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The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

work of the writing committee, without commercial support. Writing committee members volunteered their time for this activity. Guidelines are official policy of both the ACC and AHA.

transcatheter aortic valve replacement tricuspid stenosis valvular heart disease AHA/ACC GUIDELINE ACC/AHA Task Force Members, see page e1180

Over the course of the past decade, green chemistry has demonstrated how fundamental scientific methodologies can protect human health and the environment in an economically beneficial manner. Significant progress is being made in several key research areas, such as catalysis, the design of safer chemicals and environmentally benign solvents, and the development of renewable feedstocks. Current and future chemists are being trained to design products and processes with an increased awareness for environmental impact. Outreach activities within the green chemistry community highlight the potential for chemistry to solve many of the global environmental challenges we now face. The origins and basis of green chemistry chart a course for achieving environmental and economic prosperity inherent in a sustainable world.

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTFunctionalizing Nanoparticles with Biological Molecules: Developing Chemistries that Facilitate NanotechnologyKim E. Sapsford†, W. Russ Algar§, Lorenzo Berti⊥, Kelly Boeneman Gemmill‡, Brendan J. Casey†, Eunkeu Oh∥¶, Michael H. Stewart¶, and Igor L. Medintz*‡View Author Information† Division of Biology, Department of Chemistry and Materials Science, Office of Science and Engineering Laboratories, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, United States‡ ‡Center for Bio/Molecular Science and Engineering Code 6900 and ¶Division of Optical Sciences Code 5611, U.S. Naval Research Laboratory, Washington, D.C. 20375, United States§ College of Science, George Mason University, 4400 University Drive, Fairfax, Virginia 22030, United States⊥ Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Sacramento, California 95817, United States∥ Sotera Defense Solutions, Crofton, Maryland 21114, United States*E-mail: [email protected]Cite this: Chem. Rev. 2013, 113, 3, 1904–2074Publication Date (Web):February 22, 2013Publication History Received5 April 2012Published online22 February 2013Published inissue 13 March 2013https://pubs.acs.org/doi/10.1021/cr300143vhttps://doi.org/10.1021/cr300143vreview-articleACS PublicationsCopyright © 2013 American Chemical SocietyRequest reuse permissionsArticle Views71277Altmetric-Citations1151LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Chemical biology,Functionalization,Genetics,Peptides and proteins,Quantum dots Get e-Alerts

Results are presented from the second phase of the multiinstitution North American Land Data Assimilation System (NLDAS‐2) research partnership. In NLDAS, the Noah, Variable Infiltration Capacity, Sacramento Soil Moisture Accounting, and Mosaic land surface models (LSMs) are executed over the conterminous U.S. (CONUS) in realtime and retrospective modes. These runs support the drought analysis, monitoring and forecasting activities of the National Integrated Drought Information System, as well as efforts to monitor large‐scale floods. NLDAS‐2 builds upon the framework of the first phase of NLDAS (NLDAS‐1) by increasing the accuracy and consistency of the surface forcing data, upgrading the land surface model code and parameters, and extending the study from a 3‐year (1997–1999) to a 30‐year (1979–2008) time window. As the first of two parts, this paper details the configuration of NLDAS‐2, describes the upgrades to the forcing, parameters, and code of the four LSMs, and explores overall model‐to‐model comparisons of land surface water and energy flux and state variables over the CONUS. Focusing on model output rather than on observations, this study seeks to highlight the similarities and differences between models, and to assess changes in output from that seen in NLDAS‐1. The second part of the two‐part article focuses on the validation of model‐simulated streamflow and evaporation against observations. The results depict a higher level of agreement among the four models over much of the CONUS than was found in the first phase of NLDAS. This is due, in part, to recent improvements in the parameters, code, and forcing of the NLDAS‐2 LSMs that were initiated following NLDAS‐1. However, large inter‐model differences still exist in the northeast, Lake Superior, and western mountainous regions of the CONUS, which are associated with cold season processes. In addition, variations in the representation of sub‐surface hydrology in the four LSMs lead to large differences in modeled evaporation and subsurface runoff. These issues are important targets for future research by the land surface modeling community. Finally, improvement from NLDAS‐1 to NLDAS‐2 is summarized by comparing the streamflow measured from U.S. Geological Survey stream gauges with that simulated by four NLDAS models over 961 small basins.

