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PubMed1997

Undectable expression of hMLH1 protein in sporadic colorectal cancer with replication error phenotype.

PURPOSE: Four DNA mismatch repair genes have been identified as being susceptible genes for hereditary nonpolyposis colorectal cancer. Deficiency of one of the mismatch repair genes causes the replication error phenotype in more than 80 percent of patients with hereditary nonpolyposis colorectal cancer and in 10 to 30 percent of patients with sporadic colorectal cancer. To determine which mismatch repair gene is lacking the function in patients with replication error-positive colorectal cancer, several approaches have been used at the nucleic acid and protein levels. We studied replication error in 40 samples of randomly selected colorectal cancers and expression of hMSH2 and hMLH1 proteins analyzed by immunoblot in the tumor and normal tissues of the replication error-positive and replication error-negative samples. MATERIALS AND METHODS: Frozen tumor and normal tissues were obtained from 40 Japanese patients who had colorectal cancer. According to the Amsterdam criteria, those patients were classified as having 39 sporadic and 1 unknown colorectal cancers. Genomic DNA was extracted from tumor and normal tissues for determining replication error with eight microsatellite markers. Expression of hMSH2 and hMLH1 proteins in cell lysates of tumor and normal tissues of 16 patients was analyzed by immunoblot. RESULTS: The replication error phenotype was found in 6 (15 percent) of the 39 sporadic cases. hMLH1 protein was not detected in two of the six replication error-positive tumor tissues and not in the normal tissues, indicating that the tumor cells of the two patients had severe mutations in both alleles of the hMLH1 gene. Another four replication error-positive and ten replication error-negative tumors and normal tissues expressed hMLH1 protein. hMSH2 protein was detected in all samples. CONCLUSION: hMLH1 protein was undetectable in the two tumor tissues of the six replication error-positive samples of sporadic colorectal cancer. The detection procedure used here may have potential use for determining a dysfunctional mismatch repair gene product.

Adaptor Proteins, Signal Transducing↗
PubMed1990

The representativeness of observational samples of different durations.

The representativeness of behavioral observation samples with durations of less than the whole time of interest was investigated. A real-time recording system was developed to quantify the behavior of 5 profoundly mentally retarded physically handicapped adult students in an institutional training setting. Behavior was observed using six mutually exclusive and exhaustive categories during 2.5-hr observation sessions. Sample observation sessions with durations ranging from 15 to 135 min were computer simulated from the whole-session (150-min) records. It was found that the representativeness of these samples, when compared to whole-session records, was a function of the relative duration of the behavioral categories and of sample duration. The occurrence of relatively high-duration behaviors (lasting for more than 50% of the session) was estimated to within 20% error by samples of less than 60 min, but low-duration behaviors (1 to 3% of the session) were inadequately quantified even from 135-min samples. Increasing irregularity of bouts of behavior in the low-duration behaviors is suggested as the cause of the functions obtained. Implications of the findings for applied behavior analysis are discussed, with the recommendation that the adequacy of observational session durations be empirically assessed routinely.

Adult↗
PubMed2003

Explaining and controlling regression to the mean in longitudinal research designs.

This tutorial is concerned with examining how regression to the mean influences research findings in longitudinal studies of clinical populations. In such studies participants are often obtained because of performance that deviates systematically from the population mean and are then subsequently studied with respect to change in the trait used for this selection. It is shown that in such research there is a potential for the estimates of change to be erroneous due to the effect of regression to the mean. The source of the regression effect is shown to arise from measurement error and a sampling bias of this measurement error in the process of selecting on extreme scores. It is also shown that regression effects are greater with measures that are less reliable and with samples that are selected with more extreme scores. Furthermore, it is shown that regression effects are particularly prominent when measures of change are based on changes in dichotomous states formed from quantitative, normally distributed traits. In addition to a formal analysis of the regression to the mean, the features of regression to the mean are demonstrated via a simulation.

Humans↗
PubMed2006

Sampling variability and estimates of density dependence: a composite-likelihood approach.

