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Water permeability in resting and stimulated crayfish nerve.

The hydraulic conductivity, L(p), was determined in single axons of the crayfish, Procambarus clarkii, by injecting a hypertonic sample between two drops of silicone oil and photographing the volume increase of the sample. The method has the advantage of minimizing errors due to hydrostatic pressure differences across the membrane. In resting axons an L(p) of 0.236 x 10(-8) cm/ sec per cm H(2)O was found and similar values were obtained with low external calcium concentration and when the nerve was continuously stimulated at 20-30 impulses/sec. Thus the experiments have failed to demonstrate any change of water permeability in cases in which the ionic conductance is known to change. Some possible implications of this are discussed.

Animals↗

Correction of proton resonance frequency shift temperature maps for magnetic field disturbances caused by breathing.

Respiratory induced resonance offset (RIRO) is a periodic disturbance of a magnetic field due to breathing. Such disturbance handicaps the accuracy of the proton resonance frequency shift (PRFS) method of MRI temperature mapping in anatomies situated nearby the lungs and chest wall. In this work, we propose a method capable of minimizing errors caused by RIRO in PRFS temperature maps. In this method, a set of baseline images characterizing RIRO at a variety of respiratory cycle instants is acquired before the thermal treatment starts. During the treatment, the temperature evolution is found from two successive images. Then, the calculated temperature changes are corrected for the additional contribution caused by RIRO using the pre-treatment baseline images acquired at the identical instances of the respiratory cycle. Our method is shown to improve the accuracy and stability of PRFS temperature maps in the presence of RIRO and inter-scan motion in phantom and volunteers' breathing experiments. Our method is also shown to be applicable to anatomies moving during breathing if a proper registration procedure is applied.

Electromagnetic Fields↗

Precision-controlled elution of a 82Sr/82Rb generator for cardiac perfusion imaging with positron emission tomography.

A rubidium-82 ((82)Rb) elution system is described for use with positron emission tomography. Due to the short half-life of (82)Rb (76 s), the system physics must be modelled precisely to account for transport delay and the associated activity decay and dispersion. Saline flow is switched between a (82)Sr/(82)Rb generator and a bypass line to achieve a constant-activity elution of (82)Rb. Pulse width modulation (PWM) of a solenoid valve is compared to simple threshold control as a means to simulate a proportional valve. A predictive-corrective control (PCC) algorithm is developed which produces a constant-activity elution within the constraints of long feedback delay and short elution time. The system model parameters are adjusted through a self-tuning algorithm to minimize error versus the requested time-activity profile. The system is self-calibrating with 2.5% repeatability, independent of generator activity and elution flow rate. Accurate 30 s constant-activity elutions of 10-70% of the total generator activity are achieved using both control methods. The combined PWM-PCC method provides significant improvement in precision and accuracy of the requested elution profiles. The (82)Rb elution system produces accurate and reproducible constant-activity elution profiles of (82)Rb activity, independent of parent (82)Sr activity in the generator. More reproducible elution profiles may improve the quality of clinical and research PET perfusion studies using (82)Rb.

Algorithms↗

An application of reversible-jump Markov chain Monte Carlo to spike classification of multi-unit extracellular recordings.

Multi-electrode recordings in neural tissue contain the action potential waveforms of many closely spaced neurons. While we can observe the action potential waveforms, we cannot observe which neuron is the source for which waveform nor how many source neurons are being recorded. Current spike-sorting algorithms solve this problem by assuming a fixed number of source neurons and assigning the action potentials given this fixed number. We model the spike waveforms as an anisotropic Gaussian mixture model and present, as an alternative, a reversible-jump Markov chain Monte Carlo (MCMC) algorithm to simultaneously estimate the number of source neurons and to assign each action potential to a source. We derive this MCMC algorithm and illustrate its application using simulated three-dimensional data and real four-dimensional feature vectors extracted from tetrode recordings of rat entorhinal cortex neurons. In the analysis of the simulated data our algorithm finds the correct number of mixture components (sources) and classifies the action potential waveforms with minimal error. In the analysis of real data, our algorithm identifies clusters closely resembling those previously identified by a user-dependent graphical clustering procedure. Our findings suggest that a reversible-jump MCMC algorithm could offer a new strategy for designing automated spike-sorting algorithms.

