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The experiences of bedside nurses delivering an intensive care sedation study: a process evaluation within the A2B trial
Get PDFSedation management in ICUs is essential for patient safety and comfort, allowing critically ill patients to tolerate mechanical ventilation, minimise discomfort, and avoid agitation. Traditionally, ICU sedation has favoured deeper sedation to ensure ventilator compliance and reduce risks like agitation or accidental self-extubation, although recent evidence challenges this paradigm.1 Deep sedation, while effective in the short term, is linked to poorer outcomes such as prolonged mechanical ventilation and ICU stays. Evidence suggests lighter sedation strategies may improve outcomes but could pose risks to long-term psychological well-being.2,3 Propofol, typically used with intravenous (IV) opioid infusions, is recommended as first-line sedation in clinical guidelines. The alpha-2 agonist dexmedetomidine is also being increasingly used due to its capacity for lighter sedation and analgesic properties that might reduce opioid use.4 Clonidine is an alpha-2-agonist used widely in the UK, instead of dexmedetomidine. A one-day point prevalence of UK ICU sedation practices reported 10.4% of ventilated patients were receiving dexmedetomidine, as opposed to 5.5% receiving clonidine.5The Alpha-2 Agonists for Sedation to Produce Better Outcomes from Critical Illness (A2B) trial compared dexmedetomidine and clonidine to standard propofol sedation. The primary outcome was time to successful extubation, with secondary outcomes including ICU mortality, time to discharge, sedation quality, delirium rates, and cardiovascular events. Patients were randomised into three groups (propofol, dexmedetomidine, clonidine) accompanied by an IV opioid infusion, with additional pain relief as needed, and continued propofol permitted in the alpha-2 agonist groups where necessary. The goal across all groups was to maintain light sedation (Richmond Agitation-Sedation Scale (RASS) of -2 to +1) meaning patients were calm but easily rousable. For alpha-2 agonist groups, rapidly increasing trial medication post-randomisation was crucial, aiming for sedation primarily via the allocated drug.The trial found no significant difference in time to extubation or sedation quality and delirium measures.6 However, significantly higher agitation and bradycardia rates occurred in alpha-2 agonist groups. Continued low-level propofol use (20-30%) persisted in both intervention groups, and around 25% of patients required deeper sedation during the intervention illustrating the complexity of changing sedation practices within trial conditions.Nurses are central in ICU sedation protocol implementation, managing titration and monitoring. Their experiences significantly influence intervention feasibility and fidelity. The A2B trial required addressing entrenched practices like overnight deeper sedation or beliefs that deeper sedation is ‘safer’ for avoiding adverse events. However, lighter sedation was accepted as best practice across all trial groups and was not an area of differentiation in the trial protocol. Managing known side-effects of alpha-2 agonists such as bradycardia, hypotension, and ileus remained challenging. Recognising ICU sedation complexity, the A2B trial included a process evaluation to examine factors such as nurse experience, unit culture, resources, and clinical decision-making, essential for optimising sedation protocols and improving outcomes.The process evaluation was conceptually informed by a framework that adapts elements from existing models for evaluating complex interventions,7-10 developed specifically to meet the challenges of research in ICU settings. This approach draws on established guidance while addressing the realities of high-acuity, team-delivered care and organisational variation. It reflects a pragmatic orientation, focused on understanding how participant- and organisational-related factors shape implementation, delivery, and intervention outcomes
Universal sectors of two-dimensional Carrollian CFTs
Get PDFWe revisit modular invariance in two-dimensional Carrollian conformal field theories from a geometric perspective. Focusing on the characters of the induced and highest-weight representations of the theory, we show that there are regions of parameter space where the vacuum character dominates in the dual channel. We use this property to zoom into different subsectors of the Carrollian theory. One of them is reminiscent of the Schwarzian sector of a relativistic CFT2 and has a flat space holographic interpretation as O-plane orbifold. It exists only for the highest-weight representation. We prove that for all sectors with vacuum dominance in the dual channel, the specific heat is negative, concurrent with the holographic interpretation of the negative specific heat of asymptotically flat spacetimes with horizons
By leaves we live: Entanglements with the 30 x 30 biodiversity challenge on veterinary campuses
