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ABSTRACT The potential benefits of 5G networks, such as faster data speeds and improved user experiences, come with a critical challenge—efficiently preserving energy in base stations (BSs). Addressing this challenge is crucial, necessitating a focus on maximizing the energy efficiency of these stations. BSs play a vital role in providing coverage and capacity by using different frequency bands adapting to diverse communication needs. The choice of a specific frequency band can impact network performance, data rates, coverage range, and signal propagation. This study emphasizes the crucial challenge of preserving energy in 5G BSs and underscores the significance of strategic frequency band selection for optimizing energy efficiency and network performance. For this, stochastic models are introduced for BSs, specifically the Markov and semi‐Markov models, which help choose frequency bands based on system traffic. Closed‐form solutions for steady‐state system size probabilities in these models are derived. A sensitivity analysis is conducted to assess power consumption in various scenarios. Furthermore, a comparison between analytical findings and simulation outcomes regarding power consumption is presented. The convergence of results in both methodologies emphasizes a significant level of agreement; that is, the introduced stochastic models provide insights and are validated by a close alignment between analytical and discrete‐event simulation outcomes. We have shown the behavior of power consumption with respect to three different distributions named deterministic, exponential, and hypo‐exponential. This research highlights the importance of strategic frequency band selection for 5G BSs to optimize energy efficiency and meet the demands of evolving communication networks. [ABSTRACT FROM AUTHOR]

Background Mounting evidence suggests that cognitive impairment is strongly associated with disability in activities of daily living (ADL disability) and long-term care (LTC) costs. However, studies forecasting future LTC costs often overlook these relationships. Consequently, this study aims to more accurately project future LTC costs in China over the next 20 years by considering the intertwined association between disability and cognitive impairment on future LTC costs. Methods Data were from 10 959 adults ≥65 years from the 2005–2018 waves of the Chinese Longitudinal Healthy Longevity Surveys. We used the Markov model to project the population of China and track the transition of older adults in the next 20 years between 4 disability–cognition states. We employed a 2-part model to estimate LTC costs (direct and indirect LTC costs) per capita. Results The proportion of disabled older adults with cognitive impairment was projected to increase from 1.4% in 2021 to 3.4% in 2040, while that of those without cognitive impairment was projected to decrease from 4.7% in 2021 to 4.5% in 2040. The direct and indirect LTC costs were projected to increase from 0.3% and 0.2% of gross domestic product (GDP) in 2021 to 1.4% and 0.7% in 2040 for disabled persons without cognitive impairment and from 0.1% and 0.1% of GDP in 2021 to 1.3% and 1.3% in 2040 for those with cognitive impairment, respectively. Conclusions Policy-makers could include the assessment of cognition in the LTC needs assessment and allocate more compensation to LTC insurance participants with cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Value-based decision-making regarding nonoperative management versus early surgical stabilization for first-time anterior shoulder instability (ASI) events remains understudied. Purpose: To perform (1) a systematic review of the current literature and (2) a Markov model–based cost-effectiveness analysis comparing an initial trial of nonoperative management to arthroscopic Bankart repair (ABR) for first-time ASI. Study Design: Economic and decision analysis; Level of evidence, 3. Methods: A Markov chain Monte Carlo probabilistic model was developed to evaluate the outcomes and costs of 1000 simulated patients (mean age, 20 years; range, 12-26 years) with first-time ASI undergoing nonoperative management versus ABR. Utility values, recurrence rates, and transition probabilities were derived from the published literature. Costs were determined based on the typical patient undergoing each treatment strategy at the authors' institution. Outcome measures included costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). Results: The Markov model with Monte Carlo microsimulation demonstrated mean (± standard deviation) 10-year costs for nonoperative management and ABR of $38,649 ± $10,521 and $43,052 ± $9352, respectively. Total QALYs acquired over the 10-year time horizon were 7.67 ± 0.43 and 8.44 ± 0.46 for nonoperative management and ABR, respectively. The ICER comparing ABR with nonoperative management was found to be just $5725/QALY, which falls substantially below the $50,000 willingness-to-pay (WTP) threshold. The mean numbers of recurrences were 2.55 ± 0.31 and 1.17 ± 0.18 for patients initially assigned to the nonoperative and ABR treatment groups, respectively. Of 1000 samples run over 1000 trials, ABR was the optimal strategy in 98.7% of cases, with nonoperative management the optimal strategy in 1.3% of cases. Conclusion: ABR reduces the risk for recurrent dislocations and is more cost-effective despite higher upfront costs when compared with nonoperative management for first-time ASI in the young patient. While all these factors are important to consider in surgical decision-making, ultimate treatment decisions should be made on an individual basis and occur through a shared decision-making process. [ABSTRACT FROM AUTHOR]

Aging infrastructure is a significant concern to many system operators who might struggle to operate, maintain, and improve systems and infrastructure assets due to spatially buried assets over a large area, uncertainty about their condition, and lack of a comprehensive planning. These challenges often lead to a reactive approach to maintenance, causing emergency situations due to unexpected asset failures. This study proposes a suite of risk-based asset management plan tools to extend the service life of a drainage pipe network with a length of 580 km managed by a city council in Australia. The proposed management plan tools are based on a reactive–proactive approach to manage risk in which proactive condition monitoring is applied to critical and important pipes for detecting failure conditions in a timely manner. A sample of critical closed-circuit television (CCTV) inspected pipes selected from pipe network is used to predict the current and future condition of the pipe network using a Markov deterioration model. The predicted condition is used to support various implementation tasks of an asset management plan and accounting requirements. The key findings of the case study include a calibrated Markov deterioration curve showing slow rate of deterioration for a drainage network, average service life estimation (120–180 years) for drainage pipes, lowest-cost inspection interval determination (i.e., 7–14 years) for detecting poor condition, and estimated annual inspection and replacement cost for a drainage network. Practical Applications: A significant number of local governments and city councils around the world manage drainage pipe networks as high capital asset value. Extending the service life of drainage pipes with reduced life-cycle cost and managed failure risk is a challenge and an essential task for asset management. This study introduces a proactive–reactive asset management strategy and a suite of decision support tools to assist in achieving such challenging tasks. For example, instead of using the common design service life of 80–100 years for asset renewal planning, this study demonstrates, through a case study, that service life can be extended to 120–180 years, resulting in significant savings of capital investment. To control failure risk and reduce life-cycle cost during the extended service life, a suite of decision support models including an optimal inspection model, a failure risk model, and others can be used to justify annual maintenance funding, timely detecting poor condition, and suggesting appropriate maintenance and rehabilitation planning. The results show that the inspection interval can be 7–14 years, and the Markov deterioration model predicted that the current network has 7% of pipe in a failure condition, which will increase by 1.67% over the next 10 years, which can justify renewal funding. [ABSTRACT FROM AUTHOR]

Aims Design, setting and participants Measurements Findings Conclusions To assess the cost‐effectiveness of the Cessation of Smoking Trial in Emergency Department (COSTED) intervention compared with signposting to local stop smoking service (SSS) from the National Health Service (NHS) and personal social services (PSS) perspective.This was a two‐group, multi‐centre, pragmatic, individually randomized controlled trial set in six Emergency Departments (EDs) in urban and rural areas in the United Kingdom. Adult (≥ 18 years) daily smokers (at least one cigarette or equivalent per day) but not daily e‐cigarette users, with carbon monoxide reading ≥ 8 parts per million, attending the ED (n = 972) were included. The intervention consisted of provision of an e‐cigarette starter kit plus brief smoking cessation advice and referral to a local SSS. Control was an information card on how to access local SSS.Intervention costs included costs of training and delivery. Control costs included costs of printing information cards. Costs of smoking cessation and health‐care services were estimated based on quantities reported by participants and unit costs extracted from secondary sources. The effects were measured by quality‐adjusted life years (QALYs) derived from EQ‐5D‐5L. Other outcomes were smoking cessation measures. The primary outcome was incremental cost‐effectiveness ratio (ICER), which was calculated by dividing the difference in costs by the difference in QALYs between groups.The mean intervention costs were £48 [standard error (SE) = £0] per participant and the mean control costs were £0.2 (SE = £0) per participant. Using regression estimates, total costs were £31 [95% confidence interval (CI) = –£341 to £283] higher and 6‐month QALYs were 0.004 (95% CI = –0.004 to 0.014) higher in the intervention group than in the control group. The ICER was calculated at £7750 (probability of cost‐effective at range £20 000–30 000: 72.2–76.5%).The UK Cessation of Smoking Trial in Emergency Department (COSTED) intervention (provision of an e‐cigarette starter kit plus brief smoking cessation advice) was cost‐effective compared with signposting to local stop smoking services under the current recommendations of the maximum acceptable thresholds. [ABSTRACT FROM AUTHOR]

