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A Study of Time to Recovery Following Loss of Neuromonitoring Signal of the Recurrent Laryngeal Nerve in Thyroid Surgery
Get PDFBackground: Injuries of the recurrent laryngeal nerve (RLN) during thyroidectomy although infrequent can lead to major morbidity. Permanent RLN injury is uncommon; however, temporary neurapraxia and loss of signal (LOS) during intraoperative neuromonitoring (IONM) are seen more frequently. This study aimed to identify factors associated with type I (segmental) and II (global) LOS of the RLN during thyroid surgery and to analyze time to recovery of vocal cord function. Methods: This observational retrospective cohort study included 3806 patients (2924 female, 76.8% and 882 male, 23.2%) who underwent hemi or total thyroidectomy in a tertiary center between January 2015 and March 2021. Regression analyses determined factors associated with LOS. Postoperative fibreoptic laryngoscopy was used to measure time to recovery of vocal cord function. Results: RLN LOS occurred in 167 (2.7%) of 5983 nerves at risk during surgery. The rate of Type I and Type II LOS per nerve at risk was 1.4% and 1.3%, respectively. Compared with an indication of malignancy, toxic nodule was associated with 96% increased odds of LOS independent of age and sex (P < 0.001). Time to recovery was reduced for those with a Type II LOS (median 4 weeks) compared to Type I LOS (median 8 weeks and p = 0.04). Female sex and increasing age were independently associated with a longer duration to return of vocal cord function. Conclusions: Time to recovery of RLN function is significantly reduced for patients with Type II LOS. Toxic thyroid nodules were associated with a higher risk of LOS, and female sex and age are significantly associated with a longer time to recovery
Multibrand price dispersion
No full textWe study a market in which firms each might supply a number of variants, or "brands", of fundamentally the same product. Consumers differ in the sets of brands they consider, and firms compete using (multi-dimensional) mixed pricing strategies. We show when firms apply uniform pricing across their brands, and when they use segmented pricing so that one "discount" brand is priced below another "premium" brand. We study the case of symmetric brands in particular, and discuss the impact of a firm introducing a new brand, of imposing a requirement to set uniform prices across brands, and of mergers between firms
Political economy of finance: securities markets regulation
No full textWhat explains ‘regulatory stringency’ in financial markets? I define regulatory stringency as the change in the extent and scope of a regulatory burden imposed on regulated firms (or regulatees). The level of competition, conceptualised as heterogeneity of regulatees’ regulatory preferences, is central to explaining the extent of rule stringency, either rule weakening or rule strengthening. If regulatees compete due to heterogeneous preferences (i.e. disagree on a specific rule proposed by the regulator), then regulators hold more bargaining power to promulgate stronger, more burdensome regulation. Alternatively, when regulatees have homogeneous preferences, their power with respect to the regulator is increased and rules are consequently weakened. This central theoretical claim is developed through a more nuanced theoretical account, which is inspired by six streams of literature: international political economy of finance, organisational reputation, business conflict, interest groups, capture theory (economics of regulations), and strategic provision of information. In order to systematically examine the extent of regulatees’ influence on rulemaking in securities markets, the thesis engages in two complementary empirical endeavours: first, the large N study, which is based on a new data set on securities market regulation that spans 13 years of rulemaking (2004–2016) with 200 rules and 7,873 individual submissions to the regulator – the European Securities and Markets Authority (ESMA); second, the case studies on the Markets in Financial Instruments Directive (MiFID II), which focus on the research inducement regime (‘research unbundling’), transparency thresholds in fixed income and derivatives, and dark trading
Clinical guidelines on self-harm and suicide prevention: taking uncertainty into account in the evidence base
