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Robust inference of baseline optical properties of the human head with three-dimensional segmentation from magnetic resonance imaging.

We model the capability of a small (6-optode) time-resolved diffuse optical tomography (DOT) system to infer baseline absorption and reduced scattering coefficients of the tissues of the human head (scalp, skull, and brain). Our heterogeneous three-dimensional diffusion forward model uses tissue geometry from segmented magnetic resonance (MR) data. Handling the inverse problem by use of Bayesian inference and introducing a realistic noise model, we predict coefficient error bars in terms of detected photon number and assumed model error. We demonstrate the large improvement that a MR-segmented model can provide: 2-10% error in brain coefficients (for 2 x 10(6) photons, 5% model error). We sample from the exact posterior and show robustness to numerical model error. This opens up the possibility of simultaneous DOT and MR for quantitative cortically constrained functional neuroimaging.

Bayes Theorem↗

Construction of an internal standard used in RT nested PCR for Borna Disease Virus RNA detection in biological samples.

The highly neurotropic Borna Disease Virus (BDV), which belongs to the Mononegavirales order--Bornaviridae family--is generally detected using the RT-nested-PCR. If false positive results (often caused by laboratory contaminations) can be avoided, some false negative results which are mostly due to inhibitory effects of some reaction components and/or to sample preparation errors, can occur. Thus, in order to control the RT-PCR sample, an RNA internal standard molecule named "mimic" was constructed with the same primer recognition sites as the viral nucleic acids, flanking a heterologous DNA fragment of distinct molecular weight. Because of their different sizes, the mimic and viral PCR products can be easily discriminated by agarose gel electrophoresis. The co-amplification of both BDV and mimic RNA was performed on infected cells and on biological tissues such as the brain and blood, commonly known to contain PCR inhibitor components. After mimic sensitivity studies were achieved (2.5 fg of "p40 RNA mimic" and 0.25 fg of "p24 RNA mimic"), the competitive amplification reaction between both BDV and mimic RNA was performed on these tissues. The results confirmed that nervous tissue has an inhibitory effect on RT-PCR, which supports the necessity of BDV detection by a higher sensitive method such as RT nested PCR. Moreover, these results confirmed the interest of an internal standard for BDV RNA detection in biological samples.

Base Sequence↗

Rapid gridding reconstruction with a minimal oversampling ratio.

Reconstruction of magnetic resonance images from data not falling on a Cartesian grid is a Fourier inversion problem typically solved using convolution interpolation, also known as gridding. Gridding is simple and robust and has parameters, the grid oversampling ratio and the kernel width, that can be used to trade accuracy for computational memory and time reductions. We have found that significant reductions in computation memory and time can be obtained while maintaining high accuracy by using a minimal oversampling ratio, from 1.125 to 1.375, instead of the typically employed grid oversampling ratio of two. When using a minimal oversampling ratio, appropriate design of the convolution kernel is important for maintaining high accuracy. We derive a simple equation for choosing the optimal Kaiser-Bessel convolution kernel for a given oversampling ratio and kernel width. As well, we evaluate the effect of presampling the kernel, a common technique used to reduce the computation time, and find that using linear interpolation between samples adds negligible error with far less samples than is necessary with nearest-neighbor interpolation. We also develop a new method for choosing the optimal presampled kernel. Using a minimal oversampling ratio and presampled kernel, we are able to perform a three-dimensional (3-D) reconstruction in one-eighth the time and requiring one-third the computer memory versus using an oversampling ratio of two and a Kaiser-Bessel convolution kernel, while maintaining the same level of accuracy.

Algorithms↗

Effect of sampling strategy on the false-negative rate for detection of selected subgingival species.

Subgingival plaque samples were obtained from the mesial surface of each tooth (maximum 28 samples per subject) in 62 subjects with prior evidence of destructive periodontal disease. The resulting 1596 samples were evaluated for their content of 14 selected taxa using a colony lift method and DNA probes. The present investigation compared the ability of 6 sampling strategies to detect a species known to be present in a subject as determined by the 28-site sampling procedure. On average, a species was not detected in 68% of the positive subjects if only the upper right first molar was sampled; 55% of subjects if both upper first molars were sampled; 36% of subjects if the 4 first molars were sampled; 28% of subjects if the 6 Ramfjord teeth were sampled; 60% of subjects if the deepest pocket was sampled and 25% of subjects if the 4 deepest pockets were sampled. The error rate was greatest for species that were infrequently detected in plaque samples such as Actinobacillus actinomycetemcomitans serotype b. This species was not detected in 49% of positive subjects, when the 6 Ramfjord teeth were sampled and 38% of subjects when the 4 deepest pockets were sampled. The data indicated that multiple plaque samples are needed to minimize false-negative rates.

