Addressing statistical issues when leveraging external control data in pediatric clinical trials using Bayesian dynamic borrowing.

Conducting a well-powered and adequately controlled clinical trial in children is often challenging. Bayesian approaches are an attractive option for addressing such challenges as they provide a quantitatively rigorous and integrated framework that makes use of current control data to check and borrow information from historical control data. However various practical concerns and related statistical issues emerge when implementing such Bayesian borrowing approaches. In this manuscript we use a motivating case study to discuss a rigorous stepwise approach on how to address those issues within the Bayesian framework. Specifically, a comprehensive quantitative framework is proposed to assess the extent, synergy, and impact of borrowing. Steps on computing the measures to interpret borrowing are illustrated. Those measures can further help to determine whether additional discounting of external information is necessary.

Does the relative importance of the OxCAP-MH's capability items differ according to mental ill-health experience?

BACKGROUND: Some capability dimensions may be more important than others in determining someone's well-being, and these preferences might be dependent on ill-health experience. This study aimed to explore the relative preference weights of the 16 items of the German language version of the OxCAP-MH (Oxford Capability questionnaire-Mental Health) capability instrument and their differences across cohorts with alternative levels of mental ill-health experience. METHODS: A Best-Worst-Scaling (BWS) survey was conducted in Austria among 1) psychiatric patients (direct mental ill-health experience), 2) (mental) healthcare experts (indirect mental ill-health experience), and 3) primary care patients with no mental ill-health experience. Relative importance scores for each item of the German OxCAP-MH instrument were calculated using Hierarchical Bayes estimation. Rank analysis and multivariable linear regression analysis with robust standard errors were used to explore the relative importance of the OxCAP-MH items across the three cohorts. RESULTS: The study included 158 participants with complete cases and acceptable fit statistic. The relative importance scores for the full cohort ranged from 0.76 to 15.72. Findings of the BWS experiment indicated that the items Self-determination and Limitation in daily activities were regarded as the most important for all three cohorts. Freedom of expression was rated significantly less important by psychiatric patients than by the other two cohorts, while Having suitable accommodation appeared significantly less important by the expert cohort. There were no further significant differences in the relative preference weights of OxCAP-MH items between the cohorts or according to gender. CONCLUSIONS: Our study indicates significant between-item but limited mental ill-health related heterogeneity in the relative preference weights of the different capability items within the OxCAP-MH. The findings support the future development of preference-based value sets elicited from the general population for comparative economic evaluation purposes.

Monitoring tropical forest succession at landscape scales despite uncertainty in Landsat time series.

Forecasting rates of forest succession at landscape scales will aid global efforts to restore tree cover to millions of hectares of degraded land. While optical satellite remote sensing can detect regional land cover change, quantifying forest structural change is challenging. We developed a state-space modeling framework that applies Landsat satellite data to estimate variability in rates of natural regeneration between sites in a tropical landscape. Our models work by disentangling measurement error in Landsat-derived spectral reflectance from process error related to successional variability. We applied our modeling framework to rank rates of forest succession between 10 naturally regenerating sites in Southwestern Panama from about 2001 to 2015 and tested how different models for measurement error impacted forecast accuracy, ecological inference, and rankings of successional rates between sites. We achieved the greatest increase in forecasting accuracy by adding intra-annual phenological variation to a model based on Landsat-derived normalized difference vegetation index (NDVI). The best-performing model accounted for inter- and intra-annual noise in spectral reflectance and translated NDVI to canopy height via Landsat-lidar fusion. Modeling forest succession as a function of canopy height rather than NDVI also resulted in more realistic estimates of forest state during early succession, including greater confidence in rank order of successional rates between sites. These results establish the viability of state-space models to quantify ecological dynamics from time series of space-borne imagery. State-space models also provide a statistical approach well-suited to fusing high-resolution data, such as airborne lidar, with lower-resolution data that provides better temporal and spatial coverage, such as the Landsat satellite record. Monitoring forest succession using satellite imagery could play a key role in achieving global restoration targets, including identifying sites that will regain tree cover with minimal intervention.

