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Fluoroquinolones directly drive mitochondrial hyperpolarization and modulate iNOS expression in monocyte-derived macrophage populations
No full textIntroduction The fluoroquinolone levofloxacin is often selected for use prophylactically as well as during respiratory infections. However, studies on how these antibiotics may alter innate immunity, as opposed to their bactericidal activity, are limited. Materials & Methods We employed a murine model of therapeutically relevant antibiotic dosing to investigate the effect of prophylactic levofloxacin treatment on innate immunity. Results We observed mild pathology at the barrier sites of both the lung and colon in terms of alveolar space and goblet cell numbers, respectively. Although we saw no alteration in lung immune populations of neutrophils, eosinophils, or dendritic cells, we did see heightened expression of macrophage inducible nitric oxide synthase (iNOS). Interestingly this was only present in the shorter-lived CD206− interstitial macrophage subset and not observed in the long-lived resident alveolar population. Within the large intestine levofloxacin also targeted iNOS expression in the shorter-lived TIM4-CD4+ population but conversely inhibiting expression in the microbially rich colon. We therefore utilized the bone marrow-derived macrophage system, devoid of microbial interactions and demonstrated that levofloxacin had a direct effect on driving iNOS expression and increasing phagocytosis but only when present in developing macrophages and not mature macrophage populations. Our macrophage observations were replicated in ciprofloxacin, but not doxycycline-treated animals, indicating a fluoroquinolone specific action. Mechanistically, fluoroquinolone treatment was associated with mitochondrial hyperpolarization, indicating a direct alteration of macrophage immunity via off target effects. Conclusion Collectively, this study demonstrates a direct action of fluoroquinolones on macrophage immunity, which should be considered when selecting antibiotics for tissue specific and prophylactic use
Tour guides as climate change agents : conceptualizing meaningful work through agency theory in precarious employment
No full textThis paper addresses the mediating role of tour guides in educating tourists in climate sensitive regions. This role can be crucial in educating tourists about climate change and promoting environmentally responsible behaviour. However, tour guides frequently work under precarious employment conditions, such as freelancers, casual workers, or task-based labourers, which offer limited job security, benefits, or formal employment rights. Climate sensitivity offers opportunity to add meaning to work that tour guides undertake. Employing agency theory, this study addresses the gap in understanding how tour guides find meaning in their work as climate change advocates through indepth interviews with 43 casual-work tour guides. Findings reveal tour guides in climate-sensitive regions find significant meaning in their work as climate change advocates
An adaptive total sliding mode control for cascaded H-bridge multilevel converters to flexibly suppress ground fault arcs in active distribution networks
Get PDFSingle phase-to-ground (SPG) faults are the most common faults in active distribution networks, which can cause hazardous situations and consequences, such as fires, electric shocks, and power outages. Power electronic converters using typical control methods, like proportional-integral (PI) control, backstepping control (BSC), and sliding mode control (SMC), can suppress the fault current and voltage until the fault arc disappears. However, these controllers are not adaptable to the various fault resistances and have long transient DC bias decay processes, resulting in the arc not being suppressed quickly and reliably. This paper proposes a novel adaptive total sliding mode control (ATSMC) for cascaded H-bridge multilevel converters (CHMC) to not only adapt to the uncertain and various fault resistances with a wide range but also eliminate the long-term transient DC bias decay processes, and the steady-state residual fault current and voltage can be suppressed to be smaller. The proposed method satisfies Lyapunov's asymptotic stability and is also applicable to other power electronic converter topologies for suppressing fault arcs. The simulation study and experimental validation demonstrate the effectiveness of the proposed method in providing the above advantages and exhibit better overall performance, compared to those of PI, BSC, and SMC
Discussion Paper: An Illustrative Model for Estimating the Cost Savings Supported by Early Years Programme Intervention
