Fast admixture analysis and population tree estimation for SNP and NGS data.

MOTIVATION: Structure methods are highly used population genetic methods for classifying individuals in a sample fractionally into discrete ancestry components. CONTRIBUTION: We introduce a new optimization algorithm for the classical STRUCTURE model in a maximum likelihood framework. Using analyses of real data we show that the new method finds solutions with higher likelihoods than the state-of-the-art method in the same computational time. The optimization algorithm is also applicable to models based on genotype likelihoods, that can account for the uncertainty in genotype-calling associated with Next Generation Sequencing (NGS) data. We also present a new method for estimating population trees from ancestry components using a Gaussian approximation. Using coalescence simulations of diverging populations, we explore the adequacy of the STRUCTURE-style models and the Gaussian assumption for identifying ancestry components correctly and for inferring the correct tree. In most cases, ancestry components are inferred correctly, although sample sizes and times since admixture can influence the results. We show that the popular Gaussian approximation tends to perform poorly under extreme divergence scenarios e.g. with very long branch lengths, but the topologies of the population trees are accurately inferred in all scenarios explored. The new methods are implemented together with appropriate visualization tools in the software package Ohana. AVAILABILITY AND IMPLEMENTATION: Ohana is publicly available at https://github.com/jade-cheng/ohana . In addition to source code and installation instructions, we also provide example work-flows in the project wiki site. CONTACT: jade.cheng@birc.au.dk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Effects of intelligibility on within- and cross-modal sentence recognition memory for native and non-native listeners.

The goal of the study was to examine whether enhancing the clarity of the speech signal through conversational-to-clear speech modifications improves sentence recognition memory for native and non-native listeners, and if so, whether this effect would hold when the stimuli in the test phase are presented in orthographic instead of auditory form (cross-modal presentation). Sixty listeners (30 native and 30 non-native English) participated in a within-modal (i.e., audio-audio) sentence recognition memory task (Experiment I). Sixty different individuals (30 native and 30 non-native English) participated in a cross-modal (i.e., audio-textual) sentence recognition memory task (Experiment II). The results showed that listener-oriented clear speech enhanced sentence recognition memory for both listener groups regardless of whether the acoustic signal was present during the test phase (Experiment I) or absent (Experiment II). Compared to native listeners, non-native listeners had longer reaction times in the within-modal task and were overall less accurate in the cross-modal task. The results showed that more cognitive resources remained available for storing information in memory during processing of easier-to-understand clearly produced sentences. Furthermore, non-native listeners benefited from signal clarity in sentence recognition memory despite processing speech signals in a cognitively more demanding second language.

Morphological analysis of vessel elements for systematic study of three Zingiberaceae tribes.

Zingiberaceae containing over 1,000 species that are divided into four subfamilies and six tribes. In recent decades, there has been an increase in the number of studies about vessel elements in families of monocotyledon. However, there are still few studies of Zingiberaceae tribes. This study aims to establish systematic significance of studying vessel elements in two subfamilies and three tribes of Zingiberaceae. The vegetative organs of 33 species processed were analysed by light and scanning electron microscopy and Principal Component Analysis was used to elucidate genera boundaries. Characteristics of vessel elements, such as the type of perforation plate, the number of bars and type of parietal thickening, are proved to be important for establishing the relationship among taxa. Scalariform perforation plate and the scalariform parietal thickening are frequent in Zingiberaceae and may be a plesiomorphic condition for this taxon. In the Principal Component Analysis, the most significant characters of the vessel elements were: simple perforation plates and partially pitted parietal thickening, found only in Alpinieae tribe, and 40 or more bars composing the plate in Elettariopsis curtisii, Renealmia chrysotricha, Zingiber spectabile, Z. officinale, Curcuma and Globba species. Vessel elements characters of 18 species of Alpinieae, Zingibereae and Globbeae were first described in this work.

A 3-D geometric morphometric study of intraspecific variation in the ontogeny of the temporal bone in modern Homo sapiens.