Action Potentials↗

Wavelet analysis in a canine model of gastric electrical uncoupling.

Abnormal gastric motility function could be related to gastric electrical uncoupling, the lack of electrical, and respectively mechanical, synchronization in different regions of the stomach. Therefore, non-invasive detection of the onset of gastric electrical uncoupling can be important for diagnosing associated gastric motility disorders. The aim of this study is to provide a wavelet-based analysis of electrogastrograms (EGG, the cutaneous recordings of gastric electric activity), to detect gastric electric uncoupling. Eight-channel EGG recordings were acquired from 16 dogs in basal state and after each of two circular gastric myotomies. These myotomies simulated mild and severe gastric electrical uncoupling, while keeping the separated gastric sections electrophysiologically active by preserving their blood supply. After visual inspection, manually selected 10 min EGG segments were submitted to wavelet analysis. Quantitative methodology to choose an optimal wavelet was derived. This 'matching' wavelet was determined using the Pollen parametrization for 6-tap wavelet filters and error minimization criteria. After a wavelet-based compression, the distortion of the approximated EGG signals was computed. Statistical analysis on the distortion values allowed us to significantly (p < 0.05) distinguish basal state from mild and severe gastric electrical uncoupling groups in particular EGG channels.

Algorithms↗

Optimization of protein structure on lattices using a self-consistent field approach.

Lattice modeling of proteins is commonly used to study the protein folding problem. The reduced number of possible conformations of lattice models enormously facilitates exploration of the conformational space. In this work, we suggest a method to search for the optimal lattice models that reproduced the off-lattice structures with minimal errors in geometry and energetics. The method is based on the self-consistent field optimization of a combined pseudoenergy function that includes two force fields: an "interaction field," that drives the residues to optimize the chain energy, and a "geometrical field," that attracts the residues towards their native positions. By varying the contributions of these force fields in the combined pseudoenergy, one can also test the accuracy of potentials: the better the potentials, i.e., the more accurate the "interaction field," and the smaller the contribution of the "geometrical field" required for building accurate lattice models.

Models, Chemical↗

Fine-needle aspiration biopsy of synovial sarcoma. A cytomorphologic analysis of primary, recurrent, and metastatic tumors.

Thirteen fine-needle aspiration specimens from 10 patients with histologically proven synovial sarcoma are described. The aspiration biopsy specimens were obtained from the primary tumor in five cases, locally recurrent tumors in four cases, pulmonary metastases in three cases, and mediastinal metastasis in one case. Patient's ages ranged from 22 years to 65 years; there were four women and six men. All cases had a confirmation biopsy and/or resection specimen that were reviewed. Histologic subtypes included monophasic fibrous (5 cases), monophasic epithelial (1 case), biphasic (3 cases), and poorly differentiated (1 case). The majority of the aspiration biopsy specimens were similar with moderate to marked smear cellularity dominated by cohesive clusters of spindle-shaped cells with ovoid, hyperchromatic nuclei and scanty tapering cytoplasm. Nucleoli were not prominent. Epithelial tumor cells with ovoid to round, mostly regular, centrally to eccentrically located nuclei, surrounded by scant to abundant cytoplasm predominated in one case (monophasic epithelial) and were admixed with spindle cells in a second (classical biphasic). Multi-nucleated tumor giant cells were not observed in any of the tumors. In biphasic synovial sarcoma, the neoplastic spindle cells are generally more numerous and frequent than the epithelial cells, making distinction from monophasic synovial sarcoma or other spindle cell soft tissue tumors difficult. Although synovial sarcoma may be diagnosed by fine-needle aspiration cytology, clinical correlation, especially in monophasic types, is necessary to minimize errors in sarcoma classification.

Adult↗

Comparison of different melting temperature calculation methods for short DNA sequences.

