Steady-state Pulse Research Articles

Cathodoluminescence of monoclinic Li3AlF6 crystals in the spectral region of 150–600 nm

Cathodoluminescence (CL) of monoclinic LiAF crystals was studied in the spectral (150–600 nm) and temperature (78–302 K) ranges using both the steady-state CL and pulse CL (PCL) techniques. Three CL emission bands were found in the spectral range of 150–600 nm. The dominant complex CL band at 350 nm obeys the Mott law (E = 0.072 eV and ω = 750). On heating, the 172 and 208–212 nm CL bands vary in intensity non-monotonically. At T = 78 K, the CL decay kinetics comprises three components: a dominant fast exponential component with a lifetime of 750 ns, and two low-intensity components with the lifetimes of 20 and 240 μs. The last two components were fitted by a second order hyperbolic law. Time-resolved PCL spectra were recorded using time-windows corresponding to the PCL decay components. Paper discusses the reasonable interpretation of the CL emission bands.

Non-contrast-enhanced hepatic MR arteriography with balanced steady-state free-precession and time spatial labeling inversion pulse: optimization of the inversion time at 3 Tesla.

BackgroundA 3 Tesla (3 T) magnetic resonance (MR) scanner is a promising tool for upper abdominal angiography. However, no report has focused on the contrast behavior of non-contrast-enhanced hepatic MR arteriography at 3 T.PurposeTo establish the optimal inversion time (TI) for favorable selective visualization of the hepatic arteries on non-contrast-enhanced MR arteriography with time spatial labeling inversion pulse (Time-SLIP) at 3 T.Material and MethodsTwenty-five healthy volunteers were examined using respiratory-triggered three-dimensional balanced steady-state free-precession combined with Time-SLIP. According to the difference in the TI, five image groups (A, B, C, D, and E, from 1200 to 2000 ms, increasing at 200-ms intervals) were performed and compared to detect the optimal TI for hepatic artery visualization. The relative Cv-l (vessel-to-liver contrast) was quantified. For qualitative evaluation, the vessel visualization quality and order of the depicted hepatic artery branches were evaluated.ResultsIn group C (TI of 1600 ms), the Cv-l showed the highest probably due to a favorable balance between the hepatic vessel signal and signal recovery of the surrounding tissue. Regarding qualitative assessment, in group C, the mean image quality score of all hepatic arteries and mean maximal visible order of the hepatic artery branches were the highest. However, there was no significant difference between these results.ConclusionNon-contrast-enhanced hepatic MR arteriography with Time-SLIP at 3 T enabled the selective visualization of hepatic arteries at a TI of 1600 ms with an optimal balance between Cv-l and peripheral hepatic artery visualization.

Charge Separation and Catalytic Activity of Fe3 O4 @Ag "Nanospheres".

Nanospheres of Ag-coated Fe3 O4 were successfully synthesized and characterized. Photocatalytic properties of Fe3 O4 @Ag composites have been investigated using steady-state studies and laser pulse excitations. Accumulation of the electrons in the Ag shell was detected from the shift in the surface plasmon band from 430 to 405 nm, which was discharged when an electron acceptor such as O2 , Thionine (TH) or C60 was introduced into the system. Charge equilibration with redox couple such as C60 (●-) /C60 indicated the ability of these core-shell structures to carry out photocatalytic reduction reactions. As well, outer Ag layer could boost charge separation in magnetic core through dual effects of Schottky junction and localized surface plasmonic resonance (LSPR)-powered band gap breaking effect under sunlight irradiation; resulted in higher photocatalytic degradation of diphenylamine (DPA). The maximum photocatalytic degradation rate was achieved at optimum amount of Ag-NP loading to products. Adsorption studies confirmed that degradation of DPA dominantly occurred in solution. Moderately renewability of the nanocatalysts under sunlight was due to oxidation and dissolution of the outer Ag layer.

PH imaging of mouse kidneys in vivo using a frequency-dependent paraCEST agent.

