Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).

Research status and prospects of the fractal analysis of metal material surfaces and interfaces

As a mathematical analysis method,fractal analysis can be used to quantitatively describe irregular shapes with self-similar or self-affine properties.Fractal analysis has been used to characterize the shapes of metal materials at various scales and dimensions.Conventional methods make it difficult to quantitatively describe the relationship between the regular characteristics and properties of metal material surfaces and interfaces.However,fractal analysis can be used to quantitatively describe the shape characteristics of metal materials and to establish the quantitative relationships between the shape characteristics and various properties of metal materials.From the perspective of two-dimensional planes and three-dimensional curved surfaces,this paper reviews the current research status of the fractal analysis of metal precipitate interfaces,metal grain boundary interfaces,metal-deposited film surfaces,metal fracture surfaces,metal machined surfaces,and metal wear surfaces.The relationship between the fractal dimensions and properties of metal material surfaces and interfaces is summarized.Starting from three perspectives of fractal analysis,namely,research scope,image acquisition methods,and calculation methods,this paper identifies the direction of research on fractal analysis of metal material surfaces and interfaces that need to be developed.It is believed that revealing the deep influence mechanism between the fractal dimensions and properties of metal material surfaces and interfaces will be the key research direction of the fractal analysis of metal materials in the future.

A method for establishing a bearing residual life prediction model for process enhancement equipment based on rotor imbalance response analysis

A rotating packed bed is a typical chemical process enhancement equipment that can strengthen micromixing and mass transfer.During the operation of the rotating packed bed,the nonreactants and products irregularly adhere to the wire mesh packing in the rotor,thus resulting in an imbalance in the vibration of the rotor,which may cause serious damage to the bearing and material leakage.This study proposes a model prediction for estimating the bearing residual life of a rotating packed bed based on rotor imbalance response analysis.This method is used to determine the influence of the mass on the imbalance in the vibration of the rotor on bearing damage.The major influence on rotor vibration was found to be exerted by the imbalanced mass and its distribution radius,as revealed by the results of orthogonal experiments.Through implementing finite element analysis,the imbalance response curve for the rotating packed bed rotor was obtained,and a correlation among rotor imbalance mass,distribution radius of imbalance mass,and bearing residue life was established via data fitting.The predicted value of the bearing life can be used as the reference basis for an early safety warning of a rotating packed bed to effectively avoid accidents.

Seismic response and correlation analysis of a pile-supported wharf to near-fault pulse-like ground motions

Earthquake investigations have shown that near-fault pulse-like(NF-P)ground motions have unique characteristics compared to near-fault non-pulse-like(NF-NP)and far-field(FF)ground motions.It is necessary to study the seismic response of pile-supported wharf(PSW)structures under NF-P ground motions.In this study,a three-dimensional finite element numerical model is created to simulate a PSW.By imparting three types of ground motion,the engineering demand parameters(EDPs)of PSW under NF-P ground motions were analyzed and compared,in which EDPs are the maximum displacement and bending moment of the piles.Twenty intensity measures(IMs)were selected to characterize the properties of ground motions.The correlation between IMs and EDPs was explored.The results show that the piles present larger displacement and bending moment under NF-P ground motions compared to NF-NP and FF ground motions.None of the IMs have a high correlation with EDPs under NF-P ground motions,and these IMs are more applicable to FF ground motions.The correlation coefficients between EDPs and IMs under three types of ground motion were obtained,which will provide a valuable reference for the seismic design of PSWs.

Zonal Coupling Analysis Method of Seismic Response of Offshore Monopile Wind Turbine

The seismic safety of offshore wind turbines is an important issue that needs to be solved urgently.Based on a unified computing framework,this paper develops a set of seawater-seabed-wind turbine zoning coupling analysis methods.A 5 MW wind turbine and a site analysis model are established,and a seismic wave is selected to analyze the changes in the seismic response of offshore monopile wind turbines under the change of seawater depth,seabed wave velocity and seismic wave incidence angle.The analysis results show that when the seawater increases to a certain depth,the seismic response of the wind turbine increases.The shear wave velocity of the seabed affects the bending moment and displacement at the bottom of the tower.When the angle of incidence increases,the vertical displacement and the acceleration of the top of the tower increase in varying degrees.

