Evaluation of aortic stenosis severity using 4D flow jet shear layer detection for the measurement of valve effective orifice area

Aims

The objective of this study was to evaluate the potential of 4D flow MRI to assess valve effective orifice area (EOA) in patients with aortic stenosis as determined by the jet shear layer detection (JSLD) method.

Methods and Results

An in-vitro stenosis phantom was used for validation and in-vivo imaging was performed in 10 healthy controls and 40 patients with aortic stenosis. EOA was calculated by the JSLD method using standard 2D phase contrast MRI (PC-MRI) and 4D flow MRI measurements (EOA_JSLD-2D and EOA_JSLD-4D, respectively). As a reference standard, the continuity equation was used to calculate EOA (EOA_CE) with the 2D PC-MRI velocity field and compared to the EOA_JSLD measurements. The in-vitro results exhibited excellent agreement between flow theory (EOA = 0.78 cm²) and experimental measurement (EOA_JSLD-4D = 0.78 ± 0.01 cm²) for peak velocities ranging from 0.9 to 3.7 m/s. In-vivo results showed good correlation and agreement between EOA_JSLD-2D and EOA_CE (r = 0.91, p < 0.001; bias: − 0.01 ± 0.38 cm²; agreement limits: 0.75 to − 0.77 cm²), and between EOA_JSLD-4D and EOA_CE (r = 0.95, p < 0.001; bias: − 0.09 ± 0.26 cm²; limits: 0.43 to − 0.62 cm²).

Conclusion

This study demonstrates the feasibility of measuring EOA_JSLD using 4D flow MRI. The technique allows for optimization of the EOA measurement position by visualizing the 3D vena contracta, and avoids potential sources of EOA_CE measurement variability.     

Plate-based diversity subset screening: an efficient paradigm for high throughput screening of a large screening file

The screening files of many large companies, including Pfizer, have grown considerably due to internal chemistry efforts, company mergers and acquisitions, external contracted synthesis, or compound purchase schemes. In order to screen the targets of interest in a cost-effective fashion, we devised an easy-to-assemble, plate-based diversity subset (PBDS) that represents almost the entire computed chemical space of the screening file whilst comprising only a fraction of the plates in the collection. In order to create this file, we developed new design principles for the quality assessment of screening plates: the Rule of 40 (Ro40) and a plate selection process that insured excellent coverage of both library chemistry and legacy chemistry space. This paper describes the rationale, design, construction, and performance of the PBDS, that has evolved into the standard paradigm for singleton (one compound per well) high-throughput screening in Pfizer since its introduction in 2006.     

Repetitive single vortex-loop creation by a vibrating wire in superfluid 3He-B

Spectacular features are observed on the velocity-force characteristics of a vibrating wire resonator in superfluid 3He-B at ultralow temperatures. Both plateaus and discontinuities are seen in the characteristics. The plateaus seem to have two separate critical velocities where first some "event" occurs, which causes the wire to lose energy and slow down, followed by a second lower critical velocity where the event decouples. It is suggested that these events are due to vortex-loop creation at protuberances on the vibrating wire. This opens up the possibility of controlling the creation of vorticity through specially prepared protuberances.     

r-Process nucleosynthesis without excess neutrons

Matter expanding sufficiently rapidly and at high enough entropy per nucleon can enter a heavy-element synthesis regime heretofore unexplored. In this extreme regime, more similar to nucleosynthesis in the early universe than to that typical in stellar explosive environments, there is a persistent disequilibrium between free nucleons and abundant alpha particles, which allows heavy r-process nucleus production even in matter with more protons than neutrons. This observation bears on the issue of the site of the r process, on the variability of abundance yields from r-process events, and on constraints on neutrino physics derived from nucleosynthesis.     

On the topological charge concentrated at a point

For SU(2) gauge fields over the 4-dimensional sphere with a finite number of points x₁, x₂, ..., and x_N removed, there are gauge transformations which modify the topological charge concentrated at x_j by adding n_j, where n₁, n₂, …, and n_N. are integers such that Σ^N_{j = 1}n_j = 0. However, the reduction modulo Z of the topological charge at a point is well defined, being given in terms of the secondary characteristic classes of Chern and Simons, except when the topological charge is indeterminate.     

