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[A comparative study of efficiency of units designed for air sampling].

An analysis of a majority of cases of proliferation of pathogens and of contamination of personnel is indicative of the leading role of the air medium. At the same time, there is no, now, serial production of autonomous and portable air sampling devices. The purpose of the present study was to design the technical devices of a new type and to test their efficiency as compared with already known methods, equipment and devices. We worked out autonomous and portable devices of the bubble and impactor types. Comparative studies of the already known and newly designed devices point at feasibility for further studies of the construction of the latter and for the started tests; the studies also suggest that the spheres of usage of equipment designed by us could be expanded, which is confirmed by the obtained experimental data. There are reasons to believe that the devices in question could be used not only in experimental conditions but also in field studies.

Air↗

Nonmedical influences on medical decision making: an experimental technique using videotapes, factorial design, and survey sampling.

OBJECTIVE: To study nonmedical influences on the doctor-patient interaction. A technique using simulated patients and "real" doctors is described. DATA SOURCES: A random sample of physicians, stratified on such characteristics as demographics, specialty, or experience, and selected from commercial and professional listings. STUDY DESIGN: A medical appointment is depicted on videotape by professional actors. The patient's presenting complaint (e.g., chest pain) allows a range of valid interpretation. Several alternative versions are taped, featuring the same script with patient-actors of different age, sex, race, or other characteristics. Fractional factorial design is used to select a balanced subset of patient characteristics, reducing costs without biasing the outcome. DATA COLLECTION: Each physician is shown one version of the videotape appointment and is asked to describe how he or she would diagnose or treat such a patient. PRINCIPAL FINDINGS: Two studies using this technique have been completed to date, one involving chest pain and dyspnea and the other involving breast cancer. The factorial design provided sufficient power, despite limited sample size, to demonstrate with statistical significance various influences of the experimental and stratification variables, including the patient's gender and age and the physician's experience. Persistent recruitment produced a high response rate, minimizing selection bias and enhancing validity. CONCLUSION: These techniques permit us to determine, with a degree of control unattainable in observational studies, whether medical decisions as described by actual physicians and drawn from a demographic or professional group of interest, are influenced by a prescribed set of nonmedical factors.

Age Factors↗

Optimized blood sampling protocols and sequential design of kinetic experiments.

Design of optimal blood sampling protocols for kinetic experiments is discussed and evaluated, with the aid of several examples--including an endocrine system case study. The criterion of optimality is maximum accuracy of kinetic model parameter estimates. A simple example illustrates why a sequential experiment approach is required; optimal designs depend on the true model parameter values, knowledge of which is usually a primary objective of the experiment, as well as the structure of the model and the measurement error (e.g., assay) variance. The methodology is evaluated from the results of a series of experiments designed to quantify the dynamics of distribution and metabolism of three iodothyronines, T3, T4, and reverse-T3. This analysis indicates that 1) the sequential optimal experiment approach can be effective and efficient in the laboratory, 2) it works in the presence of reasonably controlled biological variation, producing sufficiently robust sampling protocols, and 3) optimal designs can be highly efficient designs in practice, requiring for maximum accuracy a number of blood samples equal to the number of independently adjustable model parameters, no more or less.

Animals↗

An integrated population-averaged approach to the design, analysis and sample size determination of cluster-unit trials.

While the mixed model approach to cluster randomization trials is relatively well developed, there has been less attention given to the design and analysis of population-averaged models for randomized and non-randomized cluster trials. We provide novel implementations of familiar methods to meet these needs. A design strategy that selects matching control communities based upon propensity scores, a statistical analysis plan for dichotomous outcomes based upon generalized estimating equations (GEE) with a design-based working correlation matrix, and new sample size formulae are applied to a large non-randomized study to reduce underage drinking. The statistical power calculations, based upon Wald tests for summary statistics, are special cases of a general power method for GEE.

Adolescent↗

Split-plot microarray experiments: issues of design, power and sample size.

This article focuses on microarray experiments with two or more factors in which treatment combinations of the factors corresponding to the samples paired together onto arrays are not completely random. A main effect of one (or more) factor(s) is confounded with arrays (the experimental blocks). This is called a split-plot microarray experiment. We utilise an analysis of variance (ANOVA) model to assess differentially expressed genes for between-array and within-array comparisons that are generic under a split-plot microarray experiment. Instead of standard t- or F-test statistics that rely on mean square errors of the ANOVA model, we use a robust method, referred to as 'a pooled percentile estimator', to identify genes that are differentially expressed across different treatment conditions. We illustrate the design and analysis of split-plot microarray experiments based on a case application described by Jin et al. A brief discussion of power and sample size for split-plot microarray experiments is also presented.

Analysis of Variance↗

[The design of ECG sample device based on Windows 98/95].

The ECG sample system which is based on Microsoft Windows98/95 and IBM-compatible PCs ISA bus, is introduced here. It includes ECG sample device, virtual device driver(VxD) and application program, By the method, we can design the device simply and make good use of the computer to programming powerful auto recognition software and telediagnosis software. The system is a cheap and mini medical apparatus. Applications in family care and community medical treatment are encouraging.

