Suitable Reference Materials Research Articles

Inter-laboratory variation for urine albumin among laboratories in a Swedish external quality assessment scheme 2005–2023

IntroductionIncreased albuminuria is associated with elevated mortality. Urine albumin (U-ALB) above 20 mg/L or albumin-to-creatinine ratio (U-ACR) of 3 g/mol are indicative of moderately increased albuminuria. Due to limited standardization among U-ALB methods, diagnosis of increased albuminuria might prove difficult. Materials and methodsData from Equalis’s external quality assessment scheme for low U-ALB levels during 2005–2023 were categorized according to manufacturer and divided into central laboratory (CLAB) and point-of-care testing (POCT) methods. Manufacturer median values were compared to total group mean consensus values and manufacturer CV% was compared at different U-ALB levels. ResultsCLAB was generally closer to consensus values and had lower CV% than POCT at U-ALB levels around 20 mg/L. For CLAB, Roche methods were approximately equal to consensus U-ALB, Abbott 4 % above, and Siemens 5 % below. For POCT, HemoCue was 1 % below, Siemens 7 % above, and Abbott 8 % below. For U-Creatinine, all manufacturers generally had a good agreement differing on average by 1–4 % from consensus. ConclusionsAlthough U-ALB methods generally meet The National Kidney Disease Education Program (NKDEP) recommendations of method bias less than 13 % and imprecision less than 30 %, differences among manufacturers have increased over the last years, with 2023 showing the largest differences between methods. This highlights the need for guidelines for albuminuria and ACR to take method differences into consideration, but also for implementation of suitable urine reference materials.

The Alzheimer's Association Global Biomarker Standardization Consortium (GBSC) plasma phospho-tau Round Robin study.

Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer's disease (AD) pathology. Multiple p-tau biomarkers on several analytical platforms are poised for clinical use. The Alzheimer's Association Global Biomarker Standardisation Consortium plasma phospho-tau Round Robin study engaged assay developers in a blinded case-control study on plasma p-tau, aiming to learn which assays provide the largest fold-changes in AD compared to non-AD, have the strongest relationship between plasma and cerebrospinal fluid (CSF), and show the most consistent relationships between methods (commutability) in measuring both patient samples and candidate reference materials (CRM). Thirty-three different p-tau biomarker assays, built on eight different analytical platforms, were used to quantify paired plasma and CSF samples from 40 participants. AD biomarker status was categorised as "AD pathology" (n=25) and "non-AD pathology" (n=15) by CSF Aβ42/Aβ40 (US-FDA; CE-IVDR) and p-tau181 (CE-IVDR) methods. The commutability of four CRM, at three concentrations, was assessed across assays. Plasma p-tau217 consistently demonstrated higher fold-changes between AD and non-AD pathology groups, compared to other p-tau epitopes. Fujirebio LUMIPULSE G, UGOT IPMS, and Lilly MSD p-tau217 assays provided the highest median fold-changes. In CSF, p-tau217 assays also performed best, and exhibited substantially larger fold-changes than their plasma counterparts, despite similar diagnostic performance. P-tau217 showed the strongest correlations between plasma assays (rho=0.81 to 0.97). Plasma p-tau levels were weakly-to-moderately correlated with CSF p-tau, and correlations were non-significant within the AD group alone. The evaluated CRM were not commutable across assays. Plasma p-tau217 measures had larger fold-changes and discriminative accuracies for detecting AD pathology, and better agreement across platforms than other plasma p-tau variants. Plasma and CSF markers of p-tau, measured by immunoassays, are not substantially correlated, questioning the interchangeability of their continuous relationship. Further work is warranted to understand the pathophysiology underlying this dissociation, and to develop suitable reference materials facilitating cross-assay standardisation. Alzheimer's Association (#ADSF-24-1284328-C).

Chromite Reference Materials and Matrix Effects in SIMS Oxygen Isotope Measurements

Secondary ion mass spectrometry (SIMS) measurements of δ18O in nine chromite (Mg, Fe)(Al, Cr, Fe)2O4 samples (Cr# = 0.58–0.79, Mg# = 0.39–0.72) from chromitites and harzburgite have confirmed their intra‐ and inter‐grain isotopic homogeneity, making them suitable reference materials for in situ analysis. The SIMS measurements of the oxygen isotopic composition of these chromites exhibit a range of instrumental mass fractionation (IMF) as a function of the end‐member compositions of the chromite, particularly the magnetite (FeOFe2O3) and spinel (MgAl2O4) components. Functional relationships have been developed to correct for IMF over the compositional range XMag = 0.01 to 0.05, and XSpl = 0.14 to 0.22. We conclude that, to be accurate, SIMS measurements of δ18O must be combined with electron probe microanalyses of the individual analysed spots.