It is well known that sampling variability, if not properly taken into account, affects various ecologically important analyses. Statistical inference for stochastic population dynamics models is difficult when, in addition to the process error, there is also sampling error. The standard maximum-likelihood approach suffers from large computational burden. In this paper, I discuss an application of the composite-likelihood method for estimation of the parameters of the Gompertz model in the presence of sampling variability. The main advantage of the method of composite likelihood is that it reduces the computational burden substantially with little loss of statistical efficiency. Missing observations are a common problem with many ecological time series. The method of composite likelihood can accommodate missing observations in a straightforward fashion. Environmental conditions also affect the parameters of stochastic population dynamics models. This method is shown to handle such nonstationary population dynamics processes as well. Many ecological time series are short, and statistical inferences based on such short time series tend to be less precise. However, spatial replications of short time series provide an opportunity to increase the effective sample size. Application of likelihood-based methods for spatial time-series data for population dynamics models is computationally prohibitive. The method of composite likelihood is shown to have significantly less computational burden, making it possible to analyze large spatial time-series data. After discussing the methodology in general terms, I illustrate its use by analyzing a time series of counts of American Redstart (Setophaga ruticilla) from the Breeding Bird Survey data, San Joaquin kit fox (Vulpes macrotis mutica) population abundance data, and spatial time series of Bull trout (Salvelinus confluentus) redds count data.

Algorithms↗
PubMed2005

Quantization of accumulated diffused errors in error diffusion.

Due to its high image quality and moderate computational complexity, error diffusion is a popular halftoning algorithm for use with inkjet printers. However, error diffusion is an inherently serial algorithm that requires buffering a full row of accumulated diffused error (ADE) samples. For the best performance when the algorithm is implemented in hardware, the ADE data should be stored on the chip on which the error diffusion algorithm is implemented. However, this may result in an unacceptable hardware cost. In this paper, we examine the use of quantization of the ADE to reduce the amount of data that must be stored. We consider both uniform and nonuniform quantizers. For the nonuniform quantizers, we build on the concept of tone-dependency in error diffusion, by proposing several novel feature-dependent quantizers that yield improved image quality at a given bit rate, compared to memoryless quantizers. The optimal design of these quantizers is coupled with the design of the tone-dependent parameters associated with error diffusion. This is done via a combination of the classical Lloyd-Max algorithm and the training framework for tone-dependent error diffusion. Our results show that 4-bit uniform quantization of the ADE yields the same halftone quality as error diffusion without quantization of the ADE. At rates that vary from 2 to 3 bits per pixel, depending on the selectivity of the feature on which the quantizer depends, the feature-dependent quantizers achieve essentially the same quality as 4-bit uniform quantization.

Algorithms↗
PubMedDate not supplied

What is an intracluster correlation coefficient? Crucial concepts for primary care researchers.

BACKGROUND: Primary care research often involves clustered samples in which subjects are randomized at a group level but analyzed at an individual level. Analyses that do not take this clustering into account may report significance where none exists. This article explores the causes, consequences, and implications of cluster data. METHODS: Using a case study with accompanying equations, we show that clustered samples are not as statistically efficient as simple random samples. RESULTS: Similarity among subjects within preexisting groups or clusters reduces the variability of responses in a clustered sample, which erodes the power to detect true differences between study arms. This similarity is expressed by the intracluster correlation coefficient, or p (rho), which compares the within-group variance with the between-group variance. Rho is used in equations along with the cluster size and the number of clusters to calculate the effective sample size (ESS) in a clustered design. The ESS should be used to calculate power in the design phase of a clustered study. Appropriate accounting for similarities among subjects in a cluster almost always results in a net loss of power, requiring increased total subject recruitment. Increasing the number of clusters enhances power more efficiently than does increasing the number of subjects within a cluster. CONCLUSIONS: Primary care research frequently uses clustered designs, whether consciously or unconsciously. Researchers must recognize and understand the implications of clusters to avoid costly sample size errors.

Cluster Analysis↗
PubMed1975

Tissue sampling as a potential source of error in experimental studies of cartilage.