This study addresses how the human temporal bone develops the population-specific pattern of morphology observed among adults and at what point in ontogeny those patterns arise. Three-dimensional temporal bone shape was captured using 15 landmarks on ontogenetic series of specimens from seven modern human populations. Discriminant function analysis revealed that population-specific temporal bone morphology is evident early in ontogeny, with significant shape differences among many human populations apparent prior to the eruption of the first molar. As early as five years of age, temporal bone shape reflects population history and can be used to reliably sort populations, although those in closer geographic proximity and molecular affinity are more likely to be misclassified. The deviation of cold-adapted populations from this general pattern of congruence between temporal bone morphology and genetic distances, identified in previous work, was confirmed here in adult and subadult specimens, and was revealed to occur earlier in ontogeny than previously recognized. Significant differences exist between the ontogenetic trajectories of some pairs of populations, but not among others, and the angles of these trajectories do not reflect genetic relationships or final adult temporal bone size. Significant intrapopulation differences are evident early in ontogeny, with differences becoming amplified by divergent trajectories in some groups. These findings elucidate how the congruence between adult human temporal bone morphology and population history develops, and reveal that this pattern corresponds closely to that described previously for facial ontogeny.

Pitfalls and challenges with population assignments of individuals from admixed populations: Applying Genogeographer on Brazilian individuals.

The assignment of individuals to a population can be of importance for the identification of mass disaster victims or criminal offenders in the field of forensic genetics. This assignment is based on biostatistical methods that process data of ancestry informative markers (AIMs), which are selected based on large allele frequency differences between the populations of interest. However, population assignments of individuals with an admixed genetic background are challenging. Admixed individuals are genetic mosaics of chromosomal segments from the parental populations, which may lead to ambiguous or no population assignment. This is problematic since admixture events are a substantial part of human history. In this study, we present challenges of interpreting the evidential weight of population assignments. We used Genogeographer for likelihood ratio (LR) calculations and Brazilians as examples of admixed individuals. Brazilians are a very heterogenous population representing a three-way admixture between Native Americans, Europeans, and Africans. Ancestry informative markers were typed in a total of 589 individuals from Brazil using the Precision ID Ancestry Panel. The Brazilians were assigned to six metapopulations (East Asia, Europe, Middle East, North Africa, South-Central Asia, Sub-Saharan Africa) defined in the Genogeographer software and LRs were calculated if the AIM profile was not an outlier in all metapopulations and simulated two-way (1:1) admixtures of the six metapopulations. Population assignments failed for 55% of the samples. These samples had significantly higher genetic contributions from East Asia, South-Central Asia and Sub-Saharan Africa, and significantly lower genetic contributions from Europe. Most of the individuals with population assignments were assigned to the metapopulations of Middle East (58%) or North Africa (36%), followed by Europe (4%), South-Central Asia (1%), and Sub-Saharan Africa (1%). For 8% of the samples, population assignments were only possible when assignments to simulated two-way (1:1) admixtures of the six metapopulations were considered. Most of these individuals were assigned to two-way admixtures of North Africa, South-Central Asia, or Sub-Saharan Africa. Relatively low median likelihood ratios (LRs<1000) were observed when comparing population likelihoods for Europe, Middle East, North Africa, South-Central Asia, or simulated 1:1 admixtures of these metapopulations. Comparisons including East Asian or Sub-Saharan African populations resulted in larger median LRs (LR>1010). The results suggested that the Precision ID Ancestry Panel provided too little information and that additional markers specifically selected for sub-continental differentiation may be required for accurate population assignment of admixed individuals. Furthermore, a Genogeographer database with additional populations including admixed populations would be advantageous for interpretation of admixed AIM profiles. It would likely increase the number of population assignments and illustrate alternatives to the most likely population, which would be valuable information for the case officer when writing the case report.

Using the intervention ladder to examine policy influencer and general public support for potential tobacco control policies in Alberta and Quebec. / Utilisation d'une échelle d'intervention pour analyser le soutien à d'éventuelles politiques de lutte contre le tabagisme de la part du grand public et d'influenceurs en matière de politiques en Alberta et au Québec.

OBJECTIVE: To assess general public and policy influencer support for population-level tobacco control policies in two Canadian provinces. METHODS: We implemented the Chronic Disease Prevention Survey in 2016 to a census sample of policy influencers (n = 302) and a random sample of members of the public (n = 2400) in Alberta and Quebec, Canada. Survey respondents ranked their support for tobacco control policy options using a Likert-style scale, with aggregate responses presented as net favourable percentages. Levels of support were further analyzed by coding each policy option using the Nuffield Council on Bioethics intervention ladder framework, to assess its level of intrusiveness on personal autonomy. RESULTS: Policy influencers and the public considered the vast majority of tobacco control policy options as "extremely" or "very" favourable, although policy influencers in Alberta and Quebec differed on over half the policies, with stronger support in Quebec. Policy influencers and the public strongly supported more intrusive tobacco control policy options, despite anticipated effects on personal autonomy (i.e. for policies targeting children/youth and emerging tobacco products like electronic cigarettes). They indicated less support for fiscally based tobacco control policies (i.e. taxation), despite these policies being highly effective. CONCLUSION: Overall, policy influencers and the general public strongly supported more restrictive tobacco control policies. This study further highlights policies where support among both population groups was unanimous (potential "quick wins" for health advocates). It also highlights areas where additional advocacy work is required to communicate the population-health benefit of tobacco control policies.

