A Simplified 4-Site Economical Intradermal Post-Exposure Rabies Vaccine Regimen: A Randomised Controlled Comparison with Standard Methods
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{"title"=>"A simplified 4-site economical intradermal post-exposure rabies vaccine regimen: A randomised controlled comparison with standard methods", "type"=>"journal", "authors"=>[{"first_name"=>"Mary J.", "last_name"=>"Warrell", "scopus_author_id"=>"57201282182"}, {"first_name"=>"Anna", "last_name"=>"Riddell", "scopus_author_id"=>"7006168817"}, {"first_name"=>"Ly Mee", "last_name"=>"Yu", "scopus_author_id"=>"7404164174"}, {"first_name"=>"Judith", "last_name"=>"Phipps", "scopus_author_id"=>"24470909800"}, {"first_name"=>"Linda", "last_name"=>"Diggle", "scopus_author_id"=>"6603245631"}, {"first_name"=>"Hervé", "last_name"=>"Bourhy", "scopus_author_id"=>"7003938340"}, {"first_name"=>"Jonathan J.", "last_name"=>"Deeks", "scopus_author_id"=>"7006087510"}, {"first_name"=>"Anthony R.", "last_name"=>"Fooks", "scopus_author_id"=>"7003456806"}, {"first_name"=>"Laurent", "last_name"=>"Audry", "scopus_author_id"=>"6507376856"}, {"first_name"=>"Sharon M.", "last_name"=>"Brookes", "scopus_author_id"=>"56261597800"}, {"first_name"=>"François Xavier", "last_name"=>"Meslin", "scopus_author_id"=>"7003475154"}, {"first_name"=>"Richard", "last_name"=>"Moxon", "scopus_author_id"=>"6603838435"}, {"first_name"=>"Andrew J.", "last_name"=>"Pollard", "scopus_author_id"=>"7103193821"}, {"first_name"=>"David A.", "last_name"=>"Warrell", "scopus_author_id"=>"7102334232"}], "year"=>2008, "source"=>"PLoS Neglected Tropical Diseases", "identifiers"=>{"doi"=>"10.1371/journal.pntd.0000224", "sgr"=>"48949107710", "pui"=>"352002916", "scopus"=>"2-s2.0-48949107710", "issn"=>"1935-2735", "pmid"=>"18431444", "isbn"=>"1935-2735 (Electronic)\\r1935-2727 (Linking)"}, "id"=>"4ebdacad-a684-358e-b046-be0c689d5e50", "abstract"=>"BACKGROUND: The need for economical rabies post-exposure prophylaxis (PEP) is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID) vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods. METHODS: Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90); or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available. FINDINGS: All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method. CONCLUSIONS: This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be introduced without further studies. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN 30087513.", "link"=>"http://www.mendeley.com/research/simplified-4site-economical-intradermal-postexposure-rabies-vaccine-regimen-randomised-controlled-co", "reader_count"=>23, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>3, "Other"=>2, "Student > Master"=>1, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>3, "Other"=>2, "Student > Master"=>1, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>9, "Psychology"=>1, "Immunology and Microbiology"=>1, "Linguistics"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Linguistics"=>{"Linguistics"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"Ecuador"=>1}, "group_count"=>0}

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  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"12"}
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  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"7"}
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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/932483"], "description"=>"<p>Dotted lines are the 95% agreement limit. RFFIT = rabies fluorescent focus inhibition test, FAVN = fluorescent antibody virus neutralisation.</p>", "links"=>[], "tags"=>["rffit", "favn"], "article_id"=>602913, "categories"=>["Medicine", "Infectious Diseases", "Neuroscience"], "users"=>["Mary J. Warrell", "Anna Riddell", "Ly-Mee Yu", "Judith Phipps", "Linda Diggle", "Hervé Bourhy", "Jonathan J. Deeks", "Anthony R. Fooks", "Laurent Audry", "Sharon M. Brookes", "François-Xavier Meslin", "Richard Moxon", "Andrew J. Pollard", "David A. Warrell"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000224.g005", "stats"=>{"downloads"=>2, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bland_Altman_plot_of_the_difference_between_log_RFFIT_and_log_FAVN_results_and_the_mean_of_the_two_values_/602913", "title"=>"Bland-Altman plot of the difference between log RFFIT and log FAVN results, and the mean of the two values.