A Statistical Model for Inference of Recent and Incident HIV Infection Using Surveillance Data on Individuals Newly Diagnosed With HIV Infection in Scotland.

BACKGROUND: To inform global ambitions to end AIDS, evaluation of progress toward HIV incidence reduction requires robust methods to measure incidence. Although HIV diagnosis date in routine HIV/AIDS surveillance systems are often used as a surrogate marker for incidence, it can be misleading if acquisition of transmission occurred years before testing. Other information present in data such as antibody testing dates, avidity testing result, and CD4 counts can assist, but the degree of missing data is often prohibitive. METHODS: We constructed a Bayesian statistical model to estimate the annual proportion of first ever HIV diagnoses in Scotland (period 2015-2019) that represent recent HIV infection (ie, occurring within the previous 3-4 months) and incident HIV infection (ie, infection within the previous 12 months), by synthesizing avidity testing results and surveillance data on the interval since last negative HIV test. RESULTS: Over the 5-year analysis period, the model-estimated proportion of incident infection was 43.9% (95% CI: 40.9 to 47.0), and the proportion of recent HIV infection was 21.6% (95% CI: 19.1 to 24.1). Among the mode of HIV acquisition categories, the highest proportion of recent infection was estimated for people who inject drugs: 27.4% (95% CI: 20.4 to 34.4). CONCLUSIONS: The Bayesian approach is appropriate for the high prevalence of missing data that can occur in routine surveillance data sets. The proposed model will aid countries in improving their understanding of the number of people who have recently acquired their infection, which is needed to progress toward the goal of HIV transmission elimination.

Post-selection inference in regression models for group testing data.

We develop a methodology for valid inference after variable selection in logistic regression when the responses are partially observed, that is, when one observes a set of error-prone testing outcomes instead of the true values of the responses. Aiming at selecting important covariates while accounting for missing information in the response data, we apply the expectation-maximization algorithm to compute maximum likelihood estimators subject to LASSO penalization. Subsequent to variable selection, we make inferences on the selected covariate effects by extending post-selection inference methodology based on the polyhedral lemma. Empirical evidence from our extensive simulation study suggests that our post-selection inference results are more reliable than those from naive inference methods that use the same data to perform variable selection and inference without adjusting for variable selection.

Semi-parametric benchmark dose analysis with monotone additive models.

Benchmark dose analysis aims to estimate the level of exposure to a toxin associated with a clinically significant adverse outcome and quantifies uncertainty using the lower limit of a confidence interval for this level. We develop a novel framework for benchmark dose analysis based on monotone additive dose-response models. We first introduce a flexible approach for fitting monotone additive models via penalized B-splines and Laplace-approximate marginal likelihood. A reflective Newton method is then developed that employs de Boor's algorithm for computing splines and their derivatives for efficient estimation of the benchmark dose. Finally, we develop a novel approach for calculating benchmark dose lower limits based on an approximate pivot for the nonlinear equation solved by the estimated benchmark dose. The favorable properties of this approach compared to the Delta method and a parameteric bootstrap are discussed. We apply the new methods to make inferences about the level of prenatal alcohol exposure associated with clinically significant cognitive defects in children using data from six NIH-funded longitudinal cohort studies. Software to reproduce the results in this paper is available online and makes use of the novel semibmd  R package, which implements the methods in this paper.

Accelerating joint species distribution modelling with Hmsc-HPC by GPU porting.

