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Cost-Effectiveness of Metoclopramide, Paracetamol, and Ceftriaxone for the Prevention of Infections and Fever in Elderly Patients with Acute Stroke
No full textObjective. Infections and fever after stroke are associated with poor functional outcome and death. We compared the cost-effectiveness of prophylactic metoclopramide, paracetamol, and ceftriaxone, either as monotherapies or in combination, with standard of care for reducing complications in older patients with acute stroke. Methods. We conducted a model-based analysis estimating expected lifetime costs, quality-adjusted life-years (QALYs), and net monetary benefit (NMB) from a Dutch health care perspective, given a willingness-to-pay threshold of 50,000 euros per QALY gained. The model synthesized patient-level data from the PREvention of Complications to Improve OUtcome in older patients with acute Stroke (PRECIOUS) trial with data from long-term observational studies. We conducted a value-of-information analysis to quantify the expected value of reducing decision uncertainty through additional data collection on key input parameters. Results. Combination therapy with metoclopramide, ceftriaxone, and paracetamol yielded the highest expected NMB and was the most cost-effective treatment option. When compared with standard care, this treatment option decreased costs by €6,438 and increased QALYs by 0.10, resulting in an incremental NMB of €11,721. The value-of-information analysis indicated that decision uncertainty was driven by uncertainty about the treatment effects on poststroke disability, measured by the modified Rankin Scale (mRS). Moreover, the analysis suggested that the expected value of reducing uncertainty through additional data collection on acute phase mRS scores far exceeds the expected costs. Conclusion. Our economic evaluation suggests that combination therapy with metoclopramide, paracetamol, and ceftriaxone may be the most cost-effective option for treating older patients with stroke in the Netherlands. However, there is likely great value in reducing uncertainty by conducting a new study that collects additional data on acute phase mRS scores. Highlights: Prophylactic combination therapy with metoclopramide, paracetamol, and ceftriaxone may be the most cost-effective strategy for preventing infections and fever in elderly patients with acute stroke. There is substantial decision uncertainty, primarily driven by uncertainty regarding the treatment effects on functional outcome (modified Rankin Scale, mRS). Value-of-information analysis indicates that the value of reducing uncertainty through a new study on acute phase mRS scores is very high
Termination of DNA replication drives genomic instability via multiple mechanisms
No full textTermination of DNA replication is a surprisingly complex process that contributes critically to genome stability and cell viability. And even though progress was made to establish the consequences that arise if termination is going awry, the precise molecular mechanisms of fork fusion events and the coordination with key factors that ensure that DNA replication is brought to a successful conclusion remain poorly understood. We therefore investigated replication termination in Escherichia coli, focusing specifically on the interplay between replication fork fusions and genomic stability, the Tus–ter replication fork trap, and key DNA-processing enzymes. By utilizing whole genome sequencing, immunoblotting, and recombination reporter assays, we demonstrate that local hyper-recombination is induced wherever forks meet and that the combined loss of factors such as RecG helicase and 3′ exonucleases causes extreme over-replication in the terminus region of the chromosome. Unexpectedly, cells lacking Tus exhibit elevated R-loop levels, revealing an unanticipated connection between the fork trap and R-loop metabolism. These findings underscore the complexity of replication termination and its central role in maintaining bacterial genome stability, while providing mechanistic insights with implications for understanding replication termination in more complex organisms and developing new antimicrobial strategies
The Impact of Say‐On‐Pay on Firm Efficiency in Anglo‐Saxon Economies—Do CEO Personal Traits and CG Mechanisms Matter?
