RESUMO
The X-rays emitted during CT scans can increase solid cancer risks by damaging DNA, with the risk tied to patient-specific organ doses. This study aims to establish a new method to predict patient specific abdominal organ doses from CT examinations using minimized computational resources at a fast speed. The CT data of 247 abdominal patients were selected and exported to the auto-segmentation software named DeepViewer to generate abdominal regions of interest (ROIs). Radiomics feature were extracted based on the selected CT data and ROIs. Reference organ doses were obtained by GPU-based Monte Carlo simulations. The support vector regression (SVR) model was trained based on the radiomics features and reference organ doses to predict abdominal organ doses from CT examinations. The prediction performance of the SVR model was tested and verified by changing the abdominal patients of the train and test sets randomly. For the abdominal organs, the maximal difference between the reference and the predicted dose was less than 1 mGy. For the body and bowel, the organ doses were predicted with a percentage error of less than 5.2%, and the coefficient of determination (R2) reached up to 0.9. For the left kidney, right kidney, liver, and spinal cord, the mean absolute percentage error ranged from 5.1 to 8.9%, and the R2 values were more than 0.74. The SVR model could be trained to achieve accurate prediction of personalized abdominal organ doses in less than one second using a single CPU core.
Assuntos
Abdome , Aprendizado de Máquina , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Feminino , Masculino , Abdome/diagnóstico por imagem , Doses de Radiação , Pessoa de Meia-Idade , Medicina de Precisão/métodos , Idoso , Adulto , Método de Monte Carlo , Software , Radiografia Abdominal/métodos , RadiômicaRESUMO
Exposure to ionizing radiation can induce genetic aberrations via unrepaired DNA strand breaks. To investigate quantitatively the dose-effect relationship at the molecular level, we irradiated dry pBR322 plasmid DNA with 3 MeV protons and assessed fragmentation yields at different radiation doses using long-read sequencing from Oxford Nanopore Technologies. This technology applied to a reference DNA model revealed dose-dependent fragmentation, as evidenced by read length distributions, showing no discernible radiation sensitivity in specific genetic sequences. In addition, we propose a method for directly measuring the single-strand break (SSB) yield. Furthermore, through a comparative study with a collection of previous works on dry DNA irradiation, we show that the irradiation protocol leads to biases in the definition of ionizing sources. We support this scenario by discussing the size distributions of nanopore sequencing reads in the light of Geant4 and Geant4-DNA simulation toolkit predictions. We show that integrating long-read sequencing technologies with advanced Monte Carlo simulations paves a promising path toward advancing our comprehension and prediction of radiation-induced DNA fragmentation.
Assuntos
Fragmentação do DNA , Método de Monte Carlo , Plasmídeos , Plasmídeos/genética , Fragmentação do DNA/efeitos da radiação , Relação Dose-Resposta à Radiação , Análise de Sequência de DNA/métodos , Quebras de DNA de Cadeia Simples/efeitos da radiação , DNA/genéticaRESUMO
This original work investigated the optical properties and Monte-Carlo (MC) based simulation of light propagation in the flavedo of Nanfeng tangerine (NF) and Gannan navel orange (GN) infected by Penicillium italicum. The increase of absorption coefficient (µa) at around 482 nm and the decrease at around 675 nm were both observed in infected NF and GN during storage, indicating the accumulation of carotenoids and loss of chlorophyll. Particularly, the µa in NF varied more intensively than GN, but the limited differences of reduced scattering coefficient (µs') were detected while postharvest infection. Besides, MC simulation of light propagation indicated that the photon packets weight and penetration depth at 482 nm in NF were reduced more than in GN flavedo, while there were almost no changes at the relatively low absorption wavelength of 926 nm. The simulated absorption energy at 482 nm in NF and GN presented more changes than those at 675 nm during infection, thus could provide better detection of citrus diseases. Furthermore, PLS-DA models can discriminate healthy and infected citrus, with the accuracy of 95.24 % for NF and 98.67 % for GN, respectively. Consequently, these results can provide theoretical fundamentals to improve modelling prediction robustness and accuracy.
