Surrogate and reduced-order modeling: a comparison of approaches for large-scale statistical inverse problems [Chapter 7]

Solution of statistical inverse problems via the frequentist or Bayesian approaches described in earlier chapters can be a computationally intensive endeavor, particularly when faced with large-scale forward models characteristic of many engineering and science applications. High computational cost arises in several ways. First, thousands or millions of forward simulations may be required to evaluate estimators of interest or to characterize a posterior distribution. In the large-scale setting, performing so many forward simulations is often computationally intractable. Second, sampling may be complicated by the large dimensionality of the input space--as when the inputs are fields represented with spatial discretizations of high dimension--and by nonlinear forward dynamics that lead to multimodal, skewed, and/or strongly correlated posteriors. In this chapter, we present an overview of surrogate and reduced order modeling methods that address these computational challenges. For illustration, we consider a Bayesian formulation of the inverse problem. Though some of the methods we review exploit prior information, they largely focus on simplifying or accelerating evaluations of a stochastic model for the data, and thus are also applicable in a frequentist context.Sandia National Laboratories (Laboratory Directed Research and Development (LDRD) program)United States. Dept. of Energy (Contract DE-AC04-94AL85000)Singapore-MIT Alliance Computational Engineering ProgrammeUnited States. Dept. of Energy (Award Number DE-FG02-08ER25858 )United States. Dept. of Energy (Award Number DESC00025217

First steps toward harmonized human biomonitoring in Europe : demonstration project to perform human biomonitoring on a European scale

'Reproduced with permission from Environmental Health Perspectives'Background: For Europe as a whole, data on internal exposure to environmental chemicals do not yet exist. Characterization of the internal individual chemical environment is expected to enhance understanding of the environmental threats to health. Objectives: We developed and applied a harmonized protocol to collect comparable human biomonitoring data all over Europe. Methods: In 17 European countries, we measured mercury in hair and cotinine, phthalate metabolites, and cadmium in urine of 1,844 children (5–11 years of age) and their mothers. Specimens were collected over a 5-month period in 2011–2012. We obtained information on personal characteristics, environment, and lifestyle. We used the resulting database to compare concentrations of exposure biomarkers within Europe, to identify determinants of exposure, and to compare exposure biomarkers with healthbased guidelines. Results: Biomarker concentrations showed a wide variability in the European population. However, levels in children and mothers were highly correlated. Most biomarker concentrations were below the health-based guidance values. Conclusions: We have taken the first steps to assess personal chemical exposures in Europe as a whole. Key success factors were the harmonized protocol development, intensive training and capacity building for field work, chemical analysis and communication, as well as stringent quality control programs for chemical and data analysis. Our project demonstrates the feasibility of a Europe-wide human biomonitoring framework to support the decision-making process of environmental measures to protect public health.The research leading to these results received funding for the COPHES project (COnsortium to Perform Human biomonitoring on a European Scale) from the European Community’s Seventh Framework Programme [FP7/2007–2013] under grant agreement 244237. DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) was co-funded (50%:50%) by the European Commission LIFE+ Programme (LIFE09/ENV/BE/000410) and the partners. For information on both projects as well as on the national co-funding institutions, see http://www.eu-hbm.info/. The sponsors had no role in the study design, data collection, data analysis, data interpretation or writing of the report

Evaluation of quality of clinical management of neuroendocrine tumors

Abstract Background Neuroendocrine tumors (NETs) are a group of biologically and clinically heterogeneous neoplasms predominantly found in the gastrointestinal and bronchopulmonary tractus. Despite a rising incidence, implementation of evidence‐based standardized care for this heterogenous group remains challenging. The European Neuroendocrine Tumor Society regularly reviews guidelines regarding diagnostic and treatment strategies for NETs. The aim of this study is to shed light on the care of patients with a NET in Belgian Limburg, to provide data as a basis for future studies and to check whether data and results are according to consensus guidelines and outcomes described in literature. Methods Our study concerned a detailed observational data collection of two large Belgian hospitals (Jessa Hospital Hasselt and Hospital Oost‐Limburg Genk) with special interest in patient profile, quality of pathology reports, use of diagnostic imaging, and overall survival. Data on 188 patients were assembled between January 2010 and December 2014 with follow‐up until June 2016 (median follow‐up: 33.6 months). Results Fifty percent of patients were male. NETs were located mainly in the digestive tract (63.8%) and lung (20.2%). Appendiceal NETs were diagnosed at a significantly younger age than other tumors (41.3 vs. 64.0 years). Overall, a mean pathology report quality score of 3.0/5 was observed with the highest scores for small bowel NETs. Diagnostic and nuclear imaging was performed in 74.5% and 29.8% of cases, respectively. Seventy‐four percent of the population survived until the end of the observation period with highest survival rates for appendiceal and small bowel NETs. Conclusion Overall, epidemiological results were comparable with findings in the literature. Gastrointestinal NETs met most of the requirements of qualitative pathology reporting and diagnostic imaging as listed in the European Neuroendocrine Tumor Society consensus guidelines. However, consensus with regard to bronchopulmonary NETs is still scarce and remains an objective for future research. Moreover, discussing treatment strategies in specialized multidisciplinary tumor boards would facilitate regional care

