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A protocol for determining the surface free energy of dental materials.

OBJECTIVE: The purpose of this study was to develop a standard methodology for measuring the surface free energy (SFE), and its component parts, of dental biomaterials. METHODS: The contact angle of each of four samples of two materials--low density polyethylene and poly(methyl methacrylate)--was measured three times in each of six liquids (1-bromonaphthalene, diiodomethane, ethylene glycol, formamide, glycerol and distilled water). Critical surface tension estimates were obtained from Zisman plots. Data were then analyzed by the least-squares method to estimate the components of SFE. Estimates were also made for each of 12 liquid triplets, and by maximum likelihood and Bayesian analyses. RESULTS: The use of liquid triplets could yield misleading estimates of the components of SFE. A testing protocol is suggested in which multiple test liquids are used, and multiple methods of statistical analyses employed. SIGNIFICANCE: SFE is important, in that high SFE is desirable when adhesion is required, but undesirable if plaque resistance is needed. Methodology that avoids some of the limitations of existing studies has been proposed.

Bayes Theorem↗

Isolation and molecular characterization of vancomycin-resistant Enterococcus faecium in Malaysia.

Nineteen strains of vancomycin-resistant Enterococcus faecium isolated from 10 of 75 (13.3%) tenderloin beef samples were examined for resistance to selected antibiotics, presence of plasmids, and genetic diversity by random amplification of polymorphic DNA analysis. All strains showed multiple resistant to the antibiotics tested. Multiple antibiotic indexing of the vancomycin-resistant E. faecium strains showed that all (100%) originated from high risk contamination environments where antibiotics were often used. Plasmids ranging in size from 1.5 to 36 megadalton were detected in 15 of 19 (79%) strains. Thus, three plasmid profiles and eight antibiotypes were observed among the E. faecium strains. A high degree of polymorphism was obtained by combining the results of the two primers used; with the 19 E. faecium strains being differentiated into 19 RAPD-types. These preliminary results suggest that RAPD-PCR has application for epidemiologic studies and that resistance patterns and plasmid profiling could be used as an adjunct to RAPD for the typing of E. faecium in the study area.

Animals↗

Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with Burkholderia cepacia.

Most Burkholderia cepacia strains are resistant to many, or all, of the antibacterial agents commonly used in cystic fibrosis (CF), and selection of appropriate antibiotics for treatment of pulmonary exacerbations is therefore difficult. We developed a technique for rapid in vitro testing of multiple antibiotic combinations for B. cepacia isolates. For each of 119 multi-drug-resistant isolates of B. cepacia, our multiple combination bactericidal test (MCBT) studied the bactericidal activity of 10 to 15 antimicrobial agents using 225 +/- 97 single, double, and triple antibiotic combinations. Of the 119 isolates, 50% were resistant to all single antibiotics tested, 8% were resistant to all two-drug antibiotic combinations, but all were inhibited by at least one bactericidal triple-drug combination. When used alone, meropenem, ceftazidime and high-dose tobramycin (200 microg/ml) were bactericidal against only 47, 15, and 14% of in vitro isolates, respectively. Using a double antibiotic combination improved bactericidal activity; meropenem-minocycline, meropenem-amikacin, and meropenem-ceftazidime combinations were bactericidal against 76, 73, and 73% of isolates, respectively. However, 47% of isolates demonstrated antagonism (growth of an organism when a second antibiotic was added to a bactericidal single antibiotic). Triple antibiotic combinations that contained tobramycin, meropenem, and an additional antibiotic were most effective, and were bactericidal against 81 to 93% of isolates. We conclude that triple-antibiotic combinations are more likely than double and single antibiotic combinations to be bactericidal against B. cepacia in vitro. MCBT testing is a useful technique to help clinicians decide on appropriate nonantagonistic combination antibiotic therapy for patients with CF infected with B. cepacia.

Adult↗

Using the noninformative families in family-based association tests: a powerful new testing strategy.

