A Novel Role for FERM Domain-Containing Protein 3 in CKD

Background: Currently, there are limited methods to link disease severity and risk of disease progression in CKD. To better understand this potential relationship, we interrogated the renal transcriptomic profile of individuals with CKD with measures of CKD severity and identified protein 4.1, ezrin, radixin, moesin-domain containing protein 3 (FRMD3) as a candidate gene for follow-up study.MethodsRNA-sequencing was used to profile the transcriptome of CKD biopsies from the North Dublin Renal BioBank, the results of which were correlated with clinical parameters. The potential function of FRMD3 was explored by interrogating the FRMD3 interactome and assessing the effect of lentiviral mediated FRMD3 knock down on human renal proximal tubule epithelial cells by assessing cell viability, metabolic activity, and structural markers.Results: We identified a subset of 93 genes which are significantly correlated with eGFR and percentage tubulointerstitial fibrosis at time of biopsy and with CKD progression 5 years postbiopsy. These results were validated against transcriptomic data from an external cohort of 432 nephrectomy samples. One of the top-ranking genes from this subset, FRMD3, has previously been associated with the risk of developing diabetic kidney disease. Interrogating the interactome of FRMD3 in tubule epithelial cells revealed interactions with cytoskeletal components of cell-cell junctions. Knockdown of FRMD3 expression in tubule epithelial cells resulted in increased proapoptotic activity within the cells, as well as dysregulation of E-Cadherin. Conclusions: We have identified a panel of kidney-specific transcripts correlated with severity and progression of kidney disease, and from this, we have identified a possible role for FRMD3 in tubule cell structure and health.Science Foundation Irelan

Multi-Objective Grammar-Guided Genetic Programming for Grammar-Obeying Program Synthesis

Grammar-obeying program synthesis is a subfield of program syn- thesis (i.e., the task of automatically discovering an executable piece of code) that requires generated code to follow a Backus-Naur Form (BNF) grammar. Having code that obeys a grammar limits the structure of the code and the set of callable functions/method- s/libraries, thus having an impact on (i) security: e.g., using ma- licious functionalities, blacklisted libraries, and questionable con- structs, (ii) the computing environment: e.g., if the hardware is not able to run some functions or if some functions are too costly in terms of memory or energy, and (iii) code quality: improving code style and readability, reducing code smells, and enhancing consistency. Grammar-Guided Genetic Programming (G3P) is recognised as one of the most successful approaches for grammar-obeying pro- gram synthesis that evolves programs in arbitrary languages to solve program synthesis problems based on a set of input-output examples and predefined BNF grammars. Despite its success, the restriction on the evolutionary system to only leverage input-output error rate during its assessment of the programs it derives lim- its its scalability to larger and more complex program synthesis problems. Alternatively, while large language models (LLMs) are showing increasing success in program synthesis from a task de- scription, they often struggle to generate accurate code due to am- biguity in task specifications, complex programming syntax, and lack of reliability in the generated code. Furthermore, their gener- ative nature limits their ability to fix erroneous code with iterative LLM prompting. In this thesis, I focus on enhancing the performance of G3P for grammar-obeying program synthesis tasks. I begin by evaluating the state-of-the-art systems, including G3P and LLMs, in grammar- obeying program synthesis. Next, I explore how to map LLM- generated code into grammar-obeying forms, followed by seeding the grammar-mapped LLM-generated code into G3P’s initial pop- ulation to improve the evolutionary process. Building on these foundations, I investigate the potential of using code similarity measures to guide the evolution of programs, leading to the devel- opment of Bi-Objective Grammar-Guided Genetic Programming (BOG3P) and Multi-Objective Grammar-Guided Genetic Program- ming (MOG3P), which combine input-output error rate with mul- tiple similarity measures as objective functions. Finally, I integrate LLM-generated code into the MOG3P framework in two ways: (i) using LLM-generated code as a seed for the evolutionary pro- cess through a grammar-mapping phase, and (ii) leveraging multi- ple similarity measures towards LLM-generated code to guide the search process throughout the evolution. Additionally, I further extend the MOG3P framework by incorporating code from multi- ple LLMs to enhance the diversity and effectiveness of the search process

Mudie's Select Library and the Shelf Life of the Nineteenth–Century Novel

Mudie's Select Library was a major nineteenth-century literary institution. Substantially larger than its competitors, the library leveraged regional and global distribution networks and close commercial ties with publishers which allowed it to maintain a key position within the British publishing industry. In its heyday, it was widely believed that novelists and publishers were required to conform to aesthetic, moral and formal standards established by Mudie's, or risk the rejection and consequent failure of their books. However, the lack of a comprehensive study of the library's holdings leaves open questions about what the library actually stocked, and to what extent the library could determine a novel's fate. This Element describes a data analysis of a collection of Mudie's catalogues spanning eighty years, in order to reassess understandings of the library's role in the nineteenth-century publishing industry.European Commission Horizon 202

