Predicting the dynamic effects of rubella vaccination programmes

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.     

Bifurcation properties of the two process model

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.     

三次抛物线配合方法在碘缺乏病区居民患病率分析中的应用

<正>在碘缺乏病区,居民甲状腺肿患病率在年鹅分布上的特征,可用二次抛物线加以描述[l].根握资料类型的不同,可选择更为适合的三次抛物线来描述.根据现场调查资料,本文采用三次抛物线方法进行配合,并将配合结果与二     

大白鼠游泳输出功测定仪的研制和疲劳方程Y＝A＋B／T的建立

研制了可以直接连续测量大鼠游泳输出功率的仪器，建立了一个理想的动物模型，通过分析对功率曲线进行函数拟合，得出了代表疲劳发生、作功能力下降的双曲线方程，通过分析衰竭时间和功、功率等参数的关系提出了衰竭阈概念。     

Modification of DiFrancesco-Noble equations to simulate the effects of vagal stimulation onin vivo mammalian sinoatrial node electrical activity

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.     

Comparison of mathematically determined blood lactate and heart rate “threshold” points and relationship with performance

Summary The purpose of this study was to investigate the relationship between threshold points for heart rate ( ) and blood lactate (Th_1a) as determined by two objective mathematical models. The models used were the mono-segmental exponential (EXP) model of Hughson et al. and the log-log (LOG) model of Beaver et al. Inter-correlations of these threshold points and correlations with performance were also studied. Seventeen elite runners (mean, SD = 27.5, 6.5 years; 1.73, 0.05 m; 63.8, 7.3 kg; and maximum oxygen consumption of 67.8, 3.7 ml · kg^–1 · min^–1) performed two maximal multistage running field tests on a 183.9-m indoor track with inclined turns. The initial speed of 9 km · h^–1 (2.5 m · s^–1) was increased by 0.5 km · h^–1 (0.14 m · s^–1) every lap for thef _c test and by 1 km · h^–1 (0.28 m · s^–1) every 4 min for the la test. After fitting the la or thef _c data to the two mathematical models, the threshold speed was assessed in the LOG model from the intersection of the two linear segments (LOG-1a; LOG-f _c) and in the EXP model from a tangent point (TI-1a; TI-f _c). Th_1a and speeds computed with the two models were significantly different (P<0.001) and poorly correlated (LOG-1a vs LOG-f _c:r=0.36, TI-1a vs TI-f _c:r=0.13). In general, were less well correlated with performance than Th_1a. With two different objective mathematical models, this study has shown significant differences and poor correlations between Th_1a and . Thus thef _c inflection point with Conconi's protocol is a poor indicator of the la breakpoint with a conventional multistage protocol and a weaker indicator of running performance.     

Complement-derived polypeptide C3adesArg as a mediator of inflammation at the blood-brain barrier in a new experimental cat model

Summary The effect of the complement-derived polypeptide C3adesArg as a mediator of inflammation in the central nervous system was examined. Twenty-five anesthetized cats received 4 mg of this polypeptide by intraventricular injection, 20 cats who served as controls received saline. Cerebrospinal fluid (CSF) was sampled 3 h after intraventricular injection and the brains were removed. For assessment of the permeability of the blood-brain barrier the CSF penetration of four antibiotics, which were given intravenously, was measured. Five control animals were employed for each antibiotic (tobramycin, ampicillin, imipenem, fosfomycin), whereas six C3adesArg-treated animals were used for each antibiotic and seven for tobramycin. Besides CSF levels of glucose, the prostanoids 6-keto-prostaglandin F₁, thromboxane B₂ and prostaglandin E₂ were measured. The morphological examinations in the CSF sediments and histological brain sections in the C3adesArg-treated animals disclosed a distinct inflammation with leptomeningeal and perivascular infiltration of polymorphonuclear granulocytes compared to normal findings in the controls. The CSF/serum ratios of all of the antibiotics were markedly elevated compared to controls, indicating a blood-brain barrier disruption. The levels of all prostanoids were significantly higher in the treatment group than in the control group, whereas the glucose levels were lower. These findings are in accordance with a granulocytic meningitis as seen in some infections at the acute stage. It is concluded that C3adesArg acts as a mediator of inflammation in the central nervous system.     

