This codebook.txt file was generated by E. Lusczek Amended ono 20191216 by S. Hunt, DRUM curator ------------------- GENERAL INFORMATION ------------------- 1. Title of Dataset Circadian rhythms and metabolomics in ICU patients 2. Author Information Principal Investigator Contact Information Name: Elizabeth Lusczek Institution: University of Minnesota Address: 515 Delaware St. SE, Minneapolis, MN 55455 Email: lusc0006@umn.edu 3. Date of data collection (single date, range, approximate date) : 20151202-20160921 4. Geographic location of data collection (where was data collected?): University of Minnesota, Minneapolis, MN 55455 5. Information about funding sources that supported the collection of the data: Funded by the Department of Surgery, University of Minnesota -------------------------- SHARING/ACCESS INFORMATION -------------------------- 1. Licenses/restrictions placed on the data: none 2. Links to publications that cite or use the data: pending 3. Links to other publicly accessible locations of the data: none 4. Links/relationships to ancillary data sets: none 5. Was data derived from another source? No If yes, list source(s): 6. Recommended citation for the data: Lusczek, Elizabeth. (2019). Metabolomics identifies circadian desynchronization and distinct intra-patient variability patterns in critical illness. Retrieved from the Data Repository for the University of Minnesota, http://hdl.handle.net/11299/208811. --------------------- DATA & FILE OVERVIEW --------------------- 1. File List A. Filename: Vitals_DRUM.csv Short description: Serial heart rate, systolic blood pressure, diastolic blood pressure, and temperature data for 5 ICU patients and 5 healthy controls. B. Filename: Lab_Cortisol_DRUM.csv Short description: Serial cortisol levels quantified by Fairview Diagnostic Laboratories for 5 ICU patients and 5 healthy controls C. Filename: MassSpec_DRUM.csv Short description: Mass spectrometry data for approximately 20,000 features quantified in plasma samples taken every 4 hours for 24 hours in 5 ICU patients and 5 healthy controls. D. Filename: CR_P_01sound.csv Short description: Sound intensity data recorded every minute in the room of study participant CR_P_01 E. Filename: CR_P_02sound.csv Short description: Sound intensity data recorded every minute in the room of study participant CR_P_02 F. Filename: CR_P_03sound.csv Short description: Sound intensity data recorded every minute in the room of study participant CR_P_03 G. Filename: CR_P_05sound.csv Short description: Sound intensity data recorded every minute in the room of study participant CR_P_05 H. Filename: CR_P_06sound.csv Short description: Sound intensity data recorded every minute in the room of study participant CR_P_06 I. Filename: CR_P_07sound.csv Short description: Sound intensity data recorded every minute in the room of study participant CR_P_07 J. Filename: CR_P_08sound.csv Short description: Sound intensity data recorded every minute in the room of study participant CR_P_08 K. Filename: CR_P_10sound.csv Short description: Sound intensity data recorded every minute in the room of study participant CR_P_10 L. Filename: CR_P_11sound.csv Short description: Sound intensity data recorded every minute in the room of study participant CR_P_11 M. Filename: CR_P_12sound.csv Short description: Sound intensity data recorded every minute in the room of study participant CR_P_12 2. Relationship between files: Data were taken for 5 ICU patients and 5 healthy controls. Study participant ID's are preserved across the files. Healthy control IDs: CR_P_01, CR_P_02, CR_P_03, CR_P_05, CR_P_06 ICU patient IDs: CR_P_07, CR_P_08, CR_P_10, CR_P_11, CR_P_12 3. Additional related data collected that was not included in the current data package: None 4. Are there multiple versions of the dataset? No If yes, list versions: Name of file that was updated: i. Why was the file updated? ii. When was the file updated? Name of file that was updated: i. Why was the file updated? ii. When was the file updated? -------------------------- METHODOLOGICAL INFORMATION -------------------------- 1. Description of methods used for collection/generation of data: The study protocol (study number 1505M70361) was