Effects of the vasodilating beta-blocker nebivolol on smoking-induced endothelial dysfunction in young healthy volunteers

André C Schmidt1, Burkhard Flick1, Elke Jahn2, Peter Bramlage31Charité – Universitätsmedizin Berlin, Institute for Clinical Pharmacology and Toxikology, Berlin, Germany; 2Berlin-Chemie AG, Clinical Research and Medical Information, Berlin, Germany; 3Institute for Clinical Pharmacology, Medical Faculty Carl Gustav Carus, TU Dresden, GermanyObjective: To assess the effect of nebivolol, a highly selective third generation β1-adrenoceptor antagonist with an endothelium-dependent vasodilatory action, on smoking-induced endothelial dysfunction.Research design and methods: This open-label study examined the effect of 14 daily doses of 5 mg nebivolol on forearm blood flow in 21 healthy, young, male, light smokers (≤5 cigarettes/day), measured by plethysmography on Days 1, 7, and 14. The primary endpoint was the difference in forearm blood flow after smoking one standard cigarette from baseline (Day 1) until treatment end on Day 14. Secondary outcomes included the difference in forearm blood flow between Day 1 and Day 7 compared with Day 14 before and after smoking, the effect of nebivolol on blood coagulation parameters, high-sensitive-C-reactive protein (hs-CRP), and the safety and tolerability of nebivolol.Results: Nebivolol for 14 days did not significantly affect forearm blood flow after smoking. On Day 7 of nebivolol treatment, forearm blood flow after smoking was significantly greater than blood flow before smoking (increase of 0.44 mL/min; p = 0.00656). Serum level of hs-CRP showed a marked decrease from Day 1 to Day 14. No changes in coagulation parameters were observed over the course of nebivolol treatment. Nebivolol was well tolerated throughout the study.Conclusions: The increase in forearm blood flow and the marked decrease in hs-CRP over 14 days of treatment suggest that nebivolol has a positive effect on endothelial function in light smokers, but larger studies are required to confirm these observations.Keywords: C-reactive protein, endothelial dysfunction, nebivolol, nitric oxide (NO), smokin

Generating single photons at gigahertz modulation-speed using electrically controlled quantum dot microlenses

This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This article appeared in Appl. Phys. Lett. 108, 021104 (2016) and may be found at https://doi.org/10.1063/1.4939658.We report on the generation of single-photon pulse trains at a repetition rate of up to 1 GHz. We achieve this speed by modulating the external voltage applied on an electrically contacted quantum dot microlens, which is optically excited by a continuous-wave laser. By modulating the photoluminescence of the quantum dot microlens using a square-wave voltage, single-photon emission is triggered with a response time as short as (281 ± 19) ps, being 6 times faster than the radiative lifetime of (1.75 ± 0.02) ns. This large reduction in the characteristic emission time is enabled by a rapid capacitive gating of emission from the quantum dot, which is placed in the intrinsic region of a p-i-n-junction biased below the onset of electroluminescence. Here, since our circuit acts as a rectifying differentiator, the rising edge of the applied voltage pulses triggers the emission of single photons from the optically excited quantum dot. The non-classical nature of the photon pulse train generated at GHz-speed is proven by intensity autocorrelation measurements with g(2)(0) = 0.3 ± 0.1. Our results combine optical excitation with fast electrical gating and thus show promise for the generation of indistinguishable single photons at rates exceeding the limitations set by the intrinsic radiative lifetime.BMBF, 03V0630, Entwicklung einer Halbleiterbasierten Einzelphotonenquelle für die Quanteninformationstechnologie (QSOURCE)DFG, 43659573, SFB 787: Halbleiter - Nanophotonik: Materialien, Modelle, Bauelement

Multilevel Contracts for Trusted Components

This article contributes to the design and the verification of trusted components and services. The contracts are declined at several levels to cover then different facets, such as component consistency, compatibility or correctness. The article introduces multilevel contracts and a design+verification process for handling and analysing these contracts in component models. The approach is implemented with the COSTO platform that supports the Kmelia component model. A case study illustrates the overall approach.Comment: In Proceedings WCSI 2010, arXiv:1010.233

Tests of relativity using a microwave resonator

The frequencies of a cryogenic sapphire oscillator and a hydrogen maser are compared to set new constraints on a possible violation of Lorentz invariance. We determine the variation of the oscillator frequency as a function of its orientation (Michelson-Morley test) and of its velocity (Kennedy-Thorndike test) with respect to a preferred frame candidate. We constrain the corresponding parameters of the Mansouri and Sexl test theory to $\delta - \beta + 1/2 = (1.5\pm 4.2) \times 10^{-9}$ and $\beta - \alpha - 1 = (-3.1\pm 6.9) \times 10^{-7}$ which is equivalent to the best previous result for the former and represents a 30 fold improvement for the latter.Comment: 8 pages, 2 figures, submitted to Physical Review Letters (October 3, 2002

Comparative Effects of Methylphenidate, Modafinil, and MDMA on Response Inhibition Neural Networks in Healthy Subjects