Adolescent↗

Evaluation of sequential sampling plans for the larger grain borer (Coleoptera: Bostrichidae) and the maize weevil (Coleoptera: Curculionidae) and of visual grain assessment in West Africa.

Repeated sampling of rural maize stores in Benin was conducted to evaluate published parameters of a sequential sampling plan for a negative binomial distribution to determine pest status for Prostephanus truncatus (Horn) and Sitophilus zeamais Motschulsky. A computer program was used to rerandomize the data and evaluate the effects, in terms of average sample number and error rates, of different sampling plan parameter values. With respect to P. truncatus, lower and upper thresholds of 0.2 and 1.0 insects per ear and parameter values of k = 0.2 and alpha = beta = 0.1 were found to be adequate. With respect to S. zeamais, lower and upper thresholds of 10 and 20 insects per ear and parameter values of k = 1.0 and i alpha = beta = 0.1 were found to be adequate. Simplified sampling rules were proposed in which 11 ears should be sampled and if no P. truncatus are found, the population is low; otherwise the Wald plan should be followed. Owing to the lower per capita rate of damage, effective simplified sampling rules for S. zeamais were difficult to construct. An evaluation of the visual assessment scale rising whole ears showed that a visual scale estimating percentage damage rather than percentage loss, might be easy to construct and preferable for traders. Further work is needed to improve the usefulness of the visual scale in pest management decision support.

Animals↗

[Determination of five component infrared spectra system with artificial neural network].

This article demonstrates the application of artificial neural network in multi-component analysis. Parameters were obtained after the BP network was trained with large amount of simulated data. Five organic toxins whose FTIR spectra are strongly overlapped were used to make the multi-component system. The relative standard deviation(RSD%), the percent standard error of prediction samples(SEP%) and the percent standard error of calibration samples(SEC%) were used for evaluating the ability of the neural network.

Air Pollutants↗

[Identification of hashish samples with inductively coupled high-frequency plasma emission spectrometry and neutron activation analysis and data handling with neuronal networks. 1. Methods for the quantitative determination of characteristic trace elements].

Neutron activation analysis (NAA) and inductively coupled plasma emission spectrometry (ICP-AES) were used to quantify the relative contents of Fe, Sc, Ce, Pa, Cr, Co, respectively the absolute contents of Cr, Zn, Mn, Fe, Mg, Al, Cu, Ti, Ca, Sr in hashish samples, seized in different countries. The samples were processed after dry ashing by means of instrumental NAA and after wet mineralization by means of ICP-AES. For determination of the sampling and measurement errors, one of the samples was analyzed repeatedly with both methods. Classifying hashish samples with regard to concentration of certain elements could be done by artificial neural networks with a modified backpropagation algorithm. By this way, identity and non identity of one unknown sample with one of many different samples as data pool can be ascertained, on principle.

Cannabis↗

Value of duplicate smears in cervical cytology.

The cytologic accuracy, sources of error and value of duplicate samples were studied in 87 women simultaneously biopsied for cervical intraepithelial neoplasia. Separately evaluated by two laboratories, correlation with biopsy was 70% for the first cytology and 67% for the second. Discrepant cytologies were reciprocally reviewed in error analysis. The sources of error were cytologic sampling (10.9%), evaluation (5.8%) and both (4.0%). Attention is directed to the high proportion of cases (15%) in which sampling error was a factor; awareness of this observation is necessary in patient management. The duplicate second cytology was of substantial value in 7% of the cases and helpful in an additional 3.5%; both figures are lower than in recent reports. If errors in evaluation or evaluation sampling are held to a 10% level, routine duplicate studies may not be justified.

Carcinoma in Situ↗

99m Tc-ethylenedicysteine (99mTc-EC) renal clearance determination error for the multiple- and single-sample methods.

