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Yavin, Tzahi, Eugene Wang, Hu Zhang, and Michael A. Clayton. "Transition probability matrix methodology for incremental risk charge." Journal of Financial Engineering 01, no. 01 (2014): 1450010. http://dx.doi.org/10.1142/s234576861450010x.
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As part of Basel II's incremental risk charge (IRC) methodology, this paper summarizes our extensive investigations of constructing transition probability matrices (TPMs) for unsecuritized credit products in the trading book. The objective is to create monthly or quarterly TPMs with predefined sectors and ratings that are consistent with the bank's Basel PDs. Constructing a TPM is not a unique process. We highlight various aspects of three types of uncertainties embedded in different construction methods: (1) the available historical data and the bank's rating philosophy; (2) the merger of one-year Basel PD and the chosen Moody's TPMs; and (3) deriving a monthly or quarterly TPM when the generator matrix does not exist. Given the fact that TPMs and specifically their PDs are the most important parameters in IRC, it is our view that banks may need to make discretionary choices regarding their methodology, with uncertainties well understood and managed.
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Bonollo, Michele, Antonio Menegon, and Luigi Terzi. "Climate and environmental risk factors in the market risk field: An extended model." Risk Governance and Control: Financial Markets and Institutions 13, no. 2 (2023): 17–27. http://dx.doi.org/10.22495/rgcv13i2p2.
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The extension of the risk management models to the broad sustainability concept is an open issue in both the academic and financial communities. The current state of the art for the risk measurement models is not satisfactory. There are many weaknesses in the data feasibility and the debate about what the new models should measure is still open. We propose a model that aims to improve the existing market risk models by capturing the sustainability risk sources. The starting point is the incremental risk charge (IRC) model, namely a 1 year 99.9 percent value at risk that covers default and migration risk. We extend the traditional model by defining the environmental incremental risk charge (E-IRC), with two enhancements: 1) by some data analysis and statistical techniques we introduce some new environmental, social, and governance (ESG) risk factors to better explain the portfolio behavior; 2) we adjust the default probabilities provided by the rating agencies by combining the green premium (lower spread) observed in the markets with the available ESG score for each obligor. The new model was tested on a real portfolio by a Montecarlo engine. The model does not affect too much the existing IRC results, so allowing continuity in the reporting process. The main advantage of E-IRC is the availability of a more effective risk decomposition process, where the ESG contributions can be properly highlighted.
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Bonollo, Michele, Luca Di Persio, and Luca Prezioso. "The Default Risk Charge approach to regulatory risk measurement processes." Dependence Modeling 6, no. 1 (2018): 309–30. http://dx.doi.org/10.1515/demo-2018-0018.
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AbstractIn the present paper we consider the Default Risk Charge (DRC) measure as an effective alternative to the Incremental Risk Charge (IRC) one, proposing its implementation by a quasi exhaustive-heuristic algorithm to determine the minimum capital requested to a bank facing the market risk associated to portfolios based on assets issued by several financial agents. While most of the banks use the Monte Carlo simulation approach and the empirical quantile to estimate this risk measure, we provide new computational approaches, exhaustive or heuristic, currently becoming feasible because of both the new regulation and to the high speed - low cost technology available nowadays. Concrete algorithms and numerical examples are provided to illustrate the effectiveness of the proposed techniques.
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Slime, Badreddine. "Mathematical Modeling of Concentration Risk under the Default Risk Charge Using Probability and Statistics Theory." Journal of Probability and Statistics 2022 (November 1, 2022): 1–12. http://dx.doi.org/10.1155/2022/3063505.
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In the Fundamental Review of the Trading Book (FRTB), the latest regulation for minimum capital market risk requirements, one of the major changes, is replacing the Incremental Risk Charge (IRC) with the Default Risk Charge (DRC). The DRC measures only the default and does not consider the migration rating risk. The second new change in this approach was that the DRC now includes equity assets, contrary to the IRC. This paper studies DRC modeling under the Internal Model Approach (IMA) and the regulator conditions that every DRC component must respect. The FRTB presents the DRC measurement as Value at Risk (VaR) over a one-year horizon, with the quantile equal to 99.9%. We use multifactor adjustment to measure the DRC and compare it with the Monte Carlo Model to understand how the approach fits. We then define concentration in the DRC and propose two methods to quantify the concentration risk: the Ad Hoc and Add-On methods. Finally, we study the behavior of the DRC with respect to the concentration risk.
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Prorokowski, Lukasz, and Hubert Prorokowski. "Compliance with Basel 2.5: banks’ approaches to implementing stressed VaR." Journal of Financial Regulation and Compliance 22, no. 4 (2014): 339–48. http://dx.doi.org/10.1108/jfrc-10-2013-0038.
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Purpose – The purpose of this paper is to outline how banks are coping with the new regulatory challenges posed by stressed value at risk (SVaR). The Basel Committee has introduced three measures of capital charges for market risk: incremental risk charge (IRC), SVaR and comprehensive risk measure (CRM). This paper is designed to analyse the methodologies for SVaR deployed at different banks to highlight the SVaR-related challenges stemming from complying with Basel 2.5. This revised market risk framework comes into force in Europe in 2012. Among the wide range of changes is the requirement for banks to calculate SVaR at a 99 per cent confidence interval over a period of significant stress. Design/methodology/approach – The current research project is based on in-depth, semi-structured interviews with nine universal banks and one financial services company to explore the strides major banks are taking to implement SVaR methodologies while complying with Basel 2.5. Findings – This paper focuses on strengths and weaknesses of the SVaR approach while reviewing peer practices of implementing SVaR modelling. Interestingly, the surveyed banks have not indicated significant challenges associated with implementation of SVaR, and the reported problems boil down to dealing with the poor quality of market data and, as in cases of IRC and CRM, the lack of regulatory guidance. As far as peer practices of implementing SVaR modelling are concerned, the majority of the surveyed banks utilise historical simulations and apply both the absolute and relative measures of volatility for different risk factors. Originality/value – The academic studies that explicitly analyse challenges associated with implementing the stressed version of VaR are scarce. Filling in the gap in the existing academic literature, this paper aims to shed some explanatory light on the issues major banks are facing when calculating SVaR. In doing so, this study adequately bridges theory and practice by contributing to the fierce debate on compliance with Basel 2.5.
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Vie, Preben J. S., and Julia Wind. "Revisiting Pseudo-OCV Pulse-Based Incremental Capacity Analysis." ECS Meeting Abstracts MA2024-01, no. 2 (2024): 441. http://dx.doi.org/10.1149/ma2024-012441mtgabs.
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Li-ion batteries are more prone to safety incidents than other battery technologies. This is due to the inherently higher energy density as well as the flammability of especially anode materials, separator, and electrolyte solvents. During charging, metallic Lithium may form on the anode surface and could in the worst case short the battery from within and cause a fire and or explosion [1]. It is therefore vital to be able to monitor the battery’s state-of-health (SoH) and state-of-safety (SoS) [2], to avoid further use of Li-ion batteries that may have aged in a detrimental fashion and can have an increased safety risk. Especially when a battery has aged considerably (SoH < 80%) the path of ageing can significantly affect the safety properties of the battery and cause dramatic differences in the severity of a possible safety incident. Incremental capacity analysis (ICA, dQ/dV) has emerged as a very powerful diagnostic technique for Li-ion batteries. We recently used ICA to identify different degradation mechanisms in commercial Li-ion cells through classification and tracking of selected dQ/dV features [3]. This allowed us to identify safety critical ageing at an early stage. ICA requires constant charge and discharge at slow currents (C-rate < C/10) [4, 5]. However, a slow controlled constant current charge or discharge is normally not feasible and cannot be easily applied to battery systems without access to high precision battery pack testers. In this work we will revisit applying ICA on the Open-Circuit-Voltage (OCV) curve in the capacity space [6]. The OCV curve can be obtained from any sequence of current or power pulses followed by a rest period to allow the cell to reach a pseudo-OCV after each pulse. By pulsing through the entire state-of-charge window an OCV vs capacity curve can be obtained with sufficient accuracy to perform ICA. A direct comparison of conventional constant current ICA (cc-ICA) and high-resolution-OCV ICA (ocv-ICA) is presented. A strong correlation between ageing patterns is observed providing a first proof-of-concept for the method. References: Ratnakumar, B.V. and M.C. Smart, Lithium Plating Behavior in Lithium-ion Cells, in Rechargeable Lithium-Ion Batteries, M. Winter, et al., Editors. 2010, Electrochemical Soc Inc: Pennington. p. 241-252. Cabrera-Castillo, E., F. Niedermeier, and A. Jossen, Calculation of the state of safety (SOS) for lithium ion batteries. Journal of Power Sources, 2016. 324: p. 509-520. Spitthoff, L., et al., Incremental Capacity Analysis (dQ/dV) as a Tool for Analysing the Effect of Ambient Temperature And Mechanical Clamping on Degradation. Journal of Electroanalytical Chemistry, 2023. Dubarry, M., et al., Incremental capacity analysis and close-to-equilibrium OCV measurements to quantify capacity fade in commercial rechargeable lithium batteries. Electrochemical and Solid State Letters, 2006. 9(10): p. A454-A457. Dubarry, M. and D. Ansean, Best practices for incremental capacity analysis. Frontiers in Energy Research, 2022. 10: p. 18. Petzl, M. and M.A. Danzer, Advancements in OCV Measurement and Analysis for Lithium-Ion Batteries. Ieee Transactions on Energy Conversion, 2013. 28(3): p. 675-681.
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Finger, Christopher. "Benchmarking the incremental risk charge." Journal of Credit Risk 7, no. 2 (2011): 53–70. http://dx.doi.org/10.21314/jcr.2011.126.
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Hlivka, Igor. "Practical Methods for Incremental Risk Charge Calculation." Wilmott 2015, no. 77 (2015): 10–17. http://dx.doi.org/10.1002/wilm.10416.
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Griskaite, Aurelija, and Rainer Lueg. "Earnings less risk-free interest charge (ERIC) and stock returns: ERIC’s relative and incremental information content in a European sample." Corporate Ownership and Control 20, no. 2 (2023): 166–81. http://dx.doi.org/10.22495/cocv20i2art14.
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This study tests the information content of earnings less risk-free interest charge (ERIC) and analyses its ability to explain fluctuations in market-adjusted stock returns. Following Biddle et al. (1997) study design, we perform relative and incremental information content tests. Relative information content tests reveal that mandatory reporting metrics — such as earnings before extraordinary items (EBEI), cash flow from operations (CFO), and total comprehensive income (TCI) — are more highly associated with stock returns and firm values than ERIC or residual income (RI). A number of sensitivity analyses support our findings. To test incremental information content, we split ERIC into five components. Primary results indicated that components specific to ERIC — changes of net assets, after-tax interest expenses, and capital charge — do not add relative information content. Yet, sensitivity tests suggest that some ERIC components add incremental information, especially when accounting for market expectations. However, these findings are not economically substantial compared to CFO and EBEI. Overall, we conclude that mandatory metrics generally outperform ERIC and residual income. Our unique contribution lies in applying the established methodology of measuring economic value added (EVA’s) relative and incremental information content to ERIC
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Bewersdorf, Jan Philipp, George Goshua, Kishan K. Patel, et al. "Cost-Effectiveness of Liposomal Cytarabine-Daunorubicin (CPX-351) Compared to Conventional Cytarabine-Daunorubicin Chemotherapy in Acute Myeloid Leukemia." Blood 138, Supplement 1 (2021): 113. http://dx.doi.org/10.1182/blood-2021-144992.
