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Alpha's standard error (ASE): an accurate and precise confidence interval estimate.

This research presents the inferential statistics for Cronbach's coefficient alpha on the basis of the standard statistical assumption of multivariate normality. The estimation of alpha's standard error (ASE) and confidence intervals are described, and the authors analytically and empirically investigate the effects of the components of these equations. The authors then demonstrate the superiority of this estimate compared with previous derivations of ASE in a separate Monte Carlo simulation. The authors also present a sampling error and test statistic for a test of independent sample alphas. They conclude with a recommendation that all alpha coefficients be reported in conjunction with standard error or confidence interval estimates and offer SAS and SPSS programming codes for easy implementation.

Behavioral Research↗

Embryonal adenoma of the kidney: a report of two cases.

Embryonal (metanephric) adenoma of the kidney, like Wilms' tumor, exhibits small monomorphic, blue cells arranged as vague, tubular rosettes. Unlike Wilms' tumor, which requires chemotherapy or multi-modality therapy for optimal management, the available evidence indicates that embryonal adenoma is most likely cured by simple enucleation or nephrectomy. Two women, age 54 (Case 1) and 78 (Case 2), respectively, underwent needle biopsy for a radiologically well circumscribed renal lesion with associated hematuria. The cellular smears contained vague rosette-like arrangement of small, blue cells with scant cytoplasm and evenly distributed, fine, nuclear chromatin. In cell blocks, these cells were arranged as compact, primitive, tubular rosettes or rare, moresolid clusters. Assuming that the absence of undifferentiated blastema and primitive glomeruli represented a sampling error, a diagnosis suggesting of Wilms' tumor was made in Case 1. At nephrectomy, despite extensive sampling, the typical triphasic Wilms' morphology and anaplastic or necrotic areas were not seen. In the presence of architectural monotony, the diagnosis in Case 1 was amended to embryonal adenoma. Case 2 was cytologically diagnosed as embryonal adenoma of the kidney and is being followed conservatively. In our opinion, the presence of monotypic architecture at cytology/histology is very helpful in differentiating renal embryonal (metanephric) adenoma from Wilms' tumor.

Adenoma↗

Information-theoretic dissection of pairwise contact potentials.

Pairwise contact potentials have a long, successful history in protein structure prediction. They provide an easily-estimated representation of many attributes of protein structures, such as the hydrophobic effect. In order to improve on existing potentials, one should develop a clear understanding of precisely what information they convey. Here, using mutual information, we quantified the information in amino acid potentials, and the importance of hydropathy, charge, disulfide bonding, and burial. Sampling error in mutual information was controlled for by estimating how much information cannot be attributed to sampling bias. We found the information in amino acid contacts to be modest: 0.04 bits per contact. Of that, only 0.01 bits of information could not be attributed to hydropathy, charge, disulfide bonding, or burial.

Amino Acids↗

The Assessment of Goal Commitment: A Measurement Model Meta-Analysis.

Goals are central to current treatments of work motivation, and goal commitment is a critical construct in understanding the relationship between goals and performance. Inconsistency in the measurement of goal commitment hindered early research in this area but the nine-item, self-report scale developed by Hollenbeck, Williams, and Klein (1989b), and derivatives of that scale, have become the most commonly used measures of goal commitment. Despite this convergence, a few authors, based on small sample studies, have raised questions about the dimensionality of this measure. To address the conflicting recommendations in the literature regarding what items to use in assessing goal commitment, the current study combines the results of 17 independent samples and 2918 subjects to provide a more conclusive assessment by combining meta-analytic and multisample confirmatory factor analytic techniques. This effort reflects the first combined use of these techniques to test a measurement model and allowed for the creation of a database substantially larger than that of previously factor analyzed samples containing these scale items. By mitigating sampling error, the results clarified a number of debated issues that have arisen out of previous small sample factor analyses and revealed a five-item scale that is unidimensional and equivalent across measurement timing, goal origin, and task complexity. It is recommended that this five-item scale be used in future research assessing goal commitment. Copyright 2001 Academic Press.

Journal Article↗

Genetic differentiation between two host "races" and two species of cleptoparasitic bees and between their two hosts.

