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PubMed1999

Testing for multiple species in fossil samples: an evaluation and comparison of tests for equal relative variation.

Tests for equal relative variation are valuable and frequently used tools for evaluating hypotheses about taxonomic heterogeneity in fossil hominids. In this study, Monte Carlo methods and simulated data are used to evaluate and compare 11 tests for equal relative variation. The tests evaluated include CV-based parametric bootstrap tests, modifications of Levene's test, and modified weighted scores tests. The results of these simulations show that a modified version of the weighted scores test developed by Fligner and Killeen ([1976] J. Am. Stat. Assoc. 71:210-213) is the only test that maintains an acceptable balance of type I and type II errors, even under conditions where all other tests have extraordinarily high type I error rates or little power.

Animals↗
PubMed1999

Diagnosis of perinatal TORCH infections.

Collectively, TORCH infections create more neonatal morbidity than early-onset group B streptococcal sepsis. Fortunately, the incidence of maternal infection by CMV or toxoplasmosis is low (2-10 per 1,000 births). There have been tremendous advances in direct antigen testing and in the sensitivity and specificity of IgG and IgM testing. Consistently, research laboratories show more accurate results than in the past. Unfortunately, commercial laboratories are using older, single-kit testing. The relatively poor degree of reliability can lead to unnecessary obstetric intervention or elective termination. Any positive pathogen-specific IgM on maternal serum should have additional confirmatory testing in a reputable research laboratory before any intervention. Direct antigen testing or multiple testing would seem to be appropriate for confirmation. This may include amniocentesis of fetal blood sampling. The research on the newer tests is based of the evaluation of blood from seriously immunocompromised subjects. Extrapolations of test accuracy to similar tests on healthy, pregnant women and their fetuses are likely to be in error. The application of these accurate tests to the obstetric population is a critical research need.

Cytomegalovirus Infections↗
PubMed1983

Response of pulmonary rapidly adapting receptors during lung inflation.

Studies were conducted to establish the factors that determine the response of canine pulmonary rapidly adapting receptors (RAR) during lung inflation. Inflations of the lung were performed at several constant rates during which the activity of individual RAR was counted. At each rate of inflation tested multiple identical tests were performed. The volume of each test inflation was controlled. Data obtained in all tests at each flow rate were averaged to give the mean response of the receptor at that rate of inflation. These studies indicate the major response characteristics of RAR during lung inflation in conditions of relatively constant lung mechanics. First, at a constant rate of inflation, the activity of RAR augments increasingly as the lung is expanded. Second, their activity is influenced markedly by the rate of inflation. However, this sensitivity is nonlinear. Specifically, at low rates of inflation increases in flow rate produce more marked augmentation of RAR firing than do identical increases in flow at higher rates of inflation. The major difference between receptors is in their threshold; however, this too is a function of flow rate. With increasing flow rate the threshold, whether measured as the inflation volume or transpulmonary pressure at which receptors begin to fire, declines. The response of receptors, however, with thresholds over the entire range show the major features discussed above. The present results provide quantitative information which are necessary to begin to eludicate the transduction properties of this receptor type.

Animals↗
PubMed1999

Laboratory diagnosis of heparin-induced thrombocytopenia.

