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An Interlaboratory Evaluation of Drift Tube Ion Mobility-Mass Spectrometry Collision Cross Section Measurements.
Stow SM, Causon TJ, Zheng X, Kurulugama RT, Mairinger T, May JC, Rennie EE, Baker ES, Smith RD, McLean JA, Hann S, Fjeldsted JC
(2017) Anal Chem 89: 9048-9055
MeSH Terms: Calibration, Ion Mobility Spectrometry, Laboratories, Lipids, Mass Spectrometry, Molecular Structure, Nitrogen, Proteins, Reproducibility of Results
Show Abstract · Added December 17, 2018
Collision cross section (CCS) measurements resulting from ion mobility-mass spectrometry (IM-MS) experiments provide a promising orthogonal dimension of structural information in MS-based analytical separations. As with any molecular identifier, interlaboratory standardization must precede broad range integration into analytical workflows. In this study, we present a reference drift tube ion mobility mass spectrometer (DTIM-MS) where improvements on the measurement accuracy of experimental parameters influencing IM separations provide standardized drift tube, nitrogen CCS values (CCS) for over 120 unique ion species with the lowest measurement uncertainty to date. The reproducibility of these CCS values are evaluated across three additional laboratories on a commercially available DTIM-MS instrument. The traditional stepped field CCS method performs with a relative standard deviation (RSD) of 0.29% for all ion species across the three additional laboratories. The calibrated single field CCS method, which is compatible with a wide range of chromatographic inlet systems, performs with an average, absolute bias of 0.54% to the standardized stepped field CCS values on the reference system. The low RSD and biases observed in this interlaboratory study illustrate the potential of DTIM-MS for providing a molecular identifier for a broad range of discovery based analyses.
1 Communities
1 Members
0 Resources
9 MeSH Terms
Circulating concentrations of biomarkers and metabolites related to vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations.
Midttun Ø, Theofylaktopoulou D, McCann A, Fanidi A, Muller DC, Meyer K, Ulvik A, Zheng W, Shu XO, Xiang YB, Prentice R, Thomson CA, Pettinger M, Giles GG, Hodge A, Cai Q, Blot WJ, Wu J, Johansson M, Hultdin J, Grankvist K, Stevens VL, McCullough ML, Weinstein SJ, Albanes D, Langhammer A, Hveem K, Næss M, Sesso HD, Gaziano JM, Buring JE, Lee IM, Severi G, Zhang X, Han J, Stampfer MJ, Smith-Warner SA, Zeleniuch-Jacquotte A, le Marchand L, Yuan JM, Butler LM, Koh WP, Wang R, Gao YT, Ericson U, Sonestedt E, Ziegler RG, Freedman ND, Visvanathan K, Jones MR, Relton C, Brennan P, Johansson M, Ueland PM
(2017) Am J Clin Nutr 105: 1314-1326
MeSH Terms: Aged, Asia, Australia, Biomarkers, Carbon, Cross-Sectional Studies, Dietary Supplements, Female, Humans, Kynurenine, Laboratories, Male, Middle Aged, Scandinavian and Nordic Countries, Tryptophan, United States, Vitamin A, Vitamin B Complex, Vitamin D, alpha-Tocopherol
Show Abstract · Added April 21, 2017
Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies. We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions. The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory. Circulating concentrations of riboflavin, pyridoxal 5'-phosphate, folate, vitamin B-12, all- retinol, 25-hydroxyvitamin D, and α-tocopherol as well as combined vitamin scores that were based on these nutrients showed that the general B-vitamin concentration was highest in the United States and that the B vitamins and lipid soluble vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-vitamin concentration in the United States appears to be driven mainly by multivitamin-supplement users. The observed differences likely reflect the variation in intake of vitamins and, in particular, the widespread multivitamin-supplement use in the United States. The results provide valuable information about the differences in biomarker concentrations in populations across continents.