In this paper we test the following two hypotheses: (1) that apparently conspecific samples of the cleptoparasitic bee Coelioxys funeraria, differing markedly in size and reared from different host species, do indeed represent one panmictic population; (2) that bees that nest in holes in wood or twigs have higher levels of genetic variation than those nesting in the ground. Based upon 41 loci, the genetic differences between the two samples of C. funeraria could be explained entirely in terms of sampling error. In contrast, the sympatric C. moesta showed 16 fixed allelic differences from the C. funeraria samples. Similarly, the two hosts of C. funeraria, Megachile relativa and M. inermis, had 21 fixed allelic differences between them out of 42 presumptive gene loci. Heterozygosities among the wood-nesting bees were not particularly high for Hymenoptera, ranging from 0.045 to 0.054. Comparisons of heterozygosity estimates among bees remain ambiguous as to whether soil nesting confers sufficient environmental buffering effects to reduce possible advantages of heterosis in ground-nesting species.

Alleles↗

The TSH-dependent variation of the essential elements iodine, selenium and zinc within human thyroid tissues.

Instrumental Neutron Activation Analysis was used in order to measure iodine, selenium and zinc concentration in thyroid samples. A pair of samples of normal and nodular tissue were collected from the thyroid gland from 72 patients selected on the basis of pathological criteria (44 cases of multinodular goiter, 12 of chronic lymphocytic thyroiditis (CLT), 6 of thyroid adenoma (TA) and 12 of thyroid cancer (TC)). The check for tissue homogeneity and sampling error was performed by means of the coefficient of variation (CV%) of the elements in replicate samples of normal and altered tissues. High CV% values (> 15%) for iodine reflected a functional variability in thyroid follicles, while low CV% values (< 10%) for selenium and zinc indicated that the composition of selected tissues was rather homogeneous. The variation of the element's concentration was compared in normal and altered tissues. The mean element concentrations had values close to those already reported in the literature; furthermore, our patients had marginal iodine and selenium deficiency. Both normal and nodular tissues in CLT showed statistically significant lower zinc values as compared with the other thyroid diseases. To evaluate the thyroid function, thyroid stimulating hormone (TSH) and thyroxine (T4) levels were measured in the serum of patients. Two arbitrary serum-TSH threshold levels (TSH < 1.0 and > 4.0 mU/L) were introduced in order to classify, respectively, hyperthyroidism and hypothyroidism, as well as euthyroid conditions (1.0 < TSH < 4.0 mU/L), and each patient was assigned to one of these groups. The influence of TSH in the variation of the concentration of iodine, selenium and zinc in normal and altered human thyroid tissues was significant.

Adolescent↗

The potential for increased risk of infection due to the reuse of convective air-warming/cooling coverlets.

BACKGROUND: The use of convective air warming and/or cooling for the prevention of hypothermia or to induce hypothermia is growing rapidly. To date, there is no information available as to the potential risks for infection associated with either the post-surgical reuse or the repositioning of coverlets closer to the wound. We hypothesized that use of coverlets either intra- or postoperatively leads to increased contamination. METHODS: The bacterial contamination of commercially available coverlets before (control group, n = 10) and after patient application (n = 18) was investigated. From 3 predetermined sites, 1 cm x 2 cm pieces of coverlet were removed and analyzed for bacterial contamination. RESULTS: Even prior to use, coverlet samplings provided identifiable contamination (3 out of 30 sites, 10%), but this could be within our study's sampling error. Nevertheless, following clinical use the frequency of contamination was considerably increased; 17 out of 57 sampled sites (31.5%) elicited contamination (P < 0.05, Fisher's exact test). CONCLUSION: This study demonstrates that the use of the coverlets, intra- or postoperatively, can lead to significant bacterial contamination. It is concluded that it is not advisable to reuse coverlets for multiple clinical applications.

Bedding and Linens↗

Detecting failed WBC-reduction processes: computer simulations of intermittent and continuous process failure.

BACKGROUND: By regulation, ongoing process control of WBC-reduced processes is performed on 1 percent of WBC-reduced components, typically four to five samples per month. However, prospective study of the power of this small sample has been difficult. Using computer-generated "residual WBC" distributions, sample size sensitivity to continuous or intermittent WBC-reduction failure was examined. STUDY DESIGN AND METHODS: Populations of log-normally distributed values (mean +/- SD, 4.5+/-0.5; n = 10(5)) were generated. Continuous failure (log-normality maintained) was simulated by incrementally increasing the population mean or its SD. Intermittent failure (bimodal distributions with discrete subpopulations of WBCs > the FDA cutoff) was simulated by admixing increasing percentages of secondary outlier populations. Sample sizes of 4 to 60 were examined (500 repetitions each) for their power to detect drift or failure by standard control criteria. RESULTS: Normally distributed low variance failure was easily detected by comparison of the mean of four samples to an upper control limit (95% confidence of detecting 2% failure). However, 40 samples were required to detect > 5 percent intermittent (bimodal) failure or high variance failure with 90-percent confidence, and only if individual WBC values were compared to cutoff. CONCLUSION: Sampling error limits the detection of high variance or bimodal distributions. While the mean of a small sample is highly sensitive to shifts in a low-variance normal distribution, the detection of a high-variance bimodal population requires a large number of individual values compared to cutoff. Therefore, the number of samples required for confident failure detection depends on both the nature of the underlying distribution and the interpretive criteria. Further research is necessary to determine the true distributions of WBC-reduction process failure, as well as clinically relevant quality limits.