Testing the reproducibility of in situ Lu[sbnd]Hf dating using Lu-rich garnet from the Tørdal pegmatites, southern Norway

In situ LuHf geochronology offers the potential for direct dating of garnet within petrographic context. However, the method requires matrix-matched standards to calibrate measured Lu/Hf ratios. In order to assess the accuracy of this calibration, as well as the reproducibility of the resulting LuHf dates, two Lu-rich (up to 1 wt% Lu) garnet samples from the Tørdal pegmatite field in southern Norway were analysed over six analytical sessions. Multi-session isochron LuHf dates of 930.3 ± 1.4 Ma (MSWD = 1.0, 164 analyses) and 930.3 ± 1.7 Ma (MSWD = 1.5; 125 analyses) were obtained, conform with previously published age constraints. The relative standard deviation of 0.1% between the analytical sessions indicates that the dates are highly reproducible. For each individual analytical session, age uncertainties of 0.3–0.6% were achieved by measuring high Lu count rates in analog detection mode. We further describe a calibration strategy that deals with LuHf datasets where Lu is measured in both pulse and analog detector mode. Given the high analytical precision and reproducibility, we suggest that the Tørdal garnets are suitable reference materials for future LA-ICP-MS/MS LuHf studies.

Traceable characterization of hollow organosilica beads as potential reference materials for extracellular vesicle measurements with optical techniques

The concentration of cell-type specific extracellular vesicles (EVs) is a promising biomarker for various diseases. However, concentrations of EVs measured by optical techniques such as flow cytometry (FCM) or particle tracking analysis (PTA) in clinical practice are incomparable. To allow reliable and comparable concentration measurements suitable reference materials (RMs) and SI-traceable (SI—International system of units) methods are required. Hollow organosilica beads (HOBs) are promising RM candidates for concentration measurements of EVs based on light scattering, as the shape, low refractive index, and number concentration of HOBs are comparable to EVs of the respective size range that can be detected with current optical instrumentation. Here, we present traceable methods for measuring the particle size distribution of four HOB types in the size range between 200 and 500 nm by small-angle X-ray scattering (SAXS) and atomic force microscopy (AFM), as well as the number concentration by single-particle inductively coupled plasma mass spectrometry (spICP-MS). Based on the size and shape results, traceable reference values were obtained to additionally determine the refractive index of the shell of the HOB samples by FCM. Furthermore, the estimated refractive indexes of the HOBs plausibly agree with the refractive indexes of EVs of corresponding size. Due to their narrow size distribution and their similar shape, and low refractive index, all HOB samples studied are suitable RM candidates for calibration of the measured sample volume by optical methods within the photon wavelength range used, and thus for calibration of number concentration measurements of EVs in the size range indicated. This was confirmed as the number concentration values obtained by PTA and two independent flow cytometric measurements agreed with the concentration reference values obtained by two independent spICP-MS measurements within the calculated uncertainty limits.

Allanite geochronology in the Mount Isa Inlier

New allanite geochronology is presented for four mineral deposits in the Mount Isa Inlier (SWAN, Mary Kathleen, Koppany and Elaine Dorothy). The data indicate the occurrence of multiple phases of allanite formation: one at 1732 ± 8 Ma at Koppany, one at ca 1520 Ma at Mary Kathleen, Koppany and SWAN, and one at ca 1473 Ma at Mary Kathleen and Elaine Dorothy associated with vein calcite. In the Mary Kathleen–Koppany–Elaine Dorothy skarn system, there are chemical and textural differences between the three allanite generations; the ca 1520 Ma generation formed by dissolution–reprecipitation of 1732 Ma allanite, with no addition of externally sourced rare earth elements, as shown by the identical Nd isotopic compositions of these two populations. Allanite at SWAN yielded a 207Pb/206Pb ID-TIMS age of 1519.6 ± 1.1 Ma; its homogeneity, low common Pb contents and near-concordance make it a suitable reference material. Repeated remobilisation of rare earth elements in the Mary Kathleen system is surprising, given the widely accepted low solubility of these elements, but may have been restricted in spatial extent.

