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Resumen En Francia, cada ano cerca de 6.000 pacientes con insuficiencia visceral terminal reciben un trasplante de organo solido. Gracias a los avances medicos y quirurgicos, los pacientes elegibles son mayores y su esperanza de vida se ha prolongado. De este modo, la calidad de vida de estos pacientes es un nuevo objetivo y las complicaciones osteoarticulares de los pacientes trasplantados son una causa importante de la morbilidad postrasplante. Las complicaciones oseas mas frecuentes son las fracturas por fragilidad osea, la osteonecrosis aseptica y el sindrome doloroso inducido por los inhibidores de la calcineurina. Las complicaciones articulares se relacionan sobre todo con la gota, pero se deben buscar las otras causas, en particular infecciosas, debido a su gravedad y al riesgo de diseminacion sistemica en estos pacientes inmunodeprimidos. El objetivo de este articulo es detallar los conocimientos actuales sobre las complicaciones osteoarticulares despues de un trasplante de organo solido.

The evolution of the 2000 km long Mesozoic rift system underlying the Labrador-Baffin Seaway is described, with emphasis on results from geophysical data sets, which provide the timing, sediment thickness, and crustal structure of the system. The data sets include seismic reflection and refraction, gravity, and magnetic data, with additional constraints provided by near-surface geology and well data. Many features that characterize rift systems globally are displayed, including: wide and narrow rift zones; magma-rich and magma-poor margin segments; exhumation of continental mantle in distal, magma-poor zones; and occurrences of thick basalts, associated with the development of seaward-dipping reflectors, and magmatic underplating. The magma-rich regions were affected by Paleogene volcanism, perhaps associated with a hotspot or plume. Plate reconstructions help elucidate the plate tectonic history and modes of rifting in the region; however, many questions remain unanswered with respect to this rift system.

The stratigraphy and the geological evolution of the West Greenland margin from the Labrador Sea to Baffin Bay in both the onshore and offshore areas are described. The primary data sets include seismic reflection surveys, wells, and outcrops. In addition, seabed samples, seismic refraction and magnetic data, onshore and offshore maps, and stratigraphic compilations were used. The basins of the West Greenland continental margin are described in three regions from the south to the north: southern West Greenland basins, central West Greenland basins, and northern West Greenland basins. Each region includes a description of the stratigraphy and evolution from the Archean to the Quaternary, divided into six phases: pre-rift and early extension, early rift, subsidence and rifting, late rift, drift, and post-drift. Finally, the regions are correlated and described in a tectonostratigraphic context together with analogues from the Canadian conjugate margin.

Resume Les fractures osteoporotiques sont frequentes et responsables d’un retentissement medical et de couts importants. Les sites les plus frequents sont les fractures vertebrales, les fractures du poignet, de l’extremite superieure de l’humerus et de l’extremite superieure du femur. Prendre en charge l’osteoporose apres une fracture par fragilite est donc une necessite medicale : cette prise en charge est actuellement insuffisante en France alors que les outils diagnostiques (osteodensitometrie), les traitements efficaces et les recommandations pour guider cette prise en charge sont disponibles et diffuses. Il est important que les chirurgiens orthopedistes et urgentistes traumatologistes attirent l’attention des patients au moment de la prise en charge de la fracture sur la necessite de consulter leur praticien ou leur rhumatologue pour definir avec eux les modalites du diagnostic et du traitement de leur osteoporose.

In the present work, a novel application of ultrasonic measurements is detailed to characterize nano-emulsion formulations as a part of the overall Quality by Design (QbD) goal. Ultrasonic resonator technology (URT) was utilized to measure sound velocity and absorption of self-nanoemulsified drug delivery systems (SNEDDs) consisting of various ratios of oil:surfactant:co-surfactant. A QbD concept was used to create different SNEDDs formulations utilizing sweet orange oil (oil), Emulphor-620 (surfactant), and Capmul (co-surfactant) by dissolving Cyclosporine A in oil. The mixture was emulsified in water and ultrasonic measurements were carried out in an ultrasonic resonator system isothermally for a period of about 15-20min. Compressibility of the individual components in the droplets, hydration of the droplets and the influence of the composition on droplet stability were studied by systematic ultrasonic measurements at a single resonator frequency. The adiabetic compressibilities for the oil, aqueous and interfacial components were 68, 44.6, and 53 [10(-11)Pa(-1)], respectively as calculated using Urick's equation. Also the ultrasonic absorption correlated droplet size of nano-emulsions linearly with R(2) of 0.84 indicating this can be used as an additional technique to measure the droplet size of nano-emulsions. Correlation of ultrasonic data with formulation components indicated that the ultrasonic velocity correlated negatively with increasing oil amount in the formulation as well as surfactant-to-cosurfactant ratios where as droplet diameter correlated positively with these formulation factors. It can be envisioned from the results that the compressibility of the media increases with the addition of the oily component and thus reducing the sound velocity. Thus URT enabled direct and convenient analysis of the physical properties as well as influence of formulation factors of nano-emulsions which is an important indication of stability of these nano-emulsions.