Get PDFIn this study, we explore how the personal traits of CEOs and corporate governance mechanisms moderate the link between say-on-pay (SOP) votes and various aspects of firm efficiency. Our sample consists of 1931 firms listed in four Anglo-Saxon economies (i.e., USA, UK, Canada and Australia) during a period of notable regulatory changes. Our findings reveal a significant and positive impact of SOP votes on firm efficiency. This suggests that company executives recognise that lower efficiency leads to lower pay or even job loss. Interestingly, our analysis indicates that younger managers can contribute more to creating value and improving business performance compared with their older counterparts. However, the relationship between gender and firm efficiency remains inconclusive. Furthermore, our study highlights the limited involvement of the board of directors in driving firm efficiency. This could be attributed to inadequate monitoring, cooperation and communication among board members, particularly in the case of audit committees, which seem to have less skilled members. Alternatively, this lack of board engagement may be due to the influence of powerful managers within the company. This paper also offers practical implications to policymakers and practitioners and suggests avenues for future research that can build upon our evidence
Oracy for civic voice: Deconstructing practice through classroom vignettes
Get PDFThe importance of spoken language in education for curricular, pedagogical and societal purposes is well established and sometimes articulated as oracy education. This article draws on Shulman's work on learning from cases to explore critically the use of oracy to promote civic values and voice. Realising the ideals of deliberative dialogue in everyday practice in an equitable, context-sensitive way is not straightforward. There is a role, therefore, for learning from the analysis of real classroom examples as a means of particularising theory and promoting pedagogical reasoning. The article argues for the potential of learning from cases in the form of vignettes of practice and presents two vignettes based on field notes from oracy-based lessons in primary school classrooms in juxtaposition. The subsequent comparison and commentary illustrate how oracy education practices might be used to develop civic voice and show the importance of moving beyond standardised pedagogies. The common practices noted include developing authentic contexts for talk, valuing a range of linguistic registers, the creation of dialogic space and the teacher's willingness to cede centre stage. It is argued that the analysis of vignettes in this manner affords valuable opportunities for professional learning in the field of oracy and beyond
Effect of insulin resistance on ticagrelor-versus clopidogrel-based dual antiplatelet therapy for secondary prevention of stroke in carriers of CYP2C19 loss-of-function mutations
No full textBACKGROUND: Insulin resistance is associated with increased platelet reactivity. We sought to investigate the effects of insulin resistance on dual antiplatelet therapy in CYP2C19 loss-of-function carriers with minor stroke or transient ischemic attack (TIA). METHODS: We conducted a post hoc analysis of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial, in which we randomized patients with minor stroke or TIA who carried CYP2C19 loss-of-function mutations to receive ticagrelor-acetylsalicylic acid (ASA) or clopidogrel-ASA. We categorized patients by insulin resistance status using a cut-off of 8 mg/kg/min in the estimated glucose disposal rate. The primary efficacy outcome was recurrent stroke. The primary safety outcome was severe or moderate bleeding within 90 days of starting the intervention. RESULTS: Among 4954 patients included, 3122 (63.0%) had high insulin resistance and 1832 (37.0%) had low insulin resistance. Compared with clopidogrel-ASA, ticagrelor-ASA reduced the risk of recurrent stroke in the low-insulin resistance group (71 [7.8%] v. 36 [3.9%]; hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.34 to 0.79), but not in the high-insulin resistance group (120 [7.7%] v. 120 [7.7%]; HR 0.96, 95% CI 0.74 to 1.24) (p = 0.01 for interaction). Results were similar among patients with and without diabetes (p for interaction = 0.3). The benefit of ticagrelor-ASA versus clopidogrel-ASA for recurrent stroke increased continuously as insulin resistance decreased (p for interaction = 0.03). Rates of severe or moderate bleeding were similar regardless of treatment or insulin resistance group (p for interaction = 0.8). INTERPRETATION: In CYP2C19 loss-of-function carriers with minor stroke or TIA, ticagrelor-ASA use was associated with reduced future stroke risk compared with clopidogrel-ASA among patients with low insulin resistance. Insulin resistance biomarkers have a potential role in optimal selection of antiplatelet therapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04078737
Green Banking Practices, Social, Health and Environmental Disclosures and Bank Financial Performance: The Role of Innovations and Corporate Governance
No full textRegulators in the banking industry in the Sub-Saharan Africa (SSA) region are progressively concentrating on corporate innovation and bank social, health and environmental disclosures (BSHED) as crucial corporate governance (CG) structures to improve bank financial performance (BFP). Nonetheless, it is unclear whether corporate innovation and BSHED can lead to an improvement in BFP. Understanding these crucial relationships can help regulators and banking practitioners to design and implement sustainable strategies that can enhance BFP. This paper seeks to bridge this gap by investigating the effects of corporate innovation and BSHED on BFP and examining whether CG mechanisms moderate these relationships. Through the lens of multi-theoretical perspectives, the study conducts fixed effects and dynamic two-step system generalised method of moments models over a dataset of 2785 observations (220 banks) from 16 SSA countries between 2007 and 2022. The findings show that corporate innovation has a positive effect on BSHED and BFP. The study detects that corporate innovation has a positive association with BFP. We find that BSHED is positively related to BFP. The study identifies and tests possible moderators of these associations. We observe that CG mechanisms positively moderate these relationships. Finally, we establish that the predicted associations vary across different operating periods. The findings help stakeholders including corporate boards, executives and regulators to understand how innovation investments and internal governance structures such as CG mechanisms are associated with BSHED and BFP
