Transmembrane passage of cytokine-inducing bacterial products across new and reprocessed polysulfone dialyzers

The widespread use of bicarbonate dialysate and reprocessed high-efficiency and "high-flux" dialyzers has raised concerns about the increased risk of reverse-transfer of dialysate contaminants into the blood compartment. To evaluate this concern, the reverse-transfer of bacterial products from contaminated bicarbonate dialysate into the blood compartment was compared during in vitro dialysis with new or reprocessed high-flux polysulfone dialyzers. In vitro dialysis was carried out at 37 degrees C by use of a counter-current recirculating loop dialysis circuit with either new high-flux polysulfone dialyzers or dialyzers reprocessed once or 20 times with formaldehyde (0.75%) and bleach (< 1%) with an automated system. Heparinized whole blood from healthy volunteers was circulated through the blood compartment, and bicarbonate dialysate was circulated in the dialysate compartment. The dialysate was challenged sequentially by 1:1000 and 1:100 dilutions of a sterile Pseudomonas aeruginosa culture supernatant (bacterial challenge). Samples were drawn from the blood and dialysate compartments 1 h after each challenge. Peripheral blood mononuclear cells (PBMC) were harvested by Ficoll-Hypaque separation from whole blood in the blood compartment and a 5 x 10(6) PBMC/mL cell suspension was prepared. Likewise, dialysate samples (0.5 mL) were added to 0.5 mL suspension of 5 x 10(6) PBMC/mL drawn at baseline. All PBMC suspensions were incubated upright in a humidified atmosphere at 37 degrees C with 5% CO2 for 24 h, and total interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF alpha) cytokine production (cell-associated and secreted) was measured by radioimmunoassay. Eight experiments were performed for each arm of the study with the same donor for each arm. One hour after contaminating the dialysate with a 1:1000 dilution of the bacterial challenge, IL-1 alpha production by PBMC harvested from the blood compartment was 160 +/- 0, 171 +/- 11, and 270 +/- 35 pg, respectively, for new dialyzers, dialyzers reprocessed once, and dialyzers reprocessed 20 times (P = 0.004). One hour after challenging the dialysate with 1:100 dilution, IL-1 alpha production by PBMC harvested from the blood compartment was 188 +/- 20, 228 +/- 35, and 427 +/- 67 pg, respectively, for new dialyzers, dialyzers reprocessed once, and dialyzers reprocessed 20 times (P = 0.006). IL-1 alpha production by PBMC from dialyzers reprocessed 20 times was significantly greater than both new and dialyzers reprocessed once. However, there were no significant differences between new dialyzers and dialyzers reprocessed once. Similarly, after the 1:1000 challenge, TNF alpha production by PBMC harvested from the blood compartment was 160 +/- 0, 160 +/- 0, and 213 +/- 22 pg, respectively, for new dialyzers, dialyzers reprocessed once, and dialyzers reprocessed 20 times (P = 0.008). After the 1:100 challenge, TNF alpha production was 168 +/- 8, 188 +/- 20, and 225 +/- 32 pg, respectively, for new dialyzers, dialyzers reprocessed once, and dialyzers reprocessed 20 times (P = 0.20). These results demonstrate that reprocessing of high-flux polysulfone dialyzers with bleach increases the risk of reverse-transfer of bacterial products from contaminated dialysate, and this risk appears to increase with the number of reuses. Consequently, units that reprocess membranes with bleach and have suboptimal water quality might subject their patients to a higher risk of cytokine-related morbidity.     

Dynamic positioning of idle automated guided vehicles

An automated guided vehicle (AGV) is a mobile robot commonly used to carry loads in material handling systems (MHS). Once a transfer is completed, an AGV stops at a home position, a point where it can park until it is assigned a new task. Determining the home positions is an important control problem with a direct influence on the overall performance of the MHS. The problem can be viewed as a location-allocation problem on a network. In this paper two fast and effective heuristics which dynamically determine the home positions are proposed. The methods were tested using two real-world instances. The obtained results are shown and discussed.     

Bayesian analysis of repairable systems showing a bounded failure intensity

The failure pattern of repairable mechanical equipment subject to deterioration phenomena sometimes shows a finite bound for the increasing failure intensity. A non-homogeneous Poisson process with bounded increasing failure intensity is then illustrated and its characteristics are discussed. A Bayesian procedure, based on prior information on model-free quantities, is developed in order to allow technical information on the failure process to be incorporated into the inferential procedure and to improve the inference accuracy. Posterior estimation of the model-free quantities and of other quantities of interest (such as the optimal replacement interval) is provided, as well as prediction on the waiting time to the next failure and on the number of failures in a future time interval is given. Finally, numerical examples are given to illustrate the proposed inferential procedure.     

Critical Role for the Protons in FRTL-5 Thyroid Cells: Nuclear Sphingomyelinase Induced-Damage

Proliferating thyroid cells are more sensitive to UV-C radiations than quiescent cells. The effect is mediated by nuclear phosphatidylcholine and sphingomyelin metabolism. It was demonstrated that proton beams arrest cell growth and stimulate apoptosis but until now there have been no indications in the literature about their possible mechanism of action. Here we studied the effect of protons on FRTL-5 cells in culture. We showed that proton beams stimulate slightly nuclear neutral sphingomyelinase activity and inhibit nuclear sphingomyelin-synthase activity in quiescent cells whereas stimulate strongly nuclear neutral sphingomyelinase activity and do not change nuclear sphingomyelin-synthase activity in proliferating cells. The study of neutral sphingomyelinase/sphingomyelin-synthase ratio, a marker of functional state of the cells, indicated that proton beams induce FRTL-5 cells in a proapoptotic state if the cells are quiescent and in an initial apoptotic state if the cells are proliferating. The changes of cell life are accompanied by a decrease of nuclear sphingomyelin and increase of bax protein.     