reviewed and approved by the University of Minnesota Institutional Review Board in accordance with the Code of Federal Regulations, 45 CFR 46.101(b). Patient population: From 2015-2016, circadian rhythms were monitored in 5 healthy control participants and 5 intensive care unit (ICU) patients for 24 hours. Healthy controls were monitored by trained staff at the University of Minnesota’s Masonic Clinical Research Unit. Study participants were over 18 years of age with an average of 7-8 hours of sleep a night, and were in generally good health. They were screened to exclude the following factors that may affect normal circadian rhythms: shift workers, blindness, use of over-the-counter sleep aids or supplements, history of traumatic brain injury, brain surgery, or sleep apnea, smoking, use of psychotropic drugs, or current alcohol use of more than 2 drinks per day. ICU patients were recruited from the University of Minnesota Medical Center ICU according to the following criteria: age > 18 years, mechanical ventilation with sedation for at least 3 days, and any of the following: emergent surgery, emergent intubation, admission after severe trauma, damage control surgery, or admission to ICU for post-operative complication. Patients with these conditions were excluded: severe nervous system disorder such as traumatic brain injury or recent neurosurgery, confirmed or suspected drug overdose or alcohol abuse, blindness, severe renal failure, end stage liver disease or hepatic encephalopathy, extracorporeal membrane oxygenation (ECMO) use, required vasopressors or steroids, central sleep apnea, hemoglobin levels ≤8 g/dL, and dementia or delirium prior to ICU stay. Twelve participants were enrolled in the study. One healthy control was disqualified because of abnormally high blood pressure. One ICU patient was extubated during the study and disqualified. Data collection: In all 10 research participants, beginning at 9:00 AM, heart rate and blood pressure were measured every 30 minutes and temperature was measured every hour. Bedside sound levels were measured every minute (Bruel and Kjaer 2250L, Duluth, GA). For the metabolomics portion of the study, blood samples (5 mL) were drawn for metabolomics analysis every 4 hours beginning at 9:00 AM in each participant. Plasma was extracted and aliquots were stored at -80°C until preparation for analysis with mass spectrometry. Reagents were obtained from Fisher Chemical Co., and were of LC-MS grade or better. Samples were prepared according to published protocols (24, 25). Internal standards (see Supporting Information S1) were added to thawed plasma samples followed by the addition of 4 volumes of cold (-80oC) 10% acetone 90% methanol (i.e. added 400µL solvent to 100µl sample). Samples were vortexed and incubated at -20oC for 15 minutes. Samples were spun down at 13,000g for 10 minutes at 4oC and the supernatant transferred to a clean tube. The incubation and centrifugation were repeated and the final supernatant transferred to a clean tube, which was then dried under nitrogen. Preparation for reverse-phase LC-MS analysis was completed by adding a starting buffer (100 µl of 5% acetonitrile, 95% water, 0.1% formic acid). Sample pH was adjusted to approximately 2 by adding 10-20 µl of 10% formic acid. Samples were analyzed via chromatographic separation in-line with mass spectrometry. Ultra-high performance liquid chromatography (UHPLC) was performed using the Thermo Scientific Ultimate 3000 UHPLC platform. For reverse-phase analysis the instrument was fitted with a Waters Acquity BEH C-18 column (2.1x100 mm, 1.7 µm particle size). Flow rate was 0.4 mL/minute and the column compartment was set to 40oC. Ten microliters were injected onto the column. Elution solutions were A) water with 0.1% formic acid and B) acetonitrile with 0.1% formic acid. The elution gradient was as follows: 2% B for 0.5 minutes; increase to 25% B over the next 0.5 minutes; increase to 80% B over the next 7 minutes; increase to 100% B for 2 minutes; decrease to 2% B over the next 0.5 minutes; hold at 2% B for 2.5 minutes. The Q Exactive™ Quadrupole-Orbitrap mass spectrometer (Thermo Fisher Scientific, Waltham, MA) was employed for mass analysis. The