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To compare the performance of a targeted maximum likelihood estimator (TMLE) and a collaborative TMLE (CTMLE) to other estimators in a drug safety analysis, including a regression-based estimator, propensity score (PS)–based estimators, and an alternate doubly robust (DR) estimator in a real example and simulations. The real data set is a subset of observational data from Kaiser Permanente Northern California formatted for use in active drug safety surveillance. Both the real and simulated data sets include potential confounders, a treatment variable indicating use of one of two antidiabetic treatments and an outcome variable indicating occurrence of an acute myocardial infarction (AMI). In the real data example, there is no difference in AMI rates between treatments. In simulations, the double robustness property is demonstrated: DR estimators are consistent if either the initial outcome regression or PS estimator is consistent, whereas other estimators are inconsistent if the initial estimator is not consistent. In simulations with near-positivity violations, CTMLE performs well relative to other estimators by adaptively estimating the PS. Each of the DR estimators was consistent, and TMLE and CTMLE had the smallest mean squared error in simulations.

The learning-based super-resolution reconstruction method inputs a low-resolution image into a network, and learns a non-linear mapping relationship between low-resolution and high-resolution through the network. In this study, the multi-scale super-resolution reconstruction network is used to fuse the effective features of different scale images, and the non-linear mapping between low resolution and high resolution is studied from coarse to fine to realise the end-to-end super-resolution reconstruction task. The loss of some features of the low-resolution image will negatively affect the quality of the reconstructed image. To solve the problem of incomplete image features in low-resolution, this study adopts the multi-scale super-resolution reconstruction method based on guided image filtering. The high-resolution image reconstructed by the multi-scale super-resolution network and the real high-resolution image are merged by the guide image filter to generate a new image, and the newly generated image is used for secondary training of the multi-scale super-resolution reconstruction network. The newly generated image effectively compensates for the details and texture information lost in the low-resolution image, thereby improving the effect of the super-resolution reconstructed image.Compared with the existing super-resolution reconstruction scheme, the accuracy and speed of super-resolution reconstruction are improved.

BACKGROUND:Super learning is an ensemble machine learning approach used increasingly as an alternative to classical prediction techniques. When implementing super learning, however, not tuning the hyperparameters of the algorithms in it may adversely affect the performance of the super learner. METHODS:In this case study, we used data from a Canadian electronic prescribing system to predict when primary care physicians prescribed antidepressants for indications other than depression. The analysis included 73,576 antidepressant prescriptions and 373 candidate predictors. We derived two super learnersone using tuned hyperparameter values for each machine learning algorithm identified through an iterative grid search procedure and the other using the default values. We compared the performance of the tuned super learner to that of the super learner using default values (“untuned”) and a carefully constructed logistic regression model from a previous analysis. RESULTS:The tuned super learner had a scaled Brier score (R) of 0.322 (95% [confidence interval] CI = 0.267, 0.362). In comparison, the untuned super learner had a scaled Brier score of 0.309 (95% CI = 0.256, 0.353), corresponding to an efficiency loss of 4% (relative efficiency 0.96; 95% CI = 0.93, 0.99). The previously-derived logistic regression model had a scaled Brier score of 0.307 (95% CI = 0.245, 0.360), corresponding to an efficiency loss of 5% relative to the tuned super learner (relative efficiency 0.95; 95% CI = 0.88, 1.01). CONCLUSIONS:In this case study, hyperparameter tuning produced a super learner that performed slightly better than an untuned super learner. Tuning the hyperparameters of individual algorithms in a super learner may help optimize performance.