Get PDFThe National Institute for Health and Care Excellence (NICE) guideline for self-harm advises against the use of risk assessment tools to predict future occurrence of repeat self-harm or suicide in individuals who have self-harmed, or to inform decisions regarding their treatment and discharge. In this perspective article, we discuss shortcomings in the process of developing this guideline, including: (1) limitations in the NICE evidence review underpinning these recommendations, which resulted in very minimal evidence being included; (2) developing definitive recommendations and drawing strong conclusions regarding the limited predictive ability and potential harms of tools, which were almost entirely based on the committee's expertise and experience and (3) not acknowledging the uncertainty and gaps in the evidence base, particularly around model impact, acceptability and feasibility. We highlight new evidence since this 2022 guideline, including examples of international work assessing model implementation and cost-effectiveness. We propose that there is an urgent need for more rigorous primary research assessing model impact, feasibility and acceptability, as well as empirical work addressing concerns about potential harms and misuse of tools, notably the denial of care. While prediction models should not be prematurely implemented in clinical practice without adequate validation and impact assessment, well-developed and validated tools in this area have the potential to improve clinical care for individuals who self-harm. Future updates to the guideline should be informed by emerging higher quality evidence in the field
Evaluating the efficacy and immunological impact of combined ICIs and SBRT in HCC: A narrative literature review
Get PDFHepatocellular carcinoma (HCC) represents one of the leading contributors to cancer-related deaths, with the majority of patients diagnosed at stages where curative treatment is no longer possible. Combining stereotactic body radiotherapy (SBRT) with immune checkpoint inhibition (ICI) has gained increasing attention as a therapeutic approach. Beyond its ability to provide high local tumor control (LC), SBRT can provoke immunogenic tumor cell death, promote antigen release and presentation, and modulate the tumor microenvironment in ways that enhance systemic antitumor immunity. In this narrative review, we outline the scientific rationale for integrating SBRT with ICIs, discuss mechanistic and translational findings and summarize results from key clinical trials. The currently available data indicate a synergistic interaction, most notably reflected in improved survival and response rates. Nevertheless, variability in dose and fractionation schedules, treatment sequencing, and patient characteristics complicates interpretation. Well-designed prospective studies are needed to establish optimal protocols and identify predictive biomarkers to guide patient selection
Ranges of polynomials control degree ranks of Green and Tao over finite prime fields
Get PDFLet be a prime, let be integers, and let be a non-empty subset of . We establish that if a polynomial with degree is such that the image does not contain the full image of any non-constant polynomial with degree at most , then coincides on with a polynomial that in particular has bounded degree- -rank in the sense of Green and Tao. Similarly, we prove that if the assumption holds even for , then coincides on with a polynomial determined by a bounded number of coordinates
Early Methylene Blue for Mortality Reduction in High-Dose VasoPREssor-Dependent Septic Shock (EMPRESS): protocol for a multicenter randomized controlled trial
Get PDFBackground: Septic shock remains one of the most lethal emergency and critical care conditions, with underlying pathophysiology closely linked to uncontrolled vasodilation mediated by nitric oxide activation of the soluble guanylate cyclase pathway (NO–sGC–cGMP pathway). Methylene blue (MB), through its inhibition of this pathway, has demonstrated hemodynamic benefits and may serve as a targeted adjunctive therapy particularly in patients with septic shock requiring high-dose vasopressors, a severely vasoplegic subpopulation characterized by markedly elevated mortality. However, large-scale randomized controlled trials (RCTs) evaluating MB treatment for mortality benefit in high-dose vasopressor-dependent septic shock patients are currently lacking. Methods: This is an investigator-initiated, multicenter, open-label, blinded endpoint RCT that will recruit adult septic shock patients requiring norepinephrine equivalent doses > 0.3 μg/kg/min within 24 h of vasopressor initiation across multiple centers in China. A total of 566 patients will be randomized 1:1 to receive MB treatment (2 mg/kg loading dose followed by 0.25 mg/kg/h maintenance infusion for up to 48 h or 4 h after vasopressor discontinuation) or equal volume 5% dextrose control. Randomization will be stratified by baseline SOFA-1 score and study center. The primary endpoint is 28-day all-cause mortality. Secondary outcomes include ICU-free days, vasopressor-free days, ventilator-free days, in-hospital mortality, and SOFA score improvement. Discussion: This multicenter RCT will generate evidence on whether early MB administration reduces mortality in patients with high-dose vasopressor–dependent septic shock, potentially informing clinical practice regarding MB's role as an adjunctive therapy in severe septic shock management. Trial registration: ChiCTR2500112352