Assuntos
Citrus , Luz , Método de Monte Carlo , Penicillium , Citrus/microbiologia , Doenças das Plantas/microbiologia , Clorofila/análise , Frutas/microbiologia , Carotenoides/análise , Carotenoides/metabolismoRESUMO
Gas stations not only serve as sites for oil storage and refueling but also as locations where vehicles frequently brake, significantly enriching the surrounding soil with potentially toxic elements (PTEs). Herein, 117 topsoil samples from gas stations were collected in Beijing to explore the impact of gas stations on PTE accumulation. The analysis revealed that the average Pollution Index (PI) values for Cd, Hg, Pb, Cu, and Zn in the soil samples all exceeded 1. The random forest (RF) model, achieving an AUC score of 0.95, was employed to predict PTE pollution at 372 unsampled gas stations. Additionally, a Positive Matrix Factorization (PMF) model indicated that gas station operations and vehicle emissions were responsible for 70 % of the lead (Pb) enrichment. Probabilistic health risk assessments showed that the carcinogenic risk (CR) and noncarcinogenic risk (NCR) for PTE pollution to adult females were the highest, at 0.451 and 1.61E-05 respectively, but still within acceptable levels. For adult males at contaminated sites, the Pb-associated CR and NCR were approximately twice as high as those at uncontaminated sites, with increases of 107 % and 81 %, respectively. This study provides new insights for managing pollution caused by gas stations.
Assuntos
Aprendizado de Máquina , Método de Monte Carlo , Poluentes do Solo , Medição de Risco , Poluentes do Solo/análise , Pequim , Humanos , Metais Pesados/análise , Monitoramento Ambiental/métodos , Masculino , Feminino , AdultoRESUMO
This study aimed to develop a physiologically based pharmacokinetic/pharmacodynamic model (PBPK/PD) of meropenem for critically ill patients. A PBPK model of meropenem in healthy adults was established using PK-Sim software and subsequently extrapolated to critically ill patients based on anatomic and physiological parameters. The mean fold error (MFE) and geometric mean fold error (GMFE) methods were used to compare the differences between predicted and observed values of pharmacokinetic parameters Cmax, AUC0-∞, and CL to evaluate the accuracy of the PBPK model. The model was verified using meropenem plasma samples obtained from Intensive Care Unit (ICU) patients, which were determined by HPLC-MS/MS. After that, the PBPK model was combined with a PKPD model, which was developed based on f%T > MIC. Monte Carlo simulation was utilized to calculate the probability of target attainment (PTA) in patients. The developed PBPK model successfully predicted the meropenem disposition in critically ill patients, wherein the MFE average and GMFE of all predicted PK parameters were within the 1.25-fold error range. The therapeutic drug monitoring (TDM) of meropenem was conducted with 92 blood samples from 31 ICU patients, of which 71 (77.17%) blood samples were consistent with the simulated value. The TDM results showed that meropenem PBPK modeling is well simulated in critically ill patients. Monte Carlo simulations showed that extended infusion and frequent administration were necessary to achieve curative effect for critically ill patients, whereas excessive infusion time (> 4 h) was unnecessary. The PBPK/PD modeling incorporating literature and prospective study data can predict meropenem pharmacokinetics in critically ill patients correctly. Our study provides a reference for dose adjustment in critically ill patients.