Multilevel analysis of the central-peripheral-target organ pathway:contributing to recovery after peripheral nerve injury

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

Comparative analysis of thermodynamic and mechanical responses between underground hydrogen storage and compressed air energy storage in lined rock caverns

Underground hydrogen storage(UHS)and compressed air energy storage(CAES)are two viable largescale energy storage technologies for mitigating the intermittency of wind and solar power.Therefore,it is meaningful to compare the properties of hydrogen and air with typical thermodynamic storage processes.This study employs a multi-physical coupling model to compare the operations of CAES and UHS,integrating gas thermodynamics within caverns,thermal conduction,and mechanical deformation around rock caverns.Gas thermodynamic responses are validated using additional simulations and the field test data.Temperature and pressure variations of air and hydrogen within rock caverns exhibit similarities under both adiabatic and diabatic simulation modes.Hydrogen reaches higher temperature and pressure following gas charging stage compared to air,and the ideal gas assumption may lead to overestimation of gas temperature and pressure.Unlike steel lining of CAES,the sealing layer(fibre-reinforced plastic FRP)in UHS is prone to deformation but can effectively mitigates stress in the sealing layer.In CAES,the first principal stress on the surface of the sealing layer and concrete lining is tensile stress,whereas UHS exhibits compressive stress in the same areas.Our present research can provide references for the selection of energy storage methods.

Molecular cloning,characterization and promoter analysis of LbgCWIN1 and its expression profiles in response to exogenous sucrose during in vitro bulblet initiation in lily

Lily(Lilium spp.) is an important ornamental flower, which is mainly propagated by bulbs. Cell wall invertases(CWINs), which catalyze the irreversibly conversion of sucrose into glucose and fructose in the extracellular space, are key enzymes participating in sucrose allocation in higher plants. Previous studies have shown that CWINs play an essential role in bulblet initiation process in bulbous crops, but the underlying molecular mechanism remains unclear. Here, a CWIN gene of Lilium brownii var. giganteum(Lbg) was identified and amplified from genomic DNA. Quantitative RT-PCR assays revealed that the expression level of LbgCWIN1 was highly upregulated exactly when the endogenous starch degraded in non-sucrose medium during in vitro bulblet initiation in Lbg. Phylogenetic relationship, motif, and domain analysis of LbgCWIN1 protein and CWINs in other plant species showed that all sequences of these CWIN proteins were highly conserved. The promoter sequence of LbgCWIN1 possessed a number of alpha-amylase-, phytohormone-, light-and stress-responsive cis-elements. Meanwhile, β-glucuronidase(GUS) assay showed that the 459 bp upstream fragment from the translational start site displayed maximal promoter activity. These results revealed that LbgCWIN1 might function in the process of in vitro bulblet initiation and be in the response to degradation of endogenous starch.

Comparative transcriptome analysis reveals key genes and pathways in response to Alternaria alternata apple pathotype infection

Apple leaf spot,caused by the Alternaria alternata apple pathotype(AAAP),is an important fungal disease of apple.To understand the molecular basis of resistance and pathogenesis in apple leaf spot,the transcriptomes of two apple cultivars‘Hanfu'(HF)(resistant)and‘Golden Delicious'(GD)(susceptible)were analyzed at 0,6,18,24 and 48 h after AAAP inoculation by RNA-Seq.At each time point,a large number of significantly differentially expressed genes(DEGs)were screened between AAAP-inoculated and uninoculated apple leaves.Analysis of the common DEGs at four time points revealed significant differences in the resistance of‘HF'and‘GD'apple to AAAP infection.RLP,RNL,and JA signal-related genes were upregulated in both cultivars to restrict AAAP development.However,genes encoding CNLs,TNLs,WRKYs,and AP2s were only activated in‘HF'as part of the resistance response,of which,some play major roles in the regulation of ET and SA signal transduction.Further analysis showed that many DEGs with opposite expression trends in the two hosts may play important regulatory roles in response to AAAP infection.Transient expression of one such gene MdERF110 in‘GD'apple leaves improved AAAP resistance.Collectively,this study highlights the reasons for differential resistance to AAAP infection between‘HF'and‘GD'apples which can theoretically assist the molecular breeding of disease-resistant apple crops.