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2 Members
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20 MeSH Terms
Long QT Syndrome and Potentially Pathogenic Genetic Variants--In Reply.
Van Driest SL, Wells QS, Roden DM
(2016) JAMA 315: 2467-8
MeSH Terms: Arrhythmias, Cardiac, Electronic Health Records, Ether-A-Go-Go Potassium Channels, Female, Genetic Variation, Humans, Laboratories, Male, NAV1.5 Voltage-Gated Sodium Channel, Phenotype
Added April 6, 2017
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1 Members
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10 MeSH Terms
Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in Electronic Medical Records.
Van Driest SL, Wells QS, Stallings S, Bush WS, Gordon A, Nickerson DA, Kim JH, Crosslin DR, Jarvik GP, Carrell DS, Ralston JD, Larson EB, Bielinski SJ, Olson JE, Ye Z, Kullo IJ, Abul-Husn NS, Scott SA, Bottinger E, Almoguera B, Connolly J, Chiavacci R, Hakonarson H, Rasmussen-Torvik LJ, Pan V, Persell SD, Smith M, Chisholm RL, Kitchner TE, He MM, Brilliant MH, Wallace JR, Doheny KF, Shoemaker MB, Li R, Manolio TA, Callis TE, Macaya D, Williams MS, Carey D, Kapplinger JD, Ackerman MJ, Ritchie MD, Denny JC, Roden DM
(2016) JAMA 315: 47-57
MeSH Terms: Aged, Aged, 80 and over, Alleles, Arrhythmias, Cardiac, Brugada Syndrome, ERG1 Potassium Channel, Electronic Health Records, Ether-A-Go-Go Potassium Channels, Female, Genetic Predisposition to Disease, Genetic Testing, Genetic Variation, Genomics, Heterozygote, Humans, Incidental Findings, Laboratories, Male, Middle Aged, Mutation, Missense, NAV1.5 Voltage-Gated Sodium Channel, Phenotype, Prospective Studies, Random Allocation, Statistics, Nonparametric, Young Adult
Show Abstract · Added April 6, 2017
IMPORTANCE - Large-scale DNA sequencing identifies incidental rare variants in established Mendelian disease genes, but the frequency of related clinical phenotypes in unselected patient populations is not well established. Phenotype data from electronic medical records (EMRs) may provide a resource to assess the clinical relevance of rare variants.
OBJECTIVE - To determine the clinical phenotypes from EMRs for individuals with variants designated as pathogenic by expert review in arrhythmia susceptibility genes.
DESIGN, SETTING, AND PARTICIPANTS - This prospective cohort study included 2022 individuals recruited for nonantiarrhythmic drug exposure phenotypes from October 5, 2012, to September 30, 2013, for the Electronic Medical Records and Genomics Network Pharmacogenomics project from 7 US academic medical centers. Variants in SCN5A and KCNH2, disease genes for long QT and Brugada syndromes, were assessed for potential pathogenicity by 3 laboratories with ion channel expertise and by comparison with the ClinVar database. Relevant phenotypes were determined from EMRs, with data available from 2002 (or earlier for some sites) through September 10, 2014.
EXPOSURES - One or more variants designated as pathogenic in SCN5A or KCNH2.
MAIN OUTCOMES AND MEASURES - Arrhythmia or electrocardiographic (ECG) phenotypes defined by International Classification of Diseases, Ninth Revision (ICD-9) codes, ECG data, and manual EMR review.
