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PubMed1991

[A study on the serum biochemistry in carrier detection of Duchenne muscular dystrophy].

The serum levels of creatine kinase, creatine kinase isoenzyme (MB), lactate dehydrogenase, pyruvate kinase and myoglobin were studied in 85 carriers of Duchenne muscular dystrophy and 125 normal female controls. The results showed that the best single test for carrier detection was myoglobin or creatine kinase, the combination of multiple tests could increase the effectiveness of carrier detection, in which the best and most rational tests to use in combination were creatine kinase, lactate dehydrogenase and myoglobin.

Adolescent↗

PubMed1979

[Intelligence testing in early old age. The correlation between the multiple-choice vocabulary test (MCVT-B) and the progressive matrices test (PMT) in a patient cohort in early old age].

Taking a random sample of 147 patients a substantial correlation of 0.54 between the "Mehrfachwahl-Wortschatz-Test (MWT-B)" by Lehrl and the "Progressiver Matrizen-Test" by Raven could be found. The MWT-B did not show significant differences between the age groups of 34-44 years, 45-54 years and 55-64 years. In the PMT differences between the age groups only showed up when the raw-scores were converted to IQ-scores (reffering to the corresponding age groups). Using the raw-scores no significant differences could be determined. Investigating an average IQ of 109 in the PMT, we found an average IQ of 97 in the MWT-B for the same patients. A main reason for the superelevated IQ-scores in PMT seems to be the reference to different age groups. A new standardization of the test should be undertaken.

Adult↗

PubMed2005

Agreement between diagnoses reached by clinical examination and available reference standards: a prospective study of 216 patients with lumbopelvic pain.

BACKGROUND: The tissue origin of low back pain (LBP) or referred lower extremity symptoms (LES) may be identified in about 70% of cases using advanced imaging, discography and facet or sacroiliac joint blocks. These techniques are invasive and availability varies. A clinical examination is non-invasive and widely available but its validity is questioned. Diagnostic studies usually examine single tests in relation to single reference standards, yet in clinical practice, clinicians use multiple tests and select from a range of possible diagnoses. There is a need for studies that evaluate the diagnostic performance of clinical diagnoses against available reference standards. METHODS: We compared blinded clinical diagnoses with diagnoses based on available reference standards for known causes of LBP or LES such as discography, facet, sacroiliac or hip joint blocks, epidurals injections, advanced imaging studies or any combination of these tests. A prospective, blinded validity design was employed. Physiotherapists examined consecutive patients with chronic lumbopelvic pain and/or referred LES scheduled to receive the reference standard examinations. When diagnoses were in complete agreement regardless of complexity, "exact" agreement was recorded. When the clinical diagnosis was included within the reference standard diagnoses, "clinical agreement" was recorded. The proportional chance criterion (PCC) statistic was used to estimate agreement on multiple diagnostic possibilities because it accounts for the prevalence of individual categories in the sample. The kappa statistic was used to estimate agreement on six pathoanatomic diagnoses. RESULTS: In a sample of chronic LBP patients (n = 216) with high levels of disability and distress, 67% received a patho-anatomic diagnosis based on available reference standards, and 10% had more than one tissue origin of pain identified. For 27 diagnostic categories and combinations, chance clinical agreement (PCC) was estimated at 13%. "Exact" agreement between clinical and reference standard diagnoses was 32% and "clinical agreement" 51%. For six pathoanatomic categories (disc, facet joint, sacroiliac joint, hip joint, nerve root and spinal stenosis), PCC was 33% with actual agreement 56%. There was no overlap of 95% confidence intervals on any comparison. Diagnostic agreement on the six most common patho-anatomic categories produced a kappa of 0.31. CONCLUSION: Clinical diagnoses agree with reference standards diagnoses more often than chance. Using available reference standards, most patients can have a tissue source of pain identified.

Humans↗

PubMed1978

Recovery as a function of the degree of amnesia due to protein synthesis inhibition.

Retrograde amnesia following inhibition of cerebral protein synthesis has generally been explained as either a failure of consolidation or impairment of a retrieval mechanism. Major evidence for the retrieval hypothesis is provided by studies which utilize a reminder (usually footshock) to attenuate the effect of the protein inhibitor. To examine this question, mice were injected subcutaneously with anisomycin (1 mg/animal, 7 mg/animal, or 1 mg/animal every 2 hr x 7) and given one training trial in a passive avoidance box. All animals received a single retention test on each of four consecutive days, starting either 1, 7, or 21 days after training. One-half of the mice in each group received a footshock reminder 1 hr after their initial test. The footshock reminder did not attenuate the inhibitor-induced amnesia, but multiple testing did produce partial recovery in animals demonstrating some memory of training (both Saline and Anisomycin animals). Animals injected with anisomycin whose testing began 1 day after training demonstrated partial recovery irrespective of drug dosage level. The extent of amnesia and recovery were dependent upon both drug dosage and training-test interval. Implications for the consolidation and retrieval hypotheses are discussed.

