A prediction method for the individual serum concentration and therapeutic effect for optimizing adalimumab therapy in inflammatory bowel disease.

OBJECTIVES: Adalimumab (ADM) therapy is effective for inflammatory bowel disease (IBD), but a significant number of IBD patients lose response to ADM. Thus, it is crucial to devise methods to enhance ADM's effectiveness. This study introduces a strategy to predict individual serum concentrations and therapeutic effects to optimize ADM therapy for IBD during the induction phase. METHODS: We predicted the individual serum concentration and therapeutic effect of ADM during the induction phase based on pharmacokinetic and pharmacodynamic (PK/PD) parameters calculated using the empirical Bayesian method. We then examined whether the predicted therapeutic effect, defined as clinical remission or treatment failure, matched the observed effect. RESULTS: Data were obtained from 11 IBD patients. The therapeutic effect during maintenance therapy was successfully predicted at 40 of 47 time points. Moreover, the predicted effects at each patient's final time point matched the observed effects in 9 of the 11 patients. CONCLUSION: This is the inaugural report predicting the individual serum concentration and therapeutic effect of ADM using the Bayesian method and PK/PD modelling during the induction phase. This strategy may aid in optimizing ADM therapy for IBD.

The effectiveness of problem-based learning and case-based learning teaching methods in clinical practical teaching in TACE treatment for hepatocellular carcinoma in China: a bayesian network meta-analysis.

PURPOSE: To investigate the effectiveness of problem-based learning (PBL) and case-based learning (CBL) teaching methods in clinical practical teaching in transarterial chemoembolization (TACE) treatment in China. MATERIALS AND METHODS: A comprehensive search of PubMed, the Chinese National Knowledge Infrastructure (CNKI) database, the Weipu database and the Wanfang database up to June 2023 was performed to collect studies that evaluate the effectiveness of problem-based learning and case-based learning teaching methods in clinical practical teaching in TACE treatment in China. Statistical analysis was performed by R software (4.2.1) calling JAGS software (4.3.1) in a Bayesian framework using the Markov chain-Monte Carlo method for direct and indirect comparisons. The R packages "gemtc", "rjags", "openxlsx", and "ggplot2" were used for statistical analysis and data output. RESULTS: Finally, 7 studies (five RCTs and two observational studies) were included in the meta-analysis. The combination of PBL and CBL showed more effectiveness in clinical thinking capacity, clinical practice capacity, knowledge understanding degree, literature reading ability, method satisfaction degree, learning efficiency, learning interest, practical skills examination scores and theoretical knowledge examination scores. CONCLUSIONS: Network meta-analysis revealed that the application of PBL combined with the CBL teaching mode in the teaching of liver cancer intervention therapy significantly improves the teaching effect and significantly improves the theoretical and surgical operations, meeting the requirements of clinical education.

Common Methods for Phylogenetic Tree Construction and Their Implementation in R.

A phylogenetic tree can reflect the evolutionary relationships between species or gene families, and they play a critical role in modern biological research. In this review, we summarize common methods for constructing phylogenetic trees, including distance methods, maximum parsimony, maximum likelihood, Bayesian inference, and tree-integration methods (supermatrix and supertree). Here we discuss the advantages, shortcomings, and applications of each method and offer relevant codes to construct phylogenetic trees from molecular data using packages and algorithms in R. This review aims to provide comprehensive guidance and reference for researchers seeking to construct phylogenetic trees while also promoting further development and innovation in this field. By offering a clear and concise overview of the different methods available, we hope to enable researchers to select the most appropriate approach for their specific research questions and datasets.

Order selection for heterogeneous semiparametric hidden Markov models.

Hidden Markov models (HMMs), which can characterize dynamic heterogeneity, are valuable tools for analyzing longitudinal data. The order of HMMs (ie, the number of hidden states) is typically assumed to be known or predetermined by some model selection criterion in conventional analysis. As prior information about the order frequently lacks, pairwise comparisons under criterion-based methods become computationally expensive with the model space growing. A few studies have conducted order selection and parameter estimation simultaneously, but they only considered homogeneous parametric instances. This study proposes a Bayesian double penalization (BDP) procedure for simultaneous order selection and parameter estimation of heterogeneous semiparametric HMMs. To overcome the difficulties in updating the order, we create a brand-new Markov chain Monte Carlo algorithm coupled with an effective adjust-bound reversible jump strategy. Simulation results reveal that the proposed BDP procedure performs well in estimation and works noticeably better than the conventional criterion-based approaches. Application of the suggested method to the Alzheimer's Disease Neuroimaging Initiative research further supports its usefulness.