Electrocardiography↗

Sample size requirements for case-control study designs.

BACKGROUND: Published formulas for case-control designs provide sample sizes required to determine that a given disease-exposure odds ratio is significantly different from one, adjusting for a potential confounder and possible interaction. RESULTS: The formulas are extended from one control per case to F controls per case and adjusted for a potential multi-category confounder in unmatched or matched designs. Interactive FORTRAN programs are described which compute the formulas. The effect of potential disease-exposure-confounder interaction may be explored. CONCLUSIONS: Software is now available for computing adjusted sample sizes for case-control designs.

Case-Control Studies↗

Optimisation of alachlor solid-phase microextraction from water samples using experimental design.

We have tested screening and response surface experimental designs to optimise the solid-phase microextraction (SPME) of the widely used herbicide alachlor. Extraction time and sample volume were the only statistically significant factors from those studied. In the final optimised conditions the procedure was applied to the SPME-HPLC analysis of alachlor in spiked water samples with excellent figures of merit.

Acetamides↗

Evaluation of the Biological Sampling Kit (BiSKit) for large-area surface sampling.

Current surface sampling methods for microbial contaminants are designed to sample small areas and utilize culture analysis. The total number of microbes recovered is low because a small area is sampled, making detection of a potential pathogen more difficult. Furthermore, sampling of small areas requires a greater number of samples to be collected, which delays the reporting of results, taxes laboratory resources and staffing, and increases analysis costs. A new biological surface sampling method, the Biological Sampling Kit (BiSKit), designed to sample large areas and to be compatible with testing with a variety of technologies, including PCR and immunoassay, was evaluated and compared to other surface sampling strategies. In experimental room trials, wood laminate and metal surfaces were contaminated by aerosolization of Bacillus atrophaeus spores, a simulant for Bacillus anthracis, into the room, followed by settling of the spores onto the test surfaces. The surfaces were sampled with the BiSKit, a cotton-based swab, and a foam-based swab. Samples were analyzed by culturing, quantitative PCR, and immunological assays. The results showed that the large surface area (1 m2) sampled with the BiSKit resulted in concentrations of B. atrophaeus in samples that were up to 10-fold higher than the concentrations obtained with the other methods tested. A comparison of wet and dry sampling with the BiSKit indicated that dry sampling was more efficient (efficiency, 18.4%) than wet sampling (efficiency, 11.3%). The sensitivities of detection of B. atrophaeus on metal surfaces were 42 +/- 5.8 CFU/m2 for wet sampling and 100.5 +/- 10.2 CFU/m2 for dry sampling. These results demonstrate that the use of a sampling device capable of sampling larger areas results in higher sensitivity than that obtained with currently available methods and has the advantage of sampling larger areas, thus requiring collection of fewer samples per site.

Air Pollution, Indoor↗

Predictive Array Design. A method for sampling combinatorial chemistry library space.

A method, Predictive Array Design, is presented for sampling combinatorial chemistry space and selecting a subarray for synthesis based on the experimental design method of Latin Squares. The method is appropriate for libraries with three sites of variation. Libraries with four sites of variation can be designed using the Graeco-Latin Square. Simulated annealing is used to optimise the physicochemical property profile of the sub-array. The sub-array can be used to make predictions of the activity of compounds in the all combinations array if we assume each monomer has a relatively constant contribution to activity and that the activity of a compound is composed of the sum of the activities of its constitutive monomers.

Chemistry↗

Flavin radicals, conformational sampling and robust design principles in interprotein electron transfer: the trimethylamine dehydrogenase-electron-transferring flavoprotein complex.

TMADH (trimethylamine dehydrogenase) is a complex iron-sulphur flavoprotein that forms a soluble electron-transfer complex with ETF (electron-transferring flavoprotein). The mechanism of electron transfer between TMADH and ETF has been studied using stopped-flow kinetic and mutagenesis methods, and more recently by X-ray crystallography. Potentiometric methods have also been used to identify key residues involved in the stabilization of the flavin radical semiquinone species in ETF. These studies have demonstrated a key role for 'conformational sampling' in the electron-transfer complex, facilitated by two-site contact of ETF with TMADH. Exploration of three-dimensional space in the complex allows the FAD of ETF to find conformations compatible with enhanced electronic coupling with the 4Fe-4S centre of TMADH. This mechanism of electron transfer provides for a more robust and accessible design principle for interprotein electron transfer compared with simpler models that invoke the collision of redox partners followed by electron transfer. The structure of the TMADH-ETF complex confirms the role of key residues in electron transfer and molecular assembly, originally suggested from detailed kinetic studies in wild-type and mutant complexes, and from molecular modelling.

Animals↗

The value of information and optimal clinical trial design.

