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Biomedical subjects

J F Vibert

Publications and source records attributed to J F Vibert.

At least 19 recordsLinked to original sources

Virtual surveillance of communicable diseases: a 20-year experience in France.

Inserm has developed, since 1984, an information system based on a computer network of physicians in France. It allows for constitution of large databases on diseases, with individual description of cases, and to explore some aspects of the mathematical theory of communicable diseases. We developed user-friendly interfaces for remote data entry and GIS tools providing real-time atlas of the epidemiologic situation in any location. The continuous and ongoing surveillance network is constituted of about 1200 sentinel voluntary and unpaid investigators. We studied their motivation, reasons for either withdrawal or compliance using survival analyses. We implemented early warning systems for outbreak detection and for time-space forecasting. We conducted epidemiological surveys for investigating outbreaks. Large available time and space series allowed us to calibrate and explore synchronism of influenza epidemics, to test the assumption of panmixing in susceptibles-infectious-removed type models and to study the role of closing school in influenza morbidity and mortality in elderly. More than 250 000 cases of influenza, 150 000 cases of acute diarrheas, 35,000 patients for whom HIV tests have been prescribed by general practitioners and 25,000 cases of chickenpox have been collected. Detection of regional influenza or acute diarrhea outbreaks and forecasting of epidemic trends three weeks ahead are currently broadcasted to the French media and published on Sentiweb on a weekly basis. Age-cohort-period models assessed field effectiveness of mass immunization strategies against measles and influenza in the country. Case-control studies with more than 1200 sets of cases of acute diarrheas and their matched controls showed the role of calicivirus and rotavirus as probable major causes of gastroenteritis during recurrent widespread outbreaks in winter in France. An age-specific model for chickenpox showed the probable role of children in disease transmission to their susceptible parents or grandparents. High level of synchronism between influenza epidemics has been demonstrated, either at a regional level (in France) or between France and the USA. The designation of our lab as a WHO collaborating center for electronic disease surveillance stimulates the development of global monitoring of diseases. We developed operational systems that are now available for the global monitoring of influenza (FluNet), and human and animal rabies (RABNET). Extension of electronic syndromic surveillance is needed in the world for improving surveillance capacities and real-time response against emerging diseases.

Case-Control Studies↗

Epidemic spread and bifurcation effects in two-dimensional network models with viral dynamics.

We extend a previous network model of viral dynamics to include host populations distributed in two space dimensions. The basic dynamical equations for the individual viral and immune effector densities within a host are bilinear with a natural threshold condition. In the general model, transmission between individuals is governed by three factors: a saturating function g( small middle dot) describing emission as a function of originating host virion level; a four-dimensional array B that determines transmission from each individual to every other individual; and a nonlinear function F, which describes the absorption of virions by a host for a given net arrival rate. A summary of the properties of the viral-effector dynamical system in a single host is given. In the numerical network studies, individuals are placed at the mesh points of a uniform rectangular grid and are connected with an m(2)xn(2) four-dimensional array with terms that decay exponentially with distance between hosts; g is linear and F has a simple step threshold. In a population of N=mn individuals, N0 are chosen randomly to be initially infected with the virus. We examine the dependence of maximal population viral load on the population dynamical parameters and find threshold effects that can be related to a transcritical bifurcation in the system of equations for individual virus and host effector populations. The effects of varying demographic parameters are also examined. Changes in alpha, which is related to mobility, and contact rate beta also show threshold effects. We also vary the density of (randomly chosen) initially infected individuals. The distribution of final size of the epidemic depends strongly on N0 but is invariably bimodal with mass concentrated mainly near either or both ends of the interval [1,N]. Thus large outbreaks may occur, with small probability, even with only very few initially infected hosts. The effects of immunization of various fractions of the population on the final size of the epidemic are also explored. The distribution of the final percentage infected is estimated by simulation. The mean of this quantity is obtained as a function of immunization rate and shows an almost linear decline for immunization rates up to about 0.2. When the immunization rate is increased past 0.2, the extra benefit accrues more slowly. We include a discussion of some approximations that illuminate threshold effects in demographic parameters and indicate how a mean-field approximation and more detailed studies of various geometries and rates of immunization could be a useful direction for future analysis.

