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Nevin Manimala Statistics

Regularized ensemble Kalman inversion for robust and efficient gravity data modeling to identify mineral and ore deposits

Sci Rep. 2025 Nov 27. doi: 10.1038/s41598-025-30141-y. Online ahead of print.

ABSTRACT

Modeling mineral and ore bodies from gravity anomalies remains challenging in geophysical exploration due to the ill-posed and non-unique nature of the inverse problem, particularly under conditions of noisy or sparse data. Established inversion methods, including local optimization and metaheuristic algorithms, often require extensive parameter tuning and may yield unstable or poorly constrained solutions. This study proposes a regularized ensemble Kalman inversion (EKI) framework enhanced by Tikhonov regularization to improve numerical stability and mitigate sensitivity to ensemble degeneracy, thereby enabling efficient uncertainty quantification through ensemble statistics. Controlled numerical experiments show that the ensemble size is larger than [Formula: see text] with moderate regularization, we can achieve an optimal balance between convergence stability and model resolution. Benchmarking against established metaheuristic algorithms (PSO, VFSA, and BA) suggests superior computational efficiency and stable convergence. Synthetic and real gravity data inversion (chromite, Pb-Zn, sulphide, and Cu-Au deposits) suggests that the regularized EKI yields stable, geologically consistent results with prior interpretations and drilling data. These results highlight the regularized EKI framework as a robust and efficient tool for mitigating mining risks and supporting strategic decision-making in mineral exploration.

PMID:41310348 | DOI:10.1038/s41598-025-30141-y

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Nevin Manimala Statistics

Effects of combined group reminiscence and exercise therapy on psychological wellbeing and functional fitness among older adults with dementia

Sci Rep. 2025 Nov 27;15(1):42449. doi: 10.1038/s41598-025-26503-1.

ABSTRACT

Reminiscence therapy and exercise therapy have both proven beneficial for individuals with dementia. However, there is limited information on the effects of combining these two approaches in older adults with dementia. Our study aimed to investigate the impact of combined group reminiscence therapy (GRT) and group exercise therapy (GET) on psychological well-being and functional fitness in this population. A total of 32 older adults with mild to moderate dementia living in care homes were randomly assigned into either intervention or usual care groups. The study was conducted from January to June 2021. Intervention: Participants in intervention group received weekly an hour session of GRT and biweekly 1.25-hour session of GET. Reminiscence therapy was based on Remembering Yesterday and Caring Today module, adapted and modified according to participants’ cultural background. GET consisted of stretching, strengthening, aerobic and multicomponent exercises. Outcome measures include the Quality of Life – Alzheimer’s Disease (QOL-AD), Addenbrooke’s Cognitive Examination-III (ACE-III), Beck Anxiety Inventory (BAI), Satisfaction with Life Scale (SWLS), Geriatric Depression Scale (GDS), and Functional Fitness MOT (FFMOT). Independent sample t-test and Mann-Whitney U test show that the participants from the GRT + GET group reported statistically significant higher quality of life and satisfaction with life, with a medium to large effect size. There are no other statistically significant results found for other psychosocial measures. FFMOT was found to deteriorate in both groups with a lesser amount in the intervention group. This study suggests that combined GRT and GET may induce some psychosocial benefits, in particular quality of life and some positive trend in deceleration of functional fitness deterioration among older adults with mild to moderate dementia. Preserving psychological and physical wellbeing is essential for older adults with dementia to maintain their functional independence for as long as possible.

PMID:41310327 | DOI:10.1038/s41598-025-26503-1

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Nevin Manimala Statistics

Inter-operator reliability of the total decomposition score (TDS) method for estimating the post-mortem interval (PMI) in outdoor cases

Int J Legal Med. 2025 Nov 28. doi: 10.1007/s00414-025-03681-1. Online ahead of print.

