bluuebunny/crossref_metadata_2025 huggingface dataset:
Dispersion of solute in a packed cylindrical tube with wall reaction
Authors: Meganathan Ajith , Debnath Sudip
Published: October 2024

The study aims to investigate the transport of solute in a packed cylindrical tube, analytically. At the wall, the solute experiences an irreversible chemical reaction of order-one. The combined action of moments method with integral transform technique has been introduced to employ the Gill’s generalized dispersion model. The main goal is to investigate a full time evaluation of various transport coefficients in different superficial flow through porous media together with wall reaction. This study provides a perspective on how porous media influences the migration of solutes in the presence of wall reactions. Exchange coefficient is shown to be solely dependent on wall absorption. In the presence of porosity, wall absorption causes an increase in the advection coefficient’s magnitudes; however, the dispersion coefficient exhibits the reverse behavior. Fluid velocity is always suppressed by damping factor, and thus advection and dispersion coefficients both controlled by damping factor. Increase in porosity parameter will reduces the axial concentration distribution. This work could have applications in areas such as groundwater flow, contaminant transport, or chemical reactions within porous materials.
Cyclin A/Cdk1 promotes chromosome alignment and timely mitotic progression
Authors: Valles Sarah Y. , Bural Shrea , Godek Kristina M. , Compton Duane A.
Published: October 2024

To ensure genomic fidelity, a series of spatially and temporally coordinated events is executed during prometaphase of mitosis, including bipolar spindle formation, chromosome attachment to spindle microtubules at kinetochores, the correction of erroneous kinetochore-microtubule (k-MT) attachments, and chromosome congression to the spindle equator. Cyclin A/Cdk1 kinase plays a key role in destabilizing k-MT attachments during prometaphase to promote correction of erroneous k-MT attachments. However, it is unknown whether Cyclin A/Cdk1 kinase regulates other events during prometaphase. Here, we investigate additional roles of Cyclin A/Cdk1 in prometaphase by using an siRNA knockdown strategy to deplete endogenous Cyclin A from human cells. We find that depleting Cyclin A significantly extends mitotic duration, specifically prometaphase, because chromosome alignment is delayed. Unaligned chromosomes display erroneous monotelic, syntelic, or lateral k-MT attachments suggesting that bioriented k-MT attachment formation is delayed in the absence of Cyclin A. Mechanistically, chromosome alignment is likely impaired because the localization of the kinetochore proteins BUB1 kinase, KNL1, and MPS1 kinase are reduced in Cyclin A-depleted cells. Moreover, we find that Cyclin A promotes BUB1 kinetochore localization independently of its role in destabilizing k-MT attachments. Thus, Cyclin A/Cdk1 facilitates chromosome alignment during prometaphase to support timely mitotic progression.
G3BP isoforms differentially affect stress granule assembly and gene expression during cellular stress
Authors: Liboy-Lugo José M. , Espinoza Carla A. , Sheu-Gruttadauria Jessica , Park Jesslyn E. , Xu Albert , Jowhar Ziad , Gao Angela L. , Carmona-Negrón José A. , Wittmann Torsten , Jura Natalia , Floor Stephen N.
Published: October 2024

Stress granules (SGs) are macromolecular assemblies that form under cellular stress. Formation of these membraneless organelles is driven by the condensation of RNA and RNA-binding proteins such as G3BPs. G3BPs form SGs following stress-induced translational arrest. Three G3BP paralogues (G3BP1, G3BP2A, and G3BP2B) have been identified in vertebrates. However, the contribution of different G3BP paralogues to SG formation and gene expression changes is incompletely understood. Here, we probed the functions of G3BPs by identifying important residues for SG assembly at their N-terminal domain such as V11. This conserved amino acid is required for formation of the G3BP–Caprin-1 complex, hence promoting SG assembly. Total RNA sequencing and ribosome profiling revealed that a G3BPV11A mutant leads to changes in mRNA levels and ribosome engagement during the integrated stress response (ISR). Moreover, we found that G3BP2B preferentially forms SGs and promotes changes in mRNA expression under endoplasmic reticulum (ER) stress. Furthermore, our work is a resource for researchers to study gene expression changes under cellular stress. Together, this work suggests that perturbing protein–protein interactions mediated by G3BPs affect SG assembly and gene expression during the ISR, and such functions are differentially regulated by G3BP paralogues under ER stress.
The rat bladder umbrella cell keratin network: Organization, dependence on the plectin cytolinker, and responses to bladder filling
Authors: Ruiz Wily G. , Clayton Dennis R. , Parakala-Jain Tanmay , Dalghi Marianela G. , Franks Jonathan , Apodaca Gerard
Published: October 2024