instrument profiles for both high mass accuracy (<2 ppm) and spectral resolution (typically at 70,000 resolution in full scan mode). Analysis was performed in positive mode over a mass range of 70-1050 m/z. 2. Methods for processing the data: Evaluation of sound levels. Differences in bedside sound levels in the study participants’ rooms were evaluated using nonparametric tests with the R software package (26). Sound meter data were discarded for three study subjects (one healthy control and two ICU patients) because there was very little variation in the sound levels recorded (mean LAeq=49.0 dB, standard deviation=7.03 dB for analyzed participants; mean LAeq=25.7 dB, standard deviation=0.184 dB for the three participants with flat noise levels). Plasma metabolites were tentatively identified with the Progenesis QI (Nonlinear Dynamics, Durham, NC) and Xcalibur (Thermo Fisher Scientific, Waltham, MA) software packages in conjunction with the Metlin (29) and HMDB (30) databases and an in-house database compiled by the facility performing the spectrometry. A group of previously identified circadian metabolites were targeted (23, 31). Principal component analysis of all features identified with Progenesis QI was performed using the R software package after intensities were log-transformed (26). Features were filtered by ANOVA p-value<0.05 using the ICU vs Healthy Control design, resulting in a list of 15,000 identified features distinguishing ICU patients from healthy controls. This reduced dataset was linked with HMDB identifiers and used as input for Ingenuity Pathway Analysis (QIAGEN Inc., https://www.qiagenbioinformatics.com/products/ingenuitypathway-analysis). 3. Instrument- or software-specific information needed to interpret the data: 4. Standards and calibration information, if appropriate: 5. Environmental/experimental conditions: 6. Describe any quality-assurance procedures performed on the data: 7. People involved with sample collection, processing, analysis and/or submission: Mass spectrometry data was collected by the Stephen Harvey PhD at the Center for Mass Spectrometry and Proteomics, University of Minnesota, Minneapolis, MN. ----------------------------------------- DATA-SPECIFIC INFORMATION FOR: Vitals_DRUM.csv ----------------------------------------- 1. Number of variables: 9 2. Number of cases/rows: 490 3. Missing data codes: Code/symbol Definition: data not recorded 4. Variable List A. Name: Patient_ID Description: de-identified indicator of individual research participant B. Name: Group Description: Participant group Healthy = healthy control ICU = ICU patient C. Name: Date Description: Date data was taken, format YYYYMMDD D. Name: Time Description: Time data was taken, format HHMM F. Name: HR Description: Heart rate (beats per minute) G. Name: SBP Description: Systolic blood pressure (mmHg) H. Name: DBP Description: Diastolic blood pressure (mmHg) I. Name: Temp Description: Temperature (degrees Fahrenheit) ----------------------------------------- DATA-SPECIFIC INFORMATION FOR: Lab_Cortisol_DRUM.csv ----------------------------------------- 1. Number of variables: 5 2. Number of cases/rows: 60 3. Missing data codes: Code/symbol Definition: data not recorded 4. Variable List A. Name: Patient_ID Description: de-identified indicator of individual research participant B. Name: Group Description: Participant group Healthy = healthy control ICU = ICU patient C. Name: Date Description: Date data was taken, format YYYYMMDD D. Name: Time Description: Time data was taken, format HHMM E. Name: Cortisol Description: Serum cortisol (ug/dL) ----------------------------------------- DATA-SPECIFIC INFORMATION FOR: MassSpec_DRUM.csv ----------------------------------------- 1. Number of variables: 66 2. Number of cases/rows: 24561 3. Missing data codes: Code/symbol Definition: data not recorded 4. Variable List A. Name: Feature Description: Unique identifier of individual spectral features by retention time and mass to charge ratio Format: RT_m/z B. Name: Neutral mass Description: Mass of neutral atoms or molecules C. Name: Retention time Description: Recorded time for solute to pass through column D. Name: CR_P_01_0HR Description: Column of