ABSTRACT

In the estimation of the Post-Mortem Interval (PMI), semi-quantitative methods have been proposed to overcome the challenges associated with determining the time of death. Among these, the Total Decomposition Score (TDS) method, developed by Gelderman et al., offers a systematic and semi-quantitative approach for estimating PMI. The aim of this study was to evaluate the reliability of the TDS by assessing its interoperator variability and comparing the results obtained with known reference data. A TDS-based questionnaire was administered to 100 participants – including forensic pathologists, residents in forensic medicine and professionals in forensic thanatology – using a dataset of six outdoor cadavers representing different decomposition stages. Data were analyzed using Fleiss’ Kappa (K) to assess inter-rater agreement and Spearman’s rank correlation to evaluate consistency. The results showed moderate overall agreement, with inter-rater reliability decreasing in cases with PMI exceeding 30 days. Linear regression analyses between estimated and actual post-mortem intervals yielded low coefficients of determination, with R² = 34.1% for the TDS-based model and R² = 20.5% for the ADD-based model, indicating that both methods explain only a limited portion of the variance in the actual PMI (PMIa). No statistically significant differences were observed among the professional categories, supporting the method’s applicability across different levels of expertise. While TDS shows promise as a practical tool for PMI estimation in field conditions, inter-operator variability remains a limiting factor in advanced decomposition stages.

PMID:41310302 | DOI:10.1007/s00414-025-03681-1

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Nevin Manimala Statistics

Machine Learning Algorithms for Predicting Injurious Fall Risk Among Older Adults With Depression: A Prognostic Modeling Study

Pharmacotherapy. 2025 Nov 27. doi: 10.1002/phar.70087. Online ahead of print.

ABSTRACT

BACKGROUND: Falls and related injuries (FRI) pose a large burden among older adults with depression. Proactively identifying individuals at high FRI risk enables timely and tailored interventions, reducing unnecessary health care resource utilization. However, prior prediction models relied on fixed time intervals and failed to capture dynamic changes in health status over time.

OBJECTIVES: To develop and validate machine-learning algorithms (i.e., elastic net, random forest, and gradient boosting machine) for predicting 3-month FRI risk among older adults with depression.

METHODS: This prognostic modeling study included fee-for-service Medicare beneficiaries aged 65 years or older with a depression diagnosis in 2017. Beneficiaries were followed in 3-month episodes from the first depression diagnosis until the earliest of death, hospice services or nursing facility utilization, switching to Medicare Advantage plans, or the end of the study period (i.e., December 31, 2019). A total of 261 time-varying predictors, spanning patient-, provider-, health system- and region-related factors, were updated every 3 months to predict incident FRI risk in the subsequent 3 months. We assessed prediction performance using c-statistics and stratified patients into different risk subgroups using the best-performing model.

RESULTS: Among 274,268 eligible beneficiaries, the mean age was 74.6 (standard deviation [SD] = 7.2) years, 32.0% were male, 85.2% were White, and 15.1% experienced at least one FRI event throughout the study period. Using the random forest model (c-statistics = 0.68), 68.9% of the actual FRI cases were captured in the top three deciles of predicted risk. Individuals in the bottom seven deciles had a minimal FRI incidence (< 1.7%). Key predictors included frailty, age, prior FRI history, and daily dose of antidepressants.

CONCLUSION: Using a nationally representative cohort and time-varying predictors, our model offers a practical approach for efficiently identifying older adults at high FRI risk, which can be updated over time. This approach can inform clinical decision-making and optimize the allocation of fall prevention resources.

PMID:41310296 | DOI:10.1002/phar.70087

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Nevin Manimala Statistics

Strategic Timing of Larval Harvest as a Practical Approach to Increase Baculovirus Mass Production

Neotrop Entomol. 2025 Nov 27;54(1):121. doi: 10.1007/s13744-025-01341-y.