BACKGROUND: The aim of this work has been to assay determination error values for the clearance determined by single- and multi-sample method and to compare the error values obtained for both methods. METHODS: The assay has been conducted by two independent methods (Monte Carlo simulation, total differential). RESULTS: The results indicate that the relative root mean square error of the clearance determination by multisample method is practically constant above CI values 150 ml/min and amounts to ab +/-3-4%. For values below 150 ml/min the error increases and reaches +/-12% at CI=70 ml/min. The one sample method is less accurate and error increases from +/-(8-9)% 550 ml/min to +/- 25% at 70 ml/min. Moreover, for the multisample method the error estimated from total differential exceeds that obtained from Monte Carlo produced by factory of 3 to 4. For the one sample clearance determination both error estimates yield similar results. In both methods of clearance determination inaccurate pipetting makes a dominant contribution to the overall error. CONCLUSIONS: Form monitoring of patients' condition the multisample method should be employed. The use of one sample method should be limited to screening tests and for obtaining additional information, supplementing the dynamic scintigraphic studies

Journal Article↗

A probabilistic approach to the single-point, single-dose problem.

A general probabilistic approach is applied to the single-point, single-dose method for estimating individual infusion rates and serum drug concentrations. By using transformations of probability density functions, the effects of variations in the elimination rate constant upon pharmacokinetic variables may be studied and optimal sampling times may be chosen. Although this study treats the case of error-free sampling in a single-compartment model with a normal distribution of rate constants, the methods presented can be extended to more general situations.

Metabolic Clearance Rate↗

Heritability estimate for refractive errors--a population-based sample of adult twins.

The population-based Finnish Twin Cohort study was used to establish a heritability estimate for refractive errors especially for myopia. The twin cohort was derived from adult same-sexed twins in Finland. The total number of twins with both members alive in 1984 was 23,570. Of these, 3,676 twin pairs were monozygotic, and 8,109 pairs dizygotic. The sample for the present study was linked from the Finnish Police Force data base in 1984, where information of a person's possession of a driver's license and the obligation to wear glasses for far correction when driving a motor vehicle is recorded. Correlations in liability were estimated according to a multifactorial method of Smith. Falconer's heritability was 0.62 among males and 0.98 among females in the age group 28-29 years. When compared to previous twin studies of myopia, the proband concordance rates were higher for both MZ and DZ twin pairs.

Adult↗

Adequacy of screening cervical cytology among human immunodeficiency virus-seropositive women.

OBJECTIVE: To evaluate the adequacy of cytology in detecting cervical intraepithelial neoplasia (CIN) among human immunodeficiency virus (HIV)-seropositive women compared to controls. METHODS: A cross-sectional study was carried out evaluating 241 HIV-seropositive women and 991 controls (404 HIV seronegative and 587 of unknown HIV status) at risk for CIN attending a vaginitis clinic. All patients had a Pap smear and a standard colposcopic examination of the lower genital tract. Cervical biopsies were taken as indicated by colposcopy. Cytology and histology slides were read by a cytopathologist blinded to patients' serostatus. False-negative cytologic cases were reviewed by three independent cytopathologists to estimate sampling and screening error rates. Sensitivity, specificity, and false-negative rate of cytologic smears were compared between HIV seropositives and controls. We estimated the sampling and screening error rates among cases with false-negative cytology. RESULTS: Among seropositives, the sensitivity, specificity, and the false-negative smear rate for CIN were 73.4% (47/64), 97.1% (134/138), and 26.6% (17/64), respectively. The corresponding figures in controls were 83.8% (83/99), 99.04% (825/833), and 16.2% (16/99), respectively, and did not differ significantly from those of seropositives. The negative predictive value of cytology was lower among seropositives (134/151) than in controls (825/841, chi2 = 34.8, P < .001). The agreement between cytologic readings and combined colposcopy and histology was stronger among controls (kappa = 0.789, 95% CI 0.723 to 0.856) than among seropositives (kappa = 0. 593, 95% CI 0.475 to 0.712). Three independent cytopathologists were unable to detect atypical cells in 52.9% (9/17) of false-negative smears taken from seropositive women as opposed to 37.5% (6/16) of controls. CONCLUSIONS: The sensitivity, specificity, and false negative rate of screening cytology for CIN among HIV seropositive women are comparable with those in the general population. Since almost 50% of false-negative results could be attributed to sampling errors, more frequent cytological screening may prove to be beneficial to this high-risk group.

Adult↗

Frequency of replication/transcription errors in (A)/(T) runs of human genes.

