Production system-based model for defining economic thresholds in preweaner beef cattle, Bos taurus, infested with the lone star tick, Amblyomma americanum (Acari: Ixodidae).
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Auditory-evoked potentials, originating from the brain stem and the forebrain, were studied in 30 unanesthetized kittens during the first 3 months of postnatal life, and from a smaller set of animals before and after surgical exposure of their tympanic membranes. In intact animals, responses to 135-dB peak SPL clicks were first reliably discernible on the seventh postnatal day; when stimuli were presented directly to the exposed tympanic membrane, responses were observed several days earlier. Responses progressed through three stages during maturation: an early period of gross insensitivity during which responses are evoked only by high-intensity stimuli and whose response thresholds remain essentially constant (week 1); a middle period characterized by rapid acquisition of sensitivity to near-adult values (week 2); and a late period during which adult thresholds and latencies are acquired. A sequential stage model of threshold maturation is proposed, in which thresholds decline linearly during stage two and exponentially during stage three. It is hypothesized that mechanical reorganization of the cochlea during the first 2 to 3 postnatal weeks and development of the stria vascularis are primarily responsible for the linear stage, and that neural factors primarily underlie the exponential stage and account for the gradual acquisition of adult thresholds. Rates of maturation for brain stem responses are frequency dependent, with responses to high frequencies achieving adult thresholds earlier than those to low frequencies.
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To obtain the best statistical model for a previous study of cataract prevalence in atomic-bomb survivors, we tested the fitness of the threshold model in an updated dataset of the study, utilizing re-diagnosis by a single ophthalmologist, use of the DS02 dosimetry system, and separation of the in utero group. The results suggest that, in 730 atomic-bomb survivors, we cannot conclude thresholds are greater than 0 Sv in cortical cataract and posterior sub-capsular opacity since the lower 90% confidence limits of the thresholds were 0 Sv. Threshold dose point estimates were 0.6 Sv (90% CI, <0.0-1.2 Sv) and 0.7 Sv (90% CI, <0.0-2.8 Sv) for cortical cataract and posterior sub-capsular opacity, respectively. Detailed regression analyses with no threshold model showed that nuclear color and nuclear opacity have no dose responses (p > 0.40). Cortical cataract showed a significant dose effect (p = 0.002), with an odds ratio (OR)/Sv of 1.30 (95% CI, 1.10-1.53) and no dose-effect modifiers. Posterior sub-capsular opacity showed a significant dose effect (p < 0.001), with an OR/Sv of 1.44 at age of exposure of 10 y (95% CI, 1.19-1.73). The dose effect decreased significantly with increasing age at exposure (p = 0.022). No dose response was observed for in utero survivors (p > 0.20).
To estimate the risk of decompression sickness (DCS) for direct ascents from depth to the sea surface for personnel who are saturated with hyperbaric nitrogen, we analyzed 586 experimental air or nitrogen-based saturation dives. No DCS occurred on shallow saturation dives between 12.0 and 20.5 feet of seawater, gauge (fswg) but incidence of DCS rose abruptly when depth was deeper than 20.5 fswg, reaching 27% at 30 fswg. This is evidence of a threshold for clinical DCS. A model based on a Hill function that provides for a threshold predicts the observations better than a model having no threshold provision; the no-threshold model overestimates risk shallower than 20.5 fswg and underestimates risk between 20.5 and 30 fswg. For situations such as submarine rescues, we recommend our threshold model when the exposure pressure is 33 fswg or less. We also discuss deeper dives where there are no human data; extrapolations can be quite different for models that provide for a threshold than for models that do not.
To explore the timing and the underlying neural dynamics of visual perception, we analyzed the relationship between the manual reaction time (RT) to the onset of a visual stimulus and the time course of the evoked neural response simultaneously measured by magnetoencephalography (MEG). The visual stimuli were a transition from incoherent to coherent motion of random dots and an onset of a chromatic grating from a uniform field, which evoke neural responses in different cortical sites. For both stimuli, changes in median RT with changing stimulus strength (motion coherence or chromatic contrast) were accurately predicted, with a stimulus-independent postdetection delay, from the time that the temporally integrated MEG response crossed a threshold (integrator model). In comparison, the prediction of RT was less accurate from the peak MEG latency, or from the time that the nonintegrated MEG response crossed a threshold (level detector model). The integrator model could also account for, at least partially, intertrial changes in RT or in perception (hit/miss) to identical stimuli. Although we examined MEG-RT relationships mainly for data averaged over trials, the integrator model could show some correlations even for single-trial data. The model predictions deteriorated when only early visual responses presumably originating from the striate cortex were used as the input to the integrator model. Our results suggest that the perceptions for visual stimulus appearances are established in extrastriate areas [around MT (middle temporal visual area) for motion and around V4 (fourth visual area) for color] approximately 150-200 ms before subjects manually react to the stimulus.
