Apheresis donors and platelet function: inherent platelet responsiveness influences platelet quality

BACKGROUND: Process-induced platelet (PLT) activation occurs with all production methods, including apheresis. Recent studies have highlighted the range and consistence of interindividual variation in the PLT response, but little is known about the contribution of a donors' inherent PLT responsiveness to the activation state of the apheresis PLTs or the effect of frequent apheresis on donors' PLTs. STUDY DESIGN AND METHODS: The relationship between the donors' PLT response on the apheresis PLTs was studied in 47 individuals selected as having PLTs with inherently low, intermediate, or high responsiveness. Whole-blood flow cytometry was used to measure PLT activation (levels of bound fibrinogen) before donation and in the apheresis PLTs. The effects of regular apheresis on the activation status of donors' PLTs were studied by comparing the in vivo activation status of PLTs from apheresis (n = 349) and whole-blood donors (n = 157), before donation. The effect of apheresis per se on PLT activation was measured in 10 apheresis donors before and after donation. RESULTS: The level of PLT activation in the apheresis packs was generally higher than in the donor, and the most activated PLTs were from high-responder donors. There was no significant difference in PLT activation before donation between the apheresis and whole-blood donors (p = 0.697), and there was no consistent evidence of activation in the donors immediately after apheresis. CONCLUSION: The most activated apheresis PLTs were obtained from donors with more responsive PLTs. Regular apheresis, however, does not lead to PLT activation in the donors.

Trade-offs and responsiveness of the single-layer urban canopy parametrization in WRF: an offline evaluation using the MOSCEM optimization algorithm and field observations

For an increasing number of applications, mesoscale modelling systems now aim to better represent urban areas. The complexity of processes resolved by urban parametrization schemes varies with the application. The concept of fitness-for-purpose is therefore critical for both the choice of parametrizations and the way in which the scheme should be evaluated. A systematic and objective model response analysis procedure (Multiobjective Shuffled Complex Evolution Metropolis (MOSCEM) algorithm) is used to assess the fitness of the single-layer urban canopy parametrization implemented in the Weather Research and Forecasting (WRF) model. The scheme is evaluated regarding its ability to simulate observed surface energy fluxes and the sensitivity to input parameters. Recent amendments are described, focussing on features which improve its applicability to numerical weather prediction, such as a reduced and physically more meaningful list of input parameters. The study shows a high sensitivity of the scheme to parameters characterizing roof properties in contrast to a low response to road-related ones. Problems in partitioning of energy between turbulent sensible and latent heat fluxes are also emphasized. Some initial guidelines to prioritize efforts to obtain urban land-cover class characteristics in WRF are provided. Copyright © 2010 Royal Meteorological Society and Crown Copyright.

Irreversible compressible work and APE dissipation in turbulent stratified fluid

Although it plays a key role in the theory of stratified turbulence, the concept of available potential energy (APE) dissipation has remained until now a rather mysterious quantity, owing to the lack of rigorous result about its irreversible character or energy conversion type. Here, we show by using rigorous energetics considerations rooted in the analysis of the Navier-Stokes for a fully compressible fluid with a nonlinear equation of state that the APE dissipation is an irreversible energy conversion that dissipates kinetic energy into internal energy, exactly as viscous dissipation. These results are established by showing that APE dissipation contributes to the irreversible production of entropy, and by showing that it is a part of the work of expansion/contraction. Our results provide a new interpretation of the entropy budget, that leads to a new exact definition of turbulent effective diffusivity, which generalizes the Osborn-Cox model, as well as a rigorous decomposition of the work of expansion/contraction into reversible and irreversible components. In the context of turbulent mixing associated with parallel shear flow instability, our results suggests that there is no irreversible transfer of horizontal momentum into vertical momentum, as seems to be required when compressible effects are neglected, with potential consequences for the parameterisations of momentum dissipation in the coarse-grained Navier-Stokes equations.

