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Publication Record


Eichman BF
(2017) Methods Enzymol 591: xv-xviii
MeSH Terms: DNA Damage, DNA Repair, DNA Repair Enzymes, Methods
Added August 26, 2019
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Preserving temporal relations in clinical data while maintaining privacy.
Hripcsak G, Mirhaji P, Low AF, Malin BA
(2016) J Am Med Inform Assoc 23: 1040-1045
MeSH Terms: Confidentiality, Data Anonymization, Electronic Health Records, Health Insurance Portability and Accountability Act, Humans, Methods, Observational Studies as Topic, Time, United States
Show Abstract · Added April 10, 2018
OBJECTIVE - Maintaining patient privacy is a challenge in large-scale observational research. To assist in reducing the risk of identifying study subjects through publicly available data, we introduce a method for obscuring date information for clinical events and patient characteristics.
METHODS - The method, which we call Shift and Truncate (SANT), obscures date information to any desired granularity. Shift and Truncate first assigns each patient a random shift value, such that all dates in that patient's record are shifted by that amount. Data are then truncated from the beginning and end of the data set.
RESULTS - The data set can be proven to not disclose temporal information finer than the chosen granularity. Unlike previous strategies such as a simple shift, it remains robust to frequent - even daily - updates and robust to inferring dates at the beginning and end of date-shifted data sets. Time-of-day may be retained or obscured, depending on the goal and anticipated knowledge of the data recipient.
CONCLUSIONS - The method can be useful as a scientific approach for reducing re-identification risk under the Privacy Rule of the Health Insurance Portability and Accountability Act and may contribute to qualification for the Safe Harbor implementation.
© The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Broadscale resolving power performance of a high precision uniform field ion mobility-mass spectrometer.
May JC, Dodds JN, Kurulugama RT, Stafford GC, Fjeldsted JC, McLean JA
(2015) Analyst 140: 6824-33
MeSH Terms: Analytic Sample Preparation Methods, Mass Spectrometry, Pressure
Show Abstract · Added December 17, 2018
An extensive study of two current ion mobility resolving power theories ("conditional" and "semi-empirical") was undertaken using a recently developed drift tube ion mobility-mass spectrometer. The current study investigates the quantitative agreement between experiment and theory at reduced pressure (4 Torr) for a wide range of initial ion gate widths (100 to 500 μs), and ion mobility values (K0 from 0.50 to 3.0 cm(2) V(-1) s(-1)) representing measurements obtained in helium, nitrogen, and carbon dioxide drift gas. Results suggest that the conditional resolving power theory deviates from experimental results for low mobility ions (e.g., high mass analytes) and for initial ion gate widths beyond 200 μs. A semi-empirical resolving power theory provided close-correlation of predicted resolving powers to experimental results across the full range of mobilities and gate widths investigated. Interpreting the results from the semi-empirical theory, the performance of the current instrumentation was found to be highly linear for a wide range of analytes, with optimal resolving powers being accessible for a narrow range of drift fields between 14 and 17 V cm(-1). While developed using singly-charged ion mobility data, preliminary results suggest that the semi-empirical theory has broader applicability to higher-charge state systems.
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Timing of solid food introduction is associated with urinary F2-isoprostane concentrations in childhood.
Frederiksen BN, Seifert J, Kroehl M, Lamb MM, Milne GL, Rewers M, Norris JM
(2015) Pediatr Res 78: 451-6
MeSH Terms: Age Factors, Biomarkers, Breast Feeding, Child, Child, Preschool, F2-Isoprostanes, Feeding Methods, Female, Humans, Infant, Infant Food, Linear Models, Longitudinal Studies, Male, Prospective Studies, Protective Factors, Risk Factors, Time Factors
Show Abstract · Added March 10, 2016
BACKGROUND - Timing of solid food introduction in infancy has been associated with several chronic diseases. To explore potential mechanisms, we investigated the relationship between timing of solid food introduction and F2-isoprostanes-a marker of oxidative stress.
METHODS - Urinary F2-isoprostanes were assessed in 336 healthy children aged less than 11.5 y with 1,266 clinic visits (mean = 3.8 visits per child) in the Diabetes Autoimmunity Study in the Young. We analyzed the association between F2-isoprostane concentrations and infant diet exposures using linear mixed models adjusted for age, age(2), HLA-DR3/4,DQB1*0302 genotype, first-degree relative with type 1 diabetes, maternal age, maternal education, sex, and exposure to in utero cigarette smoke.
