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PubMed1993

Assessment of regional myocardial performance with end-systolic pressure length and thickness relationships.

Although end-systolic pressure length and thickness relationships (ESPLR, ESPTR) are now widely used as substitutes for the end-systolic pressure volume relationships, there are some reservations about their use as an index of left ventricular (LV) performance. This study addressed three issues, namely: (1) which loading technique (decreasing preload by inferior vena cava (IVC) balloon occlusion or increasing systolic pressure by aortic constriction) is the most likely to yield usable data; (2) reproducibility of these relationships over a 30 min period; and (3) whether by using end-ejection (zero aortic flow) as a definition of end-systole, ESPLR and ESPTR can be used to characterize myocardial performance independent of load. Thirteen anesthetized beagles, weighing 16-25 kg, were used for this study, and were instrumented with sonomicrometers. We found that when ESPLR and ESPTR were constructed from data derived during aortic constriction, the slopes of these relationships were steeper and more curvilinear than when they were constructed from data recorded during IVC occlusion. In addition, the mean between ESPLR, ESPTR obtained 30 min apart was small, although there was a fair degree of variability between the first and second measurements. Using end-ejection to define end-systole, both ESPLR and ESPTR were relatively insensitive to loading conditions (LV end-diastolic pressure of 8-12 mmHg and 14-18 mmHg, aortic systolic pressure of 7-10 mmHg and 20-25 mmHg above baseline (in terms of the slope and shift (leftward or rightward) in these relationships, but were sensitive to inotropic interventions (dobutamine 2.5 micrograms/kg per min and 5 micrograms/kg per min). We conclude that, ESPLR and ESPTR, defined from measurements at end-ejection, can be used as adequate descriptors of regional myocardial performance if they were constructed from data over a similar pressure range during IVC balloon occlusion.

Animals↗

PubMed2004

Gene expression quantitation technology summary.

Scientists routinely talk and write about gene expression and the abundance of transcripts, but in reality they extrapolate this information from the various measurements that a variety of different technologies provide. Indeed, there are many reasons why applying different technologies to the problem of transcript abundance may give different results, owing to an incomplete understanding of the gene in question or from shortcomings in the applications of the technologies. There are nine basic considerations for making a technology choice for quantitating gene expression that will impact the overall outcome: architecture, specificity, sensitivity, sample requirement, coverage, throughput, cost, reproducibility, and data management. These considerations will be discussed in the context of available technologies.

Computational Biology↗

PubMed1994

Mathematical modelling of industrial pilot-plant penicillin-G fed-batch fermentations.

Penicillin-G fermentation with industrial media in 1 m3 stirred tank bioreactors was studied. A model based on the Bajpai-Reuss model structure was developed. Under typical production conditions catabolite repression is nonidentifiable and extensive mycelium differentiation occurs. Thus, the original model was reformulated, neglecting glucose repression of penicillin production and including biomass autolysis. The multi-substrate nature of industrial media was critically analysed. By combining the two most important carbon substrates present, a simple and applicable model was obtained. Model predictions agreed well with experimental data and reproduced the general characteristics observed in the fermentations. The predictive power of the model was tested for fermentations with different sugar feed rate profiles and raw materials (corn-steep liquor and sugar syrup). Several aspects of parameter estimation and model development are discussed on the basis of direct experimental data inspection and a sensitivity analysis of model parameters.

Biomass↗

PubMed1989

Reproducibility of iodine-123-hippuran renoscintigraphy in the normal pig at various flow rates.

Twenty-two pigs with normal kidney function and upper urinary tracts were examined with renoscintigraphies once a week for 4 weeks. In order to study the influence of urine flow on the reproducibility, renoscintigraphies were undertaken during various urinary flow rates. Renal split function was reproducible at any level of and independent of the urinary flow rates. For parenchymal and pelvic mean transit times a normogram was constructed for selected urinary flow intervals. An inverse relationship to urine production was seen. Parenchymal and pelvic transit times were fully reproducible when data were compared in two or three consecutive examinations of the same kidney at the same urinary flow rate. Both parenchymal and pelvic mean transit times were however significantly different (p less than 0.001) in kidneys studied from one urinary flow rate to another. Single kidney hippuran clearance was fully reproducible when compared in the same urinary flow interval. However a significant difference was found (p less than 0.05) when single kidney hippuran clearance was compared in renographies undertaken at different urinary flow intervals. Furthermore the study suggests that the size of hippuran clearance is dependent on the urine production, since an increase in hippuran clearance was seen in relation to increase in urinary flow. In conclusion this pig study showed, that monitoring of the urinary flow rate is extremely important in this very commonly used clinical investigation, and that the investigation should be performed in the same state of hydration at any renography to obtain reproducible results.

