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Results for “Experimental validation”

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At least 577 records · Page 32Linked to original sources

PubMed1987

A multidimensional approach to the assessment of clinical validity in a study on CCVD treatment: dihydroergocristine versus placebo.

An example of multidimensional assessment procedure applied to the study of treatment effects in a type of pathological aging is presented in this paper. Data discussed here come from a clinical trial performed to evaluate the effects of an ergot derivate, dihydroergocristine, in CCVD memory deficits. The multidimensional assessment procedure consisted of behavioral, clinical, and psychometric measures aimed to identify both the results related to drug activity (experimental validity), and the implications that these eventual drug-induced changes have on the everyday life patients' competence (clinical validity). 97 out-patients (both sexes were represented), with a mean age of 61.21 y (SD 7.29), who suffered from mild to moderate chronic cerebro-vascular disturbances were included in this double-blind study only when they met rigid inclusion criteria. The experimental period was 12 weeks. Results indicate a pattern of convergent, statistically significant, changes which evidence how treatment-associated memory changes are accompanied by an improvement of emotional and physical well being and by a modification of behavioral structure which is characterized by greater efficiency and greater responsiveness to stimuli.

Aged↗

PubMed1989

A new method for long-term inhalation toxicity studies for bronchospasmolytic aerosol formulations in dogs.

In routine inhalation toxicity studies laboratory animals are exposed under dynamic exposure conditions to different steady-state concentrations of a test compound. The relevant exposure concentration is the analytically determined time-weighted average concentration in the vicinity of the breathing zone of the animals. If the intended use of a bronchospasmolytic aerosol is taken into account, a non-steady-state exposure regimen might be more appropriate. Using this approach local effects of high aerosol concentrations on the respiratory tract were investigated in dogs by daily head/nose-only exposure for 1 h for 4 weeks. Four groups of four dogs were exposed to 20, 40 and 80 bursts of a bronchodilator formulation using a modified metered dose inhaler. The analytically determined mean concentration of the active ingredient (prostaglandin) in the breathing zone was 43.1, 92.2 and 193.9 micrograms l-1 air, respectively. Maximum concentrations were determined by simulation. The aerosol was in the respirable range (mass median aerodynamic diameter approximately 1.2 microns, geometric standard deviation approximately 1.4). A kinetic model was developed to simulate the mean and maximum non-steady-state concentration for an exposure regimen of 20, 40 and 80 bursts per hour under dynamic exposure conditions. The model was based on first-order inhalation chamber kinetics. The kinetic model was validated experimentally by comparing measured mean and simulated mean concentrations. In all exposure groups the simulated maximum concentrations were ca. 80 mg of test compound (formulation) per litre of air. Plasma levels were elevated in a dose-dependent manner as evidence of the validity of the test model employed.

Administration, Inhalation↗

PubMed1994

Recent developments in modeling heat transfer in blood perfused tissues.

Successful hyperthermia treatment of tumors requires understanding the attendant thermal processes in both diseased and healthy tissue. Accordingly, it is essential for developers and users of hyperthermia equipment to predict, measure and interpret correctly the tissue thermal and vascular response to heating. Modeling of heat transfer in living tissues is a means towards this end. Due to the complex morphology of living tissues, such modeling is a difficult task and some simplifying assumptions are needed. Some investigators have recently argued that Pennes' interpretation of the vascular contribution to heat transfer in perfused tissues fails to account for the actual thermal equilibration process between the flowing blood and the surrounding tissue and proposed new models, presumably based on a more realistic anatomy of the perfused tissue. The present review compares and contrasts several of the new bio-heat transfer models, emphasizing the problematics of their experimental validation, in the absence of measuring equipment capable of reliable evaluation of tissue properties and their variations that occur in the spatial scale of blood vessels with diameters less than about .2 mm. For the most part, the new models still lack sound experimental grounding, and in view of their inherent complexity, the best practical approach for modeling bio-heat transfer during hyperthermia may still be the Pennes model, providing its use is based on some insights gained from the studies described here. In such cases, these models should yield a more realistic description of tissue locations and/or thermal conditions for which the Pennes' model might not apply.