Joint species distribution modelling (JSDM) is a widely used statistical method that analyzes combined patterns of all species in a community, linking empirical data to ecological theory and enhancing community-wide prediction tasks. However, fitting JSDMs to large datasets is often computationally demanding and time-consuming. Recent studies have introduced new statistical and machine learning techniques to provide more scalable fitting algorithms, but extending these to complex JSDM structures that account for spatial dependencies or multi-level sampling designs remains challenging. In this study, we aim to enhance JSDM scalability by leveraging high-performance computing (HPC) resources for an existing fitting method. Our work focuses on the Hmsc R-package, a widely used JSDM framework that supports the integration of various dataset types into a single comprehensive model. We developed a GPU-compatible implementation of its model-fitting algorithm using Python and the TensorFlow library. Despite these changes, our enhanced framework retains the original user interface of the Hmsc R-package. We evaluated the performance of the proposed implementation across various model configurations and dataset sizes. Our results show a significant increase in model fitting speed for most models compared to the baseline Hmsc R-package. For the largest datasets, we achieved speed-ups of over 1000 times, demonstrating the substantial potential of GPU porting for previously CPU-bound JSDM software. This advancement opens promising opportunities for better utilizing the rapidly accumulating new biodiversity data resources for inference and prediction.

External validation of a model using health administrative data to predict acetabular fracture probability: Brief report.

Analyses using population-based health administrative data can return erroneous results if case identification is inaccurate ("misclassification bias"). An acetabular fracture (AF) prediction model using administrative data decreased misclassification bias compared to identifying AFs using diagnostic codes. This study measured the accuracy of this AF prediction model in another hospital. We calculated AF probability in all hospitalizations in the validation hospital between 2015 and 2020. A random sample of 1000 patients stratified by expected AF probability was selected. Patient imaging studies were reviewed to determine true AF status. The validation population included 1000 people. The AF prediction model was very discriminative (c-statistic 0.90, 95% CI: 0.87-0.92) and very well calibrated (integrated calibration index 0.056, 95% CI: 0.039-0.074). AF probability can be accurately determined using routinely collected health administrative data. This observation supports using the AF prediction model to minimize misclassification bias when studying AF using health administrative data.

Transforming healthcare performance monitoring - A cutting-edge approach with generalized additive profiles: GAMs for healthcare quality monitoring.

Recent findings indicate a growing trend in data analysis within healthcare using statistical process control. However, the diversity of variables involved necessitates the expansion of new process control methodologies. This study examined control chart applications in cardiology by using generalized additive models (GAMs) to construct profiles while involving multiple healthcare variables (08). Two distinct statistics: deviation (D), and Hotelling (T2) were employed for constructing control charts: a commonly used single-variable statistic for nonparametric profiles and an innovative multivariate statistic that assesses the contribution of each element to process changes. These statistics were tested for monitoring ischemic and hemorrhagic strokes in 1-year acute stroke (369) patients at the Faisalabad Institute of Cardiology. Demographic parameters (age, gender), vascular risk factors (diabetes, family history, sleep), socioeconomic variables (smoking, location), and blood pressure are included in the model. The research includes the computation of zero-state average run length (ARL) for assessing the performance of control charts. The characteristics of the proposed profile were analyzed, such as the T2 control chart, performing better than the D chart for medium-to-large shifts (δ ≥ 0.50). On the other hand, for small δ = 0.25, the D control chart produces smaller ARL values but more significant standard deviations. While both statistics contribute to profile monitoring, T2 is more effective at identifying and tracing medium and large shifts. In conclusion, such handy tools may aid healthcare performance monitoring, especially for complicated predictor-response relationships. Monitored profiles demonstrated that GAMs are useful for healthcare analysis and process monitoring.

Exploring mixture estimators in stratified random sampling.

Advancements in sensor technology have brought a revolution in data generation. Therefore, the study variable and several linearly related auxiliary variables are recorded due to cost-effectiveness and ease of recording. These auxiliary variables are commonly observed as quantitative and qualitative (attributes) variables and are jointly used to estimate the study variable's population mean using a mixture estimator. For this purpose, this work proposes a family of generalized mixture estimators under stratified sampling to increase efficiency under symmetrical and asymmetrical distributions and study the estimator's behavior for different sample sizes for its convergence to the Normal distribution. It is found that the proposed estimator estimates the population mean of the study variable with more precision than the competitor estimators under Normal, Uniform, Weibull, and Gamma distributions. It is also revealed that the proposed estimator follows the Cauchy distribution when the sample size is less than 35; otherwise, it converges to normality. Furthermore, the implementation of two real-life datasets related to the health and finance sectors is also presented to support the proposed estimator's significance.