Conservation and production responses vary by disturbance intensity in a long-term forest management experiment.

Reductions in management intensity are often proposed to support a broader range of beneficial ecosystem responses than traditional management approaches. However, few studies evaluate ecosystem responses across approaches. Also, managers lack information about how species traits mediate responses across management approaches, a potentially substantial source of spatial and temporal variation in population and community responses that if ignored may hinder effectiveness of management programs. We used data collected over eight years from a manipulative experiment to test how four forest management strategies influenced avian community composition and wood production. After harvesting, we evaluated responses to three levels of plant cover suppression (Light, Moderate, and Intensive herbicide applications) in relation to a control without herbicide. We predicted the Moderate and Intensive treatments would exert strong negative effects on leaf-gleaning insectivores, including species of conservation concern due to long-term population declines. However, given high forest productivity, we expected temporal duration of effects to be short. Richness of leaf-gleaning bird species was reduced by 20-50% during the first four years post-harvest (when herbicide treatments were on-going), but the effect size declined over the next four years once treatments were completed (13-20% reduction). Effect sizes were substantially smaller for the non-leaf-gleaner group during years 1-4 (19-27%) and disappeared during years 5-8 (2-3%). However, in our final year of observation, we did find an average of five fewer non-leaf-gleaner species on Light vs. Control units. In the last two years of observation, turnover probabilities for the leaf-gleaner species remained higher on all treatments compared to the Control (0.11-0.21), indicating that new species continued to colonize treatments. Planted conifers were 40-44% taller and 74-81% larger in diameter in the Moderate and Intensive treatments compared to the Control, leading to substantial gains in wood biomass. Current practices provided more balance between two ecosystem responses, avian diversity and wood production, compared to less intensive alternatives. When short-term negative effects occur, the spatial distribution of harvesting and regeneration regionally indicates that habitat is often available locally to support leaf-gleaning and non-leaf-gleaning bird populations while releasing other portions of the region for high priority conservation objectives including late-successional forest reserves.

Using maintenance records from a long-term sensor monitoring network to evaluate the relationship between maintenance schedule and data quality.

Sensor-based environmental monitoring networks are beginning to provide the large-scale, long-term data required to address important fundamental and applied questions in ecology. However, the data quality from deployed sensors can be difficult and costly to ensure. In this study, we use maintenance records from the 12-year history of Louisiana's Coastwide Reference Monitoring System (CRMS) to assess the relationship between various dimensions of data quality and the frequency of field visits to the sensors. We use hierarchical Bayesian models to estimate the probability of missing data, the probability that a corrective offset of the sensor is required, and the magnitude of required offsets for water elevation and salinity data. We compared these estimates to predetermined risk thresholds to the help identify maintenance schedules that balanced the efficient use of labor resources without sacrificing data quality. We found that the relationship between data quality and increasing maintenance interval varied across metrics. Additionally, for most metrics, the maintenance interval when the metric's credible interval and risk threshold intersected varied throughout the year and with wetland type. These results suggest that complex maintenance schedules, in which field visits vary in frequency throughout the year and with environmental context, are likely to provide the best tradeoff between labor cost and data quality. This analysis demonstrates that quantitative assessment of maintenance records can positively impact the sustainability of long-term data collection projects by helping identify new potential efficiencies in monitoring program management.

A Bayesian latent variable approach to aggregation of partial and top-ranked lists in genomic studies.