Amnesia↗

PubMed1995

Pulsatile release of FSH for superovulation in cattle.

The studies reported here were directed towards the development of an implantable microcapsule which "pulses" release of follicle stimulating hormone, FSH, for application to superovulating cows. Final dose forms were administered using membrane-coated cylinders. The "pulse" of the FSH is achieved by membrane encapsulation of an effervescent/swelling core containing citric acid, sodium bicarbonate, glucose and FSH. Entry of water results in sufficient pressure increase (by gas generation) to rupture ("burst") the membrane. Time to rupture is dependent upon several factors, such as membrane permeability and thickness, and core composition and loading. The final dose forms were implanted by means of a trochar. This system was tested in sheep to substantiate in vivo "burst" times and then tested in cows to determine efficacy. In vivo burst times in sheep varied from 8 to 96 hr, based upon maximal FSH values in blood serum, and generally paralled the planned times resulting from in vitro tests. Multiple capsules designed to release FSH as a pulse or steady state were tested on a limited number of cows plus a control (n = 10). Four of the combinations resulted in 11, 11, 14 and 16 ovulations, indicating that further development has promise of providing a one-injection system using FSH for superovulating cattle.

Journal Article↗

PubMed2003

Qualitative colorimetric tests for solid phase synthesis.

Results obtained in the application of these tests are summarized in Table II. We have encountered some variations in the reproducibility and accuracy of some tests. Due to the numerous factors that can influence colorimetric test results (e.g., test reagent stability, resin type, functional group interference, and lability of protecting group) we highly recommend performing a positive and a negative control for any test applied to a new synthesis. We also emphasize the importance of reagent solution purity on the outcome of test results, hence we strongly encourage the use of correctly prepared and carefully stored reactants. To minimize false results due to lability of the resin-product bond or the product itself (such as Fmoc-protected amino acids), colorimetric tests should be performed with the utmost immediacy in regards to completion of the step to be monitored. Hence the storage of resin over long periods of time (more than 24 h) before testing is not advisable. When the result of a colorimetric test is in doubt we advise repeating the test a few times until a reproducible result is obtained. The use of multiple tests for the same functional group may elucidate ambiguous or otherwise challenging cases.

Alcohols↗

PubMed1998

Italian population data on thirteen short tandem repeat loci: HUMTH01, D21S11, D18S51, HUMVWFA31, HUMFIBRA, D8S1179, HUMTPOX, HUMCSF1PO, D16S539, D7S820, D13S317, D5S818, D3S1358.

A population study on thirteen short tandem repeat (STR) loci was performed on 223 unrelated Italian Caucasians. The DNA was amplified by PCR. Separation and detection of the amplified STR fragments was carried out by use of 377 automated system (Applied Biosystems Division/Perkin Elmer). All loci meet Hardy-Weinberg expectations, and the data show only five departures out of seventy-eight pairwise locus tests which is close to expectations of 5% (5/78 = 6.4%). When correcting for multiple tests, there is little evidence for departures from expectations between loci. The combined Power of Exclusion for the thirteen STR loci is 0.99999270. The results demonstrate that these loci will be very useful for human identification in forensic cases in Italy.

Alleles↗

PubMed2005

Empirical Bayes screening of many p-values with applications to microarray studies.

