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PubMed1985

Crisis in drug testing. Results of CDC blind study.

In response to questions about the reliability of the results of screening urine for drugs, we evaluated the performance of 13 laboratories, which serve a total of 262 methadone treatment facilities, by submitting prereferenced samples through the treatment facilities as patient samples (blind testing). Error rates for the 13 laboratories on samples containing barbiturates, amphetamines, methadone, cocaine, codeine, and morphine ranged from 11% to 94%, 19% to 100%, 0% to 33%, 0% to 100%, 0% to 100%, and 5% to 100%, respectively. Similarly, error rates on samples not containing these drugs (false-positives) ranged from 0% to 6%, 0% to 37%, 0% to 66%, 0% to 6%, 0% to 7%, and 0% to 10%, respectively. These blind tests indicate that greater care is taken with known evaluation samples than with routine samples, laboratories are often unable to detect drugs at concentrations called for by their contracts, and the observed underreporting of drugs may threaten the treatment process. Drug treatment facilities should monitor the performance of their contract laboratories with quality-control samples, preferably through blind testing.

Amphetamines↗
PubMed2006

The progressive focusing correction technique for ultrasound beamforming.

This work presents a novel method for digital ultrasound beamforming based on programmable table look-ups, in which vectors containing coded focusing information are efficiently stored, achieving an information density of a fraction of bit per acquired sample. Timing errors at the foci are within half the period of a master clock of arbitrarily high frequency to improve imaging quality with low resource requirements. The technique is applicable with conventional as well as with deltasigma converters. The bit-width of the focusing code and the number of samples per focus can be defined to improve both memory size and F# with controlled timing errors. In the static mode, the number of samples per focus is fixed, and in the dynamic approach that figure grows progressively, taking advantage of the increasing depth of focus. Furthermore, the latter has the lowest memory requirements. The technique is well suited for research purposes as well as for real-world applications, offering a degree of freedom not available with other approaches. It allows, for example, modifying the sampling instants to phase aberration correction, beamforming in layered structures, etc. The described modular and scalable prototype has been built using low-cost field programmable gate arrays (FPGAs). Experimental measurements are in good agreement with the theoretically expected errors.

Algorithms↗
PubMed2006

Ashkenazi levites' "Y modal haplotype" (LMH)-- an artificially created phenomenon?

The article on the Y chromosomes of Ashkenazi Levites (Behar et al., 2003. Am. J. Hum. Genet. 73, 768-779) is the fourth in a series on the Y chromosomes of the three Jewish male castes: Cohanim (priests), Levites (priests' helpers) and Israelites (lay people). It became apparent that there is a problem with omission of samples when the second article "Origins of Old Testament priests" (Thomas et al., 1998. Nature 394, 138-140) was published. In the fourth article a remarkable 55% of the Ashkenazi Levite samples from the earlier 1998 study are not included. This causes the "Levite modal haplotype" to double its frequency from 21% of the Ashkenazi Levite sample in 1998 to 42% of the Ashkenazi Levite sample in 2003. The authors offer three main explanations: (1) The studies are independent using different sample sets.(2) Typing errors and poor quality exclude samples from future studies.(3) Correction of typing errors means that some samples are classified under different haplotypes. The explanations offered to the problem of omitting samples from subsequent studies after their haplotypes or partial haplotypes are known, are not convincing. Consequently their sample sets cannot be considered random and non-biased. At the least, these laboratories have bad practices of sample handling and many typing errors, which are enough to invalidate their studies.

Chromosomes, Human, Y↗
PubMed2002

Self-reports of aberrant behaviour on the roads: errors and violations in a sample of Greek drivers.

