bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal serological measures of common infection in the Avon Longitudinal Study of Parents and Children cohort
Authors: Mitchell Ruth E. , Jones Hannah J. , Yolken Robert H. , Ford Glen , Jones-Brando Lorraine , Ring Susan M. , Groom Alix , FitzGibbon Sophie , Smith George Davey , Timpson Nicholas John 
Published: July 2018

Antibodies against pathogens provide information on exposure to infectious agents and are meaningful measures of past and present infection. Antibodies were measured in the plasma of children that are the offspring in a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Plasma was collected during clinics at age 5, 7, 11 and 15 years. The antigens examined include: fungal (Saccharomyces cerevisiae); protozoan (Toxoplasma gondii and surface antigen 1 of T. gondii); herpes viruses (cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1); common colds (influenza virus subtypes H1N1 and H3N2); other antigens (measles); animal (feline herpes virus, Theiler’s virus); bacteria (Helicobacter pylori); dietary antigens (bovine casein alpha protein, bovine casein beta protein). Alongside the depth of data available within the ALSPAC cohort, this longitudinal resource will enable the investigation of the association between infections and a wide variety of outcomes.
Multisourcing and Miscoordination in Supply Chain Networks
Authors: Bimpikis Kostas , Fearing Douglas , Tahbaz-Salehi Alireza 
Published: July 2018

This paper studies sourcing decisions of firms in a multitier supply chain when procurement is subject to disruption risk. We argue that features of the production process that are commonly encountered in practice (including differential production technologies and financial constraints) may result in the formation of inefficient supply chains, owing to the misalignment of the sourcing incentives of firms at different tiers. We provide a characterization of the conditions under which upstream suppliers adopt sourcing strategies that are suboptimal from the perspective of firms further downstream. Our analysis highlights that a focus on optimizing procurement decisions in each tier of the supply chain in isolation may not be sufficient for mitigating risks at an aggregate level. Rather, we argue that a holistic view of the entire supply network is necessary to properly assess and secure against disruptive events. Importantly, the misalignment we identify does not originate from cost or reliability asymmetries. Rather, firms’ sourcing decisions are driven by the interplay of the firms’ risk considerations with nonconvexities in the production process. This implies that bilateral contracts that could involve under-delivery penalties may be insufficient to align incentives. The e-companion is available at https://doi.org/10.1287/opre.2017.1708 .
Cascade Screening for Familial Hypercholesterolemia: PCR Methods with Melting-Curve Genotyping for the Targeted Molecular Detection of Apolipoprotein B and LDL Receptor Gene Mutations to Identify Affected Relatives
Authors: Pandey Sarojini , Leider Michaela , Khan Mike , Grammatopoulos Dimitris K 
Published: July 2018

Abstract

Background
A key objective of the UK National Institute for Health and Care Excellence (NICE) pathway for diagnosis of familial hypercholesterolemia (FH) is the identification of affected relatives of index cases through cascade screening. At present, there is no systematic appraisal of available methodological options to identify the appropriate diagnostic testing protocol that would allow cost-effective cascade genetic screening. The majority of FH-causing mutations identified in the LDL receptor (LDLR) or apolipoprotein B (APOB) genes are single-nucleotide changes. This pattern of mutations suggests that PCR methods using melting curve–based genotyping might offer a convenient methodological approach for screening relatives.

Methods
We developed and validated one-tube PCR methods for the mutations APOB c.10580G&gt;A (p.Arg3527Gln), LDLR c.1474G&gt;A (p.Asp492Asn), and c.2054C&gt;T (p.Pro685Leu) and 3 novel LDLR mutations identified in the Coventry and Warwickshire population: LDLR c.1567G&gt;C (p.Val523Leu), c.487dupC (p.Gln163Profs17), and c.647G&gt;C (p.Cys216Ser).

Results
These methods successfully amplified target sequence from genomic DNA extracted from either peripheral blood or saliva. They also demonstrated acceptable analytical performance characteristics (specificity of amplification, repeatability, and reproducibility) over a wide range of DNA concentrations and purity. This approach was used for cascade testing of relatives of index FH cases with confirmed mutations and identified family members with high plasma LDL cholesterol as heterozygous for disruptive alleles.

