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Amiodarone is a frequently used medication in paediatric patients to manage atrial and ventricular arrhythmias, but its acute haemodynamic effects, particularly in children, remain underexplored. This retrospective, single-centre study aimed to characterise the clinical impact of amiodarone intravenous infusions on heart rate, blood pressure, oxygen delivery, and transaminase levels within the first 48 hours of amiodarone initiation in paediatric cardiac ICU patients.
Methods:
Single-centre, retrospective study of patients receiving amiodarone infusions, with measurements taken at baseline and at various intervals up to 48 hours after initiation. The primary outcome was the effect on heart rate, while secondary outcomes included blood pressure, arterial saturation, near-infrared spectroscopy values, central venous pressure, and transaminase levels. Several types of analysis models were employed to assess the results.
Results:
Data were collected from 87 paediatric patients. No significant changes in liver enzymes, blood pressure, or renal oxygen extraction were observed. These findings provide novel insights into the acute haemodynamic effects of amiodarone infusions in paediatric patients, suggesting that while amiodarone significantly lowers heart rate, it does not substantially affect oxygen delivery or necessitate increased vasoactive support.
Conclusion:
Amiodarone infusions are associated with a significant decrease in heart rate without greatly impacting oxygen delivery or requiring increased vasoactive support. Heart rate decreases most until a cumulative dose of 30,000 mcg/kg, and heart rate decrease is most pronounced in those with ventricular tachycardia.
International organisations (IOs) hold important governance functions and power. Yet, they are several steps detached from the constituencies that have entrusted them with functions and resources to carry them out, even as accountability expectations remain significant for their legitimacy. This article presents a broadly generalisable theoretical framework for understanding the variable accountability of IOs, seeking to advance the understanding of international accountability in three new ways. First, it elaborates on the concept of the scope of IO accountability, which can vary across organisations, over time, and across contexts. The idea of a scope of accountability moves beyond the dichotomy of accountable versus non-accountable power holders and advances an understanding of accountability as a multi-layered phenomenon, whereby both the expectations and practices of accountability can evolve over time and with respect to different audiences. Second, the article identifies three political factors – namely the formal and informal excercise of power, institutional structure, and public salience – that can shape, in important ways, the variable scope of IO accountability. Finally, it critically explores the tensions and contradictions between these political dynamics, and the implications for access to and the efficacy of accountability systems.
In the introduction to this roundtable, we argue that global governance currently faces hard times because it is affected by a set of significant developments revolving around the changing distribution of state power, the rise of nationalist populism, and the frequent occurrence of transnational crises, while seeking to facilitate collective action on complex cooperation problems. Against this backdrop, the essay identifies two major institutional dynamics of global governance in hard times: first, the drift of formal intergovernmental organizations (FIGOs) that is caused by them being gridlocked in a period of significant changes in their social, (geo)political, economic, and technological environment. Second, the proliferation of various types of low-cost institutions. To help us think systematically about how these two interrelated institutional dynamics affect global governance, the essay develops the innovation thesis and the decline thesis. The “innovation thesis” suggests that by transitioning from a rather exclusive and hierarchical system revolving around FIGOs into a more inclusive and heterarchical system revolving around institutional diversity, global governance is currently being adapted to its new environment. The “decline thesis,” by contrast, argues that the two institutional dynamics undermine rules-based multilateralism and may lead to a shift back toward traditional (great) power politics that does not respect institutional constraints.
The rise of visually driven platforms like Instagram has reshaped how information is shared and understood. This study examines the role of social, cultural, and political (SCP) symbols in Instagram posts during Taiwan’s 2024 election, focusing on their influence in anti-misinformation efforts. Using large language models (LLMs)—GPT-4 Omni and Gemini Pro Vision—we analyzed thousands of posts to extract and classify symbolic elements, comparing model performance in consistency and interpretive depth. We evaluated how SCP symbols affect user engagement, perceptions of fairness, and content spread. Engagement was measured by likes, while diffusion patterns followed the SEIZ epidemiological model. Findings show that posts featuring SCP symbols consistently received more interaction, even when follower counts were equal. Although political content creators often had larger audiences, posts with cultural symbols drove the highest engagement, were perceived as more fair and trustworthy, and spread more rapidly across networks. Our results suggest that symbolic richness influences online interactions more than audience size. By integrating semiotic analysis, LLM-based interpretation, and diffusion modeling, this study offers a novel framework for understanding how symbolic communication shapes engagement on visual platforms. These insights can guide designers, policymakers, and strategists in developing culturally resonant, symbol-aware messaging to combat misinformation and promote credible narratives.