Low crosstalk in a scalable superconducting quantum lattice
Get PDFSuperconducting quantum circuits are a key platform for advancing quantum information processing and simulation. Scaling efforts currently encounter challenges such as Josephson-junction fabrication yield, design frequency targeting, and long-range crosstalk arising both from spurious microwave modes and intrinsic interactions between qubits. We demonstrate a scalable 4x4 square lattice with low crosstalk, comprising 16 fixed-frequency transmon qubits with nearest-neighbor capacitive coupling that is implemented in a tileable, 3D-integrated circuit architecture with off-chip inductive shunting to mitigate spurious enclosure modes. We report on the design and comprehensive characterization, and show that our implementation achieves targeted device parameters with very low frequency spreads, long-range parasitic couplings and simultaneous single-qubit gate errors across the device. Our results provide a promising pathway toward a scalable superconducting square lattice topology for quantum error correction and simulation
Optimising delivery of integrated palliative care and heart failure services: A realist evaluation protocol (PalliatHeartSynthesis II)
Get PDFBackground: Inequality in palliative care provision is an ongoing problem for underserved groups, such as those with heart failure (HF) placing a burden on patients, their caregivers and health services due to frequent, often avoidable hospitalisations. Our realist synthesis of integrated palliative care (PC) and HF literature found that integrated HF and PC services work best when service providers are motivated and have the opportunity and capacity to support behaviour change. However, we identified significant knowledge gaps with most studies completed in United States of America (USA) and based primarily on the views of nurses and physicians. We developed strategies to help services provide integrated PC and HF services but identified the need for United Kingdom (UK) primary data to better understand the context-specific implementation of palliative care and HF care. Methods: This project will use co-design and realist evaluation to generate data from five PC and HF integrated services in the UK, purposively sampled to provide variation in geography and service design (Research Registry 10624). The research comprises three work packages (WPs). WP1 will deliver a realist evaluation of each site including documentary analysis, observations and semi-structured interviews with service providers and users. WP2 uses co-design methods to develop a guide to help others set up and improve integrated PC and HF services. Data from both WPs will be analysed and synthesised using a realist logic of analysis. WP3 will facilitate the development of a community of practice to support those who wish to set up, sustain and embed integrated PC and HF services. Discussion: This realist evaluation of a complex intervention will improve understanding of how to tailor and implement integrated PC and HF services. The co-designed ‘how-to guide’ and community of practice will facilitate knowledge translation and ensure that evidence-based guidance is provided to assist in service development
Intercultural expectations and global ambitions: the spatial and temporal dimensions of Indigenous Amazonian adolescence
Get PDFThis article explores the experiences of Indigenous Amazonian adolescents living and studying in a Peruvian metropolis, as they navigate the complex interplay between ethnic belonging, the older generation's ‘intercultural’ expectations, and ambitions for the future within a rapidly urbanizing and globalizing society. The article illustrates how adolescence in such a context is shaped not only by its temporal dimension, as traditionally emphasized by scholarly research, but also by spatial factors. Contributing to recent anthropological interest in aspirations, it considers how Indigenous urban adolescents are encouraged by the older generation to transition from local to increasingly global scales – geographically but also temporally – as they pursue their educational and professional goals. This approach offers valuable insights for the anthropological study of adolescence – both within and beyond Amazonia – by highlighting how, despite the well‐established culturally contingent nature of adolescence, virtually every society invests significant hopes in its younger generation, deeply shaping their own ambitions for the future