spectral intensities for study participant CR_P_01 at first sampling timepoint E. Name: CR_P_02_0HR Description: Column of spectral intensities for study participant CR_P_02 at first sampling timepoint F. Name: CR_P_03_0HR Description: Column of spectral intensities for study participant CR_P_03 at first sampling timepoint G. Name: CR_P_05_0HR Description: Column of spectral intensities for study participant CR_P_05 at first sampling timepoint H. Name: CR_P_06_0HR Description: Column of spectral intensities for study participant CR_P_06 at first sampling timepoint I. Name: CR_P_07_0HR Description: Column of spectral intensities for study participant CR_P_07 at first sampling timepoint J. Name: CR_P_08_0HR Description: Column of spectral intensities for study participant CR_P_08 at first sampling timepoint K. Name: CR_P_10_0HR Description: Column of spectral intensities for study participant CR_P_10 at first sampling timepoint L. Name: CR_P_11_0HR Description: Column of spectral intensities for study participant CR_P_11 at first sampling timepoint M. Name: CR_P_12_0HR Description: Column of spectral intensities for study participant CR_P_12 at first sampling timepoint N. Name: CR_P_01_4HR Description: Column of spectral intensities for study participant CR_P_01 at first sampling timepoint O. Name: CR_P_02_4HR Description: Column of spectral intensities for study participant CR_P_02 at second sampling timepoint P. Name: CR_P_03_4HR Description: Column of spectral intensities for study participant CR_P_03 at second sampling timepoint Q. Name: CR_P_05_4HR Description: Column of spectral intensities for study participant CR_P_05 at second sampling timepoint R. Name: CR_P_06_4HR Description: Column of spectral intensities for study participant CR_P_06 at second sampling timepoint S. Name: CR_P_07_4HR Description: Column of spectral intensities for study participant CR_P_07 at second sampling timepoint T. Name: CR_P_08_4HR Description: Column of spectral intensities for study participant CR_P_08 at second sampling timepoint U. Name: CR_P_10_4HR Description: Column of spectral intensities for study participant CR_P_10 at second sampling timepoint V. Name: CR_P_11_4HR Description: Column of spectral intensities for study participant CR_P_11 at second sampling timepoint W. Name: CR_P_12_4HR Description: Column of spectral intensities for study participant CR_P_12 at second sampling timepoint X. Name: CR_P_01_8HR Description: Column of spectral intensities for study participant CR_P_01 at third sampling timepoint Y. Name: CR_P_02_8HR Description: Column of spectral intensities for study participant CR_P_02 at third sampling timepoint Z. Name: CR_P_03_8HR Description: Column of spectral intensities for study participant CR_P_03 at third sampling timepoint AA. Name: CR_P_05_8HR Description: Column of spectral intensities for study participant CR_P_05 at third sampling timepoint AB. Name: CR_P_06_8HR Description: Column of spectral intensities for study participant CR_P_06 at third sampling timepoint AC. Name: CR_P_07_8HR Description: Column of spectral intensities for study participant CR_P_07 at third sampling timepoint AD. Name: CR_P_08_8HR Description: Column of spectral intensities for study participant CR_P_08 at third sampling timepoint AE. Name: CR_P_10_8HR Description: Column of spectral intensities for study participant CR_P_10 at third sampling timepoint AF. Name: CR_P_11_8HR Description: Column of spectral intensities for study participant CR_P_11 at third sampling timepoint AG. Name: CR_P_12_8HR Description: Column of spectral intensities for study participant CR_P_12 at third sampling timepoint AH. Name: CR_P_01_12HR Description: Column of spectral intensities for study participant CR_P_01 at fourth sampling timepoint AI. Name: CR_P_02_12HR Description: Column of spectral intensities for study participant CR_P_02 at fourth sampling timepoint AJ. Name: CR_P_03_12HR Description: Column of spectral intensities for study participant CR_P_03 at fourth sampling timepoint AK. Name: CR_P_05_12HR Description: Column of spectral intensities for study participant CR_P_05 at fourth sampling timepoint AL. Name: CR_P_06_12HR Description: Column of spectral intensities