ABSTRACT

Baculoviruses are important bioinsecticides in integrated pest management, with in vivo production systems still predominant due to cost-effectiveness and scalability. However, inconsistencies in quality, such as viral infectivity and contamination, and polyhedra yield restrict their wider adoption. This study evaluated the infection dynamics of Spodoptera frugiperda multiple nucleopolyhedrovirus – Alphabaculovirus spofrugiperdae isolate 6 (SfMNPV6) in Spodoptera frugiperda larvae to determine the optimal harvest time for maximizing occlusion body (OB) yield. Larvae were exposed to three inoculum concentrations (1 × 105, 1 × 10⁶, and 1 × 10⁷ OB/mL) and monitored daily from the third to the tenth day post-infection. We assessed larval survival, tegument color as an indicator of infection symptoms, and polyhedra yield. Results indicated dose-dependent variations in disease progression, with the infection peak occurring on days seven, eight, and ten for the highest to lowest inoculum concentrations, respectively. Pinkish tegument symptom was strongly correlated with maximum OB yield, making it a reliable visual indicator for harvest timing. Statistical modeling confirmed the relationship between tegument color and OB concentration, with pinkish larvae (symptomatic) significantly outperforming green (early infection stage) and gray (post-mortem period) larvae in virus production. This symptom-based monitoring provides a low-cost, non-invasive alternative to enhance timing in baculovirus harvest protocols. These findings suggest that optimizing harvest based on larval symptoms and dose-dependent infection dynamics can improve virus yield and product quality. This approach enhances the reliability of baculovirus-based bioinsecticides, providing a more effective production strategy to meet the increasing demand for biological control agents in sustainable agriculture, particularly as global pest pressures are intensified by climate change.

PMID:41310286 | DOI:10.1007/s13744-025-01341-y

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Nevin Manimala Statistics

What are the Individual Characteristics or Skills Associated with Baseball Batting Performance? A Scoping Review

Sports Med Open. 2025 Nov 27;11(1):150. doi: 10.1186/s40798-025-00947-1.

ABSTRACT

BACKGROUND: In baseball, batting performance can be measured using game and advanced statistics as well as hitting metrics. To date, the core set of individual characteristics or skills associated with superior batting performance remains to be identified. The aim of this scoping review was to identify and classify the individual characteristics or skills associated with baseball batting performance indicators and describe the methods used to assess these individual characteristics or skills and batting performance indicators.

METHODS: A scoping review design was chosen to conduct a systematic literature search. Electronic searches of MEDLINE, SPORTDiscus, and PsycINFO databases were undertaken from inception to August 2024. Cross-sectional studies that investigated the relationship between batting performance indicators and individual characteristics or skills in male or female baseball batters were selected.

RESULTS: Twenty-two cross-sectional studies investigating potential individual characteristics or skills of baseball batting performance met the inclusion criteria. The primary baseball batting performance indicators were grouped into three categories: game statistics, advanced statistics and hitting metrics. Anthropometric measures (height, weight), physical fitness tests (1-RM bench and squat, grip strength, jumps, medicine ball throws, sprint, trunk flexibility, etc.), visual skills (visual acuity, contrast sensitivity, etc.), perceptual skills (anticipation, visual recognition, etc.) and visuomotor skills (eye-hand coordination, reaction time, etc.) were the individual characteristics or skills associated with either game statistics, advanced statistics or hitting metrics.

CONCLUSIONS: Based on the studies included in this scoping review, the results show that several anthropometrics, physical, perceptual-cognitive, and visual skills were associated with superior game statistics, advanced statistics or hitting metrics. Greater height, weight, upper- and lower-body muscle strength, power, and speed, as well as oculomotor skills, visual system characteristics, anticipation, visual recognition, and visuomotor skills corresponded to better batting performance.

PMID:41310274 | DOI:10.1186/s40798-025-00947-1

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Nevin Manimala Statistics

Kinetic control of mammalian transcription elongation

Nat Struct Mol Biol. 2025 Nov 27. doi: 10.1038/s41594-025-01707-1. Online ahead of print.