Micro defects formation and dynamic response analysis of steel plate of quasi-cracking area subjected to explosive load

As the protective component,steel plate had attracted extensive attention because of frequently threats of explosive loads.In this paper,the evolution of microstructure and the mechanism of damage in the quasi-cracking area of steel plate subjected to explosive load were discussed and the relationships between micro defects and dynamic mechanical response were revealed.After the explosion experiment,five observation points were selected equidistant from the quasi-cracking area of the section of the steel plate along the thickness direction,and the characteristics of micro defects at the observation points were analyzed by optical microscope(OM),scanning electron microscope(SEM) and electron backscattered diffraction(EBSD).The observation result shows that many slip bands(SBs) appeared,and the grain orientation changed obviously in the steel plate,the two were the main damage types of micro defects.In addition,cracks,peeling pits,grooves and other lager micro defects were appeared in the lower area of the plate.The stress parameters of the observation points were obtained through an effective numerical model.The mechanism of damage generation and crack propagation in the quasicracking area were clarified by comparing the specific impulse of each observation point with the corresponding micro defects.The result shows that the generation and expansion of micro defects are related to the stress area(i.e.the upper compression area,the neutral plane area,and the lower tension area).The micro defects gather and expand at the grain boundary,and will become macroscopic damage under the continuous action of tensile stress.Besides,the micro defects at the midpoint of the section of the steel plate in the direction away from the explosion center(i.e.the horizontal direction) were also studied.It was found that the specific impulse at these positions were much smaller than that in the thickness direction,the micro defects were only SBs and a few micro cracks,and the those decreased with the increase of the distance from the explosion center.

Improved Responses with Multitaper Spectral Analysis for Magnetotelluric Time Series Data Processing:Examples from Field Data

In order to attain good quality transfer function estimates from magnetotelluric field data(i.e.,smooth behavior and small uncertainties across all frequencies),we compare time series data processing with and without a multitaper approach for spectral estimation.There are several common ways to increase the reliability of the Fourier spectral estimation from experimental(noisy)data;for example to subdivide the experimental time series into segments,taper these segments(using single taper),perform the Fourier transform of the individual segments,and average the resulting spectra.

Systemic inflammatory response index is a predictor of prognosis in gastric cancer patients: Retrospective cohort and meta-analysis

BACKGROUND The systemic inflammatory response index(SIRI)has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms.However,research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer sur-gery.AIM To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients,who received robotic radical gastric cancer surgery.METHODS Initially,an exhaustive retrieval was performed in the PubMed,the Cochrane Library,EMBASE,Web of Science,and Scopus databases to identify relevant studies.Subsequently,a meta-analysis was executed on 6 cohort studies iden-tifying the value of the SIRI in assessing the survival of gastric cancer patients.Additionally,the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators.The association between preoperative SIRI levels and 5-year overall survival(OS)and disease-free survival(DFS)was assessed.RESULTS The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer.Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer.SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities,T-stage,carcinoembryonic antigen levels,the development of early serious postoperative complications,and the rate of lymph node metastasis.CONCLUSION SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.

Microscopic defects formation and dynamic mechanical response analysis of Q345 steel plate subjected to explosive load

As the basic protective element, steel plate had attracted world-wide attention because of frequent threats of explosive loads. This paper reports the relationships between microscopic defects of Q345 steel plate under the explosive load and its macroscopic dynamics simulation. Firstly, the defect characteristics of the steel plate were investigated by stereoscopic microscope(SM) and scanning electron microscope(SEM). At the macroscopic level, the defect was the formation of cave which was concentrated in the range of 0-3.0 cm from the explosion center, while at the microscopic level, the cavity and void formation were the typical damage characteristics. It also explains that the difference in defect morphology at different positions was the combining results of high temperature and high pressure. Secondly, the variation rules of mechanical properties of steel plate under explosive load were studied. The Arbitrary Lagrange-Euler(ALE) algorithm and multi-material fluid-structure coupling method were used to simulate the explosion process of steel plate. The accuracy of the method was verified by comparing the deformation of the simulation results with the experimental results, the pressure and stress at different positions on the surface of the steel plate were obtained. The simulation results indicated that the critical pressure causing the plate defects may be approximately 2.01 GPa. On this basis, it was found that the variation rules of surface pressure and microscopic defect area of the Q345 steel plate were strikingly similar, and the corresponding mathematical relationship between them was established. Compared with Monomolecular growth fitting models(MGFM) and Logistic fitting models(LFM), the relationship can be better expressed by cubic polynomial fitting model(CPFM). This paper illustrated that the explosive defect characteristics of metal plate at the microscopic level can be explored by analyzing its macroscopic dynamic mechanical response.