A non-negative spike-and-slab lasso generalized linear stacking prediction modeling method for high-dimensional omics data.

BACKGROUND: High-dimensional omics data are increasingly utilized in clinical and public health research for disease risk prediction. Many previous sparse methods have been proposed that using prior knowledge, e.g., biological group structure information, to guide the model-building process. However, these methods are still based on a single model, offen leading to overconfident inferences and inferior generalization. RESULTS: We proposed a novel stacking strategy based on a non-negative spike-and-slab Lasso (nsslasso) generalized linear model (GLM) for disease risk prediction in the context of high-dimensional omics data. Briefly, we used prior biological knowledge to segment omics data into a set of sub-data. Each sub-model was trained separately using the features from the group via a proper base learner. Then, the predictions of sub-models were ensembled by a super learner using nsslasso GLM. The proposed method was compared to several competitors, such as the Lasso, grlasso, and gsslasso, using simulated data and two open-access breast cancer data. As a result, the proposed method showed robustly superior prediction performance to the optimal single-model method in high-noise simulated data and real-world data. Furthermore, compared to the traditional stacking method, the proposed nsslasso stacking method can efficiently handle redundant sub-models and identify important sub-models. CONCLUSIONS: The proposed nsslasso method demonstrated favorable predictive accuracy, stability, and biological interpretability. Additionally, the proposed method can also be used to detect new biomarkers and key group structures.

Linking Acrosome Size and Genetic Divergence in an Inter-Oceanic Mussel from the Pacific and Atlantic Coasts: A Case of Incipient Speciation?

In recent years, advances in analyses of the sperm morphology and genetics of Perumytilus purpuratus have allowed to two evolutionary scenarios for this mussel to be suggested: (1) the scenario of cryptic species and (2) the scenario of incipient or in progress speciation. For a better understanding of the evolutionary history of P. purpuratus, we performed extensive sampling along a latitudinal gradient of ca. 7180 km of coastline-from the Southern Pacific Ocean to the Atlantic Ocean-and we delved deeper into the sperm morphology of P. purpuratus, exploring its association with the phylogeny and population genetics to determine whether the variability in sperm traits between the northern and southern regions was a signal of cryptic or incipient species. Overall, our results showed that sperm sizes were strongly correlated with the genetic structure in males of P. purpuratus. We identified at 37° S on the Pacific coast a coincident break of both sperm size and genetic disruption that can be explained by historical events and postglacial recolonization as causal phenomena for the observed divergences. Furthermore, evidence of genetic admixture between lineages was found at 38° S, suggesting the presence of an introgressive hybridization zone and incomplete reproductive isolation in an in fraganti or incipient speciation process.

Seamless Micro-Electro-Mechanical System-Inertial Navigation System/Polarization Compass Navigation Method with Data and Model Dual-Driven Approach.

The integration of micro-electro-mechanical system-inertial navigation systems (MEMS-INSs) with other autonomous navigation sensors, such as polarization compasses (PCs) and geomagnetic compasses, has been widely used to improve the navigation accuracy and reliability of vehicles in Internet of Things (IoT) applications. However, a MEMS-INS/PC integrated navigation system suffers from cumulative errors and time-varying measurement noise covariance in unknown, complex occlusion, and dynamic environments. To overcome these problems and improve the integrated navigation system's performance, a dual data- and model-driven MEMS-INS/PC seamless navigation method is proposed. This system uses a nonlinear autoregressive neural network (NARX) based on the Gauss-Newton Bayesian regularization training algorithm to model the relationship between the MEMS-INS outputs composed of the specific force and angular velocity data and the PC heading's angular increment, and to fit the integrated navigation system's dynamic characteristics, thus realizing data-driven operation. In the model-driven part, a nonlinear MEMS-INS/PC loosely coupled navigation model is established, the variational Bayesian method is used to estimate the time-varying measurement noise covariance, and the cubature Kalman filter method is then used to solve the nonlinear problem in the model. The robustness and effectiveness of the proposed method are verified experimentally. The experimental results show that the proposed method can provide high-precision heading information stably in complex, occluded, and dynamic environments.