Role of Tyrosine Kinase Syk in Thrombus Stabilisation at High Shear

Understanding the pathways involved in the formation and stability of the core and shell regions of a platelet-rich arterial thrombus may result in new ways to treat arterial thrombosis. The distinguishing feature between these two regions is the absence of fibrin in the shell which indicates that in vitro flow-based assays over thrombogenic surfaces, in the absence of coagulation, can be used to resemble this region. In this study, we have investigated the contribution of Syk tyrosine kinase in the stability of platelet aggregates (or thrombi) formed on collagen or atherosclerotic plaque homogenate at arterial shear (1000 s⁻¹). We show that post-perfusion of the Syk inhibitor PRT-060318 over preformed thrombi on both surfaces enhances thrombus breakdown and platelet detachment. The resulting loss of thrombus stability led to a reduction in thrombus contractile score which could be detected as early as 3 min after perfusion of the Syk inhibitor. A similar loss of thrombus stability was observed with ticagrelor and indomethacin, inhibitors of platelet adenosine diphosphate (ADP) receptor and thromboxane A₂ (TxA₂), respectively, and in the presence of the Src inhibitor, dasatinib. In contrast, the Btk inhibitor, ibrutinib, causes only a minor decrease in thrombus contractile score. Weak thrombus breakdown is also seen with the blocking GPVI nanobody, Nb21, which indicates, at best, a minor contribution of collagen to the stability of the platelet aggregate. These results show that Syk regulates thrombus stability in the absence of fibrin in human platelets under flow and provide evidence that this involves pathways additional to activation of GPVI by collagen.     

An Analytical Model to Measure the Effectiveness of Safety Management Systems: Global Safety Improve Risk Assessment (G-SIRA) Method

The ever-increasing complexity of production systems, together with the need to obtain efficient processes with limited costs, has led companies to develop custom tools for process control and management. Even for risk assessment, the traditional models often are overcome by methods that are best suited to specific needs. In this context, the aim of this paper was to propose a new model, which we call the global safety improve risk assessment (G-SIRA). This model can classify risks and identify corrective actions that allow the best risk reduction at the lowest cost. The proposed model, which is based on improvements to previous research, uses the analytic hierarchy process approach to develop a valid and simple tool for risk management. The G-SIRA method has been tested in a real-world application, i.e., it was applied to all of the processes of a textile company, and the results were compared with those obtained from the classical approach failure mode, effects, and criticality analysis. The comparison clearly showed the effectiveness of the proposed model.     

Impact of a satellite-derived leaf area index monthly climatology in a global numerical weather prediction model

The leaf area index (LAI), defined as the one-sided green leaf area per unit ground area, is used in many numerical weather prediction (NWP) models as an indicator of the vegetation development state, which is of paramount importance to characterize land evaporation, photosynthesis, and carbon-uptake processes. LAI is often simply represented by lookup tables, dependent on the vegetation type and seasons. However, global LAI datasets derived from remote sensing observations have more recently become available. These products are based on sensors such as the Advanced Very High Resolution Radiometer (AVHRR) or the Moderate Resolution Imaging Spectroradiometer (MODIS), onboard polar orbiting satellites that can cover the entire globe within typically 3 days and with a spatial resolution of the order of 1 km.

We examine the meteorological impact of satellite-derived LAI products on near-surface air temperature and humidity, which comes both from the stomatal transpiration of leaves and from the intercepted water on the surface of leaves, re-evaporating into the atmosphere.

Two distinct monthly LAI climatology datasets derived respectively from AVHRR and MODIS sensors are tested. A set of forecasts and data assimilation experiments with the integrated forecasting system of the European Centre for Medium-range Weather Forecasts is performed with the monthly LAI climatology datasets as opposed to a vegetation-dependent constant LAI. The monthly LAI is shown to improve the forecasts of near-surface (screen-level) air temperature and relative humidity through its effect on evapotranspiration, with the largest impact obtained over needleleaf forests, crops, and grassland. At longer time-scales, the introduction of the monthly LAI is shown to have a positive impact on the model climate particularly during the boreal spring, where the LAI climatology has a large seasonal cycle.     

Hexagrid – hexagonal tube structures for tall buildings: patterns,modeling, and design

This paper provides a first insight on tube configurations based on the hexagonal shape (hexagrid) for tall buildings. The idea is to investigate the mechanical properties of hexagrid to assess their applicability in tall buildings and to compare their potential efficiency to the more popular diagrid systems. For the above purposes, a general homogenization approach has been established for dealing with any structural patterns, and a methodology for characterizing the structural patterns from the mechanical point of view has been developed and specified for hexagrids and diagrids. Then on the basis of a simple stiffness criterion, a design procedure has been proposed and applied to a tall building case study, and several structural solutions (both hexagrids and diagrids) have been designed and assessed by varying the major geometrical parameters of the patterns. Copyright © 2015 John Wiley & Sons, Ltd.