For genetic association studies with multiple phenotypes, we propose a new strategy for multiple testing with family-based association tests (FBATs). The strategy increases the power by both using all available family data and reducing the number of hypotheses tested while being robust against population admixture and stratification. By use of conditional power calculations, the approach screens all possible null hypotheses without biasing the nominal significance level, and it identifies the subset of phenotypes that has optimal power when tested for association by either univariate or multivariate FBATs. An application of our strategy to an asthma study shows the practical relevance of the proposed methodology. In simulation studies, we compare our testing strategy with standard methodology for family studies. Furthermore, the proposed principle of using all data without biasing the nominal significance in an analysis prior to the computation of the test statistic has broad and powerful applications in many areas of family-based association studies.

Analysis of Variance↗

Prediction of bone marrow iron findings from tests performed on peripheral blood.

After evaluating multiple tests, the authors have devised a scheme to predict bone marrow iron findings from tests performed on peripheral blood. They examined bone marrows from 97 consecutive patients with anemia who were divided into five marrow morphologic groups: (1) iron deficiency; (2) anemia of chronic disease; (3) abnormal sideroblasts; (4) ring sideroblasts; and (5) other. Tests of peripheral blood included hemoglobin, hematocrit, red blood cell count and red blood cell indices, reticulocyte count, sedimentation rate or zetacrit, ferritin, iron, iron binding capacity, free erythrocyte protoporphyrin, and tests of hepatic and renal function. Cluster analysis, multidimensional scaling, and logistic discriminant analysis were used to derive a graph of serum ferritin with the sedimentation rate, allowing accurate confirmation or exclusion of iron deficiency in most patients. Percent saturation of serum transferrin and serum ferritin allowed identification of only 50 percent of patients with abnormal or ring sideroblasts while excluding 100 percent of patients without abnormal or ring sideroblasts. In three years of follow-up, two of 19 patients with abnormal or ring sideroblast have developed the dysmyelopoietic syndrome or ANLL, respectively. With the aid of the two parameter graphs described, the authors believe the differential diagnosis of the hypoproliferative anemias relating to iron metabolism can frequently be made without examination of the bone marrow.

Anemia↗

Multiplicity-adjusted sample size requirements: a strategy to maintain statistical power with Bonferroni adjustments.

BACKGROUND: A researcher must carefully balance the risk of 2 undesirable outcomes when designing a clinical trial: false-positive results (type I error) and false-negative results (type II error). In planning the study, careful attention is routinely paid to statistical power (i.e., the complement of type II error) and corresponding sample size requirements. However, Bonferroni-type alpha adjustments to protect against type I error for multiple tests are often resisted. Here, a simple strategy is described that adjusts alpha for multiple primary efficacy measures, yet maintains statistical power for each test. METHOD: To illustrate the approach, multiplicity-adjusted sample size requirements were estimated for effects of various magnitude with statistical power analyses for 2-tailed comparisons of 2 groups using chi2 tests and t tests. These analyses estimated the required sample size for hypothetical clinical trial protocols in which the prespecified number of primary efficacy measures ranged from 1 to 5. Corresponding Bonferroni-adjusted alpha levels were used for these calculations. RESULTS: Relative to that required for 1 test, the sample size increased by about 20% for 2 dependent variables and 30% for 3 dependent variables. CONCLUSION: The strategy described adjusts alpha for multiple primary efficacy measures and, in turn, modifies the sample size to maintain statistical power. Although the strategy is not novel, it is typically overlooked in psychopharmacology trials. The number of primary efficacy measures must be prespecified and carefully limited when a clinical trial protocol is prepared. If multiple tests are designated in the protocol, the alpha-level adjustment should be anticipated and incorporated in sample size calculations.

Clinical Protocols↗

Comparison of a frequency-based analysis of electroencephalograms (Z-ratio) and visual scoring on the multiple sleep latency test.

