Reference Values for Cardiorespiratory Fitness in Patients Aged 6 to 18 Years.

OBJECTIVE: To develop reference values for cardiorespiratory fitness, as quantified by peak oxygen uptake (VO2peak) and treadmill time, in patients aged 6 through 18 years referred for cardiopulmonary exercise testing (CPET). STUDY DESIGN: We reviewed a clinical pediatric CPET database for fitness data in children aged 6-18 years with no underlying heart disease. CPET was obtained via the Bruce protocol utilizing objectively confirmed maximal effort via respiratory exchange ratio. Fitness data (VO2peak and treadmill test duration) were analyzed to determine age- and sex-specific reference values for this pediatric cohort. RESULTS: Data from 2025 pediatric CPETs (53.2% female) were included in the analyses. VO2peak increased with age in males, but not females. Treadmill test duration increased with age in both males and females. Fitness was generally higher in males when compared with females in the same age groups. CONCLUSIONS: Our study provides extensive reference values for both VO2peak and total treadmill test time via the Bruce protocol for a pediatric population without known cardiac disease. Furthermore, the inclusion of objectively confirmed maximal exercise effort increases confidence in these findings compared with prior studies in this area. Clinicians performing CPET in pediatric populations can utilize these reference values to characterize test results according to representative peer data.

Evidence-based definition of hypoprolactinemia in European men aged 40-86 years: the European male ageing study.

Empirical evidence for a low normal or reference interval for serum prolactin (PRL) is lacking for men, while the implications of very low PRL levels for human health have never been studied. A clinical state of "PRL deficiency" has not been defined except in relation to lactation. Using data from the European Male Ageing Study (EMAS), we analyzed the distribution of PRL in 3,369 community-dwelling European men, aged 40-80 years at phase-1 and free from acute illnesses. In total, 2,948 and 2,644 PRL samples were collected during phase-1 and phase-2 (3 to 5.7 years later). All samples were analysed in the same centre with the same assay. After excluding individuals with known pituitary diseases, PRL ≥ 35 ng/ml, and PRL-altering drugs including antipsychotic agents, selective serotonin reuptake inhibitors, or dopamine agonists, 5,086 data points (2,845 in phase-1 and 2,241 in phase-2) were available for analysis. The results showed that PRL declined minimally with age (slope = -0.02) and did not correlate with BMI. The positively skewed PRL distribution was log-transformed to a symmetrical distribution (skewness reduced from 13.3 to 0.015). Using two-sigma empirical rule (2[]SD about the mean), a threshold at 2.5% of the lower end of the distribution was shown to correspond to a PRL value of 2.98ng/ml. With reference to individuals with PRL levels of 5-34.9 ng/ml (event rate = 6.3%), the adjusted risk of developing type 2 diabetes increased progressively in those with PRL levels of 3-4.9 ng/ml: event rate = 9.3%, OR (95% CI) 1.59 (0.93-2.71), and more so with PRL levels of 0.3-2.9 ng/ml: event rate = 22.7%, OR 5.45 (1.78-16.62). There was also an increasing trend in prediabetes and diabetes based on fasting blood glucose levels was observed with lower categories of PRL. However, PRL levels were not associated with cancer, cardiovascular diseases, depressive symptoms or mortality. Our findings suggest that a PRL level below 3 ng/ml (64 mlU/l) significantly identifies European men with a clinically-important outcome (of type 2 diabetes), offering a lower reference-value for research and clinical practice.

Cardiovascular MRI Reference Ranges for Heart, Aorta, and Pulmonary Artery in Healthy Chinese Children.