Mercury analysis in hair: Comparability and quality assessment within the transnational COPHES/DEMOCOPHES project

Human biomonitoring (HBM) is an effective tool for assessing actual exposure to chemicals that takes into account all routes of intake. Although hair analysis is considered to be an optimal biomarker for assessing mercury exposure, the lack of harmonization as regards sampling and analytical procedures has often limited the comparison of data at national and international level. The European-funded projects COPHES and DEMOCOPHES developed and tested a harmonized European approach to Human Biomonitoring in response to the European Environment and Health Action Plan. Herein we describe the quality assurance program (QAP) for assessing mercury levels in hair samples from more than 1800 mother–child pairs recruited in 17 European countries. To ensure the comparability of the results, standard operating procedures (SOPs) for sampling and for mercury analysis were drafted and distributed to participating laboratories. Training sessions were organized for field workers and four external quality-assessment exercises (ICI/EQUAS), followed by the corresponding web conferences, were organized between March 2011 and February 2012. ICI/EQUAS used native hair samples at two mercury concentration ranges (0.20–0.71 and 0.80–1.63) per exercise. The results revealed relative standard deviations of 7.87–13.55% and 4.04–11.31% for the low and high mercury concentration ranges, respectively. A total of 16 out of 18 participating laboratories the QAP requirements and were allowed to analyze samples from the DEMOCOPHES pilot study. Web conferences after each ICI/EQUAS revealed this to be a new and effective tool for improving analytical performance and increasing capacity building. The procedure developed and tested in COPHES/DEMOCOPHES would be optimal for application on a global scale as regards implementation of the Minamata Convention on Mercury

Pilot study testing a European human biomonitoring framework for biomarkers of chemical exposure in children and their mothers: experiences in the UK

Exposure to a number of environmental chemicals in UK mothers and children has been assessed as part of the European biomonitoring pilot study, Demonstration of a Study to Coordinate and Perform Human Biomonitoring on a European Scale (DEMOCOPHES). For the European-funded project, 17 countries tested the biomonitoring guidelines and protocols developed by COPHES. The results from the pilot study in the UK are presented; 21 school children aged 6-11 years old and their mothers provided hair samples to measure mercury and urine samples, to measure cadmium, cotinine and several phthalate metabolites: mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethylhexyl)phthalate (MEHP), mono-ethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP), mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP). Questionnaire data was collected on environment, health and lifestyle. Mercury in hair was higher in children who reported frequent consumption of fish (geometric mean 0.35 μg/g) compared to those that ate fish less frequently (0.13 μg/g, p = 0.002). Cadmium accumulates with age as demonstrated by higher levels of urinary cadmium in the mothers (geometric mean 0.24 μg/L) than in the children(0.14 μg/L). None of the mothers reported being regular smokers, and this was evident with extremely low levels of cotinine measured (maximum value 3.6 μg/L in mothers, 2.4 μg/L in children). Very low levels of the phthalate metabolites were also measured in both mothers and children (geometric means in mothers: 5OH-MEHP 8.6 μg/L, 5oxo-MEHP 5.1 μg/L, MEHP 1.2 μg/L, MEP 26.8 μg/L, MiBP 17.0 μg/L, MBzP 1.6 μg/L and MnBP 13.5 μg/L; and in children: 5OH-MEHP 18.4 μg/L, 5oxo-MEHP 11.4 μg/L, MEHP 1.4 μg/L, MEP 14.3 μg/L, MiBP 25.8 μg/L, MBzP 3.5 μg/L and MnBP 22.6 μg/L). All measured biomarker levels were similar to or below population-based reference values published by the US National Health and Nutrition Examination Survey (NHANES) and Germany's GerES surveys. No results were above available health guidance values and were of no concern with regards to health. The framework and techniques learnt here will assist with future work on biomonitoring in the UK.status: publishe