Psychostimulants such as methylphenidate and modafinil are increasingly used by healthy people for cognitive enhancement purposes, whereas the acute effect of 3,4-methylenedioxymethamphetamine (ecstasy) on cognitive functioning in healthy subjects remains unclear. This study directly compared the acute effects of methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine on the neural mechanisms underlying response inhibition in healthy subjects.; Using a double-blind, within-subject, placebo-controlled, cross-over design, methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine were administrated to 21 healthy subjects while performing a go/no-go event-related functional magnetic resonance imaging task to assess brain activation during motor response inhibition.; Relative to placebo, methylphenidate and modafinil but not 3,4-methylenedioxymethamphetamine improved inhibitory performance. Methylphenidate significantly increased activation in the right middle frontal gyrus, middle/superior temporal gyrus, inferior parietal lobule, presupplementary motor area, and anterior cingulate cortex compared with placebo. Methylphenidate also induced significantly higher activation in the anterior cingulate cortex and presupplementary motor area and relative to modafinil. Relative to placebo, modafinil significantly increased activation in the right middle frontal gyrus and superior/inferior parietal lobule, while 3,4-methylenedioxymethamphetamine significantly increased activation in the right middle/inferior frontal gyrus and superior parietal lobule.; Direct comparison of methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine revealed broad recruitment of fronto-parietal regions but specific effects of methylphenidate on middle/superior temporal gyrus, anterior cingulate cortex, and presupplementary motor area activation, suggesting dissociable modulations of response inhibition networks and potentially the superiority of methylphenidate in the enhancement of cognitive performance in healthy subjects

Rationale and design of XAMOS: noninterventional study of rivaroxaban for prophylaxis of venous thromboembolism after major hip and knee surgery

Venous thromboembolism is a frequent and potentially life-threatening complication of orthopedic surgery. Rivaroxaban is an oral direct factor Xa inhibitor, which was shown to be effective for the prevention of venous thromboembolism after elective hip and knee arthroplasty in the RECORD study program. Rivaroxaban has the potential to overcome the limitations of the current standards of care in the prevention of venous thromboembolism. XAMOS (Xarelto® in the prophylaxis of post-surgical venous thromboembolism after elective major orthopedic surgery of hip or knee) is an international, noninterventional, parallel-group study to gain insight into the safety (major bleeding, side effects) and effectiveness (prevention of symptomatic thromboembolic events) of rivaroxaban in daily clinical practice. XAMOS will follow 15,000 patients after major orthopedic surgery in approximately 200 centers worldwide, with about 7500 patients receiving rivaroxaban and about 7500 standard of care. XAMOS will supplement the clinical data obtained in the Phase III RECORD 1, 2, 3, and 4 trials in which rivaroxaban was shown to be superior for the primary efficacy endpoints, and with a safety profile similar to that of enoxaparin after hip or knee replacement surgery. XAMOS was started in 2009 and will complete recruitment and follow-up in 2011

Statistical analysis of the mass-to-flux ratio in turbulent cores: effects of magnetic field reversals and dynamo amplification

We study the mass-to-flux ratio (M/\Phi) of clumps and cores in simulations of supersonic, magnetohydrodynamical turbulence for different initial magnetic field strengths. We investigate whether the (M/\Phi)-ratio of core and envelope, R = (M/\Phi)_{core}/(M/\Phi)_{envelope} can be used to distinguish between theories of ambipolar diffusion and turbulence-regulated star formation. We analyse R for different Lines-of-Sight (LoS) in various sub-cubes of our simulation box. We find that, 1) the average and median values of |R| for different times and initial magnetic field strengths are typically greater, but close to unity, 2) the average and median values of |R| saturate at average values of |R| ~ 1 for smaller magnetic fields, 3) values of |R| < 1 for small magnetic fields in the envelope are caused by field reversals when turbulence twists the field lines such that field components in different directions average out. Finally, we propose two mechanisms for generating values |R| ~< 1 for the weak and strong magnetic field limit in the context of a turbulent model. First, in the weak field limit, the small-scale turbulent dynamo leads to a significantly increased flux in the core and we find |R| ~< 1. Second, in the strong field limit, field reversals in the envelope also lead to values |R| ~< 1. These reversals are less likely to occur in the core region where the velocity field is more coherent and the internal velocity dispersion is typically subsonic.Comment: 12 pages, 8 figures, accepted for publication in MNRA

Impact of glycemic control on the incidence of acute kidney injury in critically ill patients: a comparison of two strategies using the RIFLE criteria

OBJECTIVE: To compare the renal outcome in patients submitted to two different regimens of glycemic control, using the RIFLE criteria to define acute kidney injury. INTRODUCTION: The impact of intensive insulin therapy on renal function outcome is controversial. The lack of a criterion for AKI definition may play a role on that. METHODS: Included as the subjects were 228 randomly selected, critically ill patients engaged in intensive insulin therapyor in a carbohydrate-restrictive strategy. Renal outcome was evaluated through the comparison of the last RIFLE score obtained during the ICU stay and the RIFLE score at admission; the outcome was classified as favorable, stable or unfavorable. RESULTS: The two groups were comparable regarding demographic data. AKI developed in 52% of the patients and was associated with a higher mortality (39.4%) compared with those who did not have AKI (8.2%) (p<0.001). Renal function outcome was comparable between the two groups (p=0.37). We observed a significant correlation between blood glucose levels and the incidence of acute kidney injury (p=0.007). In the multivariate logistic regression analysis, only APACHE III scores higher than 60 were identified as an independent risk factor for unfavorable renal outcome. APACHE III scores>60, acute kidney injury and hypoglycemia were risk factors for mortality. CONCLUSION: Intensive insulin therapy and a carbohydrate-restrictive strategy were comparable regarding the incidence of acute kidney injury evaluated using RIFLE criteria