Blood Component Removal↗

Estimation of metabolic rate constants in PBPK-models from liver slice experiments: what are the experimental needs?

A mechanistic model is presented describing the clearance of a compound in a precision-cut liver slice that is incubated in a culture medium. The problem of estimating metabolic rate constants in PBPK models from liver slice experiments is discussed using identifiability analysis. From the identifiability problem analysis, it appears that in addition to the clearance, the compound's free fraction in the slice and the diffusion rate of the exchange of the compound between culture medium and liver slice should be identified. In addition, knowledge of the culture medium volume, the slice volume, the compound's free fraction, and octanol-water-based partition between medium and slice is presupposed. The formal solution for identification is discussed from the perspective of experimental practice. A formally necessary condition for identification is the sampling of parent compound in liver slice or culture medium. However, due to experimental limitations and errors, sampling the parent compound in the slice together with additional sampling of metabolite pooled from the medium and the slice is required for identification in practice. Moreover, it appears that identification results are unreliable when the value of the intrinsic clearance exceeds the value of the diffusion coefficient, a condition to be verified a posteriori.

Animals↗

A comparison of exact, mid-P, and score tests for matched case-control studies.

A recently developed algorithm for generating the distribution of sufficient statistics for conditional logistic models can be put to a twofold use. First, it provides an avenue for performing inference for matched case-control studies that does not rely on the assumption of a large sample size. Second, joint distributions generated by this algorithm can be used to make comparisons of various inferential procedures that are free from Monte Carlo sampling errors. In this paper, these two features of the algorithm are utilized to compare small-sample properties of the exact, mid-P value, and score tests for a conditional logistic model with two unmatched binary covariates. Both uniparametric and multiparametric tests, performed at a nominal significance level of .05, were studied. It was found that the actual significance levels of the mid-P test tend to be closer to the nominal level when compared with those of the other two tests.

Algorithms↗

Estimating misclassification error with small samples via bootstrap cross-validation.

MOTIVATION: Estimation of misclassification error has received increasing attention in clinical diagnosis and bioinformatics studies, especially in small sample studies with microarray data. Current error estimation methods are not satisfactory because they either have large variability (such as leave-one-out cross-validation) or large bias (such as resubstitution and leave-one-out bootstrap). While small sample size remains one of the key features of costly clinical investigations or of microarray studies that have limited resources in funding, time and tissue materials, accurate and easy-to-implement error estimation methods for small samples are desirable and will be beneficial. RESULTS: A bootstrap cross-validation method is studied. It achieves accurate error estimation through a simple procedure with bootstrap resampling and only costs computer CPU time. Simulation studies and applications to microarray data demonstrate that it performs consistently better than its competitors. This method possesses several attractive properties: (1) it is implemented through a simple procedure; (2) it performs well for small samples with sample size, as small as 16; (3) it is not restricted to any particular classification rules and thus applies to many parametric or non-parametric methods.

Algorithms↗

A comparison of vertical versus transverse sections in the evaluation of alopecia biopsy specimens.