Integrating social marketing into sustainable resource management at Padre Island National Seashore: an attitude-based segmentation approach.

High demand for outdoor recreation and increasing diversity in outdoor recreation participants have imposed a great challenge on the National Park Service (NPS), which is tasked with the mission to provide open access for quality outdoor recreation and maintain the ecological integrity of the park system. In addition to management practices of education and restrictions, building a sense of natural resource stewardship among visitors may also facilitate the NPS ability to react to this challenge. The purpose of our study is to suggest a segmentation approach that is built on the social marketing framework and aimed at influencing visitor behaviors to support conservation. Attitude toward natural resource management, an indicator of natural resource stewardship, is used as the basis for segmenting park visitors. This segmentation approach is examined based on a survey of 987 visitors to the Padre Island National Seashore (PAIS) in Texas in 2003. Results of the K-means cluster analysis identify three visitor segments: Conservation-Oriented, Development-Oriented, and Status Quo visitors. This segmentation solution is verified using respondents' socio-demographic backgrounds, use patterns, experience preferences, and attitudes toward a proposed regulation. Suggestions are provided to better target the three visitor segments and facilitate a sense of natural resource stewardship among them.

[Different classification of an adult population by two validated indexes of adherence to the Mediterranean diet]. / Diferente clasificación de una población adulta por dos índices validados de adherencia a la dieta mediterránea.

INTRODUCTION: Background: the Mediterranean diet (MD) has been related to a good state of health. There are different index to evaluate the adherence to Mediterranean dietary pattern. Objective: the purpose of the study was to evaluate the classification of the adult population of the Comunitat Valenciana according to their suitability to the MD using two validated indexes, and analyze the degree of agreement between them. Methods: methodological study of the concordance of classification of a population through two instruments for measuring adherence to MD, of a representative sample of 2,728 adult of the Comunitat Valenciana. Data obtained from Encuesta de Nutrición de la Comunitat Valenciana 2010-2011. The adhesion was determined by "Puntuación Modificada de Dieta Mediterránea" and "Cribado de Adherencia de Dieta Mediterránea". The population was classified as low, medium or high according to each index. A statistical analysis was performed for qualitative and quantitative variables. The concordance of the indexes was evaluated by the Kappa test. Results: in both indixes, the highest percentage (41% and 71%, respectively) of the population was in medium adherence to MD. Between both indexes, the value of the kappa index was 0.169, for men 0.163 and for women 0.174. By age groups: 0.158 for those aged 16-24 years, 0.139 for 25-44 years, 0.185 for 45-64 years, and 0.161 for those over 64 years. Conclusions: the two indexes tested showed a degree of poor agreement and classified the same population differently.

INTRODUCCIÓN: Introducción: la dieta mediterránea (DM) se relaciona con un buen estado de salud. Existen diferentes propuestas validadas de índices para evaluar la adherencia al patrón dietético mediterráneo. Objetivos: la finalidad del estudio fue evaluar la clasificación de la población adulta de la Comunitat Valenciana según su adecuación a la DM, utilizando dos índices validados y analizar el grado de concordancia entre ellos. Métodos: estudio metodológico sobre la concordancia de clasificación de una población a través de dos instrumentos de medición de la adhesión a la DM, sobre una muestra representativa de 2.728 individuos adultos de la Comunitat Valenciana. Datos obtenidos de la Encuesta de Nutrición de la Comunitat Valenciana 2010-2011. La adhesión se determinó mediante "Puntuación Modificada de Dieta Mediterránea" y "Cribado de Adherencia de Dieta Mediterránea". La población se clasificó en adhesión baja, media o alta según cada índice. Se realizó un análisis estadístico para variables cualitativas y cuantitativas. Se evaluó la concordancia de los índices por la prueba Kappa. Resultados: en ambos índices, el mayor porcentaje (41% y 71%, respectivamente) de población se situó en una adhesión media a la DM. Entre ambos índices el valor del índice kappa fue de 0,169, para hombres de 0,163 y para mujeres de 0,174. Por grupos de edad: 0,158 para los de 16-24 años, 0,139 para 25-44 años, 0,185 para 45-64 años y, 0,161 para mayores de 64 años. Conclusiones: los dos índices testados mostraron entre si un grado de acuerdo pobre y clasificaron de forma diferente a una misma población.