The characteristics of the currently available platelet function assays (platelet aggregation, serotonin release, and flow cytometry) and enzyme-linked immunosorbent assays that quantitate antiheparin-platelet factor 4 antibody titers were studied using sera collected from clinically diagnosed heparin-induced thrombocytopenia patients, patients without heparin-induced thrombocytopenia, patients with platelet immune disorders other than heparin-induced thrombocytopenia, and normal individuals. The platelet aggregation assay was less sensitive than the serotonin release assay, which was less sensitive than the enzyme-linked immunosorbent assay (p < 0.001). Yet heparin-induced thrombocytopenia was identified by platelet aggregation assay in cases where the serotonin release assay and/or the enzyme-linked immunosorbent assay were negative. Patients with heparin-induced thrombocytopenia and thrombosis were more often positive than heparin-induced thrombocytopenia patients without thrombosis (p < 0.05). Positive platelet aggregation assay and serotonin release assay results were generally associated with a higher antibody titer; however, a minimum critical titer could not be identified. Over a 30-day period the percentage of positive responses did not change significantly even though clinical symptoms corrected in most heparin-induced thrombocytopenia patients. Multiple testing over several days enhanced the chance of detecting a positive, and combined results of the three assays further enhanced the positive response (p < 0.005). In patients without heparin-induced thrombocytopenia, false-positive results were obtained with the enzyme-linked immunosorbent assay. These data demonstrate that there is no direct correlation between the positive responses of these assays, that clinically positive patients can be missed by all assays, and the presence of antibody alone does not determine clinical heparin-induced thrombocytopenia. With these limitations, the combination of aggregation, serotonin release, and enzyme-linked immunosorbent assay testing with multiple samples offers the best chance of identifying a positive heparin-induced thrombocytopenia patient. Caution is advised for all assays as none is optimal.

Anticoagulants↗
PubMed1994

Automation and quality control in the coagulation laboratory.

Hemostasis is a balance between complex interactions of directly opposing systems (coagulation and fibrinolysis) with seemingly unrelated systems at both the enzymatic and cellular levels (platelets, endothelium, leukocytes). It should not be surprising that coagulation disorders often accompany many different disease states. Because the function of each protein involved in coagulation is now better defined, newer methodologies have been developed to assay them. In this regard, the hemostasis laboratory can take a two-step approach to diagnosis: global screening and targeted analysis. Several new global test systems provide more detailed, quantitative, and more physiologically relevant evaluations than earlier assays allowed. In addition, individual enzymes, inhibitors, cellular release products, and low molecular weight products of activation reactions (molecular markers) can now be measured in sensitive, specific assays. With this new perspective, genetic predisposition to pathologic hemostatic conditions can be identified through molecular biology and can be identified during the early stages of disease (i.e., at subclinical stages before major pathologic complications are established), and more specifically targeted prophylactic, as well as therapeutic drug interventions, can be administered. The molecular markers of hemostatic activation that can be assessed by various immunochemical methods provide very early evidence of thrombotic, fibrinolytic, or platelet-involved aberrations. Technological advances in methodology and instrumentation have changed the scope of all clinical laboratories but, in particular, that of the coagulation laboratory. The dramatic growth and development have resulted from the influences of clinical chemistry, clinical immunology, pharmacology, biochemistry, and biotechnology. Analytical instruments for use in hemostatic testing go beyond plasma or whole blood clot-based readers, platelet aggregometers, and microscopes to a range of automated, discrete, chemistrylike analyzers, spectrophotometers, microliter ELISA systems, RIA systems, and multiprobe instruments designed to measure simultaneously the different assay end-points of colorimetric and clotting assays and flow cytometers. Instruments are designed for batch processing of single tests on multiple samples or multiple test panels on a single sample. Versatility ranges from instruments that measure only the final reaction solution, by end-point or kinetic analysis, to instruments that automatically pipet reagents and sample, incubate, and analyze the reaction for truly walk-away assay performance. Typically, a wider range of assays are available in automated laboratories as opposed to laboratories performing manual assays.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMedDate not supplied

Albuterol delivery by metered-dose inhaler with a pediatric mechanical ventilatory circuit model.

