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Medical device innovation in remote heart failure monitoring using the Stanford biodesign process
No full textDespite clinical advances in its treatment, heart failure (HF) is associated with significant adverse clinical outcomes and is among the greatest drivers of healthcare utilisation. Outpatient management of HF remains suboptimal, with gaps in the provision of evidence-based therapies, and difficulties in predicting and managing clinical decompensation. Remote patient monitoring has emerged as a promising avenue to tackle these quandaries, drawing heightened attention from HF clinicians and health systems. However, even after years of dedicated research and investment, a definitive solution that truly aligns with the demands and expectations of both clinicians, patients and payers is yet to be achieved. In this context, we delve into this intricate landscape of remote HF monitoring, the underlying disease state and an innovative solution all developed using the infamous Biodesign methodology during the BioInnovate programme.2026-06-0
Debriefing nontechnical skills in healthcare simulation: A facilitators guide
No full textIt has been suggested that facilitators often find it challenging to observe and debrief nontechnical skills [1]. Nontechnical skills are the cognitive, personal resource, and social skills that complement a healthcare worker’s technical ability, and are crucial to safe and effective team performance [2]. This guide will provide: (i) a brief overview of the nontechnical skills that are particularly important for healthcare practitioners, (ii) common issues associated with each skill that are observed during simulation training, and (iii) examples of questions facilitators can ask about these nontechnical skills during the debriefing. The nontechnical skills that will be covered in this guide include: • Situation awareness • Decision making • Communication • Teamworking • Leadership • Managing stress This guide provides a brief introduction to nontechnical skills and how to debrief them. For guidance on debriefing and healthcare simulation more broadly, we suggest reading O’Connor et al’s [3] introductory text on healthcare simulation. If you are interested in human factors more broadly, we suggest reading O’Connor & O’Dea’s [4] guide to human factors in healthcare. At the end of each section we have identified particular issues –related to each non technical skill - that may occur during a team simulation event, that facilitators can look out for. Additionally we present potential questions you might use to open a discussion on these issues during the debriefing. This is not intended to be an exhaustive list of possible issues and questions, and you may only cover one or two issues on each skill. Similarly, you are unlikely to cover every nontechnical skill during a debrief. A summary of the points to look out for during the scenario, and accompanying questions, for all of the nontechnical skills is provided in the appendix at the end of this document
Antecedents and consequences of technostress in online labour markets
No full textTechnology plays a pivotal role in the digitalisation of work practices, and that led to the emergence of new forms of employment, including digital gig work facilitated by online platforms that match employers and workers through online labour markets. Despite the apparent simplicity of joining these platforms, sustaining and thriving in such work environments presents challenges, often impacting worker well-being. Given that platform work is deeply embedded in technology use workers are more prone to technology-induced stress also known as technostress. This thesis investigates the impact of technostress on the well-being of platform workers, highlighting the complexities inherent in this novel work. Platform work is unique in that algorithms control various aspects of work organisation, feedback and evaluation systems, and the probability of participation. Technostress can be exacerbated by factors such as competition, algorithmic control, work intensification, unpredictable schedules, multitasking, surveillance, low wages, and precarious conditions. This thesis is based on three core articles. The first article discusses the concept of technostress in detail, explores how this phenomenon has evolved with the changing nature of work and identifies the gap in understanding it within the context of platforms. The second article investigates platform-specific technology and job characteristics that can result in technostress creating an impact on worker well being. The third, article examines the technostress concept through the lens of temporal characteristics and its impact on work outcomes. To investigate the research questions, the thesis develops research models and employs a quantitative survey design, conducted specifically on Amazon Mechanical Turk (MTurk), a widely used online labour market. The surveys are designed following the protocols of conducting behavioural research on MTurk and structural equational modelling partial least square (SEM-PLS) is used to empirically analyse the results of the research models. In doing so, the research adopts both aggregated and disaggregated approaches to examine technostress. The findings demonstrate that job and temporal characteristics play significant roles in shaping the technostress experience within online labour markets. The research contributes to technostress research by going beyond the notion of technology characteristics solely as environmental antecedents and identifying technostress related outcomes in the unique context of platforms. The results show that technology complexity, feedback and time pressure shape the technostress process in these platforms. The research also contributes by exploring the concept of technostress from a positive perspective, aligning with the call made by many recent studies. The research findings contribute to our understanding of technostress and establish a foundation for future research in the platform context. Furthermore, the findings help in the development of strategies aimed at promoting well-being and mitigating technostress in this novel type of work
