The plasma protein fibrinogen stabilizes clusters of red blood cells in microcapillary flows.

The supply of oxygen and nutrients and the disposal of metabolic waste in the organs depend strongly on how blood, especially red blood cells, flow through the microvascular network. Macromolecular plasma proteins such as fibrinogen cause red blood cells to form large aggregates, called rouleaux, which are usually assumed to be disaggregated in the circulation due to the shear forces present in bulk flow. This leads to the assumption that rouleaux formation is only relevant in the venule network and in arterioles at low shear rates or stasis. Thanks to an excellent agreement between combined experimental and numerical approaches, we show that despite the large shear rates present in microcapillaries, the presence of either fibrinogen or the synthetic polymer dextran leads to an enhanced formation of robust clusters of red blood cells, even at haematocrits as low as 1%. Robust aggregates are shown to exist in microcapillaries even for fibrinogen concentrations within the healthy physiological range. These persistent aggregates should strongly affect cell distribution and blood perfusion in the microvasculature, with putative implications for blood disorders even within apparently asymptomatic subjects.

Quantification of depletion-induced adhesion of red blood cells.

Red blood cells (RBCs) are known to form aggregates in the form of rouleaux due to the presence of plasma proteins under physiological conditions. The formation of rouleaux can also be induced in vitro by the addition of macromolecules to the RBC suspension. Current data on the adhesion strength between red blood cells in their natural discocyte shapes mostly originate from indirect measurements such as flow chamber experiments, but data is lacking at the single cell level. Here, we present measurements on the dextran-induced aggregation of red blood cells using atomic force microscopy-based single cell force spectroscopy. The effects of dextran concentration and molecular weight on the interaction energy of adhering RBCs were determined. The results on adhesion energy are in excellent agreement with a model based on the depletion effect and previous experimental studies. Furthermore, our method allowed to determine the adhesion force, a quantity that is needed in theoretical investigations on blood flow.

An elasto-visco-plastic model of cell aggregates.

Concentrated cell suspensions exhibit different mechanical behavior depending on the mechanical stress or deformation they undergo. They have a mixed rheological nature: cells behave elastically or viscoelastically, they can adhere to each other whereas the carrying fluid is usually Newtonian. We report here on a new elasto-visco-plastic model which is able to describe the mechanical properties of a concentrated cell suspension or aggregate. It is based on the idea that the rearrangement of adhesion bonds during the deformation of the aggregate is related to the existence of a yield stress in the macroscopic constitutive equation. We compare the predictions of this new model with five experimental tests: steady shear rate, oscillatory shearing tests, stress relaxation, elastic recovery after steady prescribed deformation, and uniaxial compression tests. All of the predictions of the model are shown to agree with these experiments.

Traction patterns of tumor cells.

The traction exerted by a cell on a planar deformable substrate can be indirectly obtained on the basis of the displacement field of the underlying layer. The usual methodology used to address this inverse problem is based on the exploitation of the Green tensor of the linear elasticity problem in a half space (Boussinesq problem), coupled with a minimization algorithm under force penalization. A possible alternative strategy is to exploit an adjoint equation, obtained on the basis of a suitable minimization requirement. The resulting system of coupled elliptic partial differential equations is applied here to determine the force field per unit surface generated by T24 tumor cells on a polyacrylamide substrate. The shear stress obtained by numerical integration provides quantitative insight of the traction field and is a promising tool to investigate the spatial pattern of force per unit surface generated in cell motion, particularly in the case of such cancer cells.

Fractal approach to the rheology of concentrated cell suspensions.

Results on the rheological behavior of Chinese hamster ovary cell suspensions in a large range of concentrations are reported. The concentration-dependent yield stress and elastic plateau modulus are formalized in the context of fractal aggregates under shear, and quite different exponents are found as compared to the case of red blood cell suspensions. This is explained in terms of intrinsic microscopic parameters such as the cell-cell adhesion energy and cell elasticity but also the cell's individual dynamic properties, found to correlate well with viscoelastic data at large concentrations (phi>or=0.5).

The Rhône-Alpes health platform.

OBJECTIVES: The purpose of this work is to develop a health information platform connecting most health facilities in the Rhône-Alpes region. The health platform called SIS-RA is used through a Web interface. An iconic interface is dedicated to the platform and presents information in a unique way for all users. METHODS: New techniques have been used to develop this platform which will be used by a great number of Rhône-Alpes doctors in the future. We chose a usercentered design which takes into account doctors' requirements (hospital and GP). We also consider that no system has to be rebuilt, but a direct connection to the legacy systems should be provided. RESULTS: The platform permits fast and more appropriate medical decisions than those made without this information system. The iconic interface presents all medical documents in a uniform way. Currently, 11 healthcare facilities and 15 community health networks are connected to SIS-RA sharing more than 60,000 records with 1.2 million indexed items. 3200 doctors use the system. CONCLUSION: The platform is approved by French supervision authorities (regional hospitals association (ARH)), regional practitioners union (URML) and Rhônes-Alpes region administration and is known as the official shared health record.

