Tracing an Osmium Solution Standard to the International System of Units (SI).

The purpose of this work was to develop an accurate osmium (Os) solution standard that is traceable to the International System of Units, the SI. A gravimetric reduction (GR) method was developed to accurately assay the Os in ammonium hexachloroosmate salt, (NH4)2OsCl6, the chosen starting material for the Os solution standard. This GR method was also applied to -200 mesh high-purity Os metal powder, which served as an independent source of Os for comparison. An alkali fusion method was developed to create water-soluble salts from the Os metal GR products of both the (NH4)2OsCl6 and -200 mesh high-purity Os metal powder. Quantitatively prepared Os solutions from each of these water-soluble salts were compared by inductively coupled plasma spectrometry, ICP-OES. The purities of the Os starting materials were determined by quantitatively performed trace metallic impurities analysis, by ICP-OES and ICP-MS; the O, N, and H impurities were determined by inert gas fusion analysis. The percent purities of the starting materials were applied as corrections to the Os assay results obtained by GR. The agreement between these Os solutions, corrected for random and systematic errors by error budget analysis, confirmed the accuracy of the Os assay in the (NH4)2OsCl6. The SI traceability of the Os assay in the (NH4)2OsCl6 salt was established through the GR procedure and the purity analysis of this material. An SI traceable Os solution standard was gravimetrically prepared from this batch of (NH4)2OsCl6, based on the accurate Os assay and the percent purity of the starting material.

Redefinition of the Mole in the Revised International System of Units and the Ongoing Importance of Metrology for Accurate Chemical Measurements.

This Feature highlights the role of metrology, the science of measurement, in maintaining the infrastructure we all rely on for accurate chemical measurements. In particular, the recent change to the definition of the mole, the unit of chemistry, is explained.

[Redefinition of the International System of Units (SI) and Related Quantities in the Field of Ionizing Radiation].

The International System of Units (SI) is recommended for the practical system of units of measurement. The decision of redefining the seven base units of the SI (the second, the meter, the kilogram, the ampere, the kelvin, the mole and the candela) was made at the 26th meeting of the General Conference on Weights and Measures on 16 November 2018. This redefinition came into force starting 20 May 2019, and it became a big historic turning point for the metrology society. This is because the kilogram, the unit of mass, was defined only by an artifact as the international prototype of the kilogram, has been kept for 130 years since its determination in 1889, and was finally changed to the new definition by taking the fixed numerical value of the Planck constant on that day.It is easily imagined that the redefinition of the SI base units has a strong impact on our daily life or the field of science. The reason why the SI redefinition had to be adapted is introduced firstly. Then, how the new definitions are applied now after a year from the redefinition and future prospective of the new definitions are discussed. In the last, the impacts of the SI redefinition in the field of the ionizing radiation, especially in the fields of the medical application of the ionizing radiation, are discussed.

Insulin Units and Conversion Factors: A Story of Truth, Boots, and Faster Half-Truths.

Conventional insulin concentration units (IU/mL or just U/mL) are bioefficacy based, whereas the Système International (SI) units (pmol/L) are mass based. In converting between these two different approaches, there are at least 2 well-accepted conversion factors, where there should be only 1. The correct value is not the most-used or well-accepted using online calculators, some journal styles, laboratory reports, and published articles. In short, an incorrect insulin conversion factor is widely used which underreports insulin concentrations by ~15%, with potentially significant research and clinical implications. This short commentary describes the history of insulin IU definitions and conversion factors, and highlights the widespread nature of conversion factor misuse, to provoke deeper interest and thought regarding numbers we so often use without thinking.

Plasminogen activator system homeostasis and its dysregulation by ethanol in astrocyte cultures and the developing brain.