Available potential energy density for a multicomponent Boussinesq fluid with arbitrary nonlinear equation of state

In this paper, the concept of available potential energy (APE) density is extended to a multicomponent Boussinesq fluid with a nonlinear equation of state. As shown by previous studies, the APE density is naturally interpreted as the work against buoyancy forces that a parcel needs to perform to move from a notional reference position at which its buoyancy vanishes to its actual position; because buoyancy can be defined relative to an arbitrary reference state, so can APE density. The concept of APE density is therefore best viewed as defining a class of locally defined energy quantities, each tied to a different reference state, rather than as a single energy variable. An important result, for which a new proof is given, is that the volume integrated APE density always exceeds Lorenz’s globally defined APE, except when the reference state coincides with Lorenz’s adiabatically re-arranged reference state of minimum potential energy. A parcel reference position is systematically defined as a level of neutral buoyancy (LNB): depending on the nature of the fluid and on how the reference state is defined, a parcel may have one, none, or multiple LNB within the fluid. Multiple LNB are only possible for a multicomponent fluid whose density depends on pressure. When no LNB exists within the fluid, a parcel reference position is assigned at the minimum or maximum geopotential height. The class of APE densities thus defined admits local and global balance equations, which all exhibit a conversion with kinetic energy, a production term by boundary buoyancy fluxes, and a dissipation term by internal diffusive effects. Different reference states alter the partition between APE production and dissipation, but neither affect the net conversion between kinetic energy and APE, nor the difference between APE production and dissipation. We argue that the possibility of constructing APE-like budgets based on reference states other than Lorenz’s reference state is more important than has been previously assumed, and we illustrate the feasibility of doing so in the context of an idealised and realistic oceanic example, using as reference states one with constant density and another one defined as the horizontal mean density field; in the latter case, the resulting APE density is found to be a reasonable approximation of the APE density constructed from Lorenz’s reference state, while being computationally cheaper.

Evidence for a genetic interaction in allergy-related responsiveness to vitamin D deficiency

Our study on white European adults was consistent with a previous study on children from largely non-white ethnic groups, suggesting that IL4 and MS4A2 genotypes modify the association between VDD and allergy risk. The risk allele in IL4 is present in nearly 90% of white Europeans, while less than a quarter are carriers in some other populations, highlighting the need to consider possible ethnic differences in allergy-related responsiveness to VDD.

Efficient fully nonlinear data assimilation for geophysical fluid dynamics

A potential problem with Ensemble Kalman Filter is the implicit Gaussian assumption at analysis times. Here we explore the performance of a recently proposed fully nonlinear particle filter on a high-dimensional but simplified ocean model, in which the Gaussian assumption is not made. The model simulates the evolution of the vorticity field in time, described by the barotropic vorticity equation, in a highly nonlinear flow regime. While common knowledge is that particle filters are inefficient and need large numbers of model runs to avoid degeneracy, the newly developed particle filter needs only of the order of 10-100 particles on large scale problems. The crucial new ingredient is that the proposal density cannot only be used to ensure all particles end up in high-probability regions of state space as defined by the observations, but also to ensure that most of the particles have similar weights. Using identical twin experiments we found that the ensemble mean follows the truth reliably, and the difference from the truth is captured by the ensemble spread. A rank histogram is used to show that the truth run is indistinguishable from any of the particles, showing statistical consistency of the method.

Tracking (poly)phenol components from raspberries in ileal fluid

The (poly)phenols in ileal fluid after ingestion of raspberries were analysed by targeted and non-targeted LC-MSn approaches. Targeted approaches identified major anthocyanin and ellagitannin components at varying recoveries and with considerable inter-individual variation. Non-targeted LC-MSn analysis using an Orbitrap mass spectrometer gave exact mass MS data which was sifted using a software program to select peaks that changed significantly after supplementation. This method confirmed the recovery of the targeted components but also identified novel raspberry-specific metabolites. Some components (including ellagitannin and previously unidentified proanthocyanidin derivatives) may have arisen from raspberry seeds that survived intact in ileal samples. Other components include potential breakdown products of anthocyanins, unidentified components and phenolic metabolites formed in either the gut epithelia or after absorption into the circulatory system and efflux back into the gut lumen. The possible physiological roles of the ileal metabolites in the large bowel are discussed.