Although it might seem trite to point out that tissue sampling is a potential source of experimental error, this survey disclosed that even experienced investigators in fact often work with cartilage that is contaminated by non-cartilaginous tissue of which they were unaware. Twenty-two specimens ranging from chick embryo sternum to bovine nasal septum were studied by serial sectioning. Eighteen of the 22 contained extraneous tissue comprising from 3 to 50% of the cross-sectional area. The impact of the contamination depends on the use being made of the material and probably is greatest in cell culture studies because chondrocytes and fibroblasts have large differences in population doubling time. Several approaches for minimizing the error are suggested by the findings. Histological examination of specimen material is thus a desirable quality control procedure in the design and interpretation of experiments on cartilage as well as other tissues.

Animals↗
PubMed1993

Principles of digital sampling of a physiologic signal.

The practice of clinical neurophysiology requires fast, reliable and accurate assessment of a variety of biologic signals. Appropriate filters and rates of analog-to-digital sampling must be used to avoid distorting the signal. Using principles of sampling theory and examples, we describe the frequency content of signals encountered in clinical neurophysiology laboratories, offer guidelines for band-limiting frequencies, and give rules for determining minimal sampling frequencies. Errors introduced by undersampling (aliasing) are illustrated. When sophisticated computational techniques, such as discrete Fourier transform, are used to reconstruct the original wave form, a sampling frequency just above the double of the highest frequency content of the signal is adequate. Sampling neurophysiologic wave forms for direct display, however, requires a sampling frequency at least 4 times as high as that of the upper frequency filter.

Electromyography↗
PubMed1976

Errors of parameters of distribution functions for spherical bodies stochastically estimated on a random test plane.

The parameters of some distribution functions for the radius of spherical bodies randomly dispersed in a three-dimensional space can be estimated on a random test plane of unit surface area. In this estimation the set of measured Nao, delta and (delta2) or that of Nlambdao, lambda and (lambda2) is used. They are number of circles, arithmetical mean and secondary moment of circle diameters or number of chords delivered by intersection of a test line of unit length with circles, arithmetical mean and secondary moment of chord length, respectively. Provided that the region of measurement is sufficiently large, intraregional errors of these quantities expressed as the squares of coefficient of variation C are approximately: [C(Nao)]omega2=1/Nao, [C(delta)omega2=(32/3pi2)(Q3/Q2(2))(1/Nao) and [C(delta2)]omega2=(6/5)(Q5/Q3(2))(1/Nao); [C(Nlambdao)]omega2=1/MNlambdao, [C(lambda)]omega2=(9/8)(Q4Q2/Q3(2))(1/MNlambdao) and [C(lambda2)]omega2=(4/3)(Q6Q2/Q4(2))(1/MNlambdao). In these expressions Qn is a quotient defined by (Dn)/Dn, D and n being sphere diameter and a positive integer, respectively. The first three expressions may be used in these forms as the errors for the total region containing spheres. In the second three expressions M is the number of random test lines of unit length. When M is small, they can stand for the errors of the total region. In the case of large M, however, interregional errors or errors of sampling have to be added to them. The geometrical parameter of a distribution function of D is estimated from (delta2)/delta2 or (lambda2)/lambda2. The error of this ratio W is given by: [C(W)]2=[C(X2)-2C(X)]2, where X stands for delta or lambda.

Mathematics↗
PubMed1997

Sample filtration as a source of error in the determination of trace metals in marine waters.

Adequate performance in interlaboratory proficiency tests using filtered, pre-treated or pre-digested test materials does not necessarily demonstrate that laboratories' data are of adequate comparability. Sample handling can be an important source of error which is not examined by routine proficiency tests. This paper reports a study of sample filtration as a source error in the determination of trace metals in marine water samples. The results indicate that that current practice may need to be reviewed if important contamination errors are to be controlled.

Equipment Contamination↗
PubMed2003

[Precision of internal standard method in HPLC analysis].

The internal standard methods are known to compensate for the errors from sample preparation and injection into an analytical instrument. However, recent HPLC apparatuses have injectors of excellent repeatability and it is dubious whether the cancellation of injection error can lead to substantial improvement in the precision of analysis. This paper answers the above question experimentally and theoretically. The HPLC analysis of butylscopolamine bromide is taken as an example. The relative standard deviations (RSD) of measurements in the internal standard method and absolute calibration curve method are compared and the advantages of these methods are discussed. The measurement RSD is shown to be well estimated by the (function of mutual information) (FUMI) theory without repeating measurements. This report also demonstrates simple equations for calculating the measurement RSD at an arbitrary concentration of analyte and for selecting the better method between the internal standard method and absolute calibration curve method under specific experimental conditions.