This article examines the process of drafting the authoritarian Portuguese Constitution of 1933, which took place during the military regime. The aim is to identify the powers involved, their objectives and the strategies they developed, and to find insights that shed light on the adoption of constitutions by authoritarianisms. The results suggest that conflict between political forces is endemic to the constitutional process, and that those who hegemonise support and aim to demilitarise the system are able to impose the new constitution even without guaranteeing the existence of democratic political parties. There is also a promising point of analysis: the emergence of an authoritarian constitution is based on path dependence, ie, it has many links with the material constitutionalism that precedes it, where there are already normalised authoritarian elements.
This article examines how subnational fiscal competition over foreign direct investment affects both the siting of new projects and the ability of local governments to raise tax revenue for social spending. We leverage a quasi-natural experiment, an unexpected declaration by the Brazilian Supreme Court in 2017 that reduced states’ ability to offer investors differentiated tax subsidies. Our results show that disadvantaged regions did not see a major shift in investment patterns after the change in investment law. We do not find a consistent relationship between the incentive law change and state revenue generation, but we do find that incentives are associated with less revenue. The results are consistent with arguments that investment incentives exacerbate inequality by reducing states’ capacity to collect revenue while doing little to affect investment location. Our results illustrate that economic agglomeration is difficult to reverse through tax policy and that fiscal federalism often cannot provide strong enough inducements to drive investment into less advantaged regions.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment, significantly affecting patients’ quality of life. Current pharmacological treatments are often ineffective or poorly tolerated, necessitating alternative therapeutic approaches. Scrambler Therapy (ST), a non-invasive neuromodulation technique, has shown potential for reducing neuropathic pain, but optimal dosing regimens remain undefined.
Objective
This case study aims to evaluate the effectiveness of Scrambler Therapy in reducing pain levels and improving functional status in a patient with chemotherapy-induced peripheral neuropathy.
Methods
A single patient diagnosed with CIPN was treated with Scrambler Therapy over a series of sessions. Pain levels and functional status were measured using standardized assessment tools before, during, and after the therapy to evaluate the impact of ST on symptom relief and daily functioning.
Results
After completing the Scrambler Therapy sessions, the patient reported significant reductions in pain intensity and notable improvements in functional status. These improvements were sustained several weeks and months following the therapy, indicating the potential long-term benefits of ST for managing CIPN.
Conclusion
This case study demonstrates the potential of Scrambler Therapy as an effective treatment option for reducing pain and improving functional status in patients with chemotherapy-induced peripheral neuropathy. These findings suggest that ST may provide a promising non-invasive alternative to current treatments for managing neuropathic pain in cancer patients.
This study introduces a custom implementation of the Ensemble Kalman Filter (EnKF) for calibrating a three-dimensional glacier evolution model. The EnKF can assimilate observations as they become available and provides uncertainty measures for the initial state after calibration. We calibrate an elevation-dependent surface mass balance (SMB) model using elevation change observations and test the EnKF’s performance in a Twin Experiment by varying internal and external hyperparameters. The best-performing configuration is applied to the Rhône Glacier in a Real-World Experiment. Using satellite-based elevation change fields for calibration, the EnKF estimates an average equilibrium line altitude of $2920 \pm 37$ m for the period 2000–19. A comparison of the results with glaciological measurements demonstrates the capabilities of the EnKF to simultaneously calibrate multiple SMB parameters. With this proof of concept, we expect that our methodology is readily extendable to other map or point observations and their combination, as well as to other calibration parameters.