Algorithms↗

Enhancement of epidemic spread by noise and stochastic resonance in spatial network models with viral dynamics.

We extend a previous dynamical viral network model to include stochastic effects. The dynamical equations for the viral and immune effector densities within a host population of size n are bilinear, and the noise is white, additive, and Gaussian. The individuals are connected with an n x n transmission matrix, with terms which decay exponentially with distance. In a single individual, for the range of noise parameters considered, it is found that increasing the amplitude of the noise tends to decrease the maximum mean virion level, and slightly accelerate its attainment. Two different spatial dynamical models are employed to ascertain the effects of environmental stochasticity on viral spread. In the first model transmission is unrestricted and there is no threshold within individuals. This model has the advantage that it can be analyzed using a Fokker-Planck approach. The noise is found both to synchronize and uniformize the trajectories of the viral levels across the population of infected individuals, and thus to promote the epidemic spread of the virus. Quantitative measures of the speed of spread and overall amplitude of the epidemic are obtained as functions of the noise and virulence parameters. The mean amplitude increases steadily without threshold effects for a fixed value of the virulence as the noise amplitude sigma is increased, and there is no evidence of a stochastic resonance. However, the speed of transmission, both with respect to its mean and variance, undergoes rapid increases as sigma changes by relatively small amounts. In the second, more realistic, model, there is a threshold for infection and an upper limit to the transmission rate. There may be no spread of infection at all in the absence of noise. With increasing noise level and a low threshold, the mean maximum virion level grows quickly and shows a broad-based stochastic resonance effect. When the threshold within individuals is increased, the mean population virion level increases only slowly as sigma increases, until a critical value is reached at which the mean infection level suddenly increases. Similar results are obtained when the parameters of the model are also randomized across the population. We conclude with a discussion and a description of a diffusion approximation for a model in which stochasticity arises through random contacts rather than fluctuation in ambient virion levels.

Epidemiologic Methods↗

Small intestine protection from radiation by means of a removable adapted prosthesis.

BACKGROUND: A prosthesis has been designed to protect intestinal loops from radiation when postsurgical radiotherapy is necessary in cancer treatment. It is a silicone balloon that allows the small bowel to be pushed back away from the radiation field, and it is easily removed at the conclusion of radiotherapy. METHODS: The device was used in 22 patients: 5 retroperitoneal tumors and 17 pelvic cancers. After surgical resection of the tumor, the device is placed either in the retroperitoneal area or in the pelvic cavity. A polyglactine 910 mesh is placed between the spacer and the bowel to prevent incarceration of the loops. The prosthesis can be filled or emptied between each radiation course and finally removed by means of a short incision under local or locoregional anesthesia. RESULTS: The tolerance of the small intestine to radiation therapy has been satisfactory in each case, with a mean follow-up of 24.5 months (range 10 to 73). No modification of biological parameters was observed during the pelvic radiation therapy at 30, 45, and 65 Gy. CONCLUSION: This device should appears to efficient for prevention of bowel injury during postsurgical radiation in successful treatment of abdominal, pelvic, or retroperitoneal tumors when indicated.

Abdominal Neoplasms↗

SHARE: a tool to analyze and assess strategies in health care organization management.

In health care organizations, management of both human and material resources implies decision making. When seemingly equivalent strategies are possible, simulation can help to make a decision on better grounds. The SHARE workframe was designed to address the specificities of health care and to provide a comprehensive environment for modelling and simulating health care processes. The typology of objects is defined as Actors, subdivided in Clients and Resources and Elementary Operations. Graphical tools allow us to build processes from these objects and to create their relationships. Various strategies based on either clinical or managerial changes may be investigated. After a simulation, graphical tools allow us to display summary information on the utilization of all actors, waiting times, and goodness of execution. The use of SHARE is exemplified with the analysis and simulation of changes in the Pulmonary Function Testing Laboratory of the Saint-Antoine Hospital, Paris.

Computer Simulation↗

Periodically-modulated inhibition of living pacemaker neurons--III. The heterogeneity of the postsynaptic spike trains, and how control parameters affect it.

