title: Preventing Data Ambiguity in Infectious Diseases with Four-Dimensional and Personalized Evaluations.
abstract: BACKGROUND
  Diagnostic errors can occur, in infectious diseases, when anti-microbial immune responses involve several temporal scales. When responses span from nanosecond to week and larger temporal scales, any pre-selected temporal scale is likely to miss some (faster or slower) responses. Hoping to prevent diagnostic errors, a pilot study was conducted to evaluate a four-dimensional (4D) method that captures the complexity and dynamics of infectious diseases.
  
  
  METHODS
  Leukocyte-microbial-temporal data were explored in canine and human (bacterial and/or viral) infections, with: (i) a non-structured approach, which measures leukocytes or microbes in isolation; and (ii) a structured method that assesses numerous combinations of interacting variables. Four alternatives of the structured method were tested: (i) a noise-reduction oriented version, which generates a single (one data point-wide) line of observations; (ii) a version that measures complex, three-dimensional (3D) data interactions; (iii) a non-numerical version that displays temporal data directionality (arrows that connect pairs of consecutive observations); and (iv) a full 4D (single line-, complexity-, directionality-based) version.
  
  
  RESULTS
  In all studies, the non-structured approach revealed non-interpretable (ambiguous) data: observations numerically similar expressed different biological conditions, such as recovery and lack of recovery from infections. Ambiguity was also found when the data were structured as single lines. In contrast, two or more data subsets were distinguished and ambiguity was avoided when the data were structured as complex, 3D, single lines and, in addition, temporal data directionality was determined. The 4D method detected, even within one day, changes in immune profiles that occurred after antibiotics were prescribed.
  
  
  CONCLUSIONS
  Infectious disease data may be ambiguous. Four-dimensional methods may prevent ambiguity, providing earlier, in vivo, dynamic, complex, and personalized information that facilitates both diagnostics and selection or evaluation of anti-microbial therapies.
authors.affiliation: Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, NM, 87131, United States of America.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Iandiorio
authors.affiliation: Los Alamos National Laboratory, Global Security, Mailstop M888, Los Alamos, NM, 87545, United States of America.
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Fair
authors.affiliation: Department of Biopathology and Clinical Microbiology, Aeginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Chatzipanagiotou
authors.affiliation: Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Sparta, Greece.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Ioannidis
authors.affiliation: Department of Clinical Microbiology, "Thriasio" General Hospital, Magoula, Greece.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Trikka-Graphakos
authors.affiliation: Department of Clinical Microbiology, "Thriasio" General Hospital, Magoula, Greece.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Charalampaki
authors.affiliation: Department of Clinical Microbiology, "Thriasio" General Hospital, Magoula, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Sereti
authors.affiliation: Torrey Pines Institute for Molecular Studies, Port St. Lucie, FL, United States of America.|Department of Dermatology, Harvard Medical School, Boston, MA, United States of America.|Wellman Center for Photomedicine, Massachusetts General Hospital, Boston MA, United States of America.
authors.forename: George P
authors.initials: GP
authors.lastname: Tegos
authors.affiliation: Human Ecology Department, Centro de Investigaciones Avanzadas, Mérida, México.
authors.forename: Almira L
authors.initials: AL
authors.lastname: Hoogesteijn
authors.affiliation: Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, NM, 87131, United States of America.|Center for Global Health-Division of Infectious Diseases, School of Medicine, University of New Mexico, Albuquerque, NM, 87131, United States of America.
authors.forename: Ariel L
authors.initials: AL
authors.lastname: Rivas
mesh_terms: D000818:Animals; D003141:Communicable Diseases / Q000175:diagnosis* / Q000276:immunology / Q000382:microbiology / Q000821:virology; D003951:Diagnostic Errors / Q000517:prevention & control; D004285:Dogs; D006801:Humans; D007962:Leukocytes / Q000166:cytology; D008490:Medical Informatics / Q000379:methods*; D010865:Pilot Projects; D062211:Spatio-Temporal Analysis