Distributional Validation of Precipitation Data Products with Spatially Varying Mixture Models.

The high mountain regions of Asia contain more glacial ice than anywhere on the planet outside of the polar regions. Because of the large population living in the Indus watershed region who are reliant on melt from these glaciers for fresh water, understanding the factors that affect glacial melt along with the impacts of climate change on the region is important for managing these natural resources. While there are multiple climate data products (e.g., reanalysis and global climate models) available to study the impact of climate change on this region, each product will have a different amount of skill in projecting a given climate variable, such as precipitation. In this research, we develop a spatially varying mixture model to compare the distribution of precipitation in the High Mountain Asia region as produced by climate models with the corresponding distribution from in situ observations from the Asian Precipitation-Highly Resolved Observational Data Integration Towards Evaluation (APHRODITE) data product. Parameter estimation is carried out via a computationally efficient Markov chain Monte Carlo algorithm. Each of the estimated climate distributions from each climate data product is then validated against APHRODITE using a spatially varying Kullback-Leibler divergence measure. Supplementary materials accompanying this paper appear online. Supplementary materials for this article are available at 10.1007/s13253-022-00515-0.

Imaging biomarkers of lung ventilation in interstitial lung disease from 129Xe and oxygen enhanced 1H MRI.

PURPOSE: To compare imaging biomarkers from hyperpolarised 129Xe ventilation MRI and dynamic oxygen-enhanced MRI (OE-MRI) with standard pulmonary function tests (PFT) in interstitial lung disease (ILD) patients. To evaluate if biomarkers can separate ILD subtypes and detect early signs of disease resolution or progression. STUDY TYPE: Prospective longitudinal. POPULATION: Forty-one ILD (fourteen idiopathic pulmonary fibrosis (IPF), eleven hypersensitivity pneumonitis (HP), eleven drug-induced ILD (DI-ILD), five connective tissue disease related-ILD (CTD-ILD)) patients and ten healthy volunteers imaged at visit 1. Thirty-four ILD patients completed visit 2 (eleven IPF, eight HP, ten DIILD, five CTD-ILD) after 6 or 26 weeks. FIELD STRENGTH/SEQUENCE: MRI was performed at 1.5 T, including inversion recovery T1 mapping, dynamic MRI acquisition with varying oxygen levels, and hyperpolarised 129Xe ventilation MRI. Subjects underwent standard spirometry and gas transfer testing. ASSESSMENT: Five 1H MRI and two 129Xe MRI ventilation metrics were compared with spirometry and gas transfer measurements. STATISTICAL TEST: To evaluate differences at visit 1 among subgroups: ANOVA or Kruskal-Wallis rank tests with correction for multiple comparisons. To assess the relationships between imaging biomarkers, PFT, age and gender, at visit 1 and for the change between visit 1 and 2: Pearson correlations and multilinear regression models. RESULTS: The global PFT tests could not distinguish ILD subtypes. Percentage ventilated volumes were lower in ILD patients than in HVs when measured with 129Xe MRI (HV 97.4 ± 2.6, CTD-ILD: 91.0 ± 4.8 p = 0.017, DI-ILD 90.1 ± 7.4 p = 0.003, HP 92.6 ± 4.0 p = 0.013, IPF 88.1 ± 6.5 p < 0.001), but not with OE-MRI. 129Xe reported more heterogeneous ventilation in DI-ILD and IPF than in HV, and OE-MRI reported more heterogeneous ventilation in DI-ILD and IPF than in HP or CTD-ILD. The longitudinal changes reported by the imaging biomarkers did not correlate with the PFT changes between visits. DATA CONCLUSION: Neither 129Xe ventilation nor OE-MRI biomarkers investigated in this study were able to differentiate between ILD subtypes, suggesting that ventilation-only biomarkers are not indicated for this task. Limited but progressive loss of ventilated volume as measured by 129Xe-MRI may be present as the biomarker of focal disease progresses. OE-MRI biomarkers are feasible in ILD patients and do not correlate strongly with PFT. Both OE-MRI and 129Xe MRI revealed more spatially heterogeneous ventilation in DI-ILD and IPF.

Developing High-Resolution Population and Settlement Data for Impactful Malaria Interventions in Zambia.