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Abstract Introduction: A randomized phase III trial demonstrated improved overall survival (OS) and event-free survival (EFS) for older patients diagnosed with therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC) treated with a liposomal formulation of daunorubicin-cytarabine (CPX-351) when compared with 7+3 induction and consolidation therapy, a previous standard of care. Based on those results, CPX-351 was approved in 2017 in the United States (US) for adults with newly diagnosed t-AML and AML-MRC irrespective of age. However, the health economic implications of CPX-351 from a US payer perspective are not well-characterized. Methods: We constructed a partitioned survival analysis based on the data from the original phase III trial (Lancet et al. JCO 2018) and subsequent updates (Lancet et al. Lancet Haematology 2021) and post-hoc analyses from the landmark trial (Villa et al. JME 2019). Newly diagnosed AML patients at a median age of 68 years entered the model with active AML and received either CPX-351 or 7+3 induction and consolidation therapy followed by allogeneic hematopoietic cell transplant (allo-HCT) for some patients. Parametric survival distributions were fitted using patient-level data recreated from the Kaplan-Meier curves and at-risk tables for EFS and OS for both study arms. Log-logistic distributions demonstrated the best fit and were chosen for this model. Frequency and setting (inpatient vs outpatient) of re-induction and consolidation therapy were used as outlined in the original study. Costs and practice patterns of salvage therapy, receipt of allo-HCT, supportive care, and incidence of complications were derived from the original trial or published literature (Table). If available, costs for the Medicare population rather than commercially insured patients were used. For the CPX-351 arm, the maximum new technology add-on payment granted by the Centers for Medicare & Medicaid Services for fiscal year 2020 was added to the costs of inpatient induction and consolidation therapy in the 7+3 arm. Costs were adjusted for inflation to 2020 US dollars using the personal consumption expenditure health index. Previously published utilities were used and measured in quality-adjusted life years (QALYs). Costs and utilities were discounted by 3% annually (range 3-5% in one-way sensitivity analysis) and modelled over a 10-year time horizon. Model outputs were used to calculate the incremental cost-effectiveness ratio (ICER) for CPX-351 over 7+3. A willingness-to-pay (WTP) threshold of $150,000/QALY gained was used to determine cost-effectiveness. One-way sensitivity analyses were performed with utility values varied with a 10% range and all other variables across a 50% range. In probabilistic sensitivity analyses using 10,000 Monte Carlo simulations, beta distributions were used to describe probabilities and utilities, while gamma distributions were used for costs. Results: CPX-351 and 7+3 were associated with lifetime costs of $371,482 and $256,415, respectively, for an incremental cost of $115,066 with CPX-351. CPX-351 resulted in an incremental gain of 0.49 QALYs compared to 7+3 (CPX-351: 1.11 QALYs vs 7+3: 0.62 QALYs) resulting in an ICER of $231,563/QALY gained in the base case analysis. In one-way sensitivity analyses our model was most sensitive to the probability of receiving allo-HCT in either arm (Figure). In threshold analyses, a reduction of the CPX-351 add-on charge in the inpatient setting by 70.4% (from $47,353 to $14,004) would lower the ICER below the WTP threshold of $150,000/QALY. Probabilistic sensitivity analysis yielded a median ICER of $222,894 (95% credible interval: $142,863 - $313,289) with 7+3 favored in 96.4% of 10,000 iterations at a WTP threshold of $150,000. Conclusion: Use of CPX-351 under the current pricing model is unlikely to be cost-effective for most older patients with t-AML/AML-MRC who resemble those enrolled in the clinical trial. A reduction by 70.4% for the CPX-351 add-on charge in the inpatient setting would be necessary to lower the ICER below the conventional WTP threshold of $150,000/QALY. Higher rates of allo-HCT and outpatient consolidation with CPX-351 did not lead to gains in clinical utility or cost reductions substantial enough to make CPX-351 cost-effective. The implications of a potential outpatient administration of CPX-351 induction on its cost-effectiveness require additional studies. Figure 1 Figure 1. Disclosures Shallis: Curis: Divested equity in a private or publicly-traded company in the past 24 months. Podoltsev: PharmaEssentia: Honoraria; Blueprint Medicines: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; CTI BioPharma: Honoraria; Bristol-Myers Squib: Honoraria; Novartis: Honoraria; Celgene: Honoraria. Huntington: Bayer: Honoraria; Thyme Inc: Consultancy; Servier: Consultancy; Novartis: Consultancy; SeaGen: Consultancy; AstraZeneca: Consultancy, Honoraria; Genentech: Consultancy; TG Therapeutics: Research Funding; Flatiron Health Inc.: Consultancy; DTRM Biopharm: Research Funding; AbbVie: Consultancy; Pharmacyclics: Consultancy, Honoraria; Celgene: Consultancy, Research Funding. Zeidan: Astex: Research Funding; Amgen: Consultancy, Research Funding; Epizyme: Consultancy; BMS: Consultancy, Other: Clinical Trial Committees, Research Funding; Aprea: Consultancy, Research Funding; Cardiff Oncology: Consultancy, Other: Travel support, Research Funding; AstraZeneca: Consultancy; Janssen: Consultancy; Daiichi Sankyo: Consultancy; Jasper: Consultancy; Astellas: Consultancy; Genentech: Consultancy; Geron: Other: Clinical Trial Committees; Agios: Consultancy; Novartis: Consultancy, Other: Clinical Trial Committees, Travel support, Research Funding; BioCryst: Other: Clinical Trial Committees; Pfizer: Other: Travel support, Research Funding; Kura: Consultancy, Other: Clinical Trial Committees; Incyte: Consultancy, Research Funding; BeyondSpring: Consultancy; Gilead: Consultancy, Other: Clinical Trial Committees; Ionis: Consultancy; Loxo Oncology: Consultancy, Other: Clinical Trial Committees; ADC Therapeutics: Research Funding; Jazz: Consultancy; Boehringer Ingelheim: Consultancy, Research Funding; Acceleron: Consultancy, Research Funding; AbbVie: Consultancy, Other: Clinical Trial Committees, Research Funding.
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RODRIGUES, MATHEUS PIMENTEL, and ANDRE CURY MAIALY. "MEASURING DEFAULT RISK FOR A PORTFOLIO OF EQUITIES." International Journal of Theoretical and Applied Finance 22, no. 01 (2019): 1950012. http://dx.doi.org/10.1142/s0219024919500122.
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This work evaluates some changes proposed by the Basel Committee on Banking Supervision in regulating capital allocation in the trading book for equities following a company default. In the last decade, the committee designed some measures to account for the risk of a company default that the ten-day value-at-risk measure does not capture. The first and more conservative measure designed to capture the effect of defaults was the incremental risk charge. With time, this measure evolved into the default risk charge. We use a Merton model to compute the probability of default and compare this probability to simulated asset returns in order to compute the one-year value-at-risk and capture the risk of a company default. The analysis compares portfolios of Ibovespa companies and S&P 500 companies. Additionally, we propose a method to account for the correlation in the companies and compare the effects of the standard method of capital allocation to those of our models.
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Davis, Sarah, Emma Simpson, Jean Hamilton, et al. "Denosumab, raloxifene, romosozumab and teriparatide to prevent osteoporotic fragility fractures: a systematic review and economic evaluation." Health Technology Assessment 24, no. 29 (2020): 1–314. http://dx.doi.org/10.3310/hta24290.
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Background Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. Objectives The objectives were to evaluate the clinical effectiveness, safety and cost-effectiveness of non-bisphosphonates {denosumab [Prolia®; Amgen Inc., Thousand Oaks, CA, USA], raloxifene [Evista®; Daiichi Sankyo Company, Ltd, Tokyo, Japan], romosozumab [Evenity®; Union Chimique Belge (UCB) S.A. (Brussels, Belgium) and Amgen Inc.] and teriparatide [Forsteo®; Eli Lilly and Company, Indianapolis, IN, USA]}, compared with each other, bisphosphonates or no treatment, for the prevention of fragility fracture. Data sources For the clinical effectiveness review, nine electronic databases (including MEDLINE, EMBASE and the World Health Organization International Clinical Trials Registry Platform) were searched up to July 2018. Review methods A systematic review and network meta-analysis of fracture and femoral neck bone mineral density were conducted. A review of published economic analyses was undertaken and a model previously used to evaluate bisphosphonates was adapted. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years for a simulated cohort of patients with heterogeneous characteristics. This was done for each non-bisphosphonate treatment, a strategy of no treatment, and the five bisphosphonate treatments previously evaluated. The model was populated with effectiveness evidence from the systematic review and network meta-analysis. All other parameters were estimated from published sources. An NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture® (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX® (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net monetary benefit was estimated using non-parametric regression. A probabilistic sensitivity analysis and scenario analyses were used to assess uncertainty. Results Fifty-two randomised controlled trials of non-bisphosphonates were included in the clinical effectiveness systematic review and an additional 51 randomised controlled trials of bisphosphonates were included in the network meta-analysis. All treatments had beneficial effects compared with placebo for vertebral, non-vertebral and hip fractures, with hazard ratios varying from 0.23 to 0.94, depending on treatment and fracture type. The effects on vertebral fractures and the percentage change in bone mineral density were statistically significant for all treatments. The rate of serious adverse events varied across trials (0–33%), with most between-group differences not being statistically significant for comparisons with placebo/no active treatment, non-bisphosphonates or bisphosphonates. The incremental cost-effectiveness ratios were > £20,000 per quality-adjusted life-year for all non-bisphosphonate interventions compared with no treatment across the range of QFracture and FRAX scores expected in the population eligible for fracture risk assessment. The incremental cost-effectiveness ratio for denosumab may fall below £30,000 per quality-adjusted life-year at very high levels of risk or for high-risk patients with specific characteristics. Raloxifene was dominated by no treatment (resulted in fewer quality-adjusted life-years) in most risk categories. Limitations The incremental cost-effectiveness ratios are uncertain for very high-risk patients. Conclusions Non-bisphosphonates are effective in preventing fragility fractures, but the incremental cost-effectiveness ratios are generally greater than the commonly applied threshold of £20,000–30,000 per quality-adjusted life-year. Study registration This study is registered as PROSPERO CRD42018107651. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 29. See the NIHR Journals Library website for further project information.
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Harris, Trevor S., Urooj Khan, and Doron Nissim. "The Expected Rate of Credit Losses on Banks' Loan Portfolios." Accounting Review 93, no. 5 (2018): 245–71. http://dx.doi.org/10.2308/accr-52012.
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ABSTRACT Estimating expected credit losses on banks' portfolios is difficult. The issue has become of increasing interest to academics and regulators with the FASB and IASB issuing new regulations for loan impairment. We develop a measure of the one-year-ahead expected rate of credit losses (ExpectedRCL) that combines various measures of credit risk disclosed by banks. It uses cross-sectional analyses to obtain coefficients for estimating each period's measure of expected credit losses. ExpectedRCL substantially outperforms net charge-offs in predicting one-year-ahead realized credit losses, and reflects nearly all the credit loss-related information in the charge-offs. ExpectedRCL also contains incremental information about one-year-ahead realized credit losses relative to the allowance and provision for loan losses and the fair value of loans. It is a better predictor of the provision for loan losses than analyst provision forecasts, and is incrementally useful beyond other credit risk metrics in predicting bank failure up to one year ahead.
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Lueg, Rainer, and Jon Svennesen Toft. "Earnings Less Risk-Free Interest Charge (ERIC) and Stock Returns—A Value-Based Management Perspective on ERIC’s Relative and Incremental Information Content." Journal of Risk and Financial Management 15, no. 8 (2022): 368. http://dx.doi.org/10.3390/jrfm15080368.
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This paper investigates the relative and incremental information content of KPMG’s recently developed metric for shareholder value creation: earnings less risk-free interest charge (ERIC). We assess if ERIC has a better ability to predict stock returns than earnings, cash flow from operations (CFO), earnings before extraordinary items (EBEI), residual income (RI), or economic value added (EVA). We evaluate data from 214 companies listed on the U.S. Standard & Poor’s 500 Index from 2003 to 2012 (2354 firm-year observations). Similar to previous studies, we confirm that CFO and EBEI have the strongest association with stock returns in the short term, while EVA trails behind all other metrics. In terms of new findings, ERIC is the best predictor of stock returns over a 5-year period, as well as during times of crises (from 2009 to 2010). In this period, ERIC also adds incremental information content beyond that of EBEI. However, the low-short-/mid-term predictive ability of shareholder value metrics (EVA, ERIC) raises concerns regarding their reliable use in future research on shareholder value creation. We consequently propose a research agenda that focuses less on the measurement and more on the management of shareholder value.