Recent studies have shown that unsafe driver acts can be classified into two distinct categories (i.e.. errors and violations) entailing different measures for reducing road traffic accidents. A survey of over 1,400 drivers in Greece is reported in which a variety of aberrant driving behaviours have been identified. The present study has confirmed the results of earlier studies in the driving populations of Britain. Australia and Sweden that errors and violations are the major determinants in the factor structure of aberrant behaviours. Three types of violations were identified including, highway code-, aggressive- and parking-violations (or situational violations). Mistakes and lapses were two major forms of errors. The factor analysis identified another two classes of behaviour that could not be accounted for very well by the error-violation distinction. One class of behaviours referred to a state of low preparedness and negligence while the other class referred to communication errors and 'social disregard' for the other road users. Each class of behaviour was found to have different demographic correlates. Finally, accident liability was predicted by self-reported tendency to commit highway-code violations, but not by tendency to make errors due to failures of judgement (i.e.. mistakes) or lapses. Aggressive violations were significantly related to involvement in speeding convictions and law-breaking whilst highway-code violations were related to speeding convictions only.

Accidents, Traffic↗
PubMed2005

Process analytical technology case study part I: feasibility studies for quantitative near-infrared method development.

This article is the first of a series of articles detailing the development of near-infrared (NIR) methods for solid-dosage form analysis. Experiments were conducted at the Duquesne University Center for Pharmaceutical Technology to qualify the capabilities of instrumentation and sample handling systems, evaluate the potential effect of one source of a process signature on calibration development, and compare the utility of reflection and transmission data collection methods. A database of 572 production-scale sample spectra was used to evaluate the interbatch spectral variability of samples produced under routine manufacturing conditions. A second database of 540 spectra from samples produced under various compression conditions was analyzed to determine the feasibility of pooling spectral data acquired from samples produced at diverse scales. Instrument qualification tests were performed, and appropriate limits for instrument performance were established. To evaluate the repeatability of the sample positioning system, multiple measurements of a single tablet were collected. With the application of appropriate spectral preprocessing techniques, sample repositioning error was found to be insignificant with respect to NIR analyses of product quality attributes. Sample shielding was demonstrated to be unnecessary for transmission analyses. A process signature was identified in the reflection data. Additional tests demonstrated that the process signature was largely orthogonal to spectral variation because of hardness. Principal component analysis of the compression sample set data demonstrated the potential for quantitative model development. For the data sets studied, reflection analysis was demonstrated to be more robust than transmission analysis.

Feasibility Studies↗
PubMed1987

Sampling and distribution of Anopheles quadrimaculatus immatures in rice fields.

Dipper samples of Anopheles quadrimaculatus immatures from stocked enclosures in Arkansas rice fields were used to develop regression equations relating dipper sample counts to absolute density. Confidence limits were developed for mean number of immatures collected at each density and stadia, including combined stadia. These data can be used to estimate absolute density from mean dipper count. Distribution of rice field immatures approximated but did not fit the Poisson distribution. Sample size was calculated for 10, 25 and 50% of the true mean, at various levels of Type I and II error. A sample size of N = 6,424 was necessary to detect differences within 10% of the true mean, with 5 and 10% probability of Type I and II error, respectively.

Agriculture↗
PubMed2006

Inter-laboratory comparison of NO2 and SO2 generated by dynamic dilution system under laboratory conditions: a technical discussion.

A workshop on analytical quality control (AQC) of ambient air quality measurement methods for nitrogen dioxide (NO(2)) and sulphur dioxide (SO(2)) was conducted by Central Pollution Control Board (CPCB) for officials involved in National Ambient Air Quality Monitoring (NAAQM) in India. Concentrations of NO(2) and SO(2) were generated by dynamic dilution system under laboratory conditions at low and high levels and measured using static dilution system and wet chemical methods laid down by CPCB under section 16(2)(h) of the air act 1981. CPCB provided the measured values as reference values for comparing the means obtained by the officials participated from thirteen organizations. A tolerance limit of +/-15% of the reference values was specified to accept the results. Generated concentrations, which were unknown to the participants, were measured using gaseous sampling assembly (Envirotech APM 411, New Delhi, India), and wet chemical methods laid down by CPCB i.e. the same methodology which is used by the organizations to generate the data of NO(2) and SO(2) in ambient air. Simultaneously, concentrations were checked by CPCB using automatic analyzers as a check on reference concentration. It is observed that results of automatic analyzers for NO(2) and SO(2) were within a tolerance of +/-5% with %RSD below 3. On the other hand, results of most of the participants showed variability in the measurements with %RSD ranging between +/-0.8 and +/-88.6 and exceedences of means from the tolerance limit with bias ranging between 1.4 and -59%. To check the cause of high variability in the measurements obtained under identical conditions, duplicate sampling was performed by one of the participants for SO(2) at low concentration level. In this study, results of wet chemical methods, automatic analyzers and results of duplicate sampling are analysed statistically to assess the cause of high variability in the measurements. Analysis of t-test and analysis of variance (ANOVA) showed highly significant results for NO(2) and SO(2) at high concentration levels (alpha 0.05) and for SO(2) at both the levels (alpha 0.01) respectively indicating some bias is existing either in the sampling or in analytical technique. Duplicate sampling performed to check precision in parallel measurements showed high %RSD indicating the presence of systematic error in sampling technique as the same calibration factor (CF) was used to measure the concentration of duplicate samples. Statistical analysis of flow rates of duplicate sampling showed that the sampling assembly could not maintain the constant flow rate within the +/-10% with that measured at the start of the sampling. This resulted in high %RSD and deviation from the reference values for the results of most of the participants, even after accepting +/-15% tolerance limit. There is a need to improve and evaluate this gaseous sample collection device under laboratory conditions to generate reliable database of NO(2) and SO(2) in ambient air.