Animals↗

PubMed2004

Technology literature review: quantitative sensory testing.

The development of the personal computer has simplified the process of quantitating sensory thresholds using various testing algorithms. We reviewed the technical aspects and reproducibility of different methods to determine threshold for light touch-pressure, vibration, thermal, and pain stimuli. Clinical uses and limitations of quantitative sensory testing (QST) were also reviewed. QST is a reliable psychophysical test of large- and small-fiber sensory modalities. The results of QST are highly dependent on methodology and the full cooperation of the subject. QST has been shown to be reasonably reproducible over a period of days or weeks in normal subjects. The use of QST in research and patient care should be limited to instruments and their corresponding methodologies that have been shown to be reproducible. Literature data do not allow conclusions regarding the relative merits of individual QST instruments.

Electrodiagnosis↗

PubMed2006

Solid-state NMR analysis of a peptide (Gly-Pro-Gly-Gly-Ala)6-Gly derived from a flagelliform silk sequence of Nephila clavipes.

Solid-state NMR is especially useful when the structures of peptides and proteins should be analyzed by taking into account the structural distribution, that is, the distribution of the torsion angle of the individual residue. In this study, two-dimensional spin-diffusion solid-state NMR spectra of 13C-double-labeled model peptides (GPGGA)6G of flagelliform silk were observed for studying the local structure in the solid state. The spin-diffusion NMR spectra calculated by assuming the torsion angles of the beta-spiral structure exclusively could not reproduce the observed spectra. In contrast, the spectra calculated by taking into account the statistical distribution of the torsion angles of the individual central residues in the sequences Ala-Gly-Pro, Gly-Pro-Gly, Pro-Gly-Gly, Gly-Gly-Ala, and Gly-Ala-Gly from PDB data could reproduce the observed spectra well. This indicates that the statistical distribution of the torsion angles should be considered for the structural model of (GPGGA)6G similar to the case of the model peptide of elastin.

Animals↗

PubMedDate not supplied

Cytosolic calcium oscillators: critical discussion and stochastic modelling.

In the last few years, an immense amount of experimental data on agonist-induced cytosolic Ca2+ oscillations has emphasized the necessity of theoretical models accounting for these phenomena. In the first part of the paper, a critical analysis of different minimal Ca2+ oscillator models is presented, which reveals that not all of the so far proposed mechanisms are capable to reproduce experimental data adequately. The second part of the paper is devoted to a computational method using a stochastic simulation algorithm which describes the time evolution of Ca2+ oscillations at the molecular level. In contrast to the deterministic formulation of the models presented so far, the stochastic treatment takes account of the inherent fluctuations of cytosolic Ca2+ in cellular subcompartments. In the macroscopic limit, the stochastic models display dynamics analogous to the deterministic ones.

Animals↗

PubMed2005

Fast Fos: rapid protocols for single- and double-labeling c-Fos immunohistochemistry in fresh frozen brain sections.

Immunohistochemical localization of c-Fos immunoreactivity has been used successfully for over a decade to visualize patterns of neuronal activity in the brain and spinal cord. These experiments are extremely useful in identifying physiological or pharmacological activation of specific populations of neurons. Unfortunately, conventional c-Fos immunohistochemical protocols are very time and resource intensive. We have adapted and optimized established c-Fos immunohistochemistry (IHC) methodologies for use with fresh frozen brain tissue mounted directly onto slides. The resultant rapid protocols, which we refer to as "Fast Fos", include applications for single- and double-labeling, utilizing either enzyme-substrate or fluorescent detection systems. These protocols provide increased assay throughput and reproducibility, which can be further enhanced by use of an automated slide stainer. Taken as a whole, the c-Fos IHC protocols described in this report provide a flexible system for the identification of neuronal activation that substantially reduces time and resource expenditure while increasing quality and reproducibility of data.

Animals↗

PubMed1993

Short-term and long-term reproducibility of dietary history interview data.