Conclusions
Our study generates proof-of-concept evidence of methods suitable for detecting single nucleotide substitutions and insertions that can deliver reliable, easy, low-cost, and rapid family screening of FH patients and can be adopted by nonspecialist molecular diagnostic laboratories.
Assessment of FUS-200 Performance: Comparison with Quantitative Urine Culture Shows that Identifying the Right Cutoff for Optimizing Analyzer Performance Is Challenging
Authors: Gras Jérémie M , Henry Nathalie , Othmane Myriam , Vranken Guido R 
Published: July 2018

Abstract

Background
Urine sediment analysis is a frequently ordered test, since it permits screening for many clinical conditions. Here, the technical and bacteriuria diagnostic performance of FUS-200, a new sediment analyzer, was assessed.

Methods
Carry-over, imprecision, and linearity were measured according to CLSI protocols. FUS-200 was compared to sediMAX™, our current laboratory analyzer, in terms of particle recognition/counting in 382 fresh urine samples, and bacteriuria diagnosis was based on white blood cell (WBC) and bacteria counts in a subgroup of the same samples. In the diagnostic study, quantitative bacterial cultures served to classify the samples as bacteria-positive or bacteria-negative.

Results
FUS-200 did not show carryover for the particles tested. Total imprecision for red blood cells (RBCs) and WBCs in positive controls was 3.6%–10.5% and complied with European guidelines. RBC and WBC recovery was linear. When FUS-200 particle counts were edited by a reviewer, concordance with sediMAX improved for epithelial cells, yeast, and crystals, and recognition of casts and crystals improved. FUS-200 concordance with sediMAX varied between 97% for yeast and 58% for bacteria and was satisfactory. FUS-200 detected bacteriuria better than sediMAX (P = 0.004). FUS-200 WBC and bacteria cutoff values based on the Youden index detected bacteriuria better than manufacturer cutoffs. The best sensitivity with which FUS-200 detected bacteriuria was 79%.

Conclusions
Although casts and crystal recognition should be improved, the overall technical performance of FUS-200 was acceptable to good. FUS-200 exhibited good screening accuracy for bacteria and WBC. Editing only mildly influenced FUS-200 outcomes.
Stability of Biochemical Components in Blood Samples Transported by Tempus600/Sysmex GLP Robot Reception System
Authors: Andersen Ida Boegh , Mogensen Nina , Brandslund Ivan 
Published: July 2018

Abstract

Background
The Department of Clinical Immunology and Biochemistry, Lillebaelt Hospital, Denmark, and TIMEDICO invented and developed the Tempus600®, a pneumatic tube system (PTS). This system is only 2.5 cm in diameter and sends blood tubes directly, without packing before transport. Request forms need not be enclosed, since samples are labeled with patient and barcode ID. At the end of the pipes, a robot receives and places the tubes onto a GLP transport system after the principle of “first in, first out” (FIFO), whereafter the tubes are delivered to centrifuges and analytical equipment. The whole system has decreased the total turnaround time (ToTAT) from 2 to 3 h to &lt;60 min. The aim of the study was to validate the Tempus600/GLP robot system for the 89 most frequent or critical components.

Methods
Two sets of blood samples were drawn from 100 patients. One set was sent by the Tempus600/GLP robot system, and the other was couriered directly to the laboratory for analysis. Results were compared using difference plots.

Results
The results for 85 of the components did not deviate from the optimized fast courier reference transport more than could be expected by the analytical variation. O2 saturation, oxyhemoglobin, and partial pressure of oxygen (P o 2) deviated considerably from a clinical point of view. Partial pressure of carbon dioxide (P co 2) results were clinically acceptable for assessing patients with obstructive lung disease for hypercapnia.

Conclusions
The Tempus600/GLP robot system can be used for transport of the majority of routinely used analytical tests.
Quality Monitoring Approach for Optimizing Antinuclear Antibody Screening Cutoffs and Testing Work Flow
Authors: Tacker Danyel H , Perrotta Peter L 
Published: July 2018

Abstract

Background
An antinuclear antibody (ANA) testing strategy involving enzyme immunoassay (EIA) screening that reflexed to immunofluorescence assay (IFA) was implemented, monitored, and optimized for clinical utility.

Methods
The clinical utility, test performance, and workload implications of various ANA testing strategies were compared during the following study phases: (a) Preimplementation (n = 469) when IFA was used for all ANA screening, (b) Verification (n = 58) when EIA performance was confirmed, (c) Implementation (n = 433) when a reflexive strategy (EIA screen/IFA confirmation) was implemented, and (d) Postimplementation (n = 528) after the reflexive strategy was optimized. Sequential samples were captured in the Preimplementation, Implementation, and Postimplementation phases for clinical performance evaluation.