Assuntos
Antibacterianos , Estado Terminal , Meropeném , Meropeném/farmacocinética , Meropeném/administração & dosagem , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Adulto , Idoso , Modelos Biológicos , Método de Monte Carlo , Monitoramento de Medicamentos , Unidades de Terapia Intensiva , Testes de Sensibilidade MicrobianaRESUMO
The current research study evaluated the health and environmental risks issues associated with potentially toxic elements (PTEs) in the complex terminal aquifer located in the Algerian desert. The methods used included principal component and cluster (dendrogram) analysis to estimate source of ions and contamination. Various indices such as the Heavy Metal Pollution Index (HPI), Metal Index, hazard quotient, hazard index (HI), and cancer risk (CR) were applied to assess both environmental and human health risks. Furthermore, the Monte Carlo method was applied for probabilistic assessment of carcinogenic and non-carcinogenic risks through oral and dermal exposure routes in both adults and children. The results revealed that approximately 16% of the samples fell within the low pollution category (HPI < 100), indicating relatively lower levels of heavy metal contamination. However, the remaining 84% of the samples exhibited high pollution levels, indicating a significant presence of heavy metal pollutants in the northeastern part of the investigated area. The calculated average risk index (RI) for the collected samples was 18.99, with a range from 0.03 to 103.21. This indicates that a large portion, 82% of the samples, could cause low ecological risk (RI < 30), whereas the remaining 18% indicate a significant environmental pollution risk. The HI for oral ingestion showed that adults had HI values ranging from 0.231 to 1.54, while children exhibited higher values, ranging from 0.884 to 5.9 (Fig. 5a). For dermal exposure, HI values in adults ranged from 2.71E-07 to 8.74E-06 and in children, from 2.18E-06 to 7.03E-05. These findings highlight the potential non-carcinogenic risks associated with oral exposure to PTEs and underscore the increased vulnerability of children to metals such as Fe, Mn, Pb, and Cr. Most samples showed CR exceeding 1 × 10-4 for chromium (Cr) and lead (Pb), indicating a significant vulnerability to carcinogenic effects in both children and adults.
Assuntos
Metais Pesados , Poluentes Químicos da Água , Argélia , Medição de Risco/métodos , Humanos , Metais Pesados/análise , Metais Pesados/toxicidade , Poluentes Químicos da Água/análise , Qualidade da Água , Monitoramento Ambiental/métodos , Criança , Adulto , Método de Monte Carlo , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Água Subterrânea/química , Água Subterrânea/análiseRESUMO
Tracking trajectories of body size in children provides insight into chronic disease risk. One measure of pediatric body size is body mass index (BMI), a function of height and weight. Errors in measuring height or weight may lead to incorrect assessment of BMI. Yet childhood measures of height and weight extracted from electronic medical records often include values which seem biologically implausible in the context of a growth trajectory. Removing biologically implausible values reduces noise in the data, and thus increases the ease of modeling associations between exposures and childhood BMI trajectories, or between childhood BMI trajectories and subsequent health conditions. We developed open-source algorithms (available on github) for detecting and removing biologically implausible values in pediatric trajectories of height and weight. A Monte Carlo simulation experiment compared the sensitivity, specificity and speed of our algorithms to three published algorithms. The comparator algorithms were selected because they used trajectory information, had open-source code, and had published verification studies. Simulation inputs were derived from longitudinal epidemiological cohorts. Our algorithms had higher specificity, with similar sensitivity and speed, when compared to the three published algorithms. The results suggest that our algorithms should be adopted for cleaning longitudinal pediatric growth data.
Assuntos
Algoritmos , Índice de Massa Corporal , Humanos , Criança , Estudos Longitudinais , Estatura , Feminino , Registros Eletrônicos de Saúde , Masculino , Peso Corporal , Pré-Escolar , Método de Monte Carlo , Adolescente , LactenteRESUMO
This research examines the seismic hazard impact on railway infrastructure along the U.S. West Coast (Washington, Oregon and California), using machine learning to explore how measures of seismic hazard such as fault density, earthquake frequency, and ground shaking relate to railway infrastructure accidents. By comparing linear and non-linear models, it finds non-linear approaches superior, particularly noting that higher fault densities and stronger peak ground shaking correlate with increased infrastructure accident rates. Shallow earthquakes with magnitudes of 3.5 or greater and hypocentral depths <20 km also exhibit a pronounced correlation with the incidence of railway infrastructure accidents The study extends to financial impact analysis through Net Present Value and Monte Carlo Simulation, and evaluates damage costs from 2000-2023 to guide financial planning and risk management strategies. It highlights the crucial role of advanced financial tools in optimizing maintenance and long-term planning that could result in better preparedness in high seismic hazard regions and emphasizes the need for robust risk management strategies in enhancing railway operational safety that considers the local and regional tectonic and seismic activity and local ground shaking intensity.
