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Benchmark dose profiles for joint-action quantal data in quantitative risk assessment.

ABSTRACT: Benchmark analysis is a widely used tool in public health risk analysis. Therein, estimation of minimum exposure levels, called Benchmark Doses (BMDs), that induce a prespecified Benchmark Response (BMR) is well understood for the case of an adverse response to a single stimulus. For cases where two agents are studied in tandem, however, the benchmark approach is far less developed. This article demonstrates how the benchmark modeling paradigm can be expanded from the single-dose setting to joint-action, two-agent studies. Focus is on response outcomes expressed as proportions. Extending the single-exposure setting, representations of risk are based on a joint-action dose-response model involving both agents. Based on such a model, the concept of a benchmark profile (BMP) - a two-dimensional analog of the single-dose BMD at which both agents achieve the specified BMR - is defined for use in quantitative risk characterization and assessment. The resulting, joint, low-dose guidelines can improve public health planning and risk regulation when dealing with low-level exposures to combinations of hazardous agents.

SUBMITTER: Deutsch RC

PROVIDER: S-EPMC3539281 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Benchmark dose profiles for joint-action quantal data in quantitative risk assessment.

Deutsch Roland C RC Piegorsch Walter W WW

Biometrics 20121201 4

Benchmark analysis is a widely used tool in public health risk analysis. Therein, estimation of minimum exposure levels, called Benchmark Doses (BMDs), that induce a prespecified Benchmark Response (BMR) is well understood for the case of an adverse response to a single stimulus. For cases where two agents are studied in tandem, however, the benchmark approach is far less developed. This article demonstrates how the benchmark modeling paradigm can be expanded from the single-dose setting to join ...[more]

PMID: 23278519

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Project description:BackgroundFederated learning (FL) is a newly proposed machine-learning method that uses a decentralized dataset. Since data transfer is not necessary for the learning process in FL, there is a significant advantage in protecting personal privacy. Therefore, many studies are being actively conducted in the applications of FL for diverse areas.ObjectiveThe aim of this study was to evaluate the reliability and performance of FL using three benchmark datasets, including a clinical benchmark dataset.MethodsTo evaluate FL in a realistic setting, we implemented FL using a client-server architecture with Python. The implemented client-server version of the FL software was deployed to Amazon Web Services. Modified National Institute of Standards and Technology (MNIST), Medical Information Mart for Intensive Care-III (MIMIC-III), and electrocardiogram (ECG) datasets were used to evaluate the performance of FL. To test FL in a realistic setting, the MNIST dataset was split into 10 different clients, with one digit for each client. In addition, we conducted four different experiments according to basic, imbalanced, skewed, and a combination of imbalanced and skewed data distributions. We also compared the performance of FL to that of the state-of-the-art method with respect to in-hospital mortality using the MIMIC-III dataset. Likewise, we conducted experiments comparing basic and imbalanced data distributions using MIMIC-III and ECG data.ResultsFL on the basic MNIST dataset with 10 clients achieved an area under the receiver operating characteristic curve (AUROC) of 0.997 and an F1-score of 0.946. The experiment with the imbalanced MNIST dataset achieved an AUROC of 0.995 and an F1-score of 0.921. The experiment with the skewed MNIST dataset achieved an AUROC of 0.992 and an F1-score of 0.905. Finally, the combined imbalanced and skewed experiment achieved an AUROC of 0.990 and an F1-score of 0.891. The basic FL on in-hospital mortality using MIMIC-III data achieved an AUROC of 0.850 and an F1-score of 0.944, while the experiment with the imbalanced MIMIC-III dataset achieved an AUROC of 0.850 and an F1-score of 0.943. For ECG classification, the basic FL achieved an AUROC of 0.938 and an F1-score of 0.807, and the imbalanced ECG dataset achieved an AUROC of 0.943 and an F1-score of 0.807.ConclusionsFL demonstrated comparative performance on different benchmark datasets. In addition, FL demonstrated reliable performance in cases where the distribution was imbalanced, skewed, and extreme, reflecting the real-life scenario in which data distributions from various hospitals are different. FL can achieve high performance while maintaining privacy protection because there is no requirement to centralize the data.

Project description:Data below detection limits, left-censored data, are common in environmental microbiology, and decisions in handling censored data may have implications for quantitative microbial risk assessment (QMRA). In this paper, we utilize simulated data sets informed by real-world enterovirus water data to evaluate methods for handling left-censored data. Data sets were simulated with four censoring degrees (low [10%], medium [35%], high [65%], and severe [90%]) and one real-life censoring example (97%) and were informed by enterovirus data assuming a lognormal distribution with a limit of detection (LOD) of 2.3 genome copies/liter. For each data set, five methods for handling left-censored data were applied: (i) substitution with LOD/[Formula: see text], (ii) lognormal maximum likelihood estimation (MLE) to estimate mean and standard deviation, (iii) Kaplan-Meier estimation (KM), (iv) imputation method using MLE to estimate distribution parameters (MI method 1), and (v) imputation from a uniform distribution (MI method 2). Each data set mean was used to estimate enterovirus dose and infection risk. Root mean square error (RMSE) and bias were used to compare estimated and known doses and infection risks. MI method 1 resulted in the lowest dose and infection risk RMSE and bias ranges for most censoring degrees, predicting infection risks at most 1.17 × 10-2 from known values under 97% censoring. MI method 2 was the next overall best method. For medium to severe censoring, MI method 1 may result in the least error. If unsure of the distribution, MI method 2 may be a preferred method to avoid distribution misspecification.IMPORTANCE This study evaluates methods for handling data with low (10%) to severe (90%) left-censoring within an environmental microbiology context and demonstrates that some of these methods may be appropriate when using data containing concentrations below a limit of detection to estimate infection risks. Additionally, this study uses a skewed data set, which is an issue typically faced by environmental microbiologists.

Dataset Information

Benchmark dose profiles for joint-action quantal data in quantitative risk assessment.

Publications

Benchmark dose profiles for joint-action quantal data in quantitative risk assessment.

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