scholarly journals Pediatric Population Reference Value Distributions for Cancer Biomarkers and Covariate-Stratified Reference Intervals in the CALIPER Cohort

2014 ◽  
Vol 60 (12) ◽  
pp. 1532-1542 ◽  
Author(s):  
Victoria Bevilacqua ◽  
Man Khun Chan ◽  
Yunqi Chen ◽  
David Armbruster ◽  
Beth Schodin ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Pediatric Population ◽  
Specific Antigen ◽  
Reference Value ◽  
Cancer Biomarkers ◽  
Reference Intervals ◽  
Specific Reference ◽  
Cancer Antigen 125 ◽  
Serum Samples ◽  
Free Psa

Abstract BACKGROUND Cancer biomarkers are commonly used in pediatrics to monitor cancer progression, recurrence, and prognosis, but pediatric reference value distributions have not been well established for these markers. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) sought to develop a pediatric database of covariate-stratified reference value distributions for 11 key circulating tumor markers, including those used in assessment of patients with childhood or adult cancers. METHODS Healthy community children from birth to 18 years of age were recruited to participate in the CALIPER project with informed parental consent. We analyzed serum samples from 400–700 children (depending on the analyte in question) on the Abbott Architect ci4100 and established reference intervals for α-fetoprotein (AFP), antithyroglobulin (anti-Tg), human epididymis protein 4 (HE4), cancer antigen 125 (CA125), CA15-3, CA19-9, progastrin-releasing peptide (proGRP), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and total and free prostate specific antigen (PSA) according to CLSI C28-A3 statistical guidelines. RESULTS We observed significant fluctuations in biomarker concentrations by age and/or sex in 10 of 11 biomarkers investigated. Age partitioning was required for CA153, CA125, CA19-9, CEA, SCC, proGRP, total and free PSA, HE4, and AFP, whereas sex partitioning was also required for CA125, CA19-9, and total and free PSA. CONCLUSIONS This CALIPER study established a database of childhood reference intervals for 11 tumor biomarkers and revealed dramatic fluctuations in tumor marker concentrations between boys and girls and throughout childhood. In addition, important differences between the adult and pediatric population were observed, further highlighting the need for pediatric-specific reference intervals.

scholarly journals Early pregnancy reference intervals; 29 serum analytes from 4 to 12 weeks’ gestation in naturally conceived and uncomplicated pregnancies resulting in live births

2019 ◽  
Vol 57 (12) ◽  
pp. 1956-1967 ◽  
Author(s):  
Jesper Friis Petersen ◽  
Lennart J. Friis-Hansen ◽  
Andreas Kryger Jensen ◽  
Anders Nyboe Andersen ◽  
Ellen C.L. Løkkegaard
Keyword(s):  
Pregnant Women ◽  
Early Pregnancy ◽  
Clinical Chemistry ◽  
Clinical Care ◽  
Local Population ◽  
First Trimester ◽  
Reference Intervals ◽  
Specific Reference ◽  
Cancer Antigen 125 ◽  
Serum Samples

Abstract Background Pregnancy introduces major physiological changes that also alter biochemical analytes. Maternal and perinatal health can be optimized by early intervention and therefore, pregnancy-specific reference intervals (RIs) for the local population are warranted. While the second and third trimester-specific changes are well described, the first trimester is less well characterized. We therefore wanted to facilitate early detection of abnormalities by generating first trimester reference values for 29 common analytes. Methods In a prospective early pregnancy (PEP) cohort (2016–2017), 203 pregnant women were recruited from 4 to 8 weeks’ gestation. Consecutive blood samples were drawn every 2 weeks until an ongoing second trimester pregnancy (n = 164) or a miscarriage (n = 39) occurred. After exclusion of women with complicated pregnancies or deliveries (n = 42), 122 women were included. The serum samples collected at <6, 6–8, 8–10, 10–12 and >12 weeks’ gestation were analyzed for 29 common analytes. Subsequently the RIs were calculated according to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommendations (2.5–97.5th percentiles) and compared with the conventional RIs for non-pregnant women. Results Human chorionic gonadotropin (hCG), progesterone (P4), estradiol (E2), pregnancy-associated plasma protein A (PAPP-A), cancer antigen 125 (CA125), thyroid stimulating hormone (TSH), creatinine (CREA) and albumin (ALB) showed an early pregnancy-dependent change compared with conventional limits. For ALB the change was seen at 5.5 weeks’ gestation. Conclusions We report gestational age-specific RIs available from the early part of the first trimester applicable to everyday clinical care of pregnant women. Well-known alterations of RIs seen in later trimesters are also observed in the first.