The GABA hypothesis of kindling: Recent assay studies

The GABA (gamma-aminobutyric acid) hypothesis of kindling suggests that the permanent changes caused by the kindling procedure result from a loss of GABA-mediated inhibition. Pharmacological studies have generally supported this hypothesis: GABA-complex antagonists accelerate (or stimulate) kindling, whereas GABA-complex agonists retard (or reverse) it. Assay studies, however, have presented an inconsistent picture. Earlier studies found no GABAergic brain changes after kindling, whereas recent studies have reported postkindling changes in a number of GABA-related parameters. The crucial difference seems to be that earlier studies assayed GABA parameters in "whole tissue," whereas recent studies have concentrated on "synaptic" GABA. As indicated by recent studies, when the "metabolic pool" is excluded, kindled subjects show a variety of persistent abnormalities in the GABA system. These data are generally consistent with the GABA hypothesis of kindling.     

The middle collateral artery: anatomic basis for the “extreme” lateral arm flap

The vascularization of the posterolateral area of the arm is supplied by the terminal branches of the deep brachial artery [middle collateral artery (MCA) and posterior radial collateral artery]. Their anatomy has been a field of confusion for a long time. An extended lateral arm flap, named the extreme lateral arm flap, supplied by these branches and dissected as a retrograde island flap has been proposed as an alternative for large compound defects of the distal forearm. We carried out an extensive anatomic study of the extreme lateral arm flap on 69 upper limbs: 54 fresh injected with colored latex, 10 embalmed and 5 radiographed after Micropaque injection. Two origin levels of the MCA were found: a proximal one (37%) above the radial groove, and a distal one (63%) at the level of the groove. The deep brachial artery always bifurcated after the origin of the MCA into a posterior radial collateral artery (PRCA) and anterior radial collateral artery (ARCA). Indeed in our dissections, after the origin of the MCA from the deep brachial artery, there was always a common trunk named the radial collateral artery (RCA) which bifurcated into the ARCA and PRCA. In all dissected arms we always found the MCA anastomosed in a transverse pattern with the inferior ulnar collateral artery (IUCA), contributing to the anastomotic circle of the elbow. This circle represents the unique vascularization source of the reverse extreme lateral arm flap.     

Short-term enzyme replacement in the murine model of Sanfilippo syndrome type B

The Sanfilippo syndrome type B (MPS III B) is an autosomal recessive disease caused by deficiency of alpha-N-acetylglucosaminidase (EC 3. 2.1.50), one of the lysosomal enzymes required for the degradation of heparan sulfate. The disease is characterized by profound neurodegeneration but relatively mild somatic manifestations, and is usually fatal in the second decade. A mouse model had been generated by disruption of the Naglu gene in order to facilitate the study of pathogenesis and the development of therapy for this currently untreatable disease. Recombinant human alpha-N-acetylglucosaminidase (rhNAGLU) was prepared from secretions of Lec1 mutant Chinese hamster ovary cells. The enzyme, which has only unphosphorylated high-mannose carbohydrate chains, was endocytosed by mouse peritoneal macrophages via mannose receptors, with half-maximal uptake at ca. 10(-7) M. When administered intravenously to 3 month-old mice, rhNAGLU was taken up avidly by liver and spleen but marginally if at all by thymus, lung, kidney, heart, and brain (in order of diminishing uptake). The half-life of the enzyme was 2.5 days in liver and spleen. Immunohistochemistry and electron microscopy showed that only macrophages were involved in enzyme uptake and correction in these two organs, yet the storage of glycosaminoglycan was reduced to almost normal levels. The results show that the macrophage-targeted rhNAGLU can substantially reduce the body burden of glycosaminoglycan storage in the mouse model of Sanfilippo syndrome III B.