This study explored the feasibility of using a pH responsive paramagnetic chemical exchange saturation transfer (paraCEST) agent to image the pH gradient in kidneys of healthy mice. CEST signals were acquired on an Agilent 9.4 Tesla small animal MRI system using a steady-state gradient echo pulse sequence after a bolus injection of agent. The magnetic field inhomogeneity across each kidney was corrected using the WASSR method and pH maps were calculated by measuring the frequency of water exchange signal arising from the agent. Dynamic CEST studies demonstrated that the agent was readily detectable in kidneys only between 4 to 12 min postinjection. The CEST images showed a higher signal intensity in the pelvis and calyx regions and lower signal intensity in the medulla and cortex regions. The pH maps reflected tissue pH values spanning from 6.0 to 7.5 in kidneys of healthy mice. This study demonstrated that pH maps of the kidney can be imaged in vivo by measuring the pH-dependent chemical shift of a single water exchange CEST peak without prior knowledge of the agent concentration in vivo. The results demonstrate the potential of using a simple frequency-dependent paraCEST agent for mapping tissue pH in vivo. Magn Reson Med 75:2432-2441, 2016. © 2015 Wiley Periodicals, Inc.

EAST Full Tungsten Divertor Design

One of the most important research goals of EAST concerns long steady-state high-performance plasma pulse. It is a fusion engineering challenge for divertor to handle steady-state high heat flux form plasma. To accomplish this aim, full tungsten divertor has been designed for EAST to withstand high heat flux which is increasing rapidly. Full tungsten divertor is an ITER-like design which consists of monoblock units, end boxes and cassette body. The newest divertor of EAST will withstand more than 10 MW/m2 heat flux in target zone. The full tungsten divertor should be reliable during plasma discharge campaign to reduce the failure risk of plasma components under critical thermal power from plasma. Analysis and experiment results proved full tungsten divertor of EAST will be very reliable for future long steady-state high-performance plasma pulse. The design and application of full tungsten divertor of EAST can also bring experiences and answers for ITER or any next divertor fusion device on nuclear phase.

97 Men and Women differ in their Adaptation to Aortic Stenosis and in Reverse Remodelling following Aortic Valve Intervention

<h3>Background</h3> Outcomes following aortic valve intervention may differ according to gender. It has been suggested that men and women adapt differently to aortic stenosis (AS) but the effect of gender on left ventricular (LV) remodelling following valve intervention is not well described. We sought to establish using cardiac magnetic resonance (CMR) imaging, the reference standard non-invasive technique for the assessment of LV mass (LVM) and function, whether there was any difference between genders in LV remodelling in severe AS at baseline and reverse remodelling six months following aortic valve intervention. <h3>Methods</h3> 100 patients (60 men) with symptomatic severe AS undergoing surgical or percutaneous aortic valve intervention were prospectively recruited between April 2009 and March 2014. Patients with contraindications to CMR were excluded and all patients provided informed written consent. All patients underwent an identical 1.5T CMR protocol (Intera, Philips) prior to and at a median of 6 months following aortic valve intervention (IQR 5–6 months). Multi slice, multiphase imaging was carried out using a standard steady-state free procession pulse sequence in axial and short axis to cover the entire left heart. Quantitative analysis was performed using dedicated computer software (CVI42, Circle Cardiovascular Imaging, Alberta, Canada). <h3>Results</h3> Basic demographic, clinical and echocardiographic data can be seen in Table 1. Women were older than men but were similar in terms of co-morbidity, surgical risk and valvular haemodynamics. At baseline, women had lower indexed LVM (LVMi) than men and a smaller indexed LV end diastolic volume (LVEDVi). Baseline LV ejection fraction (LVEF) and indexed left atrial volume (LAVi) were similar between sexes. Following valvular intervention, LVMi was significantly reduced in both sexes, however, this was more marked in men (18.28 ± 10.63 vs 12.69 ± 8.84, p = 0.007). There was an improvement in LV longitudinal function and a decrease in LAVi in men but not in women. Neither group experienced a significant change in LVEF following intervention (men 54.84 ± 12.94% to 56.52 ± 10.50%, p = 0.093; women 58.61 ± 10.57 to 60.20 ± 11.00, p = 0.129). Both groups also experienced a significant reduction in LVEDVi following valve intervention, with a trend towards a more pronounced reduction in men (men 11.55 ± 20.31 ml/m² vs women 5.39 ± 14.10 ml/m², p = 0.141). <h3>Conclusion</h3> Men and women with AS remodel differently with more hypertrophy and larger LV cavity size in men. Six months following valvular intervention, men but not women experience an improvement in LV longitudinal function and a decrease in left atrial size. These surrogate markers of a reduced left atrial pressure may be accounted for by the greater magnitude of LVM regression seen in men.