STUDY OBJECTIVE: To determine albuterol delivery by metered-dose inhaler (MDI) in an in vitro pediatric mechanical ventilatory circuit model. The influence of a spacing device, endotracheal tube (ETT) diameter and length, and air humidity was also investigated. DESIGN: An albuterol MDI canister was connected to an AeroVent spacer or Airlife MDI adapter and ETT 4.0, 5.0, or 6.0 mm at commercially available and equal lengths. The ETT tip was attached to an in-line filter holder with a 1-microns type A/E glass fiber filter. Ventilator settings were fractional concentration of inspired oxygen 50%, tidal volume 250 ml, inspiratory:expiratory (I:E) ratio 1:3, rate 25 breaths/minute, temperature 35 degrees C, and a decelerating flow pattern. Ten albuterol canisters were activated two times each (total 2000 micrograms) into dry (4.0-, 5.0-, and 6.0-mm ETT) and humidified air (4.0- and 6.0-mm ETT) and repeated in triplicate. Percentage MDI output was determined by weighing the filter before and after drug administration (balance sensitivity 10 micrograms). Significant differences (p < or = 0.05) among the groups with and without a spacer and in dry and humidified air were determined by ANOVA with Scheffe's multiple comparison test. Multiple regression was used to determine significant associations between ETT diameter and length and delivery. MAIN RESULTS: With the AeroVent spacer in humidified air, delivery with the 4.0- and 6.0-mm ETT was approximately 2.3% and 5%, respectively. The spacer and dry air significantly improved delivery. CONCLUSIONS: In humidified air, the dose of albuterol by MDI with an AeroVent spacer should be doubled for children intubated with 6.0-mm ETT, and four puffs administered for every one puff desired for 4.0-mm ETT. The results of this investigation should prove useful in initial clinical trials of albuterol MDI in ventilator-dependent infants and children.

Administration, Inhalation↗
PubMed2001

Reliability of a 5-m multiple shuttle test.

The aim of the present study was to determine the reliability of a modified 5-m multiple shuttle test. The 'match-related fitness' of 23 female hockey players was assessed on four occasions within 4 weeks. The results of each test session and each shuttle were analysed using analysis of variance with repeated measures to determine the reliability of the test. The mean distance for each of the six shuttles decreased (121.2 +/- 7.5, 114.5 +/- 7.5, 112.2 +/- 7.5, 109.9 +/- 7.9, 108.4 +/- 8.1 and 108.7 +/- 8.3 m for shuttles 1-6, respectively; P < 0.001) similarly for each of the four sessions (P = 0.99). The total and peak distances covered during the tests were not significantly different (P = 0.99 and P = 0.12, respectively). The intra-class correlation coefficient (R) for these variables was 0.98 and 0.86, respectively. The delta distance and the fatigue index calculated post-test were significantly different (P = 0.001 and P = 0.006, respectively) between the four sessions. The intra-class correlation coefficient for both these variables was 0.74. Heart rate and rating of perceived exertion (RPE) were not significantly different between sessions (P = 0.42 and P = 0.095, respectively). The intra-class correlation coefficient for heart rate ranged from 0.65 to 0.97 and that for RPE from 0.85 to 0.91. We conclude that the 5-m multiple shuttle run test is a reliable measure of total and peak distances, heart rate and RPE response and is sufficiently reliabile to track changes in fitness over a season. The delta distance and fatigue index are not as reliable and should be interpreted with caution.

Adult↗
PubMed1984

Misuse of statistical methods in Arthritis and Rheumatism. 1982 versus 1967-68.

Articles published in Arthritis and Rheumatism in 1982 were compared with those from 1967-68 to evaluate trends in statistical methods and in the quantity and character of statistical misuse. Results show that among articles in 1982 using statistics, 66% contained methodologic errors. The percentage was similar in 1967-68, although fewer articles used statistics. In 1967-68 the most common error was failure to identify the statistical method used, whereas in 1982 multiple testing errors predominated, specifically, use of the t-test to compare 3 or more groups and comparison of 2 groups on multiple variables. The availability of calculators and computers which readily perform complex data analysis may underly the emergence of multiple testing errors. To compare multiple groups, we suggest using analysis of variance instead of the t-test. To avoid multiple testing errors, we recommend limiting the number of tests performed, lowering the alpha (significance) level, or using multivariate techniques.

Arthritis↗
PubMed1978

A comparison of student performance in two parallel physiology tests in multiple choice and short answer forms.

