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At least 163 records · Page 9Linked to original sources
PubMed1988

A multi-factor experimental design for evaluating random-access analyzers.

A multi-factor experimental design for evaluating random-access analyzers has been developed and tested for the Ciba Corning "550 Express" random-access analyzer. The 12-sample design estimates imprecision, slope, nonlinearity, linear drift, and reagent carryover to the next assay. The design was constructed so that estimates of the factors' effects are almost entirely uninfluenced by each other. Use of the design is illustrated by an example in which reagent-to-assay carryover was pinpointed as an apparent cause of high imprecision. This led to a modification of the analyzer such that carryover was insignificant. The appendix contains a 27-sample design that provides additional estimates. Software to perform such calculations is available on request.

Aspartate Aminotransferases↗
PubMed2003

Statistical analysis and experimental design for mapping genes of complex traits in domestic animals.

Gene mapping for complex traits has been an active and challenging research area in humans, agricultural and laboratory species. In domestic animals and poultry, the goal of gene mapping is to find genes associated with production, reproduction and health traits. In humans, gene mapping for complex diseases has been a significant challenge. Although gene mapping results are accumulating rapidly, confirmed results are scarce. In domestic animals, gene mapping results are also accumulating rapidly and several large scale mapping projects in chickens, swine, and dairy cattle are currently in progress. Although new and more reliable results can be expected in the near future, the precise understanding of genes underlying complex traits is still some distance away. Recently, the approach of mapping genes of complex traits has been applied to gene expression data to map transcription regulatory elements, adding a new dimension to gene mapping. Statistical analysis of gene mapping data and experimental design are critical components of a gene mapping research. The purpose of this review article is to discuss current status as well as future directions and challenges in statistical analysis and experimental design for mapping genes of complex traits in domestic animals and poultry.

Animals↗
PubMed2004

Targeting angiogenesis for mammary cancer prevention: factors to consider in experimental design and analysis.

An experimental model developed to investigate premalignant stages of breast cancer was used to establish a rationale for designing experiments that target angiogenesis for cancer prevention. Blood vessels were identified via CD31 immunostaining, and all vessels that occurred in a 50 microm wide region circumscribing each pathology were counted using a digital imaging technique. The blood vessel density associated with terminal end buds was unaffected by carcinogen treatment, whereas vessel density was higher in intraductal proliferations and ductal carcinoma in situ than in terminal end buds (P < 0.001) and total vascularity increased with morphologic progression. In comparison with intraductal proliferation or ductal carcinoma in situ, mammary carcinomas had higher vascular density in the tissue surrounding the cancer with a marked increase in the number of blood vessels <25 microm(2). These data suggest that antiangiogenic chemopreventive agents would inhibit cancer occurrence if initiated at any premalignant stage of the carcinogenic process. Because increased vascular density observed during premalignancy could be explained by the size expansion of the lesion and its encroachment on a preexisting blood supply, by pathology-associated vessel expansion, and/or by angiogenesis, it remains to be determined if antiangiogenic agents will reduce the prevalence of premalignant lesions or cause their accumulation by blocking conversion to carcinomas. Failure to recognize the patterns of vascularization that accompany morphologic progression could limit the success of efforts to target angiogenesis for cancer prevention and lead to misinformation about how agents that affect blood vessel formation or growth inhibit the carcinogenic process.

Angiogenesis Inducing Agents↗
PubMed1988

Chiropractic management of spondylolisthesis with spondylolysis of the pars interarticularis: an example of the single-case study experimental design.