for study participant CR_P_06 at fourth sampling timepoint AM. Name: CR_P_07_12HR Description: Column of spectral intensities for study participant CR_P_07 at fourth sampling timepoint AN. Name: CR_P_08_12HR Description: Column of spectral intensities for study participant CR_P_08 at fourth sampling timepoint AO. Name: CR_P_10_12HR Description: Column of spectral intensities for study participant CR_P_10 at fourth sampling timepoint AP. Name: CR_P_11_12HR Description: Column of spectral intensities for study participant CR_P_11 at fourth sampling timepoint AQ. Name: CR_P_12_12HR Description: Column of spectral intensities for study participant CR_P_12 at fourth sampling timepoint AR. Name: CR_P_01_16HR Description: Column of spectral intensities for study participant CR_P_01 at fifth sampling timepoint AS. Name: CR_P_02_16HR Description: Column of spectral intensities for study participant CR_P_02 at fifth sampling timepoint AT. Name: CR_P_03_16HR Description: Column of spectral intensities for study participant CR_P_03 at fifth sampling timepoint AU. Name: CR_P_05_16HR Description: Column of spectral intensities for study participant CR_P_05 at fifth sampling timepoint AV. Name: CR_P_06_16HR Description: Column of spectral intensities for study participant CR_P_06 at fifth sampling timepoint AW. Name: CR_P_07_16HR Description: Column of spectral intensities for study participant CR_P_07 at fifth sampling timepoint AX. Name: CR_P_08_16HR Description: Column of spectral intensities for study participant CR_P_08 at fifth sampling timepoint AY. Name: CR_P_10_16HR Description: Column of spectral intensities for study participant CR_P_10 at fifth sampling timepoint AZ. Name: CR_P_11_16HR Description: Column of spectral intensities for study participant CR_P_11 at fifth sampling timepoint BA. Name: CR_P_12_16HR Description: Column of spectral intensities for study participant CR_P_12 at fifth sampling timepoint BB. Name: CR_P_01_20HR Description: Column of spectral intensities for study participant CR_P_01 at sixth sampling timepoint BC. Name: CR_P_02_20HR Description: Column of spectral intensities for study participant CR_P_02 at sixth sampling timepoint BD. Name: CR_P_03_20HR Description: Column of spectral intensities for study participant CR_P_03 at sixth sampling timepoint BE. Name: CR_P_05_20HR Description: Column of spectral intensities for study participant CR_P_05 at sixth sampling timepoint BF. Name: CR_P_06_20HR Description: Column of spectral intensities for study participant CR_P_06 at sixth sampling timepoint BG. Name: CR_P_07_20HR Description: Column of spectral intensities for study participant CR_P_07 at sixth sampling timepoint BH. Name: CR_P_08_20HR Description: Column of spectral intensities for study participant CR_P_08 at sixth sampling timepoint BI. Name: CR_P_10_20HR Description: Column of spectral intensities for study participant CR_P_10 at sixth sampling timepoint BJ. Name: CR_P_11_20HR Description: Column of spectral intensities for study participant CR_P_11 at sixth sampling timepoint BK. Name: CR_P_12_20HR Description: Column of spectral intensities for study participant CR_P_12 at sixth sampling timepoint ----------------------------------------- DATA-SPECIFIC INFORMATION FOR: CR_P_01sound.csv ----------------------------------------- 1. Number of variables: 3 2. Number of cases/rows: 1440 3. Missing data codes: Code/symbol Definition: data not recorded 4. Variable List A. Name: Start.Time Description: Starting time of measurement, format MM/DD/YY HH:MM B. Name: Elapsed.Time Description: Time elapsed since previous measurement; set to one minute C. Name: LAeq Description: Equivalent continuous sound level, A-weighted (dB) ----------------------------------------- DATA-SPECIFIC INFORMATION FOR: CR_P_02sound.csv ----------------------------------------- 1. Number of variables: 3 2. Number of cases/rows: 1440 3. Missing data codes: Code/symbol Definition: data not recorded 4. Variable List A. Name: Start.Time Description: Starting time of measurement, format MM/DD/YY HH:MM B. Name: Elapsed.Time Description: Time elapsed since previous measurement; set to one minute C. Name: LAeq Description: Equivalent continuous sound level, A-weighted (dB) ----------------------------------------- DATA-SPECIFIC INFORMATION FOR: CR_P_03sound.csv ----------------------------------------- 1. Number of variables: 3 2. Number of cases/rows: 1440 3. Missing data codes: Code/symbol Definition: data not recorded 4. Variable List A. Name: Start.Time Description: Starting time of measurement, format MM/DD/YY HH:MM B. Name: Elapsed.Time Description: Time elapsed since previous measurement; set to one minute C. Name: LAeq Description: Equivalent continuous sound level, A-weighted (dB) ----------------------------------------- DATA-SPECIFIC INFORMATION FOR: CR_P_05sound.csv ----------------------------------------- 1. Number of variables: 3 2. Number of cases/rows: 1440 3. Missing data codes: Code/symbol Definition: data not recorded 4. Variable List A. Name: Start.Time Description: Starting time of measurement, format MM/DD/YY HH:MM B. Name: Elapsed.Time Description: Time elapsed since previous measurement; set to one minute C. Name: LAeq Description: Equivalent continuous sound level, A-weighted (dB) ----------------------------------------- DATA-SPECIFIC INFORMATION FOR: CR_P_06sound.csv ----------------------------------------- 1. Number of variables: 3 2. Number of cases/rows: 1315 3. Missing data codes: Code/symbol Definition: data not recorded 4. Variable List A. Name: Start.Time Description: Starting time of measurement, format MM/DD/YY HH:MM B. Name: Elapsed.Time Description: Time elapsed since previous measurement; set to one minute C. Name: LAeq Description: Equivalent continuous sound level, A-weighted (dB) ----------------------------------------- DATA-SPECIFIC INFORMATION FOR: CR_P_07sound.csv ----------------------------------------- 1. Number of variables: 3 2. Number of cases/rows: 1440 3. Missing data codes: Code/symbol Definition: data not recorded 4. Variable List A. Name: Start.Time Description: Starting time of measurement, format MM/DD/YY HH:MM B. Name: Elapsed.Time Description: Time elapsed since previous measurement; set to one minute C. Name: LAeq Description: Equivalent continuous sound level, A-weighted (dB) ----------------------------------------- DATA-SPECIFIC INFORMATION FOR: CR_P_08sound.csv ----------------------------------------- 1. Number of variables: 3 2. Number of cases/rows: 1440 3. Missing data codes: Code/symbol Definition: data not recorded 4. Variable List A. Name: Start.Time Description: Starting time of measurement, format MM/DD/YY HH:MM B. Name: Elapsed.Time Description: Time elapsed since previous measurement; set to one minute C. Name: LAeq Description: Equivalent continuous sound level, A-weighted (dB) ----------------------------------------- DATA-SPECIFIC INFORMATION FOR: CR_P_10sound.csv ----------------------------------------- 1. Number of variables: 3 2. Number of cases/rows: 1442 3. Missing data codes: Code/symbol Definition: data not recorded 4. Variable List A. Name: Start.Time Description: Starting time of measurement, format MM/DD/YY HH:MM B. Name: Elapsed.Time Description: Time elapsed since previous measurement; set to one minute C. Name: LAeq Description: Equivalent continuous sound level, A-weighted (dB) ----------------------------------------- DATA-SPECIFIC INFORMATION FOR: CR_P_11sound.csv ----------------------------------------- 1. Number of variables: 3 2. Number of cases/rows: 1440 3. Missing data codes: Code/symbol Definition: data not recorded 4. Variable List A. Name: Start.Time Description: Starting time of measurement, format MM/DD/YY HH:MM B. Name: Elapsed.Time Description: Time elapsed since previous measurement; set to one minute C. Name: LAeq Description: Equivalent continuous sound level, A-weighted (dB) ----------------------------------------- DATA-SPECIFIC INFORMATION FOR: CR_P_12sound.csv ----------------------------------------- 1. Number of variables: 3 2. Number of cases/rows: 1440 3. Missing data codes: Code/symbol Definition: data not recorded 4. Variable List A. Name: Start.Time Description: Starting time of measurement, format MM/DD/YY HH:MM B. Name: Elapsed.Time Description: Time elapsed since previous measurement; set to one minute C. Name: LAeq Description: Equivalent continuous sound level, A-weighted (dB)