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Tavares, Diana, Helena Mouriño, Cristina Antón Rodríguez, and Carlos Martín Saborido. "Cost Effectiveness of Quadrivalent Versus Trivalent Inactivated Influenza Vaccines for the Portuguese Elderly Population." Vaccines 10, no. 8 (2022): 1285. http://dx.doi.org/10.3390/vaccines10081285.
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Background: quadrivalent inactivated vaccine (QIV) has replaced trivalent inactivated vaccine (TIV). In Portugal, TIV is free of charge for risk groups, including older adults (≥65 years old). In its turn, QIV—which provides broader protection as it includes an additional lineage B strain—was introduced in Portugal in October 2018; only since the 2019/20 influenza season has it been provided free of charge for risk groups. This study evaluates the cost effectiveness of switching from TIV to QIV, from the National Health Service perspective, in the Portuguese elderly mainland population. Methods: A decision tree model was developed to compare TIV and QIV, based on Portuguese hospitalization data for the 2015/16 influenza season. The primary health economic outcome under consideration was the incremental cost-effectiveness ratio (ICER). In addition, one-way sensitivity analysis and probabilistic sensitivity analysis were performed. Results: the high cost of QIV (approximately three times the cost of TIV) would lead to a total increment of EUR 5,283,047, and the resulting ICER would be EUR 26,403,007/QALY, above the usual willingness-to-pay threshold. Conclusions: from the National Health Service perspective, our findings reveal that QIV is not cost effective for the Portuguese elderly population due to the high cost. If the QIV costs were the same as the TIV, then QIV would be cost effective.
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Deitelzweig, Steven, Stephen Thompson, Jay Lin, Donna McMorrow, and Barbara Johnson. "Impact of CMS VTE Hospital Acquired Conditions (HAC) Policy on Hospital Cost and Revenue Associated with Major Surgical Hip and Knee Procedures." Blood 116, no. 21 (2010): 3824. http://dx.doi.org/10.1182/blood.v116.21.3824.3824.
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Abstract Abstract 3824 Background: The Centers for Medicare and Medicaid Services (CMS) recently executed a policy which denies reimbursement for preventable hospital acquired conditions (HAC) (“never events”). Venous thromboembolism (VTE), which encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients undergoing major surgical hip or knee procedures was a condition selected for implementation as part of this policy in fiscal year 2009 (beginning October 2008). The objective of this analysis was to estimate the financial impact of this policy change on US hospitals. Methods: Discharge-level hospital administrative records were extracted from the Thomson Reuters MarketScan® Hospital Drug Database for patients undergoing CMS-defined surgical hip and knee procedures (total hip/knee replacement, partial hip replacement, and hip resurfacing). Discharged patients meeting the following criteria were included: admission and discharge between October 2007 and September 2008, age ≥ 18 years, Medicare as primary payer, valid CMS hospital ID and no evidence of DVT/PE on admission. The frequency of CMS defined VTE was assessed and the economic impact of the CMS HAC policy was estimated. Revenue impact, the amount of revenue lost per hospital due to CMS policy implementation, was calculated per year and per VTE discharge using the old and new CMS reimbursement rules. The incremental cost impact, the additional cost to hospitals due to VTE among hip/knee surgery patients, was also determined. Results: A total of 107 hospitals were identified to have at least one eligible surgical hip and knee surgery discharge. The total number of such discharges was 26,144. On average, there were 244.34 CMS-defined hip/knee surgery discharges per hospital. The majority of discharged patients were from urban hospitals (83.37%) in the Southern US (73.07%), without teaching status (87.98%) and with a licensed bed size of 300–499 beds (31.90%). VTE occurred in an average (± standard deviation) of 4.25 ± 6.05 hip/knee surgery discharges per hospital; DVT and PE occurred in 2.44 ± 5.11 and 1.81 ± 1.89 discharges per hospital, respectively. The average length of hospital stay was 7.56 ± 2.88 days in hip/knee discharges with VTE, compared to 4.08 ± 0.59 days in discharges without VTE. Anticoagulation was ordered in 94.70% of discharged patients with DVT and in 89.06% of discharged patients with PE. Under the CMS HAC policy for VTE, the mean loss of revenue per hospital per year was estimated to be $8,453 (95% confidence interval [CI] 6,902 – 10,005). Per VTE, the average hospital revenue loss was $2,704 per hospital per year. The mean incremental cost for a hip/knee discharge with VTE, per hospital was $6,581; for DVT and PE, incremental cost impacts were $6,751 and $8,092, respectively. The annual cost impact per hospital for hip/knee discharges with VTE was estimated at $31,609 [95% CI 23,714 – 39,505]. Conclusions: The CMS policy on average caused a loss of hospital revenue (≂f$8,500 per year). Additionally, when a VTE event does occur in patients undergoing surgical hip and knee procedures, it is associated with high incremental hospital costs (≂f$32,000). These significant costs will no longer be reimbursed under the new CMS HAC policy. Subsequently, hospitals will be responsible for covering them. Therefore, now more than ever, reducing VTE rates through appropriate prophylaxis of at-risk patients is vital in order for hospitals to lessen the economic impact associated with treating VTE events. The drive to encourage hospitals to provide more efficient and effective healthcare is becoming particularly relevant now that models of health care reform, such as the “Accountable Care Organization”, are being piloted as part of the Senate's Healthcare Reform Bill. This study was funded by sanofi-aventis U.S., Inc. The authors received editorial/writing support in the preparation of this abstract provided by Katherine Roberts, PhD of Excerpta Medica, funded by sanofi-aventis U.S., Inc. Disclosures: Deitelzweig: sanofi-aventis: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Research Funding, Speakers Bureau; Scios: Honoraria, Research Funding, Speakers Bureau; Pfizer: Speakers Bureau. Thompson:sanofi-aventis US Inc.: Employment. Lin:sanofi-aventis US Inc.: Employment, Research Funding. McMorrow:sanofi-aventis US Inc : Research Funding. Johnson:sanofi-aventis US Inc: Research Funding.
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Muya, Julio Kunda. "Article: Exploring Shortcomings in International Trade Law in Light of the Expansion of Artificial Intelligence." Global Trade and Customs Journal 19, Issue 11/12 (2024): 731–37. http://dx.doi.org/10.54648/gtcj2024082.
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The objective of this paper is to explore the shortcomings in international trade law (ITL) in view of the expansion of Artificial Intelligence (AI), and to propose some recommendations. AI is contributing to the development of international trade while giving rise to other concerns, such as nontariffs measures. Addressing the legal challenges posed by the integration of AI into various facets of society, including international trade, is of major importance. In this context, this paper explores a number of provisions of the General Agreement on Tariffs and Trade (GATT) 1994, those of the General Agreement on Trade in Services (GATS), and ends with those of the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). Finally, the article proposes some recommendations to better take into account the concerns that AI may give rise to in the multilateral trading system. It highlights the need for close partnership between the World Trade Organization (WTO), the International Standardization Organization (ISO) and the International Electrotechnical Commission (IEC) to better maximize the benefits of AI while minimizing the risks in the context of international trade. Also, it highlights the importance of harmonizing regulations on the trade of AI products and AI-driven trading and the need for a change in legal design that goes beyond mere incremental adjustments.
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Li, W. L., and L. S. Chuah. "A PV MPPT control method based on async-PSO and INC algorithm under shading condition." Journal of Optoelectronic and Biomedical Materials 16, no. 1 (2024): 17–33. http://dx.doi.org/10.15251/jobm.2024.161.17.
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For the time being, solar energy has received considerable attention and development on account of its distinct advantages, such as rich reserves and no geographical restrictions. Nevertheless, in practical applications, the photovoltaic module is easily affected by external environments, which gives rise to a decrease in photovoltaic power. The maximum power point tracking (MPPT) technology for PV power system is an effective method to elevate the efficacy of photovoltaic electricity conversion. The frequently used control methods include the perturb and observe (P&O) algorithm and the incremental conductance (INC) method, and so forth; these methods vary tremendously in terms of the required parameters, algorithm complexity, tracking speed, tracking accuracy, hardware requirements etc. This work puts forth a MPPT control method on the basis of Async-PSO and INC algorithm to achieve a better performance in the MPPT. To reflect the change of light amplitude and temperature in a day, the temperature varies from 25℃ to 60℃ and irradiance from 450W/m2 to 900W/m2 . An extensively used mono-crystalline silicon PV module with 240W was considered as the research object to compare the capability of the recommended MPPT control method. MATLAB/Simulink software was adopted to model and simulate the algorithm. Aside from that, comprehensive comparisons were made with other MPPT methods to test and verify the recommended algorithm has significantly improved the tracking speed and accuracy at the maximum power point with smaller oscillations under various conditions.
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Prorokowski, Lukasz, and Hubert Prorokowski. "Comprehensive risk measure – current challenges." Journal of Financial Regulation and Compliance 22, no. 3 (2014): 271–84. http://dx.doi.org/10.1108/jfrc-09-2013-0033.
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Purpose – This paper, based on case-studies with five universal banks from Europe and North America, aims to investigate which types of comprehensive risk measure (CRM) models are being used in the industry, the challenges being faced in implementation and how they are being currently rectified. Undoubtedly, CRM remains the most challenging and ambiguous measure applied to the correlation trading book. The turmoil surrounding the new regulatory framework boils down to the Basel Committee implementing a range of capital charges for market risk to promote “safer” banking in times of financial crisis. This report discusses current issues faced by global banks when complying with the complex set of financial rules imposed by Basel 2.5. Design/methodology/approach – The current research project is based on in-depth, semi-structured interviews with five universal banks to explore the strides major banks are taking to introduce CRM modelling while complying with the new regulatory requirements. Findings – There are three measures introduced by the Basel Committee to serve as capital charges for market risk: incremental risk charge; stressed value at risk and CRM. All of these regulatory-driven measures have met with strong criticism for their cumbersome nature and extremely high capital charges. Furthermore, with banks facing imminent implementation deadlines, all challenges surrounding CRM must be rectified. This paper provides some practical insights into how banks are finalising the new methodologies to comply with Basel 2.5. Originality/value – The introduction of CRM and regulatory approval of new internal market risk models under Basel 2.5 has exerted strong pressure on global banks. The issues and computational challenges surrounding the implementation of CRM methodologies are currently fiercely debated among the affected banks. With little guidance from regulators, it remains very unclear how to implement, calculate and validate CRM in practice. To this end, a need for a study that sheds some light on practices with developing and computing CRM emerged. On submitting this paper to the journal, we have received news that JP Morgan is to pay four regulators $920 million as a result of a CRM-related scandal.
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Lowry, D. C., R. J. Suttill, and R. J. Taylor. "ADVANCES IN RISKING EXPLORATION PROSPECTS." APPEA Journal 45, no. 1 (2005): 143. http://dx.doi.org/10.1071/aj04012.
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Assessment of prospect risk is a vital exploration activity, but technical literature on the subject shows few advances in methodologies in the last 20 years. Origin Energy has found that published procedures are not always adequate. Three perceived shortcomings are examined and techniques are proposed to overcome them.Cases where prospect risk is dependent on reserve size. Traditional methodologies assume the two are independent. This assumption is clearly inappropriate for, say, a prospect for which the success case value is based on the mapped closure, but which has suspect seal capacity that may limit the column height to something less than full-to-spill. A way forward is to build a variable risk array for a range of column heights and calculate the incremental risked NPV for each layer. The expected monetary value (EMV) is computed for a range of column heights based on the NPV of cumulative risked reserves;Cases where the estimation of chance of success (COS) based on traditional geological information needs to be combined with direct hydrocarbon indicators (DHIs) from seismic data. DHIs are not infallible indicators, however, and cannot be used to set the COS for elements such as charge to say 100%. Bayes’ Theorem can be used to combine the two sets of uncertain information.Cases where prospects are risked on very limited data. Traditional risking does not adequately incorporate the level of knowledge on which risk assessments are made. Inadequacies are identified in existing methodologies, but no simple and satisfactory solutions can be identified. We do suggest a way forward, however, for a related problem—testing the sensitivity of the EMV calculation for an exploration prospect for uncertainties in COS.