Get PDFAddressing the nature emergency on veterinary campuses will challenge us to embrace the 30x30 biodiversity challenge and explore the life-giving processes that sustain life in our bio-regional home areas. In this paper, a group of transdisciplinary collaborators explore three entanglements that profoundly represent this key aspect of the metacrisis of the Anthropocene, doing so through a series of experiential workshops. By focussing on specific entangled features of the Easter Bush campus, at the University of Edinburgh, we are able to explore boundary making practices and to develop some sense of the relational whole and our place in the whole. The features that called for our attention included the river flowing through the campus and a local badger sett, dug into the refuse tip that past generations of humans have created beside the river. This work allows a series of recommendations about outdoor learning for eco-literacy, multispecies dialogue and justice to be proposed. The inter- and intra-connections between nature restoration and human restoration uncovered through this work, highlight that there are One Health justice issues here that we would do well to pay attention to in seeking to nurture more sustainable futures. This has implications for habitat restoration on veterinary campuses, for pedagogical practice and curriculum reform. Such reforms will need to recognise the damage caused by reductive science, the absence of systems thinking and process philosophy in teaching and the failure to promote spaces and opportunities for nature connection and outdoor learning
Passive Immunity Establishment Through Colostral IgG Absorption in Neonatal Ruminants: Foundation for Efficient Ruminant Production
Get PDFPassive immunity, the acquisition of specific immune protection through external antibodies or immune components, is critically important for neonatal survival. In ruminants, however, neonatal hypogammaglobulinemia, a consequence of their epitheliochorial placental structure preventing prenatal antibody transfer, often leads to high morbidity and mortality. Consequently, neonatal ruminants are entirely dependent on the timely consumption of colostrum to acquire sufficient immunoglobulin G (IgG) for protection. Establishing robust passive immunity is therefore a cornerstone for their survival, healthy development, and future production efficiency. This review synthesizes current knowledge on the establishment of passive immunity in neonatal ruminants. We first outline the fundamental principles of passive immunity transfer, then delve into the specific pathways and molecular mechanisms in ruminants. Key factors influencing this process are subsequently discussed. Furthermore, we highlight the long-term impact of passive immunity on adult production performance. This review aims to provide a scientific foundation for optimizing colostrum management strategies and to stimulate future research into the intricate mechanisms of IgG absorption.<br/
Review article: AntArchitecture – building an age–depth model from Antarctica's radiostratigraphy to explore ice-sheet evolution
Get PDFRadio-echo sounding (RES) has revealed an internal architecture within both the West and East Antarctic ice sheets that records their depositional, deformational and melting histories. Crucially, RES-imaged internal-reflecting horizons, tied to ice-core age–depth profiles, can be treated as isochrones that record the age–depth structure across the Antarctic ice sheets. These enable the reconstruction of past climate and ice dynamical processes on large scales, which are complementary to but more spatially extensive than commonly used proxy records (e.g. former ice limits constrained by cosmogenic dating or offshore sediment sequences) around Antarctica. We review the progress towards building a pan-Antarctic age–depth model from these data by first introducing the relevant RES datasets that have been acquired across Antarctica over the last 6 decades (focussing specifically on those that detected internal-reflecting horizons) and outlining the processing steps typically undertaken to visualise, trace and date (by intersection with ice cores or modelling) the RES-imaged isochrones. We summarise the scientific applications for which Antarctica's internal architecture has been used to date and present a pathway to expanding Antarctic radiostratigraphy across the continent to provide a benchmark for a wider range of investigations: (1) identification of optimal sites for retrieving new ice-core palaeoclimate records targeting different periods; (2) reconstruction of surface mass balance on millennial or historical timescales; (3) estimation of basal melting and geothermal heat flux from radiostratigraphy and comprehensive mapping of basal-ice units to complement inferences from other geophysical and geological methods; (4) advancement of the knowledge of volcanic activity and fallout across Antarctica; and (5) refinement of numerical models that leverage radiostratigraphy to tune time-varying accumulation, basal melting and ice flow, firstly to reconstruct past behaviour and then to reduce uncertainties in projecting future ice-sheet behaviour
The Future of Abortion in Scotland:Is there a Continuing Role for the Criminal Law?