A social justice perspective on the delivery of family support
No full textFamily support as an approach to working with children, youth, parents, and families is widely practiced across Europe albeit with a range of diverse meanings and interpretations. This paper responds to this ambiguity and provides a conceptual understanding of the delivery of family support in Europe. In doing so it applies a social justice approach critically examining the extent to which Family Support reflects the right of families, children, youth, and parents to be supported. It identifies and critically examines similarities and differences in the meaning and application of family support as a key concept in the European context. It is based on a comprehensive review of literature, mapping multi-disciplinary approaches to the provision of support, based on academic material from 2015 to 2020 and adopting a broad and inclusive definition of family. The paper considers the complexities in developing a universally accepted understanding of family support that: has value for practitioners and managers; is selected as a focus by policy makers; is open to evaluation and research; is compatible with academic research; and most importantly provides responsive and effective support to children, youth, parents and families.This article is based upon work from COST Action CA18123 The European Family Support Network, supported by COST (European Cooperation in Science and Technology). www.cost.eu.peer-reviewe
An ultrasonic method to measure stress without calibration: The angled shear wave identity.
No full textMeasuring stress levels in loaded structures is crucial to assess and monitor structure health and to predict the length of remaining structural life. Many ultrasonic methods are able to accurately predict in-plane stresses inside a controlled laboratory environment but struggle to be robust outside, in a real-world setting. That is because these methods rely either on knowing beforehand the material constants (which are difficult to acquire) or require significant calibration for each specimen. This paper presents an ultrasonic method to evaluate the in-plane stress in situ directly, without knowing any material constants. The method is simple in principle, as it only requires measuring the speed of two angled shear waves. It is based on a formula that is exact for incompressible solids, such as soft gels or tissues, and is approximately true for compressible ¿hard¿ solids, such as steel and other metals. The formula is validated by finite element simulations, showing that it displays excellent accuracy, with a small error on the order of 1%A.L.G. is grateful to Professor Rob Dwyer-Joyce and Professor Roger Lewis for introducing this problem and for their collaboration. A.L.G. and M.D. are grateful for partial support from UK Acoustics Network (UKAN) Engineering and Physical Sciences Research Council (EPSRC) Grant No. EP/R005001/1.peer-reviewe
Factors influencing heterogeneity in anthropometric and metabolic responses to structured lifestyle interventions
No full textThe rising prevalence of obesity is a significant burden on affected individuals, on healthcare systems and on society. Diet and physical activity are critical determinants of body weight and obesity risk, and lifestyle modification is the cornerstone of the therapeutic approach to obesity. However, there is substantial inter-individual variation in responses to lifestyle modification. In this work, I examine some of the factors associated with variations in anthropometric and metabolic responses to structured lifestyle modification programmes. Firstly, I conducted a prospective cohort study of patients with severe obesity completing a structured diet and exercise programme, noting that older patients, males and those with lower levels of depression were more likely to complete the programme, and were more likely to achieve ≥5% weight loss. I found strong and consistent associations between the amount of weight lost and the magnitude of improvements in markers of mental, metabolic and cardiovascular health. Secondly, I completed a post hoc analysis of the Hertfordshire Physical Activity Trial, describing the effect of a supervised, structured 12-week aerobic exercise intervention on objectively measured physical activity energy expenditure in healthy older adults. There was no significant effect of the exercise intervention on overall average physical activity, but there was an effect on the three days of the week that the exercise sessions took place, suggesting that the frequency of exercise bouts, rather than their intensity or duration, may not have been adequate to exact an overall effect of the intervention. Thirdly, I conducted a cohort analysis from the same trial, describing a strong and consistent association between physical activity energy expenditure