The keratin cytoskeleton and associated desmosomes contribute to the mechanical stability of epithelial tissues, but their organization in native bladder umbrella cells and their responses to bladder filling are poorly understood. Using whole rat bladders in conjunction with confocal microscopy, super-resolution image processing, three-dimensional image reconstruction, and platinum replica electron microscopy, we identified a cortical cytoskeleton network in umbrella cells that was organized as a dense tile-like mesh comprised of tesserae bordered by cortical actin filaments, filled with keratin filaments, and cross-linked by plectin. Below these tesserae, keratin formed a subapical meshwork and at the cell periphery a band of keratin was linked via plectin to the junction-associated actin ring. Disruption of plectin led to focal keratin network dissolution, loss of the junction-associated keratin, and defects in cell-cell adhesion. During bladder filling, a junction-localized necklace of desmosomes expanded, and a subjacent girded layer formed linking the keratin network to desmosomes, including those at the umbrella cell-intermediate cell interface. Our studies reveal a novel tile- and mesh-like organization of the umbrella cell keratin network that is dependent on plectin, that reorganizes in response to bladder filling, and that likely serves to maintain umbrella cell continuity in the face of mechanical distension.
For the People?
Authors: Beitz Charles R
Published: October 2024

Disquieting symptoms of democratic failure abound in America today with gridlocked political institutions, high levels of political polarization, and pressing but unresolved problems such as immigration, inequality, and gun violence. Are these the results of political institutions that cannot provide effective democratic representative? For the People takes a realistic look at American democracy by linking the findings of political scientists to the scrutiny of political theorists. Charles Beitz provides the core analysis showing that there are truly democratic failures (alternatively the misadventures of American politics could be due to changing times that would stress any system) and that there are possibilities for better democratic competition that could improve democratic representation. Additional chapters by a political scientist, Martin Gilens, a political theorist, Jane Mansbridge, and a lawyer, Pamela S. Karlan, sharpen the analysis by providing empirical results, additional standards for successful democracy, and concerns about two non-majoritarian American institutions, the Senate and the Electoral College. Beitz ends the book with a response to the three commentators.
The Preference-Policy Link and Representation
Authors: Gilens Martin
Published: October 2024

The link between citizens’ preferences and government policy is essential to fair and effective representation, and this link must be more than simply a dyadic relationship in which individual constituents’ preferences are matched by the legislative votes of their representatives. Representatives can feign agreement with their constituents in their most visible actions (like the frequently-studied final passage roll call votes), while ignoring or undermining those policies in their less visible activities. And even true dyadic agreement might be subverted by systemic biases, such as partisan gerrymandering, working against some groups. The link must reflect genuine systemic responsiveness in which a change in citizens’ preferences is met with a change in public policy. But policymakers in America respond weakly and unequally to the preferences of citizens: policy changes favored by the well-off and by moneyed interest groups are more likely to be adopted than those that they oppose, while poor and middle-class Americans’ preferences have no discernable impact on government policymaking. The lack of responsiveness of policymakers to the preferences of middle-income, much less poor, Americans is starkly inconsistent with the most basic tenets of democracy.
Systems, Dyads, and a Contingency Theory of Competition
Authors: Mansbridge Jane
Published: October 2024

To ensure their continuing effectiveness, democratic systems must not only be responsive, fair, and decisive, Charles Beitz’s three criteria; they must also be perceived as legitimate. A legitimacy focus takes us beyond the electoral system to the contacts citizens have with the entire representative system, including legislatures, administrative agencies, the judiciary, and even civil society associations. That focus also takes us to the dyadic one-on-one interactions between citizens and their representatives. Finally, a legitimacy focus takes us to a contingency theory of competition, pointing out that in some contexts the structures and practices of intense political competition produce lower perceived legitimacy, even if they provide better public policy. Some structures long scorned in political science—such as nonpartisan or single-party cities and state legislatures, districts with long incumbencies, and ranked-choice voting—all produce less acute competition but arguably more perceived and also normative legitimacy.
Considerations across multiple stakeholder groups when implementing fall prevention programs in the acute hospital setting: a qualitative study
Authors: McLennan Charlotte , Sherrington Catherine , Tilden Wendy , Jennings Matthew , Richards Bethan , Hill Anne-Marie , Fairbrother Greg , Ling Francis , Naganathan Vasi , Haynes Abby
Published: October 2024

Background

Falls in hospital remain a common and costly patient safety issue internationally. There is evidence that falls in hospitals can be prevented by multifactorial programs and by education for patients and staff, but these are often not routinely or effectively implemented in practice. Perspectives of multiple key stakeholder groups could inform implementation of fall prevention strategies.

Methods

Clinicians of different disciplines, patients and their families were recruited from wards at two acute public hospitals. Semi-structured interviews and focus groups were conducted to gain a broad understanding of participants’ perspectives about implementing fall prevention programs. Data were analysed using an inductive thematic approach.

Results

Data from 50 participants revealed three key themes across the stakeholder groups shaping implementation of acute hospital fall prevention programs: (i) ‘Fall prevention is a priority, but whose?’ where participants agreed falls in hospital should be addressed but did not necessarily see themselves as responsible for this; (ii) ‘Disempowered stakeholders’ where participants expressed feeling frustrated and powerless with fall prevention in acute hospital settings; and (iii) ‘Shared responsibility may be a solution’ where participants were optimistic about the positive impact of collective action on effectively implementing fall prevention strategies.