Secondary school staff experiences of supporting and promoting adolescent mental health in Ireland

Teachers and other school staff are increasingly relied on to address student mental health in secondary schools in Ireland. As part of the Wellbeing Policy Statement and Framework for Practice (2019), the Department of Education set out the ambition to place the promotion of wellbeing at the core and ethos of all schools in Ireland by 2023. This study investigates secondary school staff’s experiences of addressing mental health in schools through qualitative analysis of open question data provided by n = 359 school staff. Reflexive thematic analysis was used to analyse the data, resulting in three themes. The themes highlighted the salience of mental health in schools, the wide variety of ways mental health is integrated in Irish secondary schools, and how mental health in schools can be a source of pressure for staff. The findings of this study suggest that staff, while generally positive towards mental health engagement in schools, do not feel adequately prepared to deliver this content to the extent expected of them. Findings are discussed in relation to the Wellbeing Framework as well as the existing international literature on school based mental health content, and implications for policy and practice are proposed.Irish Research CouncilUpdate citation details during checkdate report - ROR18 month embargo - RO

Radiography students' experience of clinical education amidst the COVID-19 pandemic

Purpose: The COVID-19 pandemic has signifi cantly impacted clinical practice. This study explored the impact of the pandemic on diagnostic radiography clinical education from the perspective of radiography students internationally. Materials and methods: A qualitative approach was used to gain insight into students' experience of clinical placement during the pandemic. A total of sixteen radiography students from six countries were recruited from an international Radiography summer research school. Qualitative data was gathered via three semi-structured focus groups (5-6 students per focus group). Data was analysed using Braun and Clark’s phases of thematic analysis. Results: Five key themes emerged in relation to clinical education during the COVID-19 pandemic, (i) unequal student access to personal protective equipment (PPE) (ii) challenges in achieving clinical learning outcomes (iii) impact of online education on clinical readiness (iv) emotional impact, and (v) coping strategies. Students indicated that they were particularly afraid of transmitting COVID-19 to their family and friends. Some students reported that they felt under pressure to receive COVID-19 vaccinations prior to clinical practice. Others reported confusion with respect to infection control guidelines and application of PPE. Conclusion: Student radiographers identifi ed key challenges which require consideration by educators to ensure students are appropriately prepared for and supported on clinical placement during a pandemic. Implications for practice: • The COVID-19 pandemic has impacted clinical education internationally and this study identifi es the implications for radiography students in terms of clinical readiness and their clinical placement experience. • Simulation-based in-person learning in the X-ray lab and PPE training were perceived by students to be important factors impacting clinical readiness

Enzyme-functionalized mesoporous silica nanoparticles to target Staphylococcus aureus and disperse biofilms

Background: Staphylococcus aureus biofilms pose a unique challenge in healthcare due to their tolerance to a wide range of antimicrobial agents. The high cost and lengthy timeline to develop novel therapeutic agents have pushed researchers to investigate the use of nanomaterials to deliver antibiofilm agents and target biofilm infections more efficiently. Previous studies have concentrated on improving the efficacy of antibiotics by deploying nanoparticles as nanocarriers. However, the dispersal of the extracellular polymeric substance (EPS) matrix in biofilm-associated infections is also critical to the development of novel nanoparticle-based therapies. Methods: This study evaluated the efficacy of enzyme-functionalized mesoporous silica nanoparticles (MSNs) against methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) biofilms. MSNs were functionalized with the enzyme lysostaphin, which causes cell lysis of S. aureus bacteria. This was combined with two other enzyme functionalized MSNs, serrapeptase and DNase I which will degrade protein and eDNA in the EPS matrix, to enhance eradication of the biofilm. Cell viability after treatment with enzyme-functionalized MSNs was assessed using a MTT assay and CLSM, while crystal violet staining was used to assess EPS removal. Results: The efficacy of all three enzymes against S. aureus cells and biofilms was significantly improved when they were immobilized onto MSNs. Treatment efficacy was further enhanced when the three enzymes were used in combination against both MRSA and MSSA. Regardless of biofilm maturity (24 or 48 h), near-complete dispersal and killing of MRSA biofilms were observed after treatment with the enzyme-functionalized MSNs. Disruption of mature MSSA biofilms with a polysaccharide EPS was less efficient, but cell viability was significantly reduced. Conclusion: The combination of these three enzymes and their functionalization onto nanoparticles might extend the therapeutic options for the treatment of S. aureus infections, particularly those with a biofilm component.Science Foundation Irelan