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Zeidan, Amer M., Bhavik J. Pandya, Cynthia Z. Qi, Andy Garnham, Hongbo Yang, and Manasee V. Shah. "Cost-Effectiveness Analysis of Gilteritinib Versus Best Supportive Care (BSC) for the Treatment of Relapsed or Refractory (R/R) FLT3 Mutation-Positive (FLT3mut+) Acute Myeloid Leukemia (AML)." Blood 134, Supplement_1 (2019): 5085. http://dx.doi.org/10.1182/blood-2019-123811.
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Introduction: AML is an aggressive hematopoietic malignancy, and ~30% of patients have mutations in the FLT3 gene. Historically, patients with R/R FLT3mut+ AML experienced dismal survival outcomes. The approval of FLT3-targeted agents has resulted in a paradigm change in the management of these patients. In 2018, gilteritinib was approved as the first targeted agent for R/R FLT3mut+ AML based on results of the phase 3 ADMIRAL trial, showing significantly improved median overall survival (OS) of 9.3 months. Historically, due to limited effective options and tolerability concerns, 11-40% of patients with R/R FLT3mut+ AML received BSC (defined as no active leukemia-directed therapy). Patients managed by BSC still incur substantial resource use and have poor outcomes. The estimated median OS was 2-3 months, with the majority of patients (> 90%) dying within one year. To quantify the incremental benefit and economic value of gilteritinib over BSC, a cost-effectiveness analysis (CEA) model was constructed to model disease trajectory, quality of life impact, and economic impact. Methods: A CEA was developed to compare the costs and effectiveness of gilteritinib and BSC from a US third-party payer's perspective over a lifetime horizon. The model used a 1-month cycle and 3% discount rate and comprised a decision tree followed by a three-stage partitioned survival model. In the decision tree stage, patients were first classified based on whether they received allogeneic hematopoietic stem cell transplantation (HSCT). Following stratification, patients were distributed among three health states: event-free survival (EFS), alive and post-event, and death. Due to the palliative nature of BSC, all patients in the BSC arm were assumed to start in the alive and post-event state and were not eligible to receive subsequent HSCT based on clinical inputs. For patients in the gilteritinib arm, the efficacy inputs were based on the ADMIRAL trial for patients without HSCT or literature (Evers 2018) for those with HSCT. For patients in the BSC arm, the efficacy inputs were based on available literature (Sarkozy 2013). Parametric survival models or hazard ratios were used to predict probabilities in different health states until year 3. After year 3, all patients who remained alive were considered cured with a two-fold increase in mortality risk compared to the general population. Treatment costs (drug, administration, and hospitalization), adverse event (AE) costs, subsequent HSCT costs, medical costs for health states, FLT3 testing, post-progression treatment, and terminal care costs were obtained from public databases and literature. Patients managed by BSC were assumed not to incur any costs related to treatment, AEs, or HSCT. All costs were inflated to 2018 US dollar (USD). Utilities for each health state were derived from the ADMIRAL trial and disutilities for AEs were derived from the literature. The model calculated total costs, and total effectiveness measured by life years (LYs) and quality-adjusted life years (QALYs) for gilteritinib and BSC, respectively. Incremental cost-effectiveness ratios (ICERs), defined as the incremental cost per additional gain in health effect (i.e., LY and QALY), were estimated comparing gilteritinib to BSC. To test the robustness of the results, deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were performed. Results: Over a lifetime horizon, treatment with gilteritinib, compared to BSC, was associated with an incremental LY gain of 2.82 and QALY gain of 2.32, respectively. With an additional cost of $239,623 relative to BSC, the ICER per one LY gained was $84,922, and ICER per one QALY gained was $103,110. The results were most sensitive to discount rate, cure assumptions, and gilteritinib cost. PSA showed 100% probability of being cost-effective at an acceptable willingness-to-pay threshold of $150,000/QALY in the US. Conclusions: Gilteritinib led to substantial clinical benefit compared to BSC for treatment of R/R FLT3mut+ AML. Despite the large cost difference, the ICER is still within a reasonable range of less than $150,000/QALY, as established by the US Institute for Clinical and Economic Review. Gilteritinib fulfills an important unmet need in the treatment landscape and represents a potential paradigm shift in the current management of R/R FLT3mut+ AML for patients who otherwise would not have received active therapy. Disclosures Zeidan: BeyondSpring: Honoraria; Acceleron Pharma: Consultancy, Honoraria, Research Funding; Celgene Corporation: Consultancy, Honoraria, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Trovagene: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Cardinal Health: Honoraria; Otsuka: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Jazz: Honoraria; Ariad: Honoraria; Agios: Honoraria; Novartis: Honoraria; Astellas: Honoraria; Daiichi Sankyo: Honoraria; Medimmune/AstraZeneca: Research Funding; Seattle Genetics: Honoraria. Pandya:Astellas Pharmaceuticals: Employment. Qi:Astellas: Other: I am an employee of Analysis Group, Inc., which provided paid consulting services to Astellas for the conduct of this study; Analysis Group, Inc.: Employment. Garnham:Astellas: Employment. Yang:Analysis Group, Inc.: Employment; Astellas: Other: I am an employee of Analysis Group, Inc., which provided paid consulting services to Astellas for the conduct of this study. Shah:Astellas: Employment.
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Harnan, Sue, Paul Tappenden, Katy Cooper, et al. "Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer: a systematic review and economic analysis." Health Technology Assessment 23, no. 30 (2019): 1–328. http://dx.doi.org/10.3310/hta23300.
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BackgroundBreast cancer and its treatment can have an impact on health-related quality of life and survival. Tumour profiling tests aim to identify whether or not women need chemotherapy owing to their risk of relapse.ObjectivesTo conduct a systematic review of the effectiveness and cost-effectiveness of the tumour profiling tests oncotypeDX®(Genomic Health, Inc., Redwood City, CA, USA), MammaPrint®(Agendia, Inc., Amsterdam, the Netherlands), Prosigna®(NanoString Technologies, Inc., Seattle, WA, USA), EndoPredict®(Myriad Genetics Ltd, London, UK) and immunohistochemistry 4 (IHC4). To develop a health economic model to assess the cost-effectiveness of these tests compared with clinical tools to guide the use of adjuvant chemotherapy in early-stage breast cancer from the perspective of the NHS and Personal Social Services.DesignA systematic review and health economic analysis were conducted.Review methodsThe systematic review was partially an update of a 2013 review. Nine databases were searched in February 2017. The review included studies assessing clinical effectiveness in people with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative, stage I or II cancer with zero to three positive lymph nodes. The economic analysis included a review of existing analyses and the development of a de novo model.ResultsA total of 153 studies were identified. Only one completed randomised controlled trial (RCT) using a tumour profiling test in clinical practice was identified: Microarray In Node-negative Disease may Avoid ChemoTherapy (MINDACT) for MammaPrint. Other studies suggest that all the tests can provide information on the risk of relapse; however, results were more varied in lymph node-positive (LN+) patients than in lymph node-negative (LN0) patients. There is limited and varying evidence that oncotypeDX and MammaPrint can predict benefit from chemotherapy. The net change in the percentage of patients with a chemotherapy recommendation or decision pre/post test ranged from an increase of 1% to a decrease of 23% among UK studies and a decrease of 0% to 64% across European studies. The health economic analysis suggests that the incremental cost-effectiveness ratios for the tests versus current practice are broadly favourable for the following scenarios: (1) oncotypeDX, for the LN0 subgroup with a Nottingham Prognostic Index (NPI) of > 3.4 and the one to three positive lymph nodes (LN1–3) subgroup (if a predictive benefit is assumed); (2) IHC4 plus clinical factors (IHC4+C), for all patient subgroups; (3) Prosigna, for the LN0 subgroup with a NPI of > 3.4 and the LN1–3 subgroup; (4) EndoPredict Clinical, for the LN1–3 subgroup only; and (5) MammaPrint, for no subgroups.LimitationsThere was only one completed RCT using a tumour profiling test in clinical practice. Except for oncotypeDX in the LN0 group with a NPI score of > 3.4 (clinical intermediate risk), evidence surrounding pre- and post-test chemotherapy probabilities is subject to considerable uncertainty. There is uncertainty regarding whether or not oncotypeDX and MammaPrint are predictive of chemotherapy benefit. The MammaPrint analysis uses a different data source to the other four tests. The Translational substudy of the Arimidex, Tamoxifen, Alone or in Combination (TransATAC) study (used in the economic modelling) has a number of limitations.ConclusionsThe review suggests that all the tests can provide prognostic information on the risk of relapse; results were more varied in LN+ patients than in LN0 patients. There is limited and varying evidence that oncotypeDX and MammaPrint are predictive of chemotherapy benefit. Health economic analyses indicate that some tests may have a favourable cost-effectiveness profile for certain patient subgroups; all estimates are subject to uncertainty. More evidence is needed on the prediction of chemotherapy benefit, long-term impacts and changes in UK pre-/post-chemotherapy decisions.Study registrationThis study is registered as PROSPERO CRD42017059561.FundingThe National Institute for Health Research Health Technology Assessment programme.
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Groarke, Jenny M., Janice Richmond, Mary Grace Kelly, et al. "Examining the Impact of a Personalized Self-Management Lifestyle Program Using Mobile Technology on the Health and Well-Being of Cancer Survivors: Protocol and Rationale for a Randomized Controlled Trial (The Moving On Study)." JMIR Research Protocols 8, no. 8 (2019): e13214. http://dx.doi.org/10.2196/13214.
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Background Cancer survivorship in Ireland is increasing in both frequency and longevity. However, a significant proportion of cancer survivors are overweight. This has negative implications for long-term health outcomes, including increased risk of subsequent and secondary cancers. There is a need to identify interventions, which can improve physical and psychological outcomes that are practical in modern oncology care. Mobile health (mHealth) interventions demonstrate potential for positive health behavior change, but there is little evidence for the efficacy of mobile technology to improve health outcomes in cancer survivors. Objective This study aims to investigate whether a personalized mHealth self-management lifestyle program is acceptable to participants and can improve physical and psychological outcomes of a subgroup of cancer survivors with increased health risks related to lifestyle behaviors. Methods A sample of 123 cancer survivors (body mass index >25 kg/m2) was randomly assigned to the control (n=61) or intervention (n=62) group. The intervention group attended a 4-hour tailored lifestyle information session with a physiotherapist, dietician, and clinical psychologist to support self-management of health behavior. Over the following 12 weeks, participants engaged in personalized goal setting to incrementally increase physical activity (with feedback and review of goals through short message service text messaging contact). Objective measures of health behavior (ie, physical activity) were collected using Fitbit (Fitbit, Inc). Data on anthropometric, physiological, dietary behavior, and psychological measures were collected at baseline (T0), 12 weeks (T1; intervention end), and 24 weeks (T2; follow-up). Semistructured interviews were conducted to explore the retrospective acceptability of the Moving On program from the perspective of the recipients. Results This paper details the protocol for the Moving On study. The project was funded in August 2017. Enrolment started in December 2017. Data collection completed in September 2018. Data analysis is underway, and results are expected in winter 2019. Conclusions The results of this study will determine the efficacy and acceptability of an mHealth intervention using behavior change techniques to promote health behaviors that support physical health and well-being in cancer survivors and will therefore have implications for health care providers, patients, health psychologists, and technologists. International Registered Report Identifier (IRRID) DERR1-10.2196/13214
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Sun, Shawn X., Yanyu Wu, Michael McDermott, and Marjolijn van Keep. "Cost-Effectiveness Model of Recombinant FVIII Versus Emicizumab Treatment of Patients With Severe Hemophilia A Without Inhibitors." Blood 134, Supplement_1 (2019): 2102. http://dx.doi.org/10.1182/blood-2019-124421.