Conclusion

Key stakeholder groups agree that hospital fall prevention is a priority, however, challenges related to role perception, competing priorities, workforce pressure and disempowerment mean fall prevention may often be neglected in practice. Improving shared responsibility for fall prevention implementation across disciplines, organisational levels and patients, family and staff may help overcome this.
Two kinds of failure in joint action: On disrespect and directed duties
Authors: Löhr Guido
Published: October 2024

I identify two kinds of failure in joint action. First, we can fail to ‘do our part’, that is, fail to contribute to fulfilling the joint intention. Second, we can fail to respect our collaborators. Recognizing the distinct natures of both normative relations helps us overcome a key challenge to a reductionist theory of collective intentionality posed by Margaret Gilbert. According to this objection, we have obligations towards others even in immoral joint actions – a claim that was recently supported experimentally. Except for a handful of experimental papers, work on the normativity in joint intention has stagnated. I hope the distinction breathes fresh air into the theoretical and empirical debate.
A-023 Early Concentrations of Long Cardiac Troponin T Forms in Myocardial Infarction Patients
Authors: Wittfooth S , Linko-Parvinen A , Pallari H , Teppo K , Tuominen T , Simonen S , Setola J , Salonen S , Junes H , Vasankari T , Hellman T , Strandberg M , Airaksinen J
Published: October 2024

Background

Long forms of cardiac troponin T (cTnT) represent a new promising biomarker for more specific diagnostics of myocardial infarction (MI). We studied for the first time the concentrations of long cTnT forms in a panel including very early samples of type 1 MI patients.

Methods

Heparin plasma samples were drawn from 94 type 1 MI patients 0.4-24 h after the symptom onset and analyzed with Roche hs-cTnT assay and with our novel highly sensitive upconversion luminescence-based long cTnT immunoassay. The long cTnT assay detects all cTnT forms not cleaved at the major C-terminal cleavage site at cTnT amino acid residues 189-220 while the Roche hs-cTnT assay detects all short and long cTnT forms containing the stable central part of cTnT. Troponin ratio, reflecting the fraction of the long cTnT forms, was calculated by dividing the long cTnT result by the Roche hs-cTnT result.

Results

The long cTnT and Roche hs-cTnT concentrations varied highly (median 107 [25th-75th percentile 20-1195] ng/L and 277 [62-1422] ng/L, respectively) and correlated significantly with each other (r=0.881, p<0.001). Neither had a significant correlation with time from symptom onset. Troponin ratio was highly variable especially at the first hours, but there was a clear decreasing trend in variability later (Figure). Troponin ratio showed significant negative correlation with time (r=-0.284, p=0.005) and the correlation became stronger with longer delays between symptom onset and sampling (6-24 h, r=-0.422, p<0.001).

Conclusions

A significant portion of circulating cTnT is in long forms in type 1 acute MI patients at early stage. The fraction of long cTnT forms is highly variable in the very early hours after MI, but shows a clear decreasing trend after 6 hours from the pain onset.
A-048 Reference Interval and Clinical Performance Studies for Vitros® Immunodiagnostic Products Intact PTH II Assay to Aid in Diagnosis of Calcium and Parathyroid Disorders and Intraoperative Testing
Authors: Hirsch B M , Gardner A , Potter L , Fish R , Woeller E , Atienza J , Ding Q
Published: October 2024

Background

Intact parathyroid hormone (iPTH) measurements aid in the differential diagnosis of hypercalcemia, hypocalcemia, and parathyroid disorders. The National Academy of Clinical Biochemistry has established guidelines for intraoperative PTH testing to monitor surgical success during parathyroidectomies. Studies were conducted to define the reference interval and clinical performance of the Vitros Immunodiagnostic Products Intact PTH II (Vitros iPTH II) assay, using samples from healthy individuals and patients with conditions commonly requiring iPTH testing, including intraoperative cases.

Methods

The reference interval study was conducted in accordance with Clinical and Laboratory Standards Institute (CLSI) guideline EP28-A3c in serum samples from 134 healthy individuals. For the clinical performance study, serum samples from individuals with hypoparathyroidism, primary hyperparathyroidism, chronic renal failure (secondary or tertiary hyperparathyroidism), hypercalcemia, hypercalcemia of malignancies, and hypocalcemia were tested. Intraoperative samples used were collected from parathyroidectomy patients in series at each surgical timepoint along with the standard plasma samples used to determine surgical success.

Results

The reference samples were composed of 134 serum donors that met all inclusion/exclusion criteria for healthy donors and had a normal test result on calcium, TSH, alkaline phosphatase, creatinine, and phosphate assays. The reference interval for iPTH was determined to be 14.2-75.2 pg/mL. The results in various disease states demonstrated the clinical performance of the Vitros iPTH II assay. Of 32 intraoperative sample series included in the study, three samples demonstrated no intraoperative decrease in iPTH due to surgical failures. Consistent with the goal of the parathyroidectomy procedure, at least a 50% decrease in iPTH was observed between the presurgical and post-excision samples in all other sample series. The clinical concordance with the Roche PTH assay used intraoperatively in these procedures was 100%.