Blood Physiological Phenomena↗

PubMedDate not supplied

The modular analytical procedure and validation approach and the units of measurement for genetically modified materials in foods and feeds.

Food and feed analysts are confronted with a number of common problems, irrespective of the analytical target. The analytical procedure can be described as a series of successive steps: sampling, sample processing, analyte extraction, and ending, finally, in interpretation of an analytical result produced with, e.g., real-time polymerase chain reaction. The final analytical result is dependent on proper method selection and execution and is only valid if valid methods (modules) are used throughout the analytical procedure. The final step is easy to validate-the measurement uncertainty added from this step is relatively limited and can be estimated with a high degree of precision. In contrast, the front-end sampling and processing steps have not evolved much, and the corresponding methods are rarely or never experimentally validated according to internationally harmonized protocols. In this paper, we outlined a strategy for modular validation of the entire analytical procedure, using an upstream validation approach, illustrated with methods for genetically modified materials that may partially apply also to other areas of food and feed analyses. We have also discussed some implications and consequences of this approach in relation to reference materials, measurement units, and thresholds for labelling and enforcement, and for application of the validated methods (modules) in routine food and feed analysis.

Animal Feed↗

PubMed2005

On the importance of considering porosity when simulating the fatigue of bone cement.

Fatigue cracking in the cement mantle of total hip replacement has been identified as a possible cause of implant loosening. Retrieval studies and in vitro tests have found porosity in the cement may facilitate fatigue cracking of the mantle. The fatigue process has been simulated computationally using a finite element/continuum damage mechanics (FE/CDM) method and used as a preclinical testing tool, but has not considered the effects of porosity. In this study, experimental tensile and four-point bend fatigue tests were performed. The tensile fatigue S-N data were used to drive the computational simulation (FE/CDM) of fatigue in finite element models of the tensile and four-point bend specimens. Porosity was simulated in the finite element models according to the theory of elasticity and using Monte Carlo methods. The computational fatigue simulations generated variability in the fatigue life at any given stress level, due to each model having a unique porosity distribution. The fracture site also varied between specimens. Experimental validation was achieved for four-point bend loading, but only when porosity was included. This demonstrates that the computational simulation of fatigue, driven by uniaxial S-N data can be used to simulate nonuniaxial loadcases. Further simulations of bone cement fatigue should include porosity to better represent the realities of experimental models.

Biocompatible Materials↗

PubMed2002

Modeling the dynamic composition of engineered cartilage.

Mathematical models to describe extracellular matrix (ECM) deposition and scaffold degradation in cell-polymer constructs for the design of engineered cartilage were developed and validated. The ECM deposition model characterized a product-inhibition mechanism in the concentration of cartilage molecules, collagen and glycosaminoglycans (GAG). The scaffold degradation model used first-order kinetics to describe hydrolysis (not limited by diffusion) of biodegradable polyesters, polyglycolic acid and polylactic acid. Each model was fit to published accumulation and degradation data. As experimental validation, cell-polymer constructs (n=24) and unseeded scaffolds (n=24) were cultured in vitro. Biochemical assays for ECM content and measurements of scaffold mass were performed at 1, 2, 4, 6, 8, or 10 weeks (n=8 per time point). The models demonstrated a strong fit with published data and experimental results (R(2)=0.75 to 0.99) and predicted the temporal total construct mass with reasonable accuracy (30% RMS error). This approach can elucidate mechanisms governing accumulation/degradation and may be coupled with structure-function relationships to describe time-dependent changes in construct elastic properties.

Animals↗

PubMed1999

Computational and experimental investigation of flow and particle settling in a roller bottle bioreactor.

It is shown that cell settling is a key factor affecting the performance of roller bottle bioreactors. The two-dimensional cross-sectional flow at the center of a roller bottle is simulated using a finite difference method, and the settling behavior of cells is simulated using particle dynamics algorithms and validated experimentally using fluorescent particles. The settling behavior of particles in the roller bottle flow is studied using both steady and time dependent rotation rates. Under steady flow conditions the flow is divided into two regions: one where the particles settle to the wall and one where the particles remain suspended indefinitely. The relative size of these two regions depends on the ratio of the settling velocity to the rotation rate of the bottle. For unsteady flows generated by periodic changes of the bottle rotation direction, the settling of cells is accelerated significantly, leading to complete deposition in just a few turns of the bottle.

