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How have systems approaches been used to understand how antimicrobials are used and governed in healthcare organisations? A scoping review protocol
Get PDFSepsis is a life-threatening condition requiring timely antimicrobial treatment. However, inappropriate antimicrobial use exacerbates antimicrobial resistance (AMR), creating a tension between treating sepsis promptly and minimising antimicrobial overuse. Despite numerous policies and significant research related to sepsis and AMR, there remains a persistent gap between recommendations and real-world practice due to system factors that impact normal work in all healthcare contexts. The aim of this scoping review is to understand how systems approaches have been used to study the use and governance of antimicrobials in clinical work.
Methodsd analysis
The scoping review protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Empirical research, reviews, protocols, theses/dissertations and quality improvement projects across all healthcare settings will be included if a primary focus includes studying antimicrobial use from a systems perspective. Searches will be conducted in EMBASE, MEDLINE and CINAHL with grey literature searching and backward citation tracking. Data on the geography and contexts studied, use of system theory, study design, approaches to data collection and analysis, limitations and implications will be extracted. Quantitative data will be categorised and qualitative data will be analysed thematically. Ethical approval is not required for the use of secondary, published data. Findings will be disseminated through academic publications and national and international presentations. Insights will be used to inform improvement work and empirical research to better support the sepsis-antimicrobial stewardship tension across multiple organisational levels
The emerging role of calsequestrin 2: from calcium sensor and modulator to arrhythmia driver
Get PDFCalsequestrin 2 (CASQ2) has emerged as a central sensor and modulator of calcium (Ca2+) dynamics in sarcoplasmic reticulum (SR), influencing both health and disease. This review explores the molecular architecture and multifunctional roles of CASQ2, beginning with its domain organization and Ca2+-binding properties and detecting how its folding and supramolecular assembly modulate Ca2+ storage and release within cardiac muscle. Post-translational modifications, genetic regulatory mechanisms and CASQ2’s multipartner interactome; including Ryanodine receptor 2 (RyR2), triadin and junctin are also discussed to highlight potential models in which complex stoichiometry and luminal Ca2+ dictate channel refractoriness and excitation-contraction coupling. Disruption of CASQ2 function is increasingly recognized as a driver of certain types of arrhythmias, notably catecholaminergic polymorphic ventricular tachycardia (CPVT) and heightened risk of sudden cardiac death. This review appraises contemporary therapies that focus on pharmacological and device-based interventions and surveys next-generation strategies that aim to directly stabilize CASQ2 or target its gene expression. Despite therapeutic advances, the challenges remain; and a translational agenda aligning mechanism with therapy is proposed. By integrating recent structural, functional, regulatory and pathological insights, this review provides a conceptual framework for the pivotal role of CASQ2 in arrhythmogenesis and positions CASQ2 biology at the center of precision cardiology
The monetary economy of the Seleukid Empire
Get PDFThe present thesis is a study of the monetary economy of the Seleukid empire, from its inception until the late 2nd century BC, right before its collapse. The Seleukid empire was a political entity that encompassed a large territory and a wide variety of peoples and traditions. As a result, Seleukid rule was not articulated in the same way everywhere. The study of coins obviates to some of the methodological problems traditionally posed by cross-regional comparisons of the Seleukid empire, and it also allows us to appreciate structural differences between the various phases of its existence. The aim of the thesis is to understand the reasons and the modalities in which the Seleukids produced their coins, and how the latter were used, in two different regions of the empire – Northern Syria and Western Asia Minor. The analysis of the numismatic evidence will be conducted against the historical, political, and numismatic backdrop of these two regions. As a result, in order better to understand the peculiarities of Seleukid coin-production and circulation, the present thesis adopts a long-durée approach, spanning from the 5th century BC until the late 2nd century BC. Through the comparison with the Achaemenid and early Hellenistic periods, the aim of Chapter 1 is to formulate a Seleukid model of monetary economy for Northern Syria, a region where the state was at its “strongest”. However, it will become clear that it is possible to argue that several models of the Seleukid monetary economy existed in Northern Syria, depending on the coin-types or even on the individual reigns under consideration. The results of Chapter 1 will be compared with the data from Western Asia Minor in Chapter 2 and 3. Contrary to Northern Syria, Asia Minor was a territory where royal authority over the subordinate cities and dynasts had often to be negotiated. Nonetheless, royal interference – or lack of it – in the minting activity of the cities of Western Asia Minor, and the impact of the royal troops on the patterns of coin circulation, represent important pieces of material evidence that will help shed light on the realities of Seleukid imperialism, beyond the rhetoric of the language of royal euergetism