Codings involving spike trains at synapses with inhibitory postsynaptic potentials on pacemakers were examined in crayfish stretch receptor organs by modulating presynaptic instantaneous rates periodically (triangles or sines; frequencies, slopes and depths under, respectively, 5.0 Hz, 40.0/s/s and 25.0/s). Timings were described by interspike and cross-intervals ("phases"); patterns (dispersions, sequences) and forms (timing classes) were identified using pooled graphs (instant along the cycle when a spike occurs vs preceding interval) and return maps (plots of successive intervals). A remarkable heterogeneity of postsynaptic intervals and phases characterizes each modulation. All cycles separate into the same portions: each contains a particular form and switches abruptly to the next. Forms differ in irregularity and predictability: they are (see text) "p:q alternations", "intermittent", "phase walk-throughs", "messy erratic" and "messy stammering". Postsynaptic cycles are asymmetric (hysteresis). This contrasts with the presynaptic homogeneity, smoothness and symmetry. All control parameters are, individually and jointly, strongly influential. Presynaptic slopes, say, act through a postsynaptic sensitivity to their magnitude and sign; when increasing, hysteresis augments and forms change or disappear. Appropriate noise attenuates between-train contrasts, providing modulations are under 0.5 Hz. Postsynaptic natural intervals impose critical time bases, separating presynaptic intervals (around, above or below them) with dissimilar consequences. Coding rules are numerous and have restricted domains; generalizations are misleading. Modulation-driven forms are trendy pacemaker-driven forms. However, dissimilarities, slight when patterns are almost pacemaker, increase as inhibition departs from pacemaker and incorporate unpredictable features. Physiological significance-(1) Pacemaker-driven forms, simple and ubiquitous, appear to be elementary building blocks of synaptic codings, present always but in each case distorted typically. (2) Synapses are prototype: similar behaviours should be widespread, and networks simulations benefit by nonlinear units generating all forms. (3) Relevant to periodic functions are that few variables need be involved in form selection, that distortions are susceptible to noise levels and, if periods are heterogeneous, that simple input cycles impose heterogeneous outputs. (4) Slow Na inactivations are necessary for obtaining complex forms and hysteresis. Formal significance--(1) Pacemaker-driven forms and presumably their modulation-driven counterparts, pertain to universal periodic, intermittent, quasiperiodic and chaotic categories whose formal properties carry physiological connotations. (2) Only relatively elaborate, nonlinear geometric models show all forms; simpler ones, show only alternations and walk-throughs. (3) Bifurcations resemble those of simple maps that can provide useful guidelines. (4) Heterogeneity poses the unanswered question of whether or not the entire cycle and all portions have the same behaviours: therefore, whether trajectories are continuous or have discontinuities and/or singular points.

Action Potentials↗

Modelling health care processes with SHARE.

This paper describes the "SHARE" workframe, designed to provide a comprehensive environment for modeling and simulating health care processes. The objects defined within SHARE are Actors, subdivided in Clients and Resources, and Elementary Operations. Graphical tools allow to build processes from these objects, and to specify their relationships. Various strategies based on either clinical or managerial changes may be investigated. Summary information on the utilization of all actors, on waiting times and goodness of execution may be displayed after a simulation. Better description of processes, and their study a priori will improve reliability, quality of care and satisfaction of patients.

Appointments and Schedules↗

Effect of delay on the boundary of the basin of attraction in a self-excited single graded-response neuron.

Little attention has been paid in the past to the effects of interunit transmission delays (representing axonal and synaptic delays) on the boundary of the basin of attraction of stable equilibrium points in neural networks. As a first step toward a better understanding of the influence of delay, we study the dynamics of a single graded-response neuron with a delayed excitatory self-connection. The behavior of this system is representative of that of a family of networks composed of graded-response neurons in which most trajectories converge to stable equilibrium points for any delay value. It is shown that changing the delay modifies the "location" of the boundary of the basin of attraction of the stable equilibrium points without affecting the stability of the equilibria. The dynamics of trajectories on the boundary are also delay dependent and influence the transient regime of trajectories within the adjacent basins. Our results suggest that when dealing with networks with delay, it is important to study not only the effect of the delay on the asymptotic convergence of the system but also on the boundary of the basins of attraction of the equilibria.