Get PDFAbortion remains a criminal offence in Scotland, regulated not by statute but by the common law, and permitted only through a vague and underdefined 'therapeutic exception'. While recent developments in England and Wales signal a shift towards decriminalisation-prompted by rising prosecutions and renewed commitments to bodily autonomy-Scotland's legal framework remains obscure, outdated, and largely unscrutinised. This article provides comprehensive doctrinal analysis of abortion as a criminal offence in Scots law. For the first time in Scots law literature, it is argued that the legal uncertainty surrounding the scope and application of the offence, including its supposed 'therapeutic exception', undermines access to care, exposes patients and practitioners to legal risk, and impedes meaningful reform. Contrary to previous claims that Scotland's quieter legal record reflects a more lenient or effective approach, this article contends that continued criminalisation-however latentcreates unacceptable barriers to reproductive healthcare. In light of evolving human rights norms and domestic reform efforts, the article concludes that Scotland must confront the question of decriminalisation with urgency and clarity
Cohort profiles:Personality measurements at the Estonian Biobank of the Estonian Genome Center, University of Tartu
No full textLike all behaviour, personality traits are substantially heritable, but their genetic background is poorly understood. Investigating traits’ genetic background could help explain disparities in health and other life outcomes they contribute to. We describe two cohorts of the Estonian Biobank for whom, besides self- and informant-rated personality traits, detailed data are available on a wide range of measures including health behaviour, biomarkers, anthropometric measurements, and medical diagnoses and treatments. The first cohort (Nself-report = 3,640, Ninformant-report = 3,488) filled out the NEO Personality Inventory-3 (NEO-PI-3) between 2008 and 2018. The second cohort (Nself-report = 77,400, Ninformant-report = 21,986), collected between 2021 and 2022, responded to a large and diverse item pool called the 100 Nuances of Personality (100NP) covering the Big Five and other traits. Research opportunities include investigation of personality traits’ properties, gene discovery, prediction of health and well-being, and causal modelling. New data are added periodically through additional data collection waves and linkage with various registries and databases
Ten-Year Survival after Postmastectomy Chest-Wall Irradiation in Breast Cancer
No full textBACKGROUND The role of postmastectomy chest-wall irradiation in patients with breast cancer classified as pN1 (with involvement of one to three axillary nodes) or pN0 (pathologically node negative) with additional risk factors is uncertain. METHODS In this international, phase 3, randomized trial, we evaluated the omission of chest-wall irradiation in women with “intermediate-risk” breast cancer — defined as cancer that was stage pT1N1, pT2N1, or pT3N0 or stage pT2N0 with a histologic grade of 3, lymphovascular invasion, or both (tumor size: T1, ≤2 cm; T2, >2 cm to 5 cm; or T3, >5 cm) — that was treated with mastectomy, an axillary procedure, and systemic therapy. Patients were assigned to undergo chest-wall irradiation (40 to 50 Gy; the irradiation group) or not to undergo chest-wall irradiation (the no-irradiation group). The primary end point was overall survival, with 10 years of follow-up. Chest-wall recurrence, regional recurrence, disease-free survival, distant metastasis–free survival, causes of death, and radiation-related adverse events were also assessed. RESULTS The intention-to-treat population included 808 patients in the irradiation group and 799 in the no-irradiation group. The median follow up was 9.6 years. Overall survival was 81.4% with chest-wall irradiation and 81.9% with no chest-wall irradiation according to 10-year Kaplan–Meier estimates (hazard ratio for death, 1.04; 95% confidence interval [CI], 0.82 to 1.30; P=0.80). A total of 29 patients had a chest-wall recurrence — 9 (1.1%) in the irradiation group and 20 (2.5%) in the no-irradiation group (between-group difference, <2 percentage points; hazard ratio, 0.45; 95% CI, 0.20 to 0.99). Disease-free survival was 76.2% in the irradiation group and 75.5% in the no-irradiation group (hazard ratio for recurrence or death, 0.97; 95% CI, 0.79 to 1.18), and distant metastasis–free survival was 78.2% and 79.2%, respectively (hazard ratio for distant metastasis or death, 1.06; 95% CI, 0.86 to 1.31). CONCLUSIONS In this trial, chest-wall irradiation did not result in higher overall survival than no chest-wall irradiation among patients with intermediate-risk, early breast cancer treated with mastectomy and contemporary adjuvant systemic therapy. (Funded by the Medical Research Council and others; SUPREMO ISRCTN Clinical Study Registry number, 61145589.)</p
From policy to practice: progress towards data- and code-sharing in ecology and evolution
No full textData and code are essential for ensuring the credibility of scientific results and facilitating reproducibility, areas in which journal sharing policies play a crucial role. However, in ecology and evolution, we still do not know how widespread data- and code-sharing policies are, how accessible they are, and whether journals support data and code peer review. Here, we first assessed the clarity, strictness and timing of data- and code-sharing policies across 275 journals in ecology and evolution. Second, we assessed initial compliance to journal policies using submissions from two journals: Proceedings of the Royal Society B (Mar 2023–Feb 2024: n = 2340) and Ecology Letters (Jun 2021–Nov 2023: n = 571). Our results indicate the need for improvement: across 275 journals, 22.5% encouraged and 38.2% mandated data-sharing, while 26.6% encouraged and 26.9% mandated code-sharing. Journals that mandated data- or code-sharing typically required it for peer review (59.0% and 77.0%, respectively), which decreased when journals only encouraged sharing (40.3% and 24.7%, respectively). Our evaluation of policy compliance confirmed the important role of journals in increasing data- and code-sharing but also indicated the need for meaningful changes to enhance reproducibility. We provide seven recommendations to help improve data- and code-sharing, and policy compliance
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