Results
Clinical performance of the EIA screen, per ROC analysis yielded area under the curve (AUC) of 0.846 in the Implementation phase and increased to 0.934 Postimplementation (P &lt; 0.01); AUC for IFA similarly increased, from 0.678 to 0.808 (P = 0.05). The reflexive testing strategy increased screening sensitivity from 61% Preimplementation (IFA) to 98% (EIA) at Implementation and was maintained after optimization (98%, Postimplementation). Optimization decreased the false-positive rates for both EIA (from 40% to 18%) and IFA (18% to 8%) and was associated with reductions in daily full-time equivalent (by 33%) and IFA slide use (by 50%).

Conclusions
Continuous quality monitoring approaches that incorporate sequential data sets can be used to evaluate, deploy, and optimize sensitive EIA-based ANA screening methods that can reduce manual IFA work without sacrificing clinically utility.
Interassay Comparison of the Tumor Markers CA125, CA15.3, and CA27.29
Authors: Winston-McPherson Gabrielle N , Merrill Anna E , Lo Sheng-Ying , Hoofnagle Andrew N , Greene Dina N 
Published: July 2018

Abstract

Background
Cancer antigens 125, 27.29, and 15-3 (CA125, CA27.29, and CA15-3) are markers of ovarian and breast cancer. Comparing tumor marker results across methods is challenging because of the lack of harmonization. Documenting comparability of results is important.

Methods
Siemens Advia Centaur CA125 and CA27.29 assays were compared to their corresponding Beckman Coulter DxI CA125 and CA15-3 assays. The interassay bias was determined and the manufacturer-recommended reference intervals were evaluated.

Results
The DxI CA125 assay demonstrated an overall positive 29% bias relative to the Centaur CA125 assay. The DxI CA15-3 assay demonstrated an overall negative 65% bias relative to the Centaur CA27.29 assay. For patients with multiple comparisons during the study period, the trend of results over time was similar across both sets of assays. Implementing the manufacturer-recommended reference interval for the DxI CA125 assay increased the abnormal flagging rate by 4.5%. In contrast, implementing the manufacturer-recommended reference interval for the DxI CA15-3 assay decreased the abnormal flagging rate by 13.0%.

Conclusions
The overall trends for the majority of patients were similar. Therefore, despite the overall biases, transitioning tumor marker assays should not affect clinical interpretation of results.
Analytical Validation of Relative Average Telomere Length Measurement in a Clinical Laboratory Environment
Authors: Blauwkamp Marsha N , Fasching Clare L , Lin Jue , Guegler Karl , Hytopoulos Evangelos , Watson Drew , Harley Calvin B 
Published: July 2018

Abstract

Background
Average telomere length in whole blood has become a biomarker of aging, disease, and mortality risk across a broad range of clinical conditions. The most common method of telomere length measurement for large patient sample sets is based on quantitative PCR (qPCR). For laboratory-developed tests to be performed on clinical samples, they must undergo a rigorous analytical validation, currently regulated under CLIA.

Methods
Whole blood samples from 40 donors were used in the analytical validation of methods for relative average telomere length (rATL) measurement. Three technical replicate DNA samples were extracted from each whole blood sample and placed in three independent wells on a sample plate. Each of these sample plates was assayed 12 times during the validation process. The study was conducted over a 20-day period, once in the morning and once in the evening, using 3 different operators.

Results
Our process of rATL measurement beginning with DNA extraction followed by qPCR-based assay resulted in repeatability and reproducibility CV of &lt;5% and amplification efficiencies near 100%. The validated assay was used to establish a reference interval derived from 2 cohorts of individuals: (a) San Francisco Bay area (n = 504) and (b) a US cross-sectional, demographic population (n = 357).

Conclusions
We present advances in the establishment of a highly reproducible analytically validated process for determining rATLs in a CLIA laboratory environment.
Effect of Preanalytical Factors on the Stability of Maternal Serum Biomarkers and Calculated Risk for Trisomy 21, Trisomy 18, and Open Neural Tube Defect
Authors: Walker Brandon S , Barakauskas Vilte E , Grenache David G , Schmidt Robert L 
Published: July 2018

Abstract

Background
Biochemical prenatal screening tests are used to determine the risk of fetal aneuploidy based on the concentration of several biomarkers. The concentration of these biomarkers could be affected by preanalytical factors (PAFs) such as sample type (whole blood vs serum), storage time, and storage temperature. The impact of these factors on posttest risk is unknown.