Animals↗

Single neuron model with recurrent excitation: response to slow periodic modulation.

The influence of a recurrent excitatory connection on the response of three neuron models to slow periodic modulation is analyzed. The models are the graded response model and the threshold model with and without adaptation. Lissajous displays of the system's output (discharge rate) as a function of the instantaneous input value show hysteresis in all three models. Hence, the outputs are different depending on whether the input is increasing or decreasing. Recurrent excitation increases the width of the hysteresis with (i) the frequency of the periodic modulation, (ii) the transmission delay of the recurrent connection, and (iii) the connection strength.

Action Potentials↗

Complex responses of living neurons to pacemaker inhibition: a comparison of dynamical models.

A neuron can respond to periodic inhibitory input with a variety of complex behaviors, periodic and aperiodic. We present a succession of models to test hypotheses for mechanisms underlying complex behavior generation. Model comparison using non-linear dynamics techniques indicates that long-duration IPSP aftereffects and spiking behavior are necessary for most of the basic response properties, though not sufficient for some of their more subtle aspects.

Action Potentials↗

XNBC: a simulation tool. Application to the study of neural coding using hybrid networks.

XNBC is a software package for simulating biological neural networks. Two neuron models are available, a leaky integrator model and an ion-conductance model. Inputs to the simulated neurons can be provided by experimental data stored in files, allowing the creation of 'hybrid' networks. Graphic tools are used to describe the modeled neurons as well as the network. Neuron and network parameters can be modified during the simulation, to mimic electrical stimulations and drugs action. The temporal evolution of the network and of selected neurons can be visualized. A point process, frequency or dynamic analysis of the simulator output can be performed. The successive stages of the creation of a hybrid network are explained.

Computer Graphics↗

A model for temporal and intensity coding in insect olfaction by a network of inhibitory neurons.

Female insects release sex-pheromones which attract their conspecific males. These pheromones are detected through a distinct male-specific olfactory subsystem which resides at the first stage of olfactory processing, and consists of receptor, local and projection (relay) neurons. When male insects were stimulated by female sexpheromones, some projection neurons could distinguish between different pheromones, following input and code stimulus intensity. Presented here, is a simple biophysical model that described characteristic bursting responses observed for projection neurons. The bursting behavior of the model resulted from a particular cellular mechanism and specific network architecture. At the neuron level, a rapidly activating and slowly inactivating low-threshold calcium channel provided depolarizing current for bursting, while at the network level, inhibitory neurons implementing dis-inhibition which triggered this calcium channel. Also, the network architecture provided a mechanism by which certain projection neurons coded temporal input and stimulus intensity.

Animals↗

SITIE: a health care workstation integration architecture for epidemiologists.

SITIE is a workstation devoted to epidemiological data selection, analysis, and representation. Epidemiological data are collected using the French Communicable Diseases computer Network and stored in an Oracle database. Disease selection and spatial and temporal representations can be done using a user friendly graphic interface. SITIE automatically generates SQL requests to the Oracle database, extracts the data, processes it according to the user's choice, and represents the data. SITIE is built upon the AVS graphic package and allows the creation of new applications using previously developed modules linked together to form a network. SITIE can be viewed as a tool box for epidemiological data representations. Three example applications are detailed in order to make clear the way a new application can be built using SITIE. The reusability of modules is exemplified by a compound application.

Computer Communication Networks↗

Periodically modulated inhibition and its postsynaptic consequences--I. General features. Influence of modulation frequency.