Assuntos
Terremotos , Aprendizado de Máquina , Ferrovias , Ferrovias/economia , Terremotos/economia , California , Humanos , Oregon , Acidentes/economia , Método de Monte CarloRESUMO
Evaluating test-retest reliability is crucial in biomechanical research, as it validates experimental results. While methods for reliability of scalar outcome variables are well-established, methods to assess reliability of continuous curve data (such as joint angle trajectories during gait) remain less explored. This study investigates methods for constructing confidence sets for curve-level intraclass correlation coefficients (ICC), which can be expressed as either an ICC curve or an integrated ICC. Currently, no standardised guidelines exist in biomechanics for reporting curve-level ICC uncertainty. Nonparametric bootstrapping techniques are proposed for both the ICC curve's confidence bands and the integrated ICC's confidence intervals, and these methods are validated through Monte Carlo simulations, covering various effect sizes and curve characteristics. Additionally, these methods are applied to assess the test-retest reliability of knee kinematics in three different planes during landing of one-leg hops, where less uncertainty is observed for the ICC curve and integrated ICC in the frontal plane compared to other planes. When the entire time domain is of primary empirical interest, we recommend using a rank-based bootstrap confidence band to express ICC uncertainty, as it yields increasingly precise and valid results as the number of individuals increases, with the coverage rate approaching the correct level of 95%. When a single summary metric is of primary interest, we recommend using the integrated ICC along with a typical bootstrap confidence interval based on the normal distribution, as the coverage rate remains adequately accurate and stable at around the correct level of 95% across varying number of individuals.
Assuntos
Método de Monte Carlo , Humanos , Fenômenos Biomecânicos , Reprodutibilidade dos Testes , Masculino , Articulação do Joelho/fisiologia , Marcha/fisiologia , Feminino , AdultoRESUMO
Due to rapid urbanization and industrial growth, groundwater globally is continuously deteriorating, posing significant health risks to humans. This study employed a comprehensive methodology to analyze groundwater in the Western Banat Plain (Serbia). Using Piper and Gibbs plots, hydrogeochemistry was assessed, while the entropy-weighted water quality index (EWQI) was used to evaluate groundwater quality. Pollution sources were identified using positive matrix factorization (PMF) accompanied by Pearson correlation and hierarchical cluster analysis, while Monte Carlo simulation assessed health risks associated with groundwater consumption. Results showed that groundwater, mainly Ca-Mg-HCO3 type, is mostly suitable for drinking. Geogenic pollution, agricultural activities, and sewage were major pollution sources. Consumption of contaminated groundwater poses serious non-carcinogenic and carcinogenic health risks. Additionally, arsenic from geogenic source was found to be the main health risks contributor, considering its worryingly elevated concentration, ranging up to 364 µg/L. These findings will be valuable for decision-makers and researchers in managing groundwater vulnerability. PRACTITIONER POINTS: Groundwater is severely contaminated with As in the northern part of the study area. The predominant hydrochemical type of groundwater in the area is Ca-Mg-HCO3. The PMF method apportioned three groundwater pollution sources. Monte Carlo identified rock dissolution as the primary health risk contributor. Health risks and mortality in the study area are positively correlated.