Methods
Blood samples were collected from 25 pregnant patients. Each sample was divided into 24 aliquots, and each aliquot was subjected to 1 of 24 different treatments (2 sample types × 2 temperatures × 6 storage times). The impact of each PAF on calculated risk was estimated using mixed-effects regression and simulation analysis.

Results
PAFs were associated with statistically significant changes in concentration for some analytes. Simulation studies showed that PAFs accounted for 6% of the variation in posttest risk, and analytical imprecision accounted for 94% of the variation. We estimated that the background misclassification rate due to analytical imprecision is approximately 1.37% for trisomy 21 and 0.12% for trisomy 18. Preanalytical factors increased the probability of misclassification by 0.46% and 0.06% for trisomies 21 and 18, respectively.

Conclusions
Relaxing sample specifications for biochemical prenatal serum screening tests to permit analysis of serum samples stored for up to 72 h at room temperature or 4 °C as well as serum obtained from whole blood stored similarly has a small impact in calculated posttest aneuploidy risk.
Heart Fatty Acid Binding Protein for the Diagnosis of Myocardial Ischemia and Infarction
Authors: Collinson Paul O , Hersey Jennifer , Bray Rosalind , Gaze David , Lim Pitt , Firoozi Sami , Ntalianis Argyrios , Boa Frances , Prasad Abhiram 
Published: July 2018

Abstract

Objective
To establish the analytical performance of a heart fatty acid binding protein (HFABP) method suitable for routine clinical use and examine its role for the diagnosis of myocardial ischemia and myocardial infarction.

Methods
Analyses of HFABP were performed on an Advia 2400 (Siemens Healthcare Diagnostics). Imprecision, limit of detection (LOD), limit of blank (LOB), and linearity were assessed using standard methods. Stability was assessed at 4 °C, −20 °C, and with 3 repeated freeze-thaw cycles. Clinical diagnostic performance was assessed using chest pain in patients, with a final diagnosis according to the universal definition of myocardial infarction with cardiac troponin I (cTnI) measured on the Siemens Advia Centaur (cTnI Ultra method, 99th percentile 50 ng/L, 10% CV 30 ng/L). Ischemia was detected using sampling pre- and postangioplasty.

Results
LOD and analytical imprecision exceeded the manufacturer's specification (LOD 1.128 μg/L, 20% CV 1.3 μg/L, 10% CV 2.75 μg/L). Clinical diagnostic efficiency was less than cTnI. Addition of HFABP to cTnI produced a modest increase in diagnostic sensitivity at a cost of significant loss of specificity.

Conclusions
Although the test had excellent analytical performance, it did not contribute to the clinical diagnosis of patients with chest pain. HFABP appears to be a marker of myocardial infarction not myocardial ischemia.
Stability of Fibroblast Growth Factor 23 in Human Plasma
Authors: Cui Salena , Vaingankar Sucheta M , Stenger Anneke , Waikar Sushrut S , Leaf David E 
Published: July 2018

Abstract

Background
Given the important emerging field of fibroblast growth factor 23 (FGF23) biology, there is a growing need for reliable data on FGF23 assay characteristics. We therefore evaluated the effects of different processing and storage conditions on FGF23 stability, as well as the assay precision of FGF23 measurements using 2 commercially available FGF23 ELISA kits.

Methods
We measured plasma concentrations of intact FGF23 (iFGF23) and C-terminal FGF23 (cFGF23) in duplicate in 12 patients with a wide range of kidney function. We used blinded replicate samples to calculate the interassay CV for both assays. We processed the samples immediately after collection, after 6 h at 22 °C, or after 24 h at 4 °C. We also exposed samples to 0, 1, 2, or 3 freeze-thaw cycles.

Results
The interassay CVs for iFGF23 and cFGF23 were 5.2% and 7.2%, respectively. Delayed processing for either 6 h at 22 °C or 24 h at 4 °C had no significant effect on either iFGF23 or cFGF23, although a nonsignificant trend toward decreased iFGF23 concentrations was observed compared with immediate processing (23% relative decline in concentrations under both delayed processing conditions). Three freeze-thaw cycles had no effect on either iFGF23 or cFGF23 concentrations.

