Pharmacokinetic analysis after implantation of everolimus-eluting self-expanding stents in the peripheral vasculature

Background: A novel self-expanding drug-eluting stent was designed to release everolimus 225 mu g/cm(2) to prevent restenosis following peripheral arterial intervention. The purpose of this study was to measure the pharmacokinetic profile of everolimus following stent implantation. Methods: One hundred four patients with symptomatic peripheral arterial disease underwent implantation of everolimus-eluting stents in the femoropopliteal arteries. In a prespecified subset of 26 patients, blood samples for assay of everolimus content were collected prior to stent implantation, at 1, 4, and 8 hours postprocedure, prior to discharge, and at 1 month postproccdure. Results: A total of 39 stents, ranging from 28 mm to 100 mm in length, were implanted in 26 patients, resulting in a total delivered everolimus dose range of 3.0 to 7.6 mg. Following the procedure, the maximum observed everolimus blood concentrations (C-max) varied from 1.83 +/- 0.05 ng/mL after implantation of a single 80-mm stent to 4.66 +/- 1.78 ng/mL after implantation of two 100-mm stents. The mean time to peak concentration (T-max) varied from 6.8 hours to 35 hours. The pharmacokinetics of everolimus were dose-proportional in that dose-normalized C-max and area under the curve values were constant over the studied dose range. Conclusions: After implantation of everolimus-eluting self-expanding stents in the femoropopliteal arteries, systemic blood concentrations of everolimus are predictable and considerably lower than blood concentrations observed following safe oral administration of everolimus

Monitoring of tritium purity during long-term circulation in the KATRIN test experiment LOOPINO using laser Raman spectroscopy

The gas circulation loop LOOPINO has been set up and commissioned at Tritium Laboratory Karlsruhe (TLK) to perform Raman measurements of circulating tritium mixtures under conditions similar to the inner loop system of the neutrino-mass experiment KATRIN, which is currently under construction. A custom-made interface is used to connect the tritium containing measurement cell, located inside a glove box, with the Raman setup standing on the outside. A tritium sample (purity > 95%, 20 kPa total pressure) was circulated in LOOPINO for more than three weeks with a total throughput of 770 g of tritium. Compositional changes in the sample and the formation of tritiated and deuterated methanes CT_(4-n)X_n (X=H,D; n=0,1) were observed. Both effects are caused by hydrogen isotope exchange reactions and gas-wall interactions, due to tritium {\beta} decay. A precision of 0.1% was achieved for the monitoring of the T_2 Q_1-branch, which fulfills the requirements for the KATRIN experiment and demonstrates the feasibility of high-precision Raman measurements with tritium inside a glove box

3.6 and 4.5 μ\mum Spitzer{\it Spitzer} Phase Curves of the Highly-Irradiated Hot Jupiters WASP-19b and HAT-P-7b

We analyze full-orbit phase curve observations of the transiting hot Jupiters WASP-19b and HAT-P-7b at 3.6 and 4.5 $\mu$m obtained using the Spitzer Space Telescope. For WASP-19b, we measure secondary eclipse depths of $0.485\%\pm 0.024\%$ and $0.584\%\pm 0.029\%$ at 3.6 and 4.5 $\mu$m, which are consistent with a single blackbody with effective temperature $2372 \pm 60$ K. The measured 3.6 and 4.5 $\mu$m secondary eclipse depths for HAT-P-7b are $0.156\%\pm 0.009\%$ and $0.190\%\pm 0.006\%$, which are well-described by a single blackbody with effective temperature $2667\pm 57$ K. Comparing the phase curves to the predictions of one-dimensional and three-dimensional atmospheric models, we find that WASP-19b's dayside emission is consistent with a model atmosphere with no dayside thermal inversion and moderately efficient day-night circulation. We also detect an eastward-shifted hotspot, suggesting the presence of a superrotating equatorial jet. In contrast, HAT-P-7b's dayside emission suggests a dayside thermal inversion and relatively inefficient day-night circulation; no hotspot shift is detected. For both planets, these same models do not agree with the measured nightside emission. The discrepancies in the model-data comparisons for WASP-19b might be explained by high-altitude silicate clouds on the nightside and/or high atmospheric metallicity, while the very low 3.6 $\mu$m nightside planetary brightness for HAT-P-7b may be indicative of an enhanced global C/O ratio. We compute Bond albedos of 0 ($<0.08$ at $1\sigma$) and $0.38\pm 0.06$ for WASP-19b and HAT-P-7b, respectively. In the context of other planets with thermal phase curve measurements, we show that WASP-19b and HAT-P-7b fit the general trend of decreasing day-night heat recirculation with increasing irradiation.Comment: 22 pages, 29 figures, accepted by Ap

First clinical trial of nitinol self-expanding everolimus-eluting stent implantation for peripheral arterial occlusive disease

BackgroundA novel self-expanding drug-eluting stent was designed to slowly release everolimus to prevent restenosis following peripheral arterial intervention. The purpose of the first-in-human Superficial Femoral Artery Treatment with Drug-Eluting Stents (STRIDES) trial was to evaluate the safety and efficacy of this device for the treatment of symptomatic superficial femoral and proximal popliteal arterial occlusive disease.Methods and ResultsOne hundred four patients were enrolled at 11 European investigative centers in a prospective, nonrandomized, single-arm trial. The patients had severe symptomatic vascular disease, including a significant proportion of patients with critical limb ischemia (17%), diabetes (39%), and single-vessel outflow (26%). The mean lesion length was 9.0 ± 4.3 cm. Ninety-nine percent of patients were available for 12-month follow-up, including duplex imaging in 90% and arteriography in 83%. Clinical improvement, defined as a sustained decrease in Rutherford-Becker clinical category, was achieved in 80% of patients. Primary patency (freedom from ≥50% in-stent restenosis) was 94 ± 2.3% and 68 ± 4.6% at 6 and 12 months, respectively. Plain radiographic examination of 122 implanted devices at 12 months revealed no evidence for stent fracture.ConclusionsThe everolimus-eluting self-expanding nitinol stent can be successfully implanted in patients with severe peripheral arterial disease with favorable outcomes and clinical improvements observed in the majority of patients