Conclusions

Defining the reference interval for a normal healthy population and results from the intended use population demonstrated that the Vitros iPTH II assay can be used as an aid in the diagnosis of calcium and parathyroid disorders and intraoperative testing.
A-060 Assessing Glucose Stability: A Comparison of Citrate/NaF, NaF, and Gel Separator Vacuum Tubes in Routine Medical Laboratory Practice
Authors: Kosova S
Published: October 2024

Background

In cases where a glycolysis inhibitor is not utilized, blood cells in vitro can consume glucose. Although current guidelines suggest using citrate-buffered inhibitors or ice-water slurry to mitigate this, practical and financial constraints often hinder adherence to these recommendations. Our objective was to evaluate the difference in glucose concentration in our routine sample management by employing Citrate buffered/NaF, NaF, and Gel Barrier tubes.

Methods

In this study, we utilized Greiner FCmix citrate-buffered NaF and EDTA tubes (3 mL), Becton Dickinson NaF and EDTA tubes (4 mL), and Becton Dickinson SSTII Gel Barrier tubes (5 mL). Following venipuncture, the tubes were transferred to the laboratory and centrifuged within 30 minutes. Glucose levels of 46 patients' samples were measured using a Cobas 6000 system (c501) employing the Glucose Hexokinase method, which exhibits an intermediate coefficient of variation (CV) of approximately 1.5% and no significant bias, as confirmed by monitoring with Biorad EQAS.

Results

The mean plasma glucose difference between Citrate-buffered tubes and NaF tube samples was 2.8 mg/dL with a 95% confidence interval (CI) ranging from 2.2 to 3.4 mg/dL (Mean: 0.16 mmol/L; CI: 0.12 - 0.19 mmol/L). The difference in paired samples of NaF plasma and Gel Barrier tubes serum glucose was 3.2 mg/dL with a CI of 2.5 - 3.9 mg/dL (Mean: 0.18 mmol/L; CI: 0.14 - 0.22 mmol/L). Lastly, the mean difference in Citrate-buffered plasma and serum Gel barrier tubes for 46 paired samples was 6.0 mg/dL with a CI of 5.2 - 6.7 mg/dL (Mean: 0.33 mmol/L; CI: 0.29 - 0.37 mmol/L).

Conclusions

Following guidelines, Citrate-buffered/NaF tubes demonstrate efficacy as glucose stabilizers. When compared to NaF tubes alone within a 30-minute timeframe, the mean difference between the two types of tubes was 2.8 mg/dL. Although NaF tubes are no longer recommended for glucose testing in plasma, they still outperform gel barrier serum tubes by 3.2 mg/dL. Furthermore, compared to citrate/NaF Plasma, serum glucose levels were on average 6.0 mg/dL lower. The preanalytical sample stage poses a significant obstacle to its reliable use for diagnostic or monitoring purposes. Laboratories should consider transitioning to Citrate/NaF tubes, or employ mathematical corrections if utilizing gel separator tubes for glucose testing in their established preanalytical process.
A-063 Correlation of 1,5-anhydroglucitol (AG) with A1c: understanding this relationship in terms of an established physiological model for AG mass balance as a function of [glucose]
Authors: Stickle D , Delikkaya B N , Kyle P B
Published: October 2024

Background

Diet-derived 1,5-anhydroglucitol (AG) is an unmetabolizable glucose analogue present in plasma (reference interval: 7.4-32.5 µg/mL). In diabetes, hyperglycemia can accelerate AG excretion, producing an inverse relationship between A1c and AG. There are no established guidelines regarding use or interpretation of AG in diabetes, but it is often described as being useful for detection of short-term variation in [glucose]. We examined AG usage at our institution, and, additionally, analyzed the information content of AG as derived from an established model for the relationship between AG and [glucose].

Methods

Medical records were scanned for all combined orders for AG and A1c between September 2020 and August 2023. Estimated average glucose (eAG) was calculated from A1c [PMID: 18540046]. AG vs. A1c data were compared to calculations for AG vs. eAG using an established physiological model for AG mass balance [PMID: 9357814].

Results

Among 104 AG measurements, there were 93 AG/A1c measurement pairs (see Figure). 70% had elevated A1c (n=65). 43% had decreased AG (n=40), all with elevated A1c. Among all AG/A1c pairs, 66% (closed points; n=61) were within the boundaries of model calculations for AG when assuming a simple steady-state [glucose] equal to eAG, a normal glomerular filtration rate, and a normal AG ingestion rate. AG outside of these boundaries (34%; open points, n=32) were almost entirely above the upper boundary (32%; n=30), where results are consistent either with increased AG ingestion rate, decreased glomerular filtration rate, or a discrepancy between eAG and A1c. Only two points (2.2%) were compatible with interpretation of variation in prevailing glucose from eAG.

Conclusions

For our data, paired AG/A1c measurements were in majority well characterized by a physiological model based simply on steady-state (invariant) [glucose] equal to eAG as derived from A1c alone. Only a small fraction of AG results suggested possible variation in [glucose].
A-065 The CDC HoSt Certification Requirements Have Been Met for More Than Four Years by the Atellica IM, ADVIA Centaur Testosterone II and Dimension Vista LOCI Total Testosterone Immunoassays
Authors: Abou-Diwan C , Parker N , Pagliaro S , Lewisch S , Barczak E , Shalhoub V , Oduaran E , Freeman J
Published: October 2024

Background

The CDC Hormone Standardization (CDC HoST) Certification Program, is traceable to the primary testosterone Standard National Measurement Institute (NMI) M914. The Atellica® IM, ADVIA Centaur® Testosterone II (TSTII) and Dimension Vista® LOCI Total Testosterone (TTST) assays are enrolled in the program. Certification is a yearlong process of 40 blinded samples from the CDC, 10 for testing each quarter. If 4 consecutive quarters meet bias acceptance criteria of ± 6.4%, CDC certification is achieved.

