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David K. Henderson

Bio: David K. Henderson is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Health care & Hepatitis C. The author has an hindex of 38, co-authored 175 publications receiving 6186 citations. Previous affiliations of David K. Henderson include United States Department of Health and Human Services & University of Michigan.


Papers
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Journal ArticleDOI
TL;DR: Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing revealed its origin and probable modes of transmission, and revealed the weaknesses in this medical who-done-it, informing improvements in hospital preventive measures.
Abstract: The Gram-negative bacteria Klebsiella pneumoniae is a major cause of nosocomial infections, primarily among immunocompromised patients. The emergence of strains resistant to carbapenems has left few treatment options, making infection containment critical. In 2011, the U.S. National Institutes of Health Clinical Center experienced an outbreak of carbapenem-resistant K. pneumoniae that affected 18 patients, 11 of whom died. Whole-genome sequencing was performed on K. pneumoniae isolates to gain insight into why the outbreak progressed despite early implementation of infection control procedures. Integrated genomic and epidemiological analysis traced the outbreak to three independent transmissions from a single patient who was discharged 3 weeks before the next case became clinically apparent. Additional genomic comparisons provided evidence for unexpected transmission routes, with subsequent mining of epidemiological data pointing to possible explanations for these transmissions. Our analysis demonstrates that integration of genomic and epidemiological data can yield actionable insights and facilitate the control of nosocomial transmission.

828 citations

Journal ArticleDOI
TL;DR: Two triazine ligands have been synthesized by derivatisation of cyanuric chloride: 6-(diethylamino)-2,4-disulfide group present on one ring and a co-ordinated thiolate on the second.
Abstract: Two ligands have been synthesized by derivatisation of cyanuric chloride: 6-(diethylamino)-2,4-disulfanyl-1,3,5-triazine (H2SSta) 1 and 6-(diethylamino)-2-hydroxo-4-sulfanyl-1,3,5-triazine (H2OSta) 2 have been characterised by X-ray crystallography, which shows intermolecular hydrogen bonding in the solid state, leading to dimers of 1 and ribbons of 2. On reaction with metal salts both ligands undergo oligomerisation reactions. Compound 1 reacts with nickel chloride to form a mononuclear complex, [Ni{(Sta)S(S2ta)}] 3. In 3 two triazine ligands have reacted, to form a tetradentate ligand in which two triazine rings are bridged by a sulfur group, with a co-ordinated disulfide group present on one ring and a co-ordinated thiolate on the second. Compound 2 reacts with cobalt(II) chloride to form a cage complex, [Co6NaO(OStaH)7{S(Ota)2}2(O2CPh)2(H2O)2] 4. This complicated structure contains two polydentate ligands formed by linking triazine groups through a bridging sulfur. The cage contains four cobalt(II) and two cobalt(III) sites which are assigned by bond length considerations. The compound [Co(OSta)3] 5 co-crystallises with 4, and its structure has also been determined.

495 citations

Journal ArticleDOI
TL;DR: A 6-year, ongoing, prospective study of the risk for human immunodeficiency virus type 1 (HIV-1) transmission among health care workers was conducted in this paper.
Abstract: OBJECTIVES To summarize the results of a 6-year, ongoing, prospective study of the risk for human immunodeficiency virus type 1 (HIV-1) transmission among health care workers, and to estimate the magnitude of the risk for HIV-1 infection associated with different types of occupational exposures DESIGN Prospective cohort study; the median follow-up for employees sustaining parenteral exposures was 302 months (range, 6 to 69 months) SUBJECTS Health care workers at the Clinical Center, National Institutes of Health, including those reporting parenteral and nonparenteral occupational exposures to HIV-1 MEASUREMENTS AND MAIN RESULTS One thousand three hundred and forty-four clinical health care workers reported 179 percutaneous and 346 mucous membrane exposures to fluids from HIV-1-infected patients during a 6-year period Responding to a supplementary questionnaire, 559 of these workers reported 2712 cutaneous exposures to blood from HIV-1-infected patients and more than 10,000 cutaneous exposures to blood from all patients during a 12-month period Occupational transmission of HIV-1 occurred in a single worker after a parenteral exposure to blood from an HIV-1-infected patient No infections occurred after either mucous membrane or cutaneous exposures to blood from HIV-1-infected patients Use of newer diagnostic technologies (for example, antigen detection, gene amplification) has not resulted in the identification of occupationally transmitted seronegative infections CONCLUSIONS Combining our results with those of other prospective studies, the risk for HIV-1 transmission associated with a percutaneous exposure to blood from an HIV-1-infected patient is approximately 03% per exposure (95% CI, 013% to 070%); the risks associated with occupational mucous membrane and cutaneous exposures are likely to be substantially smaller These data support the use of barrier precautions and suggest a need for strategies that change health care providers' attitudes and behaviors

420 citations

Journal ArticleDOI
TL;DR: A new DNA sequencing method is used to take a close look at one way in which antibiotic resistance spreads, and finds evidence that plasmids carrying carbapenemase genes moved from one microbial species to another within the hospital environment.
Abstract: Public health officials have raised concerns that plasmid transfer between Enterobacteriaceae species may spread resistance to carbapenems, an antibiotic class of last resort, thereby rendering common health care–associated infections nearly impossible to treat. To determine the diversity of carbapenemase-encoding plasmids and assess their mobility among bacterial species, we performed comprehensive surveillance and genomic sequencing of carbapenem-resistant Enterobacteriaceae in the National Institutes of Health (NIH) Clinical Center patient population and hospital environment. We isolated a repertoire of carbapenemase-encoding Enterobacteriaceae, including multiple strains of Klebsiella pneumoniae , Klebsiella oxytoca , Escherichia coli , Enterobacter cloacae , Citrobacter freundii , and Pantoea species. Long-read genome sequencing with full end-to-end assembly revealed that these organisms carry the carbapenem resistance genes on a wide array of plasmids. K. pneumoniae and E. cloacae isolated simultaneously from a single patient harbored two different carbapenemase-encoding plasmids, indicating that plasmid transfer between organisms was unlikely within this patient. We did, however, find evidence of horizontal transfer of carbapenemase-encoding plasmids between K. pneumoniae , E. cloacae , and C. freundii in the hospital environment. Our data, including full plasmid identification, challenge assumptions about horizontal gene transfer events within patients and identify possible connections between patients and the hospital environment. In addition, we identified a new carbapenemase-encoding plasmid of potentially high clinical impact carried by K. pneumoniae , E. coli , E. cloacae , and Pantoea species, in unrelated patients and in the hospital environment.