In a sample of multiple sleep latency test naps following nocturnal polysomnograms from a group of 13 patients of varying ages and diagnoses, we compared a computer-derived electroencephalographic (EEG) measure (z-ratio) with standard visual sleep stage scoring. In this clinical population, z-ratio scoring agreed with human scorers approximately 80% of the time when determining sleep versus wake in 30-second epochs. These results show that a single, objectively quantifiable value derived from a single channel of EEG can distinguish between sleep and wakefulness (as defined by Rechtschaffen and Kales) with at least a moderate degree of precision. When refined, the z-ratio method might be of use as the basis for a new sleep scoring system, particularly where an accurate determination of sleep onset is required.

Adolescent↗

Airway function in sarcoidosis.

Airway function was studied in 18 patients with sarcoidosis, aged 18 to 49 years. Eleven of the patients were smokers. All patients had the characteristic functional changes of restrictive lung disease: decreased lung volumes and single breath diffusing capacity, and increased static transpulmonary pressures. Abnormal airway function was demonstrated in every patient by at least one test, and nearly always by multiple tests. Specific airway conductance was abnormally low in two patients. The ratio of the 1 second forced expiratory volume to the forced vital capacity was decreased in six patients. Frequency dependence of dynamic compliance was demonstrated in eight patients. The ratio of closing volume to vital capacity was increased above age-corrected predictions in all but two patients. Upstream airway resistance was abnormally increased in 16 of the patients. These results suggest that airway dysfunction is not uncommon in sarcoidosis.

Adolescent↗

Concurrent validity of the cognitive component of schizophrenia: relationship of PANSS scores to neuropsychological assessments.

Cognitive symptoms of schizophrenia may represent a separate component of the disorder that is distinct from positive or negative syndromes. In a previous study, we reported a factor analysis of the Positive and Negative Syndrome Scale (PANSS) that revealed five components, one of which we labeled the Cognitive component. In the present study, we explored the validity of the PANSS Cognitive component by examining correlations between neuropsychological measures and the five factor-analytically derived PANSS scores for 147 subjects with diagnoses of schizophrenia or schizoaffective disorder. Higher scores on the PANSS Cognitive component were significantly correlated with poorer performance on all neuropsychological tests, including the Wisconsin Card Sorting Test (WCST), the Digit Symbol Substitution Task, the Slosson Intelligence Test, and the Gorham Proverbs Test. Multiple regression revealed that these test scores explained 37% of the variance in the Cognitive component score. Neuropsychological tests have very limited associations with the other PANSS components. These results suggest that the Cognitive component of the PANSS is a valid measure of cognitive deficits in schizophrenia, and they support the hypothesis that Cognitive impairment is a distinctive feature of schizophrenia independent of positive and negative syndromes.

Adult↗

Prognostic impact of total tumor volume and hemoglobin concentration on the outcome of patients with advanced head and neck cancer after concomitant boost radiochemotherapy.

PURPOSE: To identify prognostic clinical and treatment related factors for local control, distant metastasis-free survival, and survival by means of a multivariate analysis in patients with advanced squamous cell carcinoma of the head and neck after concomitant boost radiochemotherapy. PATIENTS AND METHODS: From 1992 to 1995, 68 patients with squamous cell cancer of the head and neck (93% stage IV disease) were treated with a simultaneous radiochemotherapy with Carboplatin using a concomitant boost technique. The total tumor volume (TTV) was quantitatively determined based on computed tomography scans in 56 patients. A Cox proportional hazards regression analysis was performed for each of the above endpoints and statistical significance of the Cox models was verified using the likelihood ratio test and Bonferroni correction for multiple testing. RESULTS: The survival and locoregional control rates at three years were 35 and 32%. The multivariate analysis revealed a significant association between the TTV and survival (P = 0.0008) and between the pretreatment serum hemoglobin concentration and locoregional control (P = 0.01) and survival (P = 0.05). The locoregional control was significantly associated with the N-stage (P = 0.007) and there was a good correlation between the N-stage and TTV in this study population. CONCLUSION: Our data corroborate the prognostic relevance of the tumor volume and hemoglobin concentration. In studies comparing the survival of patients with advanced cancer of the head and neck, the use of the TTV as a covariable may improve the statistical power.

