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The effect of threshold on the relationship between the receptive-field profile and the spatial-frequency tuning curve in simple cells of the cat's striate cortex.

It is believed that spatial summation in most simple cells is a linear process. If this were so, then the Fourier transform of a simple cell's line weighting function should predict the cell's spatial frequency tuning curve. We have compared such predictions with experimental measurements and have found a consistent discrepancy: the predicted tuning curve is much too broad. We show qualitatively that this kind of discrepancy is consistent with the well-known threshold nonlinearity shown by most cortical cells. We have tested quantitatively whether a response threshold could explain the observed disagreements between predictions and measurements: a least-squares minimization routine was used to fit the inverse Fourier Transform of the measured frequency tuning curve to the measured line weighting function. The fitting procedure permitted us to introduce a threshold to the reconstructed line weighting function. The results of the analysis show that, for all of the cells tested, the Fourier transforms produced better predictions when a response threshold was included in the model. For some cells, the actual magnitude of the response threshold was measured independently and found to be compatible with that suggested by the model. The effects of nonlinearities of spatial summation are considered.

Animals↗

Dose efficiency and low-contrast detectability of an amorphous silicon x-ray detector for digital radiography.

The effect of dose reduction on low-contrast detectability is investigated theoretically and experimentally for a production grade amorphous silicon (a-Si) x-ray detector and compared with a standard thoracic screen-film combination. A non-prewhitening matched filter observer model modified to include a spatial response function and internal noise for the human visual system (HVS) is used to calculate a signal-to-noise ratio (SNR) related to object detectability. Other inputs to the SNR calculation are the detective quantum efficiency (DQE) and the modulation transfer function (MTF) of the imaging system. Besides threshold detectability, the model predicts the equivalent perception dose ratio (EPDR), which is the fraction of the screen film exposure for which the digital detector provides equal detectability. Images of a contrast-detail phantom are obtained with the digital detector at dose levels corresponding to 27%, 41%, 63% and 100% of the dose used for screen-film. The images are used in a four-alternative forced choice (4-AFC) observer perception study in order to measure threshold detectability. A statistically significant improvement in contrast detectability is measured with the digital detector at 100% and 63% of the screen-film dose. There is no statistical difference between screen-film and digital at 41% of the dose. On average, the experimental EPDR is 44%, which agrees well with the model prediction of 40%.

Equipment Design↗

The National Morbidity, Mortality, and Air Pollution Study. Part III: PM10 concentration-response curves and thresholds for the 20 largest US cities.

Numerous studies have shown a positive association between daily mortality and particulate air pollution, even at concentrations below regulatory limits. These findings have motivated interest in the shape of the concentration-response relation. We developed flexible modeling strategies for time-series data that include spline and threshold concentration-response models. We applied these models to daily time-series data for the 20 largest US cities for 1987 through 1994, using concentration of particulate matter less than 10 microm in aerodynamic diameter (PM10*) as the exposure measure. The spline model showed a linear relation without indicating a threshold for the relative risks of death for all causes (total deaths) and for cardiovascular-respiratory causes in relation to PM10 concentration. By contrast, for causes other than cardiovascular-respiratory, the relative risk did not increase until the concentration reached approximately 50 microg/m3 PM10. For total mortality, a linear model without threshold was preferred to the threshold model and to the spline model, using the value of the Akaike information criterion (AIC). The findings were similar for combined cardiovascular and respiratory deaths. These findings indicate that linear models without a threshold are appropriate for assessing the effect of particulate air pollution on daily mortality even at current ambient levels.

Air Pollution↗

Ralitoline: a reevaluation of anticonvulsant profile and determination of "active" plasma concentrations in comparison with prototype antiepileptic drugs in mice.