Periodically correlated time series and the Variable Bandpass Periodic Block Bootstrap.

This research introduces a novel approach to resampling periodically correlated time series using bandpass filters for frequency separation called the Variable Bandpass Periodic Block Bootstrap and then examines the significant advantages of this new method. While bootstrapping allows estimation of a statistic's sampling distribution by resampling the original data with replacement, and block bootstrapping is a model-free resampling strategy for correlated time series data, both fail to preserve correlations in periodically correlated time series. Existing extensions of the block bootstrap help preserve the correlation structures of periodically correlated processes but suffer from flaws and inefficiencies. Analyses of time series data containing cyclic, seasonal, or periodically correlated principal components often seen in annual, daily, or other cyclostationary processes benefit from separating these components. The Variable Bandpass Periodic Block Bootstrap uses bandpass filters to separate a periodically correlated component from interference such as noise at other uncorrelated frequencies. A simulation study is presented, demonstrating near universal improvements obtained from the Variable Bandpass Periodic Block Bootstrap when compared with prior block bootstrapping methods for periodically correlated time series.

Prevalence estimates for COVID-19-related health behaviors based on the cheating detection triangular model.

BACKGROUND: Survey studies in medical and health sciences predominantly apply a conventional direct questioning (DQ) format to gather private and highly personal information. If the topic under investigation is sensitive or even stigmatizing, such as COVID-19-related health behaviors and adherence to non-pharmaceutical interventions in general, DQ surveys can lead to nonresponse and untruthful answers due to the influence of social desirability bias (SDB). These effects seriously threaten the validity of the results obtained, potentially leading to distorted prevalence estimates for behaviors for which the prevalence in the population is unknown. While this issue cannot be completely avoided, indirect questioning techniques (IQTs) offer a means to mitigate the harmful influence of SDB by guaranteeing the confidentiality of individual responses. The present study aims at assessing the validity of a recently proposed IQT, the Cheating Detection Triangular Model (CDTRM), in estimating the prevalence of COVID-19-related health behaviors while accounting for cheaters who disregard the instructions. METHODS: In an online survey of 1,714 participants in Taiwan, we obtained CDTRM prevalence estimates via an Expectation-Maximization algorithm for three COVID-19-related health behaviors with different levels of sensitivity. The CDTRM estimates were compared to DQ estimates and to available official statistics provided by the Taiwan Centers for Disease Control. Additionally, the CDTRM allowed us to estimate the share of cheaters who disregarded the instructions and adjust the prevalence estimates for the COVID-19-related health behaviors accordingly. RESULTS: For a behavior with low sensitivity, CDTRM and DQ estimates were expectedly comparable and in line with official statistics. However, for behaviors with medium and high sensitivity, CDTRM estimates were higher and thus presumably more valid than DQ estimates. Analogously, the estimated cheating rate increased with higher sensitivity of the behavior under study. CONCLUSIONS: Our findings strongly support the assumption that the CDTRM successfully controlled for the validity-threatening influence of SDB in a survey on three COVID-19-related health behaviors. Consequently, the CDTRM appears to be a promising technique to increase estimation validity compared to conventional DQ for health-related behaviors, and sensitive attributes in general, for which a strong influence of SDB is to be expected.

Investigating the Heterogeneity of "Study Twins".

Meta-analyses are commonly performed based on random-effects models, while in certain cases one might also argue in favor of a common-effect model. One such case may be given by the example of two "study twins" that are performed according to a common (or at least very similar) protocol. Here we investigate the particular case of meta-analysis of a pair of studies, for example, summarizing the results of two confirmatory clinical trials in phase III of a clinical development program. Thereby, we focus on the question of to what extent homogeneity or heterogeneity may be discernible and include an empirical investigation of published ("twin") pairs of studies. A pair of estimates from two studies only provide very little evidence of homogeneity or heterogeneity of effects, and ad hoc decision criteria may often be misleading.