New Potential Sulfide Reference Materials for Microbeam S‐Fe‐Cu Isotope Measurements

S‐Fe‐Cu isotope systems are powerful tracers for revealing geochemical processes. However, the microanalysis of S‐Fe‐Cu isotopes is critically limited by the lack of suitable reference materials. Herein, we present three potential reference materials Ll‐Cpy (chalcopyrite), Ll‐Po (pyrrhotite) and Ll‐Sp (sphalerite) for in situ S‐Fe‐Cu isotope measurements. Numerous in situ S‐Fe‐Cu isotope measurements were performed over two years to assess isotopic homogeneity. The bulk S isotopic compositions were determined independently in seven laboratories by isotope ratio mass spectrometry (IRMS); the preferred δ34SV‐CDT for Ll‐Cpy, Ll‐Po, Ll‐Sp are 6.13 ± 0.37‰ (2s), 6.42 ± 0.37‰ (2s) and 6.28 ± 0.38‰ (2s), respectively. The bulk Fe isotope ratios in Fe‐bearing Ll‐Cpy and Ll‐Po were determined using solution nebulisation multi‐collector inductively coupled plasma‐mass spectrometry, and the obtained δ56FeIRMM‐014 values are 0.57 ± 0.07‰ (2s) and ‐0.62 ± 0.07‰ (2s), respectively. The mean bulk δ65CuNIST SRM 976 value of Ll‐Cpy is 0.57 ± 0.06‰ (2s). All the bulk values are in good agreement with the long‐term statistical results of laser ablation‐MC‐ICP‐MS and proposed as the recommended values. These sulfides are well characterised and isotopically homogeneous (at 30–40 μm spatial resolution), and can be used as potential calibration materials for in situ S‐Fe‐Cu isotope measurements.

MAP-2 apatite: A new young age reference material for U–Pb dating with LA-ICPMS analysis

Apatite is an essential mineral for geochronology and geochemistry. Precise and accurate U–Pb Laser ablation (LA)-inductively coupled plasma mass spectrometry (ICPMS) dating of apatite requires suitable matrix-matched reference materials (RMs), but young RMs (<30Ma) are lacking from existing apatite RMs. We provided a gem-quality apatite MAP-2 collected from Myanmar and subjected it to detailed chemical composition and U–Pb dating analyses to assess its homogeneity and suitability as a reference material for LA-ICPMS age determination. The results of comprehensive analyses of multiple methods show that the MAP-2 apatite is largely free of inclusions and is relatively homogenous in chemical and isotopic content. Notably, MAP-2 apatite could be the youngest apatite U–Pb dating reference material (about 22 Ma) with relatively high U contents range from 161 μg g−1 to 231 μg g−1 and an average of 210 μg g−1. The isotope dilution-thermal ionization mass spectrometry (ID-TIMS) U–Pb measurements yielded weighted mean isotopic ratio values of 0.00345 ± 0.00003 for 206Pb/238U, 0.0243 ± 0.0039 for 207Pb/235U, 0.0512 ± 0.0082 for 207Pb/206Pb and the weighted mean 206Pb/238U ages of 22.18 ± 0.22 Ma (2SD, MSWD = 0.01, n = 6) as the recommended reference value. LA-ICPMS analyses yielded 207Pb-corrected weighted mean 206Pb/238U age of 22.0 ± 0.1/0.2 Ma (2SD, MSWD = 4.2, n = 232) and the results are consistent with ID-TIMS data within the limits of the ID-TIMS analytical uncertainly, which indicates that MAP-2 apatite has the potential as a reference material for microbeam determination of U–Pb ages.

Multi-laboratory evaluation of the reproducibility of polymer biodegradation assessments applying standardized and modified respirometry methods