The relationship between chronic disease status (CDS) and transitions in depressive symptoms (DS) remains unclear. This study explores the association between CDS and DS transitions. This cohort study analyzed data from 8175 participants aged 45+, sourced from China Family Panel Studies (2016, 2018, 2020). DS were assessed using a brief version of Center for Epidemiologic Studies Depression Scale (CES-D). CDS was categorized into healthy, single disease, and multimorbidity. Markov models were used to estimate state transition intensities, mean sojourn times and hazard ratios (HRs). DS transitions occurred between adjacent and non-adjacent states, but transition intensity between adjacent states was higher than among non-adjacent states. Self-transition intensities of severe-DS, mild-DS, and non-DS progressively increased, with average durations of 1.365, 1.482, and 7.854 years, respectively. Both single disease and multimorbidity were significantly associated with an increased risk of transitioning from non-DS to mild-DS, with multimorbidity showing a stronger association. In contrast, HRs for single diseases transitioning from mild-DS to severe-DS were significantly lower than 1. Furthermore, their HRs were almost <1 in recovery transitions but not statistically significant. Specific chronic diseases and their combinations were not analyzed. The progression of DS exhibits various pathways. CDS is associated with DS transitions, but the roles of single disease and multimorbidity may differ across different DS progression stages. Both conditions were significantly linked to the risk of new-onset DS, with multimorbidity posing a greater association. However, this relationship is not observed in other progression stages. These findings could provide insights for early prevention and intervention for DS. • This is the first study to explore the longitudinal state transitions of depressive symptoms in China. • The progression of depressive symptoms followed two pathways:gradual and leapfrogging. • Chronic disease status is associated with the state transitions of depressive symptoms. • The impacts of single disease and multimorbidity on the state transitions of depressive symptoms varied. • It could provide insights for depression prevention and intervention. [ABSTRACT FROM AUTHOR]

Genomic sequencing has become increasingly prevalent, generating massive amounts of data and facing a significant challenge in long-term storage and transmission. A solution that reduces the storage and transfer requirements without compromising data integrity is needed. The effectiveness of neural networks has already been endorsed in tasks like image and speech compression. Adapting them to recognize the intricate patterns in genomic sequences could help to find more redundancies and reduce storage requirements. The proposed method, called DNACoder, leverages deep learning techniques to achieve significant compression ratios while preserving the essential information in genomic data and offers a high-performance compression for genomic sequences in any data format. The results of the experiments clearly demonstrate the effectiveness of the method and its potential applications in genomic data storage. Our proposed method improves compression by 21.1% on bits per base compared to existing compressors on the benchmarked dataset. By using a deep learning prediction model that is structured as a convolutional layer followed by an attention-based long short-term memory network, we propose a novel lossless and reference-free compression approach (DNACoder), which can also be utilized as a reference-based compressor. The experimental outcome on the tested data illustrates that the advocated compression algorithm's CNN-LSTM model makes generalizations effectively for genomic sequence data and outperforms the state-of-the-art methods. [ABSTRACT FROM AUTHOR]

Female genital schistosomiasis is a chronic gynaecological disease caused by the waterborne parasite Schistosoma (S.) haematobium. It affects an estimated 30–56 million girls and women globally, mostly in sub‐Saharan Africa where it is endemic, and negatively impacts their sexual and reproductive life. Recent studies found evidence of an association between female genital schistosomiasis and increased prevalence of HIV and cervical precancer lesions. Despite the large population at risk, the burden and impact of female genital schistosomiasis are scarcely documented, resulting in neglect and insufficient resource allocation. There is currently no standardised method for individual or population‐based female genital schistosomiasis screening and diagnosis which hinders accurate assessment of disease burden in endemic countries. To optimise financial allocations for female genital schistosomiasis screening, it is necessary to explore the cost‐effectiveness of different strategies by combining cost and impact estimates. Yet, no economic evaluation has explored the value for money of alternative screening methods. This paper describes a novel application of health decision analytical modelling to evaluate the cost‐effectiveness of different female genital schistosomiasis screening strategies across endemic settings. The model combines a decision tree for female genital schistosomiasis screening strategies, and a Markov model for the natural history of cervical cancer to estimate the cost per disability‐adjusted life‐years averted for different screening strategies, stratified by HIV status. It is a starting point for discussion and for supporting priority setting in a data‐sparse environment. [ABSTRACT FROM AUTHOR]

Background: The HIMALAYA trial found that durvalumab plus tremelimumab significantly prolonged progression-free survival and overall survival in patients with unresectable hepatocellular carcinoma (HCC) compared with sorafenib. Objective: This study aimed to investigate the cost-effectiveness of durvalumab plus tremelimumab compared with sorafenib in the first-line HCC setting. Design: A Markov model-based cost-effectiveness analysis. Methods: We created a Markov model to compare healthcare costs and clinical outcomes of HCC patients treated with durvalumab plus tremelimumab in the first-line setting compared with sorafenib. We estimated transition probabilities from randomized trials. Lifetime direct healthcare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were calculated for first-line durvalumab plus tremelimumab compared with sorafenib from a US payer's perspective. Results: In the base case, first-line durvalumab plus tremelimumab was associated with an improvement of 0.29 QALYs compared with sorafenib. While both treatment strategies were associated with considerable lifetime expenditures, first-line durvalumab plus tremelimumab was less expensive than sorafenib ($188,405 vs $218,584). The incremental net monetary benefit for durvalumab plus tremelimumab versus sorafenib was $72,762 (valuing QALYs at $150,000 each). The results of durvalumab plus tremelimumab were better in terms of costs and health outcomes in patients with HBV-related HCC and high alpha-fetoprotein levels. Conclusion: First-line durvalumab plus tremelimumab was estimated to be dominant for the treatment of unresectable HCC compared with sorafenib from a US payer's perspective. [ABSTRACT FROM AUTHOR]

Due to the rapid evolution of autonomous driving technology and the complexity of market penetration mechanisms, establishing a reliable quantitative research approach for measuring autonomous vehicle (AV) penetration and effectively validating forecasted outcomes poses significant challenges. To address this issue, this paper overcomes data limitations by starting from the perspective of Chinese automotive market. It introduces a quantifiable Markov forecasting model that establishes the link between transition probabilities and penetration influencing factors. Through a penetration network, it visually represents the correlation and evolutionary states of AVs. Building upon the model, a framework for data quantification and analysis is formed. By quantifying model indicators with market data such as car performance and historical sales, the network parameters and transition probabilities are continuously updated in real-time. This drives the model to output short-term forecasts for AV penetration in the automotive market. In addition, we devise a two-stage simulation algorithm to accomplish parameter calibration and model validation. Through validation and comparative analysis, it is observed that, compared to direct learning from historical data, our model can more accurately forecast real market penetration trends. Furthermore, sensitivity analysis experiments on market strategies indicate that, compared to technical investment, the market exhibits a higher sensitivity to price adjustments. A strategy combination of increased technical investment in high-level vehicles and judiciously raising prices proves more advantageous for intelligent transformation in the automotive sector than a singular strategy. Additionally, as the AV market evolves, the sensitivity to favorable strategies will gradually increase. Therefore, the developmental stage of the market is a crucial factor for both car companies and investors to consider. The insights gleaned from this paper offer actionable guidance for policymakers and automotive corporations in shaping future market strategies, thereby fostering the continued growth of autonomous driving technologies within the industry. • Formulated a Markov forecasting model for autonomous vehicle market penetration. • Leveraged empirical vehicle data for robust model validation and calibration. • Explored strategic impacts for the automotive market's intelligence transition. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the economic impact of pembrolizumab combined with gemcitabine and cisplatin versus placebo combined with gemcitabine and cisplatin for the first-line treatment of patients with advanced biliary tract cancer in China. METHODS: From the perspective of China’ s health system, the willingness-to-pay (WTP) threshold was set at 3 times of China’ s gross domestic product ( GDP) per capita in 2022, that is 257 094. 00 RMB/ quality-adjusted life year (QALY), Markov model and partitioned survival model were constructed to conduct cost-effectiveness analysis, univariate sensitivity analysis and probabilistic sensitivity analysis were used to analyze the effects of parameters on the model’s robustness, and to analyze the economic outcome of pembrolizumab under the patient assistance program scenario. RESULTS: The results of Markov model analysis showed that the incremental cost-effectiveness ratio (ICER) was 2 758 043. 34 RMB/QALY for the pembrolizumab group versus the placebo group, and 730 319. 70 RMB/QALY under the patient assistance program scenario, which were both higher than the set WTP threshold; in the absence of patient assistance program, the cost-effectiveness price of pembrolizumab was 1 452. 45 RMB/100 mg, and the partitioned survival model results had validated the Markov model results. CONCLUSIONS: Under the WTP threshold of 3 times of 2022 China’s per capita GDP, pembrolizumab combined with chemotherapy for the first-line treatment of advanced biliary tract cancer does not have cost-effectiveness advantage, and lowering the price of pembrolizumab can increase the probability of its cost-effectiveness advantage. [ABSTRACT FROM AUTHOR]

The paper presents models for managing cross-domain redundancy to enhance the reliability of two priority communication channels within critical infrastructure systems. Employing Markov chain models, the paper analyzes the impact of two distinct redundancy management strategies: a unified reserve pool and a separate pool approach with cross-domain resource sharing. The study introduces reliability improvement factors to quantify system performance, exploring their dependency on the number of additional redundant elements, their inherent reliability, and the chosen strategy for managing cross-domain redundancy. An air traffic control system serves as a case study of the application of the proposed management algorithms. Results indicate that the integration of resources from different priority domains significantly improves communication reliability. The findings may be useful for the design and operation of secure communication networks. [ABSTRACT FROM AUTHOR]