Foundational high-resolution geospatial data products for population, settlements, infrastructure, and boundaries may greatly enhance the efficient planning of resource allocation during health sector interventions. To ensure the relevance and sustainability of such products, government partners must be involved from the beginning in their creation, improvement, and/or management, so they can be successfully applied to public health campaigns, such as malaria control and prevention. As an example, Zambia had an ambitious strategy of reaching the entire population with malaria vector control campaigns by late 2020 or early 2021, but they lacked the requisite accurate and up-to-date data on infrastructure and population distribution. To address this gap, the Geo-Referenced Infrastructure and Demographic Data for Development (GRID3) program, Akros, and other partners developed maps and planning templates to aid Zambia's National Malaria Elimination Program (NMEP) in operationalizing its strategy.

A Bayesian approach to real-time spatiotemporal prediction systems for bronchiolitis.

Respiratory Syncytial Virus (RSV) induced bronchiolitis is a common lung infection and a major cause of infant hospitalization and mortality. Unfortunately, there is no known cure for RSV but several vaccines are in various stages of clinical trials. Currently, immunoprophylaxis is a preventative measure consisting of a series of monthly shots that should be administered at the start, and throughout, peak RSV season. Thus, the successful implementation of immunoprophylaxis is contingent upon understanding when outbreak seasons will begin, peak, and end. In this research we estimate the seasonal epidemic curves of RSV induced bronchiolitis using a spatially varying change point model. Further, in a novel approach and using the fitted change point model, we develop a historical matching algorithm to generate real time predictions of seasonal curves for future years.

Modeling Bronchiolitis Incidence Proportions in the Presence of Spatio-Temporal Uncertainty.

Bronchiolitis (inflammation of the lower respiratory tract) in infants is primarily due to viral infection and is the single most common cause of infant hospitalization in the United States. To increase epidemiological understanding of bronchiolitis (and, subsequently, develop better prevention strategies), this research analyzes data on infant bronchiolitis cases from the U.S. Military Health System between the years 2003-2013 in Norfolk, Virginia, USA. For privacy reasons, child home addresses, birth dates, and diagnosis dates were randomized (jittered) creating spatio-temporal uncertainty in the geographic location and timing of bronchiolitis incidents. Using spatio-temporal point patterns, we created a modeling strategy that accounts for the jittering to estimate and quantify the uncertainty for the incidence proportion (IP) of bronchiolitis. Additionally, we regress the IP onto key covariates including pollution where we adequately account for uncertainty in the pollution levels (i.e., covariate uncertainty) using a land use regression model. Our analysis results indicate that the IP is positively associated with sulfur dioxide and population density. Further, we demonstrate how scientific conclusions may change if various sources of uncertainty (either spatio-temporal or covariate uncertainty) are not accounted for. Code submitted with this article was checked by an Associate Editor for Reproducibility and is available as an online supplement.

Physically constrained spatiotemporal modeling: generating clear-sky constructions of land surface temperature from sparse, remotely sensed satellite data.

Satellite remote-sensing is used to collect important atmospheric and geophysical data at various spatial resolutions, providing insight into spatiotemporal surface and climate variability globally. These observations are often plagued with missing spatial and temporal information of Earth's surface due to (1) cloud cover at the time of a satellite passing and (2) infrequent passing of polar-orbiting satellites. While many methods are available to model missing data in space and time, in the case of land surface temperature (LST) from thermal infrared remote sensing, these approaches generally ignore the temporal pattern called the 'diurnal cycle' which physically constrains temperatures to peak in the early afternoon and reach a minimum at sunrise. In order to infill an LST dataset, we parameterize the diurnal cycle into a functional form with unknown spatiotemporal parameters. Using multiresolution spatial basis functions, we estimate these parameters from sparse satellite observations to reconstruct an LST field with continuous spatial and temporal distributions. These estimations may then be used to better inform scientists of spatiotemporal thermal patterns over relatively complex domains. The methodology is demonstrated using data collected by MODIS on NASA's Aqua and Terra satellites over both Houston, TX and Phoenix, AZ USA.

Targeted isolation and cultivation of uncultivated bacteria by reverse genomics.