Methods

Initially, to standardize the assay approximately 120 samples were obtained from CDC with CDC HoST ID-LC-MS dose values to value assign master curve standards. Multiple ADVIA Centaur TSTII reagent lots were tested with CDC patient samples. Internal master curve standards were assayed as unknowns and dose values assigned using the RLU (system generated units-Relative Light Units) to CDC ID-LC-MS dose relationship. For TSTII (2019- 2023), after standard value assignment, at least 179 CDC blinded samples were tested across all platforms. Each quarter, 10 blinded samples were tested in duplicate over 2 days. Similar procedures were followed for TTST. Results were analyzed by the CDC.

Results

Correlation between the CDC assigned values and Atellica IM, ADVIA Centaur, and ADVIA Centaur CP TSTII assay results was strong across all quarters from 2019 to 2023 combined. TTST results were strong for 2023. Mean bias between TSTII and TTST results and CDC reference values was consistently <6.4%. This enabled the TSTII assays to be CDC certified for a fourth consecutive year, and TTST for 2023. The table presents TSTII (2019-2023) and TTST (2014-2023) results.

Conclusions

The TSTII assay consistently achieved CDC certification from 2019 to 2023, while the TTST assay was initially certified in 2014. Siemens Healthineers is the only testosterone immunoassay manufacturer to be currently certified, the TSTII assay has achieved certification for four consecutive years.
A-084 Performance evaluation of Sentinel Diagnostics’ Ammonia Ultra assay on Beckman Coulter AU/DxC AU Systems
Authors: Brambilla S , Barazzutti A , Bordonaro F , Coghi A , Fusi E , Lucini R , Santos Cruz J
Published: October 2024

Background

The analytical performances of the Ammonia Ultra assay for in vitro quantitative enzymatic determination of Ammonia in human plasma have been evaluated on Beckman AU/DxC AU Systems. Ammonia, derived from the amino acids catabolism and from the action of intestinal bacteria on dietary proteins, is converted to non-toxic urea by the liver. An excess of ammonia can have toxic effects on the Central Nervous System with possible neurological disturbances. Elevated ammonia levels can also be observed in severe liver failure as may occur in Reye’s syndrome, viral hepatitis or cirrhosis.

Methods

Ammonia, in the presence of glutamate dehydrogenase (GLDH), combines with alpha-ketoglutarate and NADH to yield glutamate and NAD+. The decrease in 340 nm absorbance (NADH → NAD+) is proportional to the ammonia level in the examined plasma. The reagent contains excess of lactate dehydrogenase (LDH) to rapidly reduce endogenous pyruvate and avoid its interference with the assay system. Performances evaluation have been done following current CLSI guidelines protocols.

Results

3 calibrator lots and 2 reagent lots have been used for testing. For each test and among different combinations of reagents and calibrators, worst case has been reported in the table.

Conclusions

Analytical performances of Ammonia Ultra assay on Beckman AU/DxC AU Systems meet the requirements for its use as quantitative determination of Ammonia in human plasma and make this assay very suitable for the routine measurement of this analyte.
A-099 Case Study of a Patient With Heterophile Antibodies Interfering with Both Competitive and Immunometric Assays
Authors: Palamalai V , Nwaukwe A , Ramirez R
Published: October 2024

Background

Immunoassay results may be affected by the presence of interfering substances including heterophile antibodies. These heterophile antibodies can cause either an increase or decrease in the result based on assay design and antibody target. We report a case study wherein we identified several analytes whose results were either increased or decreased by heterophile antibodies in a patient.

Methods

74 year male presented to Endocrinology with history of hypocalcemia and his previous lab tests were suggestive for idiopathic hypoparathyroidism, Hashimoto’s disease and Addison’s disease raising physician concern for a possible Type 1 autoimmune endocrinopathy. Cortisol was ordered (for an ACTH stimulation test for adrenal insufficiency); upon testing the post-stimulation cortisol result was higher than the analytical measurement range (AMR), and so the sample was diluted 1:2 and repeated. The repeat cortisol result after correction for the dilution factor was well within the AMR and prompted an investigation for an interfering substance. Serial dilution of analytes was performed and send-out testing for the same with another immunoassay from a different manufacturer and/or mass spectrometry method where available were done.

Results

The results for most analytes did not match with the reference lab results. Serial dilution showed non-parallelism in the results. For most analytes, after dilution of the sample by 1:4 or 1:8 times, the interfering substance was diluted enough to obtain a result matching the reference lab result.