In genomic research, it is becoming increasingly popular to perform meta-analysis, the practice of combining results from multiple studies that target a common essential biological problem. Rank aggregation, a robust meta-analytic approach, consolidates such studies at the rank level. There exists extensive research on this topic, and various methods have been developed in the past. However, these methods have two major limitations when they are applied in the genomic context. First, they are mainly designed to work with full lists, whereas partial and/or top-ranked lists prevail in genomic studies. Second, the component studies are often clustered, and the existing methods fail to utilize such information. To address the above concerns, a Bayesian latent variable approach, called BiG, is proposed to formally deal with partial and top-ranked lists and incorporate the effect of clustering. Various reasonable prior specifications for variance parameters in hierarchical models are carefully studied and compared. Simulation results demonstrate the superior performance of BiG compared with other popular rank aggregation methods under various practical settings. A non-small-cell lung cancer data example is analyzed for illustration.

Adult mortality in a low-density tree population using high-resolution remote sensing.

We developed a statistical framework to quantify mortality rates in canopy trees observed using time series from high-resolution remote sensing. By timing the acquisition of remote sensing data with synchronous annual flowering in the canopy tree species Handroanthus guayacan, we made 2,596 unique detections of 1,006 individual adult trees within 18,883 observation attempts on Barro Colorado Island, Panama (BCI) during an 11-yr period. There were 1,057 observation attempts that resulted in missing data due to cloud cover or incomplete spatial coverage. Using the fraction of 123 individuals from an independent field sample that were detected by satellite data (109 individuals, 88.6%), we estimate that the adult population for this species on BCI was 1,135 individuals. We used a Bayesian state-space model that explicitly accounted for the probability of tree detection and missing observations to compute an annual adult mortality rate of 0.2%·yr-1 (SE = 0.1, 95% CI = 0.06-0.45). An independent estimate of the adult mortality rate from 260 field-checked trees closely matched the landscape-scale estimate (0.33%·yr-1 , SE = 0.16, 95% CI = 0.12-0.74). Our proof-of-concept study shows that one can remotely estimate adult mortality rates for canopy tree species precisely in the presence of variable detection and missing observations.

Testing the External Validity of a Discrete Choice Experiment Method: An Application to Latent Tuberculosis Infection Treatment.

OBJECTIVES: To explore the external validity and predictive power of stated preferences obtained from a discrete choice experiment (DCE) by comparing the predicted behavior of respondents to their actual choices at an individual level. METHODS: A DCE was performed in patients before being offered treatment for latent tuberculosis infection. A mixed logit model was estimated using hierarchical Bayes. The individual-specific preference coefficients were used to calculate the expected probability of choosing the treatment by each patient. The predicted choice using this probability was compared with their actual decision. We used a receiver-operating characteristic curve and different thresholds to convert probabilities into the predicted choices. The comparability of different distributions for the random parameters was also examined. RESULTS: Our results identified significant heterogeneity in preferences for all attributes among respondents. The best model correctly predicted actual treatment decisions for 83% of the participants. The results from using different thresholds and a receiver-operating characteristic curve also confirmed the compatibility between predicted and actual choices. We showed that individual-specific coefficients reflected respondents' actual choices more closely compared with the aggregate-level estimates. CONCLUSIONS: The results of this study provided support for the external validity of DCEs on the basis of their power to predict actual behavior in this setting. Future investigations are, however, required to establish the external validity of DCEs in different settings.

Diverse foraging opportunities drive the functional response of local and landscape-scale bear predation on Pacific salmon.

The relationship between prey abundance and predation is often examined in single habitat units or populations, but predators may occupy landscapes with diverse habitats and foraging opportunities. The vulnerability of prey within populations may depend on habitat features that hinder predation, and increased density of conspecifics in both the immediate vicinity and the broader landscape. We evaluated the relative effects of physical habitat, local, and neighborhood prey density on predation by brown bears on sockeye salmon in a suite of 27 streams using hierarchical Bayesian functional response models. Stream depth and width were inversely related to the maximum proportion of salmon killed, but not the asymptotic limit on total number killed. Interannual variation in predation was density dependent; the number of salmon killed increased with fish density in each stream towards an asymptote. Seven streams in two geographical groups with ≥23 years of data in common were then analyzed for neighborhood density effects. In most (12 of 18) cases predation in a stream was reduced by increasing salmon abundance in neighboring streams. The uncertainty in the estimates for these neighborhood effects may have resulted from interactions between salmon abundance and habitat that influenced foraging by bears, and from bear behavior (e.g., competitive exclusion) and abundance. Taken together, the results indicated that predator-prey interactions depend on density at multiple spatial scales, and on habitat features of the surrounding landscape. Explicit consideration of this context dependency should lead to improved understanding of the ecological impacts of predation across ecosystems and taxa.