Our aim was to examine the relation, or "synaptic coding", between spike trains across a synapse with inhibitory postsynaptic potentials when the presynaptic rate is modulated periodically and the postsynaptic cell is a pacemaker. Experiments were on the synapse in crayfish stretch receptor organs. Spike trains were considered point processes along time; the time series of corresponding pre- and postsynaptic intervals were extracted. Analyses used displays of intervals along time and order ("basic graphs", and "rasters", respectively), displays of differences between intervals along order ("recurrence plots"), cycle histograms (as such and as Lissajous diagrams with presynaptic and postsynaptic on the abscissae and ordinate, respectively), and correlation histograms. Cycle histograms and correlation histograms demonstrated that all presynaptic modulation frequencies (1/60-10 Hz) are reflected postsynaptically; novel frequencies may arise, not always relating simply to the pre- or postsynaptic ones. The transferred frequency domain is broad and physiologically meaningful. Indeed, vitally important functions have strong periodicities in all portions of the explored domain, and so do the discharges of participating neurons. Overall, pre- and postsynaptic discharges change oppositely, one accelerating while the other slows. Locally, however, pre- and postsynaptic discharges contrast clearly in other ways. The presynaptic evolution is everywhere smooth and orderly, half-cycles usually are symmetric, and there is a single kind of discharge, as expected because the presynaptic axon follows well the controlling stimuli. The postsynaptic cycle shows marked local distortions. These involve presynaptic domains called "congruent portions" where changes are in the same sense (e.g., joint accelerations), "saturated" domains where postsynaptic discharges are arrested, and asymmetric sensitivities to presynaptic change with hysteretic loops in the Lissajous diagrams; the postsynaptic discharge is heterogeneous showing dissimilar forms in succession. Congruent portions are either "positive segments" with pre- to postsynaptic rate ratios practically 1:1, 2:1, 1:1, or parts of Lissajous loops. Different modulation frequencies have different postsynaptic consequences. Differences involve the width and number of positive segments, the proportion of the cycle with saturation, the sense, magnitude and lead-lag characteristics of the hysteretic loops, etc. Because their consequences are separable, frequencies are classified within categories labelled "low" (under 0.5 Hz), "high" (between 0.5 and 5.0 Hz) and "very high" (over 5.0 Hz). Categories arise widely but each prevails in different biological functions (e.g., low or high in, respectively, respiration or vibratory sensitivity). The refactoriness of the inhibitory fibre affects how it can be modulated: consequently, the very high category resembles pacemaker discharges and was not analysed.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Periodically modulated inhibition and its postsynaptic consequences--II. Influence of modulation slope, depth, range, noise and of postsynaptic natural discharges.

This paper examines the relation, or "synaptic coding", between the discharges of inhibitory fibres whose instantaneous firing rate is modulated periodically and pacemaker postsynaptic neurons using crayfish synapses and point process statistics. Several control parameters were varied individually, and the other maintained constant as far as possible: it extends the preceding publication that described the general features and varied only the modulation frequency [Segundo et al. (1995) Neuroscience 68, 657-692]. Statistics were mainly cycle histograms and Lissajous diagrams (with presynaptic and post-synaptic histograms on the abscissae and ordinate, respectively), complemented occasionally by displays of intervals along time and of interval differences along order ("basic graphs" and "recurrence plots", respectively). The postsynaptic influence of modulated inhibitory discharges is characteristically sensitive to all control parameters examined. (1) The frequency was reported in the companion paper [Segundo et al. (1995) Neuroscience 68, 657-692]. (2) The average slope per half-cycle, controlled via either frequency or depth, acts by way of its magnitude and sign in ways revealed by hysteretic loops. Hysteresis increases and varies as the modulation's steepness increases: it is minor and with a single clockwise loop at small slopes, but major and multi-looped at the larger ones. Slopes, because of their different postsynaptic consequences, were separated into the categories of "steep", "gentle" and "abrupt" if around, respectively, 1.0, 30.0 and 150.0 s-2. The influence of slopes in restricted portions of the cycle depends on their position on the inhibitory rate scale. (3) The modulation's range acts by way of its depth and of its position on the inhibitory rate scale. Deeper ranges, when compared with the shallower ones they contain, induce effects similar to those of shallower modulations with their central portion, plus effects peculiar to them at extreme rates. Changes in range position from the centre to the extremes of the inhibitory rate scale are influential (e.g., saturations appear). Changes within the centre can be highly influential, particularly when ranges are narrow and close to the postsynaptic natural rate, and modulation frequencies are low: relations between corresponding rates can be linear increasing, linear decreasing or piecewise linear. Changes around extreme rates are negligible, however, and saturations are present. (4) The usual modulations whose individual cycles did not differ from the cycle histogram were compared to others with the same cycle histograms but whose individual cycles had an unpredictable fast variability referred to as "noise".(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