Active case-finding of tuberculosis compared with symptom-driven standard of care: a modelling analysis.

BACKGROUND: In settings with large case detection gaps, active case-finding (ACF) may play a critical role in the uberculosis (TB) response. However, ACF is resource intensive, and its effectiveness depends on whether people detected with TB through ACF might otherwise spontaneously resolve or be diagnosed through routine care. We analysed the potential effectiveness of ACF for TB relative to the counterfactual scenario of routine care alone. METHODS: We constructed a Markov simulation model of TB natural history, diagnosis, symptoms, ACF and treatment, using a hypothetical reference setting using data from South East Asian countries. We calibrated the model to empirical data using Bayesian methods, and simulated potential 5-year outcomes with an 'aspirational' ACF intervention (reflecting maximum possible effectiveness) compared with the standard-of-care outcomes. RESULTS: Under the standard of care, 51% (95% credible interval, CrI: 31%, 75%) of people with prevalent TB at baseline were estimated to be diagnosed and linked to care over 5 years. With aspirational ACF, this increased to 88% (95% CrI: 84%, 94%). Most of this difference represented people who were diagnosed and treated through ACF but experienced spontaneous resolution under standard-of-care. Aspirational ACF was projected to reduce the average duration of TB disease by 12 months (95% CrI: 6%, 18%) and TB-associated disability-adjusted life-years by 71% (95% CrI: 67%, 76%). CONCLUSION: These data illustrate the importance of considering outcomes in a counterfactual standard of care scenario, as well as trade-offs between overdiagnosis and averted morbidity through earlier diagnosis-not just for TB, but for any disease in which population-based screening is recommended.

Impacts of reference population size and methods on the accuracy of genomic prediction for fleece traits in Inner Mongolia Cashmere Goats.

Introduction: Inner Mongolia Cashmere Goats (IMCGs) are famous for its cashmere quality and it's a unique genetic resource in China. Therefore, it is necessary to use genomic selection to improve the accuracy of selection for fleece traits in Inner Mongolia cashmere goats. The aim of this study was to determine the effect of methods (GBLUP, BayesA, BayesB, Bayesian LASSO, Bayesian Ridge Region) and the reference population size on accuracy of genomic selection in IMCGs. Methods: This study fully utilizes the pedigree and phenotype records of fleece traits in 2255 individuals, genotype of 50794 SNPs after quality control, and environmental data to perform genomic selection of fleece traits. Then GBLUP and Bayes series methods (BayesA, BayesB, Bayesian LASSO, Bayesian Ridge Region) were used to perform estimates of genetic parameter and genomic breeding value. And the accuracy of genomic estimated breeding value (GEBV) is evaluated using the five-fold cross validation method. And the analysis of variance and multiple comparison methods were used to determine the best method for genomic selection in fleece traits of IMCGs. Further the different reference population sizes (500, 1000, 1500, and 2000) was set. Then the best method was applied to estimate genome breeding values, and evaluate the impact of reference population sizes on the accuracy of genome selection for fleece traits in IMCGs. Results: It was found that the genomic prediction accuracy for each fleece trait in IMCGs by GBLUP method is highest, and it is significantly higher than that obtained by Bayesian method. The accuracy of breeding value estimation is 58.52% -68.49%. Also, it was found that the size of the reference population has a significant impact on the accuracy of genome prediction of fleece traits. When the reference population size is 2000, the accuracy of genomic prediction for each fleece trait is significantly higher than other levels, with accuracy of 55.47% -67.87%. This provides a theoretical basis for design a reasonable genome selection plan for Inner Mongolia cashmere goats in the later stag.

Comparing the Performance of Three Computational Methods for Estimating the Effective Reproduction Number.