scholarly journals Age- and sex-specific reference intervals for the serum cystatin C/creatinine ratio in healthy children (0–18 years old)

2019 ◽  
Vol 47 (7) ◽  
pp. 3151-3159 ◽  
Author(s):  
Changjin Liu ◽  
Jing Wen ◽  
Jialin Xiang ◽  
Xuhong Ouyang ◽  
Yan Yang ◽  
...  
Keyword(s):  
Cystatin C ◽  
Pediatric Population ◽  
Age Groups ◽  
Serum Markers ◽  
Reference Intervals ◽  
Specific Reference ◽  
Healthy Children ◽  
Serum Samples ◽  
Serum Cystatin C ◽  
Age And Sex

Objective This study aimed to investigate serum levels of the cystatin C (CysC)/creatinine (Cr) ratio and renal serum markers (CysC, Cr, urea, and uric acid [UA]) for different ages and by sex. We also aimed to establish pediatric reference intervals for the serum CysC/Cr ratio. Methods Serum samples were collected from 4765 healthy children (0–18 years old). Serum markers of renal function were measured, and the CysC/Cr ratio of each participant was calculated and statistically analyzed. Results The renal marker CysC did not substantially change after 1 year old. Cr, urea, and UA levels generally increased with age. However, the serum CysC/Cr ratio steadily decreased with age. The CysC/Cr ratio showed significant differences in age among all age groups and varied with sex, except for in the 1 to 6-year-old groups. The overall serum CysC/Cr ratio in girls was higher than that in boys. Conclusion Reference intervals of the serum CysC/Cr ratio in the pediatric population were established. These intervals need to be partitioned by age and sex.

Pediatric reference value distributions and covariate-stratified reference intervals for 29 endocrine and special chemistry biomarkers on the Beckman Coulter Immunoassay Systems: a CALIPER study of healthy community children

2016 ◽  
Vol 54 (4) ◽  
Author(s):  
Kimiya Karbasy ◽  
Danny C.C. Lin ◽  
Alexandra Stoianov ◽  
Man Khun Chan ◽  
Victoria Bevilacqua ◽  
...  
Keyword(s):  
Pediatric Population ◽  
Reference Value ◽  
Reference Interval ◽  
Reference Intervals ◽  
Healthy Children ◽  
Serum Samples ◽  
Laboratory Assessment ◽  
Research Initiative ◽  
Closing The Gaps ◽  
Gender Based

AbstractThe CALIPER program is a national research initiative aimed at closing the gaps in pediatric reference intervals. CALIPER previously reported reference intervals for endocrine and special chemistry markers on Abbott immunoassays. We now report new pediatric reference intervals for immunoassays on the Beckman Coulter Immunoassay Systems and assess platform-specific differences in reference values.A total of 711 healthy children and adolescents from birth to <19 years of age were recruited from the community. Serum samples were collected for measurement of 29 biomarkers on the Beckman Coulter Immunoassay Systems. Statistically relevant age and/or gender-based partitions were determined, outliers removed, and reference intervals calculated in accordance with Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines.Complex profiles were observed for all 29 analytes, necessitating unique age and/or sex-specific partitions. Overall, changes in analyte concentrations observed over the course of development were similar to trends previously reported, and are consistent with biochemical and physiological changes that occur during childhood. Marked differences were observed for some assays including progesterone, luteinizing hormone and follicle-stimulating hormone where reference intervals were higher than those reported on Abbott immunoassays and parathyroid hormone where intervals were lower.This study highlights the importance of determining reference intervals specific for each analytical platform. The CALIPER Pediatric Reference Interval database will enable accurate diagnosis and laboratory assessment of children monitored by Beckman Coulter Immunoassay Systems in health care institutions worldwide. These reference intervals must however be validated by individual labs for the local pediatric population as recommended by CLSI.