Analysis of Variance↗
PubMed2005

Estimating haplotype frequencies in pooled DNA samples when there is genotyping error.

BACKGROUND: Maximum likelihood estimates of haplotype frequencies can be obtained from pooled DNA using the expectation maximization (EM) algorithm. Through simulation, we investigate the effect of genotyping error on the accuracy of haplotype frequency estimates obtained using this algorithm. We explore model parameters including allele frequency, inter-marker linkage disequilibrium (LD), genotyping error rate, and pool size. RESULTS: Pool sizes of 2, 5, and 10 individuals achieved comparable levels of accuracy in the estimation procedure. Common marker allele frequencies and no inter-marker LD result in less accurate estimates. This pattern is observed regardless of the amount of genotyping error simulated. CONCLUSION: Genotyping error slightly decreases the accuracy of haplotype frequency estimates. However, the EM algorithm performs well even in the presence of genotyping error. Overall, pools of 2, 5, and 10 individuals yield similar accuracy of the haplotype frequency estimates, while reducing costs due to genotyping.

DNA↗
PubMed1999

Pharmacokinetic investigations with direct injection of plasma samples: possible savings using capillary electrophoresis (CE).

Capillary electrophoresis (CE) is often regarded as a separation technique of choice because of its high selectivity and its cost advantages compared to LC.RSD% of 0.5% have become standard for quality control assays. Using CE, sample pretreatment can often be significantly reduced, leading to notable savings of labor and reagent costs. Moreover, errors from sample pretreatment steps are avoided. A number of pharmaceuticals (e.g. acetaminophen, salicylic acid, sulfamethoxazole, theophylline, tolbutamide, and trimethoprim) have been determined in human plasma on underivatized fused silica capillaries by MEKC without sample pretreatment, the total analysis time being only 10 min. An sodium dodecyl sulfate-containing borate buffer (60 mM with 200 mM SDS) at pH 10 has been used. Between runs, proteins adsorbed to the capillary wall are removed by a rinsing regimen consisting of SDS buffer and either acetonitrile (e.g. 50% v/v) or isopropanol (e.g. 10% v/v). Other rinsing approaches are discussed (salts, enzyme containing solutions, organic solvents, sodium hydroxide, hydrofluoric acid). The separation system is tested in a concentration range between 10 ng/mL and 100 micrograms/mL, the detection limit being about 5 ng/mL. The sensitivity has been substantially improved compared to preceding work using field-amplified injection mechanisms and efficient computer algorithms that take advantage of multiwavelength detection. Correlations between the limit of quantitation (LOQ), the limit of detection (LOD) and the signal/noise ratio are discussed. A day-to-day precision for relative peak areas of 1 to 2% relsdv (n > 40) has been reached in the upper concentration range. Thus, not only drug monitoring but also pharmacokinetic investigations from blood plasma have become possible without further sample pretreatment.

Acetaminophen↗
PubMed1986

Weighted integration method for local cerebral blood flow measurements with positron emission tomography.