Background While obesity confers an increased risk of death in the general population, numerous studies have reported an association between obesity and improved survival among critically ill patients. This contrary finding has been referred to as the obesity paradox. In this retrospective study, two causal inference approaches were used to address whether the survival of non-obese critically ill patients would have been improved if they had been obese. Methods The study cohort comprised 6557 adult critically ill patients hospitalized at the Intensive Care Unit of the Ghent University Hospital between 2015 and 2017. Obesity was defined as a body mass index of ≥ 30 kg/m 2 . Two causal inference approaches were used to estimate the average effect of obesity in the non-obese (AON): a traditional approach that used regression adjustment for confounding and that assumed missingness completely at random and a robust approach that used machine learning within the targeted maximum likelihood estimation framework along with multiple imputation of missing values under the assumption of missingness at random. 1754 (26.8%) patients were discarded in the traditional approach because of at least one missing value for obesity status or confounders. Results Obesity was present in 18.9% of patients. The in-hospital mortality was 14.6% in non-obese patients and 13.5% in obese patients. The raw marginal risk difference for in-hospital mortality between obese and non-obese patients was − 1.06% (95% confidence interval (CI) − 3.23 to 1.11%, P  = 0.337). The traditional approach resulted in an AON of − 2.48% (95% CI − 4.80 to − 0.15%, P  = 0.037), whereas the robust approach yielded an AON of − 0.59% (95% CI − 2.77 to 1.60%, P  = 0.599). Conclusions A causal inference approach that is robust to residual confounding bias due to model misspecification and selection bias due to missing (at random) data mitigates the obesity paradox observed in critically ill patients, whereas a traditional approach results in even more paradoxical findings. The robust approach does not provide evidence that the survival of non-obese critically ill patients would have been improved if they had been obese.

Real-time traffic prediction uses past data to anticipate traffic volume. The volume of traffic in the region may be estimated using interpolation and extrapolation from library data by the trend structure. It is based on a prediction model with a linear function. From this, the distance-relevant procedures are used to conduct the vehicle traffic flow system. To improve forecast accuracy for managing traffic flow and representing the traffic pattern in the trip route, an adaptive model of optimum learning was presented for missing traffic flow predictions. To categorize and forecast the traffic flow from the database for this model, Adaptive Wildfire Optimization (AWO) with the AI method is suggested. It chooses the best features from the database's overall properties to outperform the conventional classification model in making predictions. Spatial Pattern Super Learning (SPSL), a paradigm for enhancing pattern learning, is presented to increase learning accuracy. By comparing the suggested model's overall outcomes with those of other cutting-edge techniques using statistical factors, the findings may be confirmed.

Suppose we observe n$n$ independent and identically distributed observations of a finite dimensional bounded random variable. This article is concerned with the construction of an efficient targeted minimum loss-based estimator (TMLE) of a pathwise differentiable target parameter of the data distribution based on a realistic statistical model. The only smoothness condition we will enforce on the statistical model is that the nuisance parameters of the data distribution that are needed to evaluate the canonical gradient of the pathwise derivative of the target parameter are multivariate real valued cadlag functions (right-continuous and left-hand limits, (G. Neuhaus. On weak convergence of stochastic processes with multidimensional time parameter. Ann Stat 1971;42:1285-1295.) and have a finite supremum and (sectional) variation norm. Each nuisance parameter is defined as a minimizer of the expectation of a loss function over over all functions it its parameter space. For each nuisance parameter, we propose a new minimum loss based estimator that minimizes the loss-specific empirical risk over the functions in its parameter space under the additional constraint that the variation norm of the function is bounded by a set constant. The constant is selected with cross-validation. We show such an MLE can be represented as the minimizer of the empirical risk over linear combinations of indicator basis functions under the constraint that the sum of the absolute value of the coefficients is bounded by the constant: i.e., the variation norm corresponds with this L1$L_1$-norm of the vector of coefficients. We will refer to this estimator as the highly adaptive Lasso (HAL)-estimator. We prove that for all models the HAL-estimator converges to the true nuisance parameter value at a rate that is faster than n−1/4$n^{-1/4}$ w.r.t. square-root of the loss-based dissimilarity. We also show that if this HAL-estimator is included in the library of an ensemble super-learner, then the super-learner will at minimal achieve the rate of convergence of the HAL, but, by previous results, it will actually be asymptotically equivalent with the oracle (i.e., in some sense best) estimator in the library. Subsequently, we establish that a one-step TMLE using such a super-learner as initial estimator for each of the nuisance parameters is asymptotically efficient at any data generating distribution in the model, under weak structural conditions on the target parameter mapping and model and a strong positivity assumption (e.g., the canonical gradient is uniformly bounded). We demonstrate our general theorem by constructing such a one-step TMLE of the average causal effect in a nonparametric model, and establishing that it is asymptotically efficient.