Validation of the Kinetik Blood Pressure Monitor-Series 1 for use in adults at home and in clinical settings, according to the 2002 European Society of Hypertension International Protocol on the validation of blood pressure devices

The aim of this study was to assess the blood pressure (BP) measurement accuracy of the Kinetik Blood Pressure Monitor—Series 1 (BPM-1) for use in home or clinical settings according to the 2002 European Society of Hypertension International Protocol (ESH-IP). Forty-two participants were recruited to fulfil the required number of systolic and diastolic BP measurements according to the ESH-IP. Nine sequential same-arm BP readings were measured and analysed for each participant using the test device and observer mercury standard readings according to the 2002 ESH-IP. Forty one participants were used to obtain 33 sets of systolic and diastolic BP readings and were included in the analysis. Mean difference between the device measurements and the observer (mercury standard) measurements was 1.1 ± 7.2/1.1 ± 6.8 mmHg (mean ± standard deviation; systolic/diastolic). The number of systolic BP differences between the test and observer measurements that fell within 5, 10 and 15 mmHg was 65, 86 and 92. For diastolic readings, the number of test—observer measurement differences within 5, 10 and 15 mmHg was 77, 91 and 94. The number of participants with at least two out of three differences within 5 mmHg was 28 for systolic and 40 for diastolic BP readings. Three participants had no differences between the test and observer measurements within 5 mmHg in both the systolic and diastolic measurement categories. The Kinetik BPM-1 device fulfilled the requirements of the ESH-IP validation procedure and can be recommended for clinical use and self-measurement within the home

On the lease rate, convenience yield and speculative effects in the gold futures market

By examining data on the gold forward offered rate (GOFO) and lease rates over the period 1996- 2009, we conclude that the convenience yield of gold is better approximated by the lease rate than the interest-adjusted spread of Fama & French (1983). Using the latter quantity, we study the relationship between gold leasing and the level of COMEX discretionary inventory and exhibit that lease rates are negatively related to inventories. We also show that Futures prices have increasingly exceeded forward prices over the period, and this effect increases with the speculative pressure and the maturity of the contracts

Exoplanet phase curves: observations and theory

Phase curves are the best technique to probe the three dimensional structure of exoplanets' atmospheres. In this chapter we first review current exoplanets phase curve observations and the particular challenges they face. We then describe the different physical mechanisms shaping the atmospheric phase curves of highly irradiated tidally locked exoplanets. Finally, we discuss the potential for future missions to further advance our understanding of these new worlds.Comment: Fig.5 has been updated. Table 1 and corresponding figures have been updated with new values for WASP-103b and WASP-18b. Contains a table sumarizing phase curve observation

The Political Economy of Failure: The Euro as an International Currency

How do international currencies get established and consolidated? What domestic and international political foundations support an international currency? And what kinds of macro-economic flows enable an international currency? In this essay we consider these perennial questions of modern IPE scholarship in reverse order to ask whether the euro could ever have become, or seek to become, a true international currency rivalling the US dollar, used not only for passive foreign exchange reserves but also as a major commercial currency outside the EU. We argue that the EU lacks the will, the ideas and the capacity to promote the euro into the status of an international currency. In this article, we concentrate on this final issue of capacity, as the will and ideas issues have already been well explored. Capacity is an issue coeval with, if not prior to, the first two issues. The EU's current institutional arrangements and its economic geography create macro-economic consequences that diminish the euro's capacity to operate as a top currency. These conflicts go beyond the well-recognized issue that the euro-zone is not an optimum currency area. Examining the euro's debilities sheds light not only on the euro's (in)capacity to rival the dollar as an international currency, but also on the future of both the euro and the dollar in the aftermath of the euro-zone crisis

Electron heating at Saturn's bow shock

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94695/1/jgra21551.pd

T Wave Alternans in high arrhythmic risk patients: Analysis in time and frequency domains: A pilot study

BACKGROUND: T wave alternans (TA) is a repolarisation phenomenon manifesting as a microvolt beat to beat change in the amplitude of the T wave and ST segment. TA has been shown to be a predictor of arrhythmic risk in unselected myocardial infarction populations. TA has not been used to differentiate risk within the ischaemic cardiomyopathy population. METHODS: The subjects investigated comprised, Group 1: 7 stable patients with remote (>20 months) extensive myocardial scarring and no arrhythmic events (NYHA 3 and 4). Group2: 9 post infarction patients with malignant arrhythmia and implantable defibrillator. During breath holding, 20 continuous QRST complexes from each patients X, Y and Z leads were digitally recorded. Time domain, resultant absolute difference vectors (ATA), were calculated for alternate resultant T wave sequences. Group differences between the magnitude and temporal distribution of mean ATAs and their spectral and cross-spectral analysis were compared. RESULTS: Group 1 v Group 2 mean ATAs were 10.7 (7.17) v 11.7 (8.48) respectively, not significant. Each group had a homogenous temporal distribution of ATAs. Both group's largest mean ATA frequency components were between 0 to 25 Hz, the largest ATA component being at the DC frequency. Cross spectral analysis showed no significant differences in group ATA frequency content. CONCLUSION: The frequency content and microvolt magnitude of T wave alternans was not significantly different in these two groups. The specificity of T wave alternans for differentiating arrhythmic risk in post infarction scarring and heart failure needs investigation