MOTIVATION: Statistical tests for the detection of differentially expressed genes lead to a large collection of p-values one for each gene comparison. Without any further adjustment, these p-values may lead to a large number of false positives, simply because the number of genes to be tested is huge, which might mean wastage of laboratory resources. To account for multiple hypotheses, these p-values are typically adjusted using a single step method or a step-down method in order to achieve an overall control of the error rate (the so-called familywise error rate). In many applications, this may lead to an overly conservative strategy leading to too few genes being flagged. RESULTS: In this paper we introduce a novel empirical Bayes screening (EBS) technique to inspect a large number of p-values in an effort to detect additional positive cases. In effect, each case borrows strength from an overall picture of the alternative hypotheses computed from all the p-values, while the entire procedure is calibrated by a step-down method so that the familywise error rate at the complete null hypothesis is still controlled. It is shown that the EBS has substantially higher sensitivity than the standard step-down approach for multiple comparison at the cost of a modest increase in the false discovery rate (FDR). The EBS procedure also compares favorably when compared with existing FDR control procedures for multiple testing. The EBS procedure is particularly useful in situations where it is important to identify all possible potentially positive cases which can be subjected to further confirmatory testing in order to eliminate the false positives. We illustrated this screening procedure using a data set on human colorectal cancer where we show that the EBS method detected additional genes related to colon cancer that were missed by other methods. This novel empirical Bayes procedure is advantageous over our earlier proposed empirical Bayes adjustments due to the following reasons: (i) it offers an automatic screening of the p-values the user may obtain from a univariate (i.e., gene by gene) analysis package making it extremely easy to use for a non-statistician, (ii) since it applies to the p-values, the tests do not have to be t-tests; in particular they could be F-tests which might arise in certain ANOVA formulations with expression data or even nonparametric tests, (iii) the empirical Bayes adjustment uses nonparametric function estimation techniques to estimate the marginal density of the transformed p-values rather than using a parametric model for the prior distribution and is therefore robust against model mis-specification. AVAILABILITY: R code for EBS is available from the authors upon request. SUPPLEMENTARY INFORMATION: http://www.stat.uga.edu/~datta/EBS/supp.htm

Algorithms↗

PubMed2004

The optimal measure of linkage disequilibrium reduces error in association mapping of affection status.

We have developed a simple yet powerful approach for disease gene association mapping by linkage disequilibrium (LD). This method is unique because it applies a model with evolutionary theory that incorporates a parameter for the location of the causal polymorphism. The method exploits LD maps, which assign a location in LD units (LDU) for each marker. This approach is based on single marker tests within a composite likelihood framework, which avoids the heavy Bonferroni correction through multiple testing. As a proof of principle, we tested an 890 kb region flanking the CYP2D6 gene associated with poor drug-metabolizing activity in order to refine the localization of a causal mutation. Previous LD mapping studies using single markers and haplotypes have identified a 390 kb significant region associated with the poor drug-metabolizing phenotype on chromosome 22. None of the 27 Single nucleotide polymorphisms was within the gene. Using a metric LDU map, the commonest functional polymorphism within the gene was located at 14.9 kb from its true location, surrounded within a 95% confidence interval of 172 kb. The kb map had a relative efficiency of 33% compared with the LDU map. Our findings indicate that the support interval and location error are smaller than any published results. Despite the low resolution and the strong LD in the region, our results provide evidence of the substantial utility of LDU maps for disease gene association mapping. These tests are robust to large numbers of markers and are applicable to haplotypes, diplotypes, whole-genome association or candidate region studies.

Chromosomes, Human, Pair 22↗

PubMed1988

Treatment failure in Trichomonas vaginalis infections in females. II. In-vitro estimation of the sensitivity of the organism to metronidazole.

We have developed a standard procedure to measure the susceptibility of Trichomonas vaginalis to metronidazole in vitro, by controlling the state of oxygenation of the test cultures, the size of the inocula in terms of infectivity, and providing multiple tests at each drug concentration. Estimates were made of the in-vitro sensitivity to metronidazole of T. vaginalis isolated from 11 randomly selected patients, all, except for three defaulters, known to have been treated successfully, and from six 'treatment failure' patients. Stocks isolated from 'successfully treated' patients, were all highly sensitive to metronidazole. Eighteen stocks isolated from the 'treatment failure' patients fell into two groups: (a) those clearly separable from sensitive stocks, with ED50 values (the concentration of drug at which growth is prevented in 50% of test wells) in N2 of up to 0.51 mg/l and 3.5 to 11 mg/l in N2/1%O2; (b) those giving intermediate ED50 values of up to 0.20 mg/l in N2 and 0.7 to 1.8 mg/l in N2/1%O2. The current procedure demonstrates clearly that repeated treatment failure in patients without other complication is associated with enhanced resistance to metronidazole of T. vaginalis, and it may discriminate between T. vaginalis infections that are likely to respond to higher dosage and those that are not.

Adult↗

PubMed2003

Intrinsic urethral sphincteric deficiency: critical analysis of various diagnostic modalities.