BACKGROUND: Both vertical and transverse sections are used in the histologic interpretation of alopecia biopsy specimens. Although a combination of the two may be optimal, the pathologist is frequently only provided with a single specimen. Even though the trend in recent years has been toward transverse sections in this setting, we are not aware of any published data directly comparing the two methods. METHODS: One hundred two consecutive archived hair biopsy accessions that demonstrated comparable vertical and transverse sections were examined twice, each time in a random order. The pathologist's interpretation based only on the vertical sections and an interpretation based only on the transverse sections were compared with the original biopsy report, which had been based on the combination of vertical and transverse sections. RESULTS: In 76 cases, all 3 diagnoses were concordant (ie, the diagnosis made with vertical sections alone, the diagnosis made with transverse sections alone, and the original diagnosis were all in agreement). In 2 cases, neither the diagnosis made with vertical sections alone nor the diagnosis made with transverse sections alone were in full agreement with the original diagnosis. In 20 cases, only the diagnosis made with vertical sections was concordant with the original diagnosis. In 4 cases, only the diagnosis made with transverse sections alone was concordant with the original diagnosis. LIMITATIONS: Our practice is heavily weighted toward scarring alopecia, and the results of our study may not be applicable to practices weighted toward other forms of alopecia. Because the cases had been signed out over a period of several years, the nomenclature for some entities changed. For the purposes of our study, we counted the diagnoses of follicular degeneration syndrome and idiopathic pseudopelade to be subtypes of (and concordant with) a diagnosis of central centrifugal cicatricial alopecia. In some cases, a definitive diagnosis was not possible at the time of the original diagnosis, but rather the pathologist had provided a histologic description and a differential diagnosis. For purposes of this study, an interpretation was considered to be concordant with the original descriptive diagnosis if all of the important histologic features were identified that had been described in the original report. Sampling error could have contributed to discordant diagnoses, but would be expected to affect both vertical and transverse samples in a random manner. CONCLUSION: The combination of vertical and transverse sections is superior to either alone. Although transverse sections have revolutionized the evaluation of alopecia, in this study, the diagnosis made with vertical sections alone had a higher concordance rate with the combination than did transverse sections alone. As there are advantages and disadvantages inherent in either method, when only a single biopsy specimen is submitted, it may be sectioned either vertically or transversely, at the discretion of the pathologist. With either method, serial step sections should be obtained to reduce the risk of missing important histologic findings.

Alopecia↗

[Theory, method and application of method R on estimation of (co)variance components].

Theory, method and application of Method R on estimation of (co)variance components were reviewed in order to make the method be reasonably used. Estimation requires R values,which are regressions of predicted random effects that are calculated using complete dataset on predicted random effects that are calculated using random subsets of the same data. By using multivariate iteration algorithm based on a transformation matrix,and combining with the preconditioned conjugate gradient to solve the mixed model equations, the computation efficiency of Method R is much improved. Method R is computationally inexpensive,and the sampling errors and approximate credible intervals of estimates can be obtained. Disadvantages of Method R include a larger sampling variance than other methods for the same data,and biased estimates in small datasets. As an alternative method, Method R can be used in larger datasets. It is necessary to study its theoretical properties and broaden its application range further.

Algorithms↗

Therapeutic monitoring of cyclosporine following pediatric bone marrow transplantation: problems with sampling from silicone central venous lines.

Blood concentrations are commonly used to guide dosing requirements of cyclosporine, due to large variations in pharmacokinetics both between and within individuals. Bone marrow transplant patients at The Hospital for Sick Children are prescribed intravenous cyclosporine as part of the posttransplant immunosuppression protocol. Sampling for blood concentration measurement is generally done via a single-lumen central venous line (CVL). Cyclosporine concentrations sampled by this route were compared with concentrations in peripheral capillary samples taken concurrently. Results from the CVL blood were substantially higher despite appropriate flushing of the CVL between the end of the infusion and the time of sample collection. This discrepancy disappeared once the patient was converted to oral cyclosporine. We conclude that the sampling error is due to drug adsorbed to the silicone CVL catheters during intravenous administration and displaced during blood sample collection.

Blood Specimen Collection↗

Brush cytology from the uterine cervix.

Invasive carcinoma of the uterine cervix is a common neoplasm even in countries with extensive screening programmes of several years. The incidence rate per 100,000 is still around 18 in Denmark. The reasons for these persistently high rates of incidence despite various prophylactic measures are many and have been thoroughly discussed over recent years. It is imperative, however, to avoid sampling errors in screening procedures for precancerous lesions, especially erroneous interpretations arising from insufficient cytological material. To improve cytological sampling from the uterine cervix we decided to compare a recently introduced brush technique with the routine procedure in our hospital.

Adult↗

Interinstitutional comparison of frozen section consultation in small hospitals: a College of American Pathologists Q-Probes study of 18,532 frozen section consultation diagnoses in 233 small hospitals.