Traditional sample size calculations for randomized clinical trials depend on somewhat arbitrarily chosen factors, such as type I and II errors. Type I error, the probability of rejecting the null hypothesis of no difference when it is true, is most often set to 0.05, regardless of the cost of such an error. In addition, the traditional use of 0.2 for the type II error means that the money and effort spent on the trial will be wasted 20 per cent of the time, even when the true treatment difference is equal to the smallest clinically important one and, again, will not reflect the cost of making such an error. An effectiveness trial (otherwise known as a pragmatic trial or management trial) is essentially an effort to inform decision-making, i.e. should treatment be adopted over standard? As such, a decision theoretic approach will lead to an optimal sample size determination. Using incremental net benefit and the theory of the expected value of information, and taking a societal perspective, it is shown how to determine the sample size that maximizes the difference between the cost of doing the trial and the value of the information gained from the results. The methods are illustrated using examples from oncology and obstetrics.

Bayes Theorem↗

Issues in the use of adaptive clinical trial designs.

Sequential sampling plans are often used in the monitoring of clinical trials in order to address the ethical and efficiency issues inherent in human testing of a new treatment or preventive agent for disease. Group sequential stopping rules are perhaps the most commonly used approaches, but in recent years, a number of authors have proposed adaptive methods of choosing a stopping rule. In general, such adaptive approaches come at a price of inefficiency (almost always) and clouding of the scientific question (sometimes). In this paper, I review the degree of adaptation possible within the largely prespecified group sequential stopping rules, and discuss the operating characteristics that can be characterized fully prior to collection of the data. I then discuss the greater flexibility possible when using several of the adaptive approaches receiving the greatest attention in the statistical literature and conclude with a discussion of the scientific and statistical issues raised by their use.

Clinical Trials as Topic↗

HIV vaccine trials: some design issues including sample size calculation.

Anticipating the availability of one or more candidate HIV vaccines for efficacy testing in the next few years, public health agencies are now planning for the conduct of large-scale efficacy trials. We expect these trials to be randomized, double-blind, placebo-controlled studies with prevention of infection as the primary goal. We discuss in detail factors that influence sample size. Factors most influential are the incidence rate of HIV infection in the study population and the minimum efficacy at which a vaccine is still considered acceptable. The smaller either of these factors is, the larger the sample size will be. The desire to complete trials quickly, the gradual accrual of benefit from vaccination, the inaccuracies of assays to detect infection, the need to counsel participants to avoid exposure to HIV, and loss to follow-up all tend to drive up sample size. To illustrate, 83 subjects per study arm suffice to detect 90% efficacy in a population with a 7% annual risk of infection. This assumes a 3-year study with accrual completed in 1 year, no loss to follow-up, and Types I and II error rates of 5 and 10%, respectively. In contrast, 4,254 subjects per arm are required to identify a 60% effective vaccine in a population with a 1% annual risk. The study is also shortened to 2 years, assumes a 5% annual loss to follow-up, and supposes that the full benefit of vaccination is achieved in 6 months. The most realistic assumptions indicate that trials are very likely to require several thousand participants. Limitations of the proposed designs are also discussed.

Clinical Trials as Topic↗

The population study of women in Göteborg 1974--1975--the second phase of a longitudinal study. General design, purpose and sampling results.

A study of a population sample of women in Göteborg aged 38--60 years was carried out in 1968--1969. This population sample has been re-studied during the years 1974--1975. Altogether 1302 women participated in this second study, which means 89.1% of those studied in 1968--1969 and 80.3% of those initially sampled. Twenty-six women had died during the interval between the two studies, more than half of them from neoplastic disease. Information is given about those who had moved or were inaccessible at the time of the second study or who refused to participate. The performance of the examination is described and research projects are outlined.

Adult↗

A flow injection flow cytometry system for on-line monitoring of bioreactors.

For direct and on-line study of the physiological states of cell cultures, a robust flow injection system has been designed and interfaced with flow cytometry (FI-FCM). The core of the flow injection system includes a microchamber designed for sample processing. The design of this microchamber allows not only an accurate on-line dilution but also on-line cell fixation, staining, and washing. The flow injection part of the system was tested by monitoring the optical density of a growing E.coli culture on-line using a spectrophotometer. The entire growth curve, from lag phase to stationary phase, was obtained with frequent sampling. The performance of the entire FI-FCM system is demonstrated in three applications. The first is the monitoring of green fluorescent protein fluorophore formation kinetics in E.coli by visualizing the fluorescence evolution after protein synthesis is inhibited. The data revealed a subpopulation of cells that do not become fluorescent. In addition, the data show that single-cell fluorescence is distributed over a wide range and that the fluorescent population contains cells that are capable of reaching significantly higher expression levels than that indicated by the population average. The second application is the detailed flow cytometric evaluation of the batch growth dynamics of E.coli expressing Gfp. The collected single-cell data visualize the batch growth phases and it is shown that a state of balanced growth is never reached by the culture. The third application is the determination of distribution of DNA content of a S. cerevisiae population by automatically staining cells using a DNA-specific stain. Reproducibility of the on-line staining reaction shows that the system is not restricted to measuring the native properties of cells; rather, a wider range of cellular components could be monitored after appropriate sample processing. The system is thus particularly useful because it operates automatically without direct operator supervision for extended time periods.

Bioreactors↗