A new technique called the weighted integration method for the measurement of local CBF (LCBF) in humans with positron emission tomography (PET) is presented. LCBF is calculated from weighted time integrals of the blood and tissue radioactivity curves. This method is computationally efficient and achieves nearly optimal statistical estimation of LCBF. The predicted root mean squared error of the weighted integration method is verified by simulation studies and is only 1-2% larger than the minimum possible error that can be achieved by an ideal estimation algorithm. For LCBF of greater than 30 ml/min/100 g, the weighted integration method provides reduced noise compared with the integrated projection technique, the PET autoradiographic method, and the steady-state technique. In addition, an error analysis is performed to study the sensitivity of the weighted integration method to tissue mixtures, blood sample timing errors, and changes in LCBF during the data collection period.

Brain↗
PubMed2005

Refractive index measurements of films with biaxial symmetry. 1. Determination of complex refractive indices using polarized reflectance/transmittance ratio.

A new method to extract complex refractive indices of films with biaxial symmetry from polarized transmission and reflection spectra is described. Theoretical analysis demonstrates that the reflectance/transmittance ratio (R/T ratio) of two films of different thicknesses but with the same optical anisotropy is a simple function of the refractive index (n) and extinction coefficient (k). For films with biaxial symmetry, components of n and k on symmetric axes can be extracted from either s- or p-polarized R/T ratios if the film thickness values are known. The R/T ratio method can generate n and k spectra within a particular wavelength range without assuming a specific relationship among n, k, and wavelength, which is an advantage over many currently available techniques. The R/T ratio method is used to extract the anisotropic complex refractive indices of a polyimide film with known uniaxial symmetry. The resultant n and k spectra compare well with simulations based on known n and k values. The accuracy of n and k spectra is affected mostly by data error in reflection and transmission spectra collection, thickness variation across sample films, and error in sample alignment.

Journal Article↗
PubMed1992

The epidemiology of premenstrual symptoms in a population-based sample of 2650 urban women: attributable risk and risk factors.

This epidemiologic survey achieved a reliable measure of the prevalence of premenstrual symptoms by avoiding the biases of small or selected samples, anamnestic error, and subjective expectation. From 6232 women (a 78.8% response), aged 20-49 years, identified through a random sample of urban households, the 24-hour prevalence of symptoms was obtained using the Moos' Menstrual Distress Questionnaire, administered without reference to the menstrual cycle. For 71% of the naturally cycling women, current cycle phase was determined by follow-up (n = 2650); but a higher prevalence of severe or moderately severe affective symptoms in the premenstrual compared to the mid-cycle phase was not found. However, observed risk factor interactions led to the conclusion that premenstrual distress is a discrete mood disorder, affecting women aged 25-35 years, with probable ovulatory cycles, and vulnerable to stress; and that the risk of affective symptoms attributable to the premenstrual state was one percent.

Adult↗
PubMedDate not supplied

Automated donor-recipient identification systems as a means of reducing human error in blood transfusion.

Clerical and administrative errors are the most common mistakes in blood banking, with errors of sample or patient identification accounting for the majority of mistakes. In an effort to reduce the incidence of human errors, three automated donor-recipient identification systems were developed and were evaluated under clinical conditions. After two years of development and bench testing, each set of equipment was tested, along with established procedures, at a large clinical center, a medium-sized community hospital and a regional donor center. Although none of the systems, as tested, proved acceptable under clinical conditions, a great deal was learned about prototype equipment testing in the clinical setting. Future development of identification systems for clinical use should respond to carefully defined problems, apply in all areas of the hospital or donor center, and be convenient and reliable. The development of the equipment should involve established manufacturers and be subject to exacting preclinical testing.

Blood Banks↗
PubMed2006

A dynamic programming algorithm for binning microbial community profiles.