Two parallel tests in physiology, one in multiple choice answer form and one in short answer form, were administered consecutively to a group of 104 students. The construction of the questions in the two papers and marking schedules were such that if the form of examination did not influence the students' performance, the scores obtained in the two papers could be expected to be closely similar. The results indicate that the form of the question influences the students' performance significantly. The short answer format offers certain advantages over the multiple choice format and it would appear that greater use should be made of this type of question in testing at medical schools.

Education, Medical, Undergraduate↗
PubMed1975

[Experience with the written examination (multiple choice test) in the teaching of anatomy].

All students (400 each winter-term) receive extensive information at the beginning of the course "anatomical propedeutics": a timetable with recommendations for learning, a list of instructional objectives and of terminology and an instruction for that type of test, the students never had experienced before. Feed-back is given by computer-output containing comments on the objective related to a wrong answer and indicating sub-test scores. Correlation of scores with results in the following dissection course seems to be acceptable. Questions of the multiple-choice test were compared by pairs with questions asked for in confrontation with the anatomical object. A strong coherence was found in answering correctly the multiple choice questions and the related oral exam. Over-all experience with a multiple choice test administered in Austria for the first time was rather encouraging.

Anatomy↗
PubMed1986

Antigen specific stimulation of immune responses during long-term repeated skin testing with multiple antigens.

Delayed-type hypersensitivity (DTH) skin testing as an assay of immune competence is a widely used technique. Accordingly, clinical situations frequently occur which require that skin tests be performed many times on the same patient. In the present investigation, in vivo and in vitro immune responses were studied over a 7-month period in 22 normal human volunteers, each of whom were skin tested 6 times at monthly intervals with multiple antigens. Patterns of responses to the 7 specific skin test antigens observed during repeated skin testing in vivo indicated non-significant, but detectable, declines in skin test reactivity to tetanus, diphtheria and streptococcus antigens and increases in reactivity to trichophyton, tuberculin, candida and proteus antigens. In vitro lymphocyte transformation assays (LTAs) of cell-mediated immune (CMI) activities revealed that repeated skin testing, e.g., 3-5 serial skin tests, induced significantly increased levels of CMI reactions with 3 of the 4 skin test antigens used as challenge antigens. Since no significant changes in in vitro CMI responses were detected using 3 control "non-skin test" antigens, the effects observed were confirmed to be antigen specific. Increased IgG antibody responses were detected for only the toxoid antigens during the skin testing period. For the group of 22 normal volunteers, positive statistical correlations were not observed between any individual skin test antigen and the immune reactions assayed specifically for that antigen, including DTH responses and levels of circulating antigen-specific antibodies. Short term differences were detected between tetanus, diphtheria and streptococcus antigens in their LTA response patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Multiple-choice testing in anatomy.

An analysis of 596 multiple-choice questions (MCQs) on human anatomy given at three First Professional Examinations for medical students is reported. The MCQ paper at each examination was 200 items long and consisted of three item-types: A, K and T/F. Each A-type item comprised a stem and five options, only one of the latter being the correct or best answer. Items of the K-type consisted of a stem and four responses, any number of which may be correct. The T/F items were of the three-response kind, the available options being 'true', 'false' and 'don't know'. Test reliability was computed by internal analysis, using the Kuder-Richardson 20 formula. Measures of concurrent validity were obtained by correlating the scores in the MCQ papers with the overall outcome of the First Professional Examination. Indices of item facility, discrimination and abstention were calculated. The effects of item-type and the availability of the 'don't know' option on examinee performance were also determined. Reliability (alpha) and concurrent validity (Pearson r) coefficients in the ranges of 0.71-0.85 and 0.80-0.93 (P less than 0.05) respectively were recorded. Regression analysis revealed the MCQ papers to be less sensitive predictors of the aggregate performance than the essay papers. The proportion of highly discriminatory and excessively difficult items was highest for the K-type. When the same K-type questions were re-exhibited in the indeterminate format, the examinees performed significantly better. Higher scores were also recorded when candidates were required to respond to all the questions than when they were offered the 'don't know' option and the percentage gain was higher for the low-scoring examinees. The appropriateness of multiple-choice testing as a tool for assessing student achievement in human anatomy is discussed.