The ac-dc current transfer standards at PTB have been improved in frequency and current range up to 1 MHz and 1 A using a newly designed transconductance amplifier. Up to 100 kHz and 10 A, the uncertainties could be dramatically reduced. Starting from the calculable quartz planar multifunction thermal converter at 30 mA, for currents up to 10 A, new shunts with small frequency and current level dependence and an improved measurement set-up are used

Millivolt ac-dc transfer devices and ac measuring instruments are calibrated with new micropotentiometers (mupots) with low output impedance. Newly designed output resistors of 0.2 and 0.1 Omega lead to reduced load corrections for 150 kOmega input impedance amplifiers of only a few muV/V. The higher current required is measured at 1 MHz with a 500 mA thermal current converter. At 1 MHz, expanded uncertainties (k = 2) less than 40 muV/V are achieved from 100 down to 10 mV

New micropotentiometers (/spl mu/pots) have been built with planar multijunction thermal converters (PMJTC) on Si- and SiO/sub 2/-substrates, and with new disc resistors and redesigned housings. The step down from 100 mV to 2 mV can be performed with only two /spl mu/pots. New millivolt-amplifiers with gain factors of 11, 50, and 121 in conjunction with PMJTCs are developed to measure the output voltage of the /spl mu/pots down to 2 mV. Their high input impedance of >1 M/spl Omega/ /spl par/ < 6 pF avoids the loading of the output resistor of the /spl mu/pots. These systems lead to considerable reduction of the uncertainties in the millivolt-AC-DC transfer in the frequency range from 10 Hz up to 1 MHz.

The new generation of PMJTCs on quartz membranes and on quartz crystal chips developed at the PTB results in new ac-dc current transfer standards for the current of 10 mA and the frequency range from 10 kHz to 1 MHz, accompanied with small uncertainties. For a PMJTC with a heater resistance of 240 Omega the uncertainties for frequencies up to 100 kHz are smaller than 1 muA/A and up to 1 MHz they increase to 5 muA/A (k=1). A model for the PMJTC has been developed which allows calculating the ac-dc current transfer difference as well as the attributed uncertainties. The agreement of the simulation and the measurement were tested for high heater resistances of 700 Omega and 240 Omega, for which quite large ac-dc differences are calculated. The good agreement validates the model

A computer-controlled Josephson voltage standard has been developed comprising the hybrid integration of a planar oscillator and a Josephson series array. A 10 GHz voltage controlled oscillator has been frequency-stabilized to a reference frequency by a phase-locked loop. A series array has been designed and fabricated in Nb/Al/sub 2/O/sub 3//Nb technology. To obtain quantized voltage steps with a drive frequency of 10 GHz, the critical current density of the Junctions is reduced to below 2 A/cm/sup 2/ by variation of the oxidation parameters. The hybrid integration of a Josephson circuit with a planar MESFET oscillator produced quantized voltage steps up to 980 mV with a step width of 2 /spl mu/A.

Aim of the study: Cartilage degradation in OA is mainly due to a reduced matrix protein secretion and an increase of their degradation by matrix metalloprotease (MMP). Indeed during OA an enhanced expression and activation of MMPs is observed. The major MMPs involve in matrix protein degradation are ADAMTS-4, MMP-3 or MMP-13. However, inhibition of expression or activation of MMPs might reduce matrix degradation during OA. Furin, a proprotein convertase, is responsible for the conversion of various Pro-MMPs in active MMPs. Furin activates directly ADAMTS-4 and MMP-3, while promote indirectly the maturation of MMP-13 through other MMPs. Therefore, we hypothesised that Furin may have an impact in matrix homeostasis in joint instability. Moreover, we investigated the in vitro effect of Furin in MMP expression in murin chondrocytes. Methods: DMM (destabilisation medial meniscus) was induced surgically by partial meniscectomy in 10-week-old C57Bl6 male mice. The day after surgery, the mice received twice weekly intraperitoneal injections of Furin (1U/mouse), or a1-PDX (the proprotein convertase inhibitor, 0.35 mg/g mice), or vehicle (control group) and sacrificed after 6 weeks. Joint sections were used to assess cartilage damage (OARSI score) and the number of ADAMTS-4 and MMP-13(+) cells as well as Furin expressing cells. We further assessed the signalling pathway induced by Furin in vitro. Murine primary chondrocytes (pre-treated with 10ng/ml IL-1) were cultured with Furin (10U/mL) or a1-PDX (8mM) for 48h and then analyzed the expression of MMP-13 and the phosphorylation of Smad2/3 in cell lysates by Western blot. Results:We first observed a constitutive expression of Furin in cartilage of control mice while absent in DMM mice. Furin reduces OA score (5.64 1.54) but unchangedwith a1-PDX (15.16 2.82) compared to vehicle (13.92 1.95, p

L’osteoporose postmenopausique et certaines osteoporoses secondaires, comme celles qui accompagnent les rhumatismes inflammatoires chroniques (RIC) et la corticotherapie, sont desormais dans le champ des biotherapies. Ces differentes composantes s’additionnent chez un meme malade atteint d’un RIC, ce qui concourt a accroitre le risque fracturaire.