Standardized Biogeographic Grouping System for Annotating Populations in Pharmacogenetic Research.

The varying frequencies of pharmacogenetic alleles among populations have important implications for the impact of these alleles in different populations. Current population grouping methods to communicate these patterns are insufficient as they are inconsistent and fail to reflect the global distribution of genetic variability. To facilitate and standardize the reporting of variability in pharmacogenetic allele frequencies, we present seven geographically defined groups: American, Central/South Asian, East Asian, European, Near Eastern, Oceanian, and Sub-Saharan African, and two admixed groups: African American/Afro-Caribbean and Latino. These nine groups are defined by global autosomal genetic structure and based on data from large-scale sequencing initiatives. We recognize that broadly grouping global populations is an oversimplification of human diversity and does not capture complex social and cultural identity. However, these groups meet a key need in pharmacogenetics research by enabling consistent communication of the scale of variability in global allele frequencies and are now used by Pharmacogenomics Knowledgebase (PharmGKB).

Cross classification of the New Zealand population by ethnicity and deprivation: trends from 1996 to 2006.

OBJECTIVES: To describe trends in the distribution of New Zealand's major ethnic groups by small area deprivation and trends in the ethnic composition of each deprivation category. METHODS: Data sources were the 1996, 2001 and 2006 New Zealand Census of Population and Dwellings. Ethnicity (Maori, Pacific, Asian or European/Other) was defined using total response output. Each person was assigned a deprivation score by geocoding their usual residence (as recorded in the census) to meshblock level. For each time period (1996, 2001 and 2006) the deprivation score for each meshblock was calculated by principal components analysis from nine socio-economic variables included in the corresponding census (the New Zealand Index of Deprivation). RESULTS: Throughout the observation period, Maori and Pacific ethnic groups were over-represented at the more deprived and under-represented at the less deprived end of the deprivation spectrum. The European ethnic group displayed less-marked skewing, and in the opposite direction, while the Asian ethnic group showed close to the expected uniform distribution. Neither the deprivation distribution of any ethnic group, nor the ethnic composition of any deprivation decile, showed any statistically significant change over the 10-year observation period. CONCLUSIONS: Monitoring trends in the relative deprivation distributions of the ethnic groups helps assess progress towards social justice. Similarly, monitoring trends in the ethnic compositions of the different deprivation deciles is important in the formulation of social policy. Little change was found in either of these distributions over the relatively short observation period.

Dietary intakes of European, Maori, Pacific and Asian adults living in Auckland: the Diabetes, Heart and Health Study.

OBJECTIVE: To compare dietary intakes of European, Maori, Pacific, and Asian men and women living in Auckland. METHODS: Daily nutrient intakes were calculated from a self-administered food frequency questionnaire from participants in a cross-sectional health screening study carried out between 2002 and 2003. Participants were 4,007 Maori, Pacific, Asian and European people (1,915 men, 2,092 women) aged 35 to 74 years. RESULTS: Compared with Europeans, Maori and Pacific men had higher total energy intakes per day, while Asians had lower intakes. A similar pattern was observed for carbohydrate and fat consumption. While protein and cholesterol consumption tended to be lower in Europeans than the other three ethnic groups, alcohol consumption and calcium intakes were highest among Europeans. Many of the differences between ethnic groups were attenuated when nutrient consumption was expressed as their percentage contribution to total energy intake suggesting that total food consumption was the major determinant of ethnic differences in nutrient intakes. CONCLUSIONS: There were substantial differences in dietary habits, food selections and cooking practices between European, Maori, Pacific and Asian participants. However, the observed differences were in the area of serving sizes and frequency of consumption of certain foods than to major differences in the range of foods and nutrients consumed or the percentage contribution of carbohydrate, fat or protein to total energy intake. IMPLICATIONS: The development of strategies to reduce serving sizes and the frequency of consumption of certain foods will be required to help address the major nutrition-related health problems in New Zealand.

