In the Netherlands, prepubertal girls have been vaccinated against rubella since 1974 (the UK strategy). Recently the Dutch Health Council advocated the introduction of an elimination strategy: vaccination of 1- and 9-year-old children. Dynamic effects of both strategies are studied using deterministic and stochastic models. Estimates of several epidemiological parameters are given. All computations and simulations were performed using as much field data as possible. Under the old strategy a new equilibrium is expected around the years 1995 to 2000; the new strategy is estimated to eliminate rubella (CRS) in large parts of the population 3 to 5 years after its initiation. Possible consequences of the new strategy on a cluster of people who refuse vaccination are investigated. 相似文献
The common denominator in the assessment of human balance and posture is the inverted pendulum model. If we focus on appropriate versions of the model we can use it to identify the gravitational and acceleration perturbations and pinpoint the motor mechanisms that can defend against any perturbation.
We saw that in quiet standing an ankle strategy applies only in the A/P direction and that a separate hip load/unload strategy by the hip abd/adductors is the totally dominant defence in the M/L direction when standing with feet side by side. In other standing positions (tandem, or intermediate) the two mechanisms still work separately, but their roles reverse. In the tandem position M/L balance is an ankle mechanism (invertors/evertors) while in the A/P direction a hip load/unloading mechanism dominates.
During initiation and termination of gait these two separate mechanisms control the trajectory of the COP to ensure the desired acceleration and deceleration of the COM. During initiation the initial acceleration of the COM forward towards the stance limb is achieved by a posterior and lateral movement of the COP towards the swing limb. After this release phase there is a sudden loading of the stance limb which shifts the COP to the stance limb. The COM is now accelerated forward and laterally towards the future position of the swinging foot. Also M/L shifts of the COP were controlled by the hip abductors/adductors and all A/P shifts were under the control of the ankle plantar/dorsiflexors. During termination the trajectory of both COM and COP reverse. As the final weight-bearing on the stance foot takes place the COM is passing forward along the medial border of that foot. Hyperactivity of that foot's plantarflexors takes the COP forward and when the final foot begins to bear weight the COP moves rapidly across and suddenly stops at a position ahead of the future position of the COM. Then the plantarflexors of both feet release and allow the COP to move posteriorly and approach the COM and meet it as quiet stance is achieved. The inverted pendulum model permitted us to understand the separate roles of the two mechanisms during these critical unbalancing and rebalancing periods.
During walking the inverted pendulum model explained the dynamics of the balance of HAT in both the A/P and M/L directions. Here the model includes the couple due to the acceleration of the weight-bearing hip as well as gravitational perturbations. The exclusive control of A/P balance and posture are the hip extensors and flexors, while in the M/L direction the dominant control is with the hip abductors with very minor adductor involvement. At the ankle the inverted pendulum model sees the COM passing forward along the medial border to the weight-bearing foot. The model predicts that during single support the body is falling forward and being accelerated medially towards the future position of the swing foot. The model predicts an insignificant role of the ankle invertors/evertors in the M/L control. Rather, the future position of the swing foot is the critical variable or more specifically the lateral displacement from the COM at the start of single support. The position is actually under the control of the hip abd/adductors during the previous early swing phase.
The critical importance of the hip abductors/adductors in balance during all phases of standing and walking is now evident. This separate mechanism is important from a neural control perspective and clinically it focuses major attention on therapy and potential problems with some surgical procedures. On the other hand the minuscule role of the ankle invertors/evertors is important to note. Except for the tandem standing position these muscles have negligible involvement in balance control. 相似文献
Abstract Daan's two process model is known to be one of the most powerful models, covering various situations from free-running to sleep deprivation. In this study, bifurcation properties of the model dynamics as function of a gap, D , between the threshold processes are clarified using a circle map. As a function of D , we will show that the model has the different types of the mutual entrainment regions that are intervened by the tangent bifurcation. The variable behavior of human circadian rhythm is suggested to be systematically understood based on the bifurcation properties of the two process model. 相似文献
We have established a rat model that reflects the course of development of alcohol and opiate addiction. The present study
with d-amphetamine aimed to define general principles in the development of an addiction. Male rats had a continuous free choice
between d-amphetamine solutions (100, 200 and 400 mg/l) and water for 47 weeks. An initial intake of high doses of d-amphetamine during the first weeks of drug choice was followed by an individually stable pattern of drug consumption of moderate
drug doses. During this period of controlled consumption (from week 10 to week 40), the voluntary intake of d-amphetamine depended on individual factors (dominant rats: 0.37 ± 0.02 mg/kg per day, subordinate rats: 0.57 ± 0.05 mg/kg
per day) and environmental variables (group housing: 0.21 ± 0.02 mg/kg per day, single housing: 0.41 ± 0.03 mg/kg per day).
