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    Marked elevations in pro-inflammatory polyunsaturated fatty acid metabolites in females with irritable bowel syndrome

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    Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder referred to gastroenterologists. Although the pathophysiology remains unclear, accumulating evidence points to the presence of low-level immune activation both in the gut and systemically. Circulating polyunsaturated fatty acids (PUFA) have recently attracted attention as being altered in a variety of disease states. Arachidonic acid (AA), in particular, has been implicated in the development of a pro-inflammatory profile in a number of immune-related disorders. AA is the precursor of a number of important immunomodulatory eicosanoids, including prostaglandin E2 (PGE2) and leukotriene B4 (LTB4). We investigated the hypothesis that elevated plasma AA concentrations in plasma contribute to the proposed pro-inflammatory profile in IBS. Plasma AA and related PUFA were quantified by gas chromatography analysis in IBS patients and controls. Both PGE2 and LTB4 were measured in serum using commercially available ELISA assays. AA concentrations were elevated in our patient cohort compared with healthy controls. Moreover, we demonstrated that this disturbance in plasma AA concentrations leads to downstream elevations in eicosanoids. Together, our data identifies a novel proinflammatory mechanism in irritable bowel syndrome and also suggests that elevated arachidonic acid levels in plasma may serve as putative biological markers in this condition

    “We shouldn’t waste a good crisis”: the lived experience of working on the frontline through the first surge (and beyond) of COVID-19 in the UK and Ireland

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    Objective: Frontline workers have shown extraordinary resilience and sustained efforts since the outbreak of COVID-19. The present study used semi-structured interviews with 38 frontline workers in the UK and Ireland to explore the psychological impact of working through COVID-19. Design: The qualitative data were analysed systematically using thematic analysis. Results: Four themes were interpreted: 1)) “I’ve stopped turning the telly on. I’ve had to because the news was making me ill”: An ecosystem of influence; 2) “Dead, dead, dead”: The emotional and psychological toll: 3) “It’s shone a light on what we’re failing on as well”: Injustices, hierarchies and heroes: and 4) “I definitely think COVID happened for a reason to stop us in our tracks and to slow us down”: Unexpected positives. Conclusion: This research offers insights into how frontline workers make sense of their experiences during periods of enormous societal and occupational stress. The learnings generated have relevance for government and organisational policy makers who have opportunities to shape future conditions for frontline worker

    Exploring perceptions, tensions and possibilities of an integrated approach to quality assurance in higher education: a case study in an institute of technology in Ireland

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    National rhetoric speaks of Higher Education institutions as powerhouses of knowledge and innovation and staff are hailed as one of their greatest assets. Engaging the commitment and innovation of staff is the stated function of Higher Education management. However, tensions frequently emerge between the perceptions of staff role groups and the goals of the Higher Education endeavor that can hinder rather than enhance progress. This research explored perceptions and tensions between “tribes and territories” in Higher Education to determine if a collaborative approach to quality assurance processes in Higher Education can mitigate some of these tensions and achieve better outcomes for the institution. The research provided multiple insights into perceptions of and orientations towards quality assurance in Higher Education through a study in one Institute of Technology in Ireland. The importance of context, values and attitudes as drivers of quality in Higher Education was confirmed. Cognizant of changing staff profiles and changes in student engagement, the study was novel in exploring academic staff, professional staff and student views on QA. This inclusive approach was not previously documented in the literature and is an important contribution to understanding of QA in Higher Education. The research defines a novel, collaborative and inclusive methodology for developing quality policy. Building on Lipsky’s concept of street level bureaucracy, the research moved beyond the existing focus on management and academic tribes. Broader staff and student stakeholder group views within Higher Education were included. This wider view makes the contribution to knowledge of illuminating underlying tensions between different staff role identities in Higher Education. It was an important study in its questioning of traditional views of staff roles and identities. The study reveals how staff group understanding and engagement with academic quality has evolved, as staff profiles have changed to higher levels of qualification and professionalization in the Institute of Technology sector. The research methodology included the application of the survey approach early in the study to establish the thematic areas for investigation in semi-structured depth interviews for in-depth exploration. The Delphi method was used to research QA expert, management and participant communities’ perceptions of QA management, measurement and performance. Analysis of the surveys demonstrated that despite identity differences, a significant level of agreement can be established across all staff sub-cultures and role groups with regard to QA and QA Systems. These findings from the surveys were explored in semi-structured depth interviews with expert informants. The interviews triangulated the survey views on academic QA and revealed where current QA and management thinking differs from staff views discerned through an integrated academic QA process. The main findings of the research are the potential for wider collaboration of staff in academic quality assurance and the value for HE institutions in genuinely acknowledging the centrality of staff to QA development and implementation. Collegiate culture in HE can be deepened beyond the academic community through collaboration and inclusion across role groups

