The certification of the mass concentration of immunoglobulin G proteinase 3 anti-neutrophil cytoplasmic autoantibodies (IgG PR3 ANCA) in human serum: ERM® - DA483/IFCC

This report describes the production and certification of ERM-DA483/IFCC, a serum protein reference material intended for the standardisation of measurements of immunoglobulin G proteinase 3 anti-neutrophil cytoplasmic autoantibodies (IgG PR3 ANCA). The material was produced according to ISO Guide 34:2009 and is certified in accordance with ISO Guide 35:2006. The raw material used to prepare ERM-DA483/IFCC was a plasmapheresis material containing a high concentration of IgG PR3 ANCA. After a prior commutability study lyophilised serum was selected as the best format for the reference material. The processing of the serum was based on the procedure used for the reference material ERM-DA470k/IFCC . The plasma was converted into serum which was then delipidated. After the addition of preservatives the processed serum was diluted with plasmapheresis buffer containing albumin, prior to the transfer of 1 mL aliquots to glass vials. The serum was then lyophilised and the vials were closed with rubber stoppers and screw caps under argon atmosphere prior to storage at -70 °C. The between unit-homogeneity was quantified and stability during dispatch and storage was assessed in accordance with ISO Guide 35:2006. The material was characterised by an inter-laboratory comparison exercise performed by laboratories of demonstrated competence, using a purified IgG PR3 ANCA preparation as calibrant. This was achieved by applying a value transfer protocol previously used in the characterisation of ERM-DA470k/IFCC. Technically invalid results were removed, but no outliers were eliminated on statistical grounds alone. The uncertainty of the certified value was estimated in accordance to the Guide to the Expression of Uncertainty in Measurement (GUM) and included components relating to possible lack of homogeneity, stability and the property value measured during characterisation. The main purpose of this material is to be used for the calibration of immunoassay-based in vitro diagnostic devices or control products for IgG PR3 ANCA measurements. As any reference material, it can also be used for control charts or validation studies. The CRM is available in glass vials containing approximately 0.1 g of dried powder. The minimum sample intake to be used after reconstitution of the material is 5 μL. The CRM was accepted as European Reference Material (ERM®) after peer evaluation by the partners of the European Reference Materials consortium

Certification of C-reactive Protein in Reference Material ERM-DA472/IFCC

The production and certification of ERM-DA472/IFCC, a new reference material certified for C-reactive protein (CRP), is described. ERM-DA472/IFCC was characterised using the reference material ERM-DA470 as calibrant. This achieved using a value transfer protocol that can be considered as a reference procedure. the principles used to measure the CRP concentration were immunonephelometry and immunoturbidimetry. The measurements were performed with different platform/reagent combinations (Abbott, Beckmann Immage, BN II, different Hitachi instruments, and Olympus AU640). In total 8 laboratories participated in the value assignment. The certified CRP mass concentration is 41.8 mg/L, the expanded uncertainty (k = 2) 2.5 mg/L.JRC.D.2-Reference material

The certification of mass concentration of Beta-2-microglobulin in human serum: ERM-DA470k/IFCC

This report describes the additional certification of the mass concentration of Beta-2-microglobulin (B2M) in ERM-DA470k/IFCC, a human serum material. The material was certified following ISO Guide 34:2009. The material was released in 2008 and was certified for the mass concentration of 12 proteins in human serum. A full description of the processing steps can be found in the original report. Between unit-homogeneity was quantified and stability during dispatch and storage were assessed in accordance with ISO Guide 35:2006. Within-unit homogeneity was estimated to determine the minimum sample intake. The material was characterised by an intercomparison among laboratories of demonstrated competence and adhering to ISO/IEC 17025. Uncertainties of the certified values were calculated in compliance with the Guide to the Expression of Uncertainty in Measurement (GUM) and include uncertainties related to possible inhomogeneity, to instability and to characterisation. The material is intended for the calibration of immunoassay-based in-vitro diagnostic devices or control products for the proteins certified. As for any calibrator it should be verified that it is commutable. The material is produced in a similar manner as ERM-DA470, the use of which has led to a significant reduction in the between-method and between-laboratory variation for the proteins certified (B2M was not certified in this material) [ , ]. It was verified during the value assignment procedure that there were no significant matrix effects, and that different methods produced consistent results. However, when the material is used as a calibrator, the commutability should be verified for the particular assay concerned. The Certified Reference Material (CRM) is available in the lyophilised form of a 1.0 mL portion of serum with additives (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), sodium azide, benzamidine hydrochloride, sodium chloride and aprotinin). The material is kept under nitrogen gas in threaded glass bottles with rubber stoppers and polypropylene screw caps. The water mass fraction of the sample is (4.3 ± 0.6) mg/g. The lyophilised powder has to be reconstituted with (1.00 ± 0.01) g of distilled water. The minimum amount of reconstituted sample to be used is 2 µL. The CRM was accepted as European Reference Material (ERM®) after peer evaluation by the partners of the European Reference Materials consortium.JRC.D.2-Standards for Innovation and sustainable Developmen