Abstract The purpose of this review paper is to present the technical basis for establishing sediment quality criteria using equilibrium partitioning (EqP). Equilibrium partitioning is chosen because it addresses the two principal technical issues that must be resolved: the varying bioavailability of chemicals in sediments and the choice of the appropriate biological effects concentration. The data that are used to examine the question of varying bioavailability across sediments are from toxicity and bioaccumulation experiments utilizing the same chemical and test organism but different sediments. It has been found that if the different sediments in each experiment are compared, there is essentially no relationship between sediment chemical concentrations on a dry weight basis and biological effects. However, if the chemical concentrations in the pore water of the sediment are used (for chemicals that are not highly hydrophobic) or if the sediment chemical concentrations on an organic carbon basis are used, then the biological effects occur at similar concentrations (within a factor of two) for the different sediments. In addition, the effects concentrations are the same as, or they can be predicted from, the effects concentration determined in water- only exposures. The EqP methodology rationalizes these results by assuming that the partitioning of the chemical between sediment organic carbon and pore water is at equilibrium. In each of these phases, the fugacity or activity of the chemical is the same at equilibrium. As a consequence, it is assumed that the organism receives an equivalent exposure from a water-only exposure or from any equilibrated phase, either from pore water via respiration, from sediment carbon via ingestion; or from a mixture of the routes. Thus, the pathway of exposure is not significant. The biological effect is produced by the chemical activity of the single phase or the equilibrated system. Sediment quality criteria for nonionic organic chemicals are based on the chemical concentration in sediment organic carbon. For highly hydrophobic chemicals this is necessary because the pore water concentration is, for those chemicals, no longer a good estimate of the chemical activity. The pore water concentration is the sum of the free chemical concentration, which is bioavailable and represents the chemical activity, and the concentration of chemical complexed to dissolved organic carbon, which, as the data presented below illustrate, is not bioavailable. Using the chemical concentration in sediment organic carbon eliminates this ambiguity. Sediment quality criteria also require that a chemical concentration be chosen that is sufficiently protective of benthic organisms. The final chronic value (FCV) from the U.S. Environmental Protection Agency (EPA) water quality criteria is proposed. An analysis of the data compiled in the water quality criteria documents demonstrates that benthic species, defined as either epibenthic or infaunal species, have a similar sensitivity to water column species. This is the case if the most sensitive species are compared and if all species are compared. The results of benthic colonization experiments also support the use of the FCV. Equilibrium partitioning cannot remove all the variation in the experimentally observed sediment- effects concentration and the concentration predicted from water-only exposures. A variation of approximately a factor of two to three remains. Hence, it is recognized that a quantification of this uncertainty should accompany the sediment quality criteria. The derivation of sediment quality criteria requires the octanol/water partition coefficient of the chemical. It should be measured with modern experimental techniques, which appear to remove the large variation in reported values. The derivation of the final chronic value should also be updated to include the most recent toxicological information.

BACKGROUND: Recent eHealth developments have elevated the importance of assessing the extent to which technology has empowered patients and improved health, particularly among the most vulnerable populations. With noted disparities across racial and social groups in chronic health outcomes, such as cancer, obesity, and diabetes, it is essential that researchers examine any differences in the implementation, uptake, and impact of eHealth strategies across groups that bear a disproportionate burden of disease. OBJECTIVE: The goal was to examine eHealth use by sociodemographic factors, such as race/ethnicity, socioeconomic status (SES), age, and sex. METHODS: We drew data from National Cancer Institute's 2012 Health Information National Trends Survey (HINTS) (N=3959) which is publicly available online. We estimated multivariable logistic regression models to assess sociodemographic predictors of eHealth use among adult Internet users (N=2358) across 3 health communication domains (health care, health information-seeking, and user-generated content/sharing). RESULTS: Among online adults, we saw no evidence of a digital use divide by race/ethnicity. However, there were significant differences in use by SES, particularly for health care and health information-seeking items. Patients with lower levels of education had significantly lower odds of going online to look for a health care provider (high school or less: OR 0.50, 95% CI 0.33-0.76) using email or the Internet to communicate with a doctor (high school or less: OR 0.46, 95% CI 0.29-0.72), tracking their personal health information online (high school or less: OR 0.53, 95% CI 0.32-0.84), using a website to help track diet, weight, and physical activity (high school or less: OR 0.64, 95% CI 0.42-0.98; some college: OR 0.67, 95% CI 0.49-0.93), or downloading health information to a mobile device (some college: OR 0.54, 95% CI 0.33-0.89). Being female was a consistent predictor of eHealth use across health care and user-generated content/sharing domains, whereas age was primarily influential for health information-seeking. CONCLUSIONS: This study illustrates that lower SES, older, and male online US adults were less likely to engage in a number of eHealth activities compared to their counterparts. Future studies should assess issues of health literacy and eHealth literacy and their influence on eHealth engagement across social groups. Clinical care and public health communication efforts attempting to leverage Web 2.0 and 3.0 platforms should acknowledge differential eHealth usage to better address communication inequalities and persistent disparities in health.