Modelling wound area in studies of wound healing interventions.

BACKGROUND: Experimental studies of wound healing often use survival analysis and time to event outcomes or differences in wound area at a specific time point. However, these methods do not use a potentially large number of observations made over the course of a trial and may be inefficient. A model-based approach can leverage all trial data, but there is little guidance on appropriate models and functional forms to describe wound healing. METHODS: We derive a general statistical model and review a wide range of plausible mathematical models to describe wound healing. We identify a range of possible derived estimands and their derivation from the models. Using data from a trial of an intervention to promote ulcer healing in patients affected by leprosy that included three measurement methods repeated across the course of the study, we compare the goodness-of-fit of the models using a range of methods and estimate treatment effects and healing rate functions with the best-fitting models. RESULTS: Overall, we included 5,581 ulcer measurements of 1,578 unique images from 130 patients. We examined the performance of a range of models. The square root, log square root, and log quadratic models were the best fitting models across all outcome measurement methods. The estimated treatment effects magnitude and sign varied by time post-randomisation, model type, and outcome type, but across all models there was little evidence of effectiveness. The estimated effects were significantly more precise than non-parametric alternatives. For example, estimated differences from the three outcome measurements at 42-days post-randomisation were - 0.01 cm2 (-0.77, 0.74), -0.44 cm2 (-1.64, 0.76), and 0.11 cm2 (-0.87, 1.08) using a non-parametric method versus - 0.03 cm2 (-0.14, 0.06), 0.06 cm2 (-0.05, 0.17), and 0.03 cm2 (-0.07, 0.17) using a square-root model. CONCLUSIONS: Model-based analyses can dramatically improve the precision of estimates but care must be taken to carefully compare and select the best fitting models. The (log) square-root model is strongly recommended reflecting advice from a century ago.

Adjusting for incomplete baseline covariates in randomized controlled trials: a cross-world imputation framework.

In randomized controlled trials, adjusting for baseline covariates is commonly used to improve the precision of treatment effect estimation. However, covariates often have missing values. Recently, Zhao and Ding studied two simple strategies, the single imputation method and missingness-indicator method (MIM), to handle missing covariates and showed that both methods can provide an efficiency gain compared to not adjusting for covariates. To better understand and compare these two strategies, we propose and investigate a novel theoretical imputation framework termed cross-world imputation (CWI). This framework includes both single imputation and MIM as special cases, facilitating the comparison of their efficiency. Through the lens of CWI, we show that MIM implicitly searches for the optimal CWI values and thus achieves optimal efficiency. We also derive conditions under which the single imputation method, by searching for the optimal single imputation values, can achieve the same efficiency as the MIM. We illustrate our findings through simulation studies and a real data analysis based on the Childhood Adenotonsillectomy Trial. We conclude by discussing the practical implications of our findings.

Prediction of acute onset of chronic cor pulmonale: comparative analysis of Holt-Winters exponential smoothing and ARIMA model.

BACKGROUND: The aim of this study is to analyze the trend of acute onset of chronic cor pulmonale at Chenggong Hospital of Kunming Yan'an Hospital between January 2018 and December 2022.Additionally, the study will compare the application of the ARIMA model and Holt-Winters model in predicting the number of chronic cor pulmonale cases. METHODS: The data on chronic cor pulmonale cases from 2018 to 2022 were collected from the electronic medical records system of Chenggong Hospital of Kunming Yan'an Hospital. The ARIMA and Holt-Winters models were constructed using monthly case numbers from January 2018 to December 2022 as training data. The performance of the model was tested using the monthly number of cases from January 2023 to December 2023 as the test set. RESULTS: The number of acute onset of chronic cor pulmonale in Chenggong Hospital of Kunming Yan'an Hospital exhibited a downward trend overall from 2018 to 2022. There were more cases in winter and spring, with peaks observed in November to December and January of the following year. The optimal ARIMA model was determined to be ARIMA (0,1,1) (0,1,1)12, while for the Holt-Winters model, the optimal choice was the Holt-Winters multiplicative model. It was found that the Holt-Winters multiplicative model yielded the lowest error. CONCLUSION: The Holt-Winters multiplicative model predicts better accuracy. The diagnosis of acute onset of chronic cor pulmonale is related to many risk factors, therefore, when using temporal models to fit and predict the data, we must consider such factors' influence and try to incorporate them into the models.