Targeted maximum likelihood estimation (TMLE) provides a general methodology for estimation of causal parameters in presence of high-dimensional nuisance parameters. Generally, TMLE consists of a two-step procedure that combines data-adaptive nuisance parameter estimation with semiparametric efficiency and rigorous statistical inference obtained via a targeted update step. In this paper, we demonstrate the practical applicability of TMLE based causal inference in survival and competing risks settings where event times are not confined to take place on a discrete and finite grid. We focus on estimation of causal effects of time-fixed treatment decisions on survival and absolute risk probabilities, considering different univariate and multidimensional parameters. Besides providing a general guidance to using TMLE for survival and competing risks analysis, we further describe how the previous work can be extended with the use of loss-based cross-validated estimation, also known as super learning, of the conditional hazards. We illustrate the usage of the considered methods using publicly available data from a trial on adjuvant chemotherapy for colon cancer. R software code to implement all considered algorithms and to reproduce all analyses is available in an accompanying online appendix on Github.

We consider estimation of an optimal individualized treatment rule when a high-dimensional vector of baseline variables is available. Our optimality criterion is with respect to delaying the expected time to occurrence of an event of interest. We use semiparametric efficiency theory to construct estimators with properties such as double robustness. We propose two estimators of the optimal rule, which arise from considering two loss functions aimed at directly estimating the conditional treatment effect and recasting the problem in terms of weighted classification using the 0-1 loss function. Our estimated rules are ensembles that minimize the crossvalidated risk of a linear combination in a user-supplied library of candidate estimators. We prove oracle inequalities bounding the finite-sample excess risk of the estimator. The bounds depend on the excess risk of the oracle selector and a doubly robust term related to estimation of the nuisance parameters. We discuss the convergence rates of our estimator to the oracle selector, and illustrate our methods by analysis of a phase III randomized study testing the efficacy of a new therapy for the treatment of breast cancer.

To establish a good predictive model using a deep-learning (DL)-based three-dimensional (3D) super-resolution ultrasound images for the diagnosis of benign and malignant breast lesions. This retrospective study included 333 patients with histopathologically confirmed breast lesions, randomly split into training (N=266) and testing (N=67) datasets. Eight models, including four deep learning models (ORResNet101, ORMobileNet_v2, SRResNet101, SRMobileNet_v2) and four machine learning models (OR_LR, OR_SVM, SR_LR, SR_SVM), were developed based on original and super-resolution images. The best performing model was SRMobileNet_v2, which was used to construct a nomogram integrating clinical factors. The performance of nomogram was evaluated using receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and calibration curves. SRMobileNet_v2, MobileNet_V2 based on super-resolution ultrasound images, had the best predictive performance in four traditional machine learning models and four deep learning models, with AUC improvements of 0.089 and 0.031 in the training and testing sets, relative to the ORMobileNet_v2 model based on original ultrasound images. The deep-learning nomogram was constructed using the SRMobileNet_v2 model score, tumor size, and patient age, resulting in superior predictive efficacy compared to the nomogram without the SRMobileNet_v2 model score. Furthermore, it demonstrated favorable calibration, discrimination, and clinical utility in both cohorts. The diagnostic prediction model utilizing super-resolution reconstructed ultrasound images outperforms the model based on original images in distinguishing between benign and malignant breast lesions. The nomogram based on super-resolution ultrasound images has the potential to serve as a reliable auxiliary diagnostic tool for clinicians, exhibiting superior predictive performance in distinguishing between benign and malignant breast lesions.

To improve the estimation of healthcare expenditures by introducing a novel method that is well-suited to situations where data exhibit strong skewness and zero-inflation. Simulations, and two real-world datasets: the 2016–2017 Medical Expenditure Panel Survey; the Back Pain Outcomes using Longitudinal Data. Super learner is an ensemble machine learning approach that can combine several algorithms to improve estimation. We propose a two-stage super learner that is well suited for healthcare expenditure data by separately estimating the probability of any healthcare expenditure and the mean amount of healthcare expenditure conditional on having healthcare expenditures. These estimates can then be combined to yield a single estimate of expenditures for each observation. The analytical strategy can flexibly incorporate a range of individual estimation approaches for each stage of estimation, including both regression-based approaches and machine learning algorithms such as random forests. We compare the performance of the two-stage super learner with a one-stage super learner, and with multiple individual algorithms for estimation of healthcare cost under a broad range of data settings in simulated and real data. The predictive performance was compared using Mean Squared Error and R2. Our results indicate that the two-stage super learner has better performance compared with a one-stage super learner and individual algorithms, for healthcare cost estimation under a wide variety of settings in simulations and in empirical analyses. The improvement of the two-stage super learner over the one-stage super learner was particularly evident in settings when zero-inflation is high.