In Wisconsin, herbicide resistance in waterhemp [Amaranthus tuberculatus (Moq.) Sauer] has been confirmed to five herbicide sites of action, including protoporphyrinogen oxidase (PPO) inhibitors. Following a report of a suspected PPO inhibitor–resistant A. tuberculatus population (A92 accession), our objective was to characterize resistance to PPO inhibitors applied preemergence or postemergence to this accession, along with two PPO inhibitor–susceptible control accessions (A66 and A82). We hypothesized that PPO-inhibitor resistance in A92 was driven by target site–resistance mechanisms. According to our results, the A92 accession is resistant to sulfentrazone (3.1-fold; P-value = 0.0278) and fomesafen (3.1-fold; P-value = 0.0745) preemergence and to lactofen (18.6-fold; P-value = 0.0003) and fomesafen (5.9-fold; P-value <0.0001) postemergence. Resistance to PPO inhibitors was not explained by the presence of any known target-site mutations in PPX1 or PPX2 genes. Our study represents the first confirmed case of an A. tuberculatus accession resistant to PPO inhibitors applied preemergence in Wisconsin. Consistent with previous research, our results demonstrate that the A92 accession, compared with control accessions, is less sensitive to fomesafen regardless of the application timing. Further research is necessary to identify other potential PPO-inhibitor resistance mechanisms in the A92 accession, including potential non–target site resistance mechanisms associated with cytochrome P450 monooxygenases or glutathione S-transferases.
This perspective paper examines biodesign pedagogy in higher education, focusing on the integration of plant sciences with design and technology. We propose a dual framework for teaching biodesign: nature-driven and socially driven approaches. The nature-driven approach draws inspiration from biological strategies or biotechnologies to address environmental and societal challenges, while the socially driven approach begins with identifying societal problems and exploring biological solutions. Drawing on seven years of teaching experience, we highlight student-led projects that illustrate each approach, including eco-friendly textiles derived from plant fibres and genetically engineered crops designed for sustainable urban agriculture. Our findings underscore the potential of biodesign to bridge STEM and creative disciplines, fostering interdisciplinary collaboration, enhancing scientific literacy and equipping students to tackle complex real-world challenges.
We investigate a system of modal semantics in which $\Box \phi $ is true if and only if $\phi $ is entailed by a designated set of formulas by a designated logics. We prove some strong completeness results as well as a natural connection to normal modal logics via an application of some lattice-theoretic fixpoint theorems. We raise a difficult problem that arises naturally in this setting about logics which are identical with their own ‘meta-logic’, and draw a surprising connection to recent work by Andrew Bacon and Kit Fine on McKinsey’s substitutional modal semantics.
Coastal nature-based solution (NBS) projects have been on the rise over the past few years. In France, the expression is being increasingly used at a local level, and new projects are developing on the coast. However, they face various limitations, involving both technical challenges and social acceptability issues. Based on data from the perception survey conducted by the DIGUES research programme in the Authie Bay in 2021 and a numerical model used to assess the efficiency of flood protection measures developed as part of a flood action and prevention programme, this study aimed to highlight the gap between perceptions and misconceptions surrounding NBS-like scenarios and more objective modelling data. It offers a cross-comparison of these two datasets. For this purpose, the scenarios used to assess public perception in the DIGUES survey were translated in the numerical model to study the difference between perceived protection and actual protection in the Authie Bay, the opportunity for dyke relocation in an NBS scenario, and the effectiveness of the NBSs according to their scale. Overall, these results demonstrated a real benefit for implementing dyke relocation through breaches, compared to other scenarios for the Authie Bay.
The current study probes Mandarin-learning toddlers’ sensitivity to two grammatical noun phrase orders differing in typological markedness. With three visual fixation experiments, we find that by age 2;6, children distinguish the cross-linguistically common order – but not the typologically rare one – from an ungrammatical order; however, their sensitivity to the two grammatical orders does not differ significantly. Further, we conduct a corpus analysis and demonstrate that for early acquisition, both grammatical orders are neither sufficiently nor consistently supported in the linguistic input. The sensitivity patterns and input profile outlined in our study constitute the first step of testing, in a natural language setting, a bias for typologically common ordering discussed in the artificial language learning literature. Although the findings remain inconclusive, they underscore the potential for future investigations in this direction.
In this paper, we consider an approach introduced in term rewriting for the automatic detection of non-looping non-termination from patterns of rules. We adapt it to logic programing by defining a new unfolding technique that produces patterns describing possibly infinite sets of finite rewrite sequences. We present an experimental evaluation of our contributions that we implemented in our tool NTI (Non-Termination Inference).