The effective reproduction number (Rt) is one of the most important epidemiological parameters, providing suggestions for monitoring the development trend of diseases and also for adjusting the prevention and control policies. However, a few studies have focused on the performance of some common computational methods for Rt. The purpose of this article is to compare the performance of three computational methods for Rt: the time-dependent (TD) method, the new time-varying (NT) method, and the sequential Bayesian (SB) method. Four evaluation methods-accuracy, correlation coefficient, similarity based on trend, and dynamic time warping distance-were used to compare the effectiveness of three computational methods for Rt under different time lags and time windows. The results showed that the NT method was a better choice for real-time monitoring and analysis of the epidemic in the middle and late stages of the infectious disease. The TD method could reflect the change of the number of cases stably and accurately, and was more suitable for monitoring the change of Rt during the whole process of the epidemic outbreak. When the data were relatively stable, the SB method could also provide a reliable estimate for Rt, while the error would increase when the fluctuation in the number of cases increased. The results would provide suggestions for selecting appropriate Rt estimation methods and making policy adjustments more timely and effectively according to the change of Rt.

Bayesian Methods for Information Borrowing in Basket Trials: An Overview.

Basket trials allow simultaneous evaluation of a single therapy across multiple cancer types or subtypes of the same cancer. Since the same treatment is tested across all baskets, it may be desirable to borrow information across them to improve the statistical precision and power in estimating and detecting the treatment effects in different baskets. We review recent developments in Bayesian methods for the design and analysis of basket trials, focusing on the mechanism of information borrowing. We explain the common components of these methods, such as a prior model for the treatment effects that embodies an assumption of exchangeability. We also discuss the distinct features of these methods that lead to different degrees of borrowing. Through simulation studies, we demonstrate the impact of information borrowing on the operating characteristics of these methods and discuss its broader implications for drug development. Examples of basket trials are presented in both phase I and phase II settings.

A Bayesian nonparametric approach for handling item and examinee heterogeneity in assessment data.

We propose a novel nonparametric Bayesian item response theory model that estimates clusters at the question level, while simultaneously allowing for heterogeneity at the examinee level under each question cluster, characterized by a mixture of binomial distributions. The main contribution of this work is threefold. First, we present our new model and demonstrate that it is identifiable under a set of conditions. Second, we show that our model can correctly identify question-level clusters asymptotically, and the parameters of interest that measure the proficiency of examinees in solving certain questions can be estimated at a n rate (up to a log term). Third, we present a tractable sampling algorithm to obtain valid posterior samples from our proposed model. Compared to the existing methods, our model manages to reveal the multi-dimensionality of the examinees' proficiency level in handling different types of questions parsimoniously by imposing a nested clustering structure. The proposed model is evaluated via a series of simulations as well as apply it to an English proficiency assessment data set. This data analysis example nicely illustrates how our model can be used by test makers to distinguish different types of students and aid in the design of future tests.

Optimizing dose-schedule regimens with bayesian adaptive designs: opportunities and challenges.

Due to the small sample sizes in early-phase clinical trials, the toxicity and efficacy profiles of the dose-schedule regimens determined for subsequent trials may not be well established. The recent development of novel anti-tumor treatments and combination therapies further complicates the problem. Therefore, there is an increasing recognition of the essential place of optimizing dose-schedule regimens, and new strategies are now urgently needed. Bayesian adaptive designs provide a potentially effective way to evaluate several doses and schedules simultaneously in a single clinical trial with higher efficiency, but real-world implementation examples of such adaptive designs are still few. In this paper, we cover the critical factors associated with dose-schedule optimization and review the related innovative Bayesian adaptive designs. The assumptions, characteristics, limitations, and application scenarios of those designs are introduced. The review also summarizes some unresolved issues and future research opportunities for dose-schedule optimization.

The effects of various penalty parameter values in Q.Clear algorithm for rectal cancer detection on 18F-FDG images using a BGO-based PET/CT scanner: a phantom and clinical study.