Adult↗

Large-scale admixture mapping in the All of Us Research Program improves the characterization of cross-population phenotypic differences.

Admixed individuals have been understudied in medical research largely due to their complex genetic ancestries. However, the consideration of admixture can identify ancestry-enriched genetic associations, delineating genetic underpinnings of cross-population phenotypic variation. Here, we performed admixture mapping in individuals with inferred admixture from African and European populations (N = 48,921). Across 22 traits, we identified 71 ancestry-trait associations, including loci where ancestral haplotypes explained phenotypic variation yet were missed by single-variant association testing due to their stricter multiple testing burden. One such locus where inferred local AFR ancestries are associated with increased hemoglobin A1c (HbA1c) was 12q14.3, highlighting its potential role in explaining differences between populations. Together, our results expand upon the phenotypic differences between populations and characterize loci where genetic ancestries play a critical role in the architecture of disease.

Humans↗

Relationship between histopathologic gastritis and mucosal microvascularity: observations with magnifying endoscopy.

BACKGROUND: The purpose of this study was to determine the usefulness of magnifying endoscopy for the diagnosis of Helicobacter pylori-induced histopathologic gastritis. METHODS: A total of 92 patients scheduled to undergo routine endoscopic examination were enrolled. After routine endoscopic examination, 3 sites in the stomach were studied by magnified observation. Visualized collecting venulae were classified into the following 3 patterns: regular, irregular, and obscured. The sites observed by magnifying endoscopy were assessed histopathologically with an Updated Sydney System; 4 morphologic parameters (activity, inflammation, atrophy, metaplasia) were assessed and graded from 0 to 3. RESULTS: The regular pattern cases were negative for H pylori infection at all sites observed by magnifying endoscopy (antrum greater curve, 0/11; body greater curve, 0/24; body lesser curve, 0/23). The scores for all 4 morphologic parameters were significantly lower in the regular pattern group than the irregular and obscured groups (p < 0.01). The value of the atrophy parameter in the irregular group was significantly higher than that in the obscured group (p < 0.05 for a single test of hypothesis; correction for multiple testing of data removed significance). CONCLUSION: Visibility of collecting venulae in the gastric mucosa is influenced by H pylori-induced histopathologic gastritis. Magnifying endoscopy is useful for the diagnosis of histopathologic gastritis.

Cohort Studies↗

Wheelchair armrest strength testing.

There are about 1.4 million manual wheelchair users, 100,000 electric-powered wheelchair users, and 60,000 electric-powered scooter users. The current study was undertaken to determine if the fasteners of a clamp-type armrest receiver were prone to failure. The first test was used to examine the potential misalignment of the armrest receiver components that attach it to the frame. The second test was to evaluate the entire armrest using the American National Standards Institute/Rehabilitation Engineering and Assistive Technology Society of North America armrest static strength standard. Finally, we conducted three fatigue tests. The first fatigue test was performed by repeating the static stability tests multiple times. The last two tests were a modified version of the double-drum wheelchair fatigue test used to apply repeated loading and vibration simultaneously. A paired t-test showed that there is no statistically significant difference (p = 0.08), with a confidence of 95%, between critical alignment measurements. The armrest including the receiver passed the standard requirement of a force of 760 N being applied outward at 15 degrees. During fatigue testing, we found that armrests did not exhibit any visible or functional damage. Upon completion of the tests, the armrests and receivers functioned properly. At about 100,289 cycles on a double-drum test machine, three bolts failed on each armrest receiver when the screws were loosened to have only five threads engaged prior to commencing the test. The design of the armrest tested was in compliance with existing national and international standards. Currently, both International Standards Organization and American National Standards Institute/Rehabilitation Engineering and Assistive Technology Society committees are developing standards for seating systems that will include static, impact, and fatigue strength testing of devices like lateral torso supports, lateral hip support, etc. Methods similar to those explored in this study should be considered. This study may help manufacturers when designing products and purchasers or regulatory agencies when attempting to evaluate the safety and quality of armrest assemblies.