MOTIVATION: The overall performance of several molecular biology techniques involving DNA/DNA hybridization depends on the accurate prediction of the experimental value of a critical parameter: the melting temperature Tm. Till date, many computer software programs based on different methods and/or parameterizations are available for the theoretical estimation of the experimental Tm value of any given short oligonucleotide sequence. However, in most cases, large and significant differences in the estimations of Tm were obtained while using different methods. Thus, it is difficult to decide which Tm value is the accurate one. In addition, it seems that most people who use these methods are unaware about the limitations, which are well described in the literature but not stated properly or restricted the inputs of most of the web servers and standalone software programs that implement them. RESULTS: A quantitative comparison on the similarities and differences among some of the published DNA/DNA Tm calculation methods is reported. The comparison was carried out for a large set of short oligonucleotide sequences ranging from 16 to 30 nt long, which span the whole range of CG-content. The results showed that significant differences were observed in all the methods, which in some cases depend on the oligonucleotide length and CG-content in a non-trivial manner. Based on these results, the regions of consensus and disagreement for the methods in the oligonucleotide feature space were reported. Owing to the lack of sufficient experimental data, a fair and complete assessment of accuracy for the different methods is not yet possible. Inspite of this limitation, a consensus Tm with minimal error probability was calculated by averaging the values obtained from two or more methods that exhibit similar behavior to each particular combination of oligonucleotide length and CG-content class. Using a total of 348 DNA sequences in the size range between 16mer and 30mer, for which the experimental Tm data are available, we demonstrated that the consensus Tm is a robust and accurate measure. It is expected that the results of this work would be constituted as a useful set of guidelines to be followed for the successful experimental implementation of various molecular biology techniques, such as quantitative PCR, multiplex PCR and the design of optimal DNA microarrays.

Algorithms↗

Finding differentially expressed genes for pattern generation.

MOTIVATION: It is important to consider finding differentially expressed genes in a dataset of microarray experiments for pattern generation. RESULTS: We developed two methods which are mainly based on the q-values approach; the first is a direct extension of the q-values approach, while the second uses two approaches: q-values and maximum-likelihood. We present two algorithms for the second method, one for error minimization and the other for confidence bounding. Also, we show how the method called Patterns from Gene Expression (PaGE) (Grant et al., 2000) can benefit from q-values. Finally, we conducted some experiments to demonstrate the effectiveness of the proposed methods; experimental results on a selected dataset (BRCA1 vs BRCA2 tumor types) are provided. CONTACT: alhajj@cpsc.ucalgary.ca.

Algorithms↗

Estimating substitution rates in ribosomal RNA genes.

A model is introduced describing nucleotide substitution in ribosomal RNA (rRNA) genes. In this model, substitution in the stem and loop regions of rRNA is modeled with 16- and four-state continuous time Markov chains, respectively. The mean substitution rates at nucleotide sites are assumed to follow gamma distributions that are different for the two types of regions. The simplest formulation of the model allows for explicit expressions for transition probabilities of the Markov processes to be found. These expressions were used to analyze several 16S-like rRNA genes from higher eukaryotes with the maximum likelihood method. Although the observed proportion of invariable sites was only slightly higher in the stem regions, the estimated average substitution rates in the stem regions were almost two times as high as in the loop regions. Therefore, the degree of site heterogeneity of substitution rates in the stem regions seems to be higher than in the loop regions of animal 16S-like rRNAs due to presence of a few rapidly evolving sites. The model appears to be helpful in understanding the regularities of nucleotide substitution in rRNAs and probably minimizing errors in recovering phylogeny for distantly related taxa from these genes.

Animals↗

Reducing multiple pregnancies by restricting the number of embryos transferred to two at the first embryo transfer attempt.

Though the multiple pregnancy rate in in-vitro fertilization-embryo transfer must be reduced, strict and uniform regulation of the number of embryos transferred may make it impossible for women with little natural fecundity to carry children. We therefore restricted the number of embryos per transfer. In the first half of the observation period (n = 100), we limited the number of embryos transferred to three regardless of the number of previous transfers. In the second half (n = 137), we strictly regulated the number of embryos transferred to two at the first attempt and three in the second and later attempts. The multiple pregnancy rate per pregnancy was significantly lower (P < 0.005) in the second period (20.4%) than in the first period (52.9%), while the clinical pregnancy rate and the implantation rate per transfer were similar in both observation periods. 60.7% (17/28) of the multiple pregnancies arose from the first embryo transfer attempt, and 17.9% (5/28) of them arose from a second attempt. The 18 multiple pregnancies in the first period involved six sets of triplets, while the 10 multiple pregnancies that arose in the second period all involved twins. The implantation rate per transfer at the first attempt was significantly higher than that at the second or later attempts. The criterion for determining the number of embryos transferred should be simple to minimize errors of judgement. We believe that our method of restricting the numbers of embryos transferred may be one method of reducing multiple pregnancies without eliminating the possibility of having children for women with low fecundity.