Get PDFThe Data for Children Collaborative partnered with Elevate Great, Aberlour, the Fraser of Allander Institute, and the University of Dundee to evaluate the Aberlour Early Years Outreach Programme. The aim was to test a more flexible, illustrative evaluation approach that could help other third-sector organisations demonstrate both value-for-money and broader societal benefits. This discussion paper brings together the learnings from this evaluation process, reflecting on the challenges that third-sector organisations face in quantifying the impacts of early years and preventative services. The paper highlights lessons learned throughout the evaluation that could help other third-sector organisations, commissioners, and funders improve how early-years and preventative services are evaluated- particularly when impact is broad, long-term, and not easily captured using conventional methods. While this paper does not provide a conclusive economic valuation of Aberlour’s Early Years Outreach Programme, it contributes to the ongoing conversation about how the evaluation landscape for early years and preventative services could be strengthened
Coupled deformation responses during thermoset AFP recompaction : process parameter analysis and defect mitigation viability
Get PDFThis study investigates transverse tow deformation in thermoset Automated Fibre Placement (AFP) through systematic process parameter variation, focusing on tow width change and transverse displacement under recompaction. This paper assessed whether compaction-induced width change could mitigate AFP gap defects in process. A full factorial experimental design evaluated the effects of compaction force (C), tooling temperature (T), layup speed (S), external heating (H), and lie time (L). Separate regression models and ANOVA were used to identify significant factors and interactions for each response. Distinct governing mechanisms were identified. Tow width change showed viscosity-dominated behaviour, with tooling temperature as the primary factor and compaction force significant through interaction effects. Strong multi-parameter coupling, particularly C × T × S, demonstrated that meaningful width expansion requires coordinated thermal, mechanical, and temporal control rather than single-factor optimisation. In contrast, transverse displacement was governed solely by compaction force, independent of thermal conditions, indicating a shear-driven mechanical mechanism. A focused follow-up experiment isolating compaction force at moderate temperature confirmed this asymmetry. Width change decreased even at maximum compaction, demonstrating the requirement for thermal activation, while transverse displacement remained fully active, confirming its purely mechanical nature. This coupling shows that compaction forces required for width change inevitably induce displacement, while thermal control cannot decouple the two. The study concludes that compaction-induced width change is ineffective for gap mitigation in thermoset AFP. Achievable width changes are far below gap tolerances and are accompanied by displacement that degrades placement accuracy, representing a fundamental material limitation rather than a parametric optimisation issue
Youth Defence, young people and anti-abortion activism in Ireland, c.1992-97
Get PDFThis article explores the first five years of the Irish young people’s anti-abortion group Youth Defence. Using newspaper articles and archival sources, I illustrate how the group effectively mobilised the category of ‘youth’ in their activism. ‘Youth’ was used to excuse their militant activities and any violence associated with the group. I also argue here that while the group’s activism was profoundly influenced by American campaigners, their rhetoric and activism also embodied nationalist and Catholic tropes. The establishment of Youth Defence also marked a turning point in the anti-abortion movement in Ireland. As older strategies appeared to be losing momentum, the young activists used very imaginative ways of operating but also built on older activists’ methods such as the engagement with transnational connections. I show how the activism of these young people, while focused on the abortion issue, also represented a reaction against broader social and cultural change in Irish society. In subsequent sections, I focus on the activities of Youth Defence and show how their activism, which attracted significant media attention, represented a new wave of more militant anti-abortion activity in Ireland, which provoked tensions both among the public and within the wider anti-abortion movement. Fundamentally, the article aims to show that while the anti-abortion cause was the main reason for activists joining Youth Defence, it also enabled them to channel wider anxieties around young people’s experiences, national identity and changes in Irish society, into protest. In exploring the history of Youth Defence, this article contributes to the history of conservative activism in Ireland and the wider history of the anti-abortion movement
Direct representation and Negotiorum Gestio in Scots Law