This study gives results for comparisons between dietary history interviews repeated at short-term (4-8 months) and long-term (4-7 years) intervals in conjunction with the Finnish Mobile Clinic Health Examination Survey. Interviews surveying the whole range of consumable foods over the preceding year were completed in 1967-1976. Short-term study was accomplished among 93 adults, and long-term study among 1844 adults. Comparisons were made for intakes of 32 food groups and 32 nutrient indices. In the short term, the intraclass correlation coefficients for nutrient indices ranged from 0.16 to 0.80, with 90% of values higher than 0.5. The corresponding figures for repeated measurements at long-term interval were generally poorer, being in the range 0.12-0.60, with 45% of values > 0.5. When studied in population subgroups, long-term agreement in dietary data was not found to be affected by sex, age, body mass index or smoking status, but it may be reduced among heavier drinkers (> or = 20 g alcohol per day). The intraclass correlation coefficients for separate nutrients tended to be higher than those for different food groups. In conclusion, we suggest that the reproducibility of the dietary history method used was acceptable, and that the dietary patterns of examinees were sufficiently stable to be compatible with the needs of epidemiological follow-up studies.

Diet Surveys↗

PubMedDate not supplied

Computational analysis of vertebrate phototransduction: combined quantitative and qualitative modeling of dark- and light-adapted responses in amphibian rods.

We evaluated the generality of two models of vertebrate phototransduction. The approach was to quantitatively optimize each model to the full waveform of high-quality, dark-adapted (DA), salamander rod flash responses. With the optimal parameters, each model was then used to account for signature, qualitative features of rod responses from three experimental paradigms (stimulus/response, "S/R suite"): (1) step responses; (2) the intensity dependence of the period of photocurrent saturation (Tsat vs. ln(I)); and (3) light-adapted (LA) incremental flash sensitivity as a function of background intensity. The first model was the recent successful model of Nikonov et al. (1998). The second model replaced the instantaneous Ca2+ buffering used in the Nikonov et al. model with a dynamic buffer. The results showed that, in the absence of the dynamic Ca2+ buffer, the Nikonov et al. model does not have sufficient flexibility to provide a good fit to the flash responses, and, using the same parameters, reproduce the salient features of the S/R suite--critical features at step onset and offset are absent; the Tsat function has too shallow a slope; and the model cannot generate the empirically observed I-range of Weber-Fechner LA behavior. Some features could be recovered by changing parameters, but only at the expense of the fit to the reference (Ref) data. When the dynamic buffer is added, the model is able to achieve an acceptable fit to the Ref data while reproducing several features of the S/R suite, including an empirically observed Tsat function, and an extended range of LA flash sensitivity adhering to Weber's law. The overall improved behavior of the model with a dynamic Ca2+ buffer indicates that it is an important mechanism to include in a working model of phototransduction, and that, despite the slow kinetics of amphibian rods, Ca2+ buffering should not be simulated as an instantaneous process. However, neither model was able to capture all the features with the same parameters yielding the optimal fit to the Ref data. In addition, neither model could maintain a good fit to the Ref data when five key biochemical parameters were held at their current known values. Moreover, even after optimization, a number of important parameters remained outside their empirical estimates. We conclude that other mechanisms will need to be added, including additional Ca2+-feedback mechanisms. The present research illustrates the importance of a hybrid qualitative/quantitative approach to model development, and the limitations of modeling restricted sets of data.

Adaptation, Ocular↗

PubMedDate not supplied

Factors affecting interpretation of postprandial glucose and insulin areas.

Recently there has been an increased interest in determining the circulating glucose concentration after the ingestion of various individual foods and mixed meals. The purpose of these determinations is to systematically rank foods with respect to their quantitative effect on postmeal glucose concentration. Potentially such data could be useful in designing a diet for individuals with diabetes. We believe this concept is good. However, several factors that may affect interpretation of the data used to develop this ranking need to be considered before the utility of this approach to dietary management can be assessed: 1) duration of time over which the data are collected and analyzed; 2) use of absolute versus incremental areas in the determinations; 3) inclusion or exclusion of negative areas if incremental areas are used; 4) differences in response to a given food in males compared with females; 5) severity of diabetes; 6) confounding effects of oral agents or insulin treatment; 7) reproducibility of data; 8) differences in collection of blood sample; 9) food composition, processing, and preparation; 10) the dose-response relationship to ingestion of a given carbohydrate; 11) the meal being studied, i.e., first, second, or third meal of the day; and 12) a possible effect of the composition of the previous meal, if the response is tested to any meal other than the first meal of the day.

Blood Glucose↗

PubMed2003

Separation methods in the chemistry of humic substances.