Design considerations for Factorial Adaptive Multi-Arm Multi-Stage (FAST) clinical trials.

BACKGROUND: Multi-Arm, Multi-Stage (MAMS) clinical trial designs allow for multiple therapies to be compared across a spectrum of clinical trial phases. MAMS designs fall under several overarching design groups, including adaptive designs (AD) and multi-arm (MA) designs. Factorial clinical trials designs represent a combination of factorial and MAMS trial designs and can provide increased efficiency relative to fixed, traditional designs. We explore design choices associated with Factorial Adaptive Multi-Arm Multi-Stage (FAST) designs, which represent the combination of factorial and MAMS designs. METHODS: Simulation studies were conducted to assess the impact of the type of analyses, the timing of analyses, and the effect size observed across multiple outcomes on trial operating characteristics for a FAST design. Given multiple outcomes types assessed within the hypothetical trial, the primary analysis approach for each assessment varied depending on data type. RESULTS: The simulation studies demonstrate that the proposed class of FAST trial designs can offer a framework to potentially provide improvements relative to other trial designs, such as a MAMS or factorial trial. Further, we note that the design implementation decisions, such as the timing and type of analyses conducted throughout trial, can have a great impact on trial operating characteristics. CONCLUSIONS: Motivated by a trial currently under design, our work shows that the FAST category of trial can potentially offer benefits similar to both MAMS and factorial designs; however, the chosen design aspects which can be included in a FAST trial need to be thoroughly explored during the planning phase.

A Bayesian latent-subgroup platform design for dose optimization.

The US Food and Drug Administration launched Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development, calling for the paradigm shift from finding the maximum tolerated dose to the identification of optimal biological dose (OBD). Motivated by a real-world drug development program, we propose a master-protocol-based platform trial design to simultaneously identify OBDs of a new drug, combined with standards of care or other novel agents, in multiple indications. We propose a Bayesian latent subgroup model to accommodate the treatment heterogeneity across indications, and employ Bayesian hierarchical models to borrow information within subgroups. At each interim analysis, we update the subgroup membership and dose-toxicity and -efficacy estimates, as well as the estimate of the utility for risk-benefit tradeoff, based on the observed data across treatment arms to inform the arm-specific decision of dose escalation and de-escalation and identify the OBD for each arm of a combination partner and an indication. The simulation study shows that the proposed design has desirable operating characteristics, providing a highly flexible and efficient way for dose optimization. The design has great potential to shorten the drug development timeline, save costs by reducing overlapping infrastructure, and speed up regulatory approval.

Gene sequence analysis model construction based on k-mer statistics.

With the rapid development of biotechnology, gene sequencing methods are gradually improved. The structure of gene sequences is also more complex. However, the traditional sequence alignment method is difficult to deal with the complex gene sequence alignment work. In order to improve the efficiency of gene sequence analysis, D2 series method of k-mer statistics is selected to build the model of gene sequence alignment analysis. According to the structure of the foreground sequence, the sequence to be aligned can be cut by different lengths and divided into multiple subsequences. Finally, according to the selected subsequences, the maximum dissimilarity in the alignment results is determined as the statistical result. At the same time, the research also designed an application system for the sequence alignment analysis of the model. The experimental results showed that the statistical power of the sequence alignment analysis model was directly proportional to the sequence coverage and cutting length, and inversely proportional to the K value and module length. At the same time, the model was applied to the system designed in this paper. The maximum storage capacity of the system was 71 GB, the maximum disk capacity was 135 GB, and the running time was less than 2.0s. Therefore, the k-mer statistic sequence alignment model and system proposed in this study have considerable application value in gene alignment analysis.