Conclusions
FGF23 measurements in human plasma are stable with delayed processing or after undergoing multiple freeze-thaw cycles.
Use of Dual-Force Aggregation as a Multiplexed, Rapid Point-of-Care Screening Method for White Blood Cell Counting from Whole Blood Samples
Authors: Nelson Daniel A , Hughes Jacob D , Engel Casey E , Haverstick Doris M , Landers James P 
Published: July 2018

Abstract

Background
Enumeration of blood cells is an integral metric for evaluating patient health and can be used to screen for a wide range of diseases and conditions. Conventional methods rely on large, expensive, and complicated instrumentation that requires trained technicians and is not amenable to point-of-care analysis. This work demonstrates the use of a multiplexed, bead-based assay for both rapid white blood cell (WBC) count screening and accurate, multiplexed WBC counts for point-of-care analysis.

Methods
Blood samples were lysed and diluted before being incubated with silica-coated magnetic particles under chaotropic conditions, a rotating magnetic field, and a source of agitation. The resulting bead aggregation was imaged and correlated to a known WBC count. After establishing standard curves, the WBC count for 18 whole blood samples were determined by this method and compared to values obtained conventionally.

Results
When the optimal dilution factor for lysis of whole blood samples was established, 17 of 18 samples (94.4%) were correctly screened and categorized as having high, typical, or low WBC count, while 14 of 18 samples were within 16% of the reported clinical values. The developed system provides analysis of 13 samples in &lt;3 min with a total analysis time of approximately 10 min (including incubation and dilution) and represents comparable throughput to conventional instrumentation, while providing point-of-care capability with reduced size (14 × 21 × 14 cm) and simplicity.

Conclusions
This work demonstrates the potential for a multiplexed, bead-based assay to be used as a rapid, point-of-care screening method for WBC counting from whole blood samples.
Serum Fibrosis Marker Panels FIB-4 Index and Aspartate Aminotransferase (AST)-to-Platelet Ratio Index (APRI) Are Equivalent to AST Alone at Predicting Liver Fibrosis in a Cohort of 1731 Patients Infected with Hepatitis C Virus
Authors: Drees Julia C , Wi Soora , Ready Joanna B , Dlott Richard S , Fetterman Barbara J , Seo Suk I , Pat Pauly Mary , Petrie Matthew S , Lorey Thomas S 
Published: July 2018

Abstract

Background
Efficient tools are needed to stage liver disease before treatment of patients infected with hepatitis C virus (HCV). Compared to biopsy, several studies demonstrated favorable performance of noninvasive multianalyte serum fibrosis marker panels [fibrosis-4 (FIB-4) index] and aspartate aminotransferase (AST)-to-platelet ratio index (APRI), but suggested cutoffs vary widely. Our objective was to evaluate FIB-4 index and APRI and their component tests for staging fibrosis in our HCV-infected population and to determine practical cutoffs to help triage an influx of patients requiring treatment.

Methods
Transient elastography (TE) results from 1731 HCV-infected patients were mapped to an F0–F4 equivalent scale. Each patient's APRI and FIB-4 index were calculated. Areas under the receiver operator curve (AUROCs) and false-positive and false-negative rates were calculated to retrospectively compare the performance of the indices and their component tests.

Results
The highest AUROCs for distinguishing severe (F3–F4) from mild-to-moderate (F0–F2) fibrosis had overlapping 95% CIs: APRI (0.77; 0.74–0.79), FIB-4 index (0.76; 0.73–0.78), and AST (0.74; 0.72–0.77). Cutoffs had false-negative rates of 2.7%–2.8% and false-positive rates of 6.4%–7.4% for all 3 markers.

Conclusions
AST was as effective as FIB-4 index and APRI at predicting fibrosis. Published cutoffs for APRI and FIB-4 index would have been inappropriate in our population, with false-negative rates as high as 11%. For our purposes, no serum fibrosis marker was sufficiently sensitive to rule-out significant fibrosis, but cutoffs developed for AST, FIB-4 index, and APRI all had specificities of 79.2%–80.3% for ruling-in severe fibrosis and could be used to triage 1/3 of our population for treatment without waiting for TE or liver biopsy.