Separation methods are widely used to isolate humic substances (HSs), to fractionate them before further investigation, and to obtain information about their structure and properties. Among the chromatographic methods, techniques based on a size-exclusion effect appear to be most useful, as they allow us to relate elution data to the molecular mass distribution of HSs. The limitations of this approach are discussed in this review. Gas chromatography with mass spectrometric detection is typically used to identify the products of pyrolysis or thermochemolysis of HSs; this technique is considered most important in the structural investigation of HSs. Electrophoretic methods (especially capillary zone electrophoresis) provide detailed characterization of HSs, but it is very difficult to relate the electrophoretic data to any specific subfraction, structure or properties of HSs. The electrophoretic patterns are often called "fingerprints" and can potentially be used for the identification and classification of HSs. This is limited, however, by the great diversity of the procedures employed and by the low degree of harmonization--no data on reproducibility and between-laboratory comparability are available. The same holds true, to a certain degree, for most methods utilized for the characterization of HSs. Separation methods play an important role in the examination of the interactions of HSs with heavy metals and other chemical pollutants. They allow us to determine binding constants and other data necessary to predict the mobility of chemical pollutants in the environment.

Chromatography, Gel↗

PubMedDate not supplied

Application of the can technique and radon gas analyzer for radon exhalation measurements.

A passive "can technique" and an active radon gas analyzer with an emanation container were applied for radon exhalation rate measurements from different construction materials, viz. five marble seven ceramic and 100 granite tiles used in Saudi Arabia. The marble and ceramic tiles did not show detectable radon exhalation using the active radon gas analyzer system. However the granite tiles showed relatively high radon exhalations, indicating a relatively high uranium content. A comparison of the radon exhalation rates measured by the two techniques showed a linear correlation coefficient of 0.57. The radon exhalation rates from the granites varied from 0.02 to 6.58 Bqm(-2)h(-1) with an average of 1.35+/-1.40 Bqm(-2)h(-1). The geometric mean and the geometric standard deviation of the frequency distribution were found to be 0.80 and 3.1, respectively. The track density found on the nuclear track detectors in the can technique exposed to the granites, having high exhalation rates, varied linearly with exposure time with a linear correlation coefficient of 0.99. This experimental finding agrees with the theoretical prediction. The can technique showed sensitivity to low radon exhalation rates from ceramic, marble and some granite over a period of 2 months, which were not detectable by the active radon gas analyzer system. The reproducibility of data with both measuring techniques was found to be within a 7% deviation.

Ceramics↗

PubMed1995

A comparison between radiographic and sonically produced cephalometric values.

Cephalometric radiography has become a standard and invaluable means of obtaining diagnostic information for the management of malocclusion and skeletal disharmony. However, concerns over radiographic exposure, particularly in growing individuals, may limit its use, especially in longitudinal analyses. Less invasive means of obtaining vital information would be desirable. A recently introduced system (Digigraph, Dolphin Imaging Systems; Valencia, Calif) provides sonically produced representations of cranial landmarks and has been introduced by its manufacturer as an alternative to standard cephalometric radiography. The purpose of the study was to compare the validity and reproducibility of cephalometric values generated sonically on a digital image analyzer (Digigraph) with those obtained from standard cephalometric radiographs for 43 different measurements. Although 58.1% of the sonically produced measurements showed significant correlation with radiographically produced measurements, there were no trends observed for correlation, either in dental or skeletal structure classifications. Additionally, this study found the data generated from the digital image analyzer to be markedly variable, while the radiographically obtained data were reproducible.

Adult↗

PubMed2006

An empirical method for the determination of wall perturbation factors for parallel-plate chambers in high-energy electron beams.

The calibration of ion chambers in high-energy electron beams in terms of absorbed dose to water at the National Physical Laboratory requires knowledge of the ratio of perturbation factors in graphite and water phantoms. During a review of data required for the NPL calibration procedure an empirical model was developed to calculate the perturbation due to the rear wall, pwall, of a well-guarded ion chamber in a high-energy electron beam. The overall uncertainty in this method is estimated to be 0.4%, which is the lowest value reported to date. The model reproduces measured data at the 0.1% level or better and indicates that the NACP ion chamber has a nonzero perturbation factor in electron beams due to backscatter from the rear wall. The effect is small (<0.5%) at high energies (R50>4 cm, E0>10 MeV) but becomes large at low energies-up to 1.4% at E0=4 MeV (R50=1.2 cm). The model indicates that there is a nonzero correction for the NACP chamber in both a graphite and water phantom and that material adjacent to the air cavity has a significant effect on the measured ionization. These values are consistent with previous measurements and recent Monte Carlo calculations. The model could be used in the design of ion chambers and in the estimation of corrections for non-homogeneous systems, especially in the absence of accurate Monte Carlo simulations.