This research evaluated the intra- and interlaboratory variability when applying OECD 301F and OECD 301B Ready Biodegradation respirometric test methods to quantify polymer biodegradation as well as the impact of method modifications including test duration, inoculum level and test substance concentration on results. This assessment synthesizes results of mineralization studies on 5 polymers of varying structural components, molecular weight, charge, and solubility, evaluated at 8 different laboratories in 4 different countries, providing significant geographic variation in inoculum source as well as lab to lab variations in test setup. Across all laboratories, intralaboratory variability was low (≤18 % absolute difference) indicating the reproducibility of results between replicates and uniformity of test setup in each laboratory. Interlaboratory variation was also low for all 5 polymers with extent of mineralization being comparable in all OECD 301F and 301B studies even when test methods were modified. Across all studies mean mineralization was 89 ± 5.5 % for polyethylene glycol 35,000, 85 ± 7.4 % for polyvinyl alcohol 18-88, 44 ± 13 % for carboxymethyl cellulose (DS 0.6), 48 ± 4.1 % for a modified guar gum, and 88 ± 6.2 % for microcrystalline cellulose (MCC) at study completion. Due to the lack of polymeric reference materials, MCC was evaluated and found to be a suitable reference material for polymers that biodegrade rapidly in screening studies. An additional respirometric study was conducted quantifying mineralization of the 5 polymers in river water to evaluate the relationship with OECD 301 results using activated sludge as the inoculum. A similar extent of mineralization was observed for all 5 polymers in the OECD 301 and river water studies but time to reach the maximum extent of mineralization was longer using river water as the inoculum source likely due to the lower microbial counts (106 CFU/L) in the test system.

A New Albite Microanalytical Reference Material from Piz Beverin for Na, Al and Si Determination, and the Potential for New K‐Feldspar Reference Materials

Determination of alkali elements is important to Earth scientists, yet suitable and reliable microanalytical reference materials are lacking. This paper proposes a new albite reference material and evaluates the potential for future K‐feldspar reference materials. The proposed Piz Beverin albite reference material from Switzerland yields a homogeneous composition at the centimetre‐ to micrometre‐scale for Si, Al and Na with &lt; 2000 μg g‐1 total trace elements (mostly heterogeneously distributed Ca, K and Sr). EPMA and LA‐ICP‐MS measurements confirm a composition of 99.5(2)% albite component, which is supported further by bulk XRF measurements. A round robin evaluation involving nine independent EPMA laboratories confirms its composition and homogeneity for Si, Al and Na. In addition, a set of five distinct clear K‐feldspar samples was evaluated as possible reference materials. The first two crystals of adular and orthoclase yield unacceptable inhomogeneities with &gt; 2% relative local variations of Na, K and Ba contents. The three other investigated sets of K‐feldspar crystals are yellow sanidine crystals from Itrongay (Madagascar). Despite distinct compositions, EPMA confirms they are each homogeneous at the centimetre to micrometre scale for Si, Al and K and have no apparent inclusions; further investigation to find larger amounts of these materials is therefore justified.

Development of a secondary reference material for application in carbon-14 specific activity determination by thermal oxidation and liquid scintillation counting method

Abstract Carbon-14 (14C) is a pure beta-emitting radionuclide with a half-life of 5730 ± 30 y. Considering the long half-life and its biological importance, significant attention is given to monitoring 14C in the vicinity of nuclear facilities. The 14C measurement technique employed by the majority of environmental monitoring laboratories for impact assessments in the vicinity of nuclear facilities is based on the thermal oxidization of the samples and the determination of activity by liquid scintillation counting. One of the difficulties faced by these laboratories is the nonavailability of a suitable matrix-matching reference material which is truly representative of the type of sample being analyzed. In this study, an effort has been made to develop a reference material that is representative and has a similar thermal oxidation/combustion property as that of a typical terrestrial plant biota observed in the vicinity of the nuclear power plants of India for quality assurance programs. A prebomb era wood (~150 years old) was identified as a potential secondary reference material. The stable carbon ratio (d13C) of the sample was determined by isotopic ratio mass spectrometer (IRMS), and the mean value was −26.33 ± 0.47 ‰. The 14C specific activity of the sample was determined by accelerator mass spectrometry and a mean value of 221.6 ± 0.6 Bq kg−1 C was assigned as the reference value to the prebomb wood. In addition, measurements were performed by thermal oxidation in a tube furnace and by analysis of the 14C activity in a liquid scintillation counter.