Ralitoline (RLT) is a new thiazolidinone derivative with potent anticonvulsant activity in different seizure models. During Phase I studies, RLT was well tolerated in human volunteers and showed linear pharmacokinetics in the dose range tested (up to 150 mg). Since RLT will soon be entering clinical Phase II studies, we were interested in obtaining predictive data for effective plasma concentrations in patients. For this purpose, the anticonvulsant potency of RLT was determined in four seizure models in mice, and plasma levels were measured at time of peak drug effect. The four models were the threshold for maximal (tonic extension) electroshock seizures (MES), the threshold for clonic seizures determined by i.v. infusion of pentylenetetrazol (PTZ), the traditional MES test with supramaximal (50 mA) stimulation, and generalized clonic seizures induced by s.c. administration of PTZ. Furthermore, median minimal "neurotoxic" doses (TD50s) were determined by the rotorod and chimney test for calculation of protective indices. All data obtained for RLT were compared with data obtained with standard antiepileptic drugs: phenobarbital, phenytoin, valproate, and diazepam. The onset of anticonvulsant action after i.p. injection of RLT was very rapid, and the peak drug effect was already obtained after 2 min. In the MES models, RLT was the most potent compound. "Active" plasma levels ranged from approximately 300 ng/ml in the MES threshold test to approximately 1,300 ng/ml in the MES test. RLT was also capable of increasing the PTZ threshold, whereas, possibly because of its short duration of action in mice, it was not very active in the s.c. PTZ seizure test.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Quantitative somatosensory testing of the penis: optimizing the clinical neurological examination.

PURPOSE: Quantitative somatosensory testing, including vibration, pressure, spatial perception and thermal thresholds of the penis, has demonstrated neuropathy in patients with a history of erectile dysfunction of all etiologies. We evaluated which measurement of neurological function of the penis was best at predicting erectile dysfunction and examined the impact of location on the penis for quantitative somatosensory testing measurements. MATERIALS AND METHODS: A total of 107 patients were evaluated. All patients were required to complete the erectile function domain of the International Index of Erectile Function (IIEF) questionnaire, of whom 24 had no complaints of erectile dysfunction and scored within the "normal" range on the IIEF. Patients were subsequently tested on ventral middle penile shaft, proximal dorsal midline penile shaft and glans penis (with foreskin retracted) for vibration, pressure, spatial perception, and warm and cold thermal thresholds. RESULTS: Mixed models repeated measures analysis of variance controlling for age, diabetes and hypertension revealed that method of measurement (quantitative somatosensory testing) was predictive of IIEF score (F = 209, df = 4,1315, p <0.001), while site of measurement on the penis was not. To determine the best method of measurement, we used hierarchical regression, which revealed that warm temperature was the best predictor of erectile dysfunction with pseudo R(2) = 0.19, p <0.0007. There was no significant improvement in predicting erectile dysfunction when another test was added. Using 37C and greater as the warm thermal threshold yielded a sensitivity of 88.5%, specificity 70.0% and positive predictive value 85.5%. CONCLUSIONS: Quantitative somatosensory testing using warm thermal threshold measurements taken at the glans penis can be used alone to assess the neurological status of the penis. Warm thermal thresholds alone offer a quick, noninvasive accurate method of evaluating penile neuropathy in an office setting.

Analysis of Variance↗

On-off convection: Noise-induced intermittency near the convection threshold.

A phenomenological nonlinear stochastic model of intermittency experimentally observed by Behn, Lange, and John [Phys. Rev. E 58, 2047 (1998)] in the electrohydrodynamic convection in nematics under dichotomous noise is proposed. This has the structure of the two-dimensional Swift-Hohenberg equation for local convection variable with fluctuating threshold. Numerical integration of the model equation shows intermittent emergence of convective pattern. Its statistics are found to obey those known, so far, for on-off intermittency. In the course of time, although the pattern intensity changes intermittently, no evident pattern change is observed. Adding additive noise, we observe an intermittent change of convective pattern.

Journal Article↗

Analytical modeling of the hysteresis phenomenon in guinea pig ventricular myocytes.