RESULTS - Among 2022 study participants (median age, 61 years [interquartile range, 56-65 years]; 1118 [55%] female; 1491 [74%] white), a total of 122 rare (minor allele frequency <0.5%) nonsynonymous and splice-site variants in 2 arrhythmia susceptibility genes were identified in 223 individuals (11% of the study cohort). Forty-two variants in 63 participants were designated potentially pathogenic by at least 1 laboratory or ClinVar, with low concordance across laboratories (Cohen κ = 0.26). An ICD-9 code for arrhythmia was found in 11 of 63 (17%) variant carriers vs 264 of 1959 (13%) of those without variants (difference, +4%; 95% CI, -5% to +13%; P = .35). In the 1270 (63%) with ECGs, corrected QT intervals were not different in variant carriers vs those without (median, 429 vs 439 milliseconds; difference, -10 milliseconds; 95% CI, -16 to +3 milliseconds; P = .17). After manual review, 22 of 63 participants (35%) with designated variants had any ECG or arrhythmia phenotype, and only 2 had corrected QT interval longer than 500 milliseconds.
CONCLUSIONS AND RELEVANCE - Among laboratories experienced in genetic testing for cardiac arrhythmia disorders, there was low concordance in designating SCN5A and KCNH2 variants as pathogenic. In an unselected population, the putatively pathogenic genetic variants were not associated with an abnormal phenotype. These findings raise questions about the implications of notifying patients of incidental genetic findings.
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3 Members
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26 MeSH Terms
Quality Management of the Immunohistochemistry Laboratory: A Practical Guide.
Cates JM, Troutman KA
(2015) Appl Immunohistochem Mol Morphol 23: 471-80
MeSH Terms: Humans, Immunohistochemistry, Laboratories, Hospital, Quality Control
Show Abstract · Added February 15, 2016
Governmental regulations and most published guidelines do not provide specific guidance on implementation of quality management (QM) programs for immunohistochemistry (IHC) assays in Anatomic Pathology. QM of IHC consists of 3 main components: quality control, quality assurance, and quality improvement initiatives, each entailing distinctive but interrelated objectives. Discussion of the principles and some specific practices involved in these phases of QM of the IHC laboratory are therefore offered in this review, with an admitted emphasis on pragmatism.
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4 MeSH Terms
Improving diagnostic capability for HPV disease internationally within the NIH-NIAID Division of AIDS Clinical Trial Networks.
Godfrey CC, Michelow PM, Godard M, Sahasrabuddhe VV, Darden J, Firnhaber CS, Wetherall NT, Bremer J, Coombs RW, Wilkin T, A5282 Study Team
(2013) Am J Clin Pathol 140: 881-9
MeSH Terms: Acquired Immunodeficiency Syndrome, Clinical Trials, Phase II as Topic, Female, Human Papillomavirus DNA Tests, Humans, Laboratories, Mass Screening, National Institutes of Health (U.S.), Papillomavirus Infections, Pathology, Quality Assurance, Health Care, Randomized Controlled Trials as Topic, United States, Uterine Cervical Neoplasms
Show Abstract · Added March 5, 2014
OBJECTIVES - To evaluate an external quality assurance (EQA) program for the laboratory diagnosis of human papillomavirus (HPV) disease that was established to improve international research capability within the Division of AIDS at the National Institute of Allergy and Infectious Disease-supported Adult AIDS Clinical Trials Group network.
METHODS - A three-component EQA scheme was devised comprising assessments of diagnostic accuracy of cytotechnologists and pathologists using available EQA panels, review of quality and accuracy of clinical slides from local sites by an outside expert, and HPV DNA detection using a commercially available HPV test kit.
RESULTS - Seven laboratories and 17 pathologists in Africa, India, and South America participated. EQA scores were suboptimal for EQA proficiency testing panels in three of seven laboratories. There was good agreement between the local laboratory and the central reader 70% of the time (90% confidence interval, 42%-98%). Performance on the College of American Pathologists' HPV DNA testing panel was successful in all laboratories tested.
CONCLUSIONS - The prequalifying EQA round identified correctable issues that will improve the laboratory diagnosis of HPV-related cervical disease at the participating international study sites and will provide a mechanism for ongoing education and continuous quality improvement.
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1 Members
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14 MeSH Terms
Perspectives on methodology for in vitro culture of Helicobacter pylori.