95 Left Ventricular Mass Regression Occurs very early following Transcatheter Aortic Valve Implantation for Severe Aortic Stenosis

<h3>Background</h3> The effect of transcatheter aortic valve replacement (TAVR) on very early left ventricular remodelling has not previously been evaluated. Left ventricular mass (LVM) regression at 30 days (assessed using echocardiography) has been linked to a 50% reduction in re-hospitalisation in the first year following TAVR. We sought to establish using cardiac magnetic resonance (CMR) imaging, the reference standard imaging technique for LVM quantification, whether LVM regression occurs very early following-TAVR. <h3>Methods</h3> 27 patients with symptomatic severe aortic stenosis undergoing TAVR were prospectively enrolled between June 2013 and April 2014. Patients with contraindications to CMR were excluded and all patients provided informed written consent. All patients underwent an identical 1.5T CMR protocol (Intera, Philips) prior to and at a median of 5 days following TAVR (IQR 2 days). Multislice, multi-phase cine imaging was carried out using a standard steady-state free procession pulse sequence in the short axis to cover the entire left ventricle. Quantitative analysis was performed using dedicated computer software (CVI⁴², Circle Cardiovascular Imaging, Alberta, Canada). LVM was calculated by the formula (epicardial volume – endocardial volume) x myocardial density (1.05 g/cm³). <h3>Results</h3> Basic patient, echocardiographic and procedural characteristics can be seen in Table 1. At a median of 5 days following TAVR, mean LVM regressed by 12% from 129.5 +/- 32.5 g to 114.2+/-31 g and indexed LVM (LVMi) reduced from 69.4 ± 15.2 g/m² to 61.3 ± 15.1 g/m²(Figure 1). There was no significant change in indexed left ventricular diastolic volume (96.9 ± 24.5 to 96.8 ± 19.3 ml/m², p = 0.79), LV ejection fraction (54.0 ± 14.6 to 58.4 ± 27.4%, p = 0.49) or indexed left atrial volume (71.5 ± 22.6 to 67.7 ± 22.1 ml/m², p = 0.43). Mean LVM regression was similar between the Medtronic and Boston valve types (14.3 ± 10.4 gVs 16.5 ± 9.9 g, p = 0.58). There was no correlation between Valvulo-arterial impedance (ZVA) and LVM regression (r = 0.02, p = 0.93). There was no difference in mean LVMi regression according to gender (women 8.3 ± 2.8 g/m² Vs men 8.0 ± 5.7 g/m², p = 0.83). TAVR valve size did not appear to impact on early LVM regression. LVMi regression was similar between those with a normal baseline LVM and those with an elevated baseline LVM (defined as 83 g/m² in men and 67 g/m²) in women (7.8 ± 4.8 g Vs 9.0 ± 5.7 g, p = 0.60). 16 patients had evidence of late gadolinium enhancement (LGE) at baseline. There was a trend towards increased LVMi regression in those without LGE at baseline compared with those with LGE (10.1 ± 4.7 g/m²Vs 6.4 ± 4.7 g/m², p = 0.07). <h3>Conclusions</h3> LVM regression begins very early following TAVR and occurs before changes in cavity size or ejection fraction which is likely to be a result of an immediate reduction in wall stress. The type of valve implanted does not appear to influence early LVM regression. <h3>Funding</h3> This study was part funded by the BHF (PG/11/126/29321).