97 Constant Emitting Reference Material for Material Emissions Test Procedures

Abstract In industrialised countries more than 80 % of the time is spent indoors. Products, such as building materials and furniture, emit volatile organic compounds (VOCs), which are therefore ubiquitous in indoor air. VOC in combination may, under certain environmental and occupational conditions, result in reported sensory irritation and health complaints. Emission concentrations can become further elevated in new or refurbished buildings where the rate of air exchange with fresh ambient air may be limited due to improved energy saving aspects. A healthy indoor environment can be achieved by controlling the sources and by eliminating or limiting the release of harmful substances into the air. One way is to use (building) materials proved to be low emitting. Meanwhile, a worldwide network of professional commercial and non-commercial laboratories performing emission tests for the evaluation of products for interior use has been established. Therefore, comparability of test results must be ensured. A laboratory’s proficiency can be proven by internal and external validation measures that both include the application of suitable emission reference materials (ERM). For the emission test chamber procedure according to EN 16516, no artificial ERM is commercially available. The EU-funded EMPIR project MetrIAQ aims to fill this gap by developing new and improved ERMs. The goal is to obtain a material with a reproducible and temporally constant compound release (less than 10 % variability over 14 days). Different approaches, such as the impregnation of porous materials, are being tested. The generation as well as results of the most promising materials will be presented.

Ban‐1 Zircon: A New Natural Zircon Reference Material for LA‐MC‐ICP‐MS Zr and Hf Isotopic Determinations

New zircon reference materials for in situ zircon radiogenic Hf isotope and stable Zr isotopic determinations made by laser ablation multi‐collector inductively coupled plasma‐mass spectrometry (LA‐MC‐ICP‐MS) are required due to high data productivity and consequently high reference material consumption rate. This study examines a new natural zircon for Zr isotope ratios by double spike thermal ionisation mass spectrometry (TIMS), and for Hf isotopes by bulk solution nebuliser (SN)‐MC‐ICP‐MS with both Zr and Hf determined by LA‐MC‐ICP‐MS. A total of five zirconium isotope measurements from drilled zircons, determined by TIMS, yield a mean δ94/90ZrIPGP‐Zr value of ‐0.09 ± 0.06‰ (2s). Five and eight hafnium isotope measurements for powders from the drilled zircons and Ban‐1‐4 by SN‐MC‐ICP‐MS, yield mean 176Hf/177Hf ratios of 0.282985 ± 0.000011 (2s) and 0.282982 ± 0.000007 (2s), respectively. The mean δ94/90ZrIPGP‐Zr value and 176Hf/177Hf ratio determined by LA‐MC‐ICP‐MS analyses are ‐0.06 ± 0.09‰ (2s, n = 504) and 0.282985 ± 0.000035 (2s, n = 327), respectively. The isotopic homogeneities suggest that the Ban‐1 zircon is a suitable reference material for microbeam Zr and Hf isotopic measurements.

Dating fluid infiltration and deformation in the subducted ultramafic oceanic lithosphere by perovskite geochronology

Carbonated ultramafic rocks (i.e., ophicarbonates) form by peridotite serpentinization and carbonation at the seafloor. Their metamorphic evolution is linked to that of serpentinites, hence dating deformation and metamorphism in ophicarbonates will add constraints to the P-T-t history of the subducted ultramafic lithosphere. A potential, yet underexplored, suitable mineral for geochronology in ophicarbonates is perovskite (CaTiO3). We present trace element and geochronological data (LA-ICPMS and ID-TIMS) from perovskite in ophicarbonate rocks and calcite veins from two metamorphic terranes, Lanzo Massif and Val Malenco (Alps). Metamorphic perovskite in ophicarbonates is characterized by enrichment in heavy REE, and strong negative anomalies in Zr and Hf, as well as Sr and Pb, which are attributed to coexistence of a Zr-rich phase and mobilization of these elements by fluids, respectively. Other trace elements broadly reflect the composition of the protolith and allow the distinction of perovskite from mafic and ultramafic rocks.In the Lanzo Massif, the 49.6 ± 1.0 Ma age of perovskite in shear bands constrains H2-mediated carbonate reduction and abiotic methane and graphite formation at near peak metamorphic conditions during deformation. Perovskite from Val Malenco is found in calcite veins cutting across serpentinite shear foliation and its age of 48.9 ± 0.5 Ma coincides with a major thrusting and extension event that is distinct in age from the initial nappe stacking. The Val Malenco perovskite age can be reproduced by LA-ICPMS and ID-TIMS and is proposed as a suitable secondary reference material for metamorphic, low U perovskite. These results show that metamorphic perovskite geochronology yields geologically meaningful UPb ages and is a viable tool to date deformation and fluid flow in the subducted oceanic lithosphere.

Views of the taught and the teachers on medical ethics teaching in two universities in Kenya.