PURPOSE OF REVIEW: The proper diagnosis of intrinsic urethral sphincteric deficiency among women with urinary incontinence carries important implications for determining the most effective medical or surgical therapy. Numerous diagnostic tests have been described attempting to make an accurate and comprehensive assessment of urethral function, but all suffer from a lack of standardization or inconsistently quoted reference values. This paper will review the literature on the positive aspects and limitations of commonly employed procedures to diagnose intrinsic urethral sphincteric deficiency. RECENT FINDINGS: Specific urodynamic studies, including the 'active' valsalva leak-point pressure and the 'static' urethral pressure profile are commonly used to determine urethral competence. However, these tests measure specific aspects of the continence mechanism under different clinical conditions, which limits the direct comparison between them. More complex techniques such as Doppler ultrasound, video-urodynamics and both static and dynamic magnetic resonance imaging are attempting to validate the urodynamic findings for urethral function. This approach may encourage the standardization of these procedures and parameters for diagnosing intrinsic urethral sphincteric deficiency. SUMMARY: A single definitive test for the diagnosis of intrinsic urethral sphincteric deficiency does not exist. Instead, multiple tests should be employed to reach a consensus for the diagnosis. This should include a complete voiding history, simple office examinations, and advanced studies such as urethrocystoscopy, urodynamics and possibly radiological evaluations. Understanding the limitations and variabilities of their equipment and the specific studies utilized should enable practitioners to standardize the approach for determining the extent of urethral dysfunction.

Diagnostic Techniques, Urological↗

PubMed1996

The role of microfixation in malar fractures: a quantitative biophysical study.

Microfixation and wire fixation techniques were used in combination with miniplates in the stabilization of simulated simple zygoma fractures in four fresh human cadaver heads. An orthogonal conveyer and rigid steel test frame were used to test rotational stability after deforming forces were applied. After testing multiple combinations at an initial deforming force of 5 kg, selected combinations were tested over a range of 2 to 22 kg. Evaluation of force-displacement data revealed that three-point fixation with miniplates was superior to all other methods, in agreement with previous studies. The combination of lateral buttress miniplate fixation in conjunction with microfixation at the zygomaticofrontal and infraorbital rim regions exhibited stable characteristics over the range of forces applied. Miniplate-microplate combinations exhibited greater stability than corresponding miniplate-wire combinations. The combination of miniplate-microplate fixation clinically allows a balance between stability and aesthetics in selected zygoma fractures.

Biomechanical Phenomena↗

PubMed1984

Identification of Escherichia coli K1 antigen.

We compared the use of bacteriophage sensitivity, seroagglutination with polyclonal antisera raised in rabbits or horses, seroagglutination with murine monoclonal antibody, and the serum agar precipitin technique for the detection of K1 capsular polysaccharide among clinical isolates of Escherichia coli obtained from blood stream infections. Some E. coli isolates failed to yield agreement among these tests, indicating that reliable detection of K1 antigen may require the use of multiple tests.

Agglutination Tests↗

PubMed1985

The superiority of sequential over simultaneous testing.

Diagnostic tests are typically used to help the physician select among available management options. When two or more tests are available, using them sequentially is potentially more efficient than simultaneously performing multiple tests, in that the former approach may allow the physician to perform fewer tests. In particular, we demonstrate that if two common conditions are met, any simultaneous strategy involving at least as many tests as management options can be replaced by a sequential strategy with the same outcome and a smaller expected number of tests. It follows that, in many clinical situations in which the benefits of performing fewer tests outweigh the costs that may result from delaying diagnosis, simultaneous strategies cannot be optimal. This result can decrease the number of diagnostic strategies that the physician or decision analyst needs to consider.

Decision Making↗

PubMedDate not supplied

The importance of considering single testing when two tests are available.

When considering two dichotomous tests in combination for reaching a treatment decision, the choice between single and multiple testing depends, in part, on the pretest probability of disease. The authors show that two tests are never preferred to a single test for all disease probabilities, regardless of whether the two tests are performed in parallel or in series.

Decision Making↗

PubMed1999

Using outlier events to monitor test turnaround time.