Remote Detection of Ammonium Nitrate by Nuclear Quadrupole Resonance using a Portable System

This paper shows the advances in the development of a portable system for remote detection of ammonium nitrate by nuclear quadrupole resonance. Three different probe coils were constructed and compared in terms of the signal intensity and the noise rejection under different environments, using the developed system. For the gradiometer probe coil, which showed the best performance in terms of noise rejection, the ‘90°’ equivalent pulse was determined for different distances between the sample and the probe, and the remote detection of ammonium nitrate was achieved not only in a shielded room inside the laboratory, but also in the outdoors. The system was capable of detecting 200 g ammonium nitrate at 3 cm apart from the probe within 12 s with a steady-state free precession pulse sequence. The comparable results were obtained with a free induction decay sequence in 25 min for the total acquisition time. The compact size of the system will allow the applications for the substance detection in the outdoors especially for landmines made from ammonium nitrate and fuel oil mixtures instead of military explosives.

Rapid acquisition of helium-3 and proton three-dimensional image sets of the human lung in a single breath-hold using compressed sensing.

To develop and validate a method for acquiring helium-3 ((3) He) and proton ((1) H) three-dimensional (3D) image sets of the human lung with isotropic spatial resolution within a 10-s breath-hold by using compressed sensing (CS) acceleration, and to assess the fidelity of undersampled images compared with fully sampled images. The undersampling scheme for CS acceleration was optimized and tested using (3) He ventilation data. Rapid 3D acquisition of both (3) He and (1) H data during one breath-hold was then implemented, based on a balanced steady-state free-precession pulse sequence, by random undersampling of k-space with reconstruction by means of minimizing the L1 norm and total variance. CS-reconstruction fidelity was evaluated quantitatively by comparing fully sampled and retrospectively undersampled image sets. Helium-3 and (1) H 3D image sets of the lung with isotropic 3.9-mm resolution were acquired during a single breath-hold in 12 s and 8 s using acceleration factors of 2 and 3, respectively. Comparison of fully sampled and retrospectively undersampled (3) He and (1) H images yielded mean absolute errors <10% and structural similarity indices >0.9. By randomly undersampling k-space and using CS reconstruction, high-quality (3) He and (1) H 3D image sets with isotropic 3.9-mm resolution can be acquired within an 8-s breath-hold.

Extremely short vector solitons under the conditions of conical refraction

Propagation of extremely short electromagnetic pulses in a biaxial crystal under the conditions of conical refraction has been considered. The system of wave equations taking into account the dispersion contribution of the crystal lattice ions to the polarization response of the medium and a nonlinearity of the polarization response of electrons has been derived. It has been shown that under certain conditions this system can be reduced to an equation which is integrable by means of the inverse scattering transformation method. The proper Lax pair has been found. Physical analysis of the steady-state pulse solution of the system of wave equations has been performed.

Self-navigated isotropic three-dimensional cardiac T2 mapping.

To implement and characterize an isotropic three-dimensional cardiac T2 mapping technique. A self-navigated three-dimensional radial segmented balanced steady-state free precession pulse sequence with an isotropic 1.7-mm spatial resolution was implemented at 3T with a variable T2 preparation module. Bloch equation and Monte Carlo simulations were performed to determine the influence of the heart rate, B1 inhomogeneity and noise on the T2 fitting accuracy. In a phantom study, the accuracy of the pulse sequence was studied through comparison with a gold-standard spin-echo T2 mapping method. The robustness and homogeneity of the technique were ascertained in a study of 10 healthy adult human volunteers, while first results obtained in patients are reported. The numerical simulations demonstrated that the heart rate and B1 inhomogeneity cause only minor deviations in the T2 fitting, whereas the phantom study showed good agreement of the technique with the gold standard. The volunteer study demonstrated an average myocardial T2 of 40.5 ± 3.3 ms and a <15% T2 gradient in the base-apex and anterior-inferior direction. In three patients, elevated T2 values were measured in regions with expected edema. This respiratory self-navigated isotropic three-dimensional technique allows for accurate and robust in vitro and in vivo T2 quantification.