1. We measured the modulation of the background firing rate of cat spinal motoneurons produced by simulated, repetitive excitatory postsynaptic potentials (EPSPs) to test the accuracy of several proposed motoneuron input-output functions. Rhythmic discharge was elicited in the motoneurons by injecting suprathreshold current steps 1-1.5 s in duration. On alternate trials, trains of short (0.5-5 ms) current pulses were superimposed on the current steps to stimulate the effects of trains of individual EPSPs. The increase in firing rate (delta F) due to the addition of the pulses was calculated as the difference in motoneuron discharge rate between trials with and without the superimposed pulse trains. 2. In the same motoneurons, we were able to study the effects of changes in pulse frequency, duration, and amplitude, as well as changes in the background discharge rate. A sublinear relationship between pulse rate and delta F was observed, with delta F rising relatively steeply with increasing pulse frequency at low pulse rates and saturating at high pulse rates. A similarly shaped relation was observed between delta F and pulse duration. In contrast, delta F generally increased in a greater than linear fashion with increasing pulse amplitude. 3. In previous studies we demonstrated that when a relatively constant synaptic input is produced by high-frequency synaptic activity, delta F is approximately equal to the product of the net synaptic current reaching the soma and the slope of the motoneuron's steady-state frequency-current (f-I) relation. In the present study, this input-output function consistently underestimated the observed delta F, particularly for low input rates, indicating that the transient current pulses are more effective in modulating motoneuron discharge than an equivalent amount of constant current. 4. Other investigators have proposed input-output functions derived from the relation between synaptic potential amplitude and the magnitude of the peak of a cross correlogram compiled from the discharge of the pre- and postsynaptic neurons. These functions consistently overestimated the observed delta F, particularly for high pulse rates. This overestimation may result in part from the fact that the effects of a synaptic potential (or current pulse) on postsynaptic discharge probability also include a period of decreased firing probability. Moreover, the cross correlation function may depend on the arrival rate of synaptic potentials (or current pulses). 5. Another proposed input-output function based on a simple threshold-crossing model of the motoneuron with a fixed spike threshold predicts firing rates that were often close to the observed delta F. However, the model did not reproduce the observed relations between delta F and input pulse rate or pulse duration. 6. The deficiencies of the basic threshold-crossing model may arise from the fact that it does not incorporate variations in membrane conductance and firing threshold that occur in real motoneurons. A more complete motoneuron model that incorporates both of these features was able to replicate the observed delta Fs associated with changes in input pulse frequency and duration.
This paper deals with the subject of anaerobic threshold measurements for athletes involved in aerobic or aerobic/anaerobic sports. Traditionally, anaerobic threshold has been determined using invasive tests or using a non-invasive technique using steady-state heart-rate/work rate data. Non-invasive tests have the advantage of not requiring specialised equipment, but the acquisition of steady-state information can be problematic. This paper demonstrates how dynamical data can be used to accurately determine the steady-state heart-rate/work-rate curve (SSHW curve) using neural network dynamic models.
Inadequate statistical procedures are often applied for the derivation of threshold values in various medical research areas. The frequently applied method to establish threshold values on the basis of simple comparisons between arbitrarily defined low-volume and high-volume groups may be misleading because the result depends on the preceding classification. In this paper, the possibilities and limitations of statistical regression models for the calculation of threshold values are described. The features of these models for the selection of minimum volumes for hospitals or physicians are discussed. Simulated data examples are used to demonstrate that the definition of a useful minimum provider volume should not be based upon a calculated value of purely mathematical meaning without clinically assessing the risk curve. In the application of statistical regression models to retrospective observational data it should be noticed that calculated threshold values are only of a hypothesis-generating character. In order to verify that a minimum provider volume leads to the expected quality improvement, a prospective intervention study is required.
Many studies have shown a positive association between ambient ozone levels and mortality. Typically, these findings are based on models that assume a linear relationship between log mortality and ozone level. In this study, we adapted generalized additive models in which ozone effects are presumed to occur in three different ways: as a simple linear term, as a cubic natural spline term, and as a combination of two linear terms (a threshold model). We applied these models to daily time-series data for Seoul, Korea for the years 1995-1999 and found that the threshold model always fits best among the three. A 2.6% (95% CI: 1.7-3.5) increase of estimated relative risk (RR) in the total mortality associated with a 21.5 ppb increase of daily 1-h maximum ozone lagged by 1 day was observed by linear Poisson's regression. However, a 3.4% (95% CI: 2.3-4.4) increase in the estimated RR was observed using the threshold model. Adjustments for other ambient pollutants caused little changes to these results; 2.4-2.5% in the linear models and 3.2-3.4% in the threshold models. In addition, the largest difference in the estimated RRs of the linear and threshold models was observed in the summer: 1.9% (95% CI: 0.5-3.3) by the linear model and 3.8% (95% CI: 2.0-5.7) by the threshold model. These findings indicate that the conventional time-series Poisson regression model, which dose not take threshold into consideration, could underestimate the true risk of the ozone effect on daily mortality.