To estimate the error rate of the gene expression machinery and its possible age-related increase, we compared the occurrence of polymerase errors during replication and transcription in (A)/(T) runs, in DNA and RNA of young and old individuals and of early- and late-passage cultured fibroblasts. We analyzed three human genes: TPRD, TGFBR2, and ATRX containing stretches of (A)8, (A)10, and (T)13, respectively. The error rate was determined by sequencing 100 cloned PCR or RT-PCR fragments from each DNA and RNA sample. The error rates in replication and transcription increased with the stretch length. The pooled error rates for genomic DNA were: TPRD (A)8, TGFBR2 (A)10, and ATRX (T)13: 1%+/-0.41, 15.8%+/-1.3, and 31.3%+/-2.9, while those for RNA were: 3.8%+/-0.5, 19.3%+/-2.1, and 54.3%+/-1.8, respectively. The deletions of one nucleotide were the most frequent errors. In the replication analysis, a significant difference was found in old versus young individuals for the ATRX (T)13. In the transcription analysis, significantly higher error rates were obtained in old versus young individuals for the TPRD (A)8 and TGFBR2 (A)10. For these genes, the error rate in RNA isolated from fibroblasts was significantly higher than that in blood. The data show a trend of age-related increase in replication/transcription errors; however further studies are necessary to confirm this hypothesis, since the sample size is small. This imperfect fidelity of the gene expression process may explain the evolutionary disadvantage of nucleotide repeats within coding sequences, and that these repeats are targets for mutations in human diseases.

Adult↗

Determination of monoclonal antibody production in cell culture using novel microfluidic and traditional assays.

This study compares microfluidic technology (Protein 200 LabChip Assay kit, Agilent 2100 Bioanalyzer, referred to here as Protein 200) to the traditional approach for protein analysis, one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), for the sizing and quantification of immunoglobulin G (IgG) in hybridoma cell cultures. Internal references differ between each method: purified IgG was used alone in SDS-PAGE while myosin (the upper marker) was added to each sample in Protein 200. The IgG used here were produced in cultures propagated in either a serum-free or a serum-containing medium. With serum-containing samples, there was a significant difference in the IgG concentrations (p < 0.05) between SDS-PAGE and Protein 200. The concentration determined by SDS-PAGE was significantly higher (> 30%) than by Protein 200 or by high-pressure liquid chromatography (HPLC) because the large amounts of serum albumin in the samples affect the accuracy of SDS-PAGE. Protein 200 can determine size similarly to SDS-PAGE in serum-free samples (standard error of the mean, SEM, < 1%, 95% confidence < +/-1%), unlike in serum-containing samples. The Protein 200 assay was more effective than the traditional one-dimensional SDS-PAGE in determining concentration and size of IgG in cell culture samples and it provided a miniaturized and convenient platform for rapid analysis.

Animals↗

The mathematics behind modeling.

The purpose of this chapter has been to furnish insight into the theoretical background on which compartmental modeling software packages are based. To accomplish this goal, only the basic ideas were stressed, avoiding discussion of the intricacies required for efficiency. The object was to remove the mystery from these powerful programs by examining the fundamental ideas which make them tick. The first section was concerned with how compartmental models are built up and how to obtain information concerning the system behavior described by these models. The cornerstone here is to describe a system by determining how it behaves over (typically) very short time periods. This leads to a differential equation description of a compartmental system. Information can be extracted from these equations by returning to their basic meaning, illustrated in their derivation. Computers are ideal for obtaining this information by piecing together the results obtained over short time periods, to find the behavior over long time periods. In an actual situation governed by a compartmental model, it's often the case that we may know only the form of the model, but not the values of the rate constants which must be known for its effective use. The second section of the chapter was devoted to the practical problem of determining the rate constants of the model, based on observed data. This is a matter of searching for those values which, in some sense, best fit the data. To attack this problem we need a reasonable criterion to judge how well a proposed model fits the data. We chose to use the total squared deviation, psi, which is the most common such criterion--but not the only reasonable one. The search technique we examined--steepest descent--is based on a simple idea: looking at the total squared deviation criterion geometrically. In graphical terms, the best fit corresponds to finding the low point on a surface, whose height above any point at sea level is computable. If we could imagine the view of someone trying to find the low point from some arbitrarily chosen initial position on this mountain-like surface, we would look around and find the direction where (close by) the mountain drops off most steeply. We would go in that specific direction until we reach a low point, moving only along this initially chosen direction. At this new low point, we could change again to a direction of steepest descent, and keep repeating this process until we make no further effective downward progress. No guarantee in general is made for this process, but it often works. Finally, having found the best values for the rate constants, we must recognize that if the data is affected by factors not explicitly taken into account in the model, the variability induced by these factors precludes a perfect fit. For this reason, it is finally necessary to determine how good the model is, as a description of the data, and how accurate are the fitted rate constants. For the model fit, the sample RMS error (simply related to the total squared deviation, and often the same as the sample standard deviation) may be used. For determining the accuracy of the fitted rate constants, practical methods based on computer software simulations are recommended.