Algorithms↗

PubMed2004

Phantom design method for high-field MRI human systems.

A phantom design method suitable for high-field MRI based on the RF field wave characteristics of sample and experimental validations at 7.0 T and 3.0 T are presented. The RF field distribution in a phantom with a given RF coil system is primarily determined by the sample size relative to the wavelength inside the sample, and the ratio between the displacement and conduction currents. Experimental results demonstrate that the MR image intensity patterns associated with wave behavior in human samples at a given field strength can be reproduced with a phantom at the same or different field strengths once the dimension and penetration constant are scaled by the corresponding wavelength in the sample medium.

Brain Mapping↗

PubMed2002

Theoretical and experimental study of growth and remodeling in the developing heart.

A theoretical model is presented for growth and remodeling in the developing embryonic heart. The model is a thick-walled tube composed of two layers of orthotropic pseudoelastic material. The analysis includes stress and strain dependent volumetric growth, with changes in material properties specified to reflect the evolving structure of the heart wall. For use in model validation, experimental measurements of ventricular opening angles are reported for 3-4-day old chick embryos under control and pressure overload conditions. Owing to changes in residual stress in the overloaded heart, the opening angle decreased from 31 +/- 10 degrees to -8 +/- 12 degrees (mean +/- SD) within 12 h and then increased slightly. The opening angle at 12 h was significantly less than the control value. With an appropriate choice of parameters, the model yields reasonable agreement with these and other published opening angle data, as well as with temporal changes in lumen radius, wall thickness, epicardial strains, and pressure-volume curves during development before and after birth.

Animals↗

PubMed1999

Review of mechanisms by which electrical stimulation alters the transmembrane potential.

Electrical stimuli pace, cardiovert, or defibrillate the heart by changing transmembrane potential (deltaVm). Recent simulation studies provide insights into mechanisms by which stimuli establish deltaVm. This review attempts a nonmathematical description of these mechanisms. We start with the cable model in which the intracellular core conductor is bounded by a highly resistive and capacitive membrane that separates the intracellular and extracellular spaces. Intracellular and extracellular resistances are assumed to vary linearly with position. Although this model predicts anodal extracellular stimuli hyperpolarize adjacent tissue and cathodal extracellular stimuli depolarize that tissue, it fails to reproduce regions of opposite deltaVm distant from the electrodes. We then consider the sawtooth model in which microscopic discontinuities in intracellular resistance represent gap junctions. While model studies with such discontinuities demonstrate large deltaVm at cell ends, experimental validation of such deltaVm remains elusive. Extending the analysis to the two- and three-dimensional syncytium, we also consider the bidomain model in which intracellular, extracellular, and interstitial currents are explicitly characterized. Differences in resistance to these currents gives rise to virtual electrodes, which are experimentally observed regions of large deltaVm that arise distant from the stimulating electrode. Distant deltaVm regions are also evident when macroscopic discontinuities in intracellular resistance are introduced into the bidomain model. Such discontinuities are associated with clefts or scars that give rise to "secondary sources." Albeit the cable model offers remarkable insight the bidomain model and the concept of secondary sources provide a more complete understanding of membrane excitation, especially when combined into a unifying activating function.

Action Potentials↗

PubMed2005

Validation in pharmaceutical analysis. Part II: Central importance of precision to establish acceptance criteria and for verifying and improving the quality of analytical data.

Validation of analytical procedures is a vital aspect not just for regulatory purposes, but also for their efficient and reliable long-term application. In order to address the performance of the analytical procedure adequately, the analyst is responsible to identify the relevant parameters, to design the experimental validation studies accordingly and to define appropriate acceptance criteria. Establishing an acceptable analytical variability for the given application is of central importance as many other acceptance criteria can be derived from such a precision. Acceptable precision ranges for types of control tests and/or analytes can be obtained from validation, but also related activities such as transfer, control charts, or extracted from routine applications such as batch release or stability studies (data mining). Apart from compiling a database for general benchmarking, during such an information-building process, the reliability of the analytical variability of the specific procedure is more and more increased. This is important as a reliable target variability facilitates to detect or investigate atypical or out-of specification behaviour of analytical data in a routine application, thus improving the data quality and reliability. According to the life-cycle concept of validation, measures should be taken to maintain and control the validated status of analytical procedures during long-term routine application, such as monitoring relevant performance parameters (system suitability tests), control charts, etc. If the analytical system is demonstrated to be stable, i.e. under statistical control, a major variability contribution in LC originating from the standard preparation and analysis can be reduced. A concept of quantification by pre-determined calibration parameters instead of the classical approach of simultaneous calibration is described.