Beginning with week 41, voluntary d-amphetamine consumption progressively increased (1.9 ± 0.2 mg/kg per day in week 47), although the experimental conditions
remained unchanged. Drug intake during a retest (free choice as before) after 6 months of drug deprivation revealed that the
rats had persistently lost their control over drug intake and were no longer able to adjust drug taking to internal and external
conditions. These addicted rats took very high drug doses, even when all d-amphetamine solutions but not water were adulterated with bitter tasting quinine (6.6 ± 0.6 mg/kg per day; age-matched controls:
0.37 ± 0.04 mg/kg per day). Forced intake of d-amphetamine for 47 weeks (7.1 ± 0.3 mg/kg per day) via the drinking fluid caused physical dependence (hyperreactivity during
withdrawal) but did not lead to drug addiction (voluntary intake in the retest with adulteration: 0.42 ± 0.04 mg/kg per day).
Both the temporal development and the prerequisites of psychostimulant addiction were in principle the same as for alcohol
and opiates.
Received: 3 April 1998/Final version: 26 August 1998 相似文献
Latent inhibition (LI) of a conditioned emotional response (CER) has been proposed as a quantitative measure of selective attention. We have assessed the parallels of the pharmacology of LI in rats with the clinical pharmacology of schizophrenia. Drug and vehicle treated rats were divided into groups and preexposed 20 times to cage illumination as a CS, or not preexposed. All groups were conditioned with 2 CS-footshock pairings. The following day CER, as measured by interruption of drinking in response to CS presentation, was recorded. LI was observed as a decreased CER in preexposed relative to non-preexposed animals. LI was enhanced by haloperidol 0.3 mg/kg after 7 or 14 daily treatments, but not after a single acute dose. Haloperidol doses of 0.3 and 0.03 mg/kg enhanced LI, while doses of 0.003 and 3.0 mg/kg had no effect. Haloperidol enhancement of LI was unaffected by the coadministration of the anticholinergic agent trihexyphenidyl. Enhancement of LI is exhibited by the antipsychotic drugs fluphenazine, chlorpromazine, thiothixene, thioridazine, mesoridazine, and metoclopramide but not clozapine. The non-antipsychotic drugs pentobarbital, imipramine, chlordiazepoxide, trihexyphenidyl, and promethazine failed to enhance LI. LI exhibits striking parallels to the clinical pharmacology of schizophrenia.Preliminary data were presented in part at the Society for Neuroscience Annual Meeting, Phoenix, AZ, 1989 相似文献
We present a new mathematical model for vagal control of rabbit sinoatrial (SA) node electrical activity based on the DiFrancesco-Noble
equations. The original equations were found to be unstable, resulting in progressive cycle by cycle depletion or accumulation
of ions in intra- and extracellular compartments. This problem was overcome by modifying the maximum Na−K pump current and
the time constant for uptake of intracellular calcium. We also included a formulation for the acetylcholine (ACh)-activated
potassium current which was consistent with experimental data. This formulation was based on kinetics first proposed by Osterrieder
and later modified by Yanagihara. The resulting model exhibits cycle-cycle ionic stability, and includes an ACh-activated
potassium current which accurately reproduces experimentally observed effects of vagal stimulation on both the membrane potential
and its timederivative. Simulations were performed for both brief-burst and prolonged vagal stimulation using simplified square
wave profiles for the concentration of ACh in the synaptic cleft space. This protocol permits the isolation of cardiac period
dynamics caused by changes in membrane potential and intra- and extracellular ionic concentrations from those caused by other
mechanisms including the dynamics of ACh release, diffusion, hydrolysis and washout. Simulation results for the effects of
brief-burst single cycle stimulation on the cardiac period agree closely with experimental data reported in the literature,
accurately reproducing changes in membrane potential and the phasic dependency of the response to the position of vagal stimulus
bursts within the cycle. Simulation of the effects of prolonged vagal stimulation accurately reproduced the steady-state characteristics
of heart period response, but did not yield the complex multimodal dynamics of the recovery phase, or the pronounced post
vagal tachycardia observed experimentally at the termination of the stimulus. Our results show that the major chronotropic
effects of vagal stimulation on the SA cell membrane can be explained in terms of the ACh-activated potassium current. The
effects of this membrane current however are generally fast acting and cannot contribute to any long lasting dynamics of the
cardiac period response. The modified DiFrancesco-Noble model presented in this article provides a valuable theoretical tool
for further analysis of the dynamics of vagal control of the cardiac pacemaker. 相似文献