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Introduction: The standard of care for patients with hemophilia A without inhibitors is factor VIII (FVIII) replacement therapy. The availability of non-factor therapy such as emicizumab (Hemlibra®; Genentech, Inc., South San Francisco, CA, USA) is changing the treatment landscape. A model was developed from the perspective of the US healthcare system to compare the cost-effectiveness of recombinant FVIII (rFVIII) products (standard half-life [SHL] and extended half-life [EHL]) versus non-factor therapy emicizumab in the treatment of patients with severe hemophilia A without inhibitors. Methods: The Markovian model used in this analysis included 5 mutually exclusive hemophilia A-related health states: with/without target joints (TJs), with/without arthropathy, and death. Health states changed or remained constant, depending on bleeds and recovery probability. Transition to the health state "death" was derived from mortality rates in the general US population according to age. Each health state was associated with costs and utilities that were summed over time. Estimated total costs and treatment effectiveness as measured by quality-adjusted life years (QALYs; a measure of health outcome that incorporates the impact on both quantity and quality of life) for each health state were then used to calculate incremental cost-effectiveness ratios for pairwise comparisons of treatments (prophylaxis or on-demand for a pooled analysis of 6 rFVIII products [SHL and EHL] vs emicizumab prophylaxis; Table 1) over a life-time horizon. Patient data used in the model were based on a systematic literature review and clinical trial results, and network meta-analysis. Model parameters included patient baseline characteristics, change in body weight by age, prior prophylaxis or on-demand treatment, annualized bleeding rate (ABR), probability of developing or resolving TJs or arthropathy, mortality, number infusions per bleed, medical check-ups, and hospitalization. Based on these data, patients in the model were assumed to be male and 33 years of age at baseline; 72.0% had TJs and 58.4% had arthropathy. Probability of developing TJs per joint bleed was estimated to be 0.9% (prophylaxis and on-demand treatment). Probability of developing arthropathy per joint bleed was estimated to be 2.2% for patients who received prior on-demand treatment and patients who received prior prophylaxis were assumed to have no risk of developing arthropathy. The model assumed life-long adherence to the same prophylactic hemophilia treatment. Drug cost was based on 2018 average sales price and dosing was on label. The model did not include treatment-specific adverse events or inhibitor development. Results: Prophylaxis with rFVIII (SHL and EHL) was estimated to be less costly and more effective (total $13,656,238; QALYs 17.61) versus non-factor prophylaxis with emicizumab (total $16,447,843; QALYs 17.58) over an estimated 70-year lifespan of a patient with severe hemophilia A, which suggests rFVIII prophylaxis is an economically preferable strategy. Total cost consists of costs directly related to prophylactic treatment (rFVIII $12,850,894 vs emicizumab $15,555,379) and costs associated with healthcare resources (rFVIII $805,344 vs emicizumab $892,464). rFVIII prophylaxis was also estimated to be less costly and more effective (total $13,656,238; QALYs 17.61) versus on-demand rFVIII treatment (total $13,823,123; QALYs 12.29). Conclusions: In this pooled analysis of select SHL and EHL rFVIII products, the results suggest that rFVIII prophylaxis is a cost-effective long-term intervention for patients with severe hemophilia A without inhibitors compared with non-factor prophylaxis with emicizumab and on-demand rFVIII treatment. Disclosures Sun: Shire US Inc., a Takeda company: Employment, Other: a Takeda stock owner. Wu:Shire US Inc., a Takeda company: Employment, Other: a Takeda stockowner. McDermott:BresMed Health Solutions Ltd.: Employment. van Keep:BresMed Health Solutions Ltd.: Employment.
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Dev Avasthi, Vipul, and Kapil Dev Avasthi. "Performance Evaluation of Energy Storage Systems for Different Drive Cycles in Hybrid Electric Vehicle." Journal of Futuristic Sciences and Applications 1, no. 1 (2018): 30–36. http://dx.doi.org/10.51976/jfsa.111806.
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The important control parameters for the hybrid electric vehicle are the lower and upper limit of state of charge (SOC). The vehicle’s onboard energy system defined the fuel economy and the electric range thus during the period at which the power demand is less, we will allow the ESS to get charged and they will get discharged during the period of high-power demand. ESS acts as the catalysts as they help in boosting the energy requirements. In HEVs, maintaining high energy density is a necessity while demanding higher peak power as well thus this results in doubling the incremental cost of the vehicle if approx. 15 % of all electric range is demanded. The SOC of the vehicle directly affects the economy and the emission rates. In this work the parallel HEV is modelled by using ADVISOR and Different SOC limits are taken for testing the performance and fuel economy for the same designed driving cycle. With the simulation results we will be able to specify best upper and lower limits of SOC such that vehicle will achieve best fuel economy and emission performance. The simulation is performed by taking repetitive velocity profiles (drive cycles) of four different curves i.e. UDDS, ECE, FTP and HWFET. The SOC and emission curves are observed for these different drive cycles and the results having emission rates for HC, CO and NOx (in g/miles) are tabulated.
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Gowin, Krisstina L., Amylou C. Dueck, John O. Mascarenhas, et al. "Interim Analysis of a Phase II Pilot Trial of Ruxolitinib Combined with Danazol for Patients with Primary Myelofibrosis (MF), Post Essential Thrombocythemia-Myelofibrosis (Post ET), and Post Polycythemia Vera Myelofibrosis (PV MF) Suffering from Anemia." Blood 124, no. 21 (2014): 3206. http://dx.doi.org/10.1182/blood.v124.21.3206.3206.
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Abstract Introduction: Approximately 75% of myelofibrosis (MF) patients develop anemia during evolution of the disease process predicting decreased survival. Previous studies exploring the effect of danazol in the treatment of anemia in MF demonstrate responses in anemia of 30-55%. Ruxolitinib has demonstrated improvement in MF related splenomegaly, symptom burden, and even survival yet improvements in cytopenias are uncommon. We designed a phase II multicenter pilot study to evaluate the efficacy and tolerability of combination therapy with ruxolitinib and danazol in MF patients with anemia. Methods: This is a pre-planned interim analysis of a Simon optimum two-stage phase II trial designed to include a minimum of 10 and a maximum of 27 patients. Participants received ruxolitinib 10mg (plat >75 x10x9) BID or 5mg (plat <75 x10 x9) BID with danazol 200mg orally TID. Dose escalation was allowed after completion of 28 days for lack of response or for disease progression. Patients without progression were continued for 6 cycles at 56 days each. Treatment modifications were based on adverse events including thrombocytopenia, leukopenia, and elevation in creatinine and transaminases. Treatment responses were evaluated by the IWG-MRT response criteria (Blood 2013). Patient reported outcome questionnaires (MPN-SAF and EORTC QLQ-C30) were administered at baseline, prior to treatment cycles, and at study discontinuation. Results: Patients: Ten of the 12 evaluable patients enrolled (median age 70.5, range 57-78, M:F ratio 4:1) are included in this analysis. Eight patients had primary MF (PMF), 1 had post essential thrombocytosis (ET) MF, and 1 had post polycythemia vera (PV) MF. Jak2 V617F mutation was positive in 30%. At the time of enrollment 40% had received an erythrocyte transfusion in the last month and all were DIPSS Int-2 or higher. Median baseline hemoglobin was 9.0 g/dL (range 8.3 - 12.4). Median baseline platelet level was 172 x10 (9)/L (range 56 - 346). Most (90%) had received prior therapy and many were refractory to multiple lines of therapy prior to enrollment. Three (30%) patients had previously participated in a JAK inhibitor clinical trial. Tolerability: Among 6 patients who have completed treatment, median duration of treatment was 39 days (range 24-287) with treatment discontinuation due to progression of disease in 2 patients, allogeneic stem cell transplant in 1, alternative treatment in 1, unrelated adverse event (hyponatremia) in 1, and unrelated death (leukemic transformation with intracranial hemorrhage) in 1. Hematologic Grade 3 or > adverse events included anemia (60%), neutropenia (20%), and leukopenia (10%). Non-hematologic Grade 3 or > adverse events included electrolyte abnormalities (20%), edema (10%), infection (10%), and intracranial hemorrhage (10%). Efficacy: Treatment response per IWG-MRT response criteria included stable disease (SD) in 8/10 (80%), clinical improvement in 1/10 (10%), and progressive disease (PD) in 1 (10%). The median change in hemoglobin and platelet count from baseline was -0.05 g/dL (range -0.5 - 1.8) and 28.5 x10(9)/L (range -143 – 118) respectively, however 4/10 (40%) and 7/10 (70%) had improvement at some point during treatment in level of anemia and/or thrombocytopenia. The median follow-up time was 2 months (range 0.9-9.4). Among 6 patients with a baseline and at least one post-baseline MPN-SAF TSS, 2/6 (30%) of patients had at least a 10-point (clinically meaningful) improvement, with 1 of the 2 achieving the stricter 50% improvement from baseline. Responses might have been confounded due to impact of prior therapies. Conclusions: On interim analysis, ruxolitinib and danazol combination therapy demonstrates modest additional clinical benefit, however in a group of exceedingly high risk MF patients with significant anemia and prior single agent JAK inhibitor failures. Preliminary data suggests improvement in anemia and/or thrombocytopenia in some treated patients however only one clinical improvement per IWG-MRT criteria was observed. Combination therapy was well tolerated with no major incremental toxicity attributable to the addition of danazol. Maturation of data is needed to fully evaluate efficacy of ruxolitinib and danazol combination therapy prior to continuation of accrual. Disclosures Mascarenhas: Incyte Corporation: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Research Funding. Reeder:Millennium, Celgene, Novartis: Research Funding. Tibes:Seattle Genetics, Inc.: Research Funding. Mesa:Incyte: Research Funding; Novartis: Consultancy; Gilead: Research Funding; Genentech: Research Funding; Promedior: Research Funding; Ns Pharma: Research Funding; Celgene: Research Funding; Lilly: Research Funding; Cti: Research Funding.
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Xiao, Tim. "Incremental Risk Charge Methodology." October 5, 2020. https://doi.org/10.5281/zenodo.4067123.
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The incremental risk charge (IRC) is a new regulatory requirement from the Basel Committee in response to the recent financial crisis. Notably few models for IRC have been developed in the literature. This paper proposes a methodology consisting of two Monte Carlo simulations. The first Monte Carlo simulation simulates default, migration, and concentration in an integrated way. Combining with full re-valuation, the loss distribution at the first liquidity horizon for a subportfolio can be generated. The second Monte Carlo simulation is the random draws based on the constant level of risk assumption. It convolutes the copies of the single loss distribution to produce one year loss distribution. The aggregation of different subportfolios with different liquidity horizons is addressed. Moreover, the methodology for equity is also included, even though it is optional in IRC.
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Xiao, Tim. "Incremental Risk Charge Methodology." February 18, 2019. https://doi.org/10.5281/zenodo.2572029.
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<strong>ABSTRACT</strong> The incremental risk charge (IRC) is a new regulatory requirement from the Basel Committee in response to the recent financial crisis. Notably few models for IRC have been developed in the literature. This paper proposes a methodology consisting of two Monte Carlo simulations. The first Monte Carlo simulation simulates default, migration, and concentration in an integrated way. Combining with full re-valuation, the loss distribution at the first liquidity horizon for a subportfolio can be generated. The second Monte Carlo simulation is the random draws based on the constant level of risk assumption. It convolutes the copies of the single loss distribution to produce one year loss distribution. The aggregation of different subportfolios with different liquidity horizons is addressed. Moreover, the methodology for equity is also included, even though it is optional in IRC. The empirical data are provide by FinPricing at http://finpricing.com/download.html
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Xiao, Tim. "Incremental Risk Charge Methodology." SSRN Electronic Journal, January 1, 2009. https://doi.org/10.2139/ssrn.2426836.
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In this paper, we present a methodology for calculating IRC. First, a Merton-type model is introduced for simulating default and migration. The model is modified to incorporate concentration. The calibration is also elaborated. Second, a simple approach to determine market data, including equity, in response to default and credit migration is presented. Next, a methodology toward constant level of risk is described. The details of applying the constant level of risk assumption and aggregating different subportfolios are addressed. Finally, the empirical and numerical results are presented.
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Bakeer, Abualkasim, Hossam S. Salama, and Istvan Vokony. "Integration of PV system with SMES based on model predictive control for utility grid reliability improvement." Protection and Control of Modern Power Systems 6, no. 1 (2021). http://dx.doi.org/10.1186/s41601-021-00191-1.