Cover TL
(2012) Methods Mol Biol 921: 11-5
MeSH Terms: Agar, Animals, Culture Media, Culture Techniques, Helicobacter pylori, Laboratories
Show Abstract · Added March 5, 2014
Over the past 25 years, a variety of methods have been developed for culture of Helicobacter pylori in vitro. H. pylori is a capnophilic and microaerophilic organism that is typically cultured using complex culture media. Analysis of H. pylori growth in chemically defined media has provided insight into the nutritional requirements, physiology, and metabolic capacities of this organism.
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1 Members
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6 MeSH Terms
Duloxetine inhibits effects of MDMA ("ecstasy") in vitro and in humans in a randomized placebo-controlled laboratory study.
Hysek CM, Simmler LD, Nicola VG, Vischer N, Donzelli M, Krähenbühl S, Grouzmann E, Huwyler J, Hoener MC, Liechti ME
(2012) PLoS One 7: e36476
MeSH Terms: 3,4-Methylenedioxyamphetamine, Adult, Biological Transport, Duloxetine Hydrochloride, Female, Humans, Laboratories, Male, N-Methyl-3,4-methylenedioxyamphetamine, Norepinephrine, Placebo Effect, Receptors, Adrenergic, Serotonin, Serotonin Plasma Membrane Transport Proteins, Thiophenes
Show Abstract · Added August 3, 2013
UNLABELLED - This study assessed the effects of the serotonin (5-HT) and norepinephrine (NE) transporter inhibitor duloxetine on the effects of 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence.
TRIAL REGISTRATION - Clinicaltrials.gov NCT00990067.
0 Communities
1 Members
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15 MeSH Terms
Research tools: Understand how it works.
Piston DW
(2012) Nature 484: 440-1
MeSH Terms: Automation, Education, Graduate, Equipment Design, Laboratories, Research, Research Design, Research Personnel
Added December 6, 2012
0 Communities
1 Members
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7 MeSH Terms
Performance metrics for liquid chromatography-tandem mass spectrometry systems in proteomics analyses.
Rudnick PA, Clauser KR, Kilpatrick LE, Tchekhovskoi DV, Neta P, Blonder N, Billheimer DD, Blackman RK, Bunk DM, Cardasis HL, Ham AJ, Jaffe JD, Kinsinger CR, Mesri M, Neubert TA, Schilling B, Tabb DL, Tegeler TJ, Vega-Montoto L, Variyath AM, Wang M, Wang P, Whiteaker JR, Zimmerman LJ, Carr SA, Fisher SJ, Gibson BW, Paulovich AG, Regnier FE, Rodriguez H, Spiegelman C, Tempst P, Liebler DC, Stein SE
(2010) Mol Cell Proteomics 9: 225-41
MeSH Terms: Animals, Chickens, Chromatography, Liquid, Egg Proteins, Laboratories, Proteome, Proteomics, Reproducibility of Results, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Software, Tandem Mass Spectrometry
Show Abstract · Added August 21, 2013
A major unmet need in LC-MS/MS-based proteomics analyses is a set of tools for quantitative assessment of system performance and evaluation of technical variability. Here we describe 46 system performance metrics for monitoring chromatographic performance, electrospray source stability, MS1 and MS2 signals, dynamic sampling of ions for MS/MS, and peptide identification. Applied to data sets from replicate LC-MS/MS analyses, these metrics displayed consistent, reasonable responses to controlled perturbations. The metrics typically displayed variations less than 10% and thus can reveal even subtle differences in performance of system components. Analyses of data from interlaboratory studies conducted under a common standard operating procedure identified outlier data and provided clues to specific causes. Moreover, interlaboratory variation reflected by the metrics indicates which system components vary the most between laboratories. Application of these metrics enables rational, quantitative quality assessment for proteomics and other LC-MS/MS analytical applications.
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3 Members
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12 MeSH Terms