Conclusions

Based on non-parallelism in serial dilution results, discordant results with other methods, and loss of interference after dilution it was determined that the most likely cause was a heterophile antibody. Formal testing using blocking antibodies was not done as it seemed that the reference lab used did not run our method and their assays were not affected by this particular heterophile antibody. Analysis of the assay designs and analyte results showed that competitive assays showed falsely high results, while immunometric assays showed falsely low results. The physician was contacted and the case discussed in detail and it was recommended that further testing on this individual be sent out to a reference lab using the alternate method or to use mass spectrometry based assays for further testing if needed. Today, the patient continues to have low calcium, high phosphate and an undetectable PTH suggestive of idiopathic hypoparathyroidism but his other endocrine functions are within normal limits.
A-100 Clinical Utility of Measuring Creatine Concentration in Erythrocyte
Authors: Nakahara T , Imada M , Kataoka H
Published: October 2024

Background

Shortened erythrocyte lifespan characterizes hemolytic anemia and impacts HbA1c values. Recently, erythrocyte creatine concentration (EC) measurement emerged as a new method to assess erythrocyte lifespan. However, literature reports conflicting findings regarding the association between erythrocyte lifespan and EC concentration. In our study, we noted low EC concentrations in renal diseases, typically linked to short erythrocyte lifespan, while iron deficiency anemia exhibited high EC concentrations. This contradicts established relationships, prompting a reevaluation of EC concentration assessment. The aim is to evaluate the clinical utility of EC concentration measurements by correlating them with various clinical parameters, including hematopoietic status.

Methods

EC concentrations were measured in 522 subjects (252 females, 270 males) aged 19 to 95 at Kawasaki Medical School Hospital. Medical records and laboratory test results from around one month before and after blood collection were used to create a database. Box-and-whisker plots illustrated EC concentration distribution for each disease, and scatter plots compared EC concentrations with laboratory parameters.

Results

EC concentrations were lower in renal diseases like Diabetes and Chronic Kidney Disease but higher in iron deficiency anemia (Fig. 1). Moreover, EC concentrations rose as hemoglobin concentrations declined, unaffected by CKD grade (Fig. 2).

Conclusions

While conventionally, high EC concentrations imply a short erythrocyte lifespan, our study noted the opposite trend. EC concentrations might not indicate erythrocyte lifespan but instead reflect hemoglobin synthesis. Investigating EC concentration's relationship with factors like iron and vitamin B12 involved in hemoglobin synthesis may unveil new clinical applications.
A-103 Analytical Performance Evaluation of Plasma NfL in a Clinical Diagnostic Laboratory
Authors: Frykman H , Mammel A , Pradip G , Hallett K , Mousavi A
Published: October 2024

Background

Neurofilament light chain (NfL) is a neuron-specific intermediate filament that is released at a consistent low level in normal individuals and increases with age and axonal injuries. NfL is a neurodegeneration biomarker in Alzheimer’s disease (AD), multiple sclerosis, stroke, traumatic brain injury and other neurodegenerative diseases (NDD). Here, we report the analytical performance of plasma NfL using high-sensitivity methodology in a clinical diagnostic laboratory.

Methods

The analytical performance, encompassing precision, detection limits, interference, and linearity, was evaluated. Plasma NfL levels were measured between July and October 2023 at Neurocode USA in Bellingham, WA, using a single Lumipulse G1200 instrument following CLSI guidelines, particularly for the utilization of the Fujirebio NfL Blood RUO assay as a laboratory-developed test for clinical analysis. A total of 100 healthy control samples, near the age of AD onset, were used to validate the reference ranges.

Results

The average plasma NfL concentrations varied from ≤ 8.4 to ≤ 37.9 ng/L among healthy individuals aged 20 to 80 years. The Plasma NfL assay exhibits analytical measurements, including a limit of blank (LoB) of 0.75 ng/L, a limit of detection (LoD) of 1.99 ng/ml, and a limit of quantification (LoQ) of 3.96 ng/L. Its linearity ranges from 11.08 to 741.58 ng/L, with intra-laboratory precision ≤ 9% CV. Stability is maintained at 4⁰C for ≤ 72 hours, at room temperature for ≤ 4 hours, at -20⁰C for ≤ 4 weeks, and at -80⁰C for ≤ 7 days, with freeze/thaw cycles tolerated within the specified time frame. Additionally, no interference was observed at the maximum concentrations tested for bilirubin, hemoglobin, and intralipid.

Conclusions

With a reference range between ≤ 8.4 to ≤ 37.9 ng/L and exceptional analytical performance, the measurement of plasma NfL on a state-of-the-art instrument using CLSI guidelines, can be useful in the diagnosis and monitoring of AD and other NDD.
A-110 Analytical Performance Evaluation of Vitros® Immunodiagnostic Products Intact PTH II Assay
Authors: Hirsch B M , Gardner A , Potter L , Fish R , Woeller E , Atienza J , Ding Q
Published: October 2024

Background

Intact parathyroid hormone (iPTH) is indicated to aid in the diagnosis of hyperparathyroidism, hypoparathyroidism, differential diagnosis of hypocalcemia or hypercalcemia and for intraoperative measurement of iPTH levels. Studies were conducted to evaluate the analytical performance of the Vitros Immunodiagnostic Products Intact PTH II (Vitros iPTH II) assay by determining limit of detection (LoD), limit of quantitation (LoQ), and precision. A method comparison of the Vitros iPTH II assay against the Roche Elecsys PTH assay was also conducted.