BACKGROUND: Cardiovascular magnetic resonance (cardiac MR) reference ranges in Chinese children are lacking. PURPOSE: To establish age- and sex-specific reference ranges for cardiac MR parameters in a cohort of healthy Chinese children. STUDY TYPE: Retrospective. SUBJECTS: One hundred ninety-six healthy children (mean age 9.5 ± 3.6 years, 111 boys). FIELD STRENGTH/SEQUENCE: 1.5 T; balanced steady-state free precession. ASSESSMENT: Biventricular volume and ejection fractions (EF), left atrial (LA) volume, right atrial (RA) area, left ventricular (LV) mass and thickness, aortic root (AR), and main pulmonary artery (MPA) dimensions were measured. Parameters were compared between age groups and sex. The relationships between parameters and age, body mass index (BMI) and body surface area (BSA) were investigated. STATISTICAL TESTS: Independent-samples t tests; Pearson's correlation. A P value <0.05 was considered statistically significant. RESULTS: Generally, boys exhibited greater absolute measurements of LV volume (end-diastolic: 94.4 ± 29.5 vs. 81.3 ± 31.0 mL), LA volume (end-diastolic: 42.6 ± 13.4 vs. 38.0 ± 13.3 mL), RA area (end-diastolic: 11.6 ± 2.5 vs. 10.8 ± 2.6 cm2), LV thickness (base: 4.4 ± 1.1 vs. 3.8 ± 0.9 mm), AR dimensions (annuls: 16.3 ± 2.7 vs. 15.0 ± 2.8 mm), and MPA dimensions (14.3 ± 2.3 vs. 13.1 ± 2.4 mm) than girls did. However, these differences were not observed when the measurements were normalized to BSA (LV volume: 75.3 ± 11.7 vs. 71.9 ± 12.3 mL/m2, P = 0.052; LA volume: 34.8 ± 8.9 vs. 34.5 ± 7.6 mL/m2, P = 0.783; RA area: 9.7 ± 2.3 vs. 10.2 ± 2.3 cm2/m2, P = 0.107; LV thickness: 3.6 ± 0.7 vs. 3.6 ± 0.9 mm/m2, P = 0.990; AR: 13.6 ± 2.7 vs. 14.3 ± 3.4 mm/m2, P = 0.108; MPA: 11.9 ± 2.3 vs. 12.4 ± 2.4 mm/m2, P = 0.118). Boys had greater RV volume (end-diastolic: 98.7 ± 33.5 vs. 82.7 ± 33.1 mL) and LV mass (52.6 ± 20.2 vs. 41.4 ± 16.0 g) compared to girls, irrespective of whether the values were indexed or not for BSA. Additionally, there were significant associations between age, BMI, and BSA with biventricular volume, LA volume, RA area, LV mass and thickness, AR and MPA dimensions in both boys and girls. DATA CONCLUSION: This study suggests reference ranges at 1.5 T for Chinese children. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Age- and Sex-Specific MR-Feature Tracking Reference Values of Right Atrial Deformation in Healthy Adults.

BACKGROUND: Although right atrial (RA) myocardial deformation has important implications for patient diagnosis, prognosis, and risk stratification, its implementation in clinical practice has been hampered by limited normal reference values, especially in Asian populations. PURPOSE: To establish age- and sex-specific reference values for RA strain, strain rate (SR), and displacement based on a large sample of healthy Chinese adults using MR-feature tracking (MR-FT). STUDY TYPE: Retrospective. POPULATION: 524 healthy Chinese adults (287 male; mean age 43.7 ± 11.9 years). FIELD STRENGTH/SEQUENCE: 1.5T/balanced steady-state free precession. ASSESSMENT: RA deformation parameters, including reservoir, conduit, and booster strain (εs, εe, and εa), peak positive, early negative, and late negative SR (SRs, SRe, and SRa), and total, passive, and active displacement (Ds, De, and Da), were assessed using MR-FT. STATISTICAL TESTS: Student's t-test, one-way ANOVA, coefficients of determination (r2 ), intraclass correlation coefficients (ICC), and Bland-Altman plots. A P value <0.05 was considered significant. RESULTS: Women demonstrated significantly greater magnitudes of RA deformation parameters than men: εs (57.4% ± 15.1% vs. 44.3% ± 12.6%), εe (37.5% ± 13.4% vs. 27.4% ± 10.9%), εa (19.9% ± 5.7% vs. 16.9% ± 5.0%), SRs (2.62 ± 0.88 sec-1 vs. 2.00 ± 0.63 sec-1 ), SRe (-2.98 ± 1.26 sec-1 vs. -2.16 ± 0.92 sec-1 ), SRa (-2.28 ± 0.75 sec-1 vs. -1.84 ± 0.62 sec-1 ), Ds (-7.80 ± 1.90 mm vs. -7.46 ± 1.70 mm), and De (-4.84 ± 1.31 mm vs. -4.49 ± 1.21 mm). For both sexes, aging was significantly associated with decreased RA reservoir and conduit function (εs, SRs, Ds, εe, SRe, and De), and with increased εa and Da. RA deformation measurements had good to excellent intraobserver and interobserver reproducibility, with ICCs ranging from to 0.790 to 0.972. DATA CONCLUSION: This study provides age- and sex-specific reference values of RA strain, SR, and displacement based on a large cohort of healthy Chinese adults using MR-FT. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Reference values for nerve conduction studies of the peroneal, tibial, and sural nerve derived from a large population-based cohort: Associations with demographic and anthropometric characteristics-The Maastricht study.