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AbstractThis paper describes the integration of a photovoltaic (PV) renewable energy source with a superconducting magnetic energy storage (SMES) system. The integrated system can improve the voltage stability of the utility grid and achieve power leveling. The control schemes employ model predictive control (MPC), which has gained significant attention in recent years because of its advantages such as fast response and simple implementation. The PV system provides maximum power at various irradiation levels using the incremental conductance technique (INC). The interfaced grid side converter of the SMES can control the grid voltage by regulating its injected reactive power to the grid, while the charge and discharge operation of the SMES coil can be managed by the system operator to inject/absorb active power to/from the grid to achieve the power leveling strategy. Simulation results based on MATLAB/Simulink® software prove the fast response of the system control objectives in tracking the setpoints at different loading scenarios and PV irradiance levels, while the SMES injects/absorbs active and reactive power to/from the grid during various events to improve the voltage response and achieve power leveling strategy.
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Xiao, Tim. "Incremental Risk Charge Methodology." SSRN Electronic Journal, 2009. http://dx.doi.org/10.2139/ssrn.2426836.
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Bharathulwar, Shravan V., and Bhanu Chandar Udatha. "Incremental Risk Charge Under Basel II." SSRN Electronic Journal, 2011. http://dx.doi.org/10.2139/ssrn.2136043.
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Went, Peter. "The Incremental Risk Capital Charge - A Challenge for Risk Managers." SSRN Electronic Journal, 2010. http://dx.doi.org/10.2139/ssrn.1729367.
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Yavin, Tzahi, Hu Zhang, Eugene Wang, and Michael A. Clayton. "Transition Probability Matrix Methodology for Incremental Risk Charge." SSRN Electronic Journal, 2011. http://dx.doi.org/10.2139/ssrn.1759467.
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Hasegawa, R., N. Fujiwara, Y. Kato, S. Suzuki, Y. Oikawa, and T. Uejima. "Left atrial assessment improves prediction of incident atrial fibrillation beyond CHARGE-AF risk score." European Heart Journal - Cardiovascular Imaging 26, Supplement_1 (2025). https://doi.org/10.1093/ehjci/jeae333.443.
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Abstract Background Atrial fibrillation (AF) is associated with substantial mortality and morbidity, even when it is asymptomatic and/or remains undetected. Clinical predictive models such as Charge-AF are not robust enough to be used in the clinical practice. We investigated the benefits of adding echocardiographic risk variables to Charge-AF risk model for its potential use in targeted screening for AF. Methods This study included 1108 consecutive patients aged 60±14 years old without a previous diagnosis of AF referred for echocardiographic assessment. Left atrial and ventricular functions were measured using strain analysis. Five-year predicted risk for AF was estimated, using Charge-AF risk model. The incidence of AF was ascertained from resting and exercise stress electrocardiograms and Holter recordings. Sequential Cox models were used to identify echocardiographic variables for predicting the incidence of new onset AF. Results The overall incident rate of AF was 3.1%, 5.5% and 7.2% at 1 year, 3 year and 5 year, respectively. Left atrial volume index (LAVi) predicted the incidence with a hazard ratio of 1.06 (p&lt;0.001), that was independent of and increment to Charge-AF risk estimates (figure A). The addition of E/e’ (hazard ratio=1.064, p=0.001), left atrial reservoir strain (hazard ratio=0.98, p=0.034), left atrial booster strain (hazard ratio=0.97, p=0.048) to the baseline model including Charge-AF risk estimates also showed a significant, but less incremental benefit for AF prediction, compared with LAVi. When all these echocardiographic variables were added to a stepwise nested Cox model, only LAVi was significantly and independently predictive of AF incidence beyond Charge-AF risk estimates. This finding was confirmed by Kaplan-Meier curves showing that an increase in LAVi was progressively associated with increased risk for AF (figure B). When the cumulative AF incidence was analyzed separately between patients with higher (predicted risk &gt;= 1.5%/year) and lower (predicted risk &lt; 1.5%/year) Charge-AF risk estimates, LAVi was able to sub-stratify only patients with higher Charge-AF risk estimate (figures C and D). Conclusion LAVi provided incremental value in predicting incident AF in hospital patients. The inclusion of LAVi to the diagnostic algorithm may help guide screening and further monitoring for AF risk in this population.
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Pedota, Mattia, Luca Grilli, and Lucia Piscitello. "Technological paradigms and the power of convergence." Industrial and Corporate Change, August 7, 2021. http://dx.doi.org/10.1093/icc/dtab038.
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Abstract With the advent of Industry 4.0, technological interdependence is becoming increasingly important in the delineation of technological development dynamics. In the present paper, we propose an extension of the theory of technological paradigms conceptualizing the role of technological interdependence in the emergence of paradigms and the coevolution of the corresponding trajectories. We corroborate our conceptual extension by means of an in-depth historical account of the genesis and evolution of the additive manufacturing paradigm. Accordingly, we elucidate how different technological paradigms may give rise to an aggregate paradigm through a process of convergence and how the aggregate paradigm may contribute to steering the direction of technological change alongside traditional science-push, demand-pull, institutional, and socioeconomic factors. Our work has two main implications: first, it shows that a technological paradigm may emerge from a process of incremental convergence and not only from radical innovations and scientific breakthroughs. Second, it shows that the dynamics of epistemological interdependence (i.e., interdependence between paradigms) matter significantly in the determination of technological development paths.
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Saed Alhakak, A., S. R. Biering-Sorensen, R. Mogelvang, et al. "The prognostic value of left ventricular mechanical dyssynchrony in predicting incident atrial fibrillation and ischemic stroke in the general population." European Heart Journal 41, Supplement_2 (2020). http://dx.doi.org/10.1093/ehjci/ehaa946.0082.
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Abstract Background Left ventricular mechanical dyssynchrony (LVMD) is a predictor of many cardiovascular outcomes including ventricular arrhythmias. However, the prognostic value of LVMD in predicting incident atrial fibrillation (AF) in participants from the general population is currently unknown. Purpose The aim of this study was to investigate if LVMD can be used to predict AF and ischemic stroke in the general population. Methods A total of 1282 participants (mean age 57±16 years, 42% male) from the general population underwent a health examination including two-dimensional speckle tracking echocardiography. LVMD was calculated as the standard deviation of the regional time-to-peak strain from the three apical views. The primary endpoint was incident AF at follow-up. All participants with known AF and prior stroke at baseline were excluded (n=84). The secondary endpoint consisted of the composite of AF and ischemic stroke. Results During a median follow-up of 16 years, 148 participants (12%) were diagnosed with incident AF and 88 (7%) experienced an ischemic stroke, resulting in 236 (19%) experiencing the composite outcome. The risk of AF increased incrementally with increasing tertile of LVMD, being approximately 2-fold higher in the 3rd tertile as compared to the 1st tertile (HR 1.79; 95% CI (1.22–2.63), p=0.003; figure). LVMD was a univariable predictor of AF with 7% increased risk per 10ms increase in LVMD (per 10ms: HR 1.07; 95% CI (1.03–1.12), p&lt;0.001). The association remained significant even after multivariable adjustment for age, sex, body mass index, hypertension, diabetes, previous ischemic heart disease, systolic blood pressure, diastolic blood pressure, heart rate, smoking, plasma proBNP, left ventricular ejection fraction &lt;50%, global longitudinal strain, left atrial volume index (LAVI) and E/e' (per 10ms increase: HR 1.06; 95% CI (1.01–1.12), p=0.018). LVMD was also a univariable predictor of the composite outcome of AF and ischemic stroke (per 10ms increase: HR 1.07; 95% CI (1.04–1.11), p&lt;0.001). After multivariable adjustment for the same clinical and echocardiographic parameters, LVMD remained an independent predictor of the composite outcome (per 10ms: HR 1.07; 95% CI (1.03–1.11), p=0.001). Additionally, LVMD provided incremental prognostic information with regard to predicting AF as assessed by a significant increase in the net reclassification improvement (NRI) index beyond the CHARGE-AF score (continuous NRI, 0.300; 95% CI, 0.022–0.503). Furthermore, LVMD provided additional incremental prognostic information, when added to both the CHARGE-AF score and the LAVI (continuous NRI, 0.269; 95% CI, 0.004–0.499). Conclusion In a low risk general population, LVMD provides novel prognostic information on the long-term risk of AF and ischemic stroke. In addition, LVMD provides incremental prognostic information beyond the CHARGE-AF score and LAVI in predicting AF in the general population. Funding Acknowledgement Type of funding source: None
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Yao, Yuchen, Michael J. Zhang, Wendy Wang, et al. "Multimodal Data Integration to Predict Atrial Fibrillation." European Heart Journal - Digital Health, November 4, 2024. http://dx.doi.org/10.1093/ehjdh/ztae081.
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Abstract Background Many studies have utilized data sources such as clinical variables, polygenic risk scores, ECG, and plasma proteins to predict the risk of atrial fibrillation (AF). However, few studies have integrated all four sources from a single study to comprehensively assess AF prediction. Methods We included 8374 (Visit 3, 1993-1995) and 3,730 (Visit 5, 2011-2013) participants from the Atherosclerosis Risk in Communities Study to predict incident AF and prevalent (but covert) AF. We constructed a 1) clinical risk score using CHARGE-AF clinical variables, 2) polygenic risk score using pre-determined weights, 3) protein risk score using penalized and regularized logistic regression, and 4) ECG risk score from convolutional neural network. Risk prediction performance was measured using regularized logistic regression. Results After a median follow up of 15.1 years, 1910 AF events occurred since Visit 3 and 229 participants had prevalent AF at Visit 5. The AUC improved from 0.660 to 0.752 (95% CI, 0.741-0.763) and from 0.737 to 0.854 (95% CI, 0.828-0.880) after addition of polygenic risk score to the CHARGE-AF clinical variables for predicting incident and prevalent AF, respectively. Further addition of ECG and protein risk scores improved the AUC to 0.763 (95% CI, 0.753-0.772) and 0.875 (95% CI, 0.851-0.899) for predicting incident and prevalent AF, respectively. Conclusions A combination of clinical and polygenic risk scores was the most effective and parsimonious approach to predicting AF. Further addition of an ECG risk score or protein risk score provided only modest incremental improvement for predicting AF.
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Ramkumar, S., F. Pathan, H. Kawakami, et al. "P5979Impact of disease stage on performance of strain markers for prediction of atrial fibrillation." European Heart Journal 40, Supplement_1 (2019). http://dx.doi.org/10.1093/eurheartj/ehz746.0700.
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Abstract Background Efforts to predict incident atrial fibrillation (AF) may be associated with complications, and there is interest in AF prediction in primary prevention (PP; pts with risk factors) and secondary prevention (SP; pts with possible AF complications). These pts have different risk levels, we sought whether that influenced the predictive value of LV dysfunction (measured as global longitudinal strain, GLS) or LA dysfunction (LA reservoir strain). Methods The PP cohort comprised 351 community-based pts ≥65 years with ≥1 risk factor for AF (age 70±4y,43% male, median follow-up 22 months) and the SP cohort comprised 532 pts after transient ischaemic attack or stroke (age 68±12y, 51% male, median follow-up 36 months). GLS and LA strain were measured offline (Image Arena-Tomtec, Germany). AF was diagnosed by 12 lead ECG, Holter or by single lead monitor. The clinical and echocardiographic characteristics of those with AF were compared to those in sinus rhythm. Nested Cox-regression models were used to assess for independent and incremental predictive value of LA strain/GLS in both cohorts. Results Compared to SP, PP had higher clinical AF risk (CHARGE-AF 5.6±5.5% vs 4.7±12.1%, p=0.02) but a lower thromboembolic risk (CHA2DS2-VASC 3±2 vs. 4±2, p<0.001). AF developed in 42 PP pts (12%) and 61 SP (12%). AF patients were older, with higher CHARGE-AF score, LA volume and LV mass. Pts developing AF had reduced GLS (17±4% vs. 20±3%, p<0.001), reservoir (28±11% vs. 35±8%, p<0.001) and pump strain (13±7% vs. 17±5%, p<0.001). GLS and LA strain had greater AUC in SP (0.84 vs 0.58 for GLS and 0.85 vs 0.57 for reservoir strain, both p<0.001). Nested cox-regression models showed that LA reservoir strain was independently associated with AF in both cohorts (p<0.05). GLS was only independently associated with incident AF in SP (Figure). Conclusion LA reservoir strain is independently associated with AF in different risk cohorts and its effect is incremental to clinical parameters and LA volume. GLS may be more useful in AF risk assessment in those in SP. Acknowledgement/Funding This study was partially supported by the Tasmanian Community Fund and Siemens Healthcare Australia.