Aero-Hydro-Elastic-Servo Modeling and Dynamic Response Analysis of A Monopile Offshore Wind Turbine Under Different Operating Scenarios

This paper constructs a coupled aero-hydro-elastic-servo simulation framework for a monopile offshore wind turbine(OWT).In this framework,a detailed multi-body dynamics model of the monopile OWT including the gearbox,blades,tower and other components(nacelle,hub,bedplate,etc.)has been explicitly established.The effects of pile−soil interaction,controller and operational conditions on the turbine dynamic responses are studied systematically in time domain and frequency domain.The results show that(1)a comprehensive drivetrain model has the capability to provide a more precise representation of the complex dynamic characteristics exhibited by drivetrain components,which can be used as the basis for further study on the dynamic characteristics of the drivetrain.(2)The pile−soil interaction can influence the wind turbine dynamic responses,particularly under the parked condition.(3)The effect of the pile−soil interaction on tower responses is more significant than that on blade responses.(4)The use of the controller can substantially affect the rotor characteristics,which in turn influences the turbine dynamic responses.(5)The tower and blade displacements under the operational condition are much larger than those under the parked condition.The model and methodology presented in this study demonstrate potential for examining complex dynamic behaviors of the monopile OWTs.To ensure accuracy and precision,it is imperative to construct a detailed model of the wind turbine system,while also taking into account simulation efficiency.

Analysis of pressure response at an observation well against pressure build-up by early stage of CO_(2)geological storage project

To ensure a safe and stable CO_(2)storage,pressure responses at an observation well are expected to be an important and useful field monitoring item to estimate the CO_(2)storage behaviors and the aquifer parameters during and after injecting CO_(2),because it can detect whether the injected CO_(2)leaks to the ground surface or the bottom of the sea.In this study,pressure responses were simulated to present design factors such as well location and pressure transmitter of the observation well.Numerical simulations on the pressure response and the time-delay from pressure build-up after CO_(2)injection were conducted by considering aquifer parameters and distance from the CO_(2)injection well to an observation well.The measurement resolution of a pressure transmitter installed in the observation well was presented based on numerical simulation results of the pressure response against pressure build-up at the injection well and CO_(2)plume front propagations.Furthermore,the pressure response at an observation well was estimated by comparing the numerical simulation results with the curve of CO_(2)saturation and relative permeability.It was also suggested that the analytical solution can be used for the analysis of the pressure response tendency using pressure build-up and dimensionless parameters of hydraulic diffusivity.Thus,a criterion was established for selecting a pressure transducer installed at an observation well to monitor the pressure responses with sufficient accuracy and resolution,considering the distance from the injection well and the pressure build-up at the injection well,for future carbon capture and storage(CCS)projects.

Predictive value of tumor-infiltrating lymphocytes for neoadjuvant therapy response in triple-negative breast cancer: A systematic review and meta-analysis