Cumulative Absorbed Dose and Successive Cyclic Reduction in Absorbed Dose Predict Response to <sup>177</sup> Lu-DOTATATE in Neuroendocrine Tumors
Get PDFThe aim of this study was to use image-derived dose metrics to predict the radiologic response of neuroendocrine tumors treated with [177Lu]Lu-DOTATATE. Particular focus was given to the evaluation of cyclic changes in absorbed dose per administered activity (AD/AA) as a potential prognostic factor. Methods: Data from 73 patients enrolled in the multicenter OZM-067 trial (NCT02743741) were analyzed. All patients who received 4 cycles of [177Lu]Lu-DOTATATE and underwent SPECT/CT imaging at 3 time points after each treatment were included. Tumor dosimetry was based on semiautomatic adaptive-threshold segmentations and recovery coefficient-based partial-volume correction; tumors smaller than 10 cm³ were excluded. If multiple tumors were segmented per patient, the mean absorbed dose (AD) and AD/AA were recorded at each cycle. Radiologic response was assessed using RECIST 1.1 criteria. Results: A significant decrease in AD/AA across cycles was observed, with a median decline of approximately 10% per cycle. Within this cohort, 28 patients had a partial response, 33 had stable disease, and 12 experienced disease progression. Responders exhibited a higher mean cumulative AD and greater decreases in AD/AA in successive cycles when compared with nonresponders. These metrics were uncorrelated predictors of response (P = 0.64). Notably, all 8 patients with an AD of at least 100 Gy and a decrease of at least 50% in AD/AA between cycles 1 and 4 were responders. Quantitative models combining AD and changes in AD/AA achieved an area under the receiver-operating-characteristic curve of 0.78. Conclusion: Both AD and changes in AD/AA were independently associated with radiologic response to [177Lu]Lu-DOTATATE in patients with neuroendocrine tumors. The consistent decrease in AD/AA over a course of therapy suggests a potential imaging biomarker that could inform adaptive treatment strategies, which should be further evaluated in a prospective setting and considered when designing dosimetry-guided [177Lu]Lu-DOTATATE trials
Recurrent spectres: children on the move between France and the UK
No full textAnonymous collages are evidence of the presence of children on the move who come through Calais daily. Secours Catholique keeps the vestiges of what I call their Derridean (1994) spectral absent presence next to the sketches of an artist volunteer who has also made portraits of some of these children who transit through. Through these sketches, I contend that the children are ‘living-on’ (Derrida 1994: xx), co-existing in the same space time as children who currently occupy the premises of Secours Catholique, their ghostly presences haunting the premises. Despite the ‘evolving geopolitics of compassion’ (Casavetes Bradford 2022, 209), identified in the US context, and which is also evident in France where repression has overtaken compassion (Fassin 2010, Kistnareddy 2024), charities attempt to look after children’s wellbeing while they are in transit. France’s protection of minors is contingent upon ‘the young person first requesting refugee status’ (Hernandez and Uzureau 2018, 478) and this extends to children who undergo an evaluation process to determine whether they are legally minors, much like the UK’s National Age Assessment Board. For children in transit, such protections are inexistent. They are also ghosts in a system that does not recognise them until they make their presence legally known. Drawing on fieldwork undertaken in Calais and in the UK, this paper looks at the ways in which these two places can function as a limbo space that exists outside of time as previous children and current children also co-exist with future children who are inevitably always to come due to the lack of legal routes to apply for asylum in the UK
The 2026 skyrmionics roadmap
Get PDFMagnetic skyrmions and related topological spin textures have emerged as a central topic in condensed-matter physics, combining fundamental significance with potential for transformative applications in spintronics, magnonics, and beyond. Over the past decade, advances in material platforms, imaging techniques, theoretical modeling, and device concepts have established skyrmionics as a rapidly expanding field. At the same time, challenges remain in stabilizing, controlling, and integrating such textures into functional architectures, while novel phenomena such as antiskyrmions, higher-order skyrmions, hopfions, and antiferromagnetic textures arise. The 2026 Skyrmionics Roadmap represents a collective effort of many authors, providing a comprehensive perspective on the current state-of-the-art and the outlook for the coming years. In 33 focused sections, each co-authored by two researchers, we chart progress in theory and modeling, material systems, skyrmion dynamics, and skyrmion technologies. By offering a consolidated vision, this Roadmap aims to guide both fundamental research and application-driven efforts, accelerating the transition of skyrmionics from conceptual breakthroughs toward practical technologies
