bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physician judgment in clinical settings: methodological influences and cognitive performance
Authors: Dawson N V 
Published: January 2020

Abstract
Understanding the quality of physicians' intuitive judgments is essential in determining the appropriate use of their judgments in medical decision-making (vis-a-vis analytical or actuarial approaches). As part of this process, the quality of physicians' predictions must be assessed because prediction is fundamental to common clinical tasks: determining diagnosis, prognosis, and therapy; establishing monitoring intervals; performing screening and preventive maneuvers. Critical evaluation of predictive capabilities requires an assessment of the components of the prediction process: the data available for prediction, the method used for prediction, and the accuracy of prediction. Although variation in and uncertainty about the underlying data elements are often acknowledged as a source of inaccurate predictions, prediction also can be confounded by both methodological and cognitive limitations. During the past two decades, numerous factors have been recognized that may bias test characteristics (sensitivity and specificity). These same factors may also produce bias in intuitive judgments. The use of cognitive processes to simplify judgment tasks (e.g., the availability and representativeness heuristics) and the presence of certain biases in the judgment process (e.g., ego, regret) may present obstacles to accurate estimation of probabilities by physicians. Limitations on the intuitive use of information (cognitive biases) have been demonstrated in both medical and nonmedical decision-making settings. Recent studies have led to a deepening understanding of the advantages and disadvantages of intuitive and analytical approaches to decision making. Here, many aspects of the basis for this understanding are reviewed.
Analytical goals developed from the inherent error of medical tests
Authors: Ross J W , Fraser M D 
Published: January 2020

Abstract
Biological variation is inherent in all medical tests and is a major source of error in clinical test interpretation. We use inherent test error due to biological variability as the touchstone by which to validate the clinical acceptability of analytical goals. Analytical goals should consist of sets of complementary limits for total error, bias, and imprecision and a medical usefulness criterion (MUC) to ensure that the total error goal is met with stated certainty. We propose analytical goals that are limits for the total error of a measurement system, the joint capability of the process control procedures and the measurement process. Thus, the goals are the allowable analytical error for proficiency evaluation, internal process control, and the total error budget for design of method performance characteristics. We define MUC as the allowable maximum proportion of test diagnostic efficiency lost due to analytical error near medical decision points. MUCs &lt; 0.03 are not routinely clinically useful; MUCs &gt; 0.08 allow method performance characteristics that are undesirable for general clinical use. Using MUC = 0.05 and recommendations that imprecision not exceed one-half of the biological CV, we propose that fixed bias should not exceed one-fourth to one-third of the intraindividual biological CV of the analyte and that total analytical error should not exceed 1.25 to 1.40 times the biological CV. Modification of these analytical goals may arise for reasons of documented clinical practice or process stability. Our model quantifies in medical utility terms the results of such modifications.
Cholesterol--a model system to relate medical needs with analytical performance
Authors: Wiebe D A , Westgard J O 
Published: January 2020

Abstract
The evolution of cholesterol testing provides an example of a systematic approach that developed to relate the medical use of a laboratory test with the analytical performance requirements for that test. Laboratories today have the capability to perform cholesterol testing with the accuracy and precision necessary to meet medical needs. This statement can be made because (a) a standard diagnostic process has been established by the National Cholesterol Education Program; (b) an accuracy base is provided through a reference method that is readily available to manufacturers and laboratories; (c) the precision of analytical systems has been improved by manufacturers; (d) operating specifications for all such systems can be established, with statistical quality-control rules to ensure adequate within-run method performance; and (e) analytical performance is monitored by proficiency testing by using national quality requirements defined by CLIA '88 for acceptability. This cholesterol model provides a logical and scientific approach that should be applicable with other analytes to assure that the analytical performance of the laboratory test satisfies medical needs.
Linking medical needs and performance goals: clinical and laboratory perspectives on thyroid disease
Authors: Hay I D , Klee G G 
Published: January 2020