A Partially Pooled NSUM Model: Detailed estimation of CSEM trafficking prevalence in Philippine municipalities
Get PDFEffective policy and intervention strategies to combat human trafficking for child sexual exploitation material (CSEM) production require accurate prevalence estimates. Traditional Network Scale Up Method (NSUM) models often necessitate stan-dalone surveys for each geographic region, escalating costs and complexity. This study introduces a partially pooled NSUM model, using a hierarchical Bayesian framework that efficiently aggregates and utilizes data across multiple regions without increasing sample sizes. We developed this model for a novel national survey dataset from the Philippines and we demonstrate its ability to produce detailed municipal-level prevalence estimates of trafficking for CSEM production. Our results not only underscore the model's precision in estimating hidden populations but also highlight its potential for broader application in other areas of social science and public health research, offering significant implications for resource allocation and intervention planning
CFFormer: Cross CNN-Transformer channel attention and spatial feature fusion for improved segmentation of heterogeneous medical images
No full textMedical image segmentation plays an important role in computer-aided diagnosis. Existing methods mainly utilize spatial attention to highlight the region of interest. However, due to limitations of medical imaging devices, medical images exhibit significant heterogeneity, posing challenges for segmentation. Ultrasound images, for instance, often suffer from speckle noise, low resolution, and poor contrast between target tissues and background, which may lead to inaccurate boundary delineation. To address these challenges caused by heterogeneous image quality, we propose a hybrid CNN-Transformer model, called CFFormer, which leverages effective channel feature extraction to enhance the model's ability to accurately identify tissue regions by capturing rich contextual information. The proposed architecture contains two key components: the Cross Feature Channel Attention (CFCA) module and the X-Spatial Feature Fusion (XFF) module. The model incorporates dual encoders, with the CNN encoder focusing on capturing local features and the Transformer encoder modeling global features. The CFCA module filters and facilitates interactions between the channel features from the two encoders, while the XFF module effectively reduces the significant semantic information differences in spatial features, enabling a smooth and cohesive spatial feature fusion. We evaluate our model across eight datasets covering five modalities to test its generalization capability. Experimental results demonstrate that our model outperforms current state-of-the-art methods and maintains accurate tissue region segmentation across heterogeneous medical image datasets. The code is available at https://github.com/JiaxuanFelix/CFFormer
Neural network methods for Neumann series problems of Perron-Frobenius operators
Get PDFProblems related to Perron-Frobenius operators (or transfer operators) have been extensively studied and applied across various fields. In this work, we propose neural network methods for approximating solutions to problems involving these operators. Specifically, we focus on computing the Neumann series of non-expansive Perron-Frobenius operators under a given L p-norm with a constant damping parameter in (0, 1). We use PINNs and RVPINNs to approximate solutions in their strong and variational forms, respectively. We provide a priori error estimates for quasi-minimizers of the associated loss functions. We present some numerical results for 1D and 2D examples to show the performance of our methods. We also demonstrate the applicability of our methods by approximating interior densities in a two-cavity system
Photoelectron spectroscopy and circular dichroism of an open-shell organometallic camphor complex
Get PDFWe present an investigation of one-photon valence-shell photoelectron spectroscopy and photoelectron circular dichroism (PECD) for the chiral molecule (1R,4R)-3-(heptafluorobutyryl)-(+)-camphor (HFC) and its europium complex Eu(III) tris[3-(heptafluorobutyryl)-(1R,4R)-camphorate] (Eu-HFC3), the latter of which constitutes the heaviest organometallic molecule for which PECD has yet been measured. We discuss the role of keto-enol tautomerism in HFC, both as a free molecule and complexed in Eu-HFC3. PECD is a uniquely sensitive probe of molecular chirality and structure such as absolute configuration, conformation, isomerization, and substitution, and is, in principle, well suited to unambiguously resolving tautomers; however, modeling remains challenging. For small organic molecules, theory is generally capable of accounting for experimentally measured PECD asymmetries, but significantly poorer agreement is typically achieved for the case of large open-shell systems. Here, we report PECD asymmetries, ranging up to 8% for HFC and 7% for Eu-HFC3, of similar magnitude to those reported previously for smaller isolated chiral molecules, indicating that PECD remains a practical experimental technique for the study of large, complicated chiral systems
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