    Skill acquisition practices of coaches on the British para swimming world class programme

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    This study set out to gain insight into the practices adopted by elite level Paralympic swimming coaches and to shed light on the knowledge and rationale underpinning their approaches. Coaching sessions were delivered by nine senior coaches from the British Para swimming (BPS) World Class Programme. A coaching session was observed from each coach and a semi-structured interview was recorded and transcribed to explore their intentions and rationale for the structure and content of the session delivered. Results indicated that coaches: (i) predominantly emphasised internal focus instruction and feedback cues, (ii) incorporated relatively low levels of between-skill variability and higher levels of within-skill variability, and (iii) applied mostly explicit learning techniques such as part-task training and verbal feedback, but also incorporated some implicit learning techniques such as analogies and constraints-based learning. Interview data indicated coaches had limited knowledge of key skill acquisition principles. The study serves to highlight potential gaps in understanding on the side of both research and applied practice in the hope of facilitating future collaborations between coaches and skill acquisition practitioners

    A machine learning tool to predict the antibacterial capacity of nanoparticles

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    The emergence and rapid spread of multidrug-resistant bacteria strains are a public health concern. This emergence is caused by the overuse and misuse of antibiotics leading to the evolution of antibiotic-resistant strains. Nanoparticles (NPs) are objects with all three external dimensions in the nanoscale that varies from 1 to 100 nm. Research on NPs with enhanced antimicrobial activity as alternatives to antibiotics has grown due to the increased incidence of nosocomial and community acquired infections caused by pathogens. Machine learning (ML) tools have been used in the field of nanoinformatics with promising results. As a consequence of evident achievements on a wide range of predictive tasks, ML techniques are attracting significant interest across a variety of stakeholders. In this article, we present an ML tool that successfully predicts the antibacterial capacity of NPs while the model’s validation demonstrates encouraging results (R2 = 0.78). The data were compiled after a literature review of 60 articles and consist of key physico-chemical (p-chem) properties and experimental conditions (exposure variables and bacterial clustering) from in vitro studies. Following data homogenization and pre-processing, we trained various regression algorithms and we validated them using diverse performance metrics. Finally, an important attribute evaluation, which ranks the attributes that are most important in predicting the outcome, was performed. The attribute importance revealed that NP core size, the exposure dose, and the species of bacterium are key variables in predicting the antibacterial effect of NPs. This tool assists various stakeholders and scientists in predicting the antibacterial effects of NPs based on their p-chem properties and diverse exposure settings. This concept also aids the safe-by-design paradigm by incorporating functionality tools

    Design and characterization of monoacylglycerol lipid cubic phase systems for the effective delivery of small molecule pharmaceuticals