Trait-mediated assembly processes predict successional changes in community diversity of tropical forests.

Interspecific differences in relative fitness can cause local dominance by a single species. However, stabilizing interspecific niche differences can promote local diversity. Understanding these mechanisms requires that we simultaneously quantify their effects on demography and link these effects to community dynamics. Successional forests are ideal systems for testing assembly theory because they exhibit rapid community assembly. Here, we leverage functional trait and long-term demographic data to build spatially explicit models of successional community dynamics of lowland rainforests in Costa Rica. First, we ask what the effects and relative importance of four trait-mediated community assembly processes are on tree survival, a major component of fitness. We model trait correlations with relative fitness differences that are both density-independent and -dependent in addition to trait correlations with stabilizing niche differences. Second, we ask how the relative importance of these trait-mediated processes relates to successional changes in functional diversity. Tree dynamics were more strongly influenced by trait-related interspecific variation in average survival than trait-related responses to neighbors, with wood specific gravity (WSG) positively correlated with greater survival. Our findings also suggest that competition was mediated by stabilizing niche differences associated with specific leaf area (SLA) and leaf dry matter content (LDMC). These drivers of individual-level survival were reflected in successional shifts to higher SLA and LDMC diversity but lower WSG diversity. Our study makes significant advances to identifying the links between individual tree performance, species functional traits, and mechanisms of tropical forest succession.

Bayes and empirical Bayes methods for reduced rank regression models in matched case-control studies.

Matched case-control studies are popular designs used in epidemiology for assessing the effects of exposures on binary traits. Modern studies increasingly enjoy the ability to examine a large number of exposures in a comprehensive manner. However, several risk factors often tend to be related in a nontrivial way, undermining efforts to identify the risk factors using standard analytic methods due to inflated type-I errors and possible masking of effects. Epidemiologists often use data reduction techniques by grouping the prognostic factors using a thematic approach, with themes deriving from biological considerations. We propose shrinkage-type estimators based on Bayesian penalization methods to estimate the effects of the risk factors using these themes. The properties of the estimators are examined using extensive simulations. The methodology is illustrated using data from a matched case-control study of polychlorinated biphenyls in relation to the etiology of non-Hodgkin's lymphoma.

Rapid shifts in dispersal behavior on an expanding range edge.

Dispersal biology at an invasion front differs from that of populations within the range core, because novel evolutionary and ecological processes come into play in the nonequilibrium conditions at expanding range edges. In a world where species' range limits are changing rapidly, we need to understand how individuals disperse at an invasion front. We analyzed an extensive dataset from radio-tracking invasive cane toads (Rhinella marina) over the first 8 y since they arrived at a site in tropical Australia. Movement patterns of toads in the invasion vanguard differed from those of individuals in the same area postcolonization. Our model discriminated encamped versus dispersive phases within each toad's movements and demonstrated that pioneer toads spent longer periods in dispersive mode and displayed longer, more directed movements while they were in dispersive mode. These analyses predict that overall displacement per year is more than twice as far for toads at the invasion front compared with those tracked a few years later at the same site. Studies on established populations (or even those a few years postestablishment) thus may massively underestimate dispersal rates at the leading edge of an expanding population. This, in turn, will cause us to underpredict the rates at which invasive organisms move into new territory and at which native taxa can expand into newly available habitat under climate change.

Wood production response to climate change will depend critically on forest composition and structure.