ABSTRACT

Transcription elongation by RNA polymerase II (Pol II) is an integral step in eukaryotic gene expression. The speed of Pol II is controlled by a multitude of elongation factors, but the exact regulatory mechanisms remain incompletely understood, especially for higher eukaryotes. Here we develop a single-molecule platform to visualize the dynamics of individual mammalian transcription elongation complexes (ECs) reconstituted from purified proteins. This platform allows us to follow the elongation and pausing behavior of EC in real time and unambiguously determine the role of each elongation factor in the kinetic control of Pol II. We find that the mammalian EC harbors multiple speed gears dictated by its associated factors and phosphorylation status. Moreover, the elongation factors are not functionally redundant but act hierarchically and synergistically to achieve optimal elongation activity. We propose that such elaborate kinetic regulation underlies the major speed-changing events during the transcription cycle and enables cells to adapt to a changing environment.

PMID:41310264 | DOI:10.1038/s41594-025-01707-1

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Nevin Manimala Statistics

The effect of berberine on obesity indices: a systematic review and meta-analysis

Int J Obes (Lond). 2025 Nov 27. doi: 10.1038/s41366-025-01943-x. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Obesity is an already identified risk factor for various noncommunicable diseases. Berberine is an alkaloid that has manifested a significant effect in the treatment of obesity and its complications. The aim of this systematic review and meta analysis is to evaluate the effect of berberine on obesity indices.

METHODS: We conducted a comprehensive search of Scopus, PubMed, Web of Science, and Google Scholar for randomized controlled trials (RCTs) investigating berberine’s impact on obesity indices in adults. Eligible studies included human trials with quantitative outcomes for weight, BMI, WC, or WHR. Animal studies, reviews, and non-RCTs were excluded. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. A random-effects meta-analysis was performed to calculate mean differences (MDs) and 95% confidence intervals (CIs). Heterogeneity was evaluated using I² statistics.

RESULTS: A total of 23 articles were included. Berberine significantly reduced body weight (MD of -0.88 kg, 95% CI: -1.36 to -0.39, p = 0.0003), BMI (MD of -0.48 kg/m², 95% CI: -0.89 to -0.07, p < 0.0216), and WC (MD of -1.32 kg/m², 95% CI: -2.24 to -0.41, p < 0.0046). However, berberine did not significantly reduce WHR compared to control groups (MD of -0.01, 95% CI: -0.03 to 0.01). Meta-regression revealed no association between berberine use and age.

CONCLUSION: Berberine use significantly reduces body weight, BMI, and WC but does not significantly reduce WHR. Future trials should focus on improving reporting standards for biochemical characterization (such as purity, potency and gram amounts) and address common biases such as lack of blinding and randomization to enhance the reliability of the evidence.

PMID:41310257 | DOI:10.1038/s41366-025-01943-x

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Nevin Manimala Statistics

Gender differences in patient assessment times for ambulatory emergency department patients

CJEM. 2025 Nov 28. doi: 10.1007/s43678-025-01030-0. Online ahead of print.

ABSTRACT

BACKGROUND: Gender disparities in medicine are well documented, including in emergency medicine. These disparities are influenced by a variety of factors such as payment models, patient expectations, and time spent on different aspects of care, including documentation. While gender-based differences in patient care have been associated with better outcomes for patients treated by women physicians, the underlying reasons remain unclear. This study aims to quantify and compare time spent on patient care tasks, stratified by physician gender, in an academic emergency department (ED).

METHODS: We conducted a prospective observational time-motion study from July to August 2022 in the ambulatory care area of a large tertiary academic ED. Research assistants shadowed physicians during daytime and evening shifts, timing eight predefined clinical tasks for each patient encounter while also collecting data on patient characteristics and provider demographics (gender, years of practice, training stream). Statistical analyses included Wilcoxon rank sum tests and linear regression to examine task durations and gender differences. Our sample size was determined by feasibility.