Nonenhanced renal MR angiography using steady-state free precession (SSFP) and time-spatial labeling inversion pulse (Time-SLIP): repeatability and comparison of different tagging location

To prospectively determine the repeatability of noncontrast-enhanced renal arterial angiography with steady-state free precession (SSFP) and time-spatial labeling inversion pulse (Time-SLIP), and to compare the visibility of renal artery and its branches when different locations of tagging pulse were placed. Thirty-six young healthy volunteers were enrolled in this study and were twice examined by noncontrast-enhanced renal arterial angiography with SSFP and Time-SLIP in 1.5T MR scanner. Measurement error and repeatability were assessed for each of the five major parameters [vessel-to-kidney ratio (VKR), grade of renal arterial branching, grading of image quality, diameter and area of the main renal artery] using the Bland-Altman plot. Two independent observers recorded the values of the parameters; Inter- and intra-observer agreement was assessed using the intraclass correlation coefficients (ICCs). The same parameters, acquired at the tagging pulse placed just above the superior poles of both kidneys or closer to the main renal arteries, were compared using the Wilcoxon signed-rank test. Grading of arterial branching by the Time-SLIP SSFP was satisfactorily reproducible with the mean score of greater 3.83 indicating the visibility of branches within the renal parenchyma. The image quality was excellent for Segment I (the main trunk of renal artery) and good for Segment II (segmental branches pre renal parenchyma) and III (vessels within the renal parenchyma) with a satisfying repeatability between two examinations and a good inter- and intra-observer agreement. The ICCs for the inter- and intra-observer measurements of both diameter and area of the main arteries ranged from 0.781 to 0.934, indicating very good agreement. The repeatability of VKR was poor between the two examinations and at the two different tagging pulse locations. The position of tagging pulse in the origination of the main renal arteries was better than in the superior poles of kidneys as it provided a better visualization of arterial branches. Noncontrast-enhanced renal artery angiography with SSFP and Time-SLIP yields reliable and reproducible visualization of normal renal arteries. Localization of the tagging pulse closer to the main renal arteries provides better visibility of renal artery and its branches than the tag placement just above the superior poles of both kidneys.

Quantifying direct and indirect effects of perturbations using model ecosystems

Indirect effects in ecosystems in response to perturbations remain a topic of much discussion. We continue on the theoretical path set by Nakajima and Higashi (1995, Indirect effects in ecological interaction networks (II): the conjugate variable approach. Mathematical Biosciences 130, 129–150) and extend their approach for quantifying indirect effects of press perturbations under steady-state conditions to pulse perturbations in steady state and to press and pulse perturbations under time-varying conditions. We illustrate with a commonly used lake ecosystem model how to estimate total, direct, and indirect effects on one species’ biomass (e.g., game fish) from perturbations to a second species (e.g., forage fish). We use the daily output of species biomasses from multi-year model simulations to test whether the computed total, direct, and indirect effects are equal for pulse and press perturbations of equal magnitude, and whether the types (pulse and press) and timing of perturbations alter the relative importance of indirect effects. Our results were consistent with the original theory of Nakajima and Higashi; under steady-state conditions, press and pulse perturbations to the forage fish produced similar effects on the game fish. Under these same conditions, indirect effects on the game fish were more than 3.5 times larger than the direct effects. Under time-varying conditions, all classes of pulse effects, but not press, depended on the day the perturbation was imposed. Indirect effects of pulse and press perturbations under time-varying conditions were always negative (offsetting) and of similar magnitude as the direct effects. When forage fish biomass was growing rapidly, the indirect effect on game fish biomass of a pulse perturbation was relatively smaller compared to the direct effect, whereas the indirect and direct effects were similar at other times. We consider the general implications of these results for the analysis of natural ecosystems.