Assuntos
Arsênio , Água Subterrânea , Método de Monte Carlo , Poluentes Químicos da Água , Água Subterrânea/química , Poluentes Químicos da Água/análise , Arsênio/análise , Medição de Risco , Monitoramento Ambiental , HumanosRESUMO
We introduce a new modelling for long-term survival models, assuming that the number of competing causes follows a mixture of Poisson and the Birnbaum-Saunders distribution. In this context, we present some statistical properties of our model and demonstrate that the promotion time model emerges as a limiting case. We delve into detailed discussions of specific models within this class. Notably, we examine the expected number of competing causes, which depends on covariates. This allows for direct modeling of the cure rate as a function of covariates. We present an Expectation-Maximization (EM) algorithm for parameter estimation, to discuss the estimation via maximum likelihood (ML) and provide insights into parameter inference for this model. Additionally, we outline sufficient conditions for ensuring the consistency and asymptotic normal distribution of ML estimators. To evaluate the performance of our estimation method, we conduct a Monte Carlo simulation to provide asymptotic properties and a power study of LR test by contrasting our methodology against the promotion time model. To demonstrate the practical applicability of our model, we apply it to a real medical dataset from a population-based study of incidence of breast cancer in São Paulo, Brazil. Our results illustrate that the proposed model can outperform traditional approaches in terms of model fitting, highlighting its potential utility in real-world scenarios.
Assuntos
Biometria , Neoplasias da Mama , Modelos Estatísticos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Humanos , Biometria/métodos , Feminino , Método de Monte Carlo , Funções Verossimilhança , Análise de Sobrevida , AlgoritmosRESUMO
Time-to-event data are often recorded on a discrete scale with multiple, competing risks as potential causes for the event. In this context, application of continuous survival analysis methods with a single risk suffers from biased estimation. Therefore, we propose the multivariate Bernoulli detector for competing risks with discrete times involving a multivariate change point model on the cause-specific baseline hazards. Through the prior on the number of change points and their location, we impose dependence between change points across risks, as well as allowing for data-driven learning of their number. Then, conditionally on these change points, a multivariate Bernoulli prior is used to infer which risks are involved. Focus of posterior inference is cause-specific hazard rates and dependence across risks. Such dependence is often present due to subject-specific changes across time that affect all risks. Full posterior inference is performed through a tailored local-global Markov chain Monte Carlo (MCMC) algorithm, which exploits a data augmentation trick and MCMC updates from nonconjugate Bayesian nonparametric methods. We illustrate our model in simulations and on ICU data, comparing its performance with existing approaches.
Assuntos
Algoritmos , Teorema de Bayes , Simulação por Computador , Cadeias de Markov , Método de Monte Carlo , Humanos , Análise de Sobrevida , Modelos Estatísticos , Análise Multivariada , Biometria/métodosRESUMO
This study aims to develop a nonparametric mixed exponentially weighted moving average-moving average (NPEWMA-MA) sign control chart for monitoring shifts in process location, particularly when the distribution of a critical quality characteristic is either unknown or non-normal. In literature, the variance expression of the mixed exponentially weighted moving average-moving average (EWMA-MA) statistic is calculated by allowing sequential moving averages to be independent, and thus the exclusion of covariance terms results in an inaccurate variance expression. Furthermore, the effectiveness of the EWMA-MA control chart deteriorates when the distribution of a critical quality characteristic deviates from normality. The proposed NPEWMA-MA sign control chart addresses these by utilizing the corrected variance of the EWMA-MA statistic and incorporating the nonparametric sign test into the EWMA-MA charting structure. The chart integrates the moving average (MA) statistic into the exponentially weighted moving average (EWMA) statistic. The EWMA-MA charting statistic assigns more weight to recent w samples, with weights for previous observations decling exponentially. Monte Carlo simulations assess the chart's performance using various run length (RL) characteristics such as average run length (ARL), standard deviation of run length (SDRL), and median run length (MRL). Additional measures for overall performance include the average extra quadratic loss (AEQL) and relative mean index (RMI). The proposed NPEWMA-MA sign control chart demonstrates superior performance compared to existing nonparametric control charts across different symmetrical and asymmetric distributions. It efficiently detects process shifts, as validated through both a simulated study and a real-life example from a combined cycle power plant.
