Fourier transform spectroscopy and coupled-channel deperturbation treatment of the A1Sigma+ ~ b3Pi complex of KCs molecule

The laser induced fluorescence (LIF) spectra A1Sigma ~ b3Pi --> X1Sigma+ of KCs dimer were recorded in near infrared region by Fourier Transform Spectrometer with a resolution of 0.03 cm-1. Overall more than 200 LIF spectra were rotationally assigned to 39K133Cs and 41K133Cs isotopomers yielding with the uncertainty of 0.003-0.01 cm-1 more than 3400 rovibronic term values of the strongly mixed singlet A1Sigma+ and triplet b3Pi states. Experimental data massive starts from the lowest vibrational level v_A=0 of the singlet and nonuniformly cover the energy range from 10040 to 13250 cm-1 with rotational quantum numbers J from 7 to 225. Besides of the dominating regular A1Sigma+ ~ b3P Omega=0 interactions the weak and local heterogenous A1S+ ~ b3P Omega=1 perturbations have been discovered and analyzed. Coupled-channel deperturbation analysis of the experimental 39K133Cs e-parity termvalues of the A1S+ ~ b3P complex was accomplished in the framework of the phenomenological 4 x 4 Hamiltonian accounting implicitly for regular interactions with the remote states manifold. The resulting diabatic potential energy curves of the interacting states and relevant spin-orbit coupling matrix elements defined analytically by Expanded Morse Oscillators model reproduce 95% of experimental data field of the 39K133Cs isotopomer with a standard deviation of 0.004 cm-1 which is consistent with the uncertainty of the experiment. Reliability of the derived parameters was additionally confirmed by a good agreement between the predicted and experimental termvalues of 41K133Cs isotopomer. Calculated intensity distributions in the A ~ b --> X LIF progressions are also consistent with their experimental counterparts.Comment: 17 pages, 14 figure

Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF). a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study

Background: Direct-acting oral anticoagulant use for stroke prevention in atrial fibrillation is limited by bleeding concerns. Asundexian, a novel, oral small molecule activated coagulation factor XIa (FXIa) inhibitor, might reduce thrombosis with minimal effect on haemostasis. We aimed to determine the optimal dose of asundexian and to compare the incidence of bleeding with that of apixaban in patients with atrial fibrillation. Methods: In this randomised, double-blind, phase 2 dose-finding study, we compared asundexian 20 mg or 50 mg once daily with apixaban 5 mg twice daily in patients aged 45 years or older with atrial fibrillation, a CHA2DS2-VASc score of at least 2 if male or at least 3 if female, and increased bleeding risk. The study was conducted at 93 