MOTIVATION: A number of community profiling approaches have been widely used to study the microbial community composition and its variations in environmental ecology. Automated Ribosomal Intergenic Spacer Analysis (ARISA) is one such technique. ARISA has been used to study microbial communities using 16S-23S rRNA intergenic spacer length heterogeneity at different times and places. Owing to errors in sampling, random mutations in PCR amplification, and probably mostly variations in readings from the equipment used to analyze fragment sizes, the data read directly from the fragment analyzer should not be used for down stream statistical analysis. No optimal data preprocessing methods are available. A commonly used approach is to bin the reading lengths of the 16S-23S intergenic spacer. We have developed a dynamic programming algorithm based binning method for ARISA data analysis which minimizes the overall differences between replicates from the same sampling location and time. RESULTS: In a test example from an ocean time series sampling program, data preprocessing identified several outliers which upon re-examination were found to be because of systematic errors. Clustering analysis of the ARISA from different times based on the dynamic programming algorithm binned data revealed important features of the biodiversity of the microbial communities.

Algorithms↗
PubMed1986

Precision of assessing anthelmintic efficacy.

In counting internal helminthic parasites (the "worm burden") of domestic animals, physical restrictions often lead to sampling by small aliquots of unequal size among affected organs, among animals treated alike, and among groups of animals treated differently. We assess the impact of that type of sampling on the precision of the analyzed variable (log of estimated worm burden), derive the variance of the standard nonlinear estimator of efficacy of anthelmintic treatment, and examine the problem of number of animals required for adequate sensitivity of experiments. The standard error of sample geometric mean worm burden, for a particular anthelmintic treatment, and the standard error of estimated efficacy of a treatment, relative to control, are given for the case of log-normal burdens. Small aliquots affect precision critically only if mean burden is small, i.e., when sampling by small aliquots is unnecessary, because the physical effort required is not great. The minimal number of animals per treatment, required for at least 80% power to detect efficacy of .7 or higher, is about 4 to 6 for species of parasites constituting major burdens (where the coefficient of variation of worm burden often is near .7). However, the minimal number of animals may be as high as 15 to 20 per treatment for cases with lowly-abundant species of parasites (where the coefficient of variation may be as high as 2 or 3). An example is given to illustrate procedures.

Analysis of Variance↗
PubMed1985

Alternative dual system network estimators.

"When there are two or more data systems and none of them enumerates the population at an acceptable completeness level, concern about the bias due to underenumeration suggests an estimator which makes joint use of data compiled by the combined imperfect data systems. Conventional dual system estimators are based on the existence of two separate data collection systems. Dual system network estimators assume a main survey and a follow-up quality check survey. The main survey adopts a multiplicity counting rule that combines two mutually exclusive partial counting rules." Three dual system network estimators are presented. "One was previously proposed by Sirken (1979) and is the natural analogue of the conventional dual system estimator. The two other estimators are proposed as potential improvements, although neither of them is the natural analogue of the conventional dual system estimator. The design effects of the three estimators are compared analytically and empirically with one another, and with those of the single system conventional and network estimators." (summary in FRE)

Data Collection↗
PubMed2004

[Outlier diagnosis and calibration model optimization for near infrared spectroscopy analysis].

Outlier diagnosis is a very important step in building near infrared calibration model. Data outlier includes spectral outlier and chemical value outlier. Mahalanobis' distance, ratio of spectral residual and spectral variable leverage test were used to evaluate sample spectral outlier. Cook's distance and the ratio of sample square error of chemical value and predict value to the mean square error of calibration set were used to test chemical value outlier. Three calibration models of protein content of 50 wheat samples, protein content of 90 corn samples and cyclohexane content of four compounds mixture were investigated. It is demonstrated that outlier test is very helpful for optimizing near infrared calibration model.

Calibration↗
PubMed1988

Regression analysis in biological research: sample size and statistical power.

Regression analysis is often used to demonstrate associations among variables believed to be biologically related. Failure to demonstrate a "significant" relationship may be due to two factors: 1) the variables are truly unrelated, or 2) a relationship exists but goes undetected due to inadequate statistical power. Investigators must consider the second possibility since failure to detect a statistically significant relationship is often taken as evidence for no biological relationship. These issues are addressed in the context of the interrelationship between four features common to all statistical methods: the size of effect or relationship worth detecting, the Type I (alpha) error, the sample size, and the Type II (beta) error. An example derived from published data relating morphological characteristics of muscle fiber type and isokinetic strength performance illustrates the practical significance of this dilemma.

Regression Analysis↗