Case records permeating the chiropractic literature, although claiming success utilizing conservative therapies, often are founded on isolated circumstances rather than scientific data. A detailed examination of such reports reveals a void with respect to definitive and specific approaches for the diagnosis and clinical management of disorders synonymous with chiropractic clinical practice. At best, therefore, such reports are fraught with empiricism, illustrating only the experiences of individual clinicians. The underlying difficulty encountered in reporting information on purely didactic grounds is likely due to the absence of a mechanism by which improvement in biomechanical function may be precisely and adequately quantified. In direct contrast, controlled clinical trials, as in medical research, offer the luxury of statistical clarity as to the selection of one treatment regimen over another. Researchers have indicated that the single-case study experimental design may be of value in chiropractic clinical practice, allowing for the formulation of deductive conclusions derived from each case. To facilitate the process, implementation of both retrospective and prospective aspects are proposed modifications to the general scheme. It is the purpose of this article to employ the concept of the single-case study experimental design, illustrating a condition commonly encountered in chiropractic clinical practice, that of spondylolisthesis. In so doing, we attempt to adhere to the prescribed format, while outlining both the retrospective and prospective aspects, commensurate with such a problem within the clinical setting.

Adult↗
PubMed1994

Effect of individual housing and other experimental design factors on tumor incidence in B6C3F1 mice.

The effects of individual housing and other experimental design factors on body weight, survival, and tumor incidence in 72 control groups of B6C3F1 mice were evaluated. Individually housed males showed a greatly reduced incidence of dermal/subcutaneous tumors and an improved survival relative to group-housed animals. However, there were significant body weight increases in individually housed males and females and an associated marked increase in liver tumor incidence in both sexes and a lesser increase in lung neoplasms in males. Body weights of mice as young as 19 weeks of age were predictive of subsequent liver tumor incidence. There were no major differences in tumor rates among the various types of control groups, and differences in tumor rates among laboratories were not significant for most tumors. Differences among animal suppliers may have contributed to the time-related decreased incidence of malignant lymphoma observed in control mice, particularly in females. Comparisons with earlier control tumor rates suggest that there has been little change in tumor incidence for control groups having approximately equivalent body weights. However, control groups with heavier animals have shown a striking increase in the incidence of liver tumors. The National Toxicology Program recently returned to its earlier practice of group-housing female mice, and this should reduce the incidence of liver tumors in this sex-species group. However, if measures are not taken to reduce body weights, male mice (which continue to be individually housed because of fighting problems among group-housed animals) will likely continue to show a high incidence of liver tumors and possibly also lung neoplasms.

Animals↗
PubMed2006

Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies.

The median-effect equation derived from the mass-action law principle at equilibrium-steady state via mathematical induction and deduction for different reaction sequences and mechanisms and different types of inhibition has been shown to be the unified theory for the Michaelis-Menten equation, Hill equation, Henderson-Hasselbalch equation, and Scatchard equation. It is shown that dose and effect are interchangeable via defined parameters. This general equation for the single drug effect has been extended to the multiple drug effect equation for n drugs. These equations provide the theoretical basis for the combination index (CI)-isobologram equation that allows quantitative determination of drug interactions, where CI < 1, = 1, and > 1 indicate synergism, additive effect, and antagonism, respectively. Based on these algorithms, computer software has been developed to allow automated simulation of synergism and antagonism at all dose or effect levels. It displays the dose-effect curve, median-effect plot, combination index plot, isobologram, dose-reduction index plot, and polygonogram for in vitro or in vivo studies. This theoretical development, experimental design, and computerized data analysis have facilitated dose-effect analysis for single drug evaluation or carcinogen and radiation risk assessment, as well as for drug or other entity combinations in a vast field of disciplines of biomedical sciences. In this review, selected examples of applications are given, and step-by-step examples of experimental designs and real data analysis are also illustrated. The merging of the mass-action law principle with mathematical induction-deduction has been proven to be a unique and effective scientific method for general theory development. The median-effect principle and its mass-action law based computer software are gaining increased applications in biomedical sciences, from how to effectively evaluate a single compound or entity to how to beneficially use multiple drugs or modalities in combination therapies.

Algorithms↗
PubMed2002

An experimental design methodology applied to the enantioseparation of a non-steroidal anti-inflammatory drug candidate.