Medical or clinical ethics provides guidance for health practitioners and has, hopefully, been taught to medical students during training. The teaching of clinical/medical ethics is more important in the current times because of advances in medical science and the different cultural and socioeconomic circumstances in which medicine is practised. This study sought to determine if and how clinical/medical ethics was taught at two Kenyan medical schools by conducting focus group discussions with undergraduate students and key informant interviews with lecturers teaching ethics and academic administrators. While medical/clinical ethics is a part of the medical curriculum approved by the Kenya Medical and Dental Practitioners Council (Board) and is taught during the training, we identified a gap between the theory and application of ethics education. Undergraduates, medical school administrators and lecturers from both institutions acknowledged a lack of role models and mentors, and a need for further training in communication skills since medical ethics has not been made an examinable subject and there has been no formal requirement for training of lecturers teaching ethics. For the short-term, these gaps can be addressed by training lecturers in medical/clinical ethics, and identifying and utilising suitable reference materials, while long-term measures include developing context-appropriate materials for teaching, in addition to nurturing mentorship skills among lecturers for ethical role modeling.

Accelerator mass spectrometry measurements of 93Zr for astrophysical and nuclear technology applications

Zirconium-93 is a long-lived radionuclide with a half-life of (1.61 ± 0.05) × 106 yr. Production cross sections for 93Zr by neutron capture on stable 92Zr in the keV and thermal energy ranges are important input parameters for astrophysical network calculations and nuclear industry, respectively. Despite their importance, existing experimental data suffer from large uncertainties. Here, the combination of neutron activation and accelerator mass spectrometry (AMS) is presented as an alternative method to online time-of-flight measurements for the determination of these cross sections. The main challenges for AMS of 93Zr are the interference from the stable isobar 93Nb and the production of suitable reference material. At the Heavy Ion Accelerator Facility (HIAF) the first challenge is tackled with the available high particle energies and by investigating different Zr compounds and extracted molecular beams. Using ZrF5− beams extracted from ZrF4 sample material, it is shown that the Nb background can be reduced by up to two orders of magnitude relative to the extraction of ZrO− beams from ZrO2. Using the 13+ charge state and particle energies of ∼190 MeV, 93Zr/Zr background levels in the 10−12 range are regularly achieved at HIAF. The ZrF5− output from ZrF4 samples may be highly variable but can be stabilised using an intimate mixture of ZrF4 and PbF2 at a ratio of 1:10 that has been dried down from a concentrated hydrofluoric acid solution. An option to produce a well-characterised 93Zr reference material by utilising the well-known 235U-fission yield of 93Zr is discussed. Once this remaining challenge is resolved, accurate measurements of the astrophysically and technologically relevant neutron-capture cross sections of 92Zr using AMS will be possible at HIAF.

An optimization method for untargeted MS-based isotopic tracing investigations of metabolism

IntroductionStable isotope tracer studies are increasingly applied to explore metabolism from the detailed analysis of tracer incorporation into metabolites. Untargeted LC/MS approaches have recently emerged and provide potent methods for expanding the dimension and complexity of the metabolic networks that can be investigated. A number of software tools have been developed to process the highly complex MS data collected in such studies; however, a method to optimize the extraction of valuable isotopic data is lacking.ObjectivesTo develop and validate a method to optimize automated data processing for untargeted MS-based isotopic tracing investigations of metabolism.MethodsThe method is based on the application of a suitable reference material to rationally perform parameter optimization throughout the complete data processing workflow. It was applied in the context of 13C-labelling experiments and with two different software, namely geoRge and X13CMS. It was illustrated with the study of a E. coli mutant impaired for central metabolism.ResultsThe optimization methodology provided significant gain in the number and quality of extracted isotopic data, independently of the software considered. Pascal triangle samples are well suited for such purpose since they allow both the identification of analytical issues and optimization of data processing at the same time.ConclusionThe proposed method maximizes the biological value of untargeted MS-based isotopic tracing investigations by revealing the full metabolic information that is encoded in the labelling patterns of metabolites.