A systematic approach for designing a HBM Pilot Study for Europe

© 2013 Elsevier GmbH. All rights reserved.The objective of COPHES (Consortium to Perform Human biomonitoring on a European Scale) was to develop a harmonised approach to conduct human biomonitoring on a Europeanscale. COPHES developed a systematic approach for designing and conducting a pilot study for an EU-wide cross-sectional human biomonitoring (HBM) study and for the implementation of the fieldwork procedures. The approach gave the basis for discussion of the main aspects of study design and conduct, and provided a decision making tool which can be applied to many other studies. Each decision that had to be taken was listed in a table of options with their advantages and disadvantages. Based on this the rationale of the decisions could be explained and be transparent. This was important because an EU-wide HBM study demands openness of all decisions taken to encourage as many countries as possible to participate and accept the initiative undertaken. Based on this approach the following study design was suggested: a cross-sectional study including 120 children aged 6–11 years and their mothers aged up to 45 years from each participating country. For the pilot study the children should be sampled in equal shares in an urban and a rural location. Only healthy children and mothers (no metabolic disturbances) should be included, who have a sufficient knowledge of the local language and have been living at least for 5 years at the sampling location. Occupational exposure should not be an exclusion criterion. Recruitment should be performed via inhabitant registries or schools as an alternative option. Measures suitable to increase the response rate should be applied. Preferably, the families should be visited at home and interviewed face-to-face. Various quality control measures to guarantee a good fieldwork performance were recommended.European Commission, DG for Researchand Innovation (RTD), who funded COPHES in the 7th Framework Programme (DG Research – No. 244237) and DG Environment,who co-funded DEMOCOPHES under the LIFE+ Programme (DG Environment-Life09 ENV/BE000410) together with the participating countries

Human biomonitoring pilot study DEMOCOPHES in Germany : contribution to a harmonized European approach

Human biomonitoring (HBM) is an effective tool to assess human exposure to environmental pollutants, but comparable HBM data in Europe are lacking. In order to expedite harmonization of HBM studies on a European scale, the twin projects COPHES (Consortium to Perform Human Biomonitoring on a European Scale) and DEMOCOPHES (Demonstration of a study to Coordinate and Perform Human Biomonitoring on a European Scale) were formed, comprising 35 partners from 27 European countries. In COPHES a research scheme and guidelines were developed to exemplarily measure in a pilot study mercury in hair, cadmium, cotinine and several phthalate metabolites in urine of 6-11year old children and their mothers in an urban and a rural region. Seventeen European countries simultaneously conducted this cross-sectional DEMOCOPHES feasibility study. The German study population was taken in the city of Bochum and in the Higher Sauerland District, comprising 120 mother-child pairs. In the present paper features of the study implementation are presented. German exposure concentrations of the pollutants are reported and compared with European average concentrations from DEMOCOPHES and with those measured in the representative German Environmental Survey (GerES IV). German DEMOCOPHES concentrations for mercury and cotinine were lower than the European average. However, 47% of the children were still exposed to environmental tobacco smoke (ETS) outside their home, which gives further potential for enhancing protection of children from ETS. Compared with samples from the other European countries German participating children had lower concentrations of the phthalate metabolites MEP and of the sum of 3 DEHP-metabolites (MEHP, 5OH-MEHP and 5oxo-MEHP), about the same concentrations of the phthalate metabolites MBzP and MiBP and higher concentrations of the phthalate metabolite MnBP. 2.5% of the German children had concentrations of the sum of 4 DEHP-metabolites and 4.2% had concentrations of MnBP that exceeded health based guidance values, indicating reasons for concern. Continuous HBM is necessary to track changes of pollutant exposure over time. Therefore Germany will continue to cooperate on the harmonisation of European human biomonitoring to support the chemicals regulation with the best possible exposure data to protect Europe's people against environmental health risks.We also would like to thank all DEMOCOPHES and COPHES project partners for their support. DEMOCOPHES in Germany was co-funded by the EU Commission, DG Environment under the LIFE + programme (LIFE09 ENV/BE/000410) and by the Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (FKZ 3709 62 210). COPHES was funded by DG Research and Innovation in the 7th Framework Programme (DG Research – No. 244237).S