Methods

The LoD and LoQ were determined consistent with CLSI EP17. Precision was evaluated consistent with CLSI EP05 using six patient pools for 20 days. Repeatability was determined using two replicates per run. Within-lab precision was determined using a single reagent lot and a single calibration. A quantitative comparison between the Vitros iPTH II assay on a Vitros 3600 system and the Roche Elecsys PTH assay on a Roche Cobas 8000 system was conducted in accordance with CLSI guideline EP09 using 206 endogenous patient samples. Samples were selected to cover the full measuring interval and were tested over a total of six non-consecutive days.

Results

The LoD for the Vitros iPTH II assay was determined to be 1.7 pg/mL. The claimed LoQ was determined using a precision profile approach with a %CV limit of 20% and set at 1.7 pg/mL. For mean parathyroid hormone (PTH) concentrations ranging from 15.9 to 4656 pg/mL, repeatability (within-run) percent coefficient of variation (%CV) ranged from 0.8% to 1.4% and within-lab %CV ranged from 1.5% to 3.0%. The method comparison of the Vitros iPTH II assay versus the Roche Elecsys PTH assay yielded a correlation coefficient of 0.991 and a Passing-Bablok regression slope of 1.01 and intercept of 0.3.

Conclusions

The Vitros iPTH II assay demonstrated acceptable analytical performance in these studies, with high correlation and close agreement to the Roche Elecsys PTH assay.
A-112 Reference Intervals for Serum Concentrations of N-Terminal Propeptide of Type-I Procollagen (PINP) for Greek Adult Population
Authors: Makris K , Trifonidi I , Tournis S , Chronopoulos E
Published: October 2024

Background

PINP is a sensitive indicator of the synthesis of type-I collagen. Serum PINP levels are affected by changes in bone metabolism and is a useful indicator of disease activity in Paget's disease, bone metastases of osteoblastic nature and in monitoring osteoporosis treatment. To interpret PINP, method and population specific reference intervals are needed. We aimed to determine reference intervals for serum concentrations of PINP for the Greek adult population.

Methods

We collected samples from 431 apparently healthy Greeks (140 men as well as 150 pre- and 139 post-menopausal women), who volunteered to participate in our study. Data on socio-demographic characteristics, medical histories and medications were collected and subjects with conditions or receiving medications that affecting bone metabolism were excluded. Dual-energy x-ray absorptiometry (DXA) used to measure bone mineral density (BMD) in all participants. All blood collections were performed in the morning after overnight fast. Measurements were performed by an automated chemiluminescent immunoassay on the Maglumi-X3 analyzer (Snibe, Shenzhen, China). This method measures the total-PINP in serum. The reference interval was defined as the central 95% range and determined according to CLSI guide C28-A3 using the MedCalc Software

Results

The table summarizes our results. DXA results revealed that 348 participants had normal BMD, 74 had osteopenia and 9 had osteoporosis which excluded from analysis. Since our data were not normally distributed (Shapiro-Wilk test) in any group and after the exclusion of outliers (Tukey test), we used the non-parametric method suggested by the CLSI guide in order to determine the reference intervals. Multiple regression analysis revealed that sex and menopausal status were factors affecting PINP values.

Conclusions

We provide reference intervals for the determination of PINP concentrations in serum for the Greek adult population using an automated immunoassay. Our data may aid to interpret bone turnover in the Greek adult population.
A-118 Sigma Metric Performance of Chemistry Assays on 4 Instrument Systems
Authors: Berman M , Dechert J
Published: October 2024

Background

Chemistry panels play a crucial role in determining a person’s general health and well-being. These tests evaluate electrolyte balance and the status of several major organs. The Comprehensive Metabolic Panel (CMP) and Lipid Panel constitute approximately 87% of the blood tests prescribed in medical laboratories. Laboratories monitor assay performance by performing proficiency testing using quality controls (QC). College of American Pathologists (CAP) data is useful for laboratories to compare their proficiency testing performance to other laboratories and instrument systems. Sigma metrics serve as a valuable tool for laboratories to assess the quality and accuracy of their tests. Sigma scores vary from 0 to 6, with the 6 score designated as world-class performance, 5 as excellent, 4 as good, 3 as marginal, and 2 as poor. The analytical performance of 16 clinical assays from Abbott, Beckman, Roche, and Siemens instrument systems were compared using Sigma metrics.

Methods

Sigma metrics of 16 chemistry analytes were compared across 4 instruments system using CAP data from three reports (C-A 2023, C-C 2023 and C-B 2022). The 4 systems evaluated were Abbott Alinity ci, Beckman AU, Roche COBAS c500/c303 and Siemens Atellica CH. Method imprecision was estimated for each assay using the cumulative coefficient of variation or standard deviation for each assay at a single QC concentration and calculating the average sigma. Since sigma levels can be concentration-dependent, an equivalent CAP sample concentration was chosen for each instrument system evaluation. Method bias was estimated by evaluating each method QC mean to the peer group mean. Sigma values were calculated for each method as Sigma = (TEa - |Bias|) / Precision using the allowable total error from 2014 Clinical Laboratory Improvement Amendments (CLIA) proposed acceptance limits. Average Sigma values were generated for each analyte and graded as an optimal Sigma score.