Abstract
Diagnosis and management of thyroid disease benefit substantially from close interactions between clinicians and laboratorians. Clinicians desire reliable tests for diagnosis and management of both hypothyroidism and thyrotoxicosis. Traditionally, multitiered testing has been used, beginning with an index of free thyroxine concentration, which, if abnormal, has been followed by basal thyrotropin (TSH) measurements (for hypothyroidism) or thyrotropin-releasing hormone-stimulated TSH measurements (for thyrotoxicosis). Improvements in analytical methods for TSH have made it practical to use basal TSH measurements in serum as the first-line test for thyroid disease. However, performance guidelines are needed, because not all TSH assays work well in this role. The performance guidelines developed by the American Thyroid Association are reviewed to illustrate how they help to assure consistent analytical testing. Further improvements in TSH assays (third- and fourth-generation assays), which support measurements down to 0.01 mlU/L and 0.001 mIU/L, may provide additional advantages for classifying thyrotoxic patients and monitoring thyroxine-suppressive therapy in patients with thyroid cancer. The potential advantages of these newer assays are illustrated with case examples. Additional analytical performance monitors are proposed to help ensure that these next-generation TSH assays meet the expanded clinical needs.
Analytical performance goals for measuring prostate-specific antigen
Authors: Fritsche H A , Babaian R J 
Published: January 2020

Abstract
We have assessed the feasibility of using fixed-limit criteria based on medical relevance and biological variation for evaluating the analytical performance of the prostate-specific antigen (PSA) test. The estimated within-subject variation of serum PSA is on the order of 10-20% at clinical decision points. The calculated performance goals of 5-10% CV are attainable with current immunoassay technology and agree with precision goals based on clinical experience and the current clinical use of the test. However, new clinical applications of PSA may require a degree of analytical performance that current methods may not be able to provide. The PSA model demonstrates the need for biologically based fixed-limit criteria for all tumor-marker tests.
Creatine measurement in serum and urine with an automated enzymatic method
Authors: Beyer C 
Published: January 2020

Abstract
I describe an automated enzymatic procedure to quantitate creatine in both serum and urine. In this assay, which requires no pretreatment of the sample, creatine kinase (CK; EC 2.7.3.2) and pyruvate kinase (EC 2.1.7.40) are used as auxiliary enzymes and lactate dehydrogenase (EC 1.1.1.27) is used in the indicator reaction. CK is also used as the starting reagent. Data obtained with the present method for creatine measurement in serum were compared with those from the Jaffé method and an enzymatic method: y = 1.13x - 7.58, SE = 4.48, and r = 0.925 (Jaffé); and y = 1.17x + 2.73, SE = 5.06, and r = 0.962 (enzymatic); for creatine measurement in urine: y = 0.63x + 39.74, SE = 296.7 and r = 0.719 (Jaffé). The present method provides improved precision: the total CVs for serum, determined by the present and comparative methods, respectively, were 3.5-8.9%, 8.2-43.0%, and 5.3-16%; for urine, the CVs were 3.3-5.1% and 9.6-21.2% for the present and comparative method, respectively. I established the normal reference interval as 13-74 and 13-89 mumol/L for creatine in serum, and as 175-700 and 150-1200 mumol/24 h for creatine in urine for men and women, respectively.
Europium-labeled oligonucleotides to detect point mutations: application to PIZ alpha 1-antitrypsin deficiency
Authors: Dahlén P , Carlson J , Liukkonen L , Lilja H , Siitari H , Hurskainen P , Iitä A , Jeppsson J O , Lövgren T 
Published: January 2020

Abstract
We describe a novel assay for detection of point mutations. The method combines the specificity and sensitivity of the polymerase chain reaction (PCR) and allele-specific oligonucleotides (ASO) with highly sensitive time-resolved fluorometry. ASO probes differing by a single base substitution and labeled with europium (Eu) chelates were hybridized in solution simultaneously with a biotinylated oligomer to a PCR-amplified nucleic acid fragment. The hybrids formed were then collected onto streptavidin-coated microtitration wells. Subsequently, the hybrids were washed under stringent conditions and the remaining ASO probe was measured in a time-resolved fluorometer. We discuss the strategy underlying the design of the Eu-labeled ASO probes for the solution hybridization assay. The method was applied to the detection of the Z-mutation in the alpha 1-antitrypsin gene. Evaluation of whole-blood samples spotted on Guthrie cards demonstrated successful accuracy of the method.
Trace elements determined along single strands of hair by inductively coupled plasma mass spectrometry
Authors: Yoshinaga J , Shibata Y , Morita M 
Published: January 2020