Assuntos
Método de Monte Carlo , Gases , Modelos Estatísticos , Estatísticas não Paramétricas , Simulação por Computador , AlgoritmosRESUMO
Significance: Questions about the accuracy of pulse oximeters in measuring arterial oxygen saturation ( SpO 2 ) in individuals with darker skin pigmentation have resurfaced since the COVID-19 pandemic. This requires investigation to improve patient safety, clinical decision making, and research. Aim: We aim to use computational modeling to identify the potential causes of inaccuracy in SpO 2 measurement in individuals with dark skin and suggest practical solutions to minimize bias. Approach: An in silico model of the human finger was developed to explore how changing melanin concentration and arterial oxygen saturation ( SaO 2 ) affect pulse oximeter calibration algorithms using the Monte Carlo (MC) technique. The model generates calibration curves for Fitzpatrick skin types I, IV, and VI and an SaO 2 range between 70% and 100% in transmittance mode. SpO 2 was derived by inputting the computed ratio of ratios for light and dark skin into a widely used calibration algorithm equation to calculate bias ( SpO 2 - SaO 2 ). These were validated against an experimental study to suggest the validity of the Monte Carlo model. Further work included applying different multiplication factors to adjust the moderate and dark skin calibration curves relative to light skin. Results: Moderate and dark skin calibration curve equations were different from light skin, suggesting that a single algorithm may not be suitable for all skin types due to the varying behavior of light in different epidermal melanin concentrations, especially at 660 nm. The ratio between the mean bias in White and Black subjects in the cohort study was 6.6 and 5.47 for light and dark skin, respectively, from the Monte Carlo model. A linear multiplication factor of 1.23 and exponential factor of 1.8 were applied to moderate and dark skin calibration curves, resulting in similar alignment. Conclusions: This study underpins the careful re-assessment of pulse oximeter designs to minimize bias in SpO 2 measurements across diverse populations.
Assuntos
Melaninas , Método de Monte Carlo , Oximetria , Pigmentação da Pele , Humanos , Oximetria/métodos , Melaninas/análise , Pigmentação da Pele/fisiologia , Algoritmos , Simulação por Computador , Saturação de Oxigênio/fisiologia , Calibragem , COVID-19 , Oxigênio/sangue , Oxigênio/metabolismo , SARS-CoV-2 , Luz , Pele/química , Pele/irrigação sanguínea , Dedos/irrigação sanguínea , Dedos/fisiologiaRESUMO
Traditional method of determining closure and initiation stress of fractured rocks by analyzing the stress-strain curve has problems such as strong subjectivity and large errors. This study utilized the rock closure stress values and onset stress values determined by three traditional methods, namely, axial strain method, fracture volume method and empirical value taking method, as the base database. The Student t distribution theory was used to obtain a confidence interval based on its overall distribution of values and to achieve a combination of the advantages of multiple methods. Within confidence interval, the Monte Carlo stochastic simulation was used to determine the convergence interval of the second stage to further improve the accuracy. Finally, mean value of the randomly sampled values after reaching the convergence stage was taken as the probability value of rock closure and crack initiation stress. The results showed that the 3 traditional methods for calculating rock closure and initiation stresses are significantly different. In contrast, the proposed method biases more towards multi-numerical distribution intervals and also considers the preference effects of different calculation methods. In addition, this method does not show any extreme values that deviate from the confidence intervals, and it has strong accuracy and stability compared to other methods.