Gaussia luciferase (Gluc) is currently known as the smallest naturally secreted luciferase. Due to its small molecular size, high sensitivity, short half-life, and high secretion efficiency, it has become an ideal reporter gene and is widely used in monitoring promoter activity, studying protein-protein interactions, protein localization, high-throughput drug screening, and real-time monitoring of tumor occurrence and development. Although studies have shown that different Gluc mutations exhibit different bioluminescent properties, their mechanisms have not been further investigated. The purpose of this study is to reveal the relationship between the conformational changes of Gluc mutants and their bioluminescent properties through molecular dynamics simulation combined with neural relationship inference (NRI) and Markov models. Our results indicate that, after binding to the luciferin coelenterazine (CTZ), the α-helices of the 109–119 residues of the Gluc Mutant2 (GlucM2, the flash-type mutant) are partially unraveled, while the α-helices of the same part of the Gluc Mutant1 (GlucM1, the glow-type mutant) are clearly formed. The results of Markov flux analysis indicate that the conformational differences between glow-type and flash-type mutants when combined with luciferin substrate CTZ mainly involve the helicity change of α7. The most representative conformation and active pocket distance analysis indicate that compared to the flash-type mutant GlucM2, the glow-type mutant GlucM1 has a higher degree of active site closure and tighter binding. In summary, we provide a theoretical basis for exploring the relationship between the conformational changes of Gluc mutants and their bioluminescent properties, which can serve as a reference for the modification and evolution of luciferases. [ABSTRACT FROM AUTHOR]

Introduction: Recent evidence indicates that Maternal Supplementation with Long-Chain n-3 Fatty Acids During Pregnancy Substantially Mitigates Offspring's Asthma. Adding information regarding its cost-utility will undoubtedly allow its adoption, or not, in clinical practice guidelines. This research aimed to determine the cost-utility of LCPUFA supplementation in the third trimester of pregnancy to reduce the risk of wheezing and asthma in infants in Colombia. Methods: A Markov model was formulated to estimate the cost and quality-adjusted life-years (QALYs) attributed to individuals with severe asthma in Colombia, with a time horizon of five years and a cycle length of two weeks. Probabilistic sensitivity analysis and a value of information (VOI) analysis were conducted to evaluate the uncertainties in the case base. Cost-utility was assessed at a willingness-to-pay (WTP) value of US$5180. All costs were adjusted to 2021 with a 5% annual discounting rate for cost and QALYs. Results: The mean incremental cost of LCPUFA supplementation versus no supplementation was US-43.65. The mean incremental benefit of LCPUFA supplementation versus no supplementation was 0.074 QALY. The incremental cost-utility ratio was estimated at US$590.68 per QALY. The outcomes derived from our primary analysis remained robust when subjected to variations in all underlying assumptions and parameter values. Conclusion: Supplementation strategy supplementation with long-chain n-3 fatty acids during pregnancy is cost-effective in reducing the risk of developing asthma during childhood in Colombia. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the economic value of mepolizumab as an add-on therapy to the standard of care (SoC) for patients with severe eosinophilic asthma in China. Methods: A Markov model with three health conditions was constructed to calculate the incremental cost per quality-adjusted life year (QALY) in mepolizumab with SoC and SoC only groups from the perspective of the Chinese healthcare system throughout an entire lifespan. The model was populated with local costs, while efficacy parameters were obtained from the global Phase III MENSA trial and mortality was derived from two surveys. One-way and probabilistic sensitivity analyses were conducted. Additional scenario analysis was used to estimate the cost-effectiveness impact of changes in the price of mepolizumab. Results: Over the lifetime treatment horizon, the incremental cost-effectiveness ratio (ICER) of mepolizumab plus SoC compared to SoC alone was $170 648.73 per QALY. Sensitivity analyses focused on these results. Scenario analysis showed that mepolizumab would require a price reduction of at least 82% to reach the current willingness-to-pay (WTP=$38 223.34/QALY) threshold. Conclusion: Mepolizumab is not a cost-effective healthcare resource in China at its current pricing. [ABSTRACT FROM AUTHOR]

Purpose: Molecular screening for Mycobacterium tuberculosis (MTB) can lead to rapid empirical treatment inception and reduce hospitalization time and complementary diagnostic tests. However, in low-prevalence settings, the cost-benefit balance remains controversial due to the high cost. Methods: We used a Markov model to perform an economic analysis to evaluate the profit after implementing molecular MTB screening (Period B) compared with conventional culture testing (Period A) in respiratory samples from 7,452 consecutive subjects with presumed tuberculosis (TB). Results: The proportion of positivity was comparable between both periods (P > 0.05), with a total of 2.16 and 1.78 samples/patient requested in periods A and B, respectively (P < 0.001). The mean length of hospital stay was 8.66 days (95%CI: 7.63–9.70) in Period B and 11.51 days (95%CI: 10.15–12.87) in Period A (P = 0.001). The healthcare costs associated with diagnosing patients with presumed TB were reduced by €717.95 per patient with PCR screening. The probability of remaining hospitalized and the need for a greater number of outpatient specialty care visits were the variables with the most weight in the model. Conclusion: Employing PCR as an MTB screening method in a low-prevalence setting may increase the profits to the system. [ABSTRACT FROM AUTHOR]

Finite mixture models have been used for unsupervised learning for some time, and their use within the semisupervised paradigm is becoming more commonplace. Clickstream data are one of the various emerging data types that demand particular attention because there is a notable paucity of statistical learning approaches currently available. A mixture of first‐order continuous‐time Markov models is introduced for unsupervised and semisupervised learning of clickstream data. This approach assumes continuous time, which distinguishes it from existing mixture model‐based approaches; practically, this allows account to be taken of the amount of time each user spends on each webpage. The approach is evaluated and compared with the discrete‐time approach, using simulated and real data. [ABSTRACT FROM AUTHOR]

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Technological advancements and the expanding scope of offshore dynamic positioning (DP) applications introduce new challenges in terms of safety and risk control. This paper provides an overview of a proposed methodology for reliability and risk analysis in the context of DP operations. Firstly, two typical DP operation contexts are discussed. Subsequently, a comprehensive survey is conducted to assess the reliability analysis methodologies applicable to DP systems, encompassing techniques such as Failure Mode and Effects Analysis (FMEA), fault tree analysis, Markov models, and Bayesian networks, which are employed to evaluate the technical and human reliability of DP Class 2 and Class 3 systems. Finally, the paper concludes with a discussion of future research directions and challenges pertaining to reliability analysis and risk management in DP operations. [ABSTRACT FROM AUTHOR]

Modeling the prediction of land use/land cover (LULC) change is necessary for sustainable management of natural resources and effective planning for proper urban development. The Markov chain model is the most commonly used prediction model for assessing LULC changes. This study aims to assess changes in LULC in Cuttack City from 1990 to 2020 and to predict LULC modification in 2050. For the analysis, Landsat satellite data were collected from the USGS website for 1990, 2005, and 2020. The satellite images were masked with our area of interest and classified using the maximum likelihood classifier tool in ArcGIS 10.2. The result of the multi‐temporal classification shows that the built‐up area percentage reached 45.927% in 1990 and 57.827% in 2020. Most areas of vegetation and water bodies were affected by this impromptu growth. Using the chi‐square test, the results of the Markov model are validated, which shows no significant differences between the classified and simulated areas. This model can, therefore, be accepted for our prediction. Built‐up growth has already achieved its peak in Cuttack City. There may be further growth in built‐up areas in the city shortly. These findings draw the attention of urban planners and policymakers to the stress of urban sprawl and prompt them to take stringent action to deal with this pressing issue. [ABSTRACT FROM AUTHOR]

Background: Mammography (MG) has demonstrated its effectiveness in diminishing mortality and advanced-stage breast cancer incidences in breast screening initiatives. Notably, research has accentuated the superior diagnostic efficacy and cost-effectiveness of digital breast tomosynthesis (DBT). However, the scope of evidence validating the cost-effectiveness of DBT remains limited, prompting a requisite for more comprehensive investigation. The present study aimed to rigorously evaluate the cost-effectiveness of DBT plus MG (DBT-MG) compared to MG alone within the framework of Taiwan's National Health Insurance program. Methods: All parameters for the Markov decision tree model, encompassing event probabilities, costs, and utilities (quality-adjusted life years, QALYs), were sourced from reputable literature, expert opinions, and official records. With 10,000 iterations, a 2-year cycle length, a 30-year time horizon, and a 2% annual discount rate, the analysis determined the incremental cost-effectiveness ratio (ICER) to compare the cost-effectiveness of the two screening methods. Probabilistic and one-way sensitivity analyses were also conducted to demonstrate the robustness of findings. Results: The ICER of DBT-MG compared to MG was US$5971.5764/QALYs. At a willingness-to-pay (WTP) threshold of US$33,004 (Gross Domestic Product of Taiwan in 2021) per QALY, more than 98% of the probabilistic simulations favored adopting DBT-MG versus MG. The one-way sensitivity analysis also shows that the ICER depended heavily on recall rates, biopsy rates, and positive predictive value (PPV2). Conclusion: DBT-MG shows enhanced diagnostic efficacy, potentially diminishing recall costs. While exhibiting a higher biopsy rate, DBT-MG aids in the detection of early-stage breast cancers, reduces recall rates, and exhibits notably superior cost-effectiveness. [ABSTRACT FROM AUTHOR]