Chemistry, Pharmaceutical↗

PubMed1988

A minimal mathematical model of human periodic breathing.

Numerous mathematical models of periodic breathing (PB) currently exist. These models suggest mechanisms that may underlie many known causes of PB. However, each model that has been shown to simulate PB under reasonable conditions contains greater than 15 physiological parameters. Because some parameters exhibit a wide range of values in a population, such simulations cannot test a model's ability to account for the breathing patterns of individuals. Furthermore it is impractical to perform a direct experimental validation study that would require the estimation of each of 15 or more parameters for each subject. A minimal model of PB is presented that is suitable for direct validation. Analytic expressions are given that define the conditions for PB in terms of the following: 1) CO2 sensitivity, 2) Cardiac output, 3) Mixed venous CO2, 4) Circulation time, and 5) Mean lung volume for CO2. This model is shown to be consistent with previous models and experimental data regarding the degree of hypoxia or congestive heart failure required to produce PB. A quantitative measure of relative stability is defined as a metric of comparison to the human studies described in the accompanying paper (J. Appl. Physiol. 65: 1389-1399, 1988).

Blood Circulation Time↗

PubMed2005

Systematic search for natural antisense transcripts in eukaryotes (review).

The availability of several complete genome sequences and large numbers of expressed sequences, has led to the development of bioinformatic strategies for large-scale predictions of natural antisense transcripts. In the past two years, this has given at least 1,600 human pairs and 2,500 murine pairs of natural antisense transcripts. However, due to limitations in bioinformatic search tools, experimental validation of the predicted antisense transcripts is crucial. This has been performed only for a small fraction of the large number of predicted natural antisense transcripts. Additionally, bioinformatic approaches will not allow systematic identification of natural antisense transcripts in specific cell or tissue types. More recently, an experimental approach for identification of sense-antisense transcript pairs has been developed. The principle of the strategy is based upon the selection of double-stranded cDNAs as a result of hybridization between first-strand cDNAs that should be generated in the presence of actinomycin D. This experimental strategy allows systematic analysis of sense and antisense partners in any cell or tissue type.

Animals↗

PubMed2006

Optimization of integrated chemical-biological degradation of a reactive azo dye using response surface methodology.

The integrated chemical-biological degradation combining advanced oxidation by UV/H(2)O(2) followed by aerobic biodegradation was used to degrade C.I. Reactive Azo Red 195A, commonly used in the textile industry in Australia. An experimental design based on the response surface method was applied to evaluate the interactive effects of influencing factors (UV irradiation time, initial hydrogen peroxide dosage and recirculation ratio of the system) on decolourisation efficiency and optimizing the operating conditions of the treatment process. The effects were determined by the measurement of dye concentration and soluble chemical oxygen demand (S-COD). The results showed that the dye and S-COD removal were affected by all factors individually and interactively. Maximal colour degradation performance was predicted, and experimentally validated, with no recirculation, 30 min UV irradiation and 500 mgH(2)O(2)/L. The model predictions for colour removal, based on a three-factor/five-level Box-Wilson central composite design and the response surface method analysis, were found to be very close to additional experimental results obtained under near optimal conditions. This demonstrates the benefits of this approach in achieving good predictions while minimising the number of experiments required.

Azo Compounds↗

PubMed2004

Validation of the rat limb bud micromass test in the international ECVAM validation study on three in vitro embryotoxicity tests.

