Activity of microemulsion-based nanoparticles at the human bio-nano interface: concentration-dependent effects on thrombosis and hemolysis in whole blood

Background: Although microemulsion-based nanoparticles (MEs) may be useful for drug delivery or scavenging, these benefits must be balanced against potential nanotoxicological effects in biological tissue (bio-nano interface). We investigated the actions of assembled MEs and their individual components at the bio-nano interface of thrombosis and hemolysis in human blood. Methods: Oil-in-water MEs were synthesized using ethylbutyrate, sodium caprylate, and pluronic F-68 (ME4) or F-127 (ME6) in 0.9% NaCl_w/v. The effects of MEs or components on thrombosis were determined using thrombo-elastography, platelet contractile force, clot elastic modulus, and platelet counting. For hemolysis, ME or components were incubated with erythrocytes, centrifuged, and washed for measurement of free hemoglobin by spectroscopy. Results and conclusions: The mean particle diameters (polydispersity index) for ME6 and ME4 were 23.6 ± 2.5 nm (0.362) and 14.0 ± 1.0 nm (0.008), respectively. MEs (0, 0.03, 0.3, 3 mM) markedly reduced the thromboelastograph maximal amplitude in a concentration-dependent manner (49.0 ± 4.2, 39.0 ± 5.6, 15.0 ± 8.7, 3.8 ± 1.3 mm, respectively), an effect highly correlated (r2 = 0.94) with similar changes caused by pluronic surfactants (48.7 ± 10.9, 30.7 ± 15.8, 20.0 ± 11.3, 2.0 ± 0.5) alone. Neither oil nor sodium caprylate alone affected the thromboelastograph. The clot contractile force was reduced by ME (27.3 ± 11.1–6.7 ± 3.4 kdynes/cm², P = 0.02, n = 5) whereas the platelet population not affected (175 ± 28–182 ± 23 10⁶/ml, P = 0.12, n = 6). This data suggests that MEs reduced platelet activity due to associated pluronic surfactants, but caused minimal changes in protein function necessary for coagulation. Although pharmacological concentrations of sodium caprylate caused hemolysis (EC₅₀ = 213 mM), MEs and pluronic surfactants did not disrupt erythrocytes. Knowledge of nanoparticle activity and potential associated nanotoxicity at this bio-nano interface enables rational ME design for in vivo applications.     

Order restricted randomized designs for control versus treatment comparison

We develop a method of randomizing units to treatments that relies on subjective judgement or on possible coarse modeling to produce restrictions on the randomization. The procedure thus fits within the general framework of ranked set sampling. However, instead of selecting a single unit from each set for full measurement, all units within a set are used. The units within a set are assigned to different treatments. Such an assignment translates the positive dependence among units within a set into a reduction in variation of contrasting features of the treatments. A test for treatment versus control comparison, with controlled familywise error rate, is developed along with the associated confidence intervals. The new procedure is shown to be superior to corresponding procedures based on completely randomized or ranked set sample designs. The superiority appears both in asymptotic relative efficiency and in power for finite sample sizes. Importantly, this test does not rely on perfect rankings; rather, the information in the data on the quality of rankings is exploited to maintain the level of the test when rankings are imperfect. The asymptotic relative efficiency of the test is not affected by estimation of the quality of rankings, and the finite sample performance is only mildly affected.     

Beweis eines Satzes über rationale Curven

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Bücherbesprechungen

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Studien über Kernalkylierung

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When should you sack a football manager? Results from a simple model applied to the English Premiership

What strategy should a football (soccer, in American parlance) club adopt when deciding whether to sack its manager? This paper introduces a simple model assuming that a club's objective is to maximize the number of league points that it scores per season. The club's strategy consists of three choices: the length of the honeymoon period during which it will not consider sacking a new manager, the level of the performance trapdoor below which the manager get the sack, and the weight that it will give to more recent games compared to earlier ones. Some data from the last six seasons of the English Premiership are used to calibrate the model. At this early stage of the research, the best strategy appears to have only a short honeymoon period of eight games (much less than the actual shortest period of 12 games), to set the trapdoor at 0.74 points per game, and to put 47% of the weight on the last five games. A club adopting this strategy would obtain on average 56.8 points per season, compared to a Premiership average of 51.8 points.     

Kolloidchemie und Photographie

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