[Quality assurance and management in pulmonary function labs]. / Assurance et management de la qualité en EFR.

INTRODUCTION: Pulmonary function laboratories (PFT labs) have the duty to provide diagnostic examinations at the request of clinicians. They must guarantee the accuracy and safety of these examinations while responding to the requirements of both the clinicians and the patients. BACKGROUND: After reviewing the historical background to quality standards this article details the principles that have led from quality assurance (ISO 9000 standards: 1994) to quality management (ISO 9000 standards: 2000), as well as the principles that it is advisable to implement to obtain certification or accreditation. VIEWPOINT: In order to obtain these formal recognitions a laboratory should be in a position to control all the procedures underlying these examinations and be able to set up a systematic range of preventative and corrective measures. These elements are the basis of a programme of quality assurance and management. CONCLUSION: This article outlines the approach of the pulmonary function laboratory of the Hospital Saint Antoine, Paris that is certified ISO 9001: V2000 and accredited ISO 17025 for blood gas measurements.

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.

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.

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.

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.

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.

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.

A discrete map for the dynamics of recurrent excitatory neural networks in the presence of noise.

We investigate the effect of the neuron characteristics on the behavior of a recurrent excitatory neural network model. First, we present the different types of dynamics obtained with simulations of a network of coupled excitatory spike-response neuron models placed under the influence of noise. Then, we derive a discrete map describing the dynamics of large fully connected networks. By studying the bifurcation structure of this map, we can determine for which ranges of the neuron model parameters the network will display collective oscillations or other types of dynamics.

Effects of transmission delays and noise in recurrent excitatory neural networks.

Random perturbations, referred to as noise, are omnipresent in the nervous system. We investigate how noise modifies the dynamics of the neural networks according to the delay. In this report, we examine the effect of transmission delay on both the dynamics of a single neuron receiving a recurrent excitation and the dynamics of fully interconnected excitatory networks. In the case of the single neuron with a recurrent connection, depending on the value of the delay, the discharge pattern changes from regular to multiplets. More complicated patterns appears when noise is added, and depends on both the delay and the noise intensity, but classification can be described. In certain conditions, noise reduces the synchronization, whereas in others it increases the regularity of the network activity. Finally, the same network codes the input amplitude either using mean activity amplitude coding when short delays exist, and using frequency modulation when long delays exist.

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.

Effect of delay on the boundary of the basin of attraction in a system of two neurons.

The behavior of neural networks may be influenced by transmission delays and many studies have derived constraints on parameters such as connection weights and output functions which ensure that the asymptotic dynamics of a network with delay remains similar to that of the corresponding system without delay. However, even when the delay does not affect the asymptotic behavior of the system, it may influence other important features in the system's dynamics such as the boundary of the basin of attraction of the stable equilibria. In order to better understand such effects, we study the dynamics of a system constituted by two neurons interconnected through delayed excitatory connections. We show that the system with delay has exactly the same stable equilibrium points as the associated system without delay, and that, in both the network with delay and the corresponding one without delay, most trajectories converge to these stable equilibria. Thus, the asymptotic behavior of the network with delay and that of the corresponding system without delay are similar. We obtain a theoretical characterization of the boundary separating the basins of attraction of two stable equilibria, which enables us to estimate the boundary. Our numerical investigations show that, even in this simple system, the boundary separting the basins of attraction of two stable equilibrium points depends on the value of the delays. The extension of these results to networks with an arbritrary number of units is discussed.

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.

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.

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.

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.

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.