INTRODUCTION/AIMS: Nerve conduction studies (NCSs) are widely used to support the clinical diagnosis of neuromuscular disorders. The aims of this study were to obtain reference values for peroneal, tibial, and sural NCSs and to examine the associations with demographic and anthropometric factors. METHODS: In 5099 participants (aged 40-79 years) without type 2 diabetes of The Maastricht Study, NCSs of peroneal, tibial, and sural nerves were performed. Values for compound muscle action potential (CMAP) and sensory nerve action potential amplitude, nerve conduction velocity (NCV), and distal latency were acquired. The association of age, sex, body mass index (BMI), and height with NCS values was determined using uni- and multivariate linear regression analyses. RESULTS: Detailed reference values are reported per decade for men and women. Significantly lower NCVs and longer distal latencies were observed in all nerves in older and taller individuals as well as in men. In these groups, amplitudes of the tibial and sural nerves were significantly lower, whereas a lower peroneal nerve CMAP was only significantly associated with age. BMI showed a multidirectional association. After correction for anthropometric factors in the multivariate analysis, the association between sex and NCS values was less straightforward. DISCUSSION: These values from a population-based dataset could be used as a reference for generating normative values. Our findings show the association of NCS values with anthropometric factors. In clinical practice, these factors can be considered when interpreting NCS values.

Cardiovascular magnetic resonance reference values of right ventricular volumetric variables in patients with hypoplastic left heart syndrome.

BACKGROUND: Cardiovascular magnetic resonance (CMR) has established itself as the gold standard for serial assessment of systemic right ventricular (RV) performance but due to the lack of standardized RV reference values for hypoplastic left heart syndrome (HLHS) patients, the interpretation of RV volumetric data in HLHS remains difficult. Therefore, this study aimed to close this gap by providing CMR reference values for the systemic RV in HLHS patients. METHODS: CMR scans of 160 children, adolescents, and young adults (age range 2.2-25.2 years, 106 males) with HLHS were retrospectively evaluated. All patients were studied following total cavopulmonary connection. Short-axis stacks were used to measure RV end-diastolic and end-systolic volumes (RVEDV, RVESV), RV stroke volume (RVSV), RV ejection fraction (RVEF), and RV end-diastolic myocardial mass (RVEDMM). Univariable and multiple linear regression analyses were performed to assess associations between RV parameters and demographic and anthropometric characteristics. Following the results of the regression analysis, reference graphs and tables were created with the Lambda-Mu-Sigma method. RESULTS: Multiple linear regression analysis showed strong associations between body height and RVEDV, RVESV as well as RVSV. Age was highly associated with RVEDMM. Therefore, percentile curves and tables were created with respect to body height (RVEDV, RVESV, RVSV) and age (RVEDMM). The influence of demographic and anthropometric parameters on RVEF was mild, thus no percentile curves and tables for RVEF are provided. CONCLUSION: We were able to define CMR reference values for RV volumetric variables for HLHS patients. These data might be useful for the assessment and interpretation of CMR scans in these patients and for research in this field.