Equipment Design↗

Effect of normalization on significance testing for oligonucleotide microarrays.

MOTIVATION: Normalization techniques are used to reduce variation among gene expression measurements in oligonucleotide microarrays in an effort to improve the quality of the data and the power of significance tests for detecting differential expression. Of several such proposed methods, two that have commonly been employed include median-interquartile range normalization and quantile normalization. The median-IQR method applied directly to fold-changes for paired data also was considered. Two methods for calculating gene expression values include the MAS 5.0 algorithm [Affymetrix. (2002). Statistical Algorithms Description Document. Santa Clara, CA: Affymetrix, Inc. http://www.affymetrix.com/support/technical/whitepapers/sadd-whitepaper.pdf] and the RMA method [Irizarry, R. A., Bolstad, B. M., Collin, F., Cope, L. M., Hobbs, B., Speed, T. P. (2003a). Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res. 31(4,e15); Irizarry, R. A., Hobbs, B., Collin, F., Beazer-Barclay, Y. D., Antonellis, K. J., Scherf, U., Speed, T. P. (2003b). Exploration, normalization, and summaries of high density oligonucleotide array probe-level data. Biostatistics 4(2):249-264; Irizarry, R. A., Gautier, L., Cope, L. (2003c). An R package for analysis of Affymetrix oligonucleotide arrays. In: Parmigiani, R. I. G., Garrett, E. S., Ziegler, S., eds. The Analysis of Gene Expression Data: Methods and Software. Berlin: Springer, pp. 102-119]. RESULTS: In considering these methods applied to a prostate cancer data set derived from paired samples on normal and tumor tissue, it is shown that normalization methods may lead to substantial inflation of the number of genes identified by paired-t significance tests even after adjustment for multiple testing. This is shown to be due primarily to an unintended effect that normalization has on the experimental error variance. The impact appears to be greater in the RMA method compared to the MAS 5.0 algorithm and for quantile normalization compared to median-IQR normalization.

Analysis of Variance↗

Nonparametric methods for microarray data based on exchangeability and borrowed power.

This article proposes nonparametric inference procedures for analyzing microarray gene expression data that are reliable, robust, and simple to implement. They are conceptually transparent and require no special-purpose software. The analysis begins by normalizing gene expression data in a unique way. The resulting adjusted observations consist of gene-treatment interaction terms (representing differential expression) and error terms. The error terms are considered to be exchangeable, which is the only substantial assumption. Thus, under a family null hypothesis of no differential expression, the adjusted observations are exchangeable and all permutations of the observations are equally probable. The investigator may use the adjusted observations directly in a distribution-free test method or use their ranks in a rank-based method, where the ranking is taken over the whole data set. For the latter, the essential steps are as follows: (1) Calculate a Wilcoxon rank-sum difference or a corresponding Kruskal-Wallis rank statistic for each gene. (2) Randomly permute the observations and repeat the previous step. (3) Independently repeat the random permutation a suitable number of times. Under the exchangeability assumption, the permutation statistics are independent random draws from a null cumulative distribution function (c.d.f) approximated by the empirical c.d.f Reference to the empirical c.d.f tells if the test statistic for a gene is outlying and, hence, shows differential expression. This feature is judged by using an appropriate rejection region or computing a p-value for each test statistic, taking into account multiple testing. The distribution-free analog of the rank-based approach is also available and has parallel steps which are described in the article. The proposed nonparametric analysis tends to give good results with no additional refinement, although a few refinements are presented that may interest some investigators. The implementation is illustrated with a case application involving differential gene expression in wild-type and knockout mice of an E. coli lipopolysaccharide (LPS) endotoxin treatment, relative to a baseline untreated condition.

