The Minimal Spherical Dispersion.

We prove upper and lower bounds on the minimal spherical dispersion, improving upon previous estimates obtained by Rote and Tichy in (Anz Österreich Akad Wiss Math Nat Kl 132:3-10, 1995). In particular, we see that the inverse N(ε,d) of the minimal spherical dispersion is, for fixed ε>0, linear in the dimension d of the ambient space. We also derive upper and lower bounds on the expected dispersion for points chosen independently and uniformly at random from the Euclidean unit sphere. In terms of the corresponding inverse N~(ε,d), our bounds are optimal with respect to the dependence on ε.

The coumarin osthole is a non-electrophilic agonist of TRPA1.

The naturally occurring coumarin osthole has antipruritic properties, and recent reports suggest that this effect is due an inhibition or desensitization of the cation channels TRPV1 and TRPV3. Osthole was also suggested to activate TRPA1, an effect that should rather be pruritic than antipruritic. Here we characterized the effects of osthole on TRPA1 by means of ratiometric calcium imaging and patch clamp electrophysiology. In HEK 293 expressing human (h) TRPA1, osthole induced a concentration-dependent increase in intracellular calcium that was inhibited by the TRPA1-inhibitor A967079. In mouse dorsal root ganglion (DRG) cells, osthole induced a strong calcium-influx that was partly mediated by TRPA1. Osthole evoked fully reversible membrane currents in whole-cell as well as cell-free inside-out recordings on hTRPA1. Osthole failed to activate the mutant hTRPA1-S873V/T874L, a previously described binding site for the non-electrophilic TRPA1-agonists menthol and carvacrol. The combined application of osthole and carvacrol diminished channel activation, suggesting a competitive binding. Finally, osthole failed to activate TRPM8 and TRPV4 but induced a modest activation of hTRPV1 expressed in HEK 293 cells. We conclude that osthole is a potent non-electrophilic agonist of TRPA1. The relevance of this property for the antipruritic effects needs to be further explored.

The impact of modified fluid gelatin 4% in a balanced electrolyte solution on plasma osmolality in children-A noninterventional observational study.

BACKGROUND: Intravenous fluids for perioperative infusion therapy should be isotonic to maintain the body fluid homeostasis in children. Modified fluid gelatin 4% in a balanced electrolyte solution has a theoretical osmolarity of 284 mosmol L-1 , and a real osmolality of 264 mosmol kg H2 O-1 . Because both values are lower than those of 0.9% saline or plasma, gelatin would be expected to be hypotonic in-vitro and in-vivo. AIM: We thus hypothesized that the infusion of gelatin would be expected to decrease plasma osmolality. We performed an in-vitro experiment and an in-vivo study to evaluate the impact of gelatin on the osmolality in children. METHODS: In the in-vitro experiment, full blood samples were diluted with gelatin 4% or albumin (50 g L-1 ) from 0% (pure blood) to 100% (pure colloid), and the osmolality was measured by freezing-point depression. In the in-vivo study, blood gas analyses from children undergoing major pediatric surgery were collected before and after gelatin infusion, and the osmolality was calculated by a modified version of Zander's formula. RESULTS: In the in-vitro experiment, 65 gradually diluted blood samples from five volunteers (age 25-55 years) were analyzed. The dilution with gelatin caused no significant changes in osmolality between 0% and 100%. Compared with gelatin, the osmolality in the albumin group was significantly lower between 50% and 100% dilution (p < .05). In the in-vivo study, 221 children (age 21.4 ± 30 months) were included. After gelatin infusion, the osmolality increased significantly (mean change 4.3 ± 4.8 [95% CI 3.7-4.9] mosmol kg H2 O-1 ; p < .01) within a normal range. CONCLUSIONS: Gelatin in a balanced electrolyte solution has isotonic characteristics in-vitro and in-vivo, despite the low theoretical osmolarity, probably caused by the (unmeasured) negative charges in the gelatin molecules contributing to the plasma osmolality. For a better evaluation of the (real) tonicity of gelatin-containing solutions, we suggest to calculate the osmolality (mosmol kg H2 O-1 ) using Zander's formula. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT02495285).

Perturbation bounds for Monte Carlo within Metropolis via restricted approximations.

The Monte Carlo within Metropolis (MCwM) algorithm, interpreted as a perturbed Metropolis-Hastings (MH) algorithm, provides an approach for approximate sampling when the target distribution is intractable. Assuming the unperturbed Markov chain is geometrically ergodic, we show explicit estimates of the difference between the n th step distributions of the perturbed MCwM and the unperturbed MH chains. These bounds are based on novel perturbation results for Markov chains which are of interest beyond the MCwM setting. To apply the bounds, we need to control the difference between the transition probabilities of the two chains and to verify stability of the perturbed chain.

Compatibility of common drugs with acetate-containing balanced electrolyte solutions in pediatric anesthesia.

BACKGROUND: Acetate-containing balanced electrolyte solutions are frequently used for fluid therapy in pediatric anesthesia, but no studies investigating the compatibility with common anesthetic drugs are available. AIM: To reveal possible incompatibilities between common anesthetic drugs and the acetate-containing balanced electrolyte solutions BS (Sterofundin ISO; B.Braun Melsungen AG, Melsungen, Germany) and BS-G1 (E148G1 Päd; Serumwerk Bernburg AG, Bernburg, Germany), with normal saline (NS) as control. METHODS: All tested infusion solutions were mixed 1 : 1 with 28 common anesthetic drugs in concentrations used in daily clinical practice. Electrical conductivity, pH, and turbidimetric light diffusion at 405 nm were measured. Macroscopic changes such as gross precipitation, change in color, or bubble formation were also assessed. All measurements were performed immediately after mixing as well as 30 and 60 min after. RESULTS: The vast majority of drugs showed no significant change in pH, electric conductivity, turbidimetric detectable light diffusion, or macroscopic appearance after mixing with BS, BS-G1, and NS. Phenytoin immediately precipitated in response to all tested solutions as did diazepam. Thiopental precipitated after mixing with BS only. CONCLUSIONS: Most of the tested drugs did not show any signs or evidence of incompatibility reactions. However, phenytoin and diazepam should not be in contact with the three tested solutions, including NS. Thiopental should be used with caution because it can precipitate in solutions with a low pH (e.g., BS).

International pneumococcal clones match or exceed the fitness of other strains despite the accumulation of antibiotic resistance.

A few international pneumococcal clones dominate the population of antibiotic-resistant pneumococci. Despite the scientific paradigm that a loss in fitness is the price for acquisition of resistance, these clones spread successfully. One hundred fifty-four isolates from adult patients with community-acquired pneumonia (CAP) were analyzed. Thirty percent showed a close relationship to international clones and had fitness equal to or exceeding that of other strains (P = 0.015); these factors may result in the endurance of these strains despite a reduction of antibiotic usage.