Megawatt VUV xenon laser employing coaxial electron-beam excitation

3 nsec laser pulses, of bandwidth 1.3 nm, are obtained from a 10 J, 600 keV coaxial diode electron-beam pumping arrangement. Uniform pumping, with a well defined cylindrical geometry, facilitates experimental investigation of the laser parameters. Gas heating limits the laser repetition rate. While mirror damage at present limits the peak power to ∽ 1 MW, higher powers seem available. The addition of helium results in a drastic reduction of peak molecular xenon fluorescence.     

Passive mode-locking of flashlamp pumped Rhodamine dye-lasers

A simple dye-laser system is described in which Rhodamine dyes are pumped by a co-axial linear air flashlamp in a cylindrical elliptical pumping reflector. Output pulses lasting up to 1.5sec and containing up to 250 mJ energy, have been successfully mode-locked to produce 100% modulated pulse trains. Employing a diffraction grating as cavity reflector to tune the laser frequency, in each case, for maximum absorption by the same Q-switching dye, successful mode-locking has been achieved with both Rhodamine B and Rhodamine 6G. Time resolved emission spectra have been recorded with an image tube streak camera and the effect of resonant reflectors has been studied.This work was described in a paper presented at the IEEE Conference on Laser Engineering and Applications, Washington, May 1969.     

Organo-imido alkoxides of tungsten(VI). The crystal and molecular structures of [W(NPh)(μ-OMe)(OMe)3]2 and [W(NPh)(OCMe3)3Cl(NH2CMe3)]

Reaction of phenylimido tungsten tetrachloride with MeOH and t-butylamine gave the dimeric complexes [W(NPh)(μ-OMe)(OMe)₃]₂ and [W(NPh)(μ-OMe)(OMe)₂Cl]₂. With ethanol [W(NPh)(μ-OEt)(OEt)₂Cl]₂ was formed whereas isopropyl and neopentyl alcohols gave the monomeric complexes [W(NPh)(OR)₄(NH₂CMe₃)](R = CHMe₂, CH₂CMe₃); t-butanol gave [W(NPh)(OCMe₃)3Cl(NH₂CMe₃)] which could not be converted to [W(NPh) (OCMe₃)₄]. Further reaction of [W(NPh)(μ-OMe)(OMe)₃]₂ with o-HOC₆H₄CH = NC₆H₃Me₂(salim-H) gave the salicylaldimine complex [W(NPh)(OMC)₃(salim)]. The products were characterised by analytical data, IR, ¹H NMR, ¹³C NMR and mass spectroscopy. The crystal and molecular structures of the title complexes have been determined from single crystal X-ray diffractometer data. Crystals of [W(NPh)(μ-OMe)(OMe)₃]₂are triclinic with a = 8.473(7), b = 10.776(5), c = 7.683(Å, α = 102.26(3), β = 102.68(4), γ = 71.13(6)°, space group P$\text{1}$ Crystals of 3) [W(NPh)(OCMe₃)₃Cl(NH₂CMe₃) are monoclinic with a = 9.341(2), b = 29.608(7), c = 10.257(2) Å, β = 106.28(2)°, space group, P2₁/c. Both structures were solved by Patterson and Fourier methods and refined to R = 0.075 for the 1022 observed data of [W(NPh) (μ-OMe)(OMe)₃]₂ and to R = 0.074. For the 2033 observed data of [W(NPh)(OCMe₃)₃Cl(NH₂CMe₃). The former molecule is shown to be a dimer, the two halves of the molecule being related by a centre of symmetry. Both W atoms adopt a distorted octahedral coordination geometry and they are linked by two methoxy bridges. Trans to one of the bridging donors is the phenyl imido group with a WN bond length of 1.61(4) Å; the remaining coordination sites are filled with methoxy groups. The structure of W(NPh)(OCMe₃)₃ Cl(NH₂CMe₃) is monomeric with the phenylimido group trans to the NH₂CMe₃ ligand in a distorted octahedral coordination geometry. Remaining sites are filled with the chloride and 3 OCMe₃ ligands. The WN (imido) bond length is 1.71(2) Å, whilst WN(amine) is 2.40(2) Å     

Dyad beads and the combinatorial discovery of catalysts

Dyad beads, bearing both a substrate and a catalyst, were prepared to enable direct split and mix bead based screening for catalysis.