Comparison of fecal calprotectin and pancreatic elastase assays based on proficiency testing results

BackgroundFecal calprotectin and fecal pancreatic elastase assays are not standardized because of a lack of suitable reference material. Laboratories may have difficulty in switching assays because different manufacturers do not compare well with each other despite having similar reference intervals. Data from proficiency testing performed in Germany (Fecal Diagnostics 01 Survey, INSTAND eV) were investigated to understand how results differed across eight calprotectin and five pancreatic elastase manufacturers. MethodsData were collected from participating laboratories in external quality assessment schemes from 2015 to 2020 for calprotectin and 2017 to 2020 for pancreatic elastase. The manufacturer group mean values and standard deviations were calculated. Reference points were created for each external quality assessment scheme by calculating the average of all manufacturer group means. Deming regression analyses were used to observe the differences across manufacturers. ResultsThe slopes of the Deming regression spanned 0.37–1.91 for calprotectin and 0.84–1.33 for pancreatic elastase. The calprotectin assays had a high degree of variability in quantitative results by manufacturer. However, pancreatic elastase assays appear to be harmonized across the different manufacturer when considering the qualitative interpretation. ConclusionsBoth calprotectin and pancreatic elastase assays could be improved by standardization efforts. Given the clinical utility and our data demonstrating high inter-manufacturer variability, calprotectin should be prioritized over pancreatic elastase in standardization efforts.

Isotopically characterised N2 O reference materials for use as community standards.

RationaleInformation on the isotopic composition of nitrous oxide (N2O) at natural abundance supports the identification of its source and sink processes. In recent years, a number of mass spectrometric and laser spectroscopic techniques have been developed and are increasingly used by the research community. Advances in this active research area, however, critically depend on the availability of suitable N2O isotope Reference Materials (RMs).MethodsWithin the project Metrology for Stable Isotope Reference Standards (SIRS), seven pure N2O isotope RMs have been developed and their 15N/14N, 18O/16O, 17O/16O ratios and 15N site preference (SP) have been analysed by specialised laboratories against isotope reference materials. A particular focus was on the 15N site‐specific isotopic composition, as this measurand is both highly diagnostic for source appointment and challenging to analyse and link to existing scales.ResultsThe established N2O isotope RMs offer a wide spread in delta (δ) values: δ 15N: 0 to +104‰, δ 18O: +39 to +155‰, and δ 15NSP: −4 to +20‰. Conversion and uncertainty propagation of δ 15N and δ 18O to the Air‐N2 and VSMOW scales, respectively, provides robust estimates for δ 15N(N2O) and δ 18O(N2O), with overall uncertainties of about 0.05‰ and 0.15‰, respectively. For δ 15NSP, an offset of >1.5‰ compared with earlier calibration approaches was detected, which should be revisited in the future.ConclusionsA set of seven N2O isotope RMs anchored to the international isotope‐ratio scales was developed that will promote the implementation of the recommended two‐point calibration approach. Particularly, the availability of δ 17O data for N2O RMs is expected to improve data quality/correction algorithms with respect to δ 15NSP and δ 15N analysis by mass spectrometry. We anticipate that the N2O isotope RMs will enhance compatibility between laboratories and accelerate research progress in this emerging field.

Natural Allanite Reference Materials forIn SituU‐Th‐Pb and Sm‐Nd Isotopic Measurements by LA‐(MC)‐ICP‐MS

Allanite is a common accessory mineral that generally incorporates considerable amounts of Th, U and light rare Earth elements in its structure, making it a useful mineral forin situU‐Th‐Pb geochronology and Sm‐Nd isotope measurements. Here, we presentin situU‐Th‐Pb ages and Sm‐Nd isotopic compositions for nine allanite samples considered as potential reference materials (CAPb, Tara, Daibosatsu, LE40010, LE2808, A007, A011, A012 and SQ‐51), with ages ranging from ~ 2650 Ma to ~ 12 Ma. Our study indicates that Daibosatsu and LE40010 have relatively homogeneous147Sm/144Nd and143Nd/144Nd isotopic compositions (147Sm/144Nd ratio variation is less than 2%) and, thus, can serve as primary reference materials for Sm‐Nd microanalysis. In contrast, CAPb, Tara, LE2808, A007, A011 and A012 all show homogeneous calculated initial143Nd/144Nd isotopic compositions, but with variable147Sm/144Nd compositions, and thus can be used only as secondary reference materials for Sm‐Nd microanalysis. Of these materials, LE40010 allanite can serve as a suitable primary reference material forin situU‐Pb dating, CAPballanite can serve as a suitable primary reference material forin situTh‐Pb dating, and LE2808, LE40010, A007, A011 and A012 can serve as suitable secondary reference materials forin situU‐Pb geochronology. In addition, Daibosatsu is suitable as a secondary reference material for Cenozoic Th‐Pb dating to monitor data reproducibility.