The influence of compressibility on shear flow turbulence is investigated within a self-preservation framework. This study focuses on the axisymmetric jet to examine compressibility effects in a slowly spatially evolving flow, unlike mixing layers, where the convective Mach number remains constant. Revisiting self-preservation, an a priori description of the compressible scaling for Reynolds stresses and higher-order velocity moments is developed. Turbulence moments are found to scale with powers of the spreading rate, suggesting Reynolds stress anisotropy results from compressibility effects consistent with self-preservation of the governing equations. Particle image velocimetry measurements for Mach 0.3 and perfectly expanded Mach 1.25 jets confirm the scaling predictions. The attenuation function, $\varPhi (M_c)$, describing the relationship between the convective Mach number, $M_c$, and the spreading rate, follows a similar trend in jets and mixing layers, where a higher $M_c$ results in reduced spreading rates. In the jet where $M_c$ decays, the relationship between the local $M_c$ and turbulence attenuation remains captured through $\varPhi (M_c)$, which scales proportionally with the spreading rate. A new scale is introduced, where the pressure in the mean momentum equation is substituted. The difference between the streamwise and radial-Reynolds-normal stresses was found to be a scale which is independent of Mach number and spreading rate. Further analysis of the Reynolds-stress-transport budget shows that internal redistribution of energy occurs within the Reynolds-normal stresses, and the role of pressure modification in turbulence attenuation supports previous observations. These findings confirm that the compressible axisymmetric jet exhibits self-preservation, with scaling extending into supersonic regimes.
This study examines the interplay between psychological contract fulfillment, distributive justice, and leader–member exchange (LMX) in shaping affective organizational commitment among university academics. Drawing on social exchange theory, and using simple random sampling, we propose a moderated mediation model to explore how these variables interact. To test the hypotheses, we used the linear moderated mediation test, applying PROCESS for SPSS. Specifically, on a sample of 465 academics, the study tests the hypothesis that distributive justice mediates the relationship between psychological contract fulfillment and affective commitment, with LMX acting as a moderator. Findings reveal that distributive justice is not always necessary for fostering affective commitment when psychological contracts are fulfilled, unless the quality of LMX is low. In low-quality leader–member relationships, perceptions of distributive justice become crucial when it comes to translating contract fulfillment into affective commitment. These results highlight the importance of relational dynamics in academic settings, especially when resources are limited. The study concludes with a discussion of its theoretical and practical implications, as well as limitations and avenues for future research.
This article contributes to the literature on religious soft power by considering how non-Muslim-majority great powers – China, Russia, and the US – use Islam as a foreign policy resource in their soft power strategies. We argue that these states have deployed Islam to present positive self-images on the international stage, at the same time as using negative-other strategies via soft disempowerment to construct competitor states as unfriendly and/or dangerous to Muslims. We conclude by arguing that the use of Islam by non-Muslim great powers is a potentially dangerous game. While instrumentalising Islam may provide immediate benefits, it also opens the possibility for critique, particularly around perceived inconsistencies between domestic religious practices of a state and its internationally promoted narratives. These tensions can invite accusations of illegitimacy and hypocrisy, especially when leveraged by competitors or transnational religious actors.
The capabilities of large language models (LLMs) have advanced to the point where entire textbooks can be queried using retrieval-augmented generation (RAG), enabling AI to integrate external, up-to-date information into its responses. This study evaluates the ability of two OpenAI models, GPT-3.5 Turbo and GPT-4 Turbo, to create and answer exam questions based on an undergraduate textbook. 14 exams were created with four true-false, four multiple-choice, and two short-answer questions derived from an open-source Pacific Studies textbook. Model performance was evaluated with and without access to the source material using text-similarity metrics such as ROUGE-1, cosine similarity, and word embeddings. Fifty-six exam scores were analyzed, revealing that RAG-assisted models significantly outperformed those relying solely on pre-trained knowledge. GPT-4 Turbo also consistently outperformed GPT-3.5 Turbo in accuracy and coherence, especially in short-answer responses. These findings demonstrate the potential of LLMs in automating exam generation while maintaining assessment quality. However, they also underscore the need for policy frameworks that promote fairness, transparency, and accessibility. Given regulatory considerations outlined in the European Union AI Act and the NIST AI Risk Management Framework, institutions using AI in education must establish governance protocols, bias mitigation strategies, and human oversight measures. The results of this study contribute to ongoing discussions on responsibly integrating AI in education, advocating for institutional policies that support AI-assisted assessment while preserving academic integrity. The empirical results suggest not only performance benefits but also actionable governance mechanisms, such as verifiable retrieval pipelines and oversight protocols, that can guide institutional policies.