Reference intervals and percentiles for soluble transferrin receptor and sTfR/log ferritin index in healthy children and adolescents.

OBJECTIVES: Soluble transferrin receptor (sTfR) is a marker of both erythropoiesis and iron status and is considered useful for detecting iron deficiency, especially in inflammatory conditions, but reference intervals covering the entire pediatric age spectrum are lacking. METHODS: We studied 1,064 (48.5 % female) healthy children of the entire pediatric age spectrum to determine reference values and percentiles for sTfR and the ratio of sTfR to log-ferritin (sTfR-F index) using a standard immunoturbidimetric assay. RESULTS: Soluble TfR levels were highly age-specific, with a peak in infancy and a decline in adulthood, whereas the sTfR-F index was a rather constant parameter. There were positive linear relationships for sTfR with hemoglobin (Hb) (p=0.008) and transferrin (females p<0.001; males p=0.003). A negative association was observed between sTfR and ferritin in females (p<0.0001) and for transferrin saturation and mean corpuscular volume (MCV) in both sexes (both p<0.0001). We found a positive relationship between sTfR and body height, body mass index (BMI) and inflammatory markers (CrP p<0.0001; WBC p=0.0172), while sTfR-F index was not affected by inflammation. CONCLUSIONS: Soluble TfR values appear to reflect the activity of infant erythropoiesis and to be modulated by inflammation and iron deficiency even in a healthy cohort.

Estimation of the reference values and decision limits for growth hormone in newborns using dried blood spots.

OBJECTIVES: Severe deficiency of growth hormone (GHD) of the newborn is a rare but potentially life-threatening disease. GH measured during the first week of life, using dried blood spots (DBS), may offer several advantages. Aim of the study was to estimate the reference values for GH in newborns by a new analytical method using DBS. METHODS: Using a new developed analytical method, GH was estimated from DBS of 1,036 healthy newborns attending the Neonatology Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan in the period July-October 2021. Reference values for GH deficiency were estimated by the Harrell-Davis bootstrap method, with 90 %CI calculated by the bias-corrected and accelerated bootstrap method. RESULTS: All GH measurements required 33 analytical sessions (8 months) with a CV% for calibration curve slopes equal to 6.9 %. Intermediate precision evaluated by measurement of low (3 µg/L) and high (10 µg/L) quality controls was, respectively, 14 and 6.5 %. GH reference values, estimated at percentiles 1.0st, 2.5th and 5.0th, and their 90 %CI, were, respectively, 4.5 µg/L (90 %CI 3.8-5.1), 5.9 µg/L (90 %CI 5.4-6.4) and 7.0 µg/L (90 %CI 6.7-7.3). GH levels were not associated with sex, standard deviation scores, birth weight, gestational age, type of delivery or mother's variables (age, smoking habit, gestational diabetes). CONCLUSIONS: Validation data suggest that this method can be used to measured GH in newborns using DBS. The reference values estimated in this study are in accordance with previous published works using ELISA and may help confirming the clinical suspicion of neonatal GHD.

Reference values for plasma and urine trace elements in a Swiss population-based cohort.

OBJECTIVES: Trace elements (TEs) are ubiquitous. TE concentrations vary among individuals and countries, depending on factors such as living area, workplaces and diet. Deficit or excessive TEs concentrations have consequences on the proper functioning of human organism so their biomonitoring is important. The aim of this project was to provide reference values for TEs concentrations in the Swiss population. METHODS: The 1,078 participants to the SKiPOGH cohort included in this study were aged 18-90 years. Their 24-h urine and/or plasma samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) to determine 24 TEs concentrations: Ag, Al, As, Be, Bi, Cd, Co, Cr, Cu, Hg, I, Li, Mn, Mo, Ni, Pb, Pd, Pt, Sb, Se, Sn, Tl, V and Zn. Statistical tests were performed to evaluate the influence of covariates (sex, age, BMI, smoking) on these results. Reference intervals for the Swiss adult population were also defined. RESULTS: TEs concentrations were obtained for respectively 994 and 903 persons in plasma and urine matrices. It was possible to define percentiles of interest (P50 and P95) for almost all the TEs. Differences in TEs distribution between men and women were noticed in both matrices; age was also a cofactor. CONCLUSIONS: This first Swiss biomonitoring of a large TEs-panel offers reference values in plasma and in urine for the Swiss population. The results obtained in this study were generally in line with clinical recommendations and comparable to levels reported in other population-based surveys.