BACKGROUND: The Q.Clear algorithm is a fully convergent iterative image reconstruction technique. We hypothesize that different PET/CT scanners with distinct crystal properties will require different optimal settings for the Q.Clear algorithm. Many studies have investigated the improvement of the Q.Clear reconstruction algorithm on PET/CT scanner with LYSO crystals and SiPM detectors. We propose an optimum penalization factor (ß) for the detection of rectal cancer and its metastases using a BGO-based detector PET/CT system which obtained via accurate and comprehensive phantom and clinical studies. METHODS: 18F-FDG PET-CT scans were acquired from NEMA phantom with lesion-to-background ratio (LBR) of 2:1, 4:1, 8:1, and 15 patients with rectal cancer. Clinical lesions were classified into two size groups. OSEM and Q.Clear (ß value of 100-500) reconstruction was applied. In Q.Clear, background variability (BV), contrast recovery (CR), signal-to-noise ratio (SNR), SUVmax, and signal-to-background ratio (SBR) were evaluated and compared to OSEM. RESULTS: OSEM had 11.5-18.6% higher BV than Q.Clear using ß value of 500. Conversely, RC from OSEM to Q.Clear using ß value of 500 decreased by 3.3-7.7% for a sphere with a diameter of 10 mm and 2.5-5.1% for a sphere with a diameter of 37 mm. Furthermore, the increment of contrast using a ß value of 500 was 5.2-8.1% in the smallest spheres compared to OSEM. When the ß value was increased from 100 to 500, the SNR increased by 49.1% and 30.8% in the smallest and largest spheres at LBR 2:1, respectively. At LBR of 8:1, the relative difference of SNR between ß value of 100 and 500 was 43.7% and 44.0% in the smallest and largest spheres, respectively. In the clinical study, as ß increased from 100 to 500, the SUVmax decreased by 47.7% in small and 31.1% in large lesions. OSEM demonstrated the least SUVmax, SBR, and contrast. The decrement of SBR and contrast using OSEM were 13.6% and 12.9% in small and 4.2% and 3.4%, respectively, in large lesions. CONCLUSIONS: Implementing Q.Clear enhances quantitative accuracies through a fully convergent voxel-based image approach, employing a penalization factor. In the BGO-based scanner, the optimal ß value for small lesions ranges from 200 for LBR 2:1 to 300 for LBR 8:1. For large lesions, the optimal ß value is between 400 for LBR 2:1 and 500 for LBR 8:1. We recommended ß value of 300 for small lesions and ß value of 500 for large lesions in clinical study.

BAYESIAN INFERENCE AND DYNAMIC PREDICTION FOR MULTIVARIATE LONGITUDINAL AND SURVIVAL DATA.

Alzheimer's disease (AD) is a complex neurological disorder impairing multiple domains such as cognition and daily functions. To better understand the disease and its progression, many AD research studies collect multiple longitudinal outcomes that are strongly predictive of the onset of AD dementia. We propose a joint model based on a multivariate functional mixed model framework (referred to as MFMM-JM) that simultaneously models the multiple longitudinal outcomes and the time to dementia onset. We develop six functional forms to fully investigate the complex association between longitudinal outcomes and dementia onset. Moreover, we use the Bayesian methods for statistical inference and develop a dynamic prediction framework that provides accurate personalized predictions of disease progressions based on new subject-specific data. We apply the proposed MFMM-JM to two large ongoing AD studies: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and National Alzheimer's Coordinating Center (NACC), and identify the functional forms with the best predictive performance. our method is also validated by extensive simulation studies with five settings.

Reliability assessment of permanent magnet brake based on accelerated bivariate Wiener degradation process.

Permanent magnet brake (PMB) is a safe and effective braking mechanism used to stop and hold the load in place. Due to its complex structure and high reliability, assessing the reliability of PMB remains a challenge. The main difficulty lies in that there are several performance indicators reflecting the health state of PMB, and they are correlated with each other. In order to assess the reliability of PMB more accurately, a constant stress accelerated degradation test (ADT) is carried out to collect degradation data of two main performance indicators in PMB. An accelerated bivariate Wiener degradation model is proposed to analyse the ADT data. In the proposed model, the relationship between degradation rate and stress levels is described by Arrhenius model, and a common random effect is introduced to describe the unit-to-unit variation and correlation between the two performance indicators. The Markov Chain Monte Carlo (MCMC) algorithm is performed to obtain the point and interval estimates of the model parameters. Finally, the proposed model and method are applied to analyse the accelerated degradation data of PMB, and the results show that the reliability of PMB at the used condition can be quantified quite well.

Estimating average wind speed in Thailand using confidence intervals for common mean of several Weibull distributions.