Pediatric reference intervals for 1,25-dihydroxyvitamin D using the DiaSorin LIAISON XL assay in the healthy CALIPER cohort

2018 ◽  
Vol 56 (6) ◽  
pp. 964-972 ◽  
Author(s):  
Victoria Higgins ◽  
Dorothy Truong ◽  
Nicole M.A. White-Al Habeeb ◽  
Angela W.S. Fung ◽  
Barry Hoffman ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Critical Role ◽  
Reference Interval ◽  
Reference Intervals ◽  
Biologically Active ◽  
Specific Reference ◽  
Healthy Children ◽  
Serum Samples ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D

Abstract Background: 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active vitamin D metabolite, plays a critical role in calcium and phosphate homeostasis. 1,25(OH)2D is measured to assess calcium and phosphate metabolism, particularly during periods of profound growth and development. Despite its importance, no reliable pediatric reference interval exists, with those available developed using adult populations or out-dated methodologies. Using the fully automated chemiluminescence immunoassay by DiaSorin, we established 1,25(OH)2D pediatric reference intervals using healthy children and adolescents from the CALIPER cohort. Methods: Serum samples from healthy subjects (0 to <19 years) were analyzed for 1,25(OH)2D using the DiaSorin LIAISON XL assay and age-specific reference intervals were established. The Mann-Whitney U-test was used to determine seasonal differences. Pooled neonatal and infantile samples were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine if elevated concentrations during the first year of life may be attributed to cross-reacting moieties. Results: Three reference interval age partitions were required with highest levels in subjects 0 to <1 year (77–471 pmol/L), which declined and narrowed after 1 year (113–363 pmol/L) and plateaued at 3 years (108–246 pmol/L). 1,25(OH)2D concentration was not significantly affected by seasonal variation or sex. Elevated 1,25(OH)2D concentrations in neonatal and infantile samples may be the result of an interfering substance. The absence of 3-epi-1,25-dihydroxyvitamin D in the pooled samples makes it unlikely to be the interfering moiety. Conclusions: Pediatric reference intervals for 1,25(OH)2D were established to improve test result interpretation in children and adolescents. 1,25(OH)2D is elevated in a proportion of neonates and infants, which may be the result of a cross-reacting moiety.

scholarly journals Age-Related Reference Intervals for Blood Amino Acids in Thai Pediatric Population Measured by Liquid Chromatography Tandem Mass Spectrometry

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jaraspong Uaariyapanichkul ◽  
Sirinuch Chomtho ◽  
Kanya Suphapeetiporn ◽  
Vorasuk Shotelersuk ◽  
Santi Punnahitananda ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Liquid Chromatography ◽  
Pediatric Population ◽  
Reference Intervals ◽  
Specific Reference ◽  
Tandem Mass ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Amino Acid Levels

Background. Age, race, and analytic method influence levels of blood amino acids, of which reference intervals are required for the diagnosis and management of inherited metabolic disorders.Objectives. To establish age-specific reference intervals for blood amino acids in Thai pediatric population measured by liquid chromatography tandem mass spectrometry (LC-MS/MS).Methods. A cross-sectional study of 277 healthy children from birth to 12 years was conducted. Anthropometric, clinical, and dietary information were recorded. Dried blood spots on a filtered paper were used for measurement by derivatized LC-MS/MS. Factors that might affect amino acids such as fasting time and dietary intake were analyzed using quantile regression analysis.Results. Levels of thirteen blood amino acids were reported as median and interval from 2.5th–97.5th percentiles. Compared with those of Caucasian, most blood amino acid levels of Thai children were higher. Compared with a previous study using HPLC in Thai children, many amino acid levels are different. Glycine, alanine, leucine/isoleucine, and glutamic acid sharply decreased after birth. Citrulline, arginine, and methionine stayed low from birth throughout childhood, whereas phenylalanine was at middle level and slightly increased during preadolescence.Conclusion. Reference intervals of age-specific blood amino acids using LC-MS/MS were established in the Thai pediatric population. They diverge from previous studies, substantiating the recommendation that, for the optimal clinical practice, age-specific reference intervals of amino acids should be designated for the particular population and analysis method.