Lidan Yi,1,&ast; Qiao Liu,1,&ast; Chongqing Tan,1 Xiaomin Wan,1 Xia Luo,1 Yinbo Li,2 Haiying Li,3 Xiaohui Zeng3 1Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Hunan Center for Drug Evaluation and Adverse Reaction Monitoring, Hunan Provincial Food and Drug Administration, Changsha, People’s Republic of China; 3Department of Nuclear Medicine/PET Image Center, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohui Zeng; Haiying Li, Email zengxiaohui2008@csu.edu.cn; lihaiying2013@csu.edu.cnObjective: To assess the cost-effectiveness of adding daratumumab to carfilzomib and dexamethasone (KdD) in patients with relapsed or refractory multiple myeloma (RRMM).Materials and Methods: A Markov model was established to estimate health and economic outcomes of carfilzomib and dexamethasone (Kd) with or without daratumumab for RRMM patients over a lifetime horizon. The patients and intervention of the two arms were modeled according to the CANDOR trial. Costs were collected from the Chinese health system perspective. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the robustness of our conclusions.Results: Compared with the Kd arm, KdD achieved an additional 0.537 quality-adjusted life-years (QALYs) at an incremental cost of &dollar;138,084, resulting in an incremental cost-utility ratios (ICURs) of &dollar;257,319 per QALY. Uncertainty analyses revealed that the model is robust to all the input parameters.Conclusion: From the Chinese healthcare system perspective, adding daratumumab to the Kd regimen for patients with RRMM appears to lack cost-effectiveness. Exploring alternative avenues such as negotiating for a more favorable price or introducing a financial assistance program dedicated to daratumumab and/or carfilzomib could prove to be an effective strategy in enhancing accessibility of this combination.Keywords: cost-effectiveness, daratumumab, multiple myeloma, Markov model, China

The main problem in building intelligent systems is the lack of data for machine learning, which is especially important for sign language recognition for the deaf and hard of hearing. One of the ways to increase the amount of data for training is synthesis. Unlike speech synthesis, it is impossible to create a sequence of gestures in Vietnamese and some other languages that exactly repeat the text. This is due to the significant limitations of the gesture dictionary and the different word order in sentences. The aim of the work is to enrich the educational corpus of video data for use in creating recognition systems for the Vietnamese Sign Language (ViSL). Since it is impossible to translate the words of the source text into gestures one to one, the problem of translating from a regular language into a sign language arises. The paper proposes to use a two-phase process for this. The first phase involves pre-processing the text with standardization of the text format, segmentation of words and sentences, and then encoding the words using the sign language dictionary. At this stage, it should be noted that there is no need to remove punctuation marks and stop words, since they are related to the accuracy of the N-gram model. Next, instead of using syntactic analysis, a statistical method for forming a sequence of gestures is used, and the Markov model on the transition graph between words is taken as a basis in which the probability of the next word depends only on the two previous words. Transition probabilities are calculated on the existing marked corpus of the ViSL. The Breadth-first Search method is used to compile a list of all sentences generated based on a given grammatical rule and a matrix of semantic interactions between words. The inverse of the logarithm of the product of the probabilities of co-occurrence of consecutive 3-word phrases in a sentence is used to estimate the frequency of occurrence of that sentence in a given data set. Based on the ViSL data of 3,234 words, we calculated probability matrices representing the relationships between words based on Vietnamese natural language data with 50 million sentences collected from Vietnamese newspapers and magazines. For different grammar rules, we compare the number of generated sentences and evaluate the accuracy of the 50 most frequent sentences. The average accuracy is 88 %. The accuracy of the generated sentences is estimated by manual statistical methods. The number of generated sentences depends on the number of word parts that are labeled according to the grammar rules. The semantic accuracy of the generated sentences will be very high if the search words are labeled with the correct part-of-speech tagging. Compared with machine learning methods, our proposed method gives very good results for languages without inflections and word order that follow certain rules, such as Vietnamese, and does not require large computational resources. The disadvantage of this method is that its accuracy largely depends on the type of word, sentence, and word segmentation. The relationship of words depends on the observed dataset. Future research direction is to generate paragraphs in sign language. The obtained data can be used in machine learning models for sign language processing tasks.

The objective of this paper is to identify the most sensitive component of a turbogenerator and optimize its availability. To achieve this, we begin by conducting an initial reliability, availability, maintainability, and dependability (RAMD) analysis on each component. Subsequently, a novel stochastic model is developed to analyze the steady‐state availability of the turbogenerator, employing a Markov birth‐death process. In this model, failure and repair rates are assumed to follow an exponential distribution and are statistically independent. To optimize the proposed stochastic model, we employ four population‐based meta‐heuristic approaches: the grey wolf optimization (GWO), the dragonfly algorithm (DA), the grasshopper optimization algorithm (GOA), and the whale optimization algorithm (WOA). These algorithms are utilized to find the optimal solution by iteratively improving the availability of the turbogenerator. The performance of each algorithm is evaluated in terms of system availability and execution time, allowing us to identify the most efficient algorithm for this task. Based on the numerical results, it is evident that the WOA outperforms the GWO, GOA, and DA in terms of both system availability and execution time. [ABSTRACT FROM AUTHOR]

Background: Tislelizumab combined with chemotherapy has shown significant clinical benefits in improving overall survival compared to chemotherapy alone for patients with extensive-stage small-cell lung cancer (ES-SCLC). Aim: This study aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy versus standard chemotherapy as a first-line treatment for ES-SCLC from the US payer perspective and the perspective of the Chinese healthcare system. Method: We conducted an economic evaluation using a Markov state-transition model, reflecting the US payer perspective and the perspective of the Chinese healthcare system. Baseline patient characteristics and essential clinical data were obtained from the RATIONALE-312 trial. The costs and utilities were derived from open-access databases and published literature. The primary outcomes measured included quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). Uncertainties in the model were addressed by probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OWSA). Results: In the base-case analysis, the addition of tislelizumab to chemotherapy provided an incremental gain of 0.16 QALYs at an additional cost of $7430.73, resulting in an ICER of $46,132.33 per QALY. Although above the willingness-to-pay (WTP) threshold of China of $38,042.49 per QALY, the cost-effectiveness was marginal, with an INHB of − 0.03 QALYs and an INMB of $− 1303.06. In the US, despite a slightly higher effectiveness gain of 0.28 QALYs, the increased cost of $45,157.35 resulted in an unfavorable ICER of $163,885.06 per QALY, exceeding the US WTP threshold of $150,000.00. PSA showed probabilities of cost-effectiveness of tislelizumab plus chemotherapy at 17.18% in China and 40.41% in the US. Conclusion: Tislelizumab combined with chemotherapy was not a cost-effective first-line treatment option for ES-SCLC in China or the US; however, the margin of cost-effectiveness was narrow. [ABSTRACT FROM AUTHOR]

Background: Although several pharmacoeconomic studies have assessed the cost-effectiveness of maintenance immunosuppressive regimens for heart transplant recipients, economic comparisons between various combination drug therapies remain sparse. Aim: This study used an economic evaluation based on network meta-analysis to assess the cost-effectiveness of four immunosuppressive regimens for adult heart transplant recipients in China. Method: We conducted a systematic search for clinical trials in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP database. A validated Markov model was adapted to reflect the Chinese medical landscape. Four maintenance immunosuppression regimens were considered: tacrolimus/mycophenolate mofetil (TAC/MMF), cyclosporine/mycophenolate mofetil (CSA/MMF), everolimus/cyclosporine (EVL/CSA), and sirolimus/tacrolimus (SRL/TAC). The probabilities of health events were derived from a comprehensive literature review. Direct medical costs, adjusted for 2022 values, were from public documents and websites, while utilities for quality-adjusted life-years (QALYs) were taken from previous studies. Primary outcomes were mean lifetime cost, QALYs, and cost-effectiveness, with a willingness-to-pay (WTP) threshold set at three times China's GDP per capita in 2022. Sensitivity analyses were conducted to test the robustness of the results. Results: The base case analysis identified TAC/MMF as the most cost-effective regimen, producing a mean of 6.31 QALYs per patient at a cost of Chinese Yuan (CNY) 534,182.89. Sensitivity analyses consistently reinforced TAC/MMF as the most cost-effective and robust choice. Conclusion: TAC/MMF is the most cost-effective maintenance immunosuppressive regimen for heart transplant recipients within the Chinese health system. The study findings are reinforced by sensitivity analyses, affirming their robustness amid various uncertainties. [ABSTRACT FROM AUTHOR]