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-04-23 00:48:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/932768"], "description"=>"*<p>Post hoc test: A vs E, P<0.0001; B vs E, P<0.001; D vs E, P<0.001</p>", "links"=>[], "tags"=>["symptoms"], "article_id"=>603203, "categories"=>["Medicine", "Infectious Diseases", "Neuroscience"], "users"=>["Mary J. Warrell", "Anna Riddell", "Ly-Mee Yu", "Judith Phipps", "Linda Diggle", "Hervé Bourhy", "Jonathan J. Deeks", "Anthony R. Fooks", "Laurent Audry", "Sharon M. Brookes", "François-Xavier Meslin", "Richard Moxon", "Andrew J. Pollard", "David A. Warrell"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000224.t004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Generalised_Symptoms_Reported_and_the_Possibly_or_Probably_Related_to_Vaccine_/603203", "title"=>"Generalised Symptoms Reported and the % Possibly or Probably Related to Vaccine.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-04-23 00:53:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/459721", "https://ndownloader.figshare.com/files/459729"], "description"=>"<div><h3>Background</h3><p>The need for economical rabies post-exposure prophylaxis (PEP) is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID) vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods.</p><h3>Methods</h3><p>Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90); or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available.</p><h3>Findings</h3><p>All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method.</p><h3>Conclusions</h3><p>This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be introduced without further studies.</p><h3>Trial Registration</h3><p>Controlled-Trials.com ISRCTN <a href=\"http://controlled-trials.com/ISRCTN30087513/30087513\">30087513</a></p></div>", "links"=>[], "tags"=>["simplified", "4-site", "economical", "intradermal", "post-exposure", "rabies", "randomised", "controlled", "methods"], "article_id"=>150565, "categories"=>["Medicine", "Cancer", "Neuroscience"], "users"=>["Mary J. Warrell", "Anna Riddell", "Ly-Mee Yu", "Judith Phipps", "Linda Diggle", "Hervé Bourhy", "Jonathan J. Deeks", "Anthony R. Fooks", "Laurent Audry", "Sharon M. Brookes", "François-Xavier Meslin", "Richard Moxon", "Andrew J. Pollard", "David A. Warrell"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000224.s001", "https://dx.doi.org/10.1371/journal.pntd.0000224.s002"], "stats"=>{"downloads"=>8, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Simplified_4_Site_Economical_Intradermal_Post_Exposure_Rabies_Vaccine_Regimen_A_Randomised_Controlled_Comparison_with_Standard_Methods/150565", "title"=>"A Simplified 4-Site Economical Intradermal Post-Exposure Rabies Vaccine Regimen: A Randomised Controlled Comparison with Standard Methods", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2008-04-23 00:09:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/932231"], "description"=>"<p>Symbols represent: • Group A 4-site; ▴ Group B 8-site; x Group D 2-site; □ Group E intramuscular (IM). Points are geometric mean titres with 95% confidence intervals.</p>", "links"=>[], "tags"=>["neutralising", "antibody", "rabies", "fluorescent", "inhibition"], "article_id"=>602657, "categories"=>["Medicine", "Infectious Diseases", "Neuroscience"], "users"=>["Mary J. Warrell", "Anna Riddell", "Ly-Mee Yu", "Judith Phipps", "Linda Diggle", "Hervé Bourhy", "Jonathan J. Deeks", "Anthony R. Fooks", "Laurent Audry", "Sharon M. Brookes", "François-Xavier Meslin", "Richard Moxon", "Andrew J. Pollard", "David A. Warrell"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000224.g002", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rabies_neutralising_antibody_results_by_the_rabies_fluorescent_focus_inhibition_test_RFFIT_/602657", "title"=>"Rabies neutralising antibody results by the rabies fluorescent focus inhibition test (RFFIT).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-04-23 00:44:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/932682"], "description"=>"*<p>Whole ampoule of vaccine divided between sites.