RESULTS - Later solid food introduction was associated with lower F2-isoprostane concentrations in childhood (on average, 0.10 ng/mg per month of age at introduction; estimate: -0.10 (95% confidence interval (CI): -0.18, -0.02) P value = 0.02). Moreover, childhood F2-isoprostane concentrations were, on average, 0.24 ng/mg lower in individuals breastfed at solid food introduction (estimate: -0.24 (95% CI: -0.47, -0.01) P value = 0.04) compared with those who were not. Associations remained significant after limiting analyses to F2-isoprostanes after 2 y of age.
CONCLUSION - Our results suggest a long-term protective effect of later solid food introduction and breastfeeding at solid food introduction against increased F2-isoprostane concentrations throughout childhood.
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18 MeSH Terms
A method to prevent protein delocalization in imaging mass spectrometry of non-adherent tissues: application to small vertebrate lens imaging.
Anderson DM, Floyd KA, Barnes S, Clark JM, Clark JI, Mchaourab H, Schey KL
(2015) Anal Bioanal Chem 407: 2311-20
MeSH Terms: Analytic Sample Preparation Methods, Animals, Crystallins, Female, Lens, Crystalline, Male, Mice, Mice, Inbred C57BL, Mice, Inbred ICR, Molecular Imaging, Protein Transport, Rats, Rats, Wistar, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Zebrafish
Show Abstract · Added February 12, 2015
MALDI imaging requires careful sample preparation to obtain reliable, high-quality images of small molecules, peptides, lipids, and proteins across tissue sections. Poor crystal formation, delocalization of analytes, and inadequate tissue adherence can affect the quality, reliability, and spatial resolution of MALDI images. We report a comparison of tissue mounting and washing methods that resulted in an optimized method using conductive carbon substrates that avoids thaw mounting or washing steps, minimizes protein delocalization, and prevents tissue detachment from the target surface. Application of this method to image ocular lens proteins of small vertebrate eyes demonstrates the improved methodology for imaging abundant crystallin protein products. This method was demonstrated for tissue sections from rat, mouse, and zebrafish lenses resulting in good-quality MALDI images with little to no delocalization. The images indicate, for the first time in mouse and zebrafish, discrete localization of crystallin protein degradation products resulting in concentric rings of distinct protein contents that may be responsible for the refractive index gradient of vertebrate lenses.
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15 MeSH Terms
A new approach for diagnosing type 1 diabetes in autoantibody-positive individuals based on prediction and natural history.
Sosenko JM, Skyler JS, DiMeglio LA, Beam CA, Krischer JP, Greenbaum CJ, Boulware D, Rafkin LE, Matheson D, Herold KC, Mahon J, Palmer JP, Type 1 Diabetes TrialNet Study Group, Diabetes Prevention Trial-Type 1 Study Group
(2015) Diabetes Care 38: 271-6
MeSH Terms: Adult, Autoantibodies, Biological Assay, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 1, Early Diagnosis, Epidemiologic Methods, Fasting, Female, Glucose Tolerance Test, Humans, Male, Middle Aged, ROC Curve
Show Abstract · Added March 31, 2015
OBJECTIVE - We assessed whether type 1 diabetes (T1D) can be diagnosed earlier using a new approach based on prediction and natural history in autoantibody-positive individuals.
RESEARCH DESIGN AND METHODS - Diabetes Prevention Trial-Type 1 (DPT-1) and TrialNet Natural History Study (TNNHS) participants were studied. A metabolic index, the T1D Diagnostic Index60 (Index60), was developed from 2-h oral glucose tolerance tests (OGTTs) using the log fasting C-peptide, 60-min C-peptide, and 60-min glucose. OGTTs with Index60 ≥2.00 and 2-h glucose <200 mg/dL (Ind60+Only) were compared with Index60 <2.00 and 2-h glucose ≥200 mg/dL (2hglu+Only) OGTTs as criteria for T1D. Individuals were assessed for C-peptide loss from the first Ind60+Only OGTT to diagnosis.