Assuntos
Método de Monte Carlo , Estresse Mecânico , Simulação por Computador , Modelos TeóricosRESUMO
Interrupted time series (ITS) designs are increasingly used for estimating the effect of shocks in natural experiments. Currently, ITS designs are often used in scenarios with many time points and simple data structures. This research investigates the performance of ITS designs when the number of time points is limited and with complex data structures. Using a Monte Carlo simulation study, we empirically derive the performance-in terms of power, bias and precision- of the ITS design. Scenarios are considered with multiple interventions, a low number of time points and different effect sizes based on a motivating example of the learning loss due to COVID school closures. The results of the simulation study show the power of the step change depends mostly on the sample size, while the power of the slope change depends on the number of time points. In the basic scenario, with both a step and a slope change and an effect size of 30% of the pre-intervention slope, the required sample size for detecting a step change is 1,100 with a minimum of twelve time points. For detecting a slope change the required sample size decreases to 500 with eight time points. To decide if there is enough power researchers should inspect their data, hypothesize about effect sizes and consider an appropriate model before applying an ITS design to their research. This paper contributes to the field of methodology in two ways. Firstly, the motivation example showcases the difficulty of employing ITS designs in cases which do not adhere to a single intervention. Secondly, models are proposed for more difficult ITS designs and their performance is tested.
Assuntos
COVID-19 , Análise de Séries Temporais Interrompida , Método de Monte Carlo , Pandemias , Instituições Acadêmicas , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , SARS-CoV-2/isolamento & purificação , Aprendizagem , Simulação por Computador , Tamanho da AmostraRESUMO
Early use of targeted radionuclide therapy (TRT) to eradicate disseminated tumor cells (DTCs) might offer cure. Selection of appropriate radionuclides is required. This work highlights the potential of 103Pd (T1/2 = 16.991 d) which decays to 103mRh (T1/2 = 56.12 min) then to stable 103Rh with emission of Auger and conversion electrons. Methods: The Monte Carlo track structure code CELLDOSE was used to assess absorbed doses in single cells (14-µm diameter; 10-µm nucleus) and clusters of 19 cells. The radionuclide was distributed on the cell surface, within the cytoplasm, or in the nucleus. Absorbed doses from 103Pd, 177Lu and 161Tb were compared after energy normalization. The impact of non-uniform cell targeting, and the potential benefit from dual-targeting was investigated. Additional results related to 103mRh, if used directly, are provided. Results: In the single cell, and depending on radionuclide distribution, 103Pd delivered 7- to 10-fold higher nuclear absorbed dose and 9- to 25-fold higher membrane dose than 177Lu. In the 19-cell clusters, 103Pd absorbed doses also largely exceeded 177Lu. In both situations, 161Tb stood in-between 103Pd and 177Lu. Non-uniform targeting, considering four unlabeled cells within the cluster, resulted in moderate-to-severe dose heterogeneity. For example, with intranuclear 103Pd, unlabeled cells received only 14% of the expected nuclear dose. Targeting with two 103Pd-labeled radiopharmaceuticals minimized dose heterogeneity. Conclusion: 103Pd, a next-generation Auger emitter, can deliver substantially higher absorbed doses than 177Lu to single tumor cells and cell clusters. This may open new horizons for the use of TRT in adjuvant or neoadjuvant settings, or for targeting minimal residual disease.
Assuntos
Paládio , Radioisótopos , Paládio/química , Paládio/uso terapêutico , Paládio/administração & dosagem , Radioisótopos/uso terapêutico , Radioisótopos/farmacocinética , Humanos , Lutécio/uso terapêutico , Método de Monte Carlo , Neoplasias/radioterapiaRESUMO
When large-scale electric vehicles are connected to the grid for unordered charging, it will seriously affect the stability and security of the power system. To solve this problem, this paper proposes a regional power network optimization scheduling method considering vehicle network interaction. Initially, based on the user behavior characteristics and charging and discharging characteristics of electric vehicles, a charging and discharging behavior model of electric vehicles was established. Based on the Monte Carlo sampling algorithm, the scheduling upper and lower limits of each scheduling cycle of electric vehicles were described, and the scheduling potential of each scheduling cycle of electric vehicles was obtained. Then, the electricity price is then used as an incentive parameter to guide EV users to charge during periods of low electricity prices and participate in discharge during periods of peak electricity prices. Aiming at the highest economic efficiency, the best consumption effect of new energy and the smoothest demand-side power curve of regional power grid, a three-objective optimal dispatching model was established. In the later stage, uncertainty factors are taken into consideration by introducing the concept of interval numbers, and an interval multi-objective optimization dispatching model is established. The two dispatching models are solved by NSGA-II algorithm and improved NSGA-II algorithm, and the Pareto solution set is obtained. Finally, based on the analytic Hierarchy Process (AHP), the optimal scheduling scheme is determined. The Monte Carlo sampling method is used to simulate the user side charging demand, and the effectiveness of this method is verified. In addition, the results of the interval multi-objective optimization model and the deterministic multi-objective optimization model are compared, and it is proved that the solution results of the interval multi-objective model are more adaptive, practical and robust to the uncertain factors.