Abstract Background Forecasting the intensity, source, and cost of informal care for older adults in China is essential to establish and enhance policy support systems for informal care within the context of East Asian traditional culture that emphasizes filial piety. This study aims to analyze the current situation and influencing factors for the informal care needs and predict the trends of informal care needs for older adults in China from 2020 to 2040. Methods Using the CHARLS database from 2015 to 2018, this study first combined a two-part model and a multinomial logit to analyze the influencing factors for the informal care needs of urban-rural older adults in China. Secondly, a multi-state Markov model was constructed to forecast the number of urban-rural older populations in each health state from 2020 to 2040. Finally, based on a microsimulation model, this study predicted the trends of informal care intensity, source, and cost for older adults in urban and rural areas from 2020 to 2040. Results In 2040, the size of the disabled older population in China will expand further. In rural areas, the total number of disabled people in 2040 (39.77 million) is 1.50 times higher than that in 2020; In urban areas, the total number of disabled people in 2040 (56.01 million) is 2.51 times higher than that in 2020. Compared with 2020, older adults population with mild, moderate and severe disability in 2040 would increase by 87.60%, 101.70%, and 115.08%, respectively. In 2040, the number of older adults receiving low-, medium-, and high-intensity care in China will be 38.60 million, 22.89 million, and 41.69 million, respectively, and older people will still rely on informal care provided by spouses and children (from spouses only: 39.26 million, from children only: 36.74 million, from spouses and children only: 16.79 million, other: 10.39 million). The total cost of informal care in 2040 will be 1,086.65 billion yuan, 2.22 times that of 2020 (490.31 billion yuan), which grows faster than the economic growth rate. Conclusion From 2020 to 2040, the informal care needs of older people in rural areas will increase first and then decrease due to the demographic structure and rapid urbanization. In contrast, the informal care needs of older people in urban areas will continuously increase from 2020 to 2040, with the growth rate gradually slowing down. This study provides an evidence-based rationale for scientifically measuring the economic value of informal care and reasonably allocating care resources.

Background With the gradual deepening of the comprehensive reform of community health services, the prevention and control of single diseases for the entire population in the community is also constantly being optimized, However, there is still a lack of appropriate evaluation methods in the community to reflect its prevention and control effectiveness evaluation. Objective By analyzing and exploring the cost effect of the existing whole-population prevention and control measures of osteoporosis in Fenglin community, from 2016 to 2022, this paper answers the initial results and possible problems of the whole-population prevention and control of single disease in the community. Methods This study conducted a cost-effectiveness analysis on 4 293 community residents who received osteoporosis prevention and treatment in Fenglin community from 2016 to 2022. Divide the research object into three states based on bone density values: healthy, low bone mass, and osteoporosis, and construct a Markov model to analyze the influencing factors of different state transitions. And based on the predicted values of the Markov model combined with quality adjusted life years (QALY) , the increment of quality adjusted life years (QALY) is calculated. All costs invested in prevention and control work from 2016 to 2022 are counted, and the effectiveness of prevention and control is evaluated by the cost/quality adjusted life year increment ratio. Quality adjusted life years (QALY) are obtained by calculating the health utility value and expected life determined through literature search. Results The total cost of osteoporosis prevention and treatment in Fenglin community was 33 814 102.15 yuan. The total quality-adjusted life years of 4 293 community osteoporosis prevention and treatment population were 77 098.288 9 at the first diagnosis, the average per capita was 17.959, and the standard deviation was 9.34. At the second diagnosis, the total quality-adjusted life years were 79 616.936 1, the mean per capita was 18.546, the standard deviation was 9.342, and the difference between the two diagnoses was 2 518.647 2. The incremental cost-effectiveness ratio (ICER) is 2 132.907 0 yuan /QALY, and the incremental cost-effectiveness ratio (ICER) is less than 1 times (66 965.10 yuan) per capita GDP, indicating that the intervention scheme is fully cost-effective. Conclusion This study combined Markov model and quality-adjusted life years (QALY) to make a preliminary evaluation of the prevention and treatment effect of osteoporosis in Fenglin community. The results showed that the intervention program of osteoporosis prevention and treatment in Fenglin community was worth investing, and provided a certain basis for the accurate prevention and treatment decision of osteoporosis in the future.

Abstract Breast cancer is one of the tumors with the highest prevalence rate among women in the world, and its BRCA1/2 gene is a common mutation site. Talazoparib, as a targeted PARP inhibitor, can effectively control the occurrence and development of breast cancer with BRCA1/2 gene mutation, and play a therapeutic role. Based on the findings from the Phase III EMBRACE trial (NCT01945775 clinical trial), our analysis reveals that the talazoparib group demonstrated a significant extension in progression-free survival, along with improved response markers and patient-reported outcomes when compared to conventional therapies. This study aims to assess the cost-effectiveness of talazoparib for treating advanced breast cancer with germline BRCA1/2 mutations and HER2 negativity, considering the perspectives of health services in China and the United States. The results obtained will serve as a valuable reference for promoting rational drug utilization and enhancing medical resource efficiency. To evaluate the cost-effectiveness of Talazoparib more scientifically and provide clinicians with chemotherapy options, this paper developed a Markov model based on the EMBRACA clinical trial (clinical Trails.gov No., NCT01945775) to simulate the survival events of breast cancer patients in the Talazoparib group and the standard treatment group. The state transition probability and clinical data of breast cancer patients during treatment were extracted from the phase III EMBRACA clinical trial. The cost data generated during the treatment process comes from local hospital pricing, other references, and expert consultation. This article uses US dollars to calculate the treatment cost and incremental cost-effectiveness ratio. Health outcomes are expressed in Quality Adjusted Life Years (QALYs). In addition, Outcomes were measured in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio, which robustness was evaluated by deterministic and probabilistic sensitivity analyses. This article establishes a Markov model for single-item sensitivity analysis. The results show that the economic benefits of using Talazoparib as a new treatment strategy in both China and the United States are higher than other drugs, and it is cost-effective. Compared to the control group, the incremental cost incurred by the Talazoparib treatment group in China was $2484.48/QALY, with an incremental QALY of 1.5. However, Talazoparib in the United States holds a dominant position, saving costs of $10,223.43 and increasing QALYs by 1.5. The clinical treatment effect of Talazoparib group in BRCA1/2 mutant advanced breast cancer patients is better than that of the standard treatment group, and the progression free survival period is significantly prolonged. From the perspective of medical and health services in China and the United States, the Talazoparib group is more economical than the standard treatment group in treating patients with BRCA1/2 mutant advanced breast cancer.

Background: Forecasting the intensity, source, and cost of informal care for older adults in China is essential to establish and enhance policy support systems for informal care within the context of East Asian traditional culture that emphasizes filial piety. This study aims to analyze the current situation and influencing factors for the informal care needs and predict the trends of informal care needs for older adults in China from 2020 to 2040. Methods: Using the CHARLS database from 2015 to 2018, this study first combined a two-part model and a multinomial logit to analyze the influencing factors for the informal care needs of urban-rural older adults in China. Secondly, a multi-state Markov model was constructed to forecast the number of urban-rural older populations in each health state from 2020 to 2040. Finally, based on a microsimulation model, this study predicted the trends of informal care intensity, source, and cost for older adults in urban and rural areas from 2020 to 2040. Results: In 2040, the size of the disabled older population in China will expand further. In rural areas, the total number of disabled people in 2040 (39.77 million) is 1.50 times higher than that in 2020; In urban areas, the total number of disabled people in 2040 (56.01 million) is 2.51 times higher than that in 2020. Compared with 2020, older adults population with mild, moderate and severe disability in 2040 would increase by 87.60%, 101.70%, and 115.08%, respectively. In 2040, the number of older adults receiving low-, medium-, and high-intensity care in China will be 38.60 million, 22.89 million, and 41.69 million, respectively, and older people will still rely on informal care provided by spouses and children (from spouses only: 39.26 million, from children only: 36.74 million, from spouses and children only: 16.79 million, other: 10.39 million). The total cost of informal care in 2040 will be 1,086.65 billion yuan, 2.22 times that of 2020 (490.31 billion yuan), which grows faster than the economic growth rate. Conclusion: From 2020 to 2040, the informal care needs of older people in rural areas will increase first and then decrease due to the demographic structure and rapid urbanization. In contrast, the informal care needs of older people in urban areas will continuously increase from 2020 to 2040, with the growth rate gradually slowing down. This study provides an evidence-based rationale for scientifically measuring the economic value of informal care and reasonably allocating care resources. [ABSTRACT FROM AUTHOR]