Most microorganisms from all taxonomic levels are uncultured. Single-cell genomes and metagenomes continue to increase the known diversity of Bacteria and Archaea; however, while 'omics can be used to infer physiological or ecological roles for species in a community, most of these hypothetical roles remain unvalidated. Here, we report an approach to capture specific microorganisms from complex communities into pure cultures using genome-informed antibody engineering. We apply our reverse genomics approach to isolate and sequence single cells and to cultivate three different species-level lineages of human oral Saccharibacteria (TM7). Using our pure cultures, we show that all three Saccharibacteria species are epibionts of diverse Actinobacteria. We also isolate and cultivate human oral SR1 bacteria, which are members of a lineage of previously uncultured bacteria. Reverse-genomics-enabled cultivation of microorganisms can be applied to any species from any environment and has the potential to unlock the isolation, cultivation and characterization of species from as-yet-uncultured branches of the microbial tree of life.

A Case Study Competition Among Methods for Analyzing Large Spatial Data.

The Gaussian process is an indispensable tool for spatial data analysts. The onset of the "big data" era, however, has lead to the traditional Gaussian process being computationally infeasible for modern spatial data. As such, various alternatives to the full Gaussian process that are more amenable to handling big spatial data have been proposed. These modern methods often exploit low-rank structures and/or multi-core and multi-threaded computing environments to facilitate computation. This study provides, first, an introductory overview of several methods for analyzing large spatial data. Second, this study describes the results of a predictive competition among the described methods as implemented by different groups with strong expertise in the methodology. Specifically, each research group was provided with two training datasets (one simulated and one observed) along with a set of prediction locations. Each group then wrote their own implementation of their method to produce predictions at the given location and each was subsequently run on a common computing environment. The methods were then compared in terms of various predictive diagnostics. Supplementary materials regarding implementation details of the methods and code are available for this article online. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary materials for this article are available at 10.1007/s13253-018-00348-w.

MARPLE, a point-of-care, strain-level disease diagnostics and surveillance tool for complex fungal pathogens.

BACKGROUND: Effective disease management depends on timely and accurate diagnosis to guide control measures. The capacity to distinguish between individuals in a pathogen population with specific properties such as fungicide resistance, toxin production and virulence profiles is often essential to inform disease management approaches. The genomics revolution has led to technologies that can rapidly produce high-resolution genotypic information to define individual variants of a pathogen species. However, their application to complex fungal pathogens has remained limited due to the frequent inability to culture these pathogens in the absence of their host and their large genome sizes. RESULTS: Here, we describe the development of Mobile And Real-time PLant disEase (MARPLE) diagnostics, a portable, genomics-based, point-of-care approach specifically tailored to identify individual strains of complex fungal plant pathogens. We used targeted sequencing to overcome limitations associated with the size of fungal genomes and their often obligately biotrophic nature. Focusing on the wheat yellow rust pathogen, Puccinia striiformis f.sp. tritici (Pst), we demonstrate that our approach can be used to rapidly define individual strains, assign strains to distinct genetic lineages that have been shown to correlate tightly with their virulence profiles and monitor genes of importance. CONCLUSIONS: MARPLE diagnostics enables rapid identification of individual pathogen strains and has the potential to monitor those with specific properties such as fungicide resistance directly from field-collected infected plant tissue in situ. Generating results within 48 h of field sampling, this new strategy has far-reaching implications for tracking plant health threats.

Estimating seasonal onsets and peaks of bronchiolitis with spatially and temporally uncertain data.

RSV bronchiolitis (an acute lower respiratory tract viral infection in infants) is the most common cause of infant hospitalizations in the United States (US). The only preventive intervention currently available is monthly injections of immunoprophylaxis. However, this treatment is expensive and needs to be administered simultaneously with seasonal bronchiolitis cycles in order to be effective. To increase our understanding of bronchiolitis timing, this research focuses on identifying seasonal bronchiolitis cycles (start times, peaks, and declinations) throughout the continental US using data on infant bronchiolitis cases from the US Military Health System Data Repository. Because this data involved highly personal information, the bronchiolitis dates in the dataset were "jittered" in the sense that the recorded dates were randomized within a time window of the true date. Hence, we develop a statistical change point model that estimates spatially varying seasonal bronchiolitis cycles while accounting for the purposefully introduced jittering in the data. Additionally, by including temperature and humidity data as regressors, we identify a relationship between bronchiolitis seasonality and climate. We found that, in general, bronchiolitis seasons begin earlier and are longer in the southeastern states compared to the western states with peak times lasting approximately 1 month nationwide.