Rigorous pH measurement in non-aqueous solution: measurement method and reference values in ethanol.

The recently introduced unified pH ([Formula: see text]) concept enables rigorous pH measurements in non-aqueous and mixed media while at the same time maintaining comparability to the conventional aqueous pH scale. However, its practical application is hindered by a shortage of reference [Formula: see text] values. In order to improve this situation, the European Metrology Research Project (EMPIR) UnipHied ("Realisation of a UnipHied pH scale") launched an interlaboratory comparison among highly experienced electrochemistry expert laboratories to assign the first such reference [Formula: see text] values by adopting an extensive statistical treatment of the reported measurement data: to phosphate buffer in water-ethanol mixture (50 wt% of ethanol) and ammonium formate buffer in pure ethanol. Two different measurement setups - one capable of being easily adopted in industrial applications - have been used to demonstrate the robustness of [Formula: see text] measurement. This is an important step towards wider adoption of the [Formula: see text] concept in practice, like liquid chromatography, biofuels analysis and electrocatalysis.

Randomized, crossover trial: comparing the effects of standardized egg-white meal and Vital® on global gastric emptying parameters and intragastric meal distribution in healthy Asian participants.

BACKGROUND AND AIM: Measurements of gastric emptying and accommodation for alternative test-meal protocol during gastric emptying scintigraphy (GES), such as high-calorie nutrient drinks, are not fully established. We aimed to compare the effects of standardized egg-white meal (EWM) versus high-calorie nutrient drink (Vital®; Abbott Laboratories) on global GES parameters and intragastric meal distribution at immediate scan (IMD0h). METHODS: Of 84 screened participants, 60 asymptomatic healthy Asian population (38 females; 24.0 ± 1.5 years; 23.8 ± 2.6 kg/m2) were recruited in this 2 × 2 (AB/BA) crossover trial. Participants were randomized to a 4-h GES with 99mTc-radiolabeled EWM (~255.8 kcal), followed by a 200 mL Vital® (300 kcal), or vice versa, separated by a 2-week washout period. Global meal retention (GMR), power-exponential model emptying parameters (half-emptying [T1/2], lag phases [Tlag2%, Tlag5%, Tlag10%]), and IMD0h were determined and compared. RESULTS: GMRs for both test meals were within the international standard references for solid GES. Compared to EWM, Vital® exhibited significantly lower GMRs (faster emptying) from 0.5 to 3 h (all P < 0.001) but comparable at 4 h (P = 0.153). Similar observations were found for the model-based T1/2 and the different Tlag thresholds (all P < 0.001). Furthermore, IMD0h was found to be lower with Vital®, indicating lower gastric accommodation (faster antral filling) immediately post-ingestion (P < 0.001). Both test meals showed significant moderate-to-strong positive associations at the late-phase GE (GMR 2-4 h, T1/2) (all P < 0.05). CONCLUSIONS: Overall, Vital® is an acceptable alternative test meal to the EWM for GES; however, exercise caution when interpreting early-phase GE. The normative values for global GES parameters and IMD0h are also established.

Exposure of the general French population to metals and metalloids in 2014-2016: Results from the Esteban study.