Human papillomavirus (HPV) is a known cause of cervical cancers, as well as some vulvar, vaginal, penile, oropharyngeal, anal, and rectal cancers (1,2). Although most HPV infections are asymptomatic and clear spontaneously, persistent infections with one of 13 oncogenic HPV types can progress to precancer or cancer. To assess the incidence of HPV-associated cancers, CDC analyzed 2008-2012 high-quality data from the CDC's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology, and End Results program. During 2008-2012, an average of 38,793 HPV-associated cancers were diagnosed annually, including 23,000 (59%) among females and 15,793 (41%) among males. By multiplying these counts by the percentages attributable to HPV (3), CDC estimated that approximately 30,700 new cancers were attributable to HPV, including 19,200 among females and 11,600 among males. Cervical precancers can be detected through screening, and treatment can prevent progression to cancer; HPV vaccination can prevent infection with HPV types that cause cancer at cervical and other sites (3). Vaccines are available for HPV types 16 and 18, which cause 63% of all HPV-associated cancers in the United States, and for HPV types 31, 33, 45, 52, and 58, which cause an additional 10% (3). Among the oncogenic HPV types, HPV 16 is the most likely to both persist and to progress to cancer (3). The impact of these primary and secondary prevention interventions can be monitored using surveillance data from population-based cancer registries.

Probabilistic linkage technology makes it feasible and efficient to link large public health databases in a statistically justifiable manner. The problem addressed by the methodology is that of matching two files of individual data under conditions of uncertainty. Each field is subject to error which is measured by the probability that the field agrees given a record pair matches (called the m probability) and probabilities of chance agreement of its value states (called the u probability). Fellegi and Sunter pioneered record linkage theory. Advances in methodology include use of an EM algorithm for parameter estimation, optimization of matches by means of a linear sum assignment program, and more recently, a probability model that addresses both m and u probabilities for all value states of a field. This provides a means for obtaining greater precision from non-uniformly distributed fields, without the theoretical complications arising from frequency-based matching alone. The model includes an iterative parameter estimation procedure that is more robust than pre-match estimation techniques. The methodology was originally developed and tested by the author at the U.S. Census Bureau for census undercount estimation. The more recent advances and a new generalized software system were tested and validated by linking highway crashes to Emergency Medical Service (EMS) reports and to hospital admission records for the National Highway Traffic Safety Administration (NHTSA).

Abstract Literature regrading azo dye carcinogenicity was examined to establish, if possible, guidelines to predict the human health risks of new azo dyes. Three different mechanisms for azo dye carcinogenicity were identified, all involving metabolic activation to reactive electrophilic intermediates that covalently bind DNA. In the order of decreasing number of published references, these mechanisms are Azo dyes that are toxic only after reduction and cleavage of the azo linkage to give aromatic amines, mostly via intestinal anaerobic bacteria. The aromatic amines are met‐abolically oxidized to reactive electrophilic species that covalently bind DNA. Azo dyes with structures containing free aromatic amine groups that can be meta‐bolically oxidized without azo reduction. Azo dyes that may be activated via direct oxidation of the azo linkage to highly reactive electrophilic diazonium salts. Each mechanism may be compound specific, thus azo toxicity is probably caused by more than one mechanism. Although i...

Coral reef ecosystems have suffered an unprecedented loss of habitat-forming hard corals in recent decades. While marine conservation has historically focused on passive habitat protection, demand for and interest in active restoration has been growing in recent decades. However, a disconnect between coral restoration practitioners, coral reef managers and scientists has resulted in a disjointed field where it is difficult to gain an overview of existing knowledge. To address this, we aimed to synthesise the available knowledge in a comprehensive global review of coral restoration methods, incorporating data from the peer-reviewed scientific literature, complemented with grey literature and through a survey of coral restoration practitioners. We found that coral restoration case studies are dominated by short-term projects, with 60% of all projects reporting less than 18 months of monitoring of the restored sites. Similarly, most projects are relatively small in spatial scale, with a median size of restored area of 100 m2. A diverse range of species are represented in the dataset, with 229 different species from 72 coral genera. Overall, coral restoration projects focused primarily on fast-growing branching corals (59% of studies), and report survival between 60 and 70%. To date, the relatively young field of coral restoration has been plagued by similar 'growing pains' as ecological restoration in other ecosystems. These include 1) a lack of clear and achievable objectives, 2) a lack of appropriate and standardised monitoring and reporting and, 3) poorly designed projects in relation to stated objectives. Mitigating these will be crucial to successfully scale up projects, and to retain public trust in restoration as a tool for resilience based management. Finally, while it is clear that practitioners have developed effective methods to successfully grow corals at small scales, it is critical not to view restoration as a replacement for meaningful action on climate change.