Discordant prostate specific antigen test results despite WHO assay standardization

2018 ◽  
Vol 33 (3) ◽  
pp. 275-282 ◽  
Author(s):  
Martin Boegemann ◽  
Christian Arsov ◽  
Boris Hadaschik ◽  
Kathleen Herkommer ◽  
Florian Imkamp ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Early Detection ◽  
Specific Antigen ◽  
Test Results ◽  
Serum Samples ◽  
Prostate Specific Antigen Test ◽  
Free Psa ◽  
Prostate Biopsies ◽  
Cancer Early Detection ◽  
Total Psa

Introduction: Total PSA (tPSA) and free PSA (fPSA) are the most commonly used biomarkers for early detection of prostate cancer. Despite standardization efforts, many available PSA assays may still produce discordant results. In the present study, we compared four PSA assays calibrated to the WHO standards 96/670 and 96/668 for tPSA and fPSA, respectively. Methods: Within the scope of the Prostate Cancer Early Detection Study Based on a ‘‘Baseline’’ PSA Value in Young Men (PROBASE), we tested tPSA and fPSA in serum samples from 50 patients in the four different PROBASE sites using four WHO-calibrated assays from Roche (Elecsys, Cobas), Beckman-Coulter (Access-II) and Siemens (ADVIA Centaur). The comparison was performed using the Passing–Bablok regression method. Results: Compared to Access, the median tPSA levels for Centaur, Elecsys, and Cobas were +3%, +11%–20%, and +17%–23%, respectively, while for median fPSA levels the differences for Centaur, Elecsys, and Cobas were +49%, +29%–31%, and +22%, respectively. Discussion: Despite all investigated assays being WHO-calibrated, the Elecsys and Cobas tPSA assays produced considerably higher results than the Access and Centaur assays. Differences in fPSA-recovery between all investigated assays were even more pronounced. When applying the tPSA cutoff of 3.1 μg/L recommended for WHO-calibrated assays, the use of higher calibrated assays may lead to unnecessary prostate biopsies. Conversely, if the historical threshold of 4 μg/L is applied when using WHO-calibrated assays, it could lead to falsely omitted prostate biopsies.

scholarly journals Reference Reagents for Prostate-specific Antigen (PSA): Establishment of the First International Standards for Free PSA and PSA (90:10)

2000 ◽  
Vol 46 (9) ◽  
pp. 1310-1317 ◽  
Author(s):  
Brian Rafferty ◽  
Peter Rigsby ◽  
Matthew Rose ◽  
Thomas Stamey ◽  
Rose Gaines Das
Keyword(s):  
Confidence Interval ◽  
Prostate Specific Antigen ◽  
Recombinant Dna ◽  
Collaborative Study ◽  
Specific Antigen ◽  
International Standards ◽  
Serum Samples ◽  
International Standard ◽  
Free Psa ◽  
Total Psa

Abstract Background: Prostate-specific antigen (PSA) measurements in serum by immunoassay are widely used in the screening, diagnosis, and monitoring of patients with prostate cancer although the lack of common reference reagents has led in the past to wide differences in estimates. We report here the results of a WHO international collaborative study in which two preparations of PSA representative of the main immunoreactive components in serum, free PSA and PSA 90:10, and a preparation of recombinant DNA-derived PSA were assessed as potential standards for the calibration of diagnostic immunoassays for PSA. Methods: Coded vials of the candidate materials and serum preparations containing PSA in the clinically important range were provided to the 10 laboratories in the study, and participants were asked to perform PSA assays currently in use in their laboratories. Data from 89 immunoassays by 26 different method-laboratory combinations were contributed to the study and analyzed centrally at the National Institute for Biological Standards and Control. Results: Potency estimates of the preparations relative to the in-house calibrators were in good agreement with the target value of 1 μg of total PSA/vial, the preparation of free PSA giving 1.10 μg/vial (95% confidence interval, 0.99–1.21 μg/vial) and PSA 90:10, 1.11 μg/vial (95% confidence interval, 1.04–1.18 μg/vial). No immunoreactivity was detected in ampoules containing the recombinant material. Use of a common standard of PSA 90:10 significantly reduced the between-laboratory geometric coefficients of variation for serum samples included in the study and gave a much narrower range of potency estimates. Conclusions: The preparation of free PSA was established by WHO as the First International Standard for PSA (free) with an assigned content of 1 μg of total PSA per vial. In addition, the preparation of bound PSA was established as the First International Standard for PSA (90:10) with an assigned content of 1 μg of total PSA per vial.