BACKGROUND The association between tumor-infiltrating lymphocyte(TIL)levels and the res-ponse to neoadjuvant therapy(NAT)in patients with triple-negative breast cancer(TNBC)remains unclear.AIM To investigate the predictive potential of TIL levels for the response to NAT in TNBC patients.METHODS A systematic search of the National Center for Biotechnology Information PubMed database was performed to collect relevant published literature prior to August 31,2023.The correlation between TIL levels and the NAT pathologic com-plete response(pCR)in TNBC patients was assessed using a systematic review and meta-analysis.Subgroup analysis,sensitivity analysis,and publication bias analysis were also conducted.RESULTS A total of 32 studies were included in this meta-analysis.The overall meta-ana-lysis results indicated that the pCR rate after NAT treatment in TNBC patients in the high TIL subgroup was significantly greater than that in patients in the low TIL subgroup(48.0%vs 27.7%)(risk ratio 2.01;95%confidence interval 1.77-2.29;P<0.001,I2=56%).Subgroup analysis revealed that the between-study hetero-geneity originated from differences in study design,TIL level cutoffs,and study populations.Publication bias could have existed in the included studies.The meta-analysis based on different NAT protocols revealed that all TNBC patients with high levels of TILs had a greater rate of pCR after NAT treatment in all protocols(all P≤0.01),and there was no significant between-protocol difference in the statistics among the different NAT protocols(P=0.29).Additionally,sensitivity analysis demonstrated that the overall results of the meta-analysis remained consistent when the included studies were individually excluded.CONCLUSION TILs can serve as a predictor of the response to NAT treatment in TNBC patients.TNBC patients with high levels of TILs exhibit a greater NAT pCR rate than those with low levels of TILs,and this predictive capability is con-sistent across different NAT regimens.

Systematic analysis of corporate environmental responsibility:elements,structure,function,and principles

Corporate Environmental Responsibility(CER) is the subsystem of Corporate Social Responsibility(CSR),which continues to increase prominence in the global economy.Nowadays,CER becomes more important in corporate sustainable development.Based on Carroll's pyramid mode of CSR,this article explores the systematic feature of CER.From a systematic perspective,it sorts out its elements,structure,function,and principles of CER.And the four levels of economic,legal,ethical,and charitable structure are emphasized.With these considerations interpreted into practice,success will be achieved in potential cost savings,technological innovation,increased public acceptance,and better relations with governments.

Analysis of Factors Related to Vasovagal Response in Apheresis Blood Donors and the Establishment of Prediction Model Based on BP Neural Network Algorithm

Objective:To analyze the factors related to vessel vasovagal reaction(VVR)in apheresis donors,establish a mathematical model for predicting the correlation factors and occurrence risk,and use the prediction model to intervene in high-risk VVR blood donors,improve the blood donation experience,and retain blood donors.Methods:A total of 316 blood donors from the Xi'an Central Blood Bank from June to September 2022 were selected to statistically analyze VVR-related factors.A BP neural network prediction model is established with relevant factors as input and DRVR risk as output.Results:First-time blood donors had a high risk of VVR,female risk was high,and sex difference was significant(P value<0.05).The blood pressure before donation and intergroup differences were also significant(P value<0.05).After training,the established BP neural network model has a minimum RMS error of o.116,a correlation coefficient R=0.75,and a test model accuracy of 66.7%.Conclusion:First-time blood donors,women,and relatively low blood pressure are all high-risk groups for VVR.The BP neural network prediction model established in this paper has certain prediction accuracy and can be used as a means to evaluate the risk degree of clinical blood donors.

Analysis and Response of Steel Stacking Accidents in Hot Rolling Coilers

Through long-term production and maintenance practice,various types of stacking steel in the 2250mm hot rolling coiler of Ma Steel were tracked and analyzed,and the causes of stacking steel were summarized.Cor-responding measures were formulated to effectively reduce the probability of stacking steel.

MAPOD Analysis in Eddy Current Testing of Flaws Considering Multiple Response Signals and Multiple Flaw Parameters

The reliability of the eddy current testing (ECT) in flaw detection is quantitatively evaluated by theprobability of detection (POD). Precise and efficient modeling of POD gives direction for the implement of ECTon sites to avoid false or missing flaw detection. Traditional POD analysis focuses on single uncertain factor orsingle response signal with limited credibility in engineering. This paper considers multiple response signals andmultiple flaw parameters to perform POD. The flaw length, the flaw depth, the coil impedance, and the magneticflux density are comprehensively studied under various lift-off distances. A finite element model (FEM) of ECT isestablished and verified with experiments to obtain sufficient simulation data for discrete POD modeling. Thecontinuous POD function is then fitted based on the discrete values to show the superiority of integrating multiplefactors. A comparison with conventional POD analysis further demonstrates the higher reliability of ECT flawdetection considering multiple flaw parameters and multiple response signals, especially for small flaws.