MicroRNAs (miRNAs) have been used as cancer-related biomarkers. Hepatocellular carcinoma (HCC) is an aggressive cancer with a dismal outcome largely due to metastasis and postsurgical recurrence. We investigated whether the expression of certain miRNAs are associated with HCC metastasis. We examined the miRNA expression profiles of 482 cancerous and noncancerous specimens from radical resection of 241 patients with HCC. Using a supervised algorithm and a clinically well-defined cohort of 131 cases, we built a unique 20-miRNA metastasis signature that could significantly predict (P < 0.001) primary HCC tissues with venous metastases from metastasis-free solitary tumors with 10-fold cross-validation. However, significant miRNAs could not be identified from the corresponding noncancerous hepatic tissues. A survival risk prediction analysis revealed that a majority of the metastasis-related miRNAs were associated with survival. Furthermore, the 20-miRNA tumor signature was validated in 110 additional cases as a significant independent predictor of survival (P = 0.009) and was significantly associated with both survival and relapse in 89 cases of early stage HCC (P = 0.022 and 0.002, respectively). These 20 miRNAs may provide a simple profiling method to assist in identifying patients with HCC who are likely to develop metastases/recurrence. In addition, functional analysis of these miRNAs may enhance our biological understanding of HCC metastasis.

Inhibitors of the JAK family of nonreceptor tyrosine kinases have demonstrated clinical efficacy in rheumatoid arthritis and other inflammatory disorders; however, the precise mechanisms by which JAK inhibition improves inflammatory immune responses remain unclear. In this study, we examined the mode of action of tofacitinib (CP-690,550) on JAK/STAT signaling pathways involved in adaptive and innate immune responses. To determine the extent of inhibition of specific JAK/STAT-dependent pathways, we analyzed cytokine stimulation of mouse and human T cells in vitro. We also investigated the consequences of CP-690,550 treatment on Th cell differentiation of naive murine CD4(+) T cells. CP-690,550 inhibited IL-4-dependent Th2 cell differentiation and interestingly also interfered with Th17 cell differentiation. Expression of IL-23 receptor and the Th17 cytokines IL-17A, IL-17F, and IL-22 were blocked when naive Th cells were stimulated with IL-6 and IL-23. In contrast, IL-17A production was enhanced when Th17 cells were differentiated in the presence of TGF-β. Moreover, CP-690,550 also prevented the activation of STAT1, induction of T-bet, and subsequent generation of Th1 cells. In a model of established arthritis, CP-690,550 rapidly improved disease by inhibiting the production of inflammatory mediators and suppressing STAT1-dependent genes in joint tissue. Furthermore, efficacy in this disease model correlated with the inhibition of both JAK1 and JAK3 signaling pathways. CP-690,550 also modulated innate responses to LPS in vivo through a mechanism likely involving the inhibition of STAT1 signaling. Thus, CP-690,550 may improve autoimmune diseases and prevent transplant rejection by suppressing the differentiation of pathogenic Th1 and Th17 cells as well as innate immune cell signaling.

BACKGROUND: Noncigarette tobacco products are evolving rapidly, with increasing popularity in the United States. METHODS: We present prevalence estimates for 12 types of tobacco products, using data from 45,971 adult and youth participants (≥12 years of age) from Wave 1 (September 2013 through December 2014) of the Population Assessment of Tobacco and Health (PATH) Study, a large, nationally representative, longitudinal study of tobacco use and health in the United States. Participants were asked about their use of cigarettes, e-cigarettes, traditional cigars, cigarillos, filtered cigars, pipe tobacco, hookah, snus pouches, other smokeless tobacco, dissolvable tobacco, bidis, and kreteks. Estimates of the prevalence of use for each product were determined according to use category (e.g., current use or use in the previous 30 days) and demographic subgroup, and the prevalence of multiple-product use was explored. RESULTS: More than a quarter (27.6%) of adults were current users of at least one type of tobacco product in 2013 and 2014, although the prevalence varied depending on use category. A total of 8.9% of youths had used a tobacco product in the previous 30 days; 1.6% of youths were daily users. Approximately 40% of tobacco users, adults and youths alike, used multiple tobacco products; cigarettes plus e-cigarettes was the most common combination. Young adults (18 to 24 years of age), male adults and youths, members of racial minorities, and members of sexual minorities generally had higher use of tobacco than their counterparts. CONCLUSIONS: During this study, 28% of U.S. adults were current users of tobacco, and 9% of youths had used tobacco in the previous 30 days. Use of multiple products was common among tobacco users. These findings will serve as baseline data to examine between-person differences and within-person changes over time in the use of tobacco products. (Funded by the National Institute on Drug Abuse and the Food and Drug Administration.).