Established forests currently function as a major carbon sink, sequestering as woody biomass about 26% of global fossil fuel emissions. Whether forests continue to act as a global sink will depend on many factors, including the response of aboveground wood production (AWP; MgC ha(-1 ) yr(-1) ) to climate change. Here, we explore how AWP in New Zealand's natural forests is likely to change. We start by statistically modelling the present-day growth of 97 199 individual trees within 1070 permanently marked inventory plots as a function of tree size, competitive neighbourhood and climate. We then use these growth models to identify the factors that most influence present-day AWP and to predict responses to medium-term climate change under different assumptions. We find that if the composition and structure of New Zealand's forests were to remain unchanged over the next 30 years, then AWP would increase by 6-23%, primarily as a result of physiological responses to warmer temperatures (with no appreciable effect of changing rainfall). However, if warmth-requiring trees were able to migrate into currently cooler areas and if denser canopies were able to form, then a different AWP response is likely: forests growing in the cool mountain environments would show a 30% increase in AWP, while those in the lowland would hardly respond (on average, -3% when mean annual temperature exceeds 8.0 °C). We conclude that response of wood production to anthropogenic climate change is not only dependent on the physiological responses of individual trees, but is highly contingent on whether forests adjust in composition and structure.

A Hierarchical Bayesian approach to small area estimation of health insurance coverage in Ethiopian administrative zones for better policies and programs.

Sample surveys are extensively used to provide reliable direct estimates for large areas or domains with enough sample sizes at national and regional levels. However, zones are unplanned domains by the Demographic and Health Survey (DHS) program and need more sample sizes to produce direct survey estimates with adequate precision. Conducting surveys in small areas (like zones) is too expensive and time-consuming, making it unfeasible for developing countries like Ethiopia. Therefore, this study aims to use the Hierarchical Bayes (HB) Small Area Estimation (SAE) model to estimate the Community-Based Health Insurance (CBHI) coverage at the zone levels in Ethiopia. To achieve this, we combined the 2019 Ethiopia Mini-Demographic and Health Survey (EMDHS) data with the 2007 population census data. SAE has addressed the challenge of producing reliable parameter estimates for small or even zero sample sizes across Ethiopian zones by utilizing auxiliary information from the population census. The results show that model-based estimates generated by the SAE approach are more accurate than direct survey estimates of CBHI. A map of CBHI scheme coverage was also used to visualize the spatial variation in the distribution of CBHI scheme coverage. From the CBHI scheme coverage map, we noticed notable variations in CBHI scheme coverage across Ethiopian zones. Additionally, this research identified areas with high and low CBHI scheme coverage to improve decision-making and increase coverage in Ethiopia. One of the novelties of this paper is estimating the non-sampled zones; therefore, the policymakers will give equal attention similar to the sampled zones.

Bayesian analysis of multivariate mixed models for a prospective cohort study using skew-elliptical distributions.

Classical multivariate mixed models that acknowledge the correlation of patients through the incorporation of normal error terms are widely used in cohort studies. Violation of the normality assumption can make the statistical inference vague. In this paper, we propose a Bayesian parametric approach by relaxing this assumption and substituting some flexible distributions in fitting multivariate mixed models. This strategy allows for the skewness and the heavy tails of error-term distributions and thus makes inferences robust to the violation. This approach uses flexible skew-elliptical distributions, including skewed, fat, or thin-tailed distributions, and imposes the normal model as a special case. We use real data obtained from a prospective cohort study on the low back pain to illustrate the usefulness of our proposed approach.

Effects of Multi-Level Eco-Labels on the Product Evaluation of Meat and Meat Alternatives-A Discrete Choice Experiment.