In the present study, we have demonstrated hysteresis phenomena in the excitability of single, enzymatically dissociated guinea pig ventricular myocytes. Membrane potentials were recorded with patch pipettes in the whole-cell current clamp configuration. Repetitive stimulation with depolarizing current pulses of constant cycle length and duration but varying strength led to predictable excitation (1:1) and non-excitation (1:0) patterns depending on current strength. In addition, transition between patterns depended on the direction of current intensity change and stable hysteresis loops were obtained in stimulus:response pattern vs. current intensity plots in 14 cells. Increase of pulse duration and decrease of stimulation rate contributed to a reduction in hysteresis loop areas. Changes in amplitude and shape of the subthreshold responses during the transitions from one stable pattern to the other, suggested that activity led to an increase in membrane resistance, particularly in the voltage domain between resting potential, and threshold. Therefore, we modelled the dynamic behaviour of the single cells as a function of diastolic membrane resistance, using previously published analytical solutions. Numerical iteration of the analytical model equations closely reproduced the experimental hysteresis loops in both qualitative and quantitative ways. In particular, the effect of stimulation frequency on the model was similar to the experimental findings. The overall study suggests that the excitability pattern of guinea pig ventricular myocytes accounts for hysteresis and bistabilities when current intensity is allowed to fluctuate around threshold levels.

Action Potentials↗

Lung preservation threshold in a compromised septic lung injury model.

BACKGROUND: Discrepancy between clinical and research works in lung transplantation could be due to differences between compromised clinical donor lungs and intact research lungs. The purpose of this laboratory study was to produce compromised lungs to compare with normal ones. METHODS: Sprague-Dawley rats were continuously infused with lipopolysaccharide (5 mg/kg) for 24 hours before organ harvest. Lungs were stored in University of Wisconsin solution at 4 degrees C for the following period: group 1: intact lungs, no storage (n = 12); group 2: septic lungs, no storage (n = 6); group 3: septic lungs for 6 hours (n = 5); and group 4: septic lungs for 12 hours (n = 5). All lungs were reperfused for 2 hours with venous blood using an isolated, pulsatile perfused lung system. RESULTS: Experimental variables were comparable between groups 1, 2, and 3. All septic lungs stored for 12 hours (group 4) failed within 1 hour of perfusion. CONCLUSIONS: These results indicate that compromised lungs with septic injury functioned at near control levels after 6 hours of preservation. Six hours may be a safe limit for human donor lungs, all of which are compromised in some way by the time of harvest.

Animals↗

A chi(2) test for model determination and sublevel detection in ion channel analysis.

A chi(2) test is proposed that provides a means of discriminating between different Markov models used for the description of a measured (patch clamp) time series. It is based on a test statistic constructed from the measured and the predicted number of transitions between the current levels. With a certain probability, this test statistic is below a threshold if the model with a reduced number of degrees of freedom is compatible with the data. A second criterion is provided by the dependence of the test statistic on the number of data points. For data generated by the alternative model it increases linearly. The applicability of this test for verifying and rejecting models is illustrated by means of time series generated by two distinct channels with different conductances and by time series generated by one channel with two conductance levels. For noisy data, a noise correction is proposed, which eliminates noise-induced false jumps that would interfere with the test. It is shown that the test can also be extended to aggregated Markov models.

Chi-Square Distribution↗

Use of randomization testing to detect multiple epistatic QTLs.

Here, we describe a randomization testing strategy for mapping interacting quantitative trait loci (QTLs). In a forward selection strategy, non-interacting QTLs and simultaneously mapped interacting QTL pairs are added to a total genetic model. Simultaneous mapping of epistatic QTLs increases the power of the mapping strategy by allowing detection of interacting QTL pairs where none of the QTL can be detected by their marginal additive and dominance effects. Randomization testing is used to derive empirical significance thresholds for every model selection step in the procedure. A simulation study was used to evaluate the statistical properties of the proposed randomization tests and for which types of epistasis simultaneous mapping of epistatic QTLs adds power. Least squares regression was used for QTL parameter estimation but any other QTL mapping method can be used. A genetic algorithm was used to search for interacting QTL pairs, which makes the proposed strategy feasible for single processor computers. We believe that this method will facilitate the evaluation of the importance at epistatic interaction among QTLs controlling multifactorial traits and disorders.

Algorithms↗