Anatomy↗
PubMed2001

The multiple tasks test. Strategies in Parkinson's disease.

The clinical balance tests presently used cannot predict falls in Parkinson's disease (PD), perhaps because they probe fairly isolated "components" of postural control. The Multiple Tasks Test (MTT) is a new balance test that simultaneously assesses multiple components of postural control. We investigated whether this MTT can detect postural abnormalities in PD patients. Fifty young controls (mean age 27.6 years), 20 elderly controls (mean age 62.5 years), and 20 PD patients (mean age 61.8 years, mean Hoehn and Yahr stage 2.2) participated. The MTT consisted of eight separate tasks of increasing complexity, which were executed sequentially. These tasks were composed of several motor components (standing up, walking, avoiding obstacles, touching the floor, turning around, and sitting down) and one cognitive component (answering serial questions). Four additional components included carrying an empty or loaded tray, wearing slippery shoes, and reduced illumination. All components within each task had to be performed simultaneously or directly sequentially. Errors were defined as Hesitations (slowed performance) or Blocks (complete cessation), which were scored separately for execution of the motor and cognitive components. Speed of performance was not stressed, but we did measure the time taken to complete all tasks. The complete MTT was performed by all subjects, except for a subgroup of seven patients and seven elderly controls who performed a shortened version, with only three of the eight sequential tasks (simple, intermediate, and most difficult). The number of subjects that produced Hesitations or Blocks for the motor components differed between the three groups [two-way repeated measures MANOVA, F(2.7) = 20.56; P < 0.001], patients making more errors than young and elderly controls. Furthermore, the number of subjects that made motor errors increased as the tasks became more complex [F(2.7) = 6.69; P < 0.001]. This increase differed across the three groups [significant interaction effect; F(2.7) = 3.31; P < 0.001] because particularly patients produced motor errors during the more complex tasks. In both control groups, 62% performed all eight consecutive tasks without errors in the motor components. In contrast, only 8% of the patients completed all tasks without motor errors (log rank test, P < 0.0001). This difference between patients and controls disappeared if the cognitive component was also scored, because more controls made cognitive errors during complex tasks than patients. Controls apparently gave priority to execution of the motor components, which they performed significantly faster than the patients. Both patients and controls made more errors during the shortened MTT, suggesting that learning effects (gain in performance through practice) influenced performance on the complete test. The MTT is a new balance test that clearly discriminates between healthy subjects and PD patients. Unlike controls, PD patients lend less priority to motor tasks over cognitive tasks. In addition, impaired motor learning may partially explain the higher error rate in PD. Future studies must determine if impaired MTT performance can predict actual falls in daily life.

Adult↗
PubMed1988

The dot plot. A starting point for evaluating test performance.

We suggest that evaluations of diagnostic tests start with dot plots that depict multiple test results over multiple clinical states. From this starting point we can calculate posttest probabilities for multiple clinical states at multiple test results. Also, we can project one subset of clinical states as "disease positive" and a second subset as "disease negative" to provide standard analyses such as likelihood ratios, relative operating characteristic curves, posttest/pretest probability plots, sensitivity, specificity, and predictive value. Finally, this starting point provides an excellent basis for comparing multiple studies of diagnostic performance. The advantages of dot plots are illustrated with data on serum ferritin levels over multiple clinical states.

Ferritins↗
PubMed2024

Phase Transition of Wax Enabling CRISPR Diagnostics for Automatic At-Home Testing of Multiple Sexually Transmitted Infection Pathogens.