Eco-labels are an instrument for enabling informed food choices and supporting a demand-sided change towards an urgently needed sustainable food system. Lately, novel eco-labels that depict a product's environmental life cycle assessment on a multi-level scale are being tested across Europe's retailers. This study elicits consumers' preferences and willingness to pay (WTP) for a multi-level eco-label. A Discrete Choice Experiment was conducted; a representative sample (n = 536) for the Austrian population was targeted via an online survey. Individual partworth utilities were estimated by means of the Hierarchical Bayes. The results show higher WTP for a positively evaluated multi-level label, revealing consumers' perceived benefits of colorful multi-level labels over binary black-and-white designs. Even a negatively evaluated multi-level label was associated with a higher WTP compared to one with no label, pointing towards the limited effectiveness of eco-labels. Respondents' preferences for eco-labels were independent from their subjective eco-label knowledge, health consciousness, and environmental concern. The attribute "protein source" was most important, and preference for an animal-based protein source (beef) was strongly correlated with consumers' meat attachment, implying that a shift towards more sustainable protein sources is challenging, and sustainability labels have only a small impact on the meat product choice of average consumers.

scMET: Bayesian modeling of DNA methylation heterogeneity at single-cell resolution.

High-throughput single-cell measurements of DNA methylomes can quantify methylation heterogeneity and uncover its role in gene regulation. However, technical limitations and sparse coverage can preclude this task. scMET is a hierarchical Bayesian model which overcomes sparsity, sharing information across cells and genomic features to robustly quantify genuine biological heterogeneity. scMET can identify highly variable features that drive epigenetic heterogeneity, and perform differential methylation and variability analyses. We illustrate how scMET facilitates the characterization of epigenetically distinct cell populations and how it enables the formulation of novel hypotheses on the epigenetic regulation of gene expression. scMET is available at https://github.com/andreaskapou/scMET .

Patient Preferences for Attributes of Chemotherapy for Lung Cancer: Discrete Choice Experiment Study in Japan.

Our study objective was to determine lung cancer chemotherapy attributes that are important to patients in Japan. A discrete choice experiment survey in an anonymous web-based questionnaire format with a reward was completed by 200 lung cancer patients in Japan from November 25, 2019, to November 27, 2019. The relative importance of patient preferences for each attribute was estimated using a conditional logit model. A hierarchical Bayesian logit model was also used to estimate the impact of each demographic characteristic on the relative importance of each attribute. Of the 200 respondents, 191 with consistent responses were included in the analysis. In their preference, overall survival was the most important, followed by diarrhea, nausea, rash, bone marrow suppression (BMS), progression-free survival, fatigue, interstitial lung disease, frequency of administration, and duration of administration. The preferences were influenced by demographic characteristics (e.g., gender and age) and disease background (e.g., cancer type and stage). Interestingly, the experience of cancer drug therapies and adverse events had a substantial impact on the hypothetical drug preferences. For the Japanese lung cancer patients, improved survival was the most important attribute that influenced their preference for chemotherapy, followed by adverse events, including diarrhea, nausea, rash, and BMS. The preferences varied depending on the patient's demographic and experience. As drug attributes can affect patient preferences, pharmaceutical companies should be aware of the patient preferences and develop drugs that respond to segmented market needs.

Hierarchal Bayes model with AlexNet for characterization of M-FISH chromosome images.

The analysis of chromosomes is a significant and challenging task for clinical diagnosis and biological research. The technique based on color imaging is a multiplex fluorescent in situ hybridization (M-FISH), which was implemented to ease the exploration of the chromosomes. Thus, in this paper, we propose a novel quasi-Newton-based K-means clustering for the M-FISH image segmentation. Then, we use the expectation-maximization-based hierarchical Bayes model to characterize the M-FISH images. The contextual-based classification and region merging of chromosomal images is made to avoid any misclassification, and we made use of AlexNet, by modifying the activation functions of the sigmoid and softmax layer and for the optimum classification between the autosomal chromosomes and the sex chromosome. Finally, we conducted a performance analysis by measuring accuracy, recall, sensitivity, specificity, PPV, NPV, F-score, kappa, Jaccard, and Dice coefficient and compared with other existing methods and found that our proposed methodology can achieve more percentage of accuracy (6.96%) than the state of the art methods.