Management of trauma in special populations after a disaster.

Special populations are particularly vulnerable to mental health problems in the aftermath of a disaster. Efficient delivery of mental health services, the integrated use of psychosocial services and mental health facilities, and the active intervention of trained community health care workers can offer effective management of the psychosocial problems of special populations. Women, children, adolescents, the poor, the elderly, and individuals with preexisting health problems have been identified as special populations who often suffer psychological morbidity as a result of a catastrophic disaster. Understanding the cultural, ethnic, and socioeconomic factors in a postdisaster situation is crucial to helping special populations overcome debilitating mental illness and declining quality of life. Planning the delivery of mental health services is critical and includes hazard mapping to identify vulnerable geographic and social areas, screening instruments to identify at-risk populations, and education of community leaders and health care workers. An integrated approach using psychosocial and institutionalized interventions can provide better outcomes than either approach alone. A community-based approach with trained grassroots health care workers can provide effective psychosocial support and rehabilitation services.

Sporadic amyotrophic lateral sclerosis as an infectious disease: a possible role of cyanobacteria?

The available epidemiological data for amyotrophic lateral sclerosis (ALS) support an infectious etiology and lead us to propose a new hypothesis. We examined older epidemiological data concerning categories of the population with increased incidence (aged people, people living in rural areas, farmers, breeders), more recent epidemiological reports regarding Italian soccer players, AIDS patients, people living in highly polluted areas, and reports of cases of conjugal and pregnancy-associated ALS. The toxic and infectious hypotheses lead us to suggest a role for cyanobacteria in the production of endogenous beta-N-methylamino-L-alanine. Infection from a cyanobacterium, or another ubiquitous bacterium having similar characteristics, may be the missing clue to the etiology of ALS. We speculate that ubiquitous bacteria secreting toxic amino acids and "colonizing" tissues and organs in the human body might be the common element linking motor neuron diseases in Guam to sporadic ALS in the rest of the world.

Motivation to control prejudice predicts categorization of multiracials.

Multiracial individuals often do not easily fit into existing racial categories. Perceivers may adopt a novel racial category to categorize multiracial targets, but their willingness to do so may depend on their motivations. We investigated whether perceivers' levels of internal motivation to control prejudice (IMS) and external motivation to control prejudice (EMS) predicted their likelihood of categorizing Black-White multiracial faces as Multiracial. Across four studies, IMS positively predicted perceivers' categorizations of multiracial faces as Multiracial. The association between IMS and Multiracial categorizations was strongest when faces were most racially ambiguous. Explicit prejudice, implicit prejudice, and interracial contact were ruled out as explanations for the relationship between IMS and Multiracial categorizations. EMS may be negatively associated with the use of the Multiracial category. Therefore, perceivers' motivations to control prejudice have important implications for racial categorization processes.

Validación del poder predictivo de los Grupos de Morbilidad Ajustada (GMA) respecto de otras herramientas de estratificación de la población / Validity of predictive power of the Adjusted Morbidity Groups (AMG) with respect to others population stratification tools

OBJETIVO: Este trabajo se realizó con el objetivo de conseguir elementos objetivos de juicio que apoyasen la evolución de un estratificador de la población nacional desarrollado en base a los Grupos de Morbilidad Ajustada (GMA). Para ello se validó el poder predictivo de esta herramienta de estratificación sobre determinadas variables de resultado, mediante comparación con otros estratificadores como ACG® (Adjusted Clinical Groups) y CRG® (Clinical Risk Group), utilizados en algunas comunidades autónomas (CCAA) como Aragón, Canarias y Castilla y León. MÉTODOS: Se realizó un estudio analítico transversal en la población con derecho a la asistencia sanitaria. Se evaluó la capacidad predictiva del peso de complejidad obtenido con cada una de las herramientas de estratificación en el primer año, mediante un método de clasificación simple que comparó las áreas bajo las curvas ROC sobre las siguientes variables de resultado que sucedieron en el año siguiente: probabilidad de muerte; probabilidad de tener al menos un ingreso hospitalario urgente; número total de asistencias a urgencias hospitalarias; número total de visitas a Atención Primaria (AP); número total de consultas externas de Atención Hospitalaria (AH) y gasto farmacéutico. RESULTADOS: Los resultados obtenidos mostraron que los GMA® fueron buenos predictores de casi todas las variables analizadas (Resultados Curvas ROC AUC>0,7; p < 0,05) para las distintas comunidades autónomas, al comparar con los ACG® o los CRG®. Únicamente para la variable de asistencia a urgencias hospitalarias en el caso de Aragón y Canarias, y las derivaciones a AH en el caso de Aragón, la capacidad predictiva no fue adecuada con ninguna de las herramientas de estratificación comparadas. CONCLUSIONES: La herramienta GMA® es un sistema de estratificación de la población adecuado y tan útil como otras alternativas existentes