Sexually transmitted infections (STIs) significantly impact women's reproductive health. Rapid, sensitive, and affordable detection of these pathogens is essential, especially for home-based self-testing, which is crucial for individuals who prioritize privacy or live in areas with limited access to healthcare services. Herein, an automated diagnostic system called Wax-CRISPR has been designed specifically for at-home testing of multiple STIs. This system employs a unique strategy by using the solid-to-liquid phase transition of wax to sequentially isolate and mix recombinase polymerase amplification (RPA) and CRISPR assays in a microfluidic chip. By incorporating a home-built controlling system, Wax-CRISPR achieves true one-pot multiplexed detection. The system can simultaneously detect six common critical gynecological pathogens (CT, MG, UU, NG, HPV 16, and HPV 18) within 30&#xa0;min, with a detection limit reaching 10-18 M. Clinical evaluation demonstrates that the system achieves a sensitivity of 96.8% and a specificity of 97.3% across 100 clinical samples. Importantly, eight randomly recruited untrained operators performe a double-blinded test and successfully identified the STI targets in 33 clinical samples. This wax-transition-based one-pot CRISPR assay offers advantages such as low-cost, high-stability, and user-friendliness, making it a useful platform for at-home or field-based testing of multiple pathogen infections.

Sexually Transmitted Diseases↗
PubMed1992

Empirical estimates of Bonferroni corrections for use in chromosome mapping studies with the BXD recombinant inbred strains.

Most chromosome mapping efforts with the BXD recombinant inbred (RI) strains involve comparisons between a trait of interest and each of a large number of marker loci for evidence of linkage. Such multiple tests or comparisons greatly increase the Type I error rate compared to the single-test situation. Perhaps the most direct way to obtain multiple-test error rates is to employ a Bonferroni correction, where the single-test alpha is multiplied by the number of independent (nonredundant) comparisons (k) to yield a multiple-test alpha that protects against even one fortuitous association with any of the markers. Several empirical estimates of k are discussed for the published BXD marker set of 142 mapped loci and the newer unpublished marker set (October 1991) comprised of 352 marker loci. Reasonable estimates of k appear to be roughly 40 and 65 for these two marker sets, respectively.

Animals↗
PubMed1998

Multiple antiphospholipid tests do not increase the diagnostic yield in antiphospholipid syndrome.

The family of antiphospholipid antibodies (aPL) includes a heterogeneous population of autoantibodies whose specificity is directed against not only phospholipids, but their complex with plasma proteins. Anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) tests are widely performed to screen the aPL family which is associated with thrombotic complications in patients with systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). The clinical significance of other aPL tests, including antibodies against phosphatidylserine (aPS), phosphatidylinositol (aPI), phosphatidic acid (aPA), phosphatidylcholine (aPC) and phosphatidylethanolamine (aPE), has not been established. The purpose of this study was to evaluate whether multiple aPL tests have enhanced diagnostic value for APS. We tested IgG/M/A aPS, aPI, aPA, aPC and aPE by ELISA using 10% bovine serum as blocking and sample diluent in 26 SLE patients with clinical manifestations of APS, but negative for both aCL and LA (Group 1). The results were compared with 32 SLE patients without any features of APS (Group 2) and 24 SLE patients with APS (aCL and/or LA positive) (Group 3). In Group 1, 1/26 (4%) was positive for IgA aPE, less frequent than in other groups, and none of the patients had any other aPL. In Group 2, 1/32 (3%) was positive for aPS, two (6%) for aPI, one (3%) for aPA and four (12.5%) for aPE. None was positive for aPC. In the third group, 13/24 (54%) were positive for aPS, 11 (46%) for aPI, 15 (63%) for aPA, four (17%) for aPC and seven (29%) for aPE. Since aPE was found in some patients, we extended the study, including 207 SLE patients, and tested aPE. IgG/M/A aPE was found in six (3%), 10(5%) and 21 (10%), respectively, but no association was found between aPE and any clinical features of APS. This study suggests that screening by multiple aPL tests does not increase the diagnostic yield in APS.

Adolescent↗