292 citations

Journal ArticleDOI
TL;DR: To ensure timely postexposure management and administration of HIV PEP, clinicians should consider occupational exposures as urgent medical concerns, and institutions should take steps to ensure that staff are aware of both the importance of and the institutional mechanisms available for reporting and seeking care for such exposures.
Abstract: This report updates US Public Health Service recommendations for the management of healthcare personnel (HCP) who experience occupational exposure to blood and/or other body fluids that might contain human immunodeficiency virus (HIV). Although the principles of exposure management remain unchanged, recommended HIV postexposure prophylaxis (PEP) regimens and the duration of HIV follow-up testing for exposed personnel have been updated. This report emphasizes the importance of primary prevention strategies, the prompt reporting and management of occupational exposures, adherence to recommended HIV PEP regimens when indicated for an exposure, expert consultation in management of exposures, follow-up of exposed HCP to improve adherence to PEP, and careful monitoring for adverse events related to treatment, as well as for virologic, immunologic, and serologic signs of infection. To ensure timely postexposure management and administration of HIV PEP, clinicians should consider occupational exposures as urgent medical concerns, and institutions should take steps to ensure that staff are aware of both the importance of and the institutional mechanisms available for reporting and seeking care for such exposures. The following is a summary of recommendations: (1) PEP is recommended when occupational exposures to HIV occur; (2) the HIV status of the exposure source patient should be determined, if possible, to guide need for HIV PEP; (3) PEP medication regimens should be started as soon as possible after occupational exposure to HIV, and they should be continued for a 4-week duration; (4) new recommendation-PEP medication regimens should contain 3 (or more) antiretroviral drugs (listed in Appendix A ) for all occupational exposures to HIV; (5) expert consultation is recommended for any occupational exposures to HIV and at a minimum for situations described in Box 1 ; (6) close follow-up for exposed personnel ( Box 2 ) should be provided that includes counseling, baseline and follow-up HIV testing, and monitoring for drug toxicity; follow-up appointments should begin within 72 hours of an HIV exposure; and (7) new recommendation-if a newer fourth-generation combination HIV p24 antigen-HIV antibody test is utilized for follow-up HIV testing of exposed HCP, HIV testing may be concluded 4 months after exposure ( Box 2 ); if a newer testing platform is not available, follow-up HIV testing is typically concluded 6 months after an HIV exposure.

283 citations


Cited by
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01 Jun 2012
TL;DR: SPAdes as mentioned in this paper is a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler and on popular assemblers Velvet and SoapDeNovo (for multicell data).
Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

10,124 citations

Posted Content
TL;DR: Deming's theory of management based on the 14 Points for Management is described in Out of the Crisis, originally published in 1982 as mentioned in this paper, where he explains the principles of management transformation and how to apply them.
Abstract: According to W. Edwards Deming, American companies require nothing less than a transformation of management style and of governmental relations with industry. In Out of the Crisis, originally published in 1982, Deming offers a theory of management based on his famous 14 Points for Management. Management's failure to plan for the future, he claims, brings about loss of market, which brings about loss of jobs. Management must be judged not only by the quarterly dividend, but by innovative plans to stay in business, protect investment, ensure future dividends, and provide more jobs through improved product and service. In simple, direct language, he explains the principles of management transformation and how to apply them.

9,241 citations

Journal ArticleDOI
TL;DR: An integrated database, called EzBioCloud, that holds the taxonomic hierarchy of the Bacteria and Archaea, which is represented by quality-controlled 16S rRNA gene and genome sequences, with accompanying bioinformatics tools.
Abstract: The recent advent of DNA sequencing technologies facilitates the use of genome sequencing data that provide means for more informative and precise classification and identification of members of the Bacteria and Archaea. Because the current species definition is based on the comparison of genome sequences between type and other strains in a given species, building a genome database with correct taxonomic information is of paramount need to enhance our efforts in exploring prokaryotic diversity and discovering novel species as well as for routine identifications. Here we introduce an integrated database, called EzBioCloud, that holds the taxonomic hierarchy of the Bacteria and Archaea, which is represented by quality-controlled 16S rRNA gene and genome sequences. Whole-genome assemblies in the NCBI Assembly Database were screened for low quality and subjected to a composite identification bioinformatics pipeline that employs gene-based searches followed by the calculation of average nucleotide identity. As a result, the database is made of 61 700 species/phylotypes, including 13 132 with validly published names, and 62 362 whole-genome assemblies that were identified taxonomically at the genus, species and subspecies levels. Genomic properties, such as genome size and DNA G+C content, and the occurrence in human microbiome data were calculated for each genus or higher taxa. This united database of taxonomy, 16S rRNA gene and genome sequences, with accompanying bioinformatics tools, should accelerate genome-based classification and identification of members of the Bacteria and Archaea. The database and related search tools are available at www.ezbiocloud.net/.

5,027 citations

Journal ArticleDOI
TL;DR: The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012 and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery.
Abstract: The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

2,853 citations