Fabrication and Bioconjugation of Micro- and Nanoscale Structures Intended for Cancer-Specific Antigen Detection

2009 ◽  
Vol 131 (2) ◽  
Author(s):  
Kevin M. Klein ◽  
Gregory Ostrowicki ◽  
Andrew T. Gewirtz ◽  
Suresh K. Sitaraman
Keyword(s):  
Binding Affinity ◽  
Cancer Progression ◽  
Cancer Detection ◽  
Specific Antigen ◽  
Antigen Detection ◽  
Cancer Antigen 125 ◽  
Nanoscale Structures ◽  
Circulating Antigen ◽  
Circulating Antigens ◽  
Low Levels

Cleanroom processes can be used for fabricating microscale and nanoscale structures, and such structures, when bioconjugated, can be used for detecting low levels of cancer-specific circulating antigens. The concentration of such circulating antigens in human serum continues to increase with cancer progression, and therefore, detection of cancer at very early stages of the disease can be facilitated by monitoring small increases in circulating antigen concentration. Therefore, fabrication and bioconjugation are the first steps in the development of bio-assays for cancer detection. In this work, microscale and nanoscale Au/Cr thin film structures have been fabricated on Si substrate using dc sputtering and electron-beam (e-beam) evaporation in combination with photo and e-beam lithography. Using the fabricated device material stack (Au/Cr/Si), we have assessed the binding affinity of Au, Cr, and Si with Protein G, and antibodies for prostate specific antigen and cancer antigen 125, an ovarian cancer-associated antigen. Based on our experiments, we see that the thin gold layer of the Au/Cr/Si samples provides increased biomaterial binding affinity, and the chromium layer has a similar, if not less, binding affinity compared with the silicon chip alone. Thus, this work demonstrates that the fabricated material stack provides an appropriate platform for antigen detection.

scholarly journals Cross-Method Comparison of Serum Androstenedione Measurement Using Three Different Assays: The Siemens Immulite Immunoassay, the Roche Elecsys Immunoassay, and an LC/MS-MS Assay

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A730-A731
Author(s):  
Ruhan Wei ◽  
Kathleen Bowers ◽  
Grace M Kroner ◽  
Drew Payto ◽  
Jessica Colon Franco
Keyword(s):  
Clinical Performance ◽  
Polycystic Ovary ◽  
Pediatric Population ◽  
Method Comparison ◽  
Reference Intervals ◽  
Healthy Children ◽  
Healthy Male ◽  
Serum Samples ◽  
Female Sex Hormones ◽  
Deming Regression