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Kawakami, H., S. Ramkumar, F. Pathan, L. Wright, and T. H. Marwick. "3224Incremental benefit of left ventricular global longitudinal strain over clinical and left atrial parameters for predicting new-onset atrial fibrillation." European Heart Journal 40, Supplement_1 (2019). http://dx.doi.org/10.1093/eurheartj/ehz745.0043.
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Abstract Background Although LV hypertrophy and dysfunction are associated with atrial fibrillation (AF), AF often occurs in the absence of LV hypertrophy or reduced ejection fraction. The effect of subclinical LV dysfunction on AF has not been fully studied. Purpose We sought the association between subclinical LV dysfunction (measured with global longitudinal strain, GLS) and new-onset AF. Methods This observational study evaluated 531 consecutive patients (median age, 67 years [interquartile range, 56 to 78]; 56% male), without a history of AF who underwent strain echocardiography after cryptogenic stroke. The CHARGE-AF score was used to calculate the 5-year risk of developing AF. Standard echocardiographic parameters were measured, and speckle-tracking was used to measure LA (reservoir strain, pump strain, and conduit strain) and LV strain (GLS). A strain analysis was conducted using a dedicated software package, using R-R gating. The baseline clinical and echocardiographic parameters of the patients who developed AF and those who did not were compared. Results Over 2.5 years of follow-up, 61 patients (11%) had new-onset AF. Patients who developed AF were older, had a higher CHARGE-AF score, larger LA volume, worse LA strain, and worse GLS than those who did not. Areas under the receiver-operating curve for GLS (0.84) was comparable to CHARGE-AF (0.79), LA pump strain (0.83), and LA reservoir strain (0.85). In the nested Cox models, GLS demonstrated an independent and incremental predictive value over the clinical and LA parameters (Figure). Moreover, adding GLS to the combined clinical and LA parameters model resulted in a significantly improved reclassification (net reclassification improvement, 0.32; p=0.016). Importantly, the predictive value of GLS was confirmed in patients with abnormal LA volumes (LA volume index≥34ml/m2) but not in patients with normal LA volumes. Figure 1 Conclusion GLS is associated with new-onset AF, especially in patients with abnormal LA volumes. This effect is independent of and incremental to the clinical and LA parameters.
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Amin, Keval, Chansog Francis Kim, Zhifeng Yang, and FeiTeng Ye. "Politically Connected Boards and Audit Pricing: U.S. Evidence." Accounting Horizons, March 3, 2021. http://dx.doi.org/10.2308/horizons-18-157.
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This study investigates the impact of political connections, as measured by having directors that previously held political positions, on the pricing of audits. We document that auditors charge higher fees to politically connected firms than to similar non-connected firms. Our findings are robust to a battery of additional analyses including (1) propensity score matching, (2) entropy balancing, (3) changes analysis, and (4) a fixed effects model with transaction-based measures of political connections (i.e., campaign contributions and lobbying expenditures) in the model. The effect of political connections on audit fees is mitigated by independent monitoring. Moreover, the main effect is stronger in firms with more complicated operational structures and higher litigation risk, but weaker for distressed firms. Although our findings suggest that auditors exert greater effort at politically connected clients, we show that connected clients report significantly higher discretionary accruals, consistent with auditors' incremental effort being insufficient to fully offset the audit risk inherent in these engagements. Collectively, our study sheds light on how auditors perceive political connections and their impact on financial reporting quality.
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Takagi, H., T. Fairbairn, T. Akasaka, et al. "Trans-stenotic pressure gradient as derived from CT improves patient management: ADVANCE registry." European Heart Journal 42, Supplement_1 (2021). http://dx.doi.org/10.1093/eurheartj/ehab724.0196.
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Abstract Background The change in fractional flow reserve derived from CT (FFRCT) value across a coronary stenosis (ΔFFRCT) improves the physiological characterization of coronary artery disease (CAD). The role of ΔFFRCT in guiding risk-stratification and downstream testing in patients with stable CAD is unknown. Purpose To investigate the incremental value of ΔFFRCT at predicting early revascularization and improving efficacy of resource utilization. Methods Patients with CAD on CT coronary angiography (CTCA) were enrolled in an international multicenter registry. Patients with non-evaluable FFRCT analysis were excluded. The CTCA was assessed for: stenosis severity as per CAD-Reporting and Data System (CAD-RADS), lesion length and lesion-specific FFRCT measured 2 cm distal to stenosis. Risk factors and actual treatment (revascularization vs medical therapy) at 90-day follow-up were recorded. Multivariable logistic regression analysis for early revascularization was conducted. The incremental discrimination for revascularization prediction was compared among 3 models (model 1: risk factors + lesion length and location + CAD-RADS; model 2: model 1 + lesion-specific FFRCT; model 3: model 2 + ΔFFRCT). Simulating ICA referral for patients with CAD-RADS ≥3 and lesion-specific FFRCT ≤0.8, the potential impact of ΔFFRCT at reducing ICA referral and improving the ratio of subsequent revascularization was assessed. Results Of 4730 patients (66±10 years; 34% female), 2092 (42.7%) underwent ICA and 1168 (24.7%) underwent early revascularization. With increasing ΔFFRCT, a higher incidence of revascularization (Figure 1A) and an increase in the revascularization to ICA ratio was observed (Figure 1B). ΔFFRCT &gt;0.13 was the optimal cut-off for predicting revascularization as determined by the Youden index. ΔFFRCT remained an independent predictor for early revascularization (odds ratio per 0.05 increase with 95% CI, 1.31 [1.26–1.35]; p&lt;0.0001) after adjusting for risk factors, CAD-RADS, lesion length and location, and FFRCT. Among the 3 models, model 3, which included ΔFFRCT showed the highest AUC and improved discrimination power compared to model 2 (0.87 [0.86–0.88] vs 0.85 [0.84–0.86]; p&lt;0.0001] (Figure 2), with the greatest incremental value for ΔFFRCT observed in patients with lesion-specific FFRCT between 0.71–0.80. In patients with CAD-RADS ≥3 and lesion-specific FFRCT ≤0.8, a diagnostic strategy incorporating ΔFFRCT &gt;0.13 would potentially reduce ICA referral by 32.2% (1638 to 1110) and improve the revascularization to ICA ratio from 65.2% [1068/1638] to 73.1% [811/1110]. Conclusions The characterization of CAD with ΔFFRCT improves the identification of patients requiring early revascularization as compared to a standard diagnostic strategy of CTCA with FFRCT, particularly for those with lesion-specific FFRCT of 0.71–0.80. ΔFFRCT has the potential to aid decision making for ICA referral and improve the efficiency of resource utilization. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): HeartFlow, Inc., Redwood City, CA, USA ΔFFRCT and actual treatmentROC curve for early revascularization
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Saed Alhakak, A., R. Hauser, K. G. Skaarup, et al. "The prognostic value of right ventricular longitudinal strain in predicting incident atrial fibrillation and ischemic stroke in the general population." European Heart Journal 44, Supplement_2 (2023). http://dx.doi.org/10.1093/eurheartj/ehad655.108.
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Abstract Background Right ventricular (RV) longitudinal strain (RVLS) is a predictor of many cardiovascular outcomes including ventricular arrhythmias. However, the prognostic value of RVLS in predicting incident atrial fibrillation (AF) in participants from the general population is currently unknown. Purpose The aim of this study was to investigate if RVLS can be used to predict AF and ischemic stroke in the general population. Methods A total of 2794 participants (mean age 54±17 years, 42% male) from the general population underwent a health examination including two-dimensional speckle tracking echocardiography. RVLS was measured in the apical four-chamber projection optimized for a view of the RV. The RV free wall was divided into three segments, and the strain values of the three segments were averaged to obtain RVLS. The primary endpoint was incident AF at follow-up. All participants with known AF and prior stroke at baseline were excluded (n=175). The secondary endpoint consisted of the composite of AF and ischemic stroke. Results During a median follow-up of 5 years (interquartile range, 4.5-6.2 years), 110 participants (4%) were diagnosed with incident AF and 59 (2%) experienced an ischemic stroke, resulting in 169 (6%) experiencing the composite outcome. The risk of AF increased incrementally with decreasing tertile of RVLS, being approximately 3-fold higher in the 1st tertile as compared to the 3rd tertile (HR 2.71; 95% CI (1.64-4.46), p&lt;0.001; figure). RVLS was a univariable predictor of AF with 9% increased risk per 1% decrease in RVLS (per 1% decrease: HR 1.09; 95% CI (1.06-1.13), p&lt;0.001). The association remained significant even after multivariable adjustment for clinical and echocardiographic parameters (per 1% decrease: HR 1.06; 95% CI (1.01-1.11), p=0.015). RVLS was also a univariable predictor of the composite outcome of AF and ischemic stroke (per 1% decrease: HR 1.08; 95% CI (1.05-1.12), p&lt;0.001). After multivariable adjustment for the same clinical and echocardiographic parameters, RVLS remained an independent predictor of the composite outcome (per 1% decrease: HR 1.04; 95% CI (1.00-1.09), p=0.032) Additionally, RVLS provided incremental prognostic information with regard to predicting AF as assessed by a significant increase in the net reclassification improvement (NRI) index beyond the CHARGE-AF score (continuous NRI, 0.232; 95% CI, 0.011-0.570). Conclusion In a low-risk general population, RVLS provides novel prognostic information on the long-term risk of AF and ischemic stroke. In addition, RVLS provides incremental prognostic information beyond the CHARGE-AF score in predicting AF in the general population.
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Hammadah, Muhammad, Ayman Alkhoder, Nino Isakadze, et al. "Abstract 11582: Vascular, Hemodynamic and Hormonal Response to Mental Stress and Risk of Mental Stress Induced Myocardial Ischemia." Circulation 134, suppl_1 (2016). http://dx.doi.org/10.1161/circ.134.suppl_1.11582.
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Introduction: Mental stress-induced myocardial ischemia (MSIMI) has been linked to adverse cardiovascular outcomes in patients with stable CAD. However, the underlying mechanisms are not well understood. We aimed to study vasomotor, hemodynamic and hormonal responses to mental stress (MS) and their relationships with MSIMI. Methods: 660 patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging before, and during a public speaking stressor. Hemodynamic parameters (heart rate, BP, rate-pressure product [RPP]), circulating catecholamines, and peripheral arterial tonometry (PAT, Itamar Inc.) were measured at rest, during, and after MS. MSIMI was defined as myocardial perfusion impairment with MS. Results: Participant age was 63±9; 72% male. Overall, 102 (16.1%) patients developed MSIMI. During MS, there was a significant increase in heart rate, BP, RPP and epinephrine, but not norepinephrine levels. The mean PAT ratio, measured as a ratio of the lowest pulse wave amplitude during the speaking task to the final three minutes of pulse wave amplitude during rest, was 0.7 ± 0.3 indicating vasoconstriction with MS. Patients with MSIMI had a greater hemodynamic response (Figure) and a lower PAT ratio (0.6±0.3 vs 0.7±0.3, p=0.008), in comparison to those with no ischemia. After adjustment for age, CAD risk factors and beta blocker use, both higher hemodynamic response (change in RPP≥median) and more vasoconstriction (PAT ratio<median), but not catecholamine response, were independent predictors of MSIMI [OR(95%CI) of 1.8 (1.1-2.9) and 2 (1.2-3.3), p=0.02 and p=0.01, respectively]. A greater hemodynamic response and a lower PAT ratio had an incremental effect on incidence of MSIMI (Figure). Conclusion: A greater hemodynamic response and peripheral vasoconstriction are associated with MSIMI, indicating that both increased myocardial demand and potentially coronary vasoconstriction contribute to this phenomenon.