Antibiotic resistance is lower in Staphylococcus aureus isolated from antibiotic-free raw meat as compared to conventional raw meat.

The frequent use of antibiotics contributes to antibiotic resistance in bacteria, resulting in an increase in infections that are difficult to treat. Livestock are commonly administered antibiotics in their feed, but there is current interest in raising animals that are only administered antibiotics during active infections. Staphylococcus aureus (SA) is a common pathogen of both humans and livestock raised for human consumption. SA has achieved high levels of antibiotic resistance, but the origins and locations of resistance selection are poorly understood. We determined the prevalence of SA and MRSA in conventional and antibiotic-free (AF) meat products, and also measured rates of antibiotic resistance in these isolates. We isolated SA from raw conventional turkey, chicken, beef, and pork samples and also from AF chicken and turkey samples. We found that SA contamination was common, with an overall prevalence of 22.6% (range of 2.8-30.8%) in conventional meats and 13.0% (range of 12.5-13.2%) in AF poultry meats. MRSA was isolated from 15.7% of conventional raw meats (range of 2.8-20.4%) but not from AF-free meats. The degree of antibiotic resistance in conventional poultry products was significantly higher vs AF poultry products for a number of different antibiotics, and while multi-drug resistant strains were relatively common in conventional meats none were detected in AF meats. The use of antibiotics in livestock contributes to high levels of antibiotic resistance in SA found in meat products. Our results support the use of AF conditions for livestock in order to prevent antibiotic resistance development in SA.

The politics and practice of Thomas Adeoye Lambo: towards a post-colonial history of transcultural psychiatry.

This article traces the career of Thomas Adeoye Lambo, the first European-trained psychiatrist of indigenous Nigerian (Yoruba) background and one of the key contributors to the international development of transcultural psychiatry from the 1950s to the 1980s. The focus on Lambo provides some political, cultural and geographical balance to the broader history of transcultural psychiatry by emphasizing the contributions to transcultural psychiatric knowledge that have emerged from a particular non-western context. At the same time, an examination of Lambo's legacy allows historians to see the limitations of transcultural psychiatry's influence over time. Ultimately, this article concludes that the history of transcultural psychiatry might have more to tell us about the politics of the 'transcultural' than the practice of 'psychiatry' in post-colonial contexts.

The impact of temperature and relative humidity on spatiotemporal patterns of infant bronchiolitis epidemics in the contiguous United States.

Infant bronchiolitis is primarily due to infection by respiratory syncytial virus (RSV), which is highly seasonal. The goal of the study is to understand how circulation of RSV is impacted by fluctuations in temperature and humidity in order to inform prevention efforts. Using data from the Military Health System (MHS) Data Repository (MDR), we calculated rates of infant bronchiolitis for the contiguous US from July 2004 to June 2013. Monthly temperature and relative humidity were extracted from the National Climate Data Center. Using a spatiotemporal generalized linear model for binomial data, we estimated bronchiolitis rates and the effects of temperature and relative humidity while allowing them to vary over location and time. Our results indicate a seasonal pattern that begins in the Southeast during November or December, then spreading in a Northwest direction. The relationships of temperature and humidity were spatially heterogeneous, and we find that climate can partially account for early onset or longer epidemic duration. Small changes in climate may be associated with larger fluctuations in epidemic duration.

Evaluation of various glyphosate concentrations on DNA damage in human Raji cells and its impact on cytotoxicity.

Glyphosate is a highly used active compound in agriculturally based pesticides. The literature regarding the toxicity of glyphosate to human cells has been highly inconsistent. We studied the resulting DNA damage and cytotoxicity of various glyphosate concentrations on human cells to evaluate DNA damaging potential. Utilizing human Raji cells, DNA damage was quantified using the comet assay, while cytotoxicity was further analyzed using MTT viability assays. Several glyphosate concentrations were assessed, ranging from 15 mM to 0.1 µM. We found that glyphosate treatment is lethal to Raji cells at concentrations above 10 mM, yet has no cytotoxic effects at concentrations at or below 100 µM. Treatment concentrations of 1 mM and 5 mM induce statistically significant DNA damage to Raji cells following 30-60 min of treatment, however, cells show a slow recovery from initial damage and cell viability is unaffected after 2 h. At these same concentrations, cells treated with additional compound did not recover and maintained high levels of DNA damage. While the cytotoxicity of glyphosate appears to be minimal for physiologically relevant concentrations, the compound has a definitive cytotoxic nature in human cells at high concentrations. Our data also suggests a mammalian metabolic pathway for the degradation of glyphosate may be present.