Optimal Control of Medium-Voltage Drives—An Overview

Carrier modulation is the most common method for inverter control of ac drive systems. Operation at switching frequencies of several kilohertz is customary to restrain the harmonic distortion of the motor currents. Lower switching frequency is preferred for medium-voltage drives, owing to the higher switching losses of the semiconductor devices. This calls for optimizing the performance of the pulsewidth modulator. Improvements are achieved by abolishing carrier modulation with its equidistant time spacing of the voltage pulses. Optimal pulse patterns can be precalculated for every steady-state operating point of the drive. The patterns are stored in a memory of the drive system, from which they are retrieved and used for inverter control. Control at transient operation is achieved by adapting the optimal steady-state pulse patterns to the respective situation. Specific trajectories of the motor current space vector are then created by online optimization. An alternative method of online optimization relies on predicting the space vector trajectories for the next possible inverter switching states. The switching state that leads to minimum switching frequency is then selected. Optimal pulsewidth modulation reduces harmonic distortion. It permits operation at very low switching frequency and reduces the switching losses. This increases the current-carrying capability of the semiconductor devices to the extent that the power rating of an inverter approximately doubles.

Fluorescence and phosphorescence of rutin

Rutin is one of the most promising flavonoid from a pharmacological and biochemical point of view. Here we have explored its spectroscopic and photophysical properties at room temperature and 77K using steady-state absorption-luminescence methods and pulse spectroscopy equipment. By excitation into the absorption band 1 of rutin in methanol at room temperature the normal Stokes׳ shifted fluorescence with a maximum at 415nm and quantum yield of 2×10−4 was revealed. However, by excitation into the bands 2 and 3 any emission wasn’t observed. At 77K in ethanol glass we have observed fluorescence at 410nm and phosphorescence at 540nm for the first time. As a result the adequate energetic scheme including the lowest electronic excited singlet at 26000cm−1 and triplet at 19600cm−1 states was proposed.

Stages: Sub‐Fourier dynamic shim updating using nonlinear magnetic field phase preparation

Heterogeneity of the static magnetic field in magnetic resonance imaging may cause image artifacts and degradation in image quality. The field heterogeneity can be reduced by dynamically adjusting shim fields or dynamic shim updating, in which magnetic field homogeneity is optimized for each tomographic slice to improve image quality. A limitation of this approach is that a new magnetic field can be applied only once for each slice, otherwise image quality would improve somewhere to its detriment elsewhere in the slice. The motivation of this work is to overcome this limitation and develop a technique using nonlinear magnetic fields to dynamically shim the static magnetic field within a single Fourier-encoded volume or slice, called sub-Fourier dynamic shim updating. However, the nonlinear magnetic fields are not used as shim fields; instead, they impart a strong spatial dependence to the acquired MR signal by nonlinear phase preparation, which may be exploited to locally improve magnetic field homogeneity during acquisition. A theoretical description of the method is detailed, simulations and a proof-of-principle experiment are performed using a magnet coil with a known field geometry. The method is shown to remove artifacts associated with magnetic field homogeneity in balanced steady-state free-precession pulse sequences. We anticipate that this method will be useful to improve the quality of magnetic resonance images by removing deleterious artifacts associated with a heterogeneous static magnetic field.

Assessment of left and right ventricular parameters in healthy Korean volunteers using cardiac magnetic resonance imaging: change in ventricular volume and function based on age, gender and body surface area

The clinical utility of cardiac magnetic resonance imaging (CMR) is growing and is being used predominantly as a means of measuring ventricular function. The normal reference range of ventricular function may vary based on age, sex and ethnicity. At present, most CMR reference values for healthy individuals have been reported from Western countries. The intent of this study was to investigate the normal CMR reference range for left ventricular (LV) and right ventricular (RV) parameters in healthy Koreans. Healthy volunteers between the ages of 20-70years without any history of cardiovascular disease or associated risk factors were prospectively recruited to be a part of this study. A total of 124 patients were recruited for this study. Steady-state free precession pulse sequences were used to obtain the cine images for LV and RV volume analysis. All parameters were analyzed based on age and gender, and normalized to body surface area (BSA). LV volume, mass and cardiac output were significantly greater in males than in females. However, all of these parameters which are associated with BSA and gender differences disappeared when corrected for BSA. RV volume was less in females even after the data was normalized for BSA. LV and RV volumes normalized for BSA gradually decreased with greater age, whereas the ejection fraction increased with age, thus maintaining the stroke volume index and cardiac index. LV and RV volumes, mass and function values for a healthy population largely depend on BSA and should be evaluated after normalization by BSA. LV parameters show no difference based on gender, but RV volume is less in the female. Greater age is associated with less ventricular volume, suggesting the possibility of volume sensitivity in the elderly.