Modeling breakup and relaxation of Newtonian droplets using the advected phase-field approach.

The relaxation and breakup of Newtonian droplets is considered using the advected field approach. This method allows one to follow the deformation of interfaces using an order parameter field [Biben, Europhys. Lett. 63, 623 (2003)] based on a Ginzburg-Landau equation. Using this method, it is possible to follow the breakup of droplets and stability curves can be obtained in both two- and three-dimensional shear and elongational flows. Finally, relaxation of a droplet is considered, following the application of an elongational flow. The results are compared with previous experimental data [Ha and Leal, Phys. Fluids 13, 1568 (2001)], and are found to be in satisfactory agreement. The method is general enough to be applied to other non-Newtonian fluids, such as Oldroyd-B fluids or viscoplastic materials.

Elongation and burst of axisymmetric viscoelastic droplets: a numerical study.

The dynamics of elongation and burst of an isolated viscoelastic drop are investigated numerically in the special case of a viscosity ratio lambda = 1 . We show that the burst threshold is not affected by viscoelasticity itself, whereas the stationary drop morphology is. A dimple at the tips of the drop can even be observed when elastic effects are large. The burst dynamics is very sensitive to the presence of viscoelasticity: at low elasticity burst is slowed down while for large elasticity levels it becomes even faster than the Newtonian situation.

Characterization of wheat-flour-water doughs: a new method using ultrasound.

In this paper, an original method of evaluating the physical properties of wheat-flour-water systems using high-frequency low-power ultrasound is presented. Most of the experiments were performed with a reflectance technique measuring the acoustic impedance of doughs. The velocity of propagation, attenuation and viscoelastic moduli have been evaluated for both compressional and shear ultrasonic waves in the interval 2-10 MHz for doughs of different hydrations. The 53% water content was found to be critical with respect to the presence of free water. The influence of the mixing and rest times on the longitudinal ultrasonic parameters is also studied.

The influence of analytical bias on diagnostic misclassifications.

Quality specifications for analytical imprecision and bias based on the state of the art; 'biology' and 'analysis of clinical situations' have been proposed by several scientists. Most interesting is the assessment of 'diagnostic misclassifications' based on direct evaluation of the consequences of analytical bias on the percentage of false positives and false negatives from a clinical decision situation, or based on the percentage of healthy individuals outside each reference limit when common reference intervals are used. With use of graphical or computer simulations assuming increasing (positive or negative) analytical bias, the expected percentage of misclassifications can be estimated- and, for the error for which the outcome (the fraction of misclassifications) is considered unacceptable, the maximum allowable analytical bias can be defined. An overview is given of previous proposals for specification of allowable analytical bias, and new examples are presented: (i) for S-transferrin. an analytical bias of +10% will increase the percentage of healthy individuals with measured concentration values above the upper reference limit from 2.5 to 10% (ii) the percentage of healthy men with concentration values for S-cholesterol above 6.2 mmol/l (240 mg/dl) will vary between 25 and 85% for analytical bias from - 1.0 to +1.0 mmol/l (+/- 16%): (iii) for glycated haemoglobin, two examples are given which illustrate the effect of analytical bias on the risk of retinopathy and so-called 'microalbuminuria' for measured values identical to the target 7.5% and 10.1% glycated haemoglobin, respectively. It is concluded that analytical bias may have significant impact on diagnostic performance, better standardization is needed, and quality specifications for allowable analytical bias should be based on medical usefulness criteria or, if such data are not available, on biological criteria.

[Proposals for a system of managing medical information]. / Propositions pour un système de gestion de l'information médicale.

Various systems are being used for managing medical information. They have several shortcomings. Among these, one can quote: -they do not overcome the complex medical terminology and its diversity; -they do not use a common medical language -there is no easy communication between the softwares used -and so on The proposed system takes into account the multiplicity of information sources within a hospital and the need for individual decision-making from care providers.

An information system for epidemiology based on a computer-based medical record.

A new way is presented to build an information system addressed to problems in epidemiology. Based on our analysis of current and future requirements, a system is proposed which allows for collection, organization and distribution of data within a computer network. In this application, two broad communities of users-physicians and epidemiologists-can be identified, each with their own perspectives and goals. The different requirements of each community lead us to a client-service centered architecture which provides the functionality requirements of the two groups. The resulting physician workstation provides help for recording and querying medical information about patients and from a pharmacological database. All information is classified and coded in order to be retrieved for pharmaco-economic studies. The service center receives information from physician workstations and permits organizations that are in charge of statistical studies to work with "real" data recorded during patient encounters. This leads to a new approach in epidemiology. Studies can be carried out with a more efficient data acquisition. For modelling the information system, we use an object-oriented approach. We have observed that the object-oriented representation, particularly its concepts of generalization, aggregation and encapsulation, are very usable for our problem.