BACKGROUND: The purpose of the Esteban study was to describe levels of various biomarkers of exposure to several environmental pollutants, including metals and metalloids, among the French population. This paper describes the distribution of concentrations of 28 metals and metalloids in two different populations, and estimates the main determinants of exposure to total arsenic, the sum of inorganic arsenic (iAs) and its two metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), cadmium, chromium, copper, mercury and nickel. METHODS: Esteban is a cross-sectional study conducted between 2014 and 2016 on a random sample of 2503 adults (18-74 years old) and 1104 children (6-17 years old) from the general population. The data collected included biological samples (blood, hair, and urines), socio-demographic characteristics, environmental and occupational exposure, and information on dietary factors and lifestyle. The geometric mean and percentiles of the distribution were estimated for each metal. Multivariate analyses were performed to identify the determinants of exposure using a generalized linear model. RESULTS: Only four metals had a quantification rate below 90% in adults (beryllium, iridium, palladium, and platinum), and three metals in children (beryllium, iridium, and platinum). The concentrations of total arsenic, cadmium, chromium and mercury were higher than those found in most international studies. The determinants significantly associated with exposure were mainly diet and smoking. CONCLUSIONS: Esteban provided a nationwide description of 28 metal and metalloid exposure levels for adults (some never measured before) and for the first time in children. The study results highlighted widespread exposure to several metals and metalloids. These results could be used to advocate public health decisions for continued efforts to reduce harmful exposure to toxic metals. The Reference values (RV95) built from Esteban could also be used to support future government strategies.

Reference Values for Placental Weight and Placental:Fetal Weight Ratio in a Swedish Population.

INTRODUCTION: There is important clinical information from placental weight and its ratio to the fetal weight. The aim with this study was to establish reference values for the placental weight and the placental:fetal weight ratio for gestational weeks 13-43 in a Swedish population. MATERIALS AND METHODS: Cases were retrospectively collected from the database used at the Pathology Department at Karolinska University Hospital and information about the placental weight, fetal weight, and gestational age was retrieved. Conditions, which could affect the placental- or fetal weight were excluded. Thereafter percentile curves were calculated for the placental weight and the placental:fetal weight ratio for gestational weeks. RESULTS: A total of 730 cases were included and percentile curves for the placental weight for gestational week 13-43 and placental:fetal weight ratio for gestational week 18-43 are presented. CONCLUSIONS: Reference values for post fixation placental weight and its ratio to fetal weight for a Swedish population are presented. The reference values are lower than the current reference values used in our institution, and this will be of importance when interpreting findings after placental examination.

Australian population norms for health-related quality of life measured using the EQ-5D-5L, and relationships with sociodemographic characteristics.

BACKGROUND: Measuring health related quality-of-life (HRQoL) of the general population is essential to establish a reference for health outcome evaluations. This study sought to establish EQ-5D-5L population norms in Australia and to investigate the heterogeneity of HRQoL between sociodemographic variables. METHODS: A cross-sectional study comprising of a representative sample of Australia's general population (n = 9958) aged 18 or older. Recruitment quotas were set for the Australian census population by age, sex, state/territory of residence and rurality. Participants were recruited by Qualtrics through its database of over 800,000 registered panel members and asked to value their own state of health using the EQ-5D-5L domains and the EuroQol-Visual Analogue Scale (EQ-VAS). An Australian value set developed using Discreet Choice Experiment was used to calculate utility scores. RESULTS: The estimated mean EQ-5D-5L index for Australia's general population was 0.86 (standard deviation [SD] 0.19), and the EQ-VAS score was estimated as 73.2 (SD 21.7). 23.9% of the study population reported being in the best health state (11,111). Younger people, current smokers, people who are unemployed and people with more financial stress reported a lower EQ-5D-5L index score (p < 0.001). Residents in the major cities, inner regional and outer regional Australia reported higher health utility scores than those residing in remote and very remote Australia. CONCLUSIONS: This is the first Australian study to apply the EQ-5D-5L in a nationally representative sample. The EQ-5D-5L Australian population norms obtained can be used as reference scores for future population health evaluations and comparisons. The findings facilitate a national reference for clinical, economic, and policy decision-making processes and provide a fuller understanding of the Australian population's HRQoL.

Novel reference range values for serum testosterone: a cross-sectional study of 200,000 males.