Solar Flow Synthesis of Polymer Nanoparticles: Scaling Local Experiments to Global Potential
Get PDFWe present the scalable, additive‐free synthesis of polymer nanoparticles in continuous flow, using solely solar radiation. Using a custom‐made flow reactor, the UV radiation from the sun induces a Diels–Alder step‐growth polymerization between a bismaleimide and a difunctional o‐methylbenzaldehyde. The resulting photopolymer subsequently precipitates as nanoparticles without the need for any additional additives, stimuli or processing steps. The solar flow reactor was designed by first carefully assessing the underpinning photochemistry of the photo‐induced Diels–Alder reaction using photochemical action plots and then performing a kinetic investigation of the particle formation under solar irradiation. The determined kinetics allow us to extrapolate our experimental results to a worldwide particle yield by using global UV index data, validated by two highly different geographical locations, Australia and Germany. Our results clearly demonstrate the applicability of our system for the scalable, sustainable, solar‐powered production of polymeric nanoparticles in regions of high levels of solar radiation. Furthermore, our calculations function as a blueprint for how local experimental data can be extrapolated to assess the global solar photochemical potential of photochemical systems, thus making their performance comparable
Space‐use by feral cattle and horses shapes vegetation structure in a trophic rewilding area
Get PDFFeral cattle (Bos taurus) and horses (Equus ferus caballus) are commonly introduced to European rewilding areas to halt vegetation succession and to conserve light‐demanding species. Yet, we still do not understand how the habitat preference of animals shapes vegetation structure at the landscape scale. Here, we used spatial preference modeling to understand drivers of space‐use based on GPS‐collared horses and cattle in a 120‐ha rewilding area in Denmark. Using a time series of a satellite‐based vegetation productivity index, we tested the ability of animal space‐use to explain changes in vegetation, as well as the trend of its spatial variability at the reserve scale, as a measure of landscape‐scale vegetation heterogeneity. We expected that animal space‐use would be driven mainly by topography and vegetation characteristics and that highly used areas with open vegetation would remain open. We, indeed, found that vegetation density and landscape connectivity were good predictors of space‐use preference for both cattle and horses. Additionally, both cattle and horses were strongly attracted to an artificial shelter located inside the reserve, warranting consideration of the use and placement of artificial infrastructure. Space‐use diverged during periods of resource scarcity emphasizing the value of introducing a variety of herbivore functional types for optimizing structural ecosystem heterogeneity. As expected, we found that cattle and horses slow down vegetation succession in highly used areas, as shown by the negative correlation between changes in growing season productivity and intensively used areas dominated by short herbaceous and shrubby vegetation. We could also show that the highly used areas showed the largest reductions and the fastest recovery in vegetation greenness following the pan‐European drought in 2018. A ~2/3 reduction in herbivore population size subsequent to the drought was followed by a general greening of the landscape, but with no clear relationship with space‐use intensity. Our study supports that trophic rewilding with year‐round grazing can limit vegetation densification at the landscape scale under near‐natural conditions. This is pertinent in the face of accelerating succession toward increasingly dark and tree‐dominated vegetation in temperate Europe's natural areas, and the associated biodiversity loss
Investigating ethnicity-related variability in the human L-cone spectral sensitivity function
Get PDFThe human cone photoreceptor spectral sensitivities can differ between individuals. Large changes give rise to colour vision deficiencies, but even among colour-normals there is systematic individual variation. To limit the propagation of any systematic sampling bias in constructing the average spectral sensitivity functions used in research and industrial applications, it is useful to quantify the factors underlying this variation. The amino acid found at position 180 of OPN1LW, the gene responsible for encoding the L cone photopigment, is one source of individual variation in the L-cone spectral sensitivity. In this paper, group differences in the frequency of the L(S180) and L(A180) alleles are analysed from a combination of published reports and the genome sequencing database, gnomAD. We report evidence for significant group differences across ethnicity. Historical sampling bias in the data underlying the average L cone spectral sensitivity function therefore introduces ethnic bias in the applicability of these functions. We discuss the challenges of incorporating ethnicity variation in the existing L cone fundamental as adopted by the CIE Commission Internationale de l’Eclairage in 2006, and promising work on personalized cone fundamentals