Calibration↗
PubMed2004

Laboratory evaluation of a potential diesel fuel interference in the determination of polycyclic aromatic compounds on dermal samplers.

Road pavers are exposed to asphalt fumes through dermal contact, inhalation, or ingestion. These fumes contain polycyclic aromatic compounds (PACs), a class of compounds including polycyclic aromatic hydrocarbons (PAHs). The PAHs include compounds such as pyrene and benzo(a)pyrene and a large number of other compounds of known or suspected carcinogenicity. To estimate dermal deposition of asphalt fume particulate matter, polypropylene sampling patches can be worn on a worker's inside wrist. Diesel fuel used for cleaning can splash onto the dermal sampler. Exposed dermal patches were solvent extracted and PACs estimated in the extract using a modification of NIOSH Method 5800. The final solution was analyzed by high pressure liquid chromatography (HPLC) with a fluorescence detector using an excitation wavelength of 270 nanometers and an emission wavelength of 415 nanometers. The PACs were concentrated on a C-18 reverse phase guard column but not separated so that they could be measured expediently as a group. In this study we examined whether deposited diesel fuel interferes with the HPLC determination of PACs. We characterized the effect of diesel fuel contamination over broad ranges of both analyte and interferent. Two drops, or approximately 100 microL, of diesel fuel on the dermal samplers caused an overestimation of the concentration of polycyclic aromatic compounds (PACs). In the range of PACs determined in our field study (0 to 54 microg per sample), these errors could have exceeded 100%. Because 100 microL of deposited diesel fuel produced a clear visual "wetness," this observation can serve as one of the criteria for sample rejection. Sampling media must be examined carefully for visible contamination to prevent bias in the measurement of PACs deposited from asphalt fume.

Air Pollutants, Occupational↗
PubMed2006

Effects of differential genotyping error rate on the type I error probability of case-control studies.

OBJECTIVES: It is well known that genotyping error adversely affects the power of genetic case-control association studies but there is little research on its effects on type I error, and none that has addressed possible differences in genotype error rates between cases and controls. METHODS: We used simulations to examine the influence of genotyping error on the type I error probability given by case-control studies. The effect of genotyping error on the magnitude of type I error was explored for a single marker of varying minor allele frequency (MAF), and for haplotypic tests based on two markers with varying MAF and linkage disequilibrium (LD) measure r(2). RESULTS: We show that even with low genotyping error rates (<0.01), systematic differences in the error rate between samples can result in type I error rates substantially above 0.05. The effect was maximal for markers with small MAF, markers in strong LD, and where a common allele is more frequently misclassified as a rare allele than vice versa. The problem was also exacerbated by the use of large samples. CONCLUSIONS: Our results show that small differential genotyping error rates between cases and controls pose significant problems for association analyses. Differential genotyping error rates are particularly likely to arise where genotype data are combined from multiple sites, or where case genotypes are examined against archived reference population cohort genotypes that are being generated in several countries. Although these strategies may be necessary to obtain adequately powered samples, our data show the importance of stringent quality control. Furthermore, associations based on rare haplotypes should be treated with caution.

Alleles↗
PubMed1991

Effect of monitoring drug concentrations through lines used to administer the drugs: an in vitro study.

Elevated drug concentration (DC) can be caused by intentional or iatrogenic overdoses and sampling technique errors. This study examined, in vitro, technique factors that can cause and prevent false elevations of DCs when drugs are administered through the catheter lines from which blood samples are later taken for DC analysis. Digoxin, aminophylline, and phenytoin were administered through central catheters in concentrations simulating those used clinically. Drug solution remained in the lumen for a time similar to that encountered clinically, then either remained in the tubing or was flushed out with 5 ml of normal saline (NS). After 6 h, a 5-ml sample was withdrawn for DC analysis (the tip of the catheter placed in NS, which represented blood supply). Prior to final sample withdrawal, 5 ml of NS was drawn through half of the lines and discarded to simulate methods used to prevent contamination. Thus, various flushing/no flushing and sample discarding/no discarding techniques were analyzed. When diluted concentrations of drug were administered, minor artifactual DCs were observed unless the line was not flushed or sample fluid discarded prior to final sampling. With undiluted drug administration, only flushing after the dose and discarding a sample prior to final sampling prevented artifactual DCs. Clinicians should be aware of the potential for such artifactual elevations of DCs and should encourage techniques that prevent their occurrence.