OBJECTIVE: To study pathology intraoperative consultation practices and the accuracy of diagnoses made by frozen section. DESIGN: In 1994, participants in the College of American Pathologists Q-Probes laboratory quality improvement program each completed questionnaires and prospectively collected data on up to 20 frozen section procedures performed over a 5-month period. SETTING: Surgical pathology laboratories serving private and public hospitals with 300 or fewer occupied beds. PARTICIPANTS: Two hundred thirty-two North American institutions and one New Zealand institution. MAIN OUTCOME MEASURES: The discordance and deferral rates of frozen section diagnoses and the reasons for frozen section discordance relative to corresponding diagnoses made on permanent (paraffin) sections. Calculation of frozen section discordance rates excluded diagnoses of subtypes or grade of malignancy, biopsies on specimens in which there was no gross lesion (eg, mammographic specimens), thyroid follicular lesions, tissue taken only to determine adequacy for other studies (eg, estrogen-binding proteins), and frozen sections performed to evaluate margins of specimens oriented en face. RESULTS: Out of 18,532 frozen section diagnoses performed on 327,884 surgical cases, 859 (4.6%) diagnoses were deferred until permanent sections were available for review; 17,357 (98.2%) nondeferred diagnoses agreed with, and 316 (1.8%) disagreed with, those diagnoses rendered on permanent sections. The most common cause of discordance was underdiagnosis of neoplasia, usually due to block- or tissue-sampling errors. CONCLUSIONS: We recommend that laboratories routinely monitor frozen section discordance, cut additional sections deeper into the frozen block and/or sample additional tissue when the initial frozen section diagnosis is negative or nonproductive, reconcile all discordant frozen section diagnoses in the final report, and periodically assess the value of performing frozen section examinations.

Diagnostic Errors↗

Numerical study of the accuracy and efficiency of various approaches for Monte Carlo surface hopping calculations.

A one-dimensional, two-state model problem with two well-separated avoided crossing points is employed to test the efficiency and accuracy of a semiclassical surface hopping technique. The use of a one-dimensional model allows for the accurate numerical evaluation of both fully quantum-mechanical and semiclassical transition probabilities. The calculations demonstrate that the surface hopping procedure employed accounts for the interference between different hopping trajectories very well and provides highly accurate transition probabilities. It is, in general, not computationally feasible to completely sum over all hopping trajectories in the semiclassical calculations for multidimensional problems. In this case, a Monte Carlo procedure for selecting important trajectories can be employed. However, the cancellation due to the different phases associated with different trajectories limits the accuracy and efficiency of the Monte Carlo procedure. Various approaches for improving the accuracy and efficiency of Monte Carlo surface hopping procedures are investigated. These methods are found to significantly reduce the statistical sampling errors in the calculations, thereby increasing the accuracy of the transition probabilities obtained with a fixed number of trajectories sampled.

Journal Article↗

Multicenter evaluation of a new ultrasound-guided biopsy device: Improved ergonomics, sampling and rebiopsy rates.

The purpose of this study was to evaluate performance, ergonomics, and immediate rebiopsy rate of a new vacuum-assisted biopsy (VAB) device for ultrasound-guided breast biopsies. Between December 2002 and April 2003, 113 patients meeting study criteria were biopsied at four centers using the new 9 gauge VAB device. The device has a radiofrequency-tipped probe, 360 degrees vacuum, a circumferential cutter, and a coaxial cannula for multiple sampling. Patient and procedural data included breast composition, lesion characteristics, number of samples, procedure time, and complications. Quality of samples, lesion access, and ergonomic features were assessed qualitatively and compared with prior experience with other biopsy devices. Immediate rebiopsy rate included high-risk lesions requiring surgical excision (obligate rebiopsy) and lesions requiring rebiopsy due to discordance or insufficient samples yielding nondiagnostic material. Data were analyzed using the Wilcoxon signed-rank test. One hundred thirteen patients aged 20-83 years (mean 52) were successfully biopsied with dense/fibrous breast tissue in 60% and dense/fibrous lesions in 49%. Lesions measured 6-63 mm (mean 17); 97% were masses. Five circumferential specimens (range 2-19) were obtained in 6 minutes (range 2-20). Operators rated safety and comfort comparable with existing devices and rated sample quality, breast/lesion penetration, and positioning ease/accuracy superior (p < 0.01). Diagnoses included 37 cancers, 70 benign, and six high-risk lesions with one upgrade from atypical ductal hyperplasia to ductal carcinoma in situ at surgery. Excluding obligate excision in high-risk diagnoses, the immediate rebiopsy rate was 2%. No complications required intervention. The new VAB device provides diagnostic samples and reduces sampling error defined by immediate rebiopsy rate. Compared with other devices, it is more ergonomic to target and position for sampling, particularly in dense breast tissue or lesions.

Adult↗