</p>†<p>For the 8-site regimen, the intradermal (ID) dose is 0.05 ml per site. All other ID doses are 0.1 ml per site.</p><p>ID injection sites over deltoids for 1 or 2 sites. 4 sites are deltoids and thighs.</p><p>8 sites are deltoids, thighs, suprascapular, and lower anterior abdominal wall areas. Intramuscular (IM) injection into the left deltoid.</p>", "links"=>[], "tags"=>["regimens", "sites"], "article_id"=>603113, "categories"=>["Medicine", "Infectious Diseases", "Neuroscience"], "users"=>["Mary J. Warrell", "Anna Riddell", "Ly-Mee Yu", "Judith Phipps", "Linda Diggle", "Hervé Bourhy", "Jonathan J. Deeks", "Anthony R. Fooks", "Laurent Audry", "Sharon M. Brookes", "François-Xavier Meslin", "Richard Moxon", "Andrew J. Pollard", "David A. Warrell"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000224.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vaccine_Regimens_Showing_Number_of_Sites_of_Injection_/603113", "title"=>"Vaccine Regimens Showing Number of Sites of Injection.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-04-23 00:51:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/932727"], "description"=>"*<p>IU/ml.</p>", "links"=>[], "tags"=>["serology"], "article_id"=>603165, "categories"=>["Medicine", "Infectious Diseases", "Neuroscience"], "users"=>["Mary J. Warrell", "Anna Riddell", "Ly-Mee Yu", "Judith Phipps", "Linda Diggle", "Hervé Bourhy", "Jonathan J. Deeks", "Anthony R. Fooks", "Laurent Audry", "Sharon M. Brookes", "François-Xavier Meslin", "Richard Moxon", "Andrew J. Pollard", "David A. Warrell"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000224.t006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FAVN_Serology_Results_for_Day_7_/603165", "title"=>"FAVN Serology Results for Day 7.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-04-23 00:52:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/932144"], "description"=>"<p>Group A received the 4-site regimen; group B, the 8-site regimen; group D, the 2-site regimen and group E, the IM regimen.</p>", "links"=>[], "tags"=>["diagram", "subjects", "recruited", "rabies"], "article_id"=>602576, "categories"=>["Medicine", "Infectious Diseases", "Neuroscience"], "users"=>["Mary J. Warrell", "Anna Riddell", "Ly-Mee Yu", "Judith Phipps", "Linda Diggle", "Hervé Bourhy", "Jonathan J. Deeks", "Anthony R. Fooks", "Laurent Audry", "Sharon M. Brookes", "François-Xavier Meslin", "Richard Moxon", "Andrew J. Pollard", "David A. Warrell"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000224.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Flow_diagram_of_subjects_recruited_to_rabies_vaccine_study_/602576", "title"=>"Flow diagram of subjects recruited to rabies vaccine study.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-04-23 00:42:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/932806"], "description"=>"*<p>IU/ml.</p>", "links"=>[], "tags"=>["serology"], "article_id"=>603235, "categories"=>["Medicine", "Infectious Diseases", "Neuroscience"], "users"=>["Mary J. Warrell", "Anna Riddell", "Ly-Mee Yu", "Judith Phipps", "Linda Diggle", "Hervé Bourhy", "Jonathan J. Deeks", "Anthony R. Fooks", "Laurent Audry", "Sharon M. Brookes", "François-Xavier Meslin", "Richard Moxon", "Andrew J. Pollard", "David A. Warrell"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000224.t005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RFFIT_Serology_Results_/603235", "title"=>"RFFIT Serology Results.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-04-23 00:53:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/932343"], "description"=>"<p>Group A = 4-site intradermal (ID); Group B = 8-site ID; Group D = 2-site ID; Group E = intramuscular.</p>", "links"=>[], "tags"=>["14", "rabies", "fluorescent", "inhibition", "antibody", "geometric", "titres"], "article_id"=>602771, "categories"=>["Medicine", "Infectious Diseases", "Neuroscience"], "users"=>["Mary J. Warrell", "Anna Riddell", "Ly-Mee Yu", "Judith Phipps", "Linda Diggle", "Hervé Bourhy", "Jonathan J. Deeks", "Anthony R. Fooks", "Laurent Audry", "Sharon M. Brookes", "François-Xavier Meslin", "Richard Moxon", "Andrew J. Pollard", "David A. Warrell"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000224.g003", "stats"=>{"downloads"=>2, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Day_14_rabies_fluorescent_focus_inhibition_test_RFFIT_results_antibody_levels_8805_0_5_IU_ml_difference_in_proportion_between_the_geometric_mean_titres_GMTs_of_any_two_regimens_/602771", "title"=>"Day 14 rabies fluorescent focus inhibition test (RFFIT) results antibody levels ≥0.5 IU/ml: difference in proportion between the geometric mean titres (GMTs) of any two regimens.