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    To be effective, a drug must be efficiently delivered in sufficient quantities over a period of time long enough for it to carry out its desired effect. A major challenge in this sense is poor retention and bioavailability of drugs, particularly those that display poor solubility. The number of newly discovered drugs is disproportionate to the number that make it to market because of less than desirable solubility and permeability profiles, but smart drug delivery systems, such as lipid-based systems, are capable of overcoming these challenges. One particular system, the amphiphilic, biocompatible, and biodegradable lipid cubic phase, has shown promise as an effective carrier system for the controlled release of drugs varying in solubility. This work explores the behaviour of a variety of industrially relevant small molecule pharmaceuticals in lipid cubic phases formulated with different host lipids for potential controlled delivery applications. An understanding of the molecular mechanisms underlying the process of dissolution/diffusion from these phases was elucidated to support the field of controlled drug delivery using in silico molecular dynamic modelling and empirical approaches. A comprehensive characterization approach was taken both macroscopically and microscopically using small-angle X-ray scattering and polarized light to ascertain the mesophase accessed upon incorporation of molecules of varying solubilities and size. In the first instance, the influence of environmental conditions on the release profile of four antihistamine molecules was studied to establish in vitro models that might assist in predicting the dissolution behaviour of a given pharmaceutical with known physicochemical properties. Two model first-generation and two model second-generation H1 antagonist antihistamine drugs were selected and formulated in two separate monoacyglycerol-derived matrices. The impact of encapsulating the molecules in the lipid cubic systems on their mucoadhesive properties was demonstrated using multi-parametric surface plasmon resonance (MP-SPR). With a potential application in developing therapies for the treatment of allergic reactions, the ability of the formulations to inhibit mediator release utilizing RBL-2H3 mast cells with the propensity to release histamine upon induction was presented. Lipid cubic formulations can enhance the intestinal solubility and subsequent bioavailability of notoriously hydrophobic drug entities by reducing drug precipitation and facilitating mass transport to the intestinal surface for absorption. In this context, the aims of the second study were twofold: to evaluate an approach to regulate the rate of degradation of lipid cubic phase drug delivery systems by targeting the enzyme interactions responsible for their demise; and to study the subsequent drug release profiles from bulk lipid cubic gels using model drugs of contrasting hydrophobicity. In a novel approach, monoacylglycerol cubic phases were formulated with a potent lipase inhibitor tetrahydrolipstatin displaying controlled degradation with at least a 4-fold longer release compared to the blank systems. Sustained release of a model hydrophobic pharmaceutical (a clofazimine salt) was studied over 30 days to highlight the advantage of incorporating an inhibitor into the cubic network to achieve tunable lipid release systems. The final aspect of this thesis deals with the interplay between the lipolysis rate and the interfacial interaction of porcine pancreatic lipase with lipid cubic substrates encapsulating the THL. In the final chapter, inhibitor-modified monoolein lipid cubic formulations designed to encapsulate and control the release of a model BCS class IV drug paclitaxel (PTX) were examined under simulated lipolysis in the presence of lipase and its cofactors colipase and calcium. We present a combination of thermodynamic and molecular dynamics simulations of the competitive inhibition with experimental dynamic digestion studies to reveal the role and mode of action of the studied lipase effectors in designing a degradation-controlled release system for the poorly soluble drug PTX. These studies facilitated a deeper understanding of the approach described in the previous chapter, expanding the study to open new important possibilities in the field of pharmaceutical transport especially where difficult-to-formulate drugs are concerned

    Gaming disorder in adults with autism spectrum disorder

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    Gaming disorder (GD) is a clinical addiction to video or internet games. This study investigated whether GD symptoms are heightened in adults with autism spectrum disorder (ASD) in comparison to a control group, and explored predictors of GD in 230 adults with ASD and 272 controls. The relationship between GD and gelotophobia was examined. Measures included the Ten-Item Internet Gaming Disorder Test, GELOPH¿, Autism Spectrum Quotient-10 items, Inventory of Parent and Peer attachment, Emotional Regulation Questionnaire, Social Functioning Questionnaire (SFQ) and the NEO-FFI-3. Individuals in the ASD group showed significantly higher symptoms of GD. Peer-attachment, emotional regulation and extraversion significantly predicted GD scores. Gelotophobia and GD were related to each other with a small effect size