RESULTS: Thirty-seven physicians (32.4% women, 67.6% men) were observed across 65 shifts involving 1204 patient encounters. Women physicians spent significantly more time per patient than men (mean 20.9 vs. 18.1 min, + 15.5%, p = 0.015), particularly on initial assessments (7.1 vs. 6.4 min, + 10.9%, p = 0.024) and charting (6.7 vs. 5.2 min, + 28.8%, p = 0.001). No significant gender differences were found in other tasks. The additional time spent by women was not fully explained by measured tasks, suggesting other unmeasured contributors such as interruptions or workflow inefficiencies.

CONCLUSION: Women emergency physicians spend more time per patient on assessments and documentation than men physicians. These findings raise important considerations for gender equity in clinical performance metrics and documentation burden.

PMID:41310255 | DOI:10.1007/s43678-025-01030-0

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Nevin Manimala Statistics

Optimizing Air Pollution Exposure Assessment with Application to Cognitive Function

Res Rep Health Eff Inst. 2025 Aug;(228):1-117.

ABSTRACT

INTRODUCTION: Epidemiological studies often make use of exposure data that is collected in opportunistic and logistically convenient ways. And, while exposure assessment is fundamental to environmental epidemiology, little is known about what exposure assessment study designs are optimal for health inference. The objective of this project was to advance our understanding of the design of exposure assessment measurement campaigns and evaluate their impact on estimating the associations between long-term average air pollution exposure and cognitive function. This feeds into the broader goal of advancing understanding of air pollution exposure assessment design for application to epidemiological inference.

METHODS: We leveraged data from the Adult Changes in Thought (ACT3) Air Pollution study (ACT-AP) to characterize exposures for over 5,000 participants from the ongoing ACT cohort. This is a population-based cohort of urban and suburban elderly individuals in the greater Puget Sound region drawn from Group Health Cooperative, now Kaiser Permanente, starting in 1994. Participants were routinely followed with routine biennial visits until dementia incidence, drop-out, or death. Extensive health, lifestyle, biological, and demographic data were also collected. The outcome measure used in this report is cognitive function at baseline based on the Cognitive Abilities Screening Instrument derived using Item Response Theory (CASI-IRT). The IRT transformation of the CASI score improves score accuracy, measures cognitive change with less bias, and accounts for missing test items. Health association analyses were based on 5,409 participants with both a valid CASI score and who had lived in the mobile monitoring region during at least 95% of the 5 years prior to baseline. We used 5-year average exposures that accounted for residential history.

Exposure data came from two distinct exposure assessment campaigns carried out by the ACT-AP study: a campaign using low-cost sensors (2017+) that supplemented existing regulatory monitoring data for fine particles (PM2.5, 1978+) and nitrogen dioxide (NO2, 1996+), and a year-long multipollutant mobile monitoring campaign (2019-2020). The evaluation of the added value of low-cost sensor data relied on a combination of regulatory monitoring data and other high-quality data from research studies, calibrated 2-week low-cost sensor measurements from over 100 locations, which were mostly ACT cohort residences, and a snapshot campaign that measured NO2 using Ogawa samplers. Predictions were at a 2-week average time scale, used a suite of ~200 geographic covariates, and were obtained from a spatiotemporal model developed at the University of Washington. The Seattle mobile monitoring campaign collected a combination of stationary roadside and on-road measurements of ultrafine particles (UFPs, four instruments), black carbon (BC), NO2, carbon dioxide (CO2), and PM2.5. Visits were temporally balanced over 288 drive days such that all sites were visited during all seasons, days of the week, and most hours of the day (5 a.m. to 11 p.m.) approximately 29 times each. For the on-road measurements, we divided the driving route into 100-meter segments and assigned all measurements to the segment midpoint. Predictions used the same suite of geographic covariates in a spatial model fit using partial least squares (PLS) dimension reduction with universal kriging (UK-PLS) to capture the remaining spatial structure. We reported model performance metrics for both the spatial and spatiotemporal models as root mean squared error (RMSE) and mean squared error (MSE)-based R2. The reference observations for the spatiotemporal model were low-cost sensor measurements at home locations (with performance metrics averaged over their entire measurement period to approximate spatial contrasts), and for the spatial model, the reference observations were the all data long-term averages at stationary roadside locations.