and body fat, cardiovascular risk and various measures of insulin resistance, in healthy older adults. However, changes in physical activity were only associated with improvements in some of those outcomes, suggesting that the metabolic benefits of physical activity take longer than 12 weeks to become apparent. Fourthly, in a retrospective cohort study of adults with severe obesity completing a milk-based meal replacement programme, I found that a genetic risk score derived from common polymorphisms associated with central fat distribution was inversely associated with the magnitude of weight loss, the first Irish study to confirm a genetic influence on the response to a dietary intervention. Finally, in a prospective cohort study in patients undergoing the milk diet, I described associations between changes in fasting plasma ketone concentrations and weight loss. This has led to securing research funding from Science Foundation Ireland to explore the relevance of physiological ketosis in predicting and mediating responses to clinical interventions for patients with obesity, at CÚRAM.2025-04-0
Distal 11q arm breakage and reduction of H2AX copy number in breast cancer
No full textChromosome 11q alterations are frequent in hormone-positive luminal breast cancer (LBC). The 11q13 locus where the CCND1 oncogene is located is frequently amplified and the distal 11q arm is often lost. Several DNA damage response (DDR) genes, namely MRE11, RSF1, ATM, H2AX and CHEK1 map to the 11q arm. Heterozygous loss of the 11q arm may reduce DDR gene expression and promote chromosomal instability but render the tumour more sensitive to radiation and treatment through synthetic lethality approaches. Recently, complete H2AX loss in cell lines was shown to activate the epithelial-mesenchymal transition (EMT), a cellular program which allows cancer cells to metastasize to distant sites. LBC cell lines with 11q13 amplification and distal 11q loss were selected and characterised. Cytogenetic analysis revealed 11q alterations, distal 11q loss, and CCND1 amplification, likely arising through the breakage-fusion-bridge mechanism. 11q mRNA expression did not correlate with gene copy number, however cell lines with distal 11q loss exhibited increased sensitivity to ionizing radiation. T47D WT and H2AX-targeted cell pools, obtained from Synthego, allowed us to study the effects of H2AX loss on EMT. H2AX-deficient clones showed minor morphology changes, but EMT activation was not robust. These clones failed to form MDC1 foci after DNA damage, indicating DDR defects worthy of future investigation. Our study underscores the importance of in-house cytogenetic analysis to validate genomic database findings. Cell lines with distal 11q loss exhibit potential radiation sensitivity, suggesting targeted treatments for this LBC subgroup. Unexpectedly, H2AX-deficient clones did not strongly activate EMT, challenging published literature and hinting at cell-type-specific H2AX regulation of EMT. These findings contribute valuable insights into the genomic and functional aspects of 11q alterations in LBC, emphasizing the need for personalized approaches in understanding and treating this subtype of breast cancer.2026-06-0
Essays on the impact of star scientist-mobility universities, peers and stars
No full textIn the ever-evolving global innovation landscape, small open economies (SOEs) face a unique challenge: fostering robust research ecosystems despite limited resources. A critical strategy for SOEs is maximising the impact of "star scientists"- who can catalyse research productivity and knowledge creation. This thesis investigates the influence of star scientists within SOEs, examining their influence on departmental output, incumbent productivity, and their own research trajectory following relocation. This research sheds light on the complex dynamics at play by employing novel methodologies and analysing data from three SOEs - Denmark, Ireland, and New Zealand. The findings offer valuable insights for policymakers and academic institutions, informing strategies for star scientist recruitment, integration, and fostering vibrant research clusters that propel knowledge-driven economic growth within SOEs. The first essay investigates the impact of star arrival on departments in the SOEs. The arrival of a star scientist is expected to help increase departmental productivity. An event-study model estimates the dynamic effects of a star arrival on quality-adjusted research output at both the department and matched individual incumbent levels. The analysis considers the broader influence of star scientists, encompassing potential channels such as fostering new research norms, facilitating access to superior training and knowledge, and stimulating collaboration opportunities within the department. Building on the prior investigation into the impact of star arrivals on departmental research output, the following essay explores the specific mechanisms through which star scientists influence their peer's productivity. While co-authorship offers a clear path for knowledge exchange, this chapter sheds light on the more nuanced effects of "star help" - assistance provided by a star scientist that falls outside the traditional coauthorship framework. I leverage natural language processing (NLP) techniques to analyse acknowledgement sections within a vast corpus of published papers. Employing an event-study framework with matched data, I estimate the causal effect of star help on author productivity. Furthermore, the chapter explores the