focusing on larger rivers. Further to this, little work has been completed understanding the social aspect of microplastics despite it being an anthropogenically-caused pollutant. Additionally, the majority of studies completed on assessing microplastic presence are one dimensional in nature focusing on one environmental compartment, however, microplastics released into the environment can interact with numerous biota and travel between terrestrial, freshwater and marine systems. In light of these factors the research in this thesis therefore presents a holistic approach to microplastic pollution in Dundalk Bay and its associated freshwater inputs, while examining stakeholders in Irish fishing relationship with plastic. An important nursery for all commercial fish species in the Irish Sea, sustaining both a productive cockle and razor clam fishery and serving as a vital overwintering refuge for thousands of seabirds, the ecological and economic benefits of a healthy ecosystem here are numerous. In spite of these factors Dundalk Bay has until now been unstudied in terms of microplastics pollution and while its shallow nature with many freshwater inputs lend to a productive environment these factors may contribute to the accumulation of microplastics here and it being a hotspot for this pollutant. The results of this study indicate that microplastics are polluting the marine environment and associated freshwater environment of Dundalk Bay. Microplastics primarily fibrous in nature were documented in surface water, sediment and G. duebeni examined in freshwater rivers as well as in marine intertidal sediments and inhabitants of this shallow marine environment. Those surveyed within the Irish fishing community were aware of microplastic pollution pertaining to aquatic environments moreso than the terrestrial and noticed litter frequently and in large quantities when taking part in fishing activities but were also likely to remove it from the environment highlighting the role that fishers can have in reducing secondary microplastic pollution in more remote environments. The ubiquitous presence of microplastics in environs studied in this thesis highlight the need for mitigation with regards to this pollutant entering the environment
An Exploration of the Experiences of Home Health Care Assistants working through the COVID-19 pandemic
Full text linkBackground: The number of older people living in Ireland and globally has grown in recent years. The demand for home care services in Ireland is predicted to rise exponentially. However, home care organisations face challenges with the recruitment and retention of Home Health Care Assistants. Job resources have been shown to positively influence an employee’s experience of their job whilst also positively impacting retention rates. Literature on the experiences of home health care assistants (HHCAs) working in Ireland is scarce, and the resources required by HHCAs to remain in post are predominantly unexplored.
Aims: This study aimed to understand the lived experiences of HHCAS.
Objectives: The objectives of the study were to; (1) To explore the experience of delivering care as a HHCA, (2) To establish how work demands affect HHCAs (3) To identify resources needed to support retention of HHCAs.
Methods: A Qualitative explorative study consisting of online interviews with ten HHCAs who had a minimum of six months of experience working in home care settings. Thematic analysis was undertaken on the data.
Results: HHCAs experienced challenges and demands within their role before the COVID-19 pandemic. Some of these challenges were emphasised as a result of the COVID-19 pandemic. Additionally, the COVID-19 pandemic introduced new challenges within the HHCA's job. The challenges outlined by HHCAs included; time pressure, challenges to providing PCC and social isolation. Finally, this study identified that HHCAs require resources that enable them to provide PCC optimising their ability to make a difference in their clients’ lives.
Conclusion: Participants explained that their jobs as HHCAs required more than completing tasks yet also a personal and emotional connection between them and their clients. Participants described this emotional connection also extended towards their co-workers as they described a sense of community support they experienced from their colleagues. A key area that participants identified was the need for social inclusion among HHCAs. Additional research is required to establish how the addition of these resources may influence the work experience of HHCAs. Given the current recruitment and retention issues faced by HCOs across Ireland, this research offers valuable insight into the resource needs identified by HHCAs, namely the recognition of the value and importance of HHCAs to establish a positive rapport with their clients through delivering PCC
Digital bother and burden in older age: a transnational LEGO® Serious Play® exploration
Full text linkBother and burden are terms associated with older persons in the management of a range of health conditions. As healthcare becomes more digitalized, older persons are encouraged to use
digital health and wellbeing technologies to manage their own self-care. To date, however, there has been little examination of how bother, as distinct from burden, with such technologies may impact engagement with digital self-management of personal health and wellbeing. Using the LEGO® Serious Play® method, the concepts of bother and burden are examined with older persons in Ireland and Belgium. Findings have implications for the successful implementation of digital health technology solutions intended for use by older citizens as well as the use of the LEGO® Serious Play® method in living lab context
Using Agile Practices to Address Defects in Medical Device Software Development: A Survey of Medical Device Software Organisations in Ireland
Full text linkAgile Practices are widely used in the noncritical software development domain and are advocated to reduce defects. However, there is limited evidence in the existing
literature about their exclusive implementation in Medical Device Software (MDS) development. Prior research has shown that agile practices are often integrated into traditional approaches for specific purposes, but there is little evidence in the existing literature about using agile practices specifically for addressing defects in MDS development. Through a survey of MDS organisations in Ireland, this study investigated the use of agile practices for addressing defects. The findings revealed that
organisations implement agile practices for addressing defects, but prioritise identifying defects during coding and testing phases, primarily using code review, unit testing, integration testing, and coding standards. Defect identification usually occurs in the later part of the software development cycle. However, addressing defects late in the software development cycle can lead to costly rework and potential catastrophes when defects slip into the final product. We argue that in MDS development, both defect prevention and identification should be prioritised and implemented to manage defects more effectively and comprehensively. This approach could help to avoid costly rework and potential consequences arising due to defects that occur later. Agile practices can help in preventing defects early in the software development process and identifying those that slip to later stages, thereby ensuring overall software quality