Results

The sigma scores varied across assays and instrument systems. Abbott demonstrated the best overall performance. Specifically, the Abbott Alinity system had the highest number (7/16, 44%) of assays at 5 sigma or higher, with Siemens showing the lowest number of assays at 5 Sigma or higher (1/16, 6%). Of the 16 assays evaluated, Abbott has the fewest assays at or below the 3 sigma threshold (5/16) when compared to Roche (7/16), Beckman (7/16), and Siemens (9/16). Sigma scores were comparable between the Abbott ARCHITCT and Alinity clinical chemistry systems.

Conclusions

Sigma metrics are useful in assessing the performance of clinical assays. Assays with high Sigma have better performance due to lower imprecision and higher accuracy. None of the instrument systems demonstrated optimal six sigma performance for all analytes. However, Abbott demonstrated the best overall performance.
A-123 Comparative Assessment of Unmanned High-Speed Aerial Vehicles in Medical Logistics: Blood Sample Transportation Amidst Weather Variability
Authors: Stierlin N R , Hemmerle A , Risch M , Risch L
Published: October 2024

Background

Drones, as an innovative technology, hold transformative potential in the field of medical logistics, especially in the transportation of sensitive medical materials like blood samples. This study aimed to assess and compare the impact of high-speed drone transportation with conventional car transportation on the integrity and preanalytics of blood samples, taking into account various blood materials and analytes.

Methods

Blood samples, including EDTA whole blood, serum, and plasma anticoagulated with Citrate and Lithium-Heparin transported as whole blood, were subjected to transportation via both drone and car. Drone flights were tested under diverse weather conditions (ranging between 4 and 20 degrees Celsius), and results were compared to samples stored without transportation. The maximum drone speed exceeded 100 km/h. A total of 28 analytes were tested on Serum, 20 on EDTA, 26 on Lithium-Heparin, and 5 on Citrate blood. Statistical analyses were performed using Passing Bablok and Bland-Altman methods.

Results

For Serum samples, the correlation coefficient (r) ranged from 0.830 to 1.000, and slopes varied from 0.913 to 1.111. Five analytes (total bilirubin, Calcium, Ferritin, Kalium, and Sodium) exhibited discrepancies between the negative control and the transported sample, with r lower than 0.800, slopes not between 0.8 and 1.2, and mean (%) not between +/- 10%. However, no significant differences were noted between drone and car transportation.

Similar patterns emerged for EDTA, Lithium-Heparin, and Citrate samples, with r ranging from 0.829 to 0.997, 0.939 to 0.998, and 0.830 to 1.000, respectively. Slopes ranged from 0.956 to 1.051, 0.938 to 1.085, and 0.913 to 1.111. Despite identifying a few discrepancies in specific analytes, no significant differences were observed between transportation methods.

Conclusions

n comparison to transportation by car, drone transportation of blood samples did not lead to alterations in concentrations of commonly used analytes. Notably, instances of differences before and after transportation were attributed to the transportation process itself rather than the mode of transportation. This suggests that the use of drones for medical sample transport can be deemed comparable to, if not superior to, traditional car transportation methods.
A-124 Sustainable Transport: Assessing Environmental Impact in Medical Sample Transit via Drones and Vehicles
Authors: Stierlin N R , Hemmerle A , Risch M , Risch L
Published: October 2024

Background

This research explores the ecological implications associated with different methods of transporting medical samples, specifically focusing on drones, combustion cars, and electric cars within two laboratories in central European countries. With the primary goal of assessing and comparing CO2 consumption, delivery time, and overall environmental impact, the study aims to provide a basis for adopting sustainable practices in healthcare logistics.

Methods

The transportation of medical samples occurred between two laboratories in the Principality of Liechtenstein and Switzerland, utilizing authorized aerial and road routes. Various weather conditions and distances were considered for sample transports using different vehicles (8 combustion cars, two electric cars, and one drone model). Energy consumption was documented, and the CO2 footprint was calculated based on data from the Swiss Federal Office for the Environment (FOEN) for both imported and renewable electricity. Comparative analyses were conducted to quantify the environmental impact of each transportation method.

Results

In terms of CO2 footprint, combustion cars exhibited a CO2 release of 159.5 g/km, while electric cars showed 3.43g (2.15 to 4.08% of combustion cars). Drones demonstrated a minimal 0.09g CO2 emission per kilometer (0.066% of combustion car CO2 emission; 2.6% of electric car CO2 emission). The distance traveled by drones was significantly shorter (16.7% to 50%). Additionally, the efficiency of drone transport was emphasized by its ability to avoid traffic jams and associated detours, resulting in time savings ranging from 31.25 to 50% per delivery when comparing transport times during rush hour and regular hours in the selected setting.

Conclusions

The integration of drone technology emerges as a crucial strategy for establishing a “green laboratory.” The substantial reduction in CO2 emissions and enhanced delivery efficiency position drone transport as a sustainable and operationally effective solution for medical sample logistics, offering shorter delivery times. These findings highlight the potential for transformative change in healthcare logistics, aligning with the global shift towards sustainability and green practices.