Fast and accurate methods for the performance testing of highly-efficient c-Si photovoltaic modules using a 10 ms single-pulse solar simulator and customized voltage profiles

Performance testing of highly efficient, highly capacitive c-Si modules with pulsed solar simulators requires particular care. These devices in fact usually require a steady-state solar simulator or pulse durations longer than 100–200 ms in order to avoid measurement artifacts. The aim of this work was to validate an alternative method for the testing of highly capacitive c-Si modules using a 10 ms single pulse solar simulator. Our approach attempts to reconstruct a quasi-steady-state I–V (current–voltage) curve of a highly capacitive device during one single 10 ms flash by applying customized voltage profiles–-in place of a conventional V ramp—to the terminals of the device under test. The most promising results were obtained by using V profiles which we name ‘dragon-back’ (DB) profiles. When compared to the reference I–V measurement (obtained by using a multi-flash approach with approximately 20 flashes), the DB V profile method provides excellent results with differences in the estimation of Pmax (as well as of Isc, Voc and FF) below ±0.5%. For the testing of highly capacitive devices the method is accurate, fast (two flashes—possibly one—required), cost-effective and has proven its validity with several technologies making it particularly interesting for in-line testing.

28-Day safety and tolerability of umeclidinium in combination with vilanterol in COPD: A randomized placebo-controlled trial

BackgroundUmeclidinium (UMEC; GSK573719) is a new long-acting muscarinic antagonist (LAMA) currently in development in combination with vilanterol (VI), an inhaled, long-acting beta2 agonist for the treatment of chronic obstructive pulmonary disease (COPD). The primary aim of this study was to evaluate the safety and tolerability of repeat dosing of UMEC and VI in combination once daily for 28 days in patients with COPD. MethodsThis was a multicenter, double-blind, placebo-controlled, parallel group study. Patients aged ≥40 years with post-bronchodilator FEV1 ≤80% of predicted normal values and FEV1/FVC ratio ≤0.70, and a smoking history of ≥10 pack-years, were randomized 4:1 to once-daily UMEC/VI (500/25 mcg; n = 42) or placebo (n = 9). ResultsUMEC/VI was non-inferior to placebo in weighted mean pulse rate over 0–6 h at Day 28 (primary endpoint: difference of −0.5 bpm, 95% CI: −5.5 to 4.5). There was no evidence of a difference between UMEC/VI compared with placebo in blood pressure, minimum and maximum pulse rate, or QTcF assessments. Adverse events (AEs) were reported by 11 (26%) patients in the UMEC/VI group and one (11%) patient in the placebo group. No serious AEs were reported. Both UMEC and VI showed rapid absorption (median tmax ∼6 min for both drugs) with no evidence of accumulation for AUC or Cmax on Day 28 compared with Day 1 for UMEC or VI. There was no correlation between individual steady-state Cmax and pulse rate on Day 28. Change from baseline in trough FEV1 on Day 29 showed numerically greater improvements with UMEC/VI compared with placebo. ConclusionOnce-daily dosing with UMEC in combination with VI in patients with moderate-to-very-severe COPD was well tolerated over 28 days.

Frequency-specific SSFP for hyperpolarized 13C metabolic imaging at 14.1 T

Metabolic imaging of hyperpolarized [1-13C] pyruvate co-polarized with [13C]urea by dynamic nuclear polarization with rapid dissolution is a promising new method for assessing tumor metabolism and perfusion simultaneously in vivo. Novel pulse sequences are required to enable dynamic imaging of multiple 13C spectral lines with high spatiotemporal resolution. The goal of this study was to investigate a new frequency-specific approach for rapid metabolic imaging of multiple 13C resonances using the spectral selectivity of steady-state free precession pulse (SSFP) trains. Methods developed in simulations were implemented in a dynamic frequency-cycled balanced SSFP pulse sequence on a 14.1-T animal magnetic resonance imaging scanner. This acquisition was tested in thermal and hyperpolarized phantom imaging studies and in a transgenic mouse with prostate cancer.