Office of Science

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.

Introduction 1.1. Methodology and Evidence ReviewThe recommendations listed in this document are, whenever possible, evidence based.An extensive evidence review was conducted through October 2011 and includes selected other references through April 2013.Searches were extended to studies, reviews, and other evidence conducted in human subjects and that were published in English from PubMed, EMBASE, Cochrane, Agency for Healthcare Research and Quality Reports, and other selected databases relevant to this guideline.Key search words included but were not limited to the following: heart failure, cardiomyopathy, quality of life, mortality, hospitalizations, prevention, biomarkers, hypertension, dyslipidemia, imaging, cardiac catheterization, endomyocardial biopsy, angiotensin-converting enzyme inhibitors, angiotensin-receptor antagonists/blockers, beta blockers, cardiac, cardiac resynchronization therapy, defibrillator, device-based therapy, implantable cardioverterdefibrillator, device implantation, medical therapy, acute decompensated heart failure, preserved ejection fraction, terminal care and transplantation, quality measures, and performance measures.Additionally, the committee reviewed documents related to the subject matter previously published by the ACCF and AHA.References selected and published in this document are representative and not all-inclusive.To provide clinicians with a representative evidence base, whenever deemed appropriate or when published, the absolute risk difference and number needed to treat or harm are provided in the guideline (within tables), along with confidence intervals and data related to the relative treatment effects such as odds ratio, relative risk, hazard ratio, and incidence rate ratio. Organization of the Writing CommitteeThe committee was composed of physicians and a nurse with broad expertise in the evaluation, care, and management of patients with heart failure (HF).The authors included general cardiologists, HF and transplant specialists, electrophysiologists, general internists, and physicians with methodological expertise.The committee included representatives from the ACCF, AHA, American Academy of Family Physicians, American College of Chest Physicians, American College of Physicians, Heart Rhythm Society, and International Society for Heart and Lung Transplantation. 1.3.

Flutter and Macroreentrant Atrial Tachycardia . . . . . . . . . . . . . . . .e206 2.2.Mechanisms of AF and Pathophysiology . . . . . .e207 2.2.1.Atrial Structural Abnormalities . . . . . . . .e207 2.2.2.Electrophysiological Mechanisms . . . . . .e208 2.2.2.1.Triggers of AF . . . . . . . . . . . . . .e208 2.2.2.2.Maintenance of AF. . . . .

The individual reviewers' relationships with industry information is available in Appendix 2.This document was approved for publication by the governing bodies of the ASA and the AHA.It was reviewed for evidence-based integrity

Hospitalized with Laboratory-Confirmed COVID-19 -COVID-NET, 14 States, March 1-July 25, 2020 1088 Transmission of SARS-CoV-2 Involving ResidentsReceiving Dialysis in a Nursing Home -Maryland, April 2020 1094 Facility-Wide Testing for SARS-CoV-2 in Nursing Homes -Seven U.S.

◼ cardiac surgery ◼ heart valves ◼ mitral regurgitation ◼ prosthetic valves ◼ transcatheter aortic valve replacement ◼ tricuspid stenosis ◼ valvular heart disease AHA/ACC GUIDELINE ACC/AHA Task Force Members, see page e1180 *Focused Update writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information.†ACC/AHA Representative.‡ACC/

Writing committee members are required to recuse themselves from voting on

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.

The writing committee gratefully acknowledges the memory of Dr. Francis M. Fesmire (representative of the American College of Emergency Physicians), who died during the development of this document but contributed immensely to our understanding of non-ST-elevation acute coronary syndromes.*Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry and other entities may apply; see Appendix 1 for recusal information.†ACC/AHA Representative.

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.

AIM: The "2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage" replaces the 2012 "Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage." The 2023 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with aneurysmal subarachnoid hemorrhage. METHODS: A comprehensive search for literature published since the 2012 guideline, derived from research principally involving human subjects, published in English, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline, was conducted between March 2022 and June 2022. In addition, the guideline writing group reviewed documents on related subject matter previously published by the American Heart Association. Newer studies published between July 2022 and November 2022 that affected recommendation content, Class of Recommendation, or Level of Evidence were included if appropriate. Structure: Aneurysmal subarachnoid hemorrhage is a significant global public health threat and a severely morbid and often deadly condition. The 2023 aneurysmal subarachnoid hemorrhage guideline provides recommendations based on current evidence for the treatment of these patients. The recommendations present an evidence-based approach to preventing, diagnosing, and managing patients with aneurysmal subarachnoid hemorrhage, with the intent to improve quality of care and align with patients' and their families' and caregivers' interests. Many recommendations from the previous aneurysmal subarachnoid hemorrhage guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

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.

Writing committee members are required to

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.

The 2012 writing group members were required to recuse

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.