Background: Pembrolizumab is a potentially valuable treatment. However, patients, doctors, and healthcare decision-makers are uncertain about its cost-effectiveness and an appropriate pricing for this new therapy. This study aims to appraise the cost-effectiveness of pembrolizumab as a first-line treatment for advanced biliary tract cancer (BTC) patients in China and the United States (US). Methods: A Markov model was constructed from the perspectives of healthcare systems in both China and the US for pharmacoeconomic evaluation. Patient baseline characteristics and key clinical data were sourced from the KEYNOTE-966 trial (ClinicalTrials.gov, NCT04003636). Costs and utilities were collected from drug cost websites and published literature. Cumulative costs (in USD), life years (LYs), quality-adjusted life years (QALYs), and incremental costeffectiveness ratios (ICERs) were measured and compared. Price simulations were conducted under given willingness-to-pay (WTP) thresholds to provide pricing scheme references. The model's robustness was analyzed through oneway sensitivity analysis and probabilistic sensitivity analysis. Results: Basic data analysis illustrates that pembrolizumab ($2662.41/100 mg) in combination with chemotherapy regimen was not cost-effective relative to chemotherapy regimens at the WTP threshold of $38,201.19 in China, and the additional cost relative to chemotherapy regimens was $77,114.94 (ICER $556,689.47/QALY) while increasing 0.14 QALYs. Pembrolizumab ($54.71/1 mg) also increased efficacy by 0.14 QALYs in the US, but remained also not cost-effective at the US WTP threshold of $229,044, and the total cost increased by $160,425.24 (ICER $1,109,462.92/QALY). Conclusion: Compared with chemotherapy, pembrolizumab plus chemotherapy reduces the disease of burden. However, at its current price, it may not be a costeffective treatment for advanced BTC in both China and the US. This study can aid decision-makers in making optimal choices. [ABSTRACT FROM AUTHOR]

We consider a Markov model of learning consisting of three states: the state of knowledge transfer, the training state, and the state of knowledge control. Taking into account of training time within this model allows one to obtain additional information about competencies of students, to estimate the values of latent parameters, and to improve the learning process. [ABSTRACT FROM AUTHOR]

Objective To make the cost-effectiveness analysis of pembrolizumab and platinum chemotherapy as the firstline treatment for advanced non-small cell lung cancer （NSCLC） in the population with tumor proportion score （TPS） ≥ 1% of PD-L1, and provide some reference for the clinical use and future price negotiation of pembrolizumab. Methods Based on Pubmed database, the published RCT literatures of pembrolizumab were analyzed, and the survival data were extracted, combined with the treatment plan of a tertiary hospital, the Markov model were established to simulate the cost and health effectiveness of patients for twenty years, and the stability of the model was tested by one-way sensitivity analysis and probability sensitivity analysis. Results Twenty years later, the cost-effectiveness ratio of pembrolizumab group and chemotherapy group was ￥58 517.60/ quality adjusted life month (QALM) and ￥ 41 213.08/QALM. Compared with the chemotherapy group, the incremental cost effective ratio (ICER) was ￥104 485.36/QALM. Conclusion When the willingness to pay （WTP） value was ￥30 902/QALM, the pembrolizumab therapy was not more cost-effective advantages than platinum chemotherapy, and the sensitivity analysis showed that the results of the model were relatively stable. [ABSTRACT FROM AUTHOR]

Two vaccines against rotavirus diseases, Rotarix® and RotaTeq®, are being marketed in Spain; but rotavirus is not presently among the diseases covered by universal vaccination in Spain. The aim of this study was to assess the efficiency of extending Spain's current targeted rotavirus vaccination strategy including only preterm babies, to a policy of universal vaccination. A de novo cohort-based Markov model was built to evaluate the efficiency of three compared rotavirus vaccination strategies in Spain: targeted, universal, and no vaccination. Using Rotarix® or RotaTeq®, we compared the cost–utility of these strategies from both a societal perspective and Spanish National Health System (SNHS) perspective. The model represents the most important clinical events conceivably linked to rotavirus infection. Efficacy, effectiveness, safety, costs, and utilities were identified by systematic reviews. Incremental cost–utility ratio (ICUR) is EUR 23,638/QALY (Quality-Adjusted Life Year) for targeted vaccination with Rotarix® compared with no vaccination. The ICUR for the rest of the strategies evaluated are above EUR 30,000/QALY. The sensitivity analysis shows price as the only parameter that could make the universal vaccination strategy efficient. Considering a threshold of EUR 25,000/QALY, only targeted vaccination with Rotarix® would be efficient from societal perspective. Price drops of 36.9% for Rotarix® and 44.6% for RotaTeq® would make universal vaccination efficient. [ABSTRACT FROM AUTHOR]

Atherosclerosis, a leading cause of cardiovascular disease, necessitates advanced and innovative modeling techniques to better understand and predict plaque dynamics. The present work presents two distinct hypothetical models inspired by different research fields: the logistic map from chaos theory and Markov models from stochastic processes. The logistic map effectively models the nonlinear progression and sudden changes in plaque stability, reflecting the chaotic nature of atherosclerotic events. In contrast, Markov models, including traditional Markov chains, spatial Markov models, and Markov random fields, provide a probabilistic framework to assess plaque stability and transitions. Spatial Markov models, visualized through heatmaps, highlight the spatial distribution of transition probabilities, emphasizing local interactions and dependencies. Markov random fields incorporate complex spatial interactions, inspired by advances in physics and computational biology, but present challenges in parameter estimation and computational complexity. While these hypothetical models offer promising insights, they require rigorous validation with real-world data to confirm their accuracy and applicability. This study underscores the importance of interdisciplinary approaches in developing theoretical models for atherosclerotic plaques. [ABSTRACT FROM AUTHOR]

We consider the problem of constructing a vector-valued linear Markov process in continuous time, such that its first coordinate is in good agreement with given samples of the scalar autocorrelation function of an otherwise unknown stationary Gaussian process. This problem has intimate connections to the computation of a passive reduced model of a deterministic time-invariant linear system from given output data in the time domain. We construct the stochastic model in two steps. First, we employ the AAA algorithm to determine a rational function which interpolates the z-transform of the discrete data on the unit circle and use this function to assign the poles of the transfer function of the reduced model. Second, we choose the associated residues as the minimizers of a linear inequality constrained least squares problem which ensures the positivity of the transfer function’s real part for large frequencies. We apply this method to compute extended Markov models for stochastic processes obtained from generalized Langevin dynamics in statistical physics. Numerical examples demonstrate that the algorithm succeeds in determining passive reduced models and that the associated Markov processes provide an excellent match of the given data. [ABSTRACT FROM AUTHOR]

Background: Nonoperative management versus early reconstruction for partial tears of the medial ulnar collateral ligament (MUCL) remains controversial, with the most common treatment options for partial tears consisting of rest, rehabilitation, platelet-rich plasma (PRP), and/or surgical intervention. However, whether the improved outcomes reported for treatments such as MUCL reconstruction (UCLR) or nonoperative management with a series of PRP injections justifies their increased upfront costs remains unknown. Purpose: To compare the cost-effectiveness of an initial trial of physical therapy alone, an initial trial of physical therapy plus a series of PRP injections, and early UCLR to determine the preferred cost-effective treatment strategy for young, high-level baseball pitchers with partial tears of the MUCL and with aspirations to continue play at the next level (ie, collegiate and/or professional). Study Design: Economic and decision analysis; Level of evidence, 2. Methods: A Markov chain Monte Carlo probabilistic model was developed to evaluate the outcomes and costs of 1000 young, high-level, simulated pitchers undergoing nonoperative management with and without PRP versus early UCLR for partial MUCL tears. Utility values, return to play rates, and transition probabilities were derived from the published literature. Costs were determined based on the typical patient undergoing each treatment strategy at the authors' institution. Outcome measures included costs, acquired playing years (PYs), and the incremental cost-effectiveness ratio (ICER). Results: The mean total costs resulting from nonoperative management without PRP, nonoperative management with PRP, and early UCLR were $22,520, $24,800, and $43,992, respectively. On average, early UCLR produced an additional 4.0 PYs over the 10-year time horizon relative to nonoperative management, resulting in an ICER of $5395/PY, which falls well below the $50,000 willingness-to-pay threshold. Overall, early UCLR was determined to be the preferred cost-effective strategy in 77.5% of pitchers included in the microsimulation model, with nonoperative management with PRP determined to be the preferred strategy in 15% of pitchers and nonoperative management alone in 7.5% of pitchers. Conclusion: Despite increased upfront costs, UCLR is a more cost-effective treatment option for partial tears of the MUCL than an initial trial of nonoperative management for most high-level baseball pitchers. [ABSTRACT FROM AUTHOR]

Motion prediction has gotten much attention in the past few years. It has endless uses either in real life or in virtual life (gaming). The current dynamic motion prediction models, such as the Markov model, depend only on the object motions' history. They ignore the object's direction and speed, which play a key role in dynamic motion prediction. This paper introduces two new probability density functions (PDFs) for elliptic and ellipsoidal regions. Then, it introduces two new motion prediction models based on the new proposed PDFs. This paper proposes new motion detection models that depend not only on the motion's history but also on moving objects' speed and direction (objects' velocity). Moreover, it integrates the proposed models with the Markov model to attain a more precise prediction. Besides, it introduces several applications for the proposed models. [ABSTRACT FROM AUTHOR]