In utero alcohol exposure can cause fetal alcohol spectrum disorders (FASD), characterized by structural brain abnormalities and long-lasting behavioral and cognitive dysfunction. Neuronal plasticity is affected by in utero alcohol exposure and can be modulated by extracellular proteolysis. Plasmin is a major extracellular serine-protease whose activation is tightly regulated by the plasminogen activator (PA) system. In the present study we explored the effect of ethanol on the expression of the main components of the brain PA system in sex-specific cortical astrocyte primary cultures in vitro and in the cortex and hippocampus of post-natal day (PD) 9 male and female rats. We find that ethanol alters the PA system in astrocytes and in the developing brain. In particular, the expression of tissue-type PA (tPA), encoded by the gene Plat, is consistently upregulated by ethanol in astrocytes in vitro and in the cortex and hippocampus in vivo. Astrocytes exhibit endogenous plasmin activity that is increased by ethanol and recombinant tPA and inhibited by tPA silencing. We also find that tPA is expressed by astrocytes of the developing cortex and hippocampus in vivo. All components of the PA system investigated, with the exception of Neuroserpin/Serpini1, are expressed at higher levels in astrocyte cultures than in the developing brain, suggesting that astrocytes are major producers of these proteins in the brain. In conclusion, astrocyte PA system may play a major role in the modulation of neuronal plasticity; ethanol-induced upregulation of tPA levels and plasmin activity may be responsible for altered neuronal plasticity in FASD.

Fully international system of units-traceable glycated hemoglobin quantification using two stages of isotope-dilution high-performance liquid chromatography-tandem mass spectrometry.

Glycated hemoglobin (HbA1c), defined as hemoglobin (Hb) molecules having a stable adduct of glucose on the N-terminal of the ß-chains, has been endorsed as a diagnostic tool for diabetes mellitus and a prediction indicator for the development of diabetes complications. Here we describe an accurate procedure using two stages of isotope dilution-ultra performance liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) for the quantification of HbA1c that provides full traceability to International System of Units (SI). First, synthetic peptides representing specific markers of HbA1c (G-hexa) and hemoglobin A0 (Hexa) were certified by amino acid analysis via acid hydrolysis as reference materials (RMs) for the next step. For this peptide certification, three amino acids (proline, valine, and leucine) were determined by hydrolysis with 10M hydrochloric acid at 130°C for 48h followed by ID-LC-MS/MS. Then, HbA1c content in blood was quantified with the ratio of specific proteolytic peptides from HbA1c and HbA0 via enzyme digestion using ID-LC-MS/MS with the certified peptides as RMs and isotope-labeled peptides as internal standards. Results demonstrate complete traceability to SI-units throughout this procedure. Reliability was confirmed through comparative studies with commercially available RMs for HbA1c, and other routine HbA1c diagnostic methods as well. Following full method validation, we applied this procedure to the certification of candidate hemolysate-certified RMs for HbA1c content, as well as 52 real clinical samples. All of the results showed the suitability of this method to act as a primary reference measurement procedure for HbA1c in complex biological samples.

Certified Reference Material for Use in 1H, 31P, and 19F Quantitative NMR, Ensuring Traceability to the International System of Units.

In recent years, quantitative NMR (qNMR) spectroscopy has become one of the most important tools for content determination of organic substances and quantitative evaluation of impurities. Using Certified Reference Materials (CRMs) as internal or external standards, the extensively used qNMR method can be applied for purity determination, including unbroken traceability to the International System of Units (SI). The implementation of qNMR toward new application fields, e.g., metabolomics, environmental analysis, and physiological pathway studies, brings along more complex molecules and systems, thus making use of 1H qNMR challenging. A smart workaround is possible by the use of other NMR active nuclei, namely 31P and 19F. This article presents the development of three classes of qNMR CRMs based on different NMR active nuclei (1H, 31P, and 19F), and the corresponding approaches to establish traceability to the SI through primary CRMs from the National Institute of Standards and Technology and the National Metrology Institute of Japan. These TraceCERT® qNMR CRMs are produced under ISO/IEC 17025 and ISO Guide 34 using high-performance qNMR.

The ratio of glycated albumin to hemoglobin A1c measured in IFCC units accurately represents the glycation gap.