Aminophylline↗
PubMed2007

Two-sample comparison based on prediction error, with applications to candidate gene association studies.

To take advantage of the increasingly available high-density SNP maps across the genome, various tests that compare multilocus genotypes or estimated haplotypes between cases and controls have been developed for candidate gene association studies. Here we view this two-sample testing problem from the perspective of supervised machine learning and propose a new association test. The approach adopts the flexible and easy-to-understand classification tree model as the learning machine, and uses the estimated prediction error of the resulting prediction rule as the test statistic. This procedure not only provides an association test but also generates a prediction rule that can be useful in understanding the mechanisms underlying complex disease. Under the set-up of a haplotype-based transmission/disequilibrium test (TDT) type of analysis, we find through simulation studies that the proposed procedure has the correct type I error rates and is robust to population stratification. The power of the proposed procedure is sensitive to the chosen prediction error estimator. Among commonly used prediction error estimators, the .632+ estimator results in a test that has the best overall performance. We also find that the test using the .632+ estimator is more powerful than the standard single-point TDT analysis, the Pearson's goodness-of-fit test based on estimated haplotype frequencies, and two haplotype-based global tests implemented in the genetic analysis package FBAT. To illustrate the application of the proposed method in population-based association studies, we use the procedure to study the association between non-Hodgkin lymphoma and the IL10 gene.

Adult↗
PubMed1991

Ionselective minielectrode determination of ionic and total calcium concentrations in mixed saliva.

A minielectrode suitable for determination of ionized and total calcium in small volumes (5 microliters or less) of biological fluids without loss of carbon dioxide from the sample, was evaluated. The relative standard deviation ranged from 4.5-7.1%, and analytical recovery from 97-101%. Interference by hydrogen, sodium and magnesium was negligible. Small differences in ionic strength between standards and samples caused only minor analytical errors. Freezing the sample prior to analysis significantly affected the readings for ionized calcium concentration. Compared to determination by atomic absorption spectrophotometry, there was no statistical difference in the total calcium concentration of mixed saliva determined by the electrode at approximately pH 4 after addition of a known volume of hydrogen chloride. This minielectrode method evaluated allows accurate calcium analysis of fluids such as secretion from minor salivary glands or the fluid in the dental integument, with subsequent recovery of the sample for further analysis.

Calcium↗
PubMed1994

Diurnal variation of mood and neuropsychological function in major depression with melancholia.

20 DSM-III-R melancholics with clinically evident diurnal symptoms and 20 controls were assessed with a battery of neuropsychological tests, a test of maximum voluntary hand-grip, and neuroendocrine measures of hypothalamic-pituitary-adrenal axis function morning and evening in a 24-h period, using a balanced design. The morning pattern of neuropsychological impairment in the melancholics was comprehensive, affecting attention and concentration/working memory, episodic memory, reaction time and, strikingly, the speed of simultaneous match to sample, which was performed more slowly than the version of the task delayed to 0 or 4 s. The melancholics were significantly weaker than controls, on a measure of maximal voluntary contraction. Significantly improved neuropsychological function was seen in the melancholic patients in the evening, in line with diurnal improvement in mood; there was also a large increase in strength. Slowing on the digit symbol substitution test, the simultaneous match to sample task, total errors on the match to sample and hand-grip remained impaired in the evening compared to controls; other neuropsychological measures were no longer statistically different from control values which were often worsened. Neuroendocrine measures showed significantly raised levels of cortisol and ACTH morning and evening in the melancholics. Morning cortisol in the melancholics correlated with the diurnal improvement in neuropsychological functioning. The results have implications for the timing of neuropsychological assessment in major depression. Indices of neuropsychological and motor function may be as reliable quantitative estimates of illness severity as subjective estimates of mood.

Adrenocorticotropic Hormone↗