OBJECTIVE: This work was performed in order to get objective elements of judgment that support the improvement of a national population morbidity grouper based in the Adjusted Morbidity Groups (AMG). The study compared the performance in terms of predictive power on certain health and resource outcomes, in between the AMG and several existing morbidity groupers (ACG®, Adjusted Clinical Groups and CRG®, Clinical Risk Group) used in some Autonomous Regions in Spain (Aragón, Canarias y Castilla y León). METHODS: Cross-sectional analytical study in entitled/insured population with respect to rights of healthcare. Predictive capacity of the complexity weight obtained with the different stratification tools in the first year of the study period was evaluated using a simple classification method that compares the areas under the curves ROC for the following outcomes that occurred in the second year of the study period: Probability of death; probability of having at least one urgent hospital admission; total number of visits to hospital emergencies; total number of visits to primary care; total number of visits to hospital care and spending in pharmacy. RESULTS: The results showed that AMG complexity weight were good predictors for almost all the analyzed outcomes (AUC ROC>0.7; p < 0.05), for the different Autonomous Regions and compared to ACG® or CRG®. Only for the outcome of visits to hospital emergencies in Aragon and Canarias; and visits to specialized care in Aragon, the predictive power was weak for all the compared stratification tools. CONCLUSIONS: GMA® is a population stratification tool adequate and as useful as others existing morbidity groupers

Effect of race and ethnicity classification on survey estimates: Anomaly of the weighted totals of American Indians and Alaska Natives.

Racial classification is a paramount concern in data collection and analysis for American Indians and Alaska Natives (AI/ANs) and has far-reaching implications in health research. We examine how different racial classifications affect survey weights and consequently change health-related indicators for the AI/AN population in California. Using a very large random population-based sample of AI/ANs, we compared the impact of three weighting strategies on counts and rates of selected health indicators. We found that different weights examined in this study did not change the percentage estimates of health-related variables for AI/ANs, but did influence the population total estimates dramatically. In survey data, different racial classifications and tabulations of AI/ANs could yield discrepancies in weighted estimates for the AI/AN population. Policy makers need to be aware that the choice of racial classification schemes for this racial-political group can generally influence the data they use for decision making.

Reconstructing population exposures to environmental chemicals from biomarkers: challenges and opportunities.

A conceptual/computational framework for exposure reconstruction from biomarker data combined with auxiliary exposure-related data is presented, evaluated with example applications, and examined in the context of future needs and opportunities. This framework employs physiologically based toxicokinetic (PBTK) modeling in conjunction with numerical "inversion" techniques. To quantify the value of different types of exposure data "accompanying" biomarker data, a study was conducted focusing on reconstructing exposures to chlorpyrifos, from measurements of its metabolite levels in urine. The study employed biomarker data as well as supporting exposure-related information from the National Human Exposure Assessment Survey (NHEXAS), Maryland, while the MENTOR-3P system (Modeling ENvironment for TOtal Risk with Physiologically based Pharmacokinetic modeling for Populations) was used for PBTK modeling. Recently proposed, simple numerical reconstruction methods were applied in this study, in conjunction with PBTK models. Two types of reconstructions were studied using (a) just the available biomarker and supporting exposure data and (b) synthetic data developed via augmenting available observations. Reconstruction using only available data resulted in a wide range of variation in estimated exposures. Reconstruction using synthetic data facilitated evaluation of numerical inversion methods and characterization of the value of additional information, such as study-specific data that can be collected in conjunction with the biomarker data. Although the NHEXAS data set provides a significant amount of supporting exposure-related information, especially when compared to national studies such as the National Health and Nutrition Examination Survey (NHANES), this information is still not adequate for detailed reconstruction of exposures under several conditions, as demonstrated here. The analysis presented here provides a starting point for introducing improved designs for future biomonitoring studies, from the perspective of exposure reconstruction; identifies specific limitations in existing exposure reconstruction methods that can be applied to population biomarker data; and suggests potential approaches for addressing exposure reconstruction from such data.