Solution calorimetry as a tool for investigating drug interaction with intestinal fluid

Solution calorimetry offers a reproducible technique for measuring the enthalpy of solution (ΔsolH) of a solute dissolving into a solvent. The ΔsolH of two solutes, propranolol HCl and mannitol were determined in simulated intestinal fluid (SIF) solutions designed to model the fed and fasted states within the gut, and in Hanks’ balanced salt solution (HBSS) of varying pH. The bile salt and lipid within the SIF solutions formed mixed micelles. Both solutes exhibited endothermic reactions in all solvents. The ΔsolH for propranolol HCl in the SIF solutions differed from those in the HBSS and was lower in the fed state than the fasted state SIF solution, revealing an interaction between propranolol and the micellar phase in both SIF solutions. In contrast, for mannitol the ΔsolH was constant in all solutions indicating minimal interaction between mannitol and the micellar phases of the SIF solutions. In this study, solution calorimetry proved to be a simple method for measuring the enthalpy associated with the dissolution of model drugs in complex biological media such as SIF solutions. In addition, the derived power–time curves allowed the time taken for the powdered solutes to form solutions to be estimated.

Computational fluid dynamics modelling of the air movement in an environmental test chamber with a respiring manikin

In recent years, computational fluid dynamics (CFD) has been widely used as a method of simulating airflow and addressing indoor environment problems. The complexity of airflows within the indoor environment would make experimental investigation difficult to undertake and also imposes significant challenges on turbulence modelling for flow prediction. This research examines through CFD visualization how air is distributed within a room. Measurements of air temperature and air velocity have been performed at a number of points in an environmental test chamber with a human occupant. To complement the experimental results, CFD simulations were carried out and the results enabled detailed analysis and visualization of spatial distribution of airflow patterns and the effect of different parameters to be predicted. The results demonstrate the complexity of modelling human exhalation within a ventilated enclosure and shed some light into how to achieve more realistic predictions of the airflow within an occupied enclosure.

Rheological and electrical properties of NaY zeolite electrorheological fluid

The relations between the rheological and electrical properties of NaY zeolite electrorheological fluid and its solid phase are studied. It is found that then exist complex relations between its electrical and theological properties. The temperature spectra of dielectric properties of the fluid under high AC electric field are strongly field strength dependent. The relation between the DC conductivity of the fluid and the exciting electric field is experimentally presented as log sigma =A+BE1/2, when A is a strong function, but B, a very weak function of temperature. The shear stress of the fluid under a fixed electric field and temperature decreases with shear rate. A relaxation time for the adsorbed charges is estimated to be about 0.3 to 6.6 s in the temperature range from 280 to 380 K. The relaxation time qualitatively corresponds to the shear rate at which the shear stress begins to drop. The time dependent leaking current of the ER fluids under DC electric field is also measured. The conductivity increase is mainly caused by the structure evolution of particles. The experimental results can he explained with the calculations of Davis (J. Appl. Phys. 81(1997) pp.1985-1991) and Martin (J. Chem. Phys. 110(1999) pp.4854-4866). It is predicted that the NaY zeolite ER fluid strength would get degraded slowly.

Lattice Boltzmann simulation of viscous fluid systems with elastic boundaries

A lattice Boltzmann model able to simulate viscous fluid systems with elastic and movable boundaries is proposed. By introducing the virtual distribution function at the boundary, the Galilean invariance is recovered for the full system. As examples of application, the how in elastic vessels is simulated with the pressure-radius relationship similar to that of the pulmonary blood vessels. The numerical results for steady how are in good agreement with the analytical prediction, while the simulation results for pulsative how agree with the experimental observation of the aortic flows qualitatively. The approach has potential application in the study of the complex fluid systems such as the suspension system as well as the arterial blood flow.

Structure and viscoelasticity of an electrorheological fluid in oscillatory shear: computer simulation investigation

The three-dimensional molecular dynamics simulation method has been used to study the dynamic responses of an electrorheological (ER) fluid in oscillatory shear. The structure and related viscoelastic behaviour of the fluid are found to be sensitive to the amplitude of the strain. With the increase of the strain amplitude, the structure formed by the particles changes from isolated columns to sheet-like structures which may be perpendicular or parallel to the oscillating direction. Along with the structure evolution, the field-induced moduli decrease significantly with an increase in strain amplitude. The viscoelastic behaviour of the structures obtained in the cases of different strain amplitudes was examined in the linear response regime and an evident structure dependence of the moduli was found. The reason for this lies in the anisotropy of the arrangement of the particles in these structures. Short-range interactions between the particles cannot be neglected in determining the viscoelastic behaviour of ER fluids at small strain amplitude, especially for parallel sheets. The simulation results were compared with available experimental data and good agreement was reached for most of them.