An experimental design methodology has been applied to the enantioseparation of a new synthesized aryl propionic acid of pharmaceutical interest, namely 2-[(4'-benzoyloxy-2'-hydroxy)phenyl-propionic acid] (DF-1770y) by chiral capillary zone electrophoresis (CCZE). The chiral separation of the studied compound has been achieved employing vancomycin as the chiral selector. The partial filling-counter current method has been used in order to avoid the presence of the absorbing chiral selector in the path length of the detector and to increase the method sensitivity. A central composite design has been employed to optimize the experimental conditions for a fast separation of the enantiomers of the new synthesized aryl propionic acid. Critical parameters such as chiral selector concentration, pH and temperature have been studied to evaluate how they affected responses such as resolution and migration times. The desirability function approach has been employed in order to find the best compromise between the different experimental responses. The proposed CCZE method provided the baseline enantioseparation of the investigated drug. A Britton-Robinson buffer at pH 6.4 supplemented with 7 mM of vancomycin at 22 degrees C and -20 kV were the optimum experimental conditions allowing to achieve the highest enantioresolution of DF-1770y in less than 8.5 min.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Interval-specific congenic strains (ISCS): an experimental design for mapping a QTL into a 1-centimorgan interval.

A general experimental design that allows mapping of a quantitative trait locus (QTL) into a 1-cM interval is presented. The design consists of a series of strains, termed "interval-specific congenic strains (ISCS)". Each ISCS is recombinant at a specific 1-cM sub-interval out of an ordered set of sub-intervals, which together comprise a wider interval, to which a QTL was previously mapped. It is shown that a specific and previously detected QTL of moderate or even small effect can be accurately mapped into a 1-cM interval in a program involving a total of no more than 1000 individuals. Consequently, ISCS can serve as the ultimate genetic mapping procedure before the application of physical mapping tools for positional cloning of a QTL.

Chromosome Mapping↗
PubMed2003

Application of statistically-based experimental designs for the optimization of nisin production from whey.

Statistically-based experimental designs were applied for the optimization of nisin production by Lactococcus lactis in a whey-based medium. Yeast extract, KH2PO4, and MgSO4 were identified to have significant effects on nisin biosynthesis by a Plackett-Burman design. These three significant factors were subsequently optimized using central composite design, and the optimal conditions were determined to be 12.067 g l(-1) for yeast extract, 0.569 g l(-1) for KH2PO4, and 0.572 g l(-1) for MgSO4. The validity of the optimal conditions was verified by a separate experiment.

Animals↗
PubMed1986

A computer program for enzyme kinetics that combines model discrimination, parameter refinement and sequential experimental design.

A method of model discrimination and parameter estimation in enzyme kinetics is proposed. The experimental design and analysis of the model are carried out simultaneously and the stopping rule for experimentation is deduced by the experimenter when the probabilities a posteriori indicate that one model is clearly superior to the rest. A FORTRAN77 program specifically developed for joint designs is given. The method is very powerful, as indicated by its usefulness in the discrimination between models. For example, it has been successfully applied to three cases of enzyme kinetics (a single-substrate Michaelian reaction with product inhibition, a single-substrate complex reaction and a two-substrate reaction). By using this method the most probable model and the estimates of the parameters can be obtained in one experimental session. The FORTRAN77 program is deposited as Supplementary Publication SUP 50134 (19 pages) at the British Library (Lending Division), Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1986) 233, 5.

Computers↗
PubMed2002

Development of generic liquid chromatography-mass spectrometry methods using experimental design.

Standard approaches to development of liquid chromatography-mass spectrometry (LC-MS) methods, either ion-pairing or reversed-phase liquid chromatography, have been through trial and error or intentional variation of experimental factors. These approaches to method optimization fail to take into account interactions between experimental factors and therefore the results may not be optimal for the combination of experimental factors. Another approach to optimization is through the use of chemometrics. Chemometric approaches can be more efficient than trial and error or intentional variation because chemometrics make use of multivariate designs; experimental factors are varied simultaneously at the various levels. Therefore chemometrics can take into account interactions between factors. The goal of this study was to develop a generic ion-pair LC-MS method for the analysis of acidic compounds using a chemometric approach called design of experiments (DOE). Four acidic compounds which cover three classes of acidic functional groups: 1-naphthyl phosphate (1), 1-naphthalenesulfonic acid (2), 2-naphthalenesulfonic acid (3), and (1-naphthoxy)acetic acid (4) were used as model compounds to develop the generic method. This study illustrates that LC-MS conditions can be optimized efficiently with minimal amount of experimentation using a chemometric approach to experimental design.

