Antibody-mediated interferences affecting cardiac troponin assays:recommendations from the IFCC Committee on Clinical Applications of Cardiac Biomarkers

The International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers (IFCC C-CB) provides educational documents to facilitate the interpretation and use of cardiac biomarkers in clinical laboratories and practice. Our aim is to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay. Measurements of cardiac troponin (cTn) have a prominent place in the clinical work-up of patients with suspected acute coronary syndrome. It is therefore important that clinical laboratories know how to recognize and assess analytical issues. Two emerging analytical issues resulting in falsely high cTn concentrations, often several fold higher than the upper reference limit (URL), are antibody-mediated assay interference due to long-lived cTn-antibody complexes, called macrotroponin, and crosslinking antibodies that are frequently referred to as heterophilic antibodies. We provide an overview of antibody-mediated cTn assay interference and provide recommendations on how to confirm the interference and interpret the results

Cardiac troponin T levels and exercise stress testing in patients with suspected coronary artery disease: the Akershus Cardiac Examination (ACE) 1 study

Whether reversible ischaemia in patients referred for exercise stress testing and MPI (myocardial perfusion imaging) is associated with changes in circulating cTn (cardiac troponin) levels is controversial. We measured cTnT with a sensitive assay before, immediately after peak exercise and 1.5 and 4.5 h after exercise stress testing in 198 patients referred for MPI. In total, 19 patients were classified as having reversible myocardial ischaemia. cTnT levels were significantly higher in patients with reversible myocardial ischaemia on MPI at baseline, at peak exercise and after 1.5 h, but not at 4.5 h post-exercise. In patients with reversible ischaemia on MPI, cTnT levels did not change significantly after exercise stress testing [11.1 (5.2–14.9) ng/l at baseline compared with 10.5 (7.2–16.3) ng/l at 4.5 h post-exercise, P=0.27; values are medians (interquartile range)]. Conversely, cTnT levels increased significantly during testing in patients without reversible myocardial ischaemia [5.4 (3.0–9.0) ng/l at baseline compared with 7.5 (4.6–12.4) ng/l, P<0.001]. In conclusion, baseline cTnT levels are higher in patients with MPI evidence of reversible myocardial ischaemia than those without reversible ischaemia. However, although cTnT levels increase during exercise stress testing in patients without evidence of reversible ischaemia, this response appears to be blunted in patients with evidence of reversible ischaemia. Mechanisms other than reversible myocardial ischaemia may play a role for acute exercise-induced increases in circulating cTnT levels

Prediction of Mild Cognitive Impairment that Evolves into Alzheimer&apos;s Disease Dementia within Two Years using a Gene Expression Signature in Blood: A Pilot Study

Abstract. Background: The focus on Alzheimer&apos;s disease (AD) is shifting from dementia to the prodromal stage of the disorder, to a large extent due to increasing efforts in trying to develop disease modifying treatment for the disorder. For development of diseasemodifying drugs, a reliable and accurate test for identification of mild cognitive impairment (MCI) due to AD is essential. Objective: In the present study, MCI progressing to AD will be predicted using blood-based gene expression. Material and Methods: Gene expression analysis using qPCR was performed on blood RNA from a cohort of patients with amnestic MCI (aMCI; n = 66). Within the aMCI cohort, patients progressing to AD within 1 to 2 years were grouped as MCI converters (n = 34) and the patients remaining at the MCI stage after 2 years were grouped as stable MCI (n = 32). AD and control populations were also included in the study. Results: Multivariate statistical method partial least square regression was used to develop predictive models which later were tested using leave-one-out cross validation. Gene expression signatures that identified aMCI subjects that progressed to AD within 2 years with a prediction accuracy of 74%-77% were identified for the complete dataset and subsets thereof. Conclusion: The present pilot study demonstrates for the first time that MCI that evolves into AD dementia within 2 years may be predicted by analyzing gene expression in blood. Further studies will be needed to validate this gene signature as a potential test for AD in the predementia stage

Quasi-Dynamic Modelling of DC Operated Ground-Source Heat Pump

The performance of a conventional ground-source heat pump (GSHP) has been measured in the laboratory with alternating current (AC) and direct current (DC) operation using the standardised points from EN14511:2018. The results from these measurements have been used to modify a variable speed heat pump model in IDA Indoor Climate and Energy (ICE) and the annual performance of AC and DC operation have been simulated for an entire year's operation at two geographical locations in Sweden. Results show that the energy savings with DC operation from laboratory measurements span between 1.4{5.2% and when simulating the performance for an entire year's operation, the energy savings vary between 2.5{3.4%. Furthermore, the energy savings from the simulations have been compared to the bin method described in EN14825:2018.publishedVersio