RESULTS - Areas under receiver operating characteristic curves were significantly higher for Index60 than for the 2-h glucose (P < 0.001 for both DPT-1 and the TNNHS). As a diagnostic criterion, sensitivity was higher for Ind60+Only than for 2hglu+Only (0.44 vs. 0.15 in DPT-1; 0.26 vs. 0.17 in the TNNHS) OGTTs. Specificity was somewhat higher for 2hglu+Only OGTTs in DPT-1 (0.97 vs. 0.91) but equivalent in the TNNHS (0.98 for both). Positive and negative predictive values were higher for Ind60+Only OGTTs in both studies. Postchallenge C-peptide levels declined significantly at each OGTT time point from the first Ind60+Only OGTT to the time of standard diagnosis (range -22 to -34% in DPT-1 and -14 to -27% in the TNNHS). C-peptide and glucose patterns differed markedly between Ind60+Only and 2hglu+Only OGTTs.
CONCLUSIONS - An approach based on prediction and natural history appears to have utility for diagnosing T1D.
© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
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15 MeSH Terms
Meta-analysis of high- versus low-chloride content in perioperative and critical care fluid resuscitation.
Krajewski ML, Raghunathan K, Paluszkiewicz SM, Schermer CR, Shaw AD
(2015) Br J Surg 102: 24-36
MeSH Terms: Adult, Chlorides, Critical Care, Crystalloid Solutions, Epidemiologic Methods, Fluid Therapy, Humans, Hypertonic Solutions, Infusions, Intravenous, Isotonic Solutions, Perioperative Care, Rehydration Solutions, Treatment Outcome
Show Abstract · Added October 20, 2015
BACKGROUND - The objective of this systematic review and meta-analysis was to assess the relationship between the chloride content of intravenous resuscitation fluids and patient outcomes in the perioperative or intensive care setting.
METHODS - Systematic searches were performed of PubMed/MEDLINE, Embase and Cochrane Library (CENTRAL) databases in accordance with PRISMA guidelines. Randomized clinical trials, controlled clinical trials and observational studies were included if they compared outcomes in acutely ill or surgical patients receiving either high-chloride (ion concentration greater than 111 mmol/l up to and including 154 mmol/l) or lower-chloride (concentration 111 mmol/l or less) crystalloids for resuscitation. Endpoints examined were mortality, measures of kidney function, serum chloride, hyperchloraemia/metabolic acidosis, blood transfusion volume, mechanical ventilation time, and length of hospital and intensive care unit stay. Risk ratios (RRs), mean differences (MDs) or standardized mean differences (SMDs) and confidence intervals were calculated using fixed-effect modelling.
RESULTS - The search identified 21 studies involving 6253 patients. High-chloride fluids did not affect mortality but were associated with a significantly higher risk of acute kidney injury (RR 1.64, 95 per cent c.i. 1.27 to 2.13; P < 0.001) and hyperchloraemia/metabolic acidosis (RR 2.87, 1.95 to 4.21; P < 0.001). High-chloride fluids were also associated with greater serum chloride (MD 3.70 (95 per cent c.i. 3.36 to 4.04) mmol/l; P < 0.001), blood transfusion volume (SMD 0.35, 0.07 to 0.63; P = 0.014) and mechanical ventilation time (SMD 0.15, 0.08 to 0.23; P < 0.001). Sensitivity analyses excluding heavily weighted studies resulted in non-statistically significant effects for acute kidney injury and mechanical ventilation time.
CONCLUSION - A weak but significant association between higher chloride content fluids and unfavourable outcomes was found, but mortality was unaffected by chloride content.
© 2014 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.
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13 MeSH Terms
Promoting innovation and creativity in epidemiology for the 21st century.
Hiatt RA, Sulsky S, Aldrich MC, Kreiger N, Rothenberg R
(2013) Ann Epidemiol 23: 452-4
MeSH Terms: Cooperative Behavior, Creativity, Diffusion of Innovation, Epidemiologic Methods, Epidemiology, History, 21st Century, Humans
Added February 26, 2014
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7 MeSH Terms
Factors associated with satisfaction with prostate cancer care: results from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE).
Resnick MJ, Guzzo TJ, Cowan JE, Knight SJ, Carroll PR, Penson DF
(2013) BJU Int 111: 213-20
MeSH Terms: Adult, Aged, Androgen Antagonists, Epidemiologic Methods, Fear, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Patient Acceptance of Health Care, Patient Satisfaction, Prostatectomy, Prostatic Neoplasms, Quality of Health Care, Quality of Life, Radiotherapy, Adjuvant, Sexual Dysfunction, Physiological, Socioeconomic Factors, United States
Show Abstract · Added March 5, 2014
OBJECTIVE - To evaluate the impact of demographic, clinical, treatment and patient-reported parameters on satisfaction with prostate cancer care. Despite the significant worldwide impact of prostate cancer, few data are available specifically addressing satisfaction with treatment-related care.