Chromatography, Liquid↗
PubMed2004

Sample preparation optimization for assay of active pharmaceutical ingredients in a transdermal drug delivery system using experimental designs.

A simple but very effective sample preparation method is discussed for a matrix or drug-in-adhesive type of transdermal drug delivery system (TDS). The method is a one-step extraction using a methanol/water solvent system. Because of the unique design and physical property of the delivery system, special considerations were taken in selection of sample solvent, sample container and extraction enhancement device. The main focus of the article is on method optimization using experimental designs. A Plackett-Burman design was used to screen multiple method factors including extraction solvent strength, extraction solvent volume, shaking speed of a reciprocating shaker, and shaking time. Later, two of the factors were studied in more details using a 4 x 5 general factorial design. From the experimental results, the so-called main effects plots and interaction plots were generated using a statistical software. The plots are helpful in choosing the method conditions.

Administration, Cutaneous↗
PubMed1996

Rational experimental design for bioanalytical methods validation. Illustration using an assay method for total captopril in plasma.

Generally, bioanalytical chromographic methods are validated according to a predefined programme and distinguish a pre-validation phase, a main validation phase and a follow-up validation phase. In this paper, a rational, total performance evaluation programme for chromatographic methods is presented. The design was developed in particular for the pre-validation and main validation phases. The entire experimental design can be performed within six analytical runs. The first run (pre-validation phase) is used to assess the validity of the expected concentration-response relationship (lack of fit, goodness of fit), to assess specificity of the method and to assess the stability of processed samples in the autosampler for 30 h (benchtop stability). The latter experiment is performed to justify overnight analyses. Following approval of the method after the pre-validation phase, the next five runs (main validation phase) are performed to evaluate method precision and accuracy, recovery, freezing and thawing stability and over-curve control/dilution. The design is nested, i.e., many experimental results are used for the evaluation of several performance characteristics. Analysis of variance (ANOVA) is used for the evaluation of lack of fit and goodness of fit, precision and accuracy, freezing and thawing stability and over-curve control/dilution. Regression analysis is used to evaluate benchtop stability. For over-curve control/dilution, additional to ANOVA, also a paired comparison is applied. As a consequence, the recommended design combines the performance of as few independent validation experiments as possible with modern statistical methods, resulting in optimum use of information. A demonstration of the entire validation programme is given for an HPLC method for the determination of total captopril in human plasma.

Calibration↗
PubMed1998

Involving students in experimental design: three approaches.

Many faculty want to involve students more actively in laboratories and in experimental design. However, just "turning them loose in the lab" is time-consuming and can be frustrating for both students and faculty. We describe three different ways of providing structures for labs that require students to design their own experiments but guide the choices. One approach emphasizes invertebrate preparations and classic techniques that students can learn fairly easily. Students must read relevant primary literature and learn each technique in one week, and then design and carry out their own experiments in the next week. Another approach provides a "design framework" for the experiments so that all students are using the same technique and the same statistical comparisons, whereas their experimental questions differ widely. The third approach involves assigning the questions or problems but challenging students to design good protocols to answer these questions. In each case, there is a mixture of structure and freedom that works for the level of the students, the resources available, and our particular aims.

Curriculum↗
PubMed2000

Optimization study on the formulation of roxithromycin dispersible tablet using experimental design.