There has been extensive progress in understanding the cellular and molecular mechanisms of inflammation and immune regulation in allergic diseases of the skin and lungs during the last few years. Asthma and atopic dermatitis (AD) are typical diseases of type 2 immune responses. interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin are essential cytokines of epithelial cells that are activated by allergens, pollutants, viruses, bacteria, and toxins that derive type 2 responses. Th2 cells and innate lymphoid cells (ILC) produce and secrete type 2 cytokines such as IL-4, IL-5, IL-9, and IL-13. IL-4 and IL-13 activate B cells to class-switch to IgE and also play a role in T-cell and eosinophil migration to allergic inflammatory tissues. IL-13 contributes to maturation, activation, nitric oxide production and differentiation of epithelia, production of mucus as well as smooth muscle contraction, and extracellular matrix generation. IL-4 and IL-13 open tight junction barrier and cause barrier leakiness in the skin and lungs. IL-5 acts on activation, recruitment, and survival of eosinophils. IL-9 contributes to general allergic phenotype by enhancing all of the aspects, such as IgE and eosinophilia. Type 2 ILC contribute to inflammation in AD and asthma by enhancing the activity of Th2 cells, eosinophils, and their cytokines. Currently, five biologics are licensed to suppress type 2 inflammation via IgE, IL-5 and its receptor, and IL-4 receptor alpha. Some patients with severe atopic disease have little evidence of type 2 hyperactivity and do not respond to biologics which target this pathway. Studies in responder and nonresponder patients demonstrate the complexity of these diseases. In addition, primary immune deficiency diseases related to T-cell maturation, regulatory T-cell development, and T-cell signaling, such as Omenn syndrome, severe combined immune deficiencies, immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, and DOCK8, STAT3, and CARD11 deficiencies, help in our understanding of the importance and redundancy of various type 2 immune components. The present review aims to highlight recent advances in type 2 immunity and discuss the cellular sources, targets, and roles of type 2 mechanisms in asthma and AD.

Importance: Use of electronic cigarettes (e-cigarettes) is increasing. Measures of exposure to known tobacco-related toxicants among e-cigarette users will inform potential health risks to individual product users. Objectives: To estimate concentrations of tobacco-related toxicants among e-cigarette users and compare these biomarker concentrations with those observed in combustible cigarette users, dual users, and never tobacco users. Design, Setting, and Participants: A population-based, longitudinal cohort study was conducted in the United States in 2013-2014. Cross-sectional analysis was performed between November 4, 2016, and October 5, 2017, of biomarkers of exposure to tobacco-related toxicants collected by the Population Assessment of Tobacco and Health Study. Participants included adults who provided a urine sample and data on tobacco use (N = 5105). Exposures: The primary exposure was tobacco use, including current exclusive e-cigarette users (n = 247), current exclusive cigarette smokers (n = 2411), and users of both products (dual users) (n = 792) compared with never tobacco users (n = 1655). Main Outcomes and Measures: Geometric mean concentrations of 50 individual biomarkers from 5 major classes of tobacco product constituents were measured: nicotine, tobacco-specific nitrosamines (TSNAs), metals, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs). Results: Of the 5105 participants, most were aged 35 to 54 years (weighted percentage, 38%; 95% CI, 35%-40%), women (60%; 95% CI, 59%-62%), and non-Hispanic white (61%; 95% CI, 58%-64%). Compared with exclusive e-cigarette users, never users had 19% to 81% significantly lower concentrations of biomarkers of exposure to nicotine, TSNAs, some metals (eg, cadmium and lead), and some VOCs (including acrylonitrile). Exclusive e-cigarette users showed 10% to 98% significantly lower concentrations of biomarkers of exposure, including TSNAs, PAHs, most VOCs, and nicotine, compared with exclusive cigarette smokers; concentrations were comparable for metals and 3 VOCs. Exclusive cigarette users showed 10% to 36% lower concentrations of several biomarkers than dual users. Frequency of cigarette use among dual users was positively correlated with nicotine and toxicant exposure. Conclusions and Relevance: Exclusive use of e-cigarettes appears to result in measurable exposure to known tobacco-related toxicants, generally at lower levels than cigarette smoking. Toxicant exposure is greatest among dual users, and frequency of combustible cigarette use is positively correlated with tobacco toxicant concentration. These findings provide evidence that using combusted tobacco cigarettes alone or in combination with e-cigarettes is associated with higher concentrations of potentially harmful tobacco constituents in comparison with using e-cigarettes alone.