Using various approaches to sample data from these two exposure monitoring campaigns, we determined the impact on exposure prediction and estimates of health associations using two confounder models and 5-year average exposure predictions for cohort members at baseline developed from the alternative campaigns. For the low-cost sensor data, we evaluated temporally or spatially reduced subsets of low-cost sensors, as well as a comparison of the low-cost sensor versus snapshot campaigns for NO2. For the mobile monitoring data, we considered designs focused on the stationary roadside and on-road data separately. We reduced the stationary roadside data temporally by restricting seasons, times of day, or days of week for the campaign, while also considering a reduced number of visits using balanced sampling, as well as a set of unbalanced visit designs. We also reduced the on-road data spatially and temporally to assess the importance of spatially or temporally balanced data collection. In addition, we considered the impact of incorporating temporal adjustment to account for temporally unbalanced sampling, as well as plume adjustment to account for on-road sources. For each design, we evaluated prediction model performance using the all data stationary roadside observations (mobile campaign) or the measurements at homes (low-cost sensor campaign) as reference observations to ensure consistency in reported performance metrics. We also used long-term average exposures estimated from these alternative campaigns in health association analyses under two different confounder models that were adjusted by potentially confounding variables: Model 1 adjusted for age, calendar year, sex, and educational attainment; Model 2 included all Model 1 variables with the addition of race and socioeconomic status. Furthermore, using the stationary roadside data, we applied parametric and nonparametric bootstrap methods to account for Berkson-like and classical-like exposure measurement error for the UFP exposure in confounder model 1.

In a separate methods-focused aim, we developed and applied advanced statistical methods using the stationary roadside mobile monitoring data. To evaluate possible improvements in exposure model performance, we applied tree-based machine learning algorithms that also account for residual spatial structure, and compared these to UK-PLS. This led to the development of a variable importance metric that uses a leave-one-out approach to evaluate the change in predictions across various user-specified quantiles. The variable importance metric produces covariate-specific averages that reflect how the predictions, on average, vary across different quantiles of each covariate. This serves as an intuitive measure of the contribution of this covariate to the predicted outcome. A key idea in this variable importance approach is to reuse the trained mean model across all locations and to refit the covariance model in a leave-one-out manner. In separate work to address dimension reduction for multipollutant prediction, we extended classical principal component analysis (PCA) and a recently developed predictive PCA approach to optimize performance by balancing the representativeness in classical PCA with the predictive ability of predictive PCA. We called the new method representative and predictive PCA, or RapPCA.

Finally, we characterized the various exposure assessment campaigns in terms of the value of their information as quantified by cost. We calculated costs, focused predominantly on staff days of effort, for various exposure assessment designs and compared these to exposure model performance statistics.

RESULTS: We found that air pollution exposure assessment design is critical for exposure prediction, and also impacts health inference. We showed that a mobile monitoring study with stationary roadside sampling that has at least 12 visits per location in a balanced and temporally unrestricted design optimizes exposure model performance while also limiting costs. Relative to weaker alternatives, a balanced and temporally unrestricted design has improved accuracy and reduced variability of health inferences, particularly for confounder model 1. To address temporal balance, it is important that the exposure sampling in mobile monitoring campaigns cover all days of the week, most hours of the day, and at least two seasons. The popular temporally restricted business-hours sampling design had the poorest performance, which was not improved by adjusting for the temporally unbalanced sampling approach. We found similar patterns using on-road data, though the findings were weaker overall.