This study set out to improve the physical and pharmaceutical characteristics of the present formulation using an appropriate experimental design. The work described here concerns the formulation of the dispersible tablet applying direct compression method containing roxithromycin in the form of coated granules. In this study 2(3) factorial design was used as screening test model and Central Composite Design (CCC) associated with response surface methodology was used as optimization study model to develop and to optimize the proper formulation of roxithromycin dispersible tablet. The three independent variables investigated were functional excipients like binder (X1), disintegrant (X2) and lubricant (X3). The effects of these variables were investigated on the following responses: hardness (Y1), friability (Y2) and disintegration time (Y3) of tablet. Three replicates at the center levels of the each design were used to independently calculate the experimental error and to detect any curvature in the response surface. This enabled the best formulations to be selected objectively. The effect order of each term to all response variable was X3> X2> X1> X1*X2> X2*X2> X2*X3> X3*X3> X1*X3> X1*X1 and model equations on each response variables were generated. Optimized compositions of formula were accordingly computed using those model equations and confirmed by following demonstration study. As a result, this study has demonstrated the efficiency and effectiveness of using a systematic formulation optimization process to develop the tablet formulation of roxithromycin dispersible tablet with limited experiment.

Anti-Bacterial Agents↗
PubMed1991

Cancer promotion in a mouse-skin model by a 60-Hz magnetic field: I. Experimental design and exposure system.

The rationale for selection of an animal model, the experimental design, and the design and evaluation of an exposure system used in studies of 60-Hz magnetic fields are described. The studies were conceived to assay development of cancer and immune responsiveness in mice exposed to magnetic fields. The exposure system utilized a quadrupole-coil configuration to minimize stray magnetic fields. Four square-wound coil provided a uniform field within a volume occupied by 16 animal cages. The magnetic field had a mean flux density of 2 mT that varied less than +/- 10% within the volume occupied by animals' cages. The flux density decreased to less than 0.1 microT at a distance of 2 m from the coils. In each exposure system 32 animals could be housed in plastic cages.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2004

Experimental design on single-time-point high-throughput microsomal stability assay.

An experimental design for a single-time-point microsomal stability assay was evaluated as compared with multiple-time-point studies. Results obtained from single-time-point experiments are in excellent agreement with those from multiple time points. First-order reaction kinetics revealed rapid changes of predicted half-life from percent remaining of the parent compound at the inflection points, suggesting a maximum predictive limit for half-life. Selection of the incubation time in single-time-point assays is important to obtain balanced information for stable and unstable compounds. A short incubation time (e.g., 5 min) is most useful for differentiating between unstable compounds, which is beneficial to direct the synthetic efforts in projects with poor metabolic stability. A long incubation time (e.g., 30 min) is more applicable to a compound series with high metabolic stability. For screening purposes, a moderate incubation time (e.g., 15 min) is recommended to achieve good resolution and a sufficiently high maximum predictive limit for half-life. This study suggests that a single-time-point assay is sufficient for ranking compounds in early drug discovery. It increases throughput and reduces turnaround time and cost.

Animals↗
PubMed2005

Assessing statistical precision, power, and robustness of alternative experimental designs for two color microarray platforms based on mixed effects models.

Recommendations on experimental designs for two color microarray systems have been generally conflicting as they pertain to the general choice between reference and non-reference loop designs. This conflict may currently exist because many previously published assessments may not have effectively connected design layout with the level of biological relative to technical replication. We reassess various reference and non-reference designs for statistical efficiency in terms of standard errors of mean differences, power of test, and robustness using recently developed mixed model software tools. In minimally replicated cases (n = 2), it appears that the reference design outperforms the classical loop design whereby a sample from each animal is used for only one particular array hybridization. Alternatively, the reference design was consistently inferior to those connected loop designs in which a sample from each animal is used in two different hybridizations. Nevertheless, the gap in power between these two designs diminished as the biological to residual variance ratio increased. The statistical efficiency of a single large classical loop design for the comparison of many treatments was demonstrated to be highly sensitive to missing arrays relative to a common reference design (n = 2). However, the use of two loops within an interwoven loop design was shown to be substantially more robust to missing arrays and statistically more efficient relative to a common reference design. Furthermore, the use of more than one loop leads to less disparity in precision and power comparisons between any two treatments.

Animals↗