In an extension from their original use as references for measuring dc voltage, Josephson generated voltages from programmable arrays have been employed to measure waveforms differentially. In this paper, the alternative of using these Josephson voltages as a reference for ac-dc difference measurements using thermal converters and sampling techniques is presented.

In the new design of micropotentiometers (upots) planar multijunction thermal converters (PMJTCs) are used together with a new design of the housing and new disc resistors. Only two upots are needed for the step-down chain from 100 mV to 2 mV. A new mV-amplifier in conjunction with a PMJTC is designed to measure the output voltage of the upots. Its high input impedance of >1 MOmega par

A precise realization of the unit of capacitance is important for the determination of both the Josephson and the von Klitzing constants. The main design criteria of the PTB's cross capacitor, the maintenance of the unit of capacitance over the last 10 years, and a special capacitance-measuring bridge for tracing back the electrode capacitance in the absolute volt experiment to SI units are described in this paper. >

A computer-controlled Josephson voltage standard is developed comprising the hybrid integration of a planar oscillator and a Josephson series array. The 10 GHz oscillator is frequency-stabilized with a source-locking counter. A series array has been designed and fabricated in Nb/Al/sub 2/O/sub 3//Nb technology providing 648 mV when operated in a test fixture at 10 GHz.

Determinations of the conversion factor of the volt have been carried out after significant improvements to the measuring system. The mean value of 48 determinations was K/sub V/=1-0.02*10/sup -6/, with a standard deviation of the mean s/sub m/=0.064*10/sup -6/. The corresponding frequency-to-voltage quotient is K/sub J/=483597.91 GHz/V. The relative type B uncertainty of the experiment was estimated to be u=0.33*10/sup -6/. These data are preliminary, in as much as the recalibration of the standards used for the capacitance, the mass, and the displacement in terms of the SI units farad, kilogram, and meters had not yet been carried out. >

A correlation method is described for analysis of electrical impedances. The impedance is investigated as part of a four-terminal network, allowing general system analysis techniques to be applied. With a pseudorandom noise signal as input the measured cross-correlation function corresponds, under certain conditions, to the impulse response of the four-terminal network and contains the information about the network components via the time constants of the four-terminal network. The method has been applied to electrical two-terminal networks and to a liquid capacitor filled with a solution of poly- gamma -benzyl-L-glutamate in 1,2-dichloroethane. The latter application demonstrates that information on the dynamic behaviour of a chemical system and its changes with time can be obtained directly.

A method for measuring both the real and imaginary parts of complex shear-wave impedance Zs* for low viscosity liquids using a planar AT-quartz resonator (thickness shear) in an RF bridge network between 2 and 34 MHz, is described. This technique employs a PLL circuit and permits continuous quantitative recording of the sample impedance (probe volume below 1 ml). The mechanical vibration amplitude at the transducer-liquid interface is in the Angstrom range, preventing any heating and structural damage effects. Incremental Zs-resolution is better than 50 kg m-2 s-1 ( approximately 1% of water impedance at 6 MHz), as is demonstrated by test measurements on different newtonian liquids. These measurements show that Zs* values determine quantitatively the shear quartz resonator parameters. This method permits measurements of interface and surface layer properties.

A simple ultrasonic pulse cell with reduced variable pathlength for millilitre liquid samples (frequency range about 15-155 MHz) is described. The liquid cavity made from stainless steel has PTFE seals and gaskets and is resistant against many liquids. Attenuation and velocity measurements have been performed for H2O, CH3OH, C2H5OH and C2H5OC2H5 at 25 degrees C. The measurements, using a quartz effective diameter of 9 mm and pathlengths from 7-21 mm, show that diffraction correction terms are apparently not necessary.

A description is given of the measuring system set up at the PTB for the realization of the SI volt and the determination of the conversion factor Kv by means of a voltage balance. The voltage balance comprises two cylindrical electrodes to generate the electrostatic force from the measuring voltage of 10.186 kV, and a substitution balance to measure the force by comparison with the force due to gravity acting on a 2 g mass. To achieve force equilibrium a small variable voltage is added to the constant measuring voltage. The measuring voltage is generated in a two-stage 1000-fold step-up and linked up with the asmaintained volt by using a transfer standard consisting of 10 saturated standard cells connected in series. The total relative uncertainty of Kv is expected to be less than 4 parts in 107.