PURPOSE: To better understand the effects of aging, metabolic syndrome, diurnal variation, and seasonal variation on serum testosterone levels in the context of current guideline statements on testosterone deficiency. METHODS: This cross-sectional study utilized the United Kingdom Biobank. Physical examination, anthropomorphic measurements, and laboratory evaluation were performed at the time of enrollment from 2006 to 2010. The primary outcomes were the effect of age, the presence of metabolic syndrome, the time of day, and the month of the year on serum testosterone levels. RESULTS: Among 197,883 included men, the 5th, 25th, 50th, 75th and 95th percentile testosterone levels in men without metabolic syndrome were significantly higher than those in men with metabolic syndrome at every decade of life (p < 0.001). The average testosterone level within each group (men without metabolic syndrome vs. men with) was clinically similar across decade of life (12.43 in 40's 12.29 in 50's 12.24 in 60's vs. 10.69 in 40's 10.56 in 50's 10.63 in 60's respectively). Average testosterone levels decreased with blood draws later in the day ranging from 10.91 to 12.74 nmol/L (p < 0.01). Similarly, there was seasonal variation in serum testosterone ranging from 11.86 to 12.18 nmol/L (p < 0.01). CONCLUSIONS: We found significant variation in serum testosterone according to the presence of metabolic syndrome and time of laboratory draw, but not according to age. These data challenge the prior dogma of age-related hypogonadism and favor an individualized approach towards serum testosterone measurement and interpretation. However, further studies are needed to correlate these population-based data with individuals' hypogonadal symptoms.

Reference values for urinary protein, albumin, beta 2-microglobulin, and the alpha 1-microglobulin-to-creatinine ratio in Japanese children.

BACKGROUND: The importance of the ratio of creatinine to urinary protein, albumin, and low-molecular weight protein as a urinary marker in chronic kidney disease patients is widely recognized. However, no reference values have hitherto been established for these markers in Japanese children. The present study aimed to establish the reference values for these urinary markers in Japanese children. METHODS: The first morning urine was randomly collected from 1712 pupils aged ≥ 3 to < 18 years during school and kindergarten mass urinary screenings. The upper limit of the reference values was set at the 97.5th percentile of the creatinine ratio per marker. RESULTS: The urinary protein-to-creatinine ratio (PCR), urinary albumin-to-creatinine ratio (ACR), urinary beta 2-microglobulin-to-creatinine ratio (BMCR), and urinary alpha 1-microglobulin-to-creatinine ratio (AMCR) showed an age-related decrease at the 50th percentile reflecting an age-related increase in urinary creatinine. The appropriate reference value for the PCR and ACR was 0.12 g/gCr and 35 mg/gCr, respectively, in the entire cohort. The appropriate reference value for the BMCR was 0.5 µg /mgCr for age ≥ 3 to < 6 years and 0.35 µg/mgCr for age 6 years or older. The appropriate reference value for the AMCR was 5.0 µg/mgCr for age ≥ 3 to < 6 years and 3.5 µg /mgCr for age 6 years or older. CONCLUSION: The present study was the first to determine appropriate reference values for the PCR, ACR, BMCR, and AMCR based on an analysis of the first morning urine samples of a large number of children.

Development and application of a 2-step methodology to select a reference society providing Dietary Reference Values for national implementation.

OBJECTIVE: To describe and discuss a 2-step methodology developed to select a reference society that provides Dietary Reference Values (DRV) for national implementation and to illustrate its application in Switzerland with one macronutrient and one micronutrient. DESIGN: During Step 1, we searched and compared DRV and methodologies used to define DRV from eight European societies for seven selected nutrients. We repeated this procedure during Step 2 for DRV from two preselected societies for forty-four nutrients. SETTING: The 2-step methodology applied here for Switzerland may be used in other countries. PARTICIPANTS: The research team commissioned six external experts from three linguistic regions of Switzerland, who provided their opinions through two online surveys, individual interviews and a focus group. RESULTS: After Step 1, we excluded five societies because of old publication dates, irrelevant publication languages for Switzerland, difficulty in accessing documents, or because their DRV were mainly based on another society. After Step 2, the two societies were qualified based on the analysis of the values and methodologies used. The need for free and easily accessible scientific background information favoured the European Food Safety Authority (EFSA). We chose alternative societies for nine nutrients for the overall population or subgroups and for the elderly. CONCLUSIONS: To manage heterogeneous and complex data from several societies, adopting a 2-step methodology including fewer nutrients and more societies during Step 1, and fewer societies but all nutrients in Step 2, was very helpful. With some exceptions, we selected EFSA as the main society to provide DRV for Switzerland.