Quasi-Dynamic Modelling of DC Operated Ground-Source Heat Pump

The performance of a conventional ground-source heat pump (GSHP) has been measured in the laboratory with alternating current (AC) and direct current (DC) operation using the standardised points from EN14511:2018. The results from these measurements have been used to modify a variable speed heat pump model in IDA Indoor Climate and Energy (ICE) and the annual performance of AC and DC operation have been simulated for an entire year's operation at two geographical locations in Sweden. Results show that the energy savings with DC operation from laboratory measurements span between 1.4{5.2% and when simulating the performance for an entire year's operation, the energy savings vary between 2.5{3.4%. Furthermore, the energy savings from the simulations have been compared to the bin method described in EN14825:2018

Gene expression profiling of peripheral blood cells for early detection of breast cancer

Introduction Early detection of breast cancer is key to successful treatment and patient survival. We have previously reported the potential use of gene expression profiling of peripheral blood cells for early detection of breast cancer. The aim of the present study was to refine these findings using a larger sample size and a commercially available microarray platform. Methods Blood samples were collected from 121 females referred for diagnostic mammography following an initial suspicious screening mammogram. Diagnostic work-up revealed that 67 of these women had breast cancer while 54 had no malignant disease. Additionally, nine samples from six healthy female controls were included. Gene expression analyses were conducted using high density oligonucleotide microarrays. Partial Least Squares Regression (PLSR) was used for model building while a leave-one-out (LOO) double cross validation approach was used to identify predictors and estimate their prediction efficiency. Results A set of 738 probes that discriminated breast cancer and non-breast cancer samples was identified. By cross validation we achieved an estimated prediction accuracy of 79.5% with a sensitivity of 80.6% and a specificity of 78.3%. The genes deregulated in blood of breast cancer patients are related to functional processes such as defense response, translation, and various metabolic processes, such as lipid- and steroid metabolism. Conclusions We have identified a gene signature in whole blood that classifies breast cancer patients and healthy women with good accuracy supporting our previous findings

Biomarkers for Monitoring Pre-Analytical Quality Variation of mRNA in Blood Samples

<div><p>There is an increasing need for proper quality control tools in the pre-analytical phase of the molecular diagnostic workflow. The aim of the present study was to identify biomarkers for monitoring pre-analytical mRNA quality variations in two different types of blood collection tubes, K₂EDTA (EDTA) tubes and PAXgene Blood RNA Tubes (PAXgene tubes). These tubes are extensively used both in the diagnostic setting as well as for research biobank samples. Blood specimens collected in the two different blood collection tubes were stored for varying times at different temperatures, and microarray analysis was performed on resultant extracted RNA. A large set of potential mRNA quality biomarkers for monitoring post-phlebotomy gene expression changes and mRNA degradation in blood was identified. qPCR assays for the potential biomarkers and a set of relevant reference genes were generated and used to pre-validate a sub-set of the selected biomarkers. The assay precision of the potential qPCR based biomarkers was determined, and a final validation of the selected quality biomarkers using the developed qPCR assays and blood samples from 60 healthy additional subjects was performed. In total, four mRNA quality biomarkers (USP32, LMNA, FOSB, TNRFSF10C) were successfully validated. We suggest here the use of these blood mRNA quality biomarkers for validating an experimental pre-analytical workflow. These biomarkers were further evaluated in the 2^nd ring trial of the SPIDIA-RNA Program which demonstrated that these biomarkers can be used as quality control tools for mRNA analyses from blood samples.</p></div

Soapstone in the North. Quarries, Products and People 7000 BC - AD 1700

This book addresses soapstone use in Norway and the North Atlantic region, including Greenland. Although the majority of the papers deal with the Iron Age and Middle Ages, the book spans the Mesolithic to the early modern era. It deals with themes related to quarries, products and associated people and institutions in a broad context. Recent years have seen a revival of basic archaeological and geological research into the procurement and use of stone resources. With its authors drawn from the fields of archaeology, geosciences and traditional crafts, this anthology reflects cross-disciplinary work born of this revival

Time-course profile of EDTA down-regulation biomarkers in the validation study.

<p>1A: ATP2B4_S (mixed model contrasts: T₂₄ vs T₀, p-value <0.0001; T₄₈ vs T₀, p-value <0.0001); 1B: TNFRSF10C_S (mixed model contrasts: T₂₄ vs T₀, p-value <0.0001; T₄₈ vs T₀, p-value <0.0001). ΔCq = (Cq_biomarker – Cq_meanref) with Cq_meanref = mean of the Cq values of the 3 reference genes.</p

Time-course profile of EDTA up-regulation biomarkers in the validation study.

<p>2A: TFN_S (mixed model contrasts: T₂₄ vs T₀, p-value <0.0001; T₄₈ vs T₀, p-value <0.0001); 2B: FOSB_S (mixed model contrasts: T₂₄ vs T₀, p-value <0.0001; T₄₈ vs T₀, p-value <0.0001); 2C: LMNA_S (mixed model contrasts: T₂₄ vs T₀, p-value <0.0001; T_24s vs T₀, p-value <0.0001). ΔCq = (Cq_biomarker – Cq_meanref).</p