Computer Simulation↗

Evaluation of coagulation during cardiopulmonary bypass with a heparinase-modified thromboelastographic assay.

Thromboelastography (TEG) is a useful method of assessing perioperative coagulation function in patients undergoing cardiac surgery. The presence of significant amounts of heparin in blood samples, however, prevents determination of changes in coagulation function by TEG or introduces artifactual error if samples contain heparin that is not present in vivo. For these reasons, whole blood coagulation function monitoring with TEG has not been feasible during cardiopulmonary bypass (CPB) with heparin anticoagulation. In this study, data obtained from 42 volunteers are presented to describe the effects of heparinase on TEG variables in the presence and absence of heparin. These data indicate that heparinase does not affect TEG parameters of whole blood not containing heparin and reverses the TEG effects of low levels of heparin contamination. Subsequently, 51 patients undergoing coronary artery surgery were studied using a modified TEG assay that incorporates in vitro application of heparinase to allow measurement of TEG parameters before, during, and after CPB. Heparinase-modified TEG assays facilitated diagnosis of heparin contamination in preoperative blood samples and permitted baseline TEG evaluation in patients receiving preoperative heparin infusions. Heparinase-modified TEG assays revealed declines in alpha and MA values during CPB, which persisted and significantly correlated with values after protamine infusion (alpha: r = 0.77, P = 0.001; MA: r = 0.78, P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A finite-size pencil beam model for photon dose calculations in three dimensions.

A three-dimensional dose computation model employing a finite-size, diverging, pencil beam has been developed and is demonstrated for Cobalt-60 gamma rays. The square cross-section pencil beam is simulated in a semi-infinite water phantom by convolving the pencil beam photon fluence with the Monte Carlo point dose kernel for Cobalt-60. This finite-size pencil beam is calculated one time and becomes a new data base with which to build larger beams by two-dimensional superposition. The pencil beam fluence profile, angle correction for beam divergence, the Mayneord inverse square correction, radial and angular sampling rates, error propagation, and computation time have been investigated and are reported. Radial and angular sampling rates have a great effect on accuracy and their appropriate selection is important. Percent depth doses calculated by finite-size pencil beam superposition are within 1% of values calculated by full convolution and the agreement with values from the literature is within 6%. The latter disagreement is shown to be due to a low-energy photon component which is not modeled in other calculations. Computation time measurements show the pencil beam method to be faster than full convolution and one implementation of the differential-scatter-air-ratio (dSAR) method.

Cobalt Radioisotopes↗

Specific surface area of snow samples determined by CH4 adsorption at 77 K and estimated by optical microscopy and scanning electron microscopy.

Snow is a divided medium that can adsorb atmospheric trace gases. Evaluating the impact of the snow cover on atmospheric chemistry therefore requires the knowledge of the specific surface area (SSA) of snow. This paper compares the results of three methods used to measure or estimate the SSA of four snow samples: CH4 adsorption at 77 K, optical microscopy (OM), and scanning electron microscopy (SEM, used only on two samples). Within error bars, CH4 adsorption and OM yield similar results on three of the four snow samples. Values for the 4th sample are within a factor of 2. For both samples where CH4 adsorption, OM, and SEM are used, all three methods yield similar results, but CH4 adsorption always has a better accuracy and a much better precision. Thus, despite its ease of use, estimates from OM images are often not accurate enough to monitor the evolution of snow SSA. The main sources of error in the OM method are the difficulty to determine snow crystal thicknesses and to take into account the topography of the snow crystal surface. The combination of CH4 adsorption and OM or SEM can provide useful information on the evolution of both the SSA and the shape of snow crystals. This will be useful to evaluate the respective contributions of adsorption/desorption and sublimation/condensation processes to the impact of the snow cover on atmospheric chemistry.

Adsorption↗