Reproducibility

Science is allegedly in the midst of a reproducibility crisis, but questions of reproducibility and related principles date back nearly 80 years. Numerous controversies have arisen, especially since 2010, in a wide array of disciplines that stem from the failure to reproduce studies or their findings:biology, biomedical and preclinical research, business and organizational studies, computational sciences, drug discovery, economics, education, epidemiology and statistics, genetics, immunology, policy research, political science, psychology, and sociology. This monograph defines terms and constructs related to reproducible research, weighs key considerations and challenges in reproducing or replicating studies, and discusses transparency in publications that can support reproducible research goals. It attempts to clarify reproducible research, with its attendant (andconfusing or even conflicting) lexicon and aims to provide useful background, definitions, and practical guidance for all readers. Among its conclusions: First, researchers must become better educated about these issues, particularly the differences between the concepts and terms. The main benefit is being able to communicate clearly within their own fields and, more importantly, across multiple disciplines. In addition, scientists need to embrace these concepts as part of their responsibilities as good stewards of research funding and as providers of credible information for policy decision making across many areas of public concern. Finally, although focusing on transparency and documentation is essential, ultimately the goal is achieving the most rigorous, high-quality science possible given limitations on time, funding, or other resources.Publishe

Asthma symptoms in Hispanic children and daily ambient exposures to toxic and criteria air pollutants.

Although acute adverse effects on asthma have been frequently found for the U.S. Environmental Protection Agency's principal criteria air pollutants, there is little epidemiologic information on specific hydrocarbons from toxic emission sources. We conducted a panel study of 22 Hispanic children with asthma who were 10-16 years old and living in a Los Angeles community with high traffic density. Subjects filled out symptom diaries daily for up to 3 months (November 1999 through January 2000). Pollutants included ambient hourly values of ozone, nitrogen dioxide, sulfur dioxide, and carbon monoxide and 24-hr values of volatile organic compounds (VOCs), particulate matter with aerodynamic diameter < 10 microm (PM10, and elemental carbon (EC) and organic carbon (OC) PM10 fractions. Asthma symptom severity was regressed on pollutants using generalized estimating equations, and peak expiratory flow (PEF) was regressed on pollutants using mixed models. We found positive associations of symptoms with criteria air pollutants (O3, NO2, SO2, PM10), EC-OC, and VOCs (benzene, ethylbenzene, formaldehyde, acetaldehyde, acetone, 1,3-butadiene, tetrachloroethylene, toluene, m,p-xylene, and o-xylene). Selected adjusted odds ratios for bothersome or more severe asthma symptoms from interquartile range increases in pollutants were, for 1.4 ppb 8-hr NO2, 1.27 [95% confidence interval (CI), 1.05-1.54]; 1.00 ppb benzene, 1.23 (95% CI, 1.02-1.48); 3.16 ppb formaldehyde, 1.37 (95% CI, 1.04-1.80); 37 microg/m3 PM10, 1.45 (95% CI, 1.11-1.90); 2.91 microg/m3 EC, 1.85 (95% CI, 1.11-3.08); and 4.64 microg/m3 OC, 1.88 (95% CI, 1.12-3.17). Two-pollutant models of EC or OC with PM10 showed little change in odds ratios for EC (to 1.83) or OC (to 1.89), but PM10 decreased from 1.45 to 1.0. There were no significant associations with PEF. Findings support the view that air toxins in the pollutant mix from traffic and industrial sources may have adverse effects on asthma in children

Identifying and Prioritizing Chemicals with Uncertain Burden of Exposure: Opportunities for Biomonitoring and Health-Related Research.

BackgroundThe National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) initiative aims to understand the impact of environmental factors on childhood disease. Over 40,000 chemicals are approved for commercial use. The challenge is to prioritize chemicals for biomonitoring that may present health risk concerns.ObjectivesOur aim was to prioritize chemicals that may elicit child health effects of interest to ECHO but that have not been biomonitored nationwide and to identify gaps needing additional research.MethodsWe searched databases and the literature for chemicals in environmental media and in consumer products that were potentially toxic. We selected chemicals that were not measured in the National Health and Nutrition Examination Survey. From over 700 chemicals, we chose 155 chemicals and created eight chemical panels. For each chemical, we compiled biomonitoring and toxicity data, U.S. Environmental Protection Agency exposure predictions, and annual production usage. We also applied predictive modeling to estimate toxicity. Using these data, we recommended chemicals either for biomonitoring, to be deferred pending additional data, or as low priority for biomonitoring.ResultsFor the 155 chemicals, 97 were measured in food or water, 67 in air or house dust, and 52 in biospecimens. We found in vivo endocrine, developmental, reproductive, and neurotoxic effects for 61, 74, 47, and 32 chemicals, respectively. Eighty-six had data from high-throughput in vitro assays. Positive results for endocrine, developmental, neurotoxicity, and obesity were observed for 32, 11, 35, and 60 chemicals, respectively. Predictive modeling results suggested 90% are toxicants. Biomarkers were reported for 76 chemicals. Thirty-six were recommended for biomonitoring, 108 deferred pending additional research, and 11 as low priority for biomonitoring.DiscussionThe 108 deferred chemicals included those lacking biomonitoring methods or toxicity data, representing an opportunity for future research. Our evaluation was, in general, limited by the large number of unmeasured or untested chemicals. https://doi.org/10.1289/EHP5133

Use of Pharmacokinetic Modeling to Design Studies for Pathway-Specific Exposure Model Evaluation

Validating an exposure pathway model is difficult because the biomarker, which is often used to evaluate the model prediction, is an integrated measure for exposures from all the exposure routes and pathways. The purpose of this article is to demonstrate a method to use pharmacokinetic (PK) modeling and computer simulation to guide the design of field studies to validate pathway models. The children’s dietary intake model is discussed in detail as an example. Three important aspects are identified for a successful design to evaluate the children’s dietary intake model: a) longitudinally designed study with significant changes in the exposure for the route/pathway of interest, b) short biologic half-life of the selected chemical, and c) surface loading of the selected chemical at sufficient levels. Using PK modeling to guide a study design allowed a path-specific exposure model to be evaluated using urinary metabolite biomarkers

Viewing America’s energy future in three dimensions

The future of the US energy infrastructure is a major and urgent challenge for our society. This monograph was stimulated by a report of the National Academies' Committee on America's Energy Future, America's Energy Future: Technology and Transformation, Summary Edition, 2009. The report pointed out the critical but poorly understood and little explored role of societal considerations in determining the fate of national energy policies and programs. In our efforts to respond to those concerns, we have examined the thesis that the three major dimensions of the energy challenge—technology, economics, and societal—are overlapping, interactive, and inseparable; therefore, they can be understood only when considered simultaneously and discussed in terms of their interactions. Correspondingly, this monograph describes energy technologies in the context of their economic and societal contexts, energy economics in their technological and societal contexts, and the societal aspects of energy in their technological and economic contexts. The monograph then identifies social science–driven research opportunities pertaining to America’s energy challenge, with the hope that the proposed research will help not only overcome the societal barriers identified by the National Academies' report, but also harness societal forces in developing a rational energy future