No full textThe Scottish Court of Session recognised, in 1887, that ‘it is a frequent case, if a man is not able to manage his affairs, and has a relative who is willing to take the responsibility, there are many instances in which, without their coming to the court… the management goes on with his assistance’. This being an arguably frequent occurrence has not resulted in it being a commonly litigated occurrence and the topic of law engaged by this state of affairs – negotiorum gestio – is critically under-studied within Scotland (and, arguably, other Civilian and mixed legal systems). Like Louisiana, Scotland is a ‘mixed’ jurisdiction which forms a part of a much larger Common law dominated nation-state polity. Unlike Louisiana, Scotland’s law is uncodified: hence (along with South Africa) it has been described as a system of ‘living Roman law’. Within the Scots system there is a widely held view that the doctrine of negotiorum gestio was received unaltered from the law of Justinian. This article explores the extent to which this view stands up to scrutiny, considering the fact that though Scotland was indeed heavily influenced by Roman law during a crucial time in the legal system’s development, the jurisdiction has also expressly – and from an early stage – recognised concepts which were not merely unknown to, but outright rejected by, the Romans. Noting that in the early Scots case law ‘the lines between trust, mandate and negotiorum gestio are often difficult to draw’, the article suggests that the ability of a gestor to act as the direct representative of the dominus is and always has been immanent in Scottish jurisprudence, although a lack of developed case law, the absence of detailed discussion of negotiorum gestio in the institutional writings, and the relative dominance of the concept of remunerated commercial agency since the 19th century has served to stymie such recognition. Nonetheless, it is contended that the institution of negotiorum gestio is profoundly useful and that further academic discussion of the concept would be to the benefit not only of the Scots legal system, but mixed jurisdictions worldwide also
Bulk crystallization of indomethacin from simple and complex solvents
Get PDFBulk crystallization is the commonest method for the high-volume production of pharmaceutical ingredients. As the complexity of both active pharmaceutical ingredient and solvents increases, the behavior of the solute within the solvents may also increase in complexity. This paper compares the nucleation and growth processes of a pharmaceutical ingredient, indomethacin, in three solvents, which span the range of simple to complex. Much of the behavior of indomethacin is mimicked across the solvents, with the γ form of indomethacin crystallizing at low to medium supersaturations. At higher supersaturations, the complex solvents behave as do many other simple solvents in that the solvated β form of indomethacin is found. The great difference in induction time for nucleation and growth time scales for the simple and complex solvents is considered as a function of supersaturation and viscosity and shows that transport processes within the solution play an important role in the crystallization behavior of indomethacin
From borane to metal-bound boraindene : a cascade of bond breaking and making at rhodium
Get PDFFew monobenzannulated 1-boraindene compounds have been reported. Here we report the synthesis of two 1-boraindenes, accessed by a bond-breaking and -making cascade from a secondary borane and diolefin, mediated by a simple pentamethylcyclopentadienyl-ligated rhodium(i) complex, [(Cp*)Rh(η2, η2-NBD)] (Cp* = C5Me5−, NBD = norbornadiene)
Data-driven 1D design model for monotonic lateral loading of monopile foundations
Get PDFMonopiles are a widely-used foundation system for offshore wind turbine support structures. In current practice, design calculations typically employ one-dimensional (1D) models in which the monopile is represented as an embedded beam. The current study presents a data-driven 1D design model for the analysis of offshore monopiles subjected to monotonic lateral load and moment loading. The method is based on the PISA design model framework; enhancements are incorporated in the model to improve its accuracy, scalability and to facilitate applications to a wide range of geotechnical conditions. The data-driven model incorporates a spline-based parametrisation of the soil reaction curves combined with machine learning techniques. The model is calibrated using a database of previously-published three-dimensional finite element calibration analyses. The method described in the current paper is concerned with:•Modifications to the PISA design model framework to develop a data-driven 1D design model.•Calibration of the data-driven 1D model for ground conditions comprising: (i) offshore glacial tills with varying strength-stiffness properties, and (ii) sands with a wide range of relative densities.•Validation of the proposed method by comparing 1D model predictions for monopiles in homogeneous and layered soils with detailed 3D finite element analyses
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