The stabilized spatiotemporal threshold response surface can be modeled as the linear difference between the threshold response surfaces of two mechanisms, each of which is simply the product of a spatial and temporal frequency response curve. With no free parameters, the resulting model is shown to be a good fit to available data.
A double-blind, placebo-controlled, parallel-group, ascending, multiple-dose study was completed in 45 healthy male volunteers to assess the maximum tolerated dose, pharmacokinetics, and pharmacodynamics of BMS-187745, a squalene synthase inhibitor, administered as multiple oral doses of its prodrug BMS-188494. Participants received a daily oral dose of 10 mg for 2 weeks, or a daily oral dose of 25, 50, 100, or 200 mg for 4 weeks. The absorption rate constant (ka) and bioavailability (F) values were estimated by fitting the plasma BMS-187745 concentration-time data to a biexponential function with a first-order ka. Values for F were similar for all five dose levels, and thus were independent of dose. The ka values also were similar for all dose groups except the 50-mg group, for which ka values were somewhat higher. The change in urinary excretion rate of farnesyl pyrophosphate metabolite (dioic acid) was determined to be a pharmacodynamic measure. There was no significant change in dioic acid excretion at doses of less than 100 mg given for 4 weeks. An indirect pharmacodynamic response model with threshold concentration (CT) and based on inhibition of squalene synthase was proposed to describe the effect versus time data. The pharmacodynamic data from all dose levels were fitted simultaneously to the proposed model and the fitted parameters estimated as CT = 3.9 micrograms/mL, kout = 0.47 hr-1, IC50 = 4.1 micrograms/mL, and Imax = 1.0. The proposed indirect response model requiring a threshold concentration provides a useful means of quantitating responses for a new type of therapeutic agent.
The aim of the study is to determine which of the existing myelinated mammalian nerve fibre models better fits experimental data resulting from electrical stimulation of the human optic nerve and from propagation velocity measured on primates. The macroscopic electric potential is computed in a 3D, inhomogeneous and anisotropic nerve model. The Chiu-Sweeney (CS) and the Schwarz-Wesselink (SW) membrane descriptions are then considered. Variations in parameters that are not well established (encapsulation-tissue thickness, nerve-fascicle conductivity, geometric and electrochemical fibre cable parameters) are taken into account. Results demonstrate that the SW model predictions are in better agreement with the experimental data than those of the CS model, although thresholds are still too high. When channel densities are varied, the SW model turns out to be more robust than the CS model. For a suitable leakage channel density value (about 8% of the original one), the SW model predicts a conduction velocity of 11.4 ms-1 and an excitation threshold of 0.055 mA (for 0.1 ms pulse duration), which is in very good agreement with experimental values (11 ms-1 and 0.055 mA). Potassium current in the SW model is necessary for stability. Introduction of a potassium-like current can restore stability in the CS system.
This is the second in a series of papers modeling human immunodeficiency virus (HIV) infections at four levels: transmission, interaction with the immune system, gene regulation, and selection of mutants. In the previous paper (1) we described and presented a theory of the HIV cytopathic effect based upon the models (and a review of the literature). In this article we give mathematical equations of threshold conditions that connect infectivity, length of host survival, and frequency of acts conducive to transmission. The formula is derived not only for homogeneous populations but also for populations of an arbitrary number of subgroups with varying frequencies of risk behavior, varying rates of infection and latency periods, and varying frequencies of interaction with other groups.
The noise generated by the otologic drill has been implicated as a cause of sensorineural hearing loss after ear surgery. However, clinical studies on this subject are contradictory and difficult to interpret. Therefore a guinea pig model was used to study whether the level of noise generated by the otologic drill can cause threshold shifts in the auditory brainstem response (ABR). The source noise was a recording obtained during a human cadaver mastoidectomy using a microphone and an accelerometer. Ten female Topeka-strain guinea pigs were exposed to the recorded drill noise for a period of 55 minutes. Exposure included both air-conducted energy from a speaker and bone-conducted energy from a bone vibrator applied directly to the skull. ABR threshold measurements were taken pre-exposure (baseline), immediately after exposure, and at weekly intervals thereafter for 3 weeks. Three control animals were subjected to the same procedure without the sound exposure. A significant threshold shift (p < 0.0001) was seen for each frequency tested (2, 4, 8, 16, 20, and 32 kHz) immediately after exposure to noise in all experimental animals. Thresholds returned to baseline within 3 weeks. We conclude that the level of noise generated by the otologic drill in mastoid surgery can cause a temporary threshold shift in this guinea pig model.
A precise definition of the basic reproduction number, R0, is presented for a general compartmental disease transmission model based on a system of ordinary differential equations. It is shown that, if R0<1, then the disease free equilibrium is locally asymptotically stable; whereas if R0>1, then it is unstable. Thus, R0 is a threshold parameter for the model. An analysis of the local centre manifold yields a simple criterion for the existence and stability of super- and sub-threshold endemic equilibria for R0 near one. This criterion, together with the definition of R0, is illustrated by treatment, multigroup, staged progression, multistrain and vector-host models and can be applied to more complex models. The results are significant for disease control.