Abstract
Flow injection-inductively coupled plasma mass spectrometry has been evaluated for determining the distribution profile of trace elements along a single strand of hair. Hair was cut into several mm long sections from follicle to the distal end. Each section was solubilized in a capped 1.5-mL polypropylene tube with small volume of nitric acid (typically 50 microL) at room temperature. After dilution an aliquot (50 microL) was introduced into the mass spectrometer by flow injection. The limit of determination was typically 5-50 pg with 5-10% precision (CV), depending on the element examined; this corresponds to sub-microgram/g concentrations of these elements in hair segments. Recent exposure and intake history of individuals to thallium or mercury could be reconstructed by this system.
Determination of inorganic arsenic and its organic metabolites in urine by flow-injection hydride generation atomic absorption spectrometry
Authors: Hanna C P , Tyson J F , McIntosh S 
Published: January 2020

Abstract
A method has been developed for the determination of inorganic arsenic [As(III) and As(V)] and its organic metabolites (monomethylarsenic and dimethylarsenic) in urine by flow-injection hydride generation atomic absorption spectrometry. The nontoxic seafood-derived arsenobetaine and arsenocholine species were first separated by a solid-phase extraction procedure. The remaining sample was digested with a mixture of nitric and sulfuric acids and potassium dichromate, followed by attack with hydrogen peroxide. The resulting As(V) was reduced to As(III) with potassium iodide in hydrochloric acid before injection into the flow-injection manifold. The percentage analytical recoveries (mean +/- 95% confidence interval) of various arsenic species added to a urine specimen at 250 micrograms/L were 108 +/- 2, 112 +/- 11, 104 +/- 7, and 95 +/- 5 for As(III), As(V), monomethylarsenic, and dimethylarsenic, respectively. For the determination of arsenic in Standard Reference Material 2670 (toxic metals in human urine), results agreed with the certified value (480 +/- 100 micrograms/L). Analyses of samples for the Centre de Toxicologie du Quebec, containing seafood-derived species, demonstrated the viability of the separation procedure. Detection limits were between 0.1 and 0.2 microgram/L in the solution injected into the manifold, and precision at 10 micrograms/L was between 2% and 3% (CV). These preliminary results show that the method might be applicable to determinations of arsenic in a range of clinical urine specimens.
Platelet-poor plasma serotonin in normal and preeclamptic pregnancy
Authors: Middelkoop C M , Dekker G A , Kraayenbrink A A , Popp-Snijders C 
Published: January 2020

Abstract
We determined serotonin concentrations in platelet-poor plasma (PPP) from 11 preeclamptic pregnant women and 11 normal pregnant women by HPLC with electrochemical detection after a concentration step. Serotonin concentrations in PPP are very low in comparison with those in platelets, so it is very important to avoid in vitro release of serotonin from platelets. We therefore investigated three types of anticoagulants, the method of blood sampling, and the influence of whether the first or second 10 mL of blood is assayed. The type of anticoagulant proved to be important, K3-EDTA giving the best results. The serotonin concentrations in PPP from the preeclamptic pregnant women were significantly higher (P = 0.0001) than in the normal pregnant women: mean values +/- SD were 27.0 +/- 13.5 and 2.8 +/- 1.4 nmol/L, respectively. We suggest that the measurement of serotonin in PPP might be helpful in study of the role of serotonin in the development of preeclampsia.
Latex agglutination test for detecting antibodies to Treponema pallidum
Authors: Matsumoto M , Ishikawa F , Matsubayashi T , Nagao T , Inuzumi K , Araki H , Kawai K , Osato K 
Published: January 2020