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Bichon, Alexia, Sylvie Genies, Philippe AZAIS, Didier Buzon, and Olivier Raccurt. "Operando detection of Lithium Plating and Stripping in Fast‐Charging Li‐Ion Cells with Reference Electrode." Batteries & Supercaps, April 15, 2025. https://doi.org/10.1002/batt.202500071.
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Understanding degradation mechanisms in Li‐ion cells is essential for advancing fast‐charging technologies. One of the primary limitations of fast charging is the risk of lithium plating, driven by the negative electrode potential. In this study, a reference electrode was integrated into 30 mAh pouch cells to investigate aging under various charging regimes. This three‐electrode setup allowed us to monitor the potential of both electrodes, with a focus on the negative electrode. By coupling operando data with post‐mortem analysis, we linked the cell's electrical behavior to physical phenomena occurring within the cell. During fast charging at 2C, changes in the incremental capacity profile were observed and correlated with a critical threshold in the negative electrode potential, measured using the reference electrode. Post‐mortem analysis confirmed that these changes are indicative of lithium plating. Furthermore, an additional current during the potentiostatic phase of the charge was identified, correlating with a potential rises of both electrodes. This current bump is interpreted as evidence of a lithium stripping process. These findings highlight the importance of monitoring the negative electrode potential using a reference electrode to detect and mitigate the risk of lithium plating during fast charging, contributing to the optimization of battery performance and safety.
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Pezel, T., B. Ambale Venkatesh, T. Quinaglia, et al. "Change in left atrioventricular coupling index to predict incident atrial fibrillation: the multi-ethnic study of atherosclerosis (MESA)." European Heart Journal - Cardiovascular Imaging 22, Supplement_2 (2021). http://dx.doi.org/10.1093/ehjci/jeab090.080.
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Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND Left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic values as predictors of atrial fibrillation (AF). PURPOSE Due to the intrinsic physiological relationship between LA and LV, we sought to investigate the prognostic value of a left atrioventricular coupling index (LACI) as well as change in LACI to predict incident AF in a multi-ethnic population. METHODS In the Multi-Ethnic Study of Atherosclerosis (MESA), 1,911 study participants, free of clinically recognized AF and cardiovascular disease at baseline, had LACI assessed with CMR imaging at baseline (Exam 1, 2000–2002), and ten years later (Exam 5, 2010–2012). LACI was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average annualized change in LACI (ΔLACI) with incident AF. RESULTS Among the 1,911 participants (mean age 59 ± 9 years and 47.5% male participants), 87 incident AF events occurred over 3.9 ±0.9 years following the second imaging (Exam 5). After adjustment for traditional risk factors, greater LACI and ΔLACI were independently associated with AF (HR 1.69, 95% CI [1.46-1.96] and HR 1.71, 95% CI [1.50-1.94], respectively; both p &lt; 0.0001). Adjusted models for LACI and ΔLACI showed significant improvement in model discrimination compared to currently used AF risk score model for predicting AF incidence (C-statistic: 0.78 vs. 0.74, and C-statistic: 0.80 vs. 0.74, respectively). The LACI and ΔLACI also showed superior discrimination performance for AF compared to the multivariable model including CHARGE-AF score, and individual LA or LV parameters. CONCLUSIONS Atrioventricular coupling (LACI) and coupling change (ΔLACI) are strong predictors for AF incidence in a multi-ethnic population. Both have incremental prognostic value for predicting AF over traditional risk factors, and superior discrimination power compared to the CHARGE-AF score and to individual LA or LV parameters.
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Nguyen, Tracy, Belinda Tang, Krista L. Harrison, et al. "Age Self Care, a program to improve aging in place through group learning and incremental behavior change: Preliminary data." Journal of the American Geriatrics Society, November 28, 2024. http://dx.doi.org/10.1111/jgs.19289.
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AbstractBackgroundFew programs exist to support aging in place for older adults. Age Self Care is a novel program providing older adults with evidence‐based information using group sessions embedded within the structure of a community‐based organization (CBO) to facilitate behavior change and support aging in place. We report on a preliminary study of Age Self Care conducted in collaboration between the University of California, San Francisco (UCSF) Division of Geriatrics, At Home With Growing Older (AHWGO), and San Francisco Village (SF Village).MethodsWe recruited middle‐income, community‐dwelling adults aged 65+ from university outpatient clinics. Participants attended eight 90‐min, video‐based group sessions and enrolled in SF Village, a non‐profit mutual support organization for older adults. Data collection included direct observations and a participant focus group. We used rapid analysis methods informed by the COM‐B model (Capability, Opportunity, Motivation, Behavior Change) to assess behavior change.ResultsFourteen participants completed the 8‐week study (15 enrolled, 1 withdrew). Average attendance was 81% throughout the program. We found that 14 participants made concrete changes to optimize the ability to remain at home during the program. For example, participants engaged in evidence‐based falls risk reduction activities such as decluttering and improving lighting. We identified three facilitators to behavior change. First, Age Self Care promoted self‐management—the day‐to‐day management of health and chronic conditions by individuals—through education and community‐based resources. Second, peer support empowered participants to take charge of their health, home environment, and social networks. Third, the online platform created a community and was a catalyst for social opportunity. We identified one non‐modifiable barrier: pre‐existing financial barriers hindered some behavior change.ConclusionsIn this preliminary study, Age Self Care facilitated behavior change, including minor home modifications, fall risk reduction, and engagement in social networks, all of which support aging in place.
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Olsen, FJ, SZ Diederichsen, PG Jorgensen, et al. "Left atrial strain predicts subclinical atrial fibrillation detected by long-term continuous rhythm monitoring in elderly high-risk individuals." European Heart Journal - Cardiovascular Imaging 22, Supplement_1 (2021). http://dx.doi.org/10.1093/ehjci/jeaa356.189.
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Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): he Innovation Fund Denmark (grant no.: 12-135225), The Research Foundation for the Capital Region of Denmark, The Danish Heart Foundation (grant no.: 11-04-R83-A3363-22625 and 18-R125-A8534-22083), Aalborg University Talent Management Programme, Arvid Nilssons Fond, Skibsreder Per Henriksen, R. og Hustrus Fond, and Medtronic Background Left atrial (LA) speckle tracking is a novel technique that provides detailed information on atrial function. Its utility for predicting subclinical atrial fibrillation (SCAF) is, however, not well-established. Purpose To investigate whether LA speckle tracking measures are associated with SCAF as detected by long-term continuous rhythm monitoring. Methods This was an echocardiographic substudy of a randomized controlled clinical trial that enrolled elderly individuals (≥70 years) with a CHADS2-score≥2 to either no intervention or implantation of a loop recorder (Reveal LINQ) to detect SCAF (≥6 minutes). A subset of the participants receiving a loop recorder was included in this analysis. An echocardiographic examination was performed, which included conventional measurements and LA speckle tracking. LA speckle tracking allowed for assessment of reservoir, conduit, and contraction strain. Multivariable proportional hazards Cox regression was applied to adjust for the clinical risk score (CHARGE-AF) and net reclassification index (NRI) was used to assess prognostic improvement of this score. Incidence rate curves were constructed using Poisson models. Results Overall, 976 participants were eligible for analysis. Median follow-up time was 3 years (interquartile range: 1.7-4.0 years), during which 284 (29%) were diagnosed with SCAF. The mean age was 74 years, 56% were male, median CHA2DS2-VASc-score was 4. A dilated LA (LA volume≥34ml/m2) was observed in 152 (16%). LA speckle tracking revealed that both LA reservoir strain and contraction strain were univariable predictors of SCAF (HR = 1.05 (1.03-1.06) and HR = 1.07 (1.05-1.10), p &lt; 0.001, per 1% decrease), such that decreasing reservoir and contraction strain were linearly associated with an increased risk of SCAF (figure). LA conduit strain was not a predictor of SCAF. These findings were unchanged after adjusting for the CHARGE-AF score, and both LA strain measures significantly improved the NRI when added to the CHARGE-AF score by 23% and 33%, respectively. Even in participants with normal LA size, both reservoir and contraction strain were independent predictors of SCAF after multivariable adjustment (HR = 1.03 (1.01-1.05), p = 0.001 and HR = 1.06 (1.04-1.09), p &lt; 0.001, per 1% decrease). Conclusion Decreasing left atrial reservoir and contraction strain are independently associated with an increased risk of SCAF as detected by long-term continuous monitoring and provide incremental prognostic value in addition to clinical risk score. Abstract Figure.
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Pezel, T., B. Ambale Venkatesh, T. Quinaglia, et al. "Change in left atrioventricular coupling index to predict incident atrial fibrillation: the multi-ethnic study of atherosclerosis (MESA)." European Heart Journal - Cardiovascular Imaging 23, Supplement_1 (2022). http://dx.doi.org/10.1093/ehjci/jeab289.377.
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Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND Left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic values as predictors of atrial fibrillation (AF). PURPOSE To investigate the prognostic value of a left atrioventricular coupling index (LACI) and average annualized change in LACI measured by cardiac MRI to predict incident AF in a population-based sample from the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS In a secondary analysis of the prospective Multi-Ethnic Study of Atherosclerosis (MESA) study, 1,911 study participants, free of clinically recognized AF and cardiovascular disease at baseline, had LACI assessed with cardiac MRI at baseline (Exam 1, 2000-2002), and ten years later (Exam 5, 2010-2012). LACI was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average annualized change in LACI (ΔLACI) with incident AF. RESULTS Among the 1,911 participants (mean age 59 ± 9 years and 907 men), 87 incident AF events occurred over 3.9 ± 0.9 years following the second imaging (Exam 5). After adjustment for traditional risk factors, greater LACI and ΔLACI were independently associated with AF (HR 1.69, 95% CI[1.46-1.96] and HR 1.71, 95% CI[1.50-1.94], respectively; both p&lt;.001). Adjusted models for LACI and ΔLACI showed improvement in model discrimination compared to currently used AF risk score (CHARGE-AF score) model (AUC: 0.78 vs. 0.74, and AUC: 0.80 vs. 0.74, both p&lt;.001); and to the final model including individual LA or LV parameters for predicting AF incidence (AUC: 0.78 vs. 0.76, and AUC: 0.80 vs. 0.78, both p&lt;.001). CONCLUSIONS Atrioventricular coupling (LACI) and coupling change (ΔLACI) were strong predictors for AF in a multi-ethnic population. Both had incremental prognostic value for predicting AF over traditional risk factors, and superior discrimination compared to the CHARGE-AF score and to individual LA or LV parameters. ClinicalTrials.gov Identifier: NCT00005487 Abstract Figure. Kaplan-Meier curves by change in LACI Abstract Figure. Kaplan-Meier curves by ΔLACI and LACI
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Tao, Liujun, Huaiyu Wu, and Xiujuan Zheng. "Multifeature‐based online remaining useful life prediction of lithium‐ion batteries in stages using cascaded data‐driven algorithm." Quality and Reliability Engineering International, March 10, 2024. http://dx.doi.org/10.1002/qre.3524.
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AbstractAccurately predicting the remaining useful life (RUL) is crucial for the safety and stability of battery systems. Considering the inherent challenges in directly measuring the capacity of lithium‐ion batteries during operation, this paper proposes an online hybrid cascaded data‐driven prediction algorithm for RUL. Health indicators (HIs) are extracted from the charge–discharge voltage and incremental capacity curves, following which gray correlation analysis is employed to quantitatively assess the relevance between the HIs and batteries' capacities. Redundancy of HIs is eliminated through kernel principal component analysis, which enhancing the efficiency of subsequent analysis. The proposed framework incorporates the sparrow search algorithm‐based kernel extreme learning machine (SSA‐KELM) as the first‐level prediction model, establishing the relationship between HIs and capacities. The bidirectional long short‐term memory (BiLSTM) is utilized as the secondary‐level model, which integrates the preliminary capacity predictions of SSA‐KELM. Finally, experimental validation using battery datasets from NASA and Oxford showed that the method has remarkable generalization ability and superior prediction accuracy. Quantitatively, the RMSE and MAPE of NASA batteries are within 0.03, while the errors of Oxford batteries are within 0.003. The RUL prediction errors of all lithium‐ion batteries are within two cycles.