The glycation gap (G-gap: difference between measured hemoglobin A1c [A1C] and the value predicted by its regression on the fructosamine level) is stable and associated with diabetic complications. Measuring A1C level in International Federation of Clinical Chemistry (IFCC) units (A1C-SI; mmol/mol) and National Glycohemoglobin Standardization Program units (A1C-NGSP; %) and using glycated albumin (GA) level instead of fructosamine level for calculating the G-gap, we investigated whether the G-gap is better represented by GA/A1C ratio if expressed in SI units (GA/A1C-SI ratio) rather than in NGSP units (GA/A1C-% ratio). We examined 749 Japanese children with type 1 diabetes using simultaneous GA and A1C measurements. Of these, 369 patients were examined more than five times to assess the consistency of the G-gap and the GA/A1C ratio within individuals. The relationship of GA/A1C-% ratio to the corresponding A1C-NGSP was stronger than that of GA/A1C-SI ratio to A1C-IFCC. At enrollment, the inverse relationship between the GA/A1C-SI ratio and G-gap was highly significant (R(2) = 0.95) compared with that between the GA/A1C-% ratio and G-gap (R(2) = 0.69). A highly significant inverse relationship was also observed between the mean GA/A1C-SI ratio and the mean G-gaps obtained individually over time (R(2) = 0.95) compared with that using the corresponding A1C-NGSP (R(2) = 0.67). We conclude that the G-gap is better represented by the GA/A1C-SI ratio. We propose the use of mean GA/A1C-SI ratios easily obtained individually over time as reference values in Japanese children with type 1 diabetes (6.75 ± 0.60 [means ± SD]).

International reference preparations for standardization of biological medicinal products.

International standards are prepared as materials assigned an arbitrary unitage for a biological activity by the Expert Committee on Biological Standardization of the World Health Organization. Working reference materials are calibrated against international standards giving a common unit of measurement between laboratories. The references are assessed by a collaborative study including all relevant assays rather than by a single reference method as in the SI (Le Système international d'unités) system and the unitage assigned is an arbitrary value derived from a consensus of all valid methods. The process has proved valuable in assaying the activity of therapeutic biological medicines and in standardizing certain types of diagnostics. Issues arise with maintaining the unit when the primary reference must be replaced and to some extent in assessing the commutability of the reference with real life analytes.

A revolution without tooth and claw-redefining the physical base units.

A case study is presented of a recent proposal by the major metrology institutes to redefine four of the physical base units, namely kilogram, ampere, mole, and kelvin. The episode shows a number of features that are unusual for progress in an objective science: for example, the progress is not triggered by experimental discoveries or theoretical innovations; also, the new definitions are eventually implemented by means of a voting process. In the philosophical analysis, I will first argue that the episode provides considerable evidence for confirmation holism, i.e. the claim that central statements in fundamental science cannot be tested in isolation; second, that the episode satisfies many of the criteria which Kuhn requires for scientific revolutions even though one would naturally classify it as normal science. These two observations are interrelated since holism can provide within normal science a possible source of future revolutionary periods.

[From the Point of View of the Production of Reference Material].

In the international standardization of lipid measurement for TC, HDL-C, LDL-C, and TG in serum, the establishment of a measurement system and certified serum reference materials (CRM) are the most important fundamental factor. They have been fully established. Routine measurement procedures using manufacturers' reagent kits must be calibrated with the CRM and are standardized to maintain the commutability of measured values. In TC and HDL-C measurements, the commutability of measured values from reagent kits has been maintained by calibration with the CRM. However, it is likely that different values will be obtained due to the reactivity with abnormal specimens based on measurement principles and performance of the reagent kits. This different reactivity is a typical phenomenon in abnormal specimens on conducting lipid measurements. This phenomenon cannot be avoided using the CRM. On selection of the reagent kit, it is necessary to perform evaluation studies using abnormal specimens based on the comparison method. Direct methods standardized for LDL-C measurement are selected based on evaluation studies. In TG measurements for international standardization, it is necessary to change the procedure to measure the total glycerides instead of the elimination of free glycerol by the JSCC method. This is done to avoid the influence of LPL activity on heparin treatment for cardiovascular disease patients.