Demand response through reject water scheduling in water resource recovery facilities: A demonstration with BSM2

The objective of this paper is to determine the importance of integrating peak demand mitigation and future energy pricing structures for process modelling of conventional water resource recovery facilities (WRRFs) when evaluating energy cost and control strategies. The well-established benchmark simulation model (BSM2) is used to monitor energy usage, and a detailed holistic study of different flow streams is performed in order to establish potential opportunities for flexible control of WRRF energy demand. Secondly, a detailed framework is introduced to optimize scheduling control strategies for the reject water stream while considering peak electricity demand avoidance as well as completing a comprehensive energy cost model based on current and anticipated future energy tariff structures. The reject water scheduling strategies, without other active controls (e.g. aeration), revealed 63.4% average peak demand mitigation and €10,755 cumulative annual energy cost savings on a 100k population equivalent WRRF without a deterioration in effluent quality. Analysis of different reject water scheduling control strategies shows that reject water scheduling can be an effective tool for energy cost optimisation under alternative electricity tariff structures. These strategies also deliver electricity peak demand mitigation.Science Foundation Ireland (SFI

EU-Mindestlohnrichtlinie: Juristischer Paukenschlag

Für das soziale Europa hat das Jahr mit einem Paukenschlag begonnen: Am 14. Januar empfahl EU-Generalanwalt Nicholas Emiliou dem Europäischen Gerichtshof (EuGH), die Mindestlohnrichtline zu annullieren. Sein Antrag stützt eine Klage Dänemarks gegen EU-Parlament und Rat, da deren Mindestlohnrichtlinie die Autonomie der nationalen Sozialpartner untergraben würde.University College Dublin (UCD

Assessing alcohol industry penetration and government safeguards: The International Alcohol Control Study

Background The alcohol industry uses many of the tobacco industry's strategies to influence policy-making, yet unlike the Framework Convention on Tobacco Control, there is no intergovernmental guidance on protecting policies from alcohol industry influence. Systematic assessment of alcohol industry penetration and government safeguards is also lacking. Here, we aimed to identify the nature and extent of industry penetration in a cross-section of jurisdictions. Using these data, we suggested ways to protect alcohol policies and policy-makers from undue industry influence. Methods As part of the International Alcohol Control Study, researchers from 24 jurisdictions documented whether 22 indicators of alcohol industry penetration and government safeguards were present or absent in their location. Several sources of publicly available information were used, such as government or alcohol industry reports, websites, media releases, news articles and research articles. We summarised the responses quantitatively by indicator and jurisdiction. We also extracted examples provided of industry penetration and government safeguards. Results There were high levels of alcohol industry penetration overall. Notably, all jurisdictions reported the presence of transnational alcohol corporations, and most (63%) reported government officials or politicians having held industry roles. There were multiple examples of government partnerships or agreements with the alcohol industry as corporate social responsibility activities, and government incentives for the industry in the early COVID-19 pandemic. In contrast, government safeguards against alcohol industry influence were limited, with only the Philippines reporting a policy to restrict government interactions with the alcohol industry. It was challenging to obtain publicly available information on multiple indicators of alcohol industry penetration. Conclusion Governments need to put in place stronger measures to protect policies from alcohol industry influence, including restricting interactions and partnerships with the alcohol industry, limiting political contributions and enhancing transparency. Data collection can be improved by measuring these government safeguards in future studies.Te Whatu Ora–Health New Zealand)FORUT, NorwayThai Healt

Membrane bioreactors for the production of value-added products: Recent developments, challenges and perspectives

The potential of membrane bioreactors to produce value-added products such as biofuels, biopolymers, proteins, organic acids and lipids at high productivities is emerging. Despite the promising results at laboratory scale, industrial deployment of this technology is hindered due to challenges associated with scale-up. This review aims to address these challenges and create a framework to encourage further research directed towards industrial application of membrane bioreactors to produce value-added products. This review describes the current state-of-the art in such bioreactor systems by exploiting membranes to increase the mass transfer rate of the limiting substrates, reach high cell concentrations and separate the inhibitory substances that may inhibit the bioconversion reaction. It also covers the current trends in commercialization, challenges linked with membrane usage, such as high costs and membrane fouling, and proposes possible future directions for the wider application of membrane bioreactors