Animals↗

Assessing the writing of deaf college students: reevaluating a direct assessment of writing.

The NTID Writing Test was developed to assess the writing ability of postsecondary deaf students entering the National Technical Institute for the Deaf and to determine their appropriate placement into developmental writing courses. While previous research (Albertini et al., 1986; Albertini et al., 1996; Bochner, Albertini, Samar, & Metz, 1992) has shown the test to be reliable between multiple test raters and as a valid measure of writing ability for placement into these courses, changes in curriculum and the rater pool necessitated a new look at interrater reliability and concurrent validity. We evaluated the rating scores for 236 samples from students who entered the college during the fall 2001. Using a multiprong approach, we confirmed the interrater reliability and the validity of this direct measure of assessment. The implications of continued use of this and similar tests in light of definitions of validity, local control, and the nature of writing are discussed.

Adolescent↗

KOBAS server: a web-based platform for automated annotation and pathway identification.

There is an increasing need to automatically annotate a set of genes or proteins (from genome sequencing, DNA microarray analysis or protein 2D gel experiments) using controlled vocabularies and identify the pathways involved, especially the statistically enriched pathways. We have previously demonstrated the KEGG Orthology (KO) as an effective alternative controlled vocabulary and developed a standalone KO-Based Annotation System (KOBAS). Here we report a KOBAS server with a friendly web-based user interface and enhanced functionalities. The server can support input by nucleotide or amino acid sequences or by sequence identifiers in popular databases and can annotate the input with KO terms and KEGG pathways by BLAST sequence similarity or directly ID mapping to genes with known annotations. The server can then identify both frequent and statistically enriched pathways, offering the choices of four statistical tests and the option of multiple testing correction. The server also has a 'User Space' in which frequent users may store and manage their data and results online. We demonstrate the usability of the server by finding statistically enriched pathways in a set of upregulated genes in Alzheimer's Disease (AD) hippocampal cornu ammonis 1 (CA1). KOBAS server can be accessed at http://kobas.cbi.pku.edu.cn.

Alzheimer Disease↗

No compound a formation with Superia during minimal-flow sevoflurane anesthesia: a comparison with Sofnolime.

UNLABELLED: There is concern about the toxicity of Compound (Co) A. Absorbents differ in the production of Co A during minimal-flow sevoflurane anesthesia. Strong alkali-free Amsorb does not produce Co A. It was our aim to study Superia, another new NaOH- and KOH-free CO(2) absorbent, in minimal-flow anesthesia, compared with KOH-free Sofnolime. After Ethics Committee approval, 14 consenting adult patients were included randomly by using Superia or Sofnolime as the CO(2) absorbent in the compact 750-mL canister of an ADU ventilator. After propofol and remifentanil administration, sevoflurane was given in oxygen and air (500 mL/min; fraction of inspired oxygen, 0.4), aiming at an end-tidal concentration of 2.3%-2.5%; ventilation aimed for 33-35 mm Hg PETCO(2). Compound A inspired (Co A(insp)) and expired (Co A(exp)) samples were taken for analysis, and canister temperatures were measured for 150 min. Statistical analysis was performed with the Friedman test or the Mann-Whitney U-test where appropriate. Correction for multiple testing was used. In the Superia group, no significant amount of Co A was formed, whereas in the Sofnolime group, maximum median (range) inspiratory values of 25 ppm (16 ppm) were found. The intergroup difference was P < 0.05. No difference was noticed between the two groups for the canister CO(2) absorbent temperature. IMPLICATIONS: During minimal-flow 2.3%-2.5% end-tidal sevoflurane, no compound A (Co A) is formed with the NaOH- and KOH-free CO(2) absorbent Superia. Although Co A values with KOH-free Sofnolime are still within reported safe limits, Superia is definitely an alternative for safe clinical practice.

Absorption↗