Adult↗

Heterogeneous sexual activity models of HIV transmission in male homosexual populations.

A proportionate mixing one-sex model of sexual transmission of HIV is described, in which sexual activity (new partners per unit time) is defined as a continuous variable in a set of integro-partial-differential equations. A discrete activity-class approximation is developed by matching equilibrium state and rate variables as closely as possible with the continuous-variable model, and consists only of ordinary differential equations. Activity-class boundaries are arbitrary, and each class is characterized by a single level of activity. If there are N classes, the level of activity in N - 1 of them is such that the steady-state susceptible class sub-population is equal to the population in the equivalent section of the continuous model. The activity level for the remaining class is chosen such that the condition for endemicity of the infection in the approximation is equal to that for the equivalent continuous-variable model; this minimizes errors in the steady-state population. The relationship between the discrete and continuous-variable models is explored, via numerical and analytical studies, in order to evaluate the accuracy of the approximation.

Acquired Immunodeficiency Syndrome↗

Visual assessment of sporozoite and bloodmeal ELISA samples in malaria field studies.

The accuracy of visually assessing positivity for samples of field-collected Anopheles tested by enzyme-linked immunosorbent assays (ELISA) for Plasmodium falciparum sporozoites and human bloodmeals was determined during malaria field studies in Kenya. Six observers familiar with ELISAs evaluated 5,344 sporozoite ELISA samples and four observers evaluated 360 bloodmeal samples as either positive or negative based on the presence and strength of green-colored peroxidase reactions relative to controls on each microtiter plate. Interobserver agreement ranged from 97.9 to 99.8% for sporozoite samples and from 90.3 to 96.1% for bloodmeal samples. For both assays, the mean sensitivity and specificity of visual readings, compared with spectrophotometric readings, exceeded 98% when absorbance values were greater than or equal to 0.4 (on a scale of 0.0 to 2.0). Most incorrect visual readings occurred for samples with absorbance values between 0.2 and 0.4. The total percentage of samples classified correctly by visual examination ranged from 97.7 to 99.5% for the sporozoite ELISA and from 95.0 to 96.7% for the bloodmeal ELISA. Thus, there was minimal error associated with visually determining positive reactions for the ELISA assays used in malaria field studies.

Animals↗

Future directions in food composition studies.

Food composition studies are essential for many purposes in nutrition, food science, and dietetics. This article reviews uses of food composition information in food labeling, nutrition education, dietary surveys, epidemiological studies, and dietary intervention trials. Research is need to minimize the causes of variation between actual and measured diets. This involves minimizing errors in food sampling, chemical analysis, food composition table construction, nutrient data bases for food groups, and in computations using nutrient analysis systems. Critical knowledge relative to food composition necessary for food science experts, nutrition professionals and other professionals is discussed. Improving the reporting of food composition data will also require more attention by editors of journals: if they demand more documentation, they will get it.

Diet↗

Transfer RNA determinants for translational editing by Escherichia coli valyl-tRNA synthetase.

Valyl-tRNA synthetase (ValRS) has difficulty differentiating valine from structurally similar non-cognate amino acids, most prominently threonine. To minimize errors in aminoacylation and translation the enzyme catalyzes a proofreading (editing) reaction that is dependent on the presence of cognate tRNA(Val). Editing occurs at a site functionally distinct from the aminoacylation site of ValRS and previous results have shown that the 3'-terminus of tRNA(Val) is recognized differently at the two sites. Here, we extend these studies by comparing the contribution of aminoacylation identity determinants to productive recognition of tRNA(Val) at the aminoacylation and editing sites, and by probing tRNA(Val) for editing determinants that are distinct from those required for aminoacylation. Mutational analysis of Escherichia coli tRNA(Val) and identity switch experiments with non-cognate tRNAs reveal a direct relationship between the ability of a tRNA to be aminoacylated and its ability to stimulate the editing activity of ValRS. This suggests that at least a majority of editing by the enzyme entails prior charging of tRNA and that misacylated tRNA is a transient intermediate in the editing reaction.