The Weibull distribution has been used to analyze data from many fields, including engineering, survival and lifetime analysis, and weather forecasting, particularly wind speed data. It is useful to measure the central tendency of wind speed data in specific locations using statistical parameters for instance the mean to accurately forecast the severity of future catastrophic events. In particular, the common mean of several independent wind speed samples collected from different locations is a useful statistic. To explore wind speed data from several areas in Surat Thani province, a large province in southern Thailand, we constructed estimates of the confidence interval for the common mean of several Weibull distributions using the Bayesian equitailed confidence interval and the highest posterior density interval using the gamma prior. Their performances are compared with those of the generalized confidence interval and the adjusted method of variance estimates recovery based on their coverage probabilities and expected lengths. The results demonstrate that when the common mean is small and the sample size is large, the Bayesian highest posterior density interval performed the best since its coverage probabilities were higher than the nominal confidence level and it provided the shortest expected lengths. Moreover, the generalized confidence interval performed well in some scenarios whereas adjusted method of variance estimates recovery did not. The approaches were used to estimate the common mean of real wind speed datasets from several areas in Surat Thani province, Thailand, fitted to Weibull distributions. These results support the simulation results in that the Bayesian methods performed the best. Hence, the Bayesian highest posterior density interval is the most appropriate method for establishing the confidence interval for the common mean of several Weibull distributions.

A Bayesian approach to clinical trial designs in dermatology with multiple simultaneous treatments per subject and multiple raters.

We consider the statistical analysis of clinical trial designs with multiple simultaneous treatments per subject and multiple raters. The work is motivated by a clinical research project in dermatology where different hair removal techniques were assessed based on a within-subject comparison. We assume that clinical outcomes are assessed by multiple raters as continuous or categorical scores, e.g. based on images, comparing two treatments on the subject-level in a pairwise manner. In this setting, a network of evidence on relative treatment effects is generated, which bears strong similarities to the data underlying a network meta-analysis of clinical trials. We therefore build on established methodology for complex evidence synthesis and propose a Bayesian approach to estimate relative treatment effects and to rank the treatments. The approach is, in principle, applicable to situations with any number of treatment arms and/or raters. As a major advantage, all available data is brought into a network and analyzed in one single model, which ensures consistent results among the treatment comparisons. We obtain operating characteristics via simulation and illustrate the method with a real clinical trial example.

Intelligent lung cancer MRI prediction analysis based on cluster prominence and posterior probabilities utilizing intelligent Bayesian methods on extracted gray-level co-occurrence (GLCM) features.

Lung cancer is the second foremost cause of cancer due to which millions of deaths occur worldwide. Developing automated tools is still a challenging task to improve the prediction. This study is specifically conducted for detailed posterior probabilities analysis to unfold the network associations among the gray-level co-occurrence matrix (GLCM) features. We then ranked the features based on t-test. The Cluster Prominence is selected as target node. The association and arc analysis were determined based on mutual information. The occurrence and reliability of selected cluster states were computed. The Cluster Prominence at state ≤330.85 yielded ROC index of 100%, relative Gini index of 99.98%, and relative Gini index of 100%. The proposed method further unfolds the dynamics and to detailed analysis of computed features based on GLCM features for better understanding of the hidden dynamics for proper diagnosis and prognosis of lung cancer.

An Efficient Bayesian Method for Estimating the Degree of the Skewness of X Chromosome Inactivation Based on the Mixture of General Pedigrees and Unrelated Females.

Skewed X chromosome inactivation (XCI-S) has been reported to be associated with some X-linked diseases. Several methods have been proposed to estimate the degree of XCI-S (denoted as γ) for quantitative and qualitative traits based on unrelated females. However, there is no method available for estimating γ based on general pedigrees. Therefore, in this paper, we propose a Bayesian method to obtain the point estimate and the credible interval of γ based on the mixture of general pedigrees and unrelated females (called mixed data for brevity), which is also suitable for only general pedigrees. We consider the truncated normal prior and the uniform prior for γ. Further, we apply the eigenvalue decomposition and Cholesky decomposition to our proposed methods to accelerate the computation speed. We conduct extensive simulation studies to compare the performances of our proposed methods and two existing Bayesian methods which are only applicable to unrelated females. The simulation results show that the incorporation of general pedigrees can improve the efficiency of the point estimation and the precision and the accuracy of the interval estimation of γ. Finally, we apply the proposed methods to the Minnesota Center for Twin and Family Research data for their practical use.