PATIENTS AND METHODS - CaPSURE comprises participants from 40 US sites who were monitored during and after their treatment course. Participants who were diagnosed with clinically localized prostate cancer after 1999 underwent radical prostatectomy, radiation therapy or primary androgen deprivation, and those who also completed the satisfaction questionnaire within 2 years of treatment were included in the present study. Satisfaction was measured using a validated instrument that assesses contact with providers, confidence in providers, communication skills, humanness and overall satisfaction. Multivariable linear regression analysis were performed to evaluate the independent relationships between demographic, clinical, treatment and patient-reported parameters and satisfaction.
RESULTS - Of the 3056 participants, 1927 (63%) were treated with radical prostatectomy, 843 (28%) were treated with radiation therapy and 286 (9%) were treated with primary androgen deprivation. Multivariable analysis showed that multiple patient-reported factors were independently associated with satisfaction, whereas clinical, demographic and treatment parameters were not. Baseline health-related quality of life, measured by the 36-item short-form health survey, baseline fear of cancer recurrence (all P < 0.01) and declines in the sexual (P = 0.03), urinary (P < 0.01) and bowel (P = 0.02) function domains of the University of California Los Angeles Prostate Cancer Index were all independently associated with satisfaction. Patient-reported outcomes were more strongly associated with satisfaction in the low-risk subgroup.
CONCLUSIONS - Patient-reported factors such as health-related quality of life and fear of cancer recurrence are independently associated with satisfaction with care. Pretreatment parameters should be used to identify populations at-risk for dissatisfaction to allow for intervention and/or incorporation into treatment decision-making.
© 2012 The Authors. BJU International © 2012 BJU International.
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19 MeSH Terms
Orthostatic hypotension and novel blood pressure-associated gene variants: Genetics of Postural Hemodynamics (GPH) Consortium.
Fedorowski A, Franceschini N, Brody J, Liu C, Verwoert GC, Boerwinkle E, Couper D, Rice KM, Rotter JI, Mattace-Raso F, Uitterlinden A, Hofman A, Almgren P, Sjögren M, Hedblad B, Larson MG, Newton-Cheh C, Wang TJ, Rose KM, Psaty BM, Levy D, Witteman J, Melander O
(2012) Eur Heart J 33: 2331-41
MeSH Terms: Aged, Antihypertensive Agents, Atherosclerosis, Blood Pressure, Epidemiologic Methods, Female, Gene Frequency, Heterozygote, Homozygote, Humans, Hypotension, Orthostatic, Male, Middle Aged, Polymorphism, Single Nucleotide
Show Abstract · Added April 15, 2014
AIMS - Orthostatic hypotension (OH), an independent predictor of mortality and cardiovascular events, strongly correlates with hypertension. Recent genome-wide studies have identified new loci influencing blood pressure (BP) in populations, but their impact on OH remains unknown.
METHODS AND RESULTS - A total of 38 970 men and women of European ancestry from five population-based cohorts were included, of whom 2656 (6.8%) met the diagnostic criteria for OH (systolic/diastolic BP drop ≥ 20/10 mmHg within 3 min of standing). Thirty-one recently discovered BP-associated single nucleotide polymorphisms (SNPs) were examined using an additive genetic model and the major allele as referent. Relations between OH, orthostatic systolic BP response, and genetic variants were assessed by inverse variance-weighted meta-analysis. We found Bonferroni adjusted (P < 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95% confidence interval: 0.90, 0.85-0.96; P = 0.001), and nominal evidence (P < 0.05) for CYP17A1 (rs11191548: 0.85, 0.75-0.95; P = 0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.87-0.98; P= 0.009) loci. Among subjects not taking BP-lowering drugs, three SNPs within the NPPA/NPPB locus were nominally associated with increased risk of OH (rs17367504: 1.13, 1.02-1.24; P = 0.02, rs198358: 1.10, 1.01-1.20; P = 0.04, and rs5068: 1.22, 1.04-1.43; P = 0.01). Moreover, an ADM variant was nominally associated with continuous orthostatic systolic BP response in the adjusted model (P= 0.04).
CONCLUSION - The overall association between common gene variants in BP loci and OH was generally weak and the direction of effect inconsistent with resting BP findings. These results suggest that OH and resting BP share few genetic components.
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14 MeSH Terms