Objective: To compare the cost-effectiveness of serial non-echo planar diffusion weighted MRI (non-EP DW MRI) versus planned second look surgery following initial canal wall up tympanomastoidectomy for the treatment of cholesteatoma. Methods: A decision-analytic model was developed. Model inputs including residual cholesteatoma rates, rates of non-EP DW MRI positivity after surgery, and health utility scores were abstracted from published literature. Cost data were derived from the 2022 Centers for Medicare and Medicaid Services fee rates. Efficacy was defined as increase in quality-adjusted life year (QALY). One- and 2-way sensitivity analyses were performed on variables of interest to probe the model. Total time horizon was 50 years with a willingness to pay (WTP) threshold set at $50 000/QALY. Results: Base case analysis revealed that planned second-look surgery ($11 537, 17.30 QALY) and imaging surveillance with non-EP DWMRI ($10 439, 17.26 QALY) were both cost effective options. Incremental cost effectiveness ratio was $27 298/QALY, which is below the WTP threhshold. One-way sensitivity analyses showed that non-EP DW MRI was more cost effective than planned second-look surgery if the rate of residual disease after surgery increased to 48.3% or if the rate of positive MRI was below 45.9%. A probabilistic sensitivity analysis at WTP of $50 000/QALY found that second-look surgery was more cost-effective in 56.7% of iterations. Conclusion: Non-EP DW MRI surveillance is a cost-effect alternative to planned second-look surgery following primary canal wall up tympanomastoidectomy for cholesteatoma. Cholesteatoma surveillance decisions after initial canal wall up tympanomastoidectomy should be individualized. Level of Evidence: V. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to estimate and compare the lifetime clinical and economic burden of invasive pneumococcal diseases (IPD) attributable to the serotypes contained in a new 21-valent pneumococcal conjugate vaccine (V116) vs. the 20-valent pneumococcal conjugate vaccine (PCV20) among adults aged 18 years and above in the USA. Methods: A state-transition Markov model was used to track IPD cases and deaths as well as the associated direct medical costs (in 2023 US dollars) from a US healthcare payer perspective at 3% annual discount rate. The results were summarized for V116, PCV20, and eight unique serotypes contained in V116. A sensitivity analysis was conducted to determine the most influential inputs on the overall total direct lifetime cost. Results: For the total population of US adults aged 18 years and above in 2021 (approx. 258 million residents), the estimated lifetime numbers of cases of IPD, post-meningitis sequelae (PMS), and IPD-related deaths attributable to the serotypes contained in V116 were approximately 1.4 million, 17,608, and 186,200, respectively, with a total discounted lifetime direct cost of $32.6 billion. A substantial proportion (approx. 31%) of those were attributable to the unique eight serotypes. The corresponding estimates for PCV20 were approximately 35% lower—934,000, 11,500, and 120,000, respectively—with a total discounted direct lifetime cost of $21.9 billion. Conclusion: These results show that V116 serotypes (compared to PCV20) are associated with substantially higher clinical and economic burden of IPD. The addition of V116 to vaccination recommendations can help to reduce the residual burden of IPD in US adults. [ABSTRACT FROM AUTHOR]

Objective: In the double-blind, phase III, placebo-controlled RUBY randomized clinical trial, dostarlimab plus carboplatin-paclitaxel significantly increased survival among patients with primary advanced or recurrent endometrial cancer (EC). We conducted a cost-effectiveness analysis of dostarlimab in combination with chemotherapy in these patients stratified by mismatch repair-deficient (dMMR) and mismatch repair-proficient (pMMR) subgroups from the perspective of a United States payer. Materials and methods: A Markov model with three states was employed to simulate patients who were administered either dostarlimab in combination with chemotherapy or chemotherapy based on the RUBY trial. Quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER) were calculated with a willingness-to-pay (WTP) threshold of $150,000 per QALY. Both univariate and probabilistic sensitivity analyses were carried out to explore the robustness of the model. Results: In dMMR EC, the combination of dostarlimab and chemotherapy achieved an additional 5.48 QALYs at an incremental cost of $330,747 compared to chemotherapy alone, resulting in an ICER of $60,349.30 per QALY. In pMMR EC, there were 1.51 additional QALYs gained at an extra cost of $265,148, yielding an ICER of $175,788.47 per QALY. With a 15.2% discount on dostarlimab, the ICER decreased to $150,000 per QALY in the pMMR EC. The univariate sensitivity analysis revealed that the cost of dostarlimab, utility of progression-free survival (PFS), and progressive disease (PD) had the most significant impacts on the outcomes. Probabilistic sensitivity analysis revealed that dostarlimab had a 100% likelihood of being considered cost-effective for patients at a WTP threshold of $150,000 per QALY for dMMR EC, whereas this likelihood was only 0.5% for pMMR EC. Conclusion: Dostarlimab in combination with chemotherapy was cost-effective for primary advanced or recurrent dMMR EC from the perspective of a United States payer at a WTP threshold of $150,000 per QALY, but not for pMMR EC. Lowering the prices of dostarlimab could potentially enhance the cost-effectiveness of treatment for pMMR EC. [ABSTRACT FROM AUTHOR]

Background and Aims: Cardiovascular diseases (CVDs) are one of the major diseases in developing and developed countries and have high prevalence and mortality rates. Pharmacological interventions, especially the use of combination medications, can have preventive effects in patients with CVDs. Recently, in the PolyIran trial, a combination of atorvastatin, hydrochlorothiazide, aspirin, and valsartan or enalapril (Polypill) was shown to be effective in providing survival benefits as a primary prevention strategy. In the present study, we examine the cost‐effectiveness of the use of polypill compared to its individual components (named as medication monotherapy) in the prevention of CVDs in Iran. Methods: This was an economic evaluation study conducted to compare the cost‐utility of polypill with that of medication monotherapy for 10,000 hypothetical cohorts of people over 35 years of age using the Markov model and with a lifetime horizon. The study perspective was patient perspective and direct medical costs, quality‐adjusted life‐years (QALYs), and incremental cost‐effectiveness ratio were estimated. To deal with uncertaintysensitivity analyses were used. Results: The results showed that polypill, with the lowest costs (871 USD) and highest QALYs (14.55), had the most cost‐utility than medication monotherapy. Also, the results showed that the highest sensitivities were related to the utilities of angina and stroke states. At the 21,768 USD threshold, polypill had a 92% probability of being cost‐effective versus other medications. Conclusion: Considering that polypill had the most cost‐utility, it is suggested that health system policymakers pay special attention to polypill in designing clinical guidelines. Also, through covering this medication by health insurance organizations, it is possible to complete the country's medicine pharmacopeia in preventing CVDs. [ABSTRACT FROM AUTHOR]

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The aim of this research is to devise a continuous simulation model for predicting ship crane failures to increase their reliability and reduce unplanned downtime during cargo loading and unloading operations. To predict the condition of the hydraulic system, a database from the GALIOT software package was used for carrying out maintenance on cranes at m/v "O" over a period of 120,000 working hours. In the research, fault tree analysis (FTA) was used to identify causal relationships between system failures and basic events, while the Markov mathematical model was used to model the system state and predict transitions between different failure states. A system dynamics simulation model was developed to simulate the behavior of a system using POWERSIM PowerSim Constructor 2.5.d (4002), and regression analysis was performed to analyze the simulation results and understand the relationships between dependent and independent variables. The results show that a model for predicting failures in the hydraulic motors and pumps of ship cranes was developed, and the Markov model makes it possible to estimate the frequency of transitions between states under the condition that the sum of reliability equals one. The simulation model shows high reliability of the cranes and a constant frequency of failures throughout the 120,000 operating hours, while the regression analysis confirms the validity of the simulation model and shows a strong correlation between the analyzed variables. These models are used to improve the planning of ship crane maintenance, reduce unplanned downtime, and predict and promptly detect failures, which overall minimizes maintenance costs and failures. [ABSTRACT FROM AUTHOR]