influence of sustained star support, examining how ongoing engagement with a star scientist shapes an author's long-term research output. These findings provide crucial insights for policymakers and academic institutions, informing strategies for star scientist recruitment that go beyond co-authorship. While the previous essays explore the influence of star scientists on departmental productivity and incumbent output, the following essay addresses this gap in the literature by examining the research productivity of star scientists following their relocation to SOEs. I use an event-study model to isolate the causal effects of mobility on the star's productivity, comparing their performance to non-mobile star scientists within the same SOEs. This analysis explores the potential cost of mobility, investigating whether star scientists prioritise institution-building activities upon arrival, potentially at the expense of their immediate research output. Furthermore, the essay explores how career stage and scientific field may influence the impact of mobility on a star scientist's performance. By examining these dynamics, this research provides policymakers and academic institutions with evidence to support the design of star-scientist integration strategies that balance institution-building with continued research excellence from the stars themselves. The final essay investigates how the knowledge space relatedness between a star and their peers intermediates the impact on those colleagues' productivity. In particular, this chapter investigates factors that affect the "intensity" of the treatment effect. I posit a non-linear relationship between relatedness to the star and the observed productivity effect on co-located scientists. While a stronger relationship can enhance the incumbent's absorptive capacity, it might also lead to knowledge redundancy. I employ a difference-in-difference model to examine this, estimating the treatment effects for varying degrees of relatedness (proxied by my relatedness measure). Furthermore, an event-study model with coarsened exact matching is utilised to help establish causal evidence of star arrivals on incumbent scientist productivity. By disentangling these dynamics, this research offers insights for academic institutions in fostering an environment that maximises the positive spillover effects of star scientists on their colleagues
Novel statistical models and computational tools for gene set analysis
No full textThe gene is often treated as an observational unit in biology. The signals in a trancriptomic assay are mapped to genes, while the results of genomic and functional assays are frequently linked to genes to increase biological interpretability. However, the function of a particular gene is not always known and can change depending on cellular context. Furthermore, the number of genes identified as worthy of interest can be far too great for researchers to interpret and extract biological insights from them one by one. Analysing groups of genes related by function, partaking in a common biological pathway or sharing biochemical similarities can address these pitfalls. The criteria and knowledge used to construct gene sets are incorporated into the downstream analysis of transcriptomic, genomic and functional assays, focussing the researcher's attention on a comparatively small number of well-defined pathways.
In Chapter 2, we outlined the log-fold change distribution as a conceptual framework that can be used to understand the different null hypotheses being tested by various gene set analysis (GSA) tools in the context of differential gene expression. This framework led to the development of a set of GSA tests based on modelling the log-fold change (LFC) distribution as a mixture of Gaussian random variables. The different tests provide parallels to popular GSA methods with significant advantages in sensitivity and interpretability in both simulations and real data analysis.
In Chapter 3, we developed additional GSA tests to interpret the results of cell-type-specific differential expression analyses. Inference of cell-type-specific differential expression from a heterogenous sample is associated with high levels of uncertainty. This uncertainty necessitated the development of non-parametric GSA tests based on the LFC distribution, making fewer assumptions and leading to more robust results. Both parametric and non-parametric tests were made available in an R package and an Rshiny application, which allows researchers to efficiently run GSA tests and visualise and interpret results across all cells in the experiment.
In Chapter 4, the focus of the thesis shifts from enrichment in the context of differential gene expression to enrichment for variants in genomic regions. We performed genomic enrichment tests on de-novo variants in autism spectrum disorder probands. Groups of genomic regions could be compared with the rest of the genome or between cases and controls. The former tests (internal in that they compared different regions of the genome with each other) aimed to model the distribution of variants across the genome to detect regions with a significantly higher number of variants than expected. The latter (external tests), through the use of an appropriate control cohort, avoided making any assumptions about the distribution of \textit{de-novo} variants along the genome and was better suited for the testing of large numbers of variants not previously associated with the trait.Science Foundation Ireland under Grant number [18/CRT/6214