    Financial time series: market analysis techniques based on matrix profiles

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    The Matrix Profile (MP) algorithm has the potential to revolutionise many areas of data analysis. In this article, several applications to financial time series are examined. Several approaches for the identification of similar behaviour patterns (or motifs) are proposed, illustrated, and the results discussed. While the MP is primarily designed for single series analysis, it can also be applied to multi-variate financial series. It still permits the initial identification of time periods with indicatively similar behaviour across individual market sectors and indexes, together with the assessment of wider applications, such as general market behaviour in times of financial crisis. In short, the MP algorithm offers considerable potential for detailed analysis, not only in terms of motif identification in financial time series, but also in terms of exploring the nature of underlying events

    Chemical composition, antioxidant, antimicrobial and cytotoxic/cytoprotective activity of non-polar extracts of grape (vitis labrusca cv. bordeaux) and blackberry (rubus fruticosus) seeds

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    The aim of this study was to compare the influence of the extraction method, chemical composition, antimicrobial effects, antioxidant activity, and cytotoxicity on human cells of the non-polar extracts of grape (Vitis labrusca) and blackberry (Rubus fruticosus) seeds. The Soxhlet (Sox), Bligh–Dyer (BD), and ultrasound (US) methods were used for extractions. For blackberry non-polar seed extract, extraction via the BD method showed the highest mean values of total phenolic content (TPC), expressed in milligrams of gallic acid equivalent per 100 mL of non-polar seed extracts (102.37 mg GAE/100 mL), and higher antioxidant activity in relation to the 2,2-diphenyl 1-picrylhydrazyl (DPPH) radical, expressed in milligrams of gallic acid equivalent per 100 mL of non-polar seed extracts (11.50 mg AAE/100 mL), if compared with the Sox and US extractions. Similar results were obtained for the non-polar grape seed extracts, where BD extraction obtained the highest values for TPC (28.61 mg GAE/100 mL) and DPPH (35.36 mg AAE/100 mL). The type of extraction method had an impact on the composition of fatty acids. Only the non-polar blackberry and grape seed extracts obtained via the Sox method showed some in vitro inhibitory effect against Escherichia coli (IAL 2064) and Staphylococcus aureus (ATCC 13565). Regardless of the extraction method used, the non-polar blackberry and grape seed extracts did not decrease the cell viability (IC50 >1000 µg/mL) of cancer and normal cell lines, thus indicating the relative safety of the extracts. All the seed extracts decreased the generation of reactive oxygen species in the cell lines. Blackberry and grape seed lipid fractions can be utilized as antioxidants, and the extraction methods used cause significant changes in relation to their bioactivity and chemical composition

    A Place for Space: The Shift to Online Space Education During a Global Pandemic

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    The COVID-19 global pandemic has transformed the relationship between science and society. The ensuing public health crisis has placed aspects of this relationship in harsh relief; perceptions of scientific credibility, risk, uncertainty, and democracy are all publicly debated in ways unforeseen before the pandemic. This unprecedented situation presents opportunities to reassess how certain disciplines contribute to the public understanding of science. Space education has long provided a lens through which people can consider the intersection of the natural world with society. Space science is critical to understanding how human activity and pollution affect global warming, which in turn, inextricably links it to perceptions of the natural world, environmental change, science communication, and public engagement. The pandemic has caused a dramatic shift in how space education projects connect with public audiences, with participation pivoting to online engagement. This transition, coupled with the renewed societal examination of trust in science, means that it is an ideal time for the field of space education to reflect on its development. Whether it evolves into its own distinct field, or remains an area that straddles disciplinary boundaries, such as science education, communication, and public engagement, are crucial considerations when scientific trust, accountability, and responsibility are in question. This paper describes the current state of space education, recent advances in the field, and relevant COVID-19 challenges. The experience of an international space education project in adapting to online engagement is recounted, and provides a perspective on potential future directions for the field

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