Introduction: Detection of colorectal cancer (CRC) in the early stages through available screening tests increases the patient's survival chances. Multimodal screening policies can benefit patients by providing more diverse screening options and balancing the risks and benefits of screening tests. We investigate the cost-effectiveness of a wide variety of multimodal CRC screening policies. Methods: We developed a Monte Carlo simulation framework to model CRC dynamics. We proposed an innovative calibration process using machine learning models to estimate age- and size-specific adenomatous polyps' progression and regression rates. The proposed approach significantly expedites the model parameter space search. Results: Two multimodal proposed policies (i.e., 1] colonoscopy at 50 y and fecal occult blood test annually between 60 and 75 y and 2] colonoscopy at 50 and 60 y and fecal immunochemical test annually between 70 and 75 y) are identified as efficient frontier policies. Both policies are cost-effective at a willingness to pay of $50,000. Sensitivity analyses were performed to assess the sensitivity of results to a change in screening test costs as well as adherence behavior. The sensitivity analysis results suggest that the proposed policies are mostly robust to the considered changes in screening test costs, as there is a significant overlap between the efficient frontier policies of the baseline and the sensitivity analysis cases. However, the efficient frontier policies were more sensitive to changes in adherence behavior. Conclusion: Generally, combining stool-based tests with visual tests will benefit patients with higher life expectancy and a lower expected cost compared with unimodal screening policies. Colonoscopy at younger ages (when the colonoscopy complication risk is lower) and stool-based tests at older ages are shown to be more effective. Highlights: We propose a detailed Markov model to capture the colorectal cancer (CRC) dynamics. The proposed Markov model presents the detailed dynamics of adenomas progression to CRC. We use more than 44,000 colonoscopy reports and available data in the literature to calibrate the proposed Markov model using an innovative approach that leverages machine learning models to expedite the calibration process. We investigate the cost-effectiveness of a wide variety of multimodal CRC screening policies and compare their performances with the current in-practice policies. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to demonstrate a practical framework that can be applied to estimate the health impact of changes in waiting times across a range of elective procedures in the National Health Service (NHS) in England. We apply this framework by modeling 2 procedures: coronary artery bypass graft (CABG) and total hip replacement (THR). Methods: We built a Markov model capturing health pre- and postprocedure, including the possibility of exiting preprocedure to acute NHS care or self-funded private care. We estimate the change in quality-adjusted life-years (QALYs) over a lifetime horizon for 10 subgroups defined by sex and Index of Multiple Deprivation quintile groups and for 7 alternative scenarios. We include 18 wk as a baseline waiting time consistent with current NHS policy. The model was populated with data from routinely collected data sets where possible (Hospital Episode Statistics, Patient-Reported Outcome Measures, and Office for National Statistics Mortality records), supplemented by the academic literature. Results: Compared with 18 wk, increasing the wait time to 36 wk resulted in a mean discounted QALY loss in the range of 0.034 to 0.043 for CABG and 0.193 to 0.291 for THR. The QALY impact of longer NHS waits was greater for those living in more deprived areas, partly as fewer patients switch to private care. Discussion/Conclusion: The proposed framework was applied to 2 different procedures and patient populations. If applied to an expanded group of procedures, it could provide decision makers with information to inform prioritization of waiting lists. There are a number of limitations in routine data on waiting for elective procedures, primarily the lack of information on people still waiting. Highlights: We present a modeling framework that allows for an estimation of the health impact (measured in quality-adjusted life-years) of waiting for elective procedures in the NHS in England. We apply our model to waiting for coronary artery bypass graft (CABG) and total hip replacement (THR). Increasing the wait for THR results in a larger health loss than an equivalent increase in wait for CABG. This model could potentially be used to estimate the impact across an expanded group of procedures to inform prioritization of activities to reduce waiting times. [ABSTRACT FROM AUTHOR]

Pakistan is exposed to variety of hazards. Drought is one of the hydro-meteorological hazards causing loss of life and soil moisture, reduction in agricultural production and decline in groundwater level. Balochistan is the largest province of Pakistan which has been severely affected by drought. This study is an effort to analyze and forecast the spatial pattern of drought in Balochistan using Markov Model. Both primary and secondary data were utilized in Geographical Information System (GIS) environment to model the current and predict the future pattern of drought in the region. The main input spatial layers included land cover, natural difference vegetation index (NDVI), natural difference water index (NDWI), groundwater level, precipitation and current drought. The spatial pattern of drought is delineated into extreme, moderate and low/no drought zones. The analysis reveals that the currently, the extreme, moderate and low/no drought zones are spatially extended over 9.9% (37,053 km2), 83.11% (288,553 km2) and 6.21% (21,584 km2), respectively. While the predicted drought presents shocking results, where the prevalence of extreme, moderate and low/no drought zones may spatially extend over to 51.14% (191,364 km2),28.78% (99,945 km2) and 16.09 (55,881 km2). The extreme drought may encroach current moderate drought into predicted extreme drought. Additionally, the occurrence of drought in Chaghi district may be more in future, where chances of extreme drought occurrence is 20.15%. Second most prone region is Kharan, where chances of drought are 11.35% and finally, third region is Khuzdar, where the probability of extreme drought is 8.90%. However, Awaran, Panjgur, Kech, Zhob and Sherani districts are also prone to moderate drought in future. There is dire need to build mini and micro dams to conserve rain water and farmers should plant less water dependent crops. The results and findings of this study have potential to assist disaster management authorities and decision makers to formulate zone specific drought risk reduction strategies. [ABSTRACT FROM AUTHOR]

Academic research on trend-following investing has almost exclusively focused on testing various trading rules' profitability. However, all existing trend-following rules are essentially ad hoc, lacking a solid theoretical justification for their optimality. This paper aims to address this gap in the literature. Specifically, we examine the optimal trend-following when the returns follow a two-state process, randomly switching between bull and bear markets. We show that if a Markov model governs the return process, it is optimal to follow the trend using the Exponential Moving Average rule. However, the Markov model is unrealistic because it does not represent the bull and bear market duration times correctly. It is more sensible to model the return process by a semi-Markov model where the state termination probability increases with age. Under this framework, the optimal trend-following rule resembles the Moving Average Convergence/Divergence rule. We confirm the validity of the semi-Markov model with an empirical study demonstrating that the theoretically optimal trading rule outperforms the popular 10-month Simple Moving Average and 12-month Momentum rules across a universe of international markets. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the tumors with the highest prevalence rate among women in the world, and its BRCA1/2 gene is a common mutation site. Talazoparib, as a targeted PARP inhibitor, can effectively control the occurrence and development of breast cancer with BRCA1/2 gene mutation, and play a therapeutic role. Based on the findings from the Phase III EMBRACE trial (NCT01945775 clinical trial), our analysis reveals that the talazoparib group demonstrated a significant extension in progression-free survival, along with improved response markers and patient-reported outcomes when compared to conventional therapies. This study aims to assess the cost-effectiveness of talazoparib for treating advanced breast cancer with germline BRCA1/2 mutations and HER2 negativity, considering the perspectives of health services in China and the United States. The results obtained will serve as a valuable reference for promoting rational drug utilization and enhancing medical resource efficiency. To evaluate the cost-effectiveness of Talazoparib more scientifically and provide clinicians with chemotherapy options, this paper developed a Markov model based on the EMBRACA clinical trial (clinical Trails.gov No., NCT01945775) to simulate the survival events of breast cancer patients in the Talazoparib group and the standard treatment group. The state transition probability and clinical data of breast cancer patients during treatment were extracted from the phase III EMBRACA clinical trial. The cost data generated during the treatment process comes from local hospital pricing, other references, and expert consultation. This article uses US dollars to calculate the treatment cost and incremental cost-effectiveness ratio. Health outcomes are expressed in Quality Adjusted Life Years (QALYs). In addition, Outcomes were measured in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio, which robustness was evaluated by deterministic and probabilistic sensitivity analyses. This article establishes a Markov model for single-item sensitivity analysis. The results show that the economic benefits of using Talazoparib as a new treatment strategy in both China and the United States are higher than other drugs, and it is cost-effective. Compared to the control group, the incremental cost incurred by the Talazoparib treatment group in China was $2484.48/QALY, with an incremental QALY of 1.5. However, Talazoparib in the United States holds a dominant position, saving costs of $10,223.43 and increasing QALYs by 1.5. The clinical treatment effect of Talazoparib group in BRCA1/2 mutant advanced breast cancer patients is better than that of the standard treatment group, and the progression free survival period is significantly prolonged. From the perspective of medical and health services in China and the United States, the Talazoparib group is more economical than the standard treatment group in treating patients with BRCA1/2 mutant advanced breast cancer. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the working life expectancies (WLE) of men and women with depression, examining depression by symptom trajectories from the late 20s to early 50s, and to estimate WLE by race/ethnicity and educational attainment. Methods: Data from 9206 participants collected from 1979 to 2018 in the US National Longitudinal Survey of Youth 1979 cohort were used. Depression was measured using the Center for Epidemiologic Studies Depression Scale Short Form at four time points (age 28–35, age 30–37, age 40, and age 50). Labor force status was measured monthly starting at age 30 until age 58–62. Depressive symptom trajectories were estimated using growth mixture modeling and multistate modeling estimated WLE from age 30–60 for each gender and depressive symptom trajectory. Results: Five latent symptom trajectories were established: a persistent low symptom trajectory (n = 6838), an episodic trajectory with high symptoms occurring before age 40 (n = 995), an episodic trajectory with high symptoms occurring around age 40 (n = 526), a trajectory with high symptoms occurring around age 50 (n = 570), and a persistent high symptom trajectory (n = 277). The WLE for men at age 30 was 30.3 years for the persistent low symptom trajectory, 22.8 years for the episodic before 40 trajectory, 19.6 years for the episodic around age 40 trajectory, 18.6 years for the episodic around age 50 trajectory, and 13.2 years for the persistent high symptom trajectory. Results were similar for women. WLE disparities between depression trajectories grew when stratified by race/ethnicity and education level. Conclusions: Roughly a quarter of individuals experienced episodic depressive symptoms. However, despite periods of low depressive symptoms, individuals were expected to be employed ~5–17 years less at age 30 compared to those with low symptoms. Accessible employment and mental health disability support policies and programs across the working life course may be effective in maintaining work attachment and improving WLE among those who experience depression. [ABSTRACT FROM AUTHOR]