A detailed report is presented on the performance of the rat limb bud micromass (MM) test in a European Centre for the Evaluation of Alternative Methods (ECVAM)-sponsored formal validation study on three in vitro tests for embryotoxicity. Twenty coded test chemicals, classified as non-embryotoxic, weakly embryotoxic or strongly embryotoxic on the basis of their in vivo effects on animals and/or humans, were tested in four laboratories. The outcome showed that the MM test is an experimentally validated test, which holds promise for use for identifying strongly embryotoxic chemicals, but which needs to be improved before it can be recommended for use for regulatory purposes.

Animal Testing Alternatives↗

PubMed2005

Evaluation of genome-wide chromatin library of Stat5 binding sites in human breast cancer.

BACKGROUND: There is considerable interest in identifying target genes and chromatin binding sites for transcription factors in a genome-wide manner. Such information may become useful in diagnosis and treatment of disease, drug target identification, and for prognostication. In cancer diagnosis, patterns of transcription factor binding to specific regulatory chromatin elements are expected to complement and enhance current diagnostic predictions of tumor behavior based on protein and mRNA analyses. Signal transducer and activator of transcription-5 (Stat5) is a cytokine-activated transcription factor implicated in growth and progression of many malignancies, including hematopoietic, prostate, and breast cancer. We have explored immunoaffinity purification of Stat5-bound chromatin from breast cancer cells to identify Stat5 target sites in an unbiased, genome-wide manner. RESULTS: In this report, we evaluate the efficacy of a Stat5-bound chromatin library to identify valid Stat5 chromatin binding sites within the oncogenome of T-47D human breast cancer cells. A general problem with cloning of immunocaptured, transcription factor-bound chromatin fragments is contamination with non-specific chromatin. However, using an optimized strategy, five out of ten randomly selected clones could be experimentally verified to bind Stat5 both in vitro and in vivo as tested by electrophoretic mobility shift assay and chromatin immunoprecipitation, respectively. While there was no binding to fragments lacking a Stat5 consensus binding sequence, presence of a Stat5 binding sequence did not assure binding. CONCLUSION: A chromatin library coupled with experimental validation may productively identify novel in vivo Stat5 chromatin binding sites in cancer, including abnormal regulatory sites in tumor-specific neochromatin.

Binding Sites↗

PubMed2000

The thin blue line: a review and discussion of aseptic technique and postprocedural infections in rodents.

A basic tenet of animal welfare philosophy is that pain and distress must be minimized whenever possible without interfering with the goals of the research. Aseptic technique during surgical procedures is essential to prevent pain and distress associated with post-procedural infections. However, many investigators have found that applying the aseptic techniques used for large animal and human surgery is not always practical when performing surgery on small rodents. Furthermore, the efficacy of some of these techniques for preventing post-procedural infections has been questioned. This review examines what is known about the development of postprocedural infections in animals and humans and the methods used to prevent them. Detection of postprocedural infections in rodents can be difficult unless objective measurements of physiologic indices are made. These measurements should be used experimentally to assess the relative benefits of various methods for preventing postprocedural infections. Measures of contamination, such as quantitative bacterial cultures, also can be used; however, they do not reliably predict infection rates. Much of the dogma about decontamination of skin and hair prior to surgery is not supported by valid experimental evidence. Hair removal may not be necessary. Alcohol may in fact be a better disinfectant than is often credited. Draping should be used when it contributes to the maintenance of the sterile field, but when it does not, modification of surgical technique may provide more protection from infection than the drape does. The contribution of surgical technique to the prevention of postprocedural infections is probably equal to that of aseptic technique. Further research needs to be done to assess various aseptic techniques for use in rodent surgery.

Animal Welfare↗

PubMed1990

Exploring subjective vs. objective issues in the validation of computer-based critiquing advice.

Evaluation is an important part of the development of computer-based medical expert systems. Such evaluation may be particularly difficult when judging a critiquing system which responds to a proposed management strategy with a discussion of the advisability of that approach. DxCON is an expert system which produces a prose critique discussing the radiologic workup of obstructive jaundice. This paper describes DxCON, and its experimental validation by three independent judges. A central component of the validation involved allowing the judges to react to the system's advice in a quite flexible, unstructured fashion. This project provides a case study of how subjective issues impact both the design and implementation of a validation of a medical expert system whose output is explanatory prose.

Cholestasis↗