Abstract Introduction: Androstenedione is a common precursor of male and female sex hormones produced by the adrenal glands and gonads. Serum androstenedione is a helpful biomarker in the diagnostic workup of a subset of patients with polycystic ovary syndrome (PCOS), the investigation of virilizing endocrinopathies, and for monitoring pediatric patients with congenital adrenal hyperplasia. The gold standard for the measurement of androstenedione is LC-MS/MS. A newly developed androstenedione competitive immunoassay is now available in the US, the Roche Elecsys Androstenedione (ASD) immunoassay. Until recently, the Siemens Immulite assay was the only non-radioimmunologic immunoassay available. We characterized the analytical and clinical performance of the ASD across different patient populations and in comparison to the Immulite and an LC-MS/MS assay. Methods and materials: The experiments performed were: linearity and analytical measuring range (AMR), precision (intra- and inter-assay), and accuracy. Androstenedione was measured on de-identified residual serum samples (n=40) using the ASD and Immulite immunoassays and an LC-MS/MS assay. The reference intervals (RIs) provided by Roche for healthy male (0.280-1.52 ng/mL), healthy female (0.490-1.31 ng/mL), postmenopausal women (0.187-1.07 ng/mL), healthy children (&lt;0.519 ng/mL), and patients with PCOS (0.645-3.47 ng/mL) were verified with at least 20 specimens, according to CLSI C28A3. Statistical analysis was performed using EP Evaluator and R program. Results: The ASD had a linear response across the AMR of 0.3 to 10.0 ng/mL. The inter- and intra-assay coefficients of variation were 4.5% and 2.0% or lower, at concentrations 0.5-6.7 ng/mL, respectively. The ASD and LC-MS/MS assays had a mean bias of -0.0542 ng/mL (-2%), Deming regression of y = 1.000 [0.961; 1.039] x - 0.0548 [-0.1806; 0.0709], and r = 0.9930. The Immulite assay had a mean bias of 1.15 ng/mL (44%) and 1.22 ng/mL (32%) compared to the LC-MS/MS and ASD assays, respectively. The recommended RIs from Roche for healthy male, female, and postmenopausal female groups were successfully verified in our patient population. However, the androstenedione concentrations for the healthy children and PCOS groups were outside of the suggested RIs, with concentrations up to 1.41 ng/mL and 0.527-2.24 ng/mL, respectively. Unlike published elsewhere, hormone therapies such as contraceptive pills and steroid treatments did not significantly affect serum androstenedione concentrations in healthy females and patients with PCOS. Conclusion: The ASD is superior to the Immulite immunoassay, and it has excellent comparability with the LC-MS/MS for serum androstenedione measurement. The RIs published by Roche may not be universally transferable; verification is recommended, and establishing RIs for the pediatric population may be necessary.

Immunoglobulin G (IgG) and IgG subclass reference intervals in children, using Optilite® reagents

2018 ◽  
Vol 56 (8) ◽  
pp. 1319-1327 ◽  
Author(s):  
Olivier Grunewald ◽  
Benjamin Lopez ◽  
Séverine Brabant ◽  
Stéphanie Rogeau ◽  
Antoine Deschildre ◽  
...  
Keyword(s):  
Immunoglobulin G ◽  
Age Groups ◽  
Reference Intervals ◽  
Igg Subclasses ◽  
Specific Reference ◽  
Igg Subclass ◽  
Serum Samples ◽  
Gender Specific Differences ◽  
Specific Igg ◽  
Changes Over Time

Abstract Background: Immunoglobulin G (IgG) and IgG subclass assays are indicated in patients with suspected primary immunodeficiency (PID). Commercially available assays for IgG subclass determination are calibrated against various preparations, and so specific reference values are required for each of them. Using Optilite® reagents from The Binding Site Group Ltd., we sought to determine the pediatric IgG and IgG subclass reference intervals with respect to the ERM-DA470k certified reference material. Methods: Levels of IgG and IgG subclasses were analyzed in serum samples collected from a large cohort of PID-free children and adolescents. Reference intervals were calculated for previously published age groups (6–12 months, 12–18 months, 18 months–2 years, 2–3 years, 3–4 years, 4–6 years, 6–9 years, 9–12 years and 12–18 years), according to the Clinical and Laboratory Standards Institute’s C28-A3c protocol. Results: A total of 456 serum samples were analyzed. The correlation between the total IgG and the sum of the IgG subclasses was good (r2=0.96). No statistically significant gender-specific differences were observed. Our results for the changes over time in IgG and IgG subclass levels are consistent with previous reports. The differences between our lower/upper reference limits and those in the literature are probably due to variations in calibration. Conclusions: Our present results provide a reliable basis for the diagnosis of PIDs in childhood and for the accreditation of laboratories using Optilite® immunoturbidimetric reagents for IgG subclass measurement. Laboratory scientists and clinicians should be aware of the need for manufacturer-specific IgG subclass reference intervals.

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