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTAnalyzing Nanomaterial Bioconjugates: A Review of Current and Emerging Purification and Characterization TechniquesKim E. Sapsford*†, Katherine M. Tyner‡, Benita J. Dair§, Jeffrey R. Deschamps∥, and Igor L. Medintz*∥View Author Information§ †Division of Biology, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, ‡Division of Drug Safety Research, Office of Testing and Research, Office of Pharmaceutical Science Center for Drug Evaluation and Research, and §Division of Chemistry and Materials Science, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993, United States∥ Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, 4555 Overlook Avenue, S.W. Washington, DC 20375, United StatesE-mail: [email protected] (K.E.S.); [email protected] (I.L.M.).Cite this: Anal. Chem. 2011, 83, 12, 4453–4488Publication Date (Web):May 5, 2011Publication History Published online5 May 2011Published inissue 15 June 2011https://doi.org/10.1021/ac200853aCopyright © This article not subject to U.S. Copyright. Published 2011 by the American Chemical SocietyRIGHTS & PERMISSIONSArticle Views9915Altmetric-Citations381LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (13 MB) Get e-AlertsSUBJECTS:Fluorescence,Metal nanoparticles,Nanoparticles,Peptides and proteins,Quantum dots Get e-Alerts

We have developed a diabetes quality-of-life (DQOL) measure oriented toward the patient with insulin-dependent diabetes mellitus (IDDM). The DQOL was assessed for its reliability and validity in a group of patients with IDDM (n = 192). We found that the DQOL and its four scales had high degrees of internal consistency (Cronbach's r = .66-.92) and excellent test-retest reliability (r = .78-.92). Using conceptually relevant measures of psychiatric symptoms, perceived well-being and adjustment to illness, we also demonstrated convergent validity of the DQOL. This instrument was initially designed for use in the Diabetes Control and Complications Trial, a multicenter controlled clinical trial evaluating the effects of two different diabetes treatment regimens on the appearance and progression of early vascular complications. However, the DQOL may also be useful in evaluating the quality of life in other groups of patients with IDDM.

OBJECTIVE: Thousands of chemicals are in common use, but only a portion of them have undergone significant toxicologic evaluation, leading to the need to prioritize the remainder for targeted testing. To address this issue, the U.S. Environmental Protection Agency (EPA) and other organizations are developing chemical screening and prioritization programs. As part of these efforts, it is important to catalog, from widely dispersed sources, the toxicology information that is available. The main objective of this analysis is to define a list of environmental chemicals that are candidates for the U.S. EPA screening and prioritization process, and to catalog the available toxicology information. DATA SOURCES: We are developing ACToR (Aggregated Computational Toxicology Resource), which combines information for hundreds of thousands of chemicals from > 200 public sources, including the U.S. EPA, National Institutes of Health, Food and Drug Administration, corresponding agencies in Canada, Europe, and Japan, and academic sources. DATA EXTRACTION: ACToR contains chemical structure information; physical-chemical properties; in vitro assay data; tabular in vivo data; summary toxicology calls (e.g., a statement that a chemical is considered to be a human carcinogen); and links to online toxicology summaries. Here, we use data from ACToR to assess the toxicity data landscape for environmental chemicals. DATA SYNTHESIS: We show results for a set of 9,912 environmental chemicals being considered for analysis as part of the U.S. EPA ToxCast screening and prioritization program. These include high-and medium-production-volume chemicals, pesticide active and inert ingredients, and drinking water contaminants. CONCLUSIONS: Approximately two-thirds of these chemicals have at least limited toxicity summaries available. About one-quarter have been assessed in at least one highly curated toxicology evaluation database such as the U.S. EPA Toxicology Reference Database, U.S. EPA Integrated Risk Information System, and the National Toxicology Program.