Abstract
We have developed an automated latex agglutination test for Treponema pallidum (TPLA) for measurement of the concentration of treponemal antibodies in syphilitic sera. The assay needs neither a complicated pretreatment of the sera nor special techniques. Intra- and interassay precision studies showed high reproducibility. Potentially interfering substances, such as bilirubin, hemoglobin, triglycerides, and rheumatoid factor, did not affect the results. The results obtained with the TPLA test showed a strong correlation with those from conventional methods. This test for antibodies to T. pallidum may be useful for the mass screening of syphilitic infections.
Interference of polyclonal free light chains with identification of Bence Jones proteins
Authors: Hess P P , Mastropaolo W , Thompson G D , Levinson S S 
Published: January 2020

Abstract
We present a case in which kappa free light chains caused difficulty in interpreting classical urinary immunoelectrophoresis, but immunofixation electrophoresis (IFE) demonstrated the presence of a lambda-Bence Jones protein. Analysis of the urine by Ouchterlony double diffusion and IFE after gel-filtration chromatography showed that the difficulty was caused by the presence of large amounts of polyclonal free light chains. The workup also demonstrated that although IFE is the more sensitive and specific technique, IFE performed on concentrated urinary samples is especially subject to misinterpretation unless densely staining patterns are diluted and reassayed. This process of sample dilution provides a means for titrating antigen and antibody concentrations such that condition-specific patterns become visible on the gel. This workup also shows that, at some dilutions, polyclonal free light chains may migrate in the same manner as an oligoclonal band in a so-called ladder configuration. These bands were observed from both monomeric and dimeric fractions isolated by gel chromatography, consistent with reports that this pattern is largely linked to the isoelectric points of the molecules. We speculate that, in rare instances, the distinction between polyclonal and monoclonal kappa free light chains migrating as a ladder-banding pattern may be equivocal.
Urinary trans,trans-muconic acid determined by liquid chromatography: application in biological monitoring of benzene exposure
Authors: Lee B L , New A L , Kok P W , Ong H Y , Shi C Y , Ong C N 
Published: January 2020

Abstract
We describe a sensitive and specific high-performance liquid-chromatographic method for determining the benzene metabolite, trans,trans-muconic acid (ttMA) in urine by measuring ultraviolet absorbance at 265 nm. We mix 1 mL of urine sample with 2 mL of Tris buffer containing vanillic acid as internal standard (IS) and percolate this through a preconditioned ion-exchange column. After rinsing the column with phosphoric acid solution, acetate buffer, and deionized water, we elute the analytes with 2 mL of an equivolume solution of 1.5 mol/L sodium chloride and methanol. Of this, 5 microL is injected into the HPLC column. The mobile phase used consists of, per liter, 10 mL of acetic acid, 100 mL of methanol, and the rest 5 mmol/L sodium acetate. The flow rate was started at 1 mL/min and increased to 1.5 mL/min after 6 min. ttMA and IS were detected at 5.2 and 10.2 min, respectively. The lowest detection limit is 125 pg. Analytical recovery and reproducibility generally exceeded 90%. We validated the method with urine samples collected from normal persons and from refinery workers exposed to benzene concentrations &lt; 1 microL/L. The results show that urinary ttMA is a promising biological marker for risk assessment of low-concentration benzene exposure.
Quantitative measurement of duplicated DNA as a diagnostic test for Charcot-Marie-Tooth disease type 1a
Authors: Hensels G W , Janssen E A , Hoogendijk J E , Valentijn L J , Baas F , Bolhuis P A 
Published: January 2020

Abstract
Charcot-Marie-Tooth disease type 1 (CMT1) is a hereditary motor and sensory neuropathy. The autosomal dominant subtype is often linked with a large duplication on chromosome 17p11.2. The gene encoding the peripheral myelin protein PMP 22 (the critical gene in this subtype of CMT1) is located within this duplication. To detect this duplication in chromosomal DNA from individuals thought to have CMT1, we compared the hybridization signals of two DNA probes within this duplication (VAW412R3a and VAW409R3a) with the signal of a reference probe (E3.9). When duplication was present, the signals from the first two probes increased from 100% (for nonduplicated samples) to 145% and 142%, respectively. The day-to-day variance was 3.7% and 5.1%, respectively. We demonstrated this DNA duplication in 49 of 95 DNA samples from unrelated individuals thought to have CMT1. Moreover, because hereditary neuropathy with liability to pressure palsies (HNPP) is based on a DNA deletion in the same area of chromosome 17, this quantitative test may be useful in establishing the presence of HNPP. In a preliminary investigation, four unrelated patients with HNPP yielded test values of 63% and 54%, respectively, of those for nonduplicated samples (CV 19% and 18%, respectively; n = 4), suggesting a deletion in 17p11.2.
Sandwich enzyme immunoassay of cystatin C in serum with commercially available antibodies
Authors: Pergande M , Jung K 
Published: January 2020