For the alternative exposure campaign that supplemented regulatory monitoring data with low-cost sensor data, while the exposure prediction model performances improved with the inclusion of the low-cost sensors, there was little notable impact on the health inferences, and the costs were steep. Given that the supplementary exposure assessment data were sparse relative to the existing regulatory monitoring data, and that the low-cost sensor data collection used a rotating approach due to the limited number of sensors (i.e., low-cost sensor measurements were not collected using a balanced design), it was much more challenging to develop deep insights from this exposure assessment approach.

Finally, we found that leveraging spatial ensemble-learning methods for prediction did not improve exposure prediction model performances or alter health inferences. The new multipollutant dimension-reduction we developed, RapPCA, had the best predictive performance and also minimized the prediction error in comparison with both classical and predictive PCA.

CONCLUSIONS: This project has shown that there should be greater attention to the design of the exposure data collection campaigns used in epidemiological inference. Based on the multiple investigations conducted, many of which focused on UFPs, we found that exposure predictions with better performance statistics resulted in health association estimates that were generally more consistent with those obtained using the “best” exposure model predictions (the model with all data included), although the pattern of health estimates was often less conclusive than the pattern of prediction model performances. Furthermore, we found that it is possible to design air pollution exposure assessment studies that achieve good exposure prediction model performance while controlling their relative cost.

We developed strong recommendations for mobile monitoring campaign design, thanks to the well-designed and comprehensive Seattle mobile monitoring campaign. Insights from supplementing regulatory monitoring data with low-cost sensor data were less compelling, driven predominantly by a data structure with sparse and temporally unbalanced supplementary data that may not have been sufficiently comprehensive to demonstrate the impacts of alternative designs. Broadly speaking, better exposure assessment design leads to better exposure prediction model performance, which in turn can benefit estimates of health associations.

We did not find that leveraging advanced statistical methods (specifically, spatial ensemble-learning methods for prediction) improved exposure prediction model performances. This finding is not consistent with the conclusions reached by other investigators, and may have been due to the already sophisticated UK-PLS approach we used by default, and in particular its application in conjunction with the large number of covariates that we considered in the PLS model, such that the contribution of any single covariate was approximately linear. In other words, it is reasonable to believe that in the presence of the large set of covariates we considered, each can contribute an approximately linear association with the pollutant being modeled, such that the potential added value of the spatial Random Forest approach is not observed in the model fit. Other settings with a smaller number of possible covariates available may lead to different conclusions and suggest greater added value of the application of a spatial Random Forest approach.

We based our approach on leveraging the extensive air pollution exposure assessment and outcome data available from the ACT-AP study. Thus, we sampled from the existing air pollution data to evaluate exposure assessment designs that were subsets of those data. Then, conditional on each of these designs, we evaluated subsequent health inferences, which focused on cognitive function at baseline using the CASI-IRT outcome. The magnitude and uncertainty of these health association estimates were dependent upon the associations evident in the ACT cohort, and the insights we were able to develop are conditional on the strengths and weaknesses of these data. Specifically, while we observed some larger impacts on health association estimates of more poorly performing exposure models relative to the complete all data exposure model, such as the business-hours design from a mobile monitoring campaign, many of the differences were small and did not deviate meaningfully from the health association estimate obtained from the “best” exposure model. The degree of impact on the epidemiological inference depended on the magnitude of the health association estimate from the “best” exposure model and the width of its confidence interval. Future investigations should replicate and expand upon these findings in other settings, including application to new cohorts and exposure assessment data, as well as in simulation studies, which provide an alternative approach to using real-world data to evaluate a constellation of exposure models. However, while knowledge of the assumed underlying truth is an important strength of simulation studies, it is challenging to capture real-world complexity meaningfully in simulation studies.

Our foray into applying advanced machine-learning methods to improve exposure predictions produced the surprising result that our default UK-PLS approach for spatial prediction produced similar performance metrics to spatial ensemble-learning methods. Future evaluations that assess smaller subsets of exposure covariates will allow determination of the relative exposure model performance benefits of UK-PLS versus spatial ensemble-learning methods, and provide insights into the possible reason that our conclusions differ from others in the literature.

PMID:41310253