Different estimation methods of the modified Kies Topp-Leone model with applications and quantile regression.

This paper introduces the modified Kies Topp-Leone (MKTL) distribution for modeling data on the (0, 1) or [0, 1] interval. The shapes of the density and hazard rate functions manifest desirable shapes, making the MKTL distribution suitable for modeling data with different characteristics at the unit interval. Twelve different estimation methods are utilized to estimate the distribution parameters, and Monte Carlo simulation experiments are executed to assess the performance of the methods. The simulation results suggest that the maximum likelihood method is the superior method. The usefulness of the new distribution is illustrated by utilizing three data sets, and its performance is juxtaposed with that of other competing models. The findings affirm the superiority of the MKTL distribution over the other candidate models. Applying the developed quantile regression model using the new distribution disclosed that it offers a competitive fit over other existing regression models.

BayesianSSA: a Bayesian statistical model based on structural sensitivity analysis for predicting responses to enzyme perturbations in metabolic networks.

BACKGROUND: Chemical bioproduction has attracted attention as a key technology in a decarbonized society. In computational design for chemical bioproduction, it is necessary to predict changes in metabolic fluxes when up-/down-regulating enzymatic reactions, that is, responses of the system to enzyme perturbations. Structural sensitivity analysis (SSA) was previously developed as a method to predict qualitative responses to enzyme perturbations on the basis of the structural information of the reaction network. However, the network structural information can sometimes be insufficient to predict qualitative responses unambiguously, which is a practical issue in bioproduction applications. To address this, in this study, we propose BayesianSSA, a Bayesian statistical model based on SSA. BayesianSSA extracts environmental information from perturbation datasets collected in environments of interest and integrates it into SSA predictions. RESULTS: We applied BayesianSSA to synthetic and real datasets of the central metabolic pathway of Escherichia coli. Our result demonstrates that BayesianSSA can successfully integrate environmental information extracted from perturbation data into SSA predictions. In addition, the posterior distribution estimated by BayesianSSA can be associated with the known pathway reported to enhance succinate export flux in previous studies. CONCLUSIONS: We believe that BayesianSSA will accelerate the chemical bioproduction process and contribute to advancements in the field.

Discrepancy-based diffusion models for lesion detection in brain MRI.

Diffusion probabilistic models (DPMs) have exhibited significant effectiveness in computer vision tasks, particularly in image generation. However, their notable performance heavily relies on labelled datasets, which limits their application in medical images due to the associated high-cost annotations. Current DPM-related methods for lesion detection in medical imaging, which can be categorized into two distinct approaches, primarily rely on image-level annotations. The first approach, based on anomaly detection, involves learning reference healthy brain representations and identifying anomalies based on the difference in inference results. In contrast, the second approach, resembling a segmentation task, employs only the original brain multi-modalities as prior information for generating pixel-level annotations. In this paper, our proposed model - discrepancy distribution medical diffusion (DDMD) - for lesion detection in brain MRI introduces a novel framework by incorporating distinctive discrepancy features, deviating from the conventional direct reliance on image-level annotations or the original brain modalities. In our method, the inconsistency in image-level annotations is translated into distribution discrepancies among heterogeneous samples while preserving information within homogeneous samples. This property retains pixel-wise uncertainty and facilitates an implicit ensemble of segmentation, ultimately enhancing the overall detection performance. Thorough experiments conducted on the BRATS2020 benchmark dataset containing multimodal MRI scans for brain tumour detection demonstrate the great performance of our approach in comparison to state-of-the-art methods.