Abstract
We developed a sandwich enzyme immunoassay for determining cystatin C in serum by using commercially available antibodies. We optimized each assay step (e.g., concentrations of coating rabbit anti-human cystatin C antibodies and horseradish peroxidase-conjugated antibodies) and studied the binding kinetics of antigen and antibodies. The within-assay CV was &lt; 5%, the between-assay CV was 8.8%, the detection limit was 0.9 microgram/L, and the assay can be performed within 2 h. Cystatin C concentrations in sera from men were significantly higher than in women (mean and SD: 2.14 +/- 0.31 vs 1.78 +/- 0.26 mg/L). We studied the cystatin C concentrations in sera of 31 outpatients with suspected kidney damages to characterize the behavior of this low-M(r) protein as a possible indicator for estimating the glomerular filtration rate. The correlation with the values obtained by a standard isotopic method involving 99mTc-diethylenetriaminopentaacetic acid was rs = -0.89. The diagnostic sensitivity of cystatin C was 88.2% of that of the standard isotope clearance method and better than those of the conventional serum indicators of reduced kidney function, beta 2-microglobulin (64.7%) and creatinine (52.9%).
Performance of Gem Premier blood gas/electrolyte analyzer evaluated
Authors: Jacobs E , Nowakowski M , Colman N 
Published: January 2020

Abstract
We evaluated a new analyzer designed for point-of-care testing of blood gases, sodium, potassium, ionized calcium, and hematocrit. The Gem Premier (Mallinckrodt) system has two components: the analyzer and a disposable cartridge. Analysis takes place in the cartridge, which contains the electrochemical sensors, the calibrants, the reagents, the sampling stylus, and the waste container. The system was evaluated for imprecision and accuracy. With aqueous control materials, total imprecision (CV) was: pH, 0.10-0.18%; PCO2, 3.16-5.78%; PO2, 2.92-4.85%; sodium, 0.82-1.44%; potassium, 1.35-1.48%; ionized calcium, 0.75-1.45%; and hematocrit, 1.13-1.83%. Accuracy of the system was assessed by split-sample comparison with the Radiometer ABL 330 blood gas analyzer for pH and blood gases, the Nova Stat Profile 5 for whole-blood electrolyte and hematocrit analysis, and the IL Phoenix for plasma electrolyte analysis. After outlier correction, regression statistics were excellent for all analytes except sodium, which demonstrated Sy[x values between 1.80 and 2.30 mmol/L and 0.85 &lt; or = r &lt; 0.90.
A reference preparation of creatine kinase BB isoenzyme
Authors: Mathieu M , Steghens J P , Hørder M , Moss D W , Colinet E , Profilis C 
Published: January 2020

Abstract
Creatine kinase (CK; EC 2.7.3.2) catalytic activity in serum is widely measured in clinical chemistry practice and provides information for diagnosis and follow-up in many pathological conditions affecting heart, muscle, and brain. Depending on the organ involved, the predominant CK isoenzyme in serum varies. However, routine methods measure total CK catalytic activity, and standardized methods for doing so have been recommended by the International Federation of Clinical Chemistry and by several national scientific societies. Many commercial kits for those methods are now available. With use of a reference material for CK, commercial reagents can be compared with standardized methods, improving confidence in the results. Here we present a reference preparation of CK consisting of the BB isoenzyme purified from human placentae. We describe the procedure of purification and the properties of the lyophilized preparation of CK-BB, which has been certified by the Community Bureau of Reference of the Commission of the European Communities under the designation CRM 299. The preparation can be used to calibrate assays of the catalytic activity of CK-MM and CK-MB, as well as CK-BB.