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-04-23 00:46:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/932417"], "description"=>"<p>Symbols represent: • Group A 4-site; ▴ Group B 8-site; x Group D 2-site; □ Group E IM. Points are geometric mean titres with 95% confidence intervals.</p>", "links"=>[], "tags"=>["fluorescent", "inhibition", "sera", "plotted", "tested", "antibody", "neutralisation"], "article_id"=>602844, "categories"=>["Medicine", "Infectious Diseases", "Neuroscience"], "users"=>["Mary J. Warrell", "Anna Riddell", "Ly-Mee Yu", "Judith Phipps", "Linda Diggle", "Hervé Bourhy", "Jonathan J. Deeks", "Anthony R. Fooks", "Laurent Audry", "Sharon M. Brookes", "François-Xavier Meslin", "Richard Moxon", "Andrew J. Pollard", "David A. Warrell"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000224.g004", "stats"=>{"downloads"=>4, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rabies_fluorescent_focus_inhibition_test_RFFIT_results_of_the_day_7_sera_plotted_with_the_results_of_the_same_sera_tested_by_the_fluorescent_antibody_virus_neutralisation_FAVN_method_/602844", "title"=>"Rabies fluorescent focus inhibition test (RFFIT) results of the day 7 sera plotted with the results of the same sera tested by the fluorescent antibody virus neutralisation (FAVN) method.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-04-23 00:47:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/932590"], "description"=>"<p>Demographic Characteristics.</p>", "links"=>[], "tags"=>["infectious diseases/infectious diseases of the nervous system", "infectious diseases/neglected tropical diseases", "infectious diseases/tropical and travel-associated diseases", "infectious diseases/viral infections", "neurological disorders/infectious diseases of the nervous system", "public health and epidemiology/immunization", "public health and epidemiology/preventive medicine", "virology/vaccines"], "article_id"=>603005, "categories"=>["Medicine", "Infectious Diseases", "Neuroscience"], "users"=>["Mary J. Warrell", "Anna Riddell", "Ly-Mee Yu", "Judith Phipps", "Linda Diggle", "Hervé Bourhy", "Jonathan J. Deeks", "Anthony R. Fooks", "Laurent Audry", "Sharon M. Brookes", "François-Xavier Meslin", "Richard Moxon", "Andrew J. Pollard", "David A. Warrell"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000224.t002", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographic_Characteristics_/603005", "title"=>"Demographic Characteristics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-04-23 00:50:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/932642"], "description"=>"*<p>Post hoc test: A vs E, P<0.0001; B vs E, P<0.001; D vs E, P<0.001.</p>", "links"=>[], "tags"=>["infectious diseases/infectious diseases of the nervous system", "infectious diseases/neglected tropical diseases", "infectious diseases/tropical and travel-associated diseases", "infectious diseases/viral infections", "neurological disorders/infectious diseases of the nervous system", "public health and epidemiology/immunization", "public health and epidemiology/preventive medicine", "virology/vaccines"], "article_id"=>603059, "categories"=>["Medicine", "Infectious Diseases", "Neuroscience"], "users"=>["Mary J. Warrell", "Anna Riddell", "Ly-Mee Yu", "Judith Phipps", "Linda Diggle", "Hervé Bourhy", "Jonathan J. Deeks", "Anthony R. Fooks", "Laurent Audry", "Sharon M. Brookes", "François-Xavier Meslin", "Richard Moxon", "Andrew J. Pollard", "David A. Warrell"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0000224.t003", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Local_Reactions_/603059", "title"=>"Local Reactions.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-04-23 00:50:59"}

PMC Usage Stats | Further Information

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Relative Metric

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