Electronic Health Record (EHR) data are critical for advancing translational research and AI technologies. The ENACT network offers access to structured EHR data across 57 CTSA hubs. However, substantial information is contained in clinical narratives, requiring natural language processing (NLP) for research. The ENACT NLP Working Group was formed to make NLP-derived clinical information accessible and queryable across the network.
Methods:
We established the ENACT NLP Working Group with 13 sites selected based on criteria including clinical notes access, IT infrastructure, NLP expertise, and institutional support. We divided sites into five focus groups targeting clinical tasks within disease contexts. Each focus group consisted of two development sites and two validation sites. We extended the ENACT ontology to standardize NLP-derived data and conducted multisite evaluations using the Open Health Natural Language Processing (OHNLP) Toolkit.
Results:
The working group achieved 100% site retention and deployed NLP infrastructure across all sites. We developed and validated NLP algorithms for rare disease phenotyping, social determinants of health, opioid use disorder, sleep phenotyping, and delirium phenotyping. Performance varied across sites (F1 scores 0.53–0.96), highlighting data heterogeneity impacts. We extended the ENACT common data model and ontology to incorporate NLP-derived data while maintaining Shared Health Research Informatics NEtwork (SHRINE) compatibility.
Conclusion:
This demonstrates feasibility of deploying NLP infrastructure across large, federated networks. The focus group approach proved more practical than general-purpose approaches. Key lessons include the challenge of data heterogeneity and importance of collaborative governance. This work also provides a foundation that other networks can build on to implement NLP capabilities for translational research.
The Stages of Objective Memory Impairment (SOMI) system, based on the Free and Cued Selective Reminding Test (FCSRT), is a potential marker of subtle cognitive impairment in cognitively normal persons defined by a Clinical Dementia Rating (CDR) = 0. We investigated SOMI’s ability to predict incident cognitive impairment (CDR >0) in combination with demographic features and neuroimaging biomarkers.
Methods:
Cognitively unimpaired participants (CDR = 0) from the Harvard Aging Brain Study had baseline FCSRT scores, MRI, FDG-PET, and PiB-PET as well as follow-up CDRs for 5 years. Cox proportional hazards models with correction for multiple testing assessed the predictive validity of SOMI and neuroimaging biomarkers for progression (CDR >0). Comprehensive sensitivity analyses examined alternative outcomes and stricter screening criteria.
Results:
Participants (N = 231) were 73.7 years (SD = 6.0), 60.2% were female, 29.0% were APOE4 positive, and 54 (23.4%) progressed to CDR >0. At baseline, 67% were SOMI-0, 22% were SOMI-1, 4% were SOMI-2, and 7% were SOMI-3/4. After multiple testing correction, hazard ratios (HRs) using SOMI-0 as reference were: SOMI-1 = 2.06 (CI: 1.09 – 3.88), SOMI-2 = 2.85 (CI: 1.08 – 7.54), and SOMI-3/4 = 3.73 (CI: 1.58 – 8.79, p = 0.016). SOMI-3/4 remained significant across most biomarker models. Entorhinal thickness emerged as the most robust biomarker predictor (HR = 0.57 – 0.65, p ≤ 0.015). Sensitivity analyses confirmed robustness across alternative outcomes and stricter screening criteria.
Conclusions:
SOMI stages predict progression to incident cognitive impairment with SOMI-3/4 maintaining significance after rigorous multiple testing correction. Entorhinal thickness provides the strongest biomarker enhancement to prediction models. SOMI demonstrates substantial incremental predictive value beyond standard demographic and biomarker predictors.