Establishing a pediatric reference interval for plasma calprotectin.

Plasma calprotectin is a promising new biomarker of inflammatory activity and has been found to correlate well with clinical and endoscopic activity in children and adolescents with inflammatory bowel disease. A pediatric reference interval for plasma calprotectin has not been established for the Phadia 250 EliA™ Calprotectin fluoroenzyme immunoassay. In studies regarding pre-analytical properties, excellent precision and stability was found. However, sensitivity to hemolysis was demonstrated. We identified pediatric blood samples from apparently healthy children who were referred by their general practitioner for blood sampling including measurement of hemoglobin (Hb) and C-reactive protein (CRP). We excluded samples from children who had undergone additional blood sampling within 2 months before or after the index sample, if Hb was outside of local reference ranges or CRP levels were above the lower limit of the measuring interval (LLM), and any samples with a hemolysis above 0.02 mmol/L. Using this algorithm, we identified 141 blood samples. No outliers were identified. We established the following reference intervals according to CLSI C28-A3 using non-parametric statistics: 1-17 years: 16-246 µg/L. Our results may prove useful for further utilization of plasma calprotectin as a marker of inflammation in children and adolescents with inflammatory disorders.

Pediatric reference intervals for serum folate and cobalamin based on a European population without exposure to folic acid fortification.

The aim of the present study was to define pediatric reference intervals for serum cobalamin and folate utilizing data generated from a population not exposed to food fortified with folic acid. Folate and cobalamin results analyzed by electrochemiluminescence immunoassay (Roche Cobas) were obtained from 2375 children (2 months to 17.99 years of age). The serum samples were collected between 2011 and 2015 as part of the LIFE (Leipzig Research Centre for Civilization Diseases) Child cohort study in Germany, where folic acid fortification of food is not mandated. These results were used to generate age- and gender-specific reference intervals presented as non-parametric 2.5 and 97.5 percentiles. Because of a subsequent restandardisation of the Roche folate assay in 2016, folate values were recalculated accordingly for adaptation to results obtained using the present calibration. In both genders, folate concentrations decreased continuously with age, whereas cobalamin concentrations peaked at five years of age and then declined. Teenage females had higher concentrations of cobalamin in the age group 12-17.99 years.

Liver T1 and T2 mapping in a large cohort of healthy subjects: normal ranges and correlation with age and sex.

OBJECTIVE: We established normal ranges for native T1 and T2 values in the human liver using a 1.5 T whole-body imager (General Electric) and we evaluated their variation across hepatic segments and their association with age and sex. MATERIALS AND METHODS: One-hundred healthy volunteers aged 20-70 years (50% females) underwent MRI. Modified Look-Locker inversion recovery and multi-echo fast-spin-echo sequences were used to measure hepatic native global and segmental T1 and T2 values, respectively. RESULTS: T1 and T2 values exhibited good intra- and inter-observer reproducibility (coefficient of variation < 5%). T1 value over segment 4 was significantly lower than the T1 values over segments 2 and 3 (p < 0.0001). No significant regional T2 variability was detected. Segmental and global T1 values were not associated with age or sex. Global T2 values were independent from age but were significantly lower in males than in females. The lower and upper limits of normal for global T1 values were, respectively, 442 ms and 705 ms. The normal range for global T2 values was 35 ms-54 ms in males and 39 ms-54 ms in females. DISCUSSION: Liver T1 and T2 mapping is feasible and reproducible and the provided normal ranges may help to establish diagnosis and progression of various liver diseases.