Acylation↗

The effect of frequency of kinetic feedback on learning an isometric force production task in nondisabled subjects.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the effects of kinetic feedback frequency and concurrent kinetic feedback on the performance and learning of an isometric force production task in young, nondisabled adults. SUBJECTS: Twenty-four nondisabled, right-hand-dominant adults (18 male, 6 female), aged 19 to 33 years (mean = 22.5, SD = 4.1), participated in this study. METHODS: Eight subjects in each of three kinetic feedback groups performed an isometric elbow extension task in an attempt to minimize error between their effort and a force template over a 5-second period. Feedback was provided (1) concurrently with and after each attempt (concurrent feedback), (2) after each attempt (100% feedback), or (3) after every other attempt (50% feedback). Immediate and delayed (48-hour) retention tests were performed without feedback. Separate analyses of variance for repeated measures were used to compare task error among the three feedback groups for acquisition, immediate retention, and delayed retention trials. RESULTS: A significant interaction was found during the acquisition trial blocks, but at each trial block, subjects in the concurrent feedback group exhibited less error than did the subjects in either the 50% or 100% feedback group during the acquisition trials. For the immediate retention test, the 50% and 100% feedback groups exhibited 58% and 39% less error, respectively, than did the concurrent group. For the delayed retention test, the 50% and 100% feedback groups exhibited 52% and 26% less error, respectively, than did the concurrent group. In the immediate and delayed retention tests, subjects in the 50% feedback group displayed less error (31% and 36%, respectively) than did the 100% feedback group. CONCLUSION AND DISCUSSION: When permanent changes in the performance of a motor task are desired, concurrent feedback about task performance may be less desirable than feedback that is provided after the task has been completed. In addition, when feedback was used after the task had been completed, a lower frequency of feedback resulted in more permanent changes in the subjects' ability to complete the task.

Adult↗

Intrasubject reliability of spinal range of motion and velocity determined by video motion analysis.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the repeatability of spinal range of motion (ROM) and movement velocity measurements of patients with chronic low back pain, using a two-dimensional motion analysis system. This apparatus uses reflective markers placed on anatomical landmarks and video digitization to derive ROM measurements from three segments of the spine and associated velocities through the respective ROMs. SUBJECTS: Forty-two patients with chronic LBP underwent ROM and movement velocity testing. METHODS: Each subject was tested twice without removal of the markers to minimize error contribution from differences in marker placement. RESULTS: Results indicated that both the ROM measures and the velocity measures were highly repeatable. Intraclass correlations for the ROM measures ranged from .77 to .96. Velocity measures were also reliable, with intraclass correlation coefficients ranging from .75 to .97. CONCLUSION AND DISCUSSION: Overall, the results seem to indicate that the video motion analysis system used in this study yields repeatable ROM and velocity measures on a clinical population. In practice, however, the measures may reflect greater errors due to the need of examiners to relocate markers at different testing sessions. These systems also offer distinct advantages over other means of obtaining ROM and velocity measures. The results of this study indicate that these measures may be obtained without undue concern for measurement artifact due to the instrumentation reliability.

Adult↗

Forecasting surgical groups' total hours of elective cases for allocation of block time: application of time series analysis to operating room management.

BACKGROUND: Allocation of the correct amount of operating room (OR) "block time" can provide surgeons with access to sufficient OR time to complete their elective cases while optimally matching staffing with the elective case workload (to maximize labor productivity). To evaluate how to predict accurately total hours of elective cases performed by a surgical group using data from surgical services information systems, the authors addressed the following questions: (1) How many previous 4-week periods of data should be used to minimize error in forecasting a surgical group's total hours of elective cases? (2) Using the number of 4-week periods from question #1, can we detect trends or correlations between successive periods that could be used to improve forecasting accuracy? (3) How can results from questions #1 and #2 be used to calculate an upper prediction bound (upper limit) for the total hours of elective cases that will be completed in a future period? Prediction bounds can be used to budget staffing accurately. METHODS: Time series analysis was performed on total hours of elective cases over 39 consecutive 4-week periods from 17 surgical groups. RESULTS: The average of 12 consecutive periods' total hours of elective cases had an appropriate error profile. The observations within each series of 12 consecutive 4-week periods followed a normal distribution, with each observation of total hours of elective cases not correlated with the subsequent observation. CONCLUSIONS: The average of the most recent 12 4-week periods can be used to predict surgical groups' future use of block time.

Algorithms↗