OBJECTIVES: To determine the causes of excessive test turnaround time (TAT) and to identify methods of improvement by studying reasons for those tests reported in excess of 70 minutes from the time the test was ordered (ie, outliers). DESIGN: Self-directed data-gathering of stat outlier TAT events from intensive care units and emergency departments, with descriptive parameters associated with each event and additional descriptive parameters associated with the participant. PARTICIPANTS: Laboratories enrolled in the 1996 College of American Pathologists Q-Probes program. MAIN OUTCOME MEASURES: Components associated with outlier TAT events and outlier TAT rates. RESULTS: Four hundred ninety-six hospital laboratories returned data on 218 551 stat tests, of which 10.6% had TATs in excess of 70 minutes. Ten percent of stat emergency department tests and 14.7% of stat intensive care unit tests were outliers. Major areas in which delays occurred were test ordering, 29.9%; within-laboratory (analytic) phase, 28.2%; collection of the specimen, 27.4%; postanalytic phase, 1.9%; and undetermined, 12.5%. The type of test performed was a significant factor and was independent of location: Chemistry-Multiple Test appeared most frequently ( approximately 40%), followed closely by Hematology-Complete Blood Count (approximately 20%) and Chemistry-Single Test ( approximately 18%). Factors of outlier TAT components for intensive care unit specimens were identified using statistical modeling and included hour of day, type of health care personnel collecting specimen, performing the test in a stat laboratory, and reason for delay. Outlier rates were not associated with any identified factors. The practice parameters of laboratories with outlier rates in the lowest 10th percentile significantly differed from those with rates in the top 10th percentile in test request computerization, report methods, and ordering methods. CONCLUSIONS: We observed that outlier analysis yields new information, such as type of test and reason for delay, concerning test delays when compared with TAT determination alone. Laboratories experiencing stat test TAT problems should use this tool as an adjunct to routine TAT monitoring for identifying unique causes of delay.

Clinical Laboratory Techniques↗

PubMed1999

Bacteriological quality of drinking water in Punjab: evaluation of H2S strip test.

OBJECTIVE: To assess bacteriological quality of drinking water in Punjab and to evaluate usefulness of H2S strip test in comparison with multiple tube test. METHOD: Samples of water were tested using H2S strips and multiple tube test. RESULTS: Maximum bacterial contamination was observed in water from domestic pumps (95.83%). Followed by tap water in rural areas of Punjab (91.30%) and tap water in Lahore (42.85%). Bacterial contamination was significantly higher (p < 0.001) in rural areas as compared to urban areas. Comparison of results of testing water samples by H2S strip test and multiple tube test revealed that H2S strip is 87.24% sensitive and 100% specific for detection of bacterial contamination with a positive predictive value of 100%. It was also observed that 100% water samples negative for total coliforms were also negative by H2S strip method. Moreover, with increase in number of total coliforms in the water samples, positivity by H2S strip method also increased (samples with more than 10 total coliforms/100 ml were 100% positive by H2S strip method). Therefore, H2S strip test can be used as alternative to multiple tube test for detection of bacterial contamination of water supplies. CONCLUSION: It is concluded that bacterial contamination of water is a significant problem in Punjab. It can be improved by regular monitoring of water supplies. For this purpose use of H2S strip test is advocated at house hold level.

Enterobacteriaceae↗

PubMed2003

Microsleep and sleepiness: a comparison of multiple sleep latency test and scoring of microsleep as a diagnostic test for excessive daytime sleepiness.

STUDY OBJECTIVE: To compare multiple sleep latency test (MSLT) and scoring of microsleep (presence of sleep electroencephalograph between 3 and 15s in an epoch) as a diagnostic test for excessive daytime sleepiness (EDS). DESIGN: A retrospective study. SETTING: Sleep center at a tertiary care teaching hospital. SUBJECTS: Patients referred to a sleep center who had an MSLT and one or more of the following symptoms; tiredness, sleepiness, memory loss, accidents/near accidents and gap driving. INTERVENTIONS: Full night polysomnography (PSG) and next day MSLT were performed. Patients were classified as 'microsleep-positive' or 'microsleep-negative' according to presence or absence of microsleep. RESULTS: Patients (n=92) were divided into three groups according to their MSLT results; group A had an MSLT</=5min (n=38), group B had an MSLT=6-10min (n=26), and group C had an MSLT>10min (n=28). The number of patients with symptoms of tiredness and memory loss were statistically higher in group A compared with groups B and C (P=0.036). The number of patients with symptoms of EDS, in groups B and C, was significantly higher in patients with microsleep than without microsleep (P<0.05). By a paired McNemar's test, the better performance of adding microsleep to MSLT (sensitivity 42.9%; specificity 63.6%) to assess EDS was statistically significant (P=0.0096). CONCLUSIONS: Microsleep determination during an MSLT is a more sensitive and specific test for EDS as compared to MSLT alone.

Female↗