Assuntos
Algoritmos , Método de Monte Carlo , Eletricidade , Modelos Teóricos , Fontes de Energia ElétricaRESUMO
Classification of gene trees is an important task both in the analysis of multi-locus phylogenetic data, and assessment of the convergence of Markov Chain Monte Carlo (MCMC) analyses used in Bayesian phylogenetic tree reconstruction. The logistic regression model is one of the most popular classification models in statistical learning, thanks to its computational speed and interpretability. However, it is not appropriate to directly apply the standard logistic regression model to a set of phylogenetic trees, as the space of phylogenetic trees is non-Euclidean and thus contradicts the standard assumptions on covariates. It is well-known in tropical geometry and phylogenetics that the space of phylogenetic trees is a tropical linear space in terms of the max-plus algebra. Therefore, in this paper, we propose an analogue approach of the logistic regression model in the setting of tropical geometry. Our proposed method outperforms classical logistic regression in terms of Area under the ROC Curve in numerical examples, including with data generated by the multi-species coalescent model. Theoretical properties such as statistical consistency have been proved and generalization error rates have been derived. Finally, our classification algorithm is proposed as an MCMC convergence criterion for Mr Bayes. Unlike the convergence metric used by Mr Bayes which is only dependent on tree topologies, our method is sensitive to branch lengths and therefore provides a more robust metric for convergence. In a test case, it is illustrated that the tropical logistic regression can differentiate between two independently run MCMC chains, even when the standard metric cannot.
Assuntos
Algoritmos , Teorema de Bayes , Cadeias de Markov , Conceitos Matemáticos , Modelos Genéticos , Método de Monte Carlo , Filogenia , Modelos Logísticos , Curva ROC , Simulação por ComputadorRESUMO
Uncovering acquired drug resistance mechanisms has garnered considerable attention as drug resistance leads to treatment failure and death in patients with cancer. Although several bioinformatics studies developed various computational methodologies to uncover the drug resistance mechanisms in cancer chemotherapy, most studies were based on individual or differential gene expression analysis. However the single gene-based analysis is not enough, because perturbations in complex molecular networks are involved in anti-cancer drug resistance mechanisms. The main goal of this study is to reveal crucial molecular interplay that plays key roles in mechanism underlying acquired gastric cancer drug resistance. To uncover the mechanism and molecular characteristics of drug resistance, we propose a novel computational strategy that identified the differentially regulated gene networks. Our method measures dissimilarity of networks based on the eigenvalues of the Laplacian matrix. Especially, our strategy determined the networks' eigenstructure based on sparse eigen loadings, thus, the only crucial features to describe the graph structure are involved in the eigenanalysis without noise disturbance. We incorporated the network biology knowledge into eigenanalysis based on the network-constrained regularization. Therefore, we can achieve a biologically reliable interpretation of the differentially regulated gene network identification. Monte Carlo simulations show the outstanding performances of the proposed methodology for differentially regulated gene network identification. We applied our strategy to gastric cancer drug-resistant-specific molecular interplays and related markers. The identified drug resistance markers are verified through the literature. Our results suggest that the suppression and/or induction of COL4A1, PXDN and TGFBI and their molecular interplays enriched in the Extracellular-related pathways may provide crucial clues to enhance the chemosensitivity of gastric cancer. The developed strategy will be a useful tool to identify phenotype-specific molecular characteristics that can provide essential clues to uncover the complex cancer mechanism.