Haemophilus influenzae type b reemergence after combination immunization

An increase in Haemophilus influenzae type b (Hib) in British children has been linked to the widespread use of a diphtheria/tetanus/acellular pertussis combination vaccine (DTaP-Hib). We measured anti-polyribosyl-ribitol phos- phate antibody concentration and avidity before and after a Hib booster in 176 children 2–4 years of age who had received 3 doses of DTP-Hib (either DT whole cell pertus- sis-Hib or DTaP-Hib) combination vaccine in infancy. We also measured pharyngeal carriage of Hib. Antibody con- centrations before and avidity indices after vaccination were low (geometric mean concentration 0.46μg/mL, 95% confidence interval [CI] 0.36–0.58; geometric mean avidity index 0.16, 95% CI 0.14–0.18) and inversely related to the number of previous doses of DTaP-Hib (p = 0.02 and p<0.001, respectively). Hib was found in 2.1% (95% CI 0.7%–6.0%) of study participants. Our data support an association between DTaP-Hib vaccine combinations and clinical Hib disease through an effect on antibody concen- tration and avidit

Laboratory practice is central to earlier myeloma diagnosis:Utilizing a primary care diagnostic tool and laboratory guidelines integrated into haematology services

Treatment advances have greatly improved survival, but myeloma is among the worst of all cancers for delayed diagnosis, causing serious morbidities and early deaths. This delay is largely because the symptom profile of myeloma has very low specificity, and in primary care, myeloma is rare. However, initiating the journey to diagnosis simply requires considering myeloma and sending blood to test for monoclonal immunoglobulin. Laboratory tests reliably detect monoclonal immunoglobulin, which is present in 99% of myeloma cases, so why do health care systems have such a problem with delayed diagnosis? The Myeloma UK early diagnosis programme has brought together diverse expertise to investigate this problem, and this article was prepared by the programme's working group for laboratory best practice. It reviews evidence for test requesting, analysis and reporting, for which there is large variation in practice across the United Kingdom. It presents a ‘GP Myeloma diagnostic tool’ and how it can be integrated into laboratory practice alongside a laboratory best practice tool. It proposes improved requesting and integration with haematology services for reporting and interpretation. Here the laboratory has a central role in creating efficient and cost-effective pathways for appropriate and timely bone marrow examination for myeloma diagnosis.<br/

On the UV compactness and morphologies of typical Lyman α emitters from z ∼ 2 to z ∼ 6

Lyman-a (Lya) is, intrinsically, the strongest nebular emission line in actively star-forming galaxies (SFGs), but its resonant nature and uncertain escape fraction limit its applicability. The structure, size, and morphology may be key to understand the escape of Lya photons and the nature of Lya emitters (LAEs). We investigate the rest-frame UV morphologies of a large sample of ~4000 LAEs from z~2 to z~6, selected in a uniform way with 16 different narrow- and medium-bands over the full COSMOS field (SC4K, Santos et al. in prep). From the magnitudes that we measure from UV stacks, we find that these galaxies are populating the faint end of the UV luminosity function. We find also that LAEs have roughly the same morphology from z~2 to z~6. The median size (re~1 kpc), ellipticities (slightly elongated with b/a~0.45), S\'ersic index (disk-like with n 5 to SFGs being a factor of ~2-4 larger than LAEs for

Chronic Intestinal Failure in Children : An International Multicenter Cross-Sectional Survey

Background: The European Society for Clinical Nutrition and Metabolism database for chronic intestinal failure (CIF) was analyzed to investigate factors associated with nutritional status and the intravenous supplementation (IVS) dependency in children. Methods: Data collected: demographics, CIF mechanism, home parenteral nutrition program, z-scores of weight-for-age (WFA), length or height-for-age (LFA/HFA), and body mass index-for-age (BMI-FA). IVS dependency was calculated as the ratio of daily total IVS energy over estimated resting energy expenditure (%IVSE/REE). Results: Five hundred and fifty-eight patients were included, 57.2% of whom were male. CIF mechanisms at age 1-4 and 14-18 years, respectively: SBS 63.3%, 37.9%; dysmotility or mucosal disease: 36.7%, 62.1%. One-third had WFA and/or LFA/HFA z-scores 125%. Multivariate analysis showed that mechanism of CIF was associated with WFA and/or LFA/HFA z-scores (negatively with mucosal disease) and %IVSE/REE (higher for dysmotility and lower in SBS with colon in continuity), while z-scores were negatively associated with %IVSE/REE. Conclusions: The main mechanism of CIF at young age was short bowel syndrome (SBS), whereas most patients facing adulthood had intestinal dysmotility or mucosal disease. One-third were underweight or stunted and had high IVS dependency. Considering that IVS dependency was associated with both CIF mechanisms and nutritional status, IVS dependency is suggested as a potential marker for CIF severity in children.Peer reviewe