Characterizing urban vulnerability to heat stress using a spatially varying coefficient model.

Identifying and characterizing urban vulnerability to heat is a key step in designing intervention strategies to combat negative consequences of extreme heat on human health. This study combines excess non-accidental mortality counts, numerical weather simulations, US Census and parcel data into an assessment of vulnerability to heat in Houston, Texas. Specifically, a hierarchical model with spatially varying coefficients is used to account for differences in vulnerability among census block groups. Socio-economic and demographic variables from census and parcel data are selected via a forward selection algorithm where at each step the remaining variables are orthogonalized with respect to the chosen variables to account for collinearity. Daily minimum temperatures and composite heat indices (e.g. discomfort index) provide a better model fit than other ambient temperature measurements (e.g. maximum temperature, relative humidity). Positive interactions between elderly populations and heat exposure were found suggesting these populations are more responsive to increases in heat.

Extending distributed lag models to higher degrees.

Distributed lag (DL) models relate lagged covariates to a response and are a popular statistical model used in a wide variety of disciplines to analyze exposure-response data. However, classical DL models do not account for possible interactions between lagged predictors. In the presence of interactions between lagged covariates, the total effect of a change on the response is not merely a sum of lagged effects as is typically assumed. This article proposes a new class of models, called high-degree DL models, that extend basic DL models to incorporate hypothesized interactions between lagged predictors. The modeling strategy utilizes Gaussian processes to counterbalance predictor collinearity and as a dimension reduction tool. To choose the degree and maximum lags used within the models, a computationally manageable model comparison method is proposed based on maximum a posteriori estimators. The models and methods are illustrated via simulation and application to investigating the effect of heat exposure on mortality in Los Angeles and New York.

Flexible Distributed Lag Models using Random Functions with Application to Estimating Mortality Displacement from Heat-Related Deaths.

As climate continues to change, scientists are left to analyze the effects these changes will have on the public. In this article, a flexible class of distributed lag models are used to analyze the effects of heat on mortality in four major metropolitan areas in the U.S. (Chicago, Dallas, Los Angeles, and New York). Specifically, the proposed methodology uses Gaussian processes as a prior model for the distributed lag function. Gaussian processes are adequately flexible to capture a wide variety of distributed lag functions while ensuring smoothness properties of process realizations. Additionally, the proposed framework allows for probabilistic inference of the maximum lag. Applying the proposed methodology revealed that mortality displacement (or, harvesting) was present for most age groups and cities analyzed suggesting that heat advanced death in some individuals. Additionally, the estimated shape of the DL functions gave evidence that prolonged heat exposure and highly variable temperatures pose a threat to public health.

A spatio-temporal absorbing state model for disease and syndromic surveillance.

Reliable surveillance models are an important tool in public health because they aid in mitigating disease outbreaks, identify where and when disease outbreaks occur, and predict future occurrences. Although many statistical models have been devised for surveillance purposes, none are able to simultaneously achieve the important practical goals of good sensitivity and specificity, proper use of covariate information, inclusion of spatio-temporal dynamics, and transparent support to decision-makers. In an effort to achieve these goals, this paper proposes a spatio-temporal conditional autoregressive hidden Markov model with an absorbing state. The model performs well in both a large simulation study and in an application to influenza/pneumonia fatality data.

Kernel Averaged Predictors for Spatio-Temporal Regression Models.

In applications where covariates and responses are observed across space and time, a common goal is to quantify the effect of a change in the covariates on the response while adequately accounting for the spatio-temporal structure of the observations. The most common approach for building such a model is to confine the relationship between a covariate and response variable to a single spatio-temporal location. However, oftentimes the relationship between the response and predictors may extend across space and time. In other words, the response may be affected by levels of predictors in spatio-temporal proximity to the response location. Here, a flexible modeling framework is proposed to capture such spatial and temporal lagged effects between a predictor and a response. Specifically, kernel functions are used to weight a spatio-temporal covariate surface in a regression model for the response. The kernels are assumed to be parametric and non-stationary with the data informing the parameter values of the kernel. The methodology is illustrated on simulated data as well as a physical data set of ozone concentrations to be explained by temperature.