Calibration↗

PubMed2003

Parameterisation, evaluation and comparison of pesticide leaching models to data from a Bologna field site, Italy.

Effective prediction of pesticide fate using mathematical models requires good process descriptions in the models and good choice of parameter values by the user. This paper examines the ability of seven pesticide leaching models (LEACHP, MACRO, PELMO, PESTLA, PLM, PRZM and VARLEACH) to describe an arable field environment where sunflowers are grown in the Po Valley, northern Italy. Two pesticides were considered, aclonifen and ethoprophos. The models were evaluated in terms of their ability to reproduce field data of soil water content and pesticide residues in the soil and ground water. The evaluation was based on a combination of calibrated and uncalibrated runs. The results from the models were compared with each other to explore the differences between the models. The models varied in their ability to predict soil water content in the summer: the capacity models PRZM, PELMO and VARLEACH predicted less drying than MACRO, PESTLA, PLM and LEACHP. The models varied in their ability to simulate the persistence of the pesticides in the soil. Differences in the simulated pesticide degradation rate were observed between the models, due to variations in the simulated soil water content and soil temperature, and also differences in the equation linking degradation rate to soil water content. There were large differences among the predictions of the models for the mean leaching depth of ethoprophos. PRZM, PELMO, PESTLA and LEACHP all showed similar mean leaching depth to each other, whereas VARLEACH predicted lower ethoprophos mobility and PLM and MACRO predicted greater mobility. All the models overpredicted dispersion of ethoprophos through the soil profile, as compared to the field data. None of the models was able to simulate the field data of rapid leaching of pesticide to ground water except PLM after calibration of the percentage of macropores in the mobile pore space. More work is required in the parameterisation of macropore flow for those models that include this process.

Aniline Compounds↗

PubMed1999

Resistance patterns of Haemophilus influenzae.

Haemophilus influenzae is an important respiratory tract pathogen, and the prevalence of strains resistant to the antibiotics used to treat it has increased since the 1970s. Data on H. influenzae have been gathered in the Alexander Project, an ongoing, international surveillance study. They reveal that beta-lactamase production is the primary mechanism for H. influenzae resistance and that the resistance has a wide geographical variation, reaching critical levels in some countries. Unlike many techniques used in the past, Alexander Project methods provide accurate, reproducible susceptibility data, allowing the comparison of resistance prevalence over time and between areas. Traditional antimicrobial breakpoints are being superseded by more accurate and clinically relevant methods of predicting drug efficacy, such as time above the MIC, AUC:MIC ratios and pharmacodynamic breakpoints. Continued surveillance for resistance and susceptibility testing of H. influenzae is vital to maximize the benefits of antimicrobial therapy and to contain the spread of infection.

Adolescent↗

PubMed2004

Alternative approach to assessment of bone quality using micro-computed tomography.

Micro-computed tomography (micro-CT) allows for classical anatomical imaging well suited to the study of skeletal structures. Recent improvements in spatial resolution and the ability to assess cancellous bone microstructure more efficiently has led to an increase in the number of micro-CT users in both academic and commercial environments. Accurate and reproducible positioning of bone samples and image acquisition time are two limiting factors that every bio-imaging laboratory must deal with. Therefore, method improvements that may save time or improve quality and reproducibility of data are always welcome. Here, we present an "alternative" approach for performing two- (2D) and three-dimensional (3D) analysis of bone tissue using in vitro micro-CT technology. The proposed method for acquiring longitudinal images of long bones has several advantages over the "conventional" scanning method of generating axial images. The proposed method allows for more accurate and reproducible positioning of specimen for single and multi-sample scans while providing higher-resolution image sets in substantially less time, compared to the "conventional" method. In addition, longitudinal images generated with the proposed method are comparable to views obtained by classic bone histology and, thus, are more informative to bone scientists, providing an opportunity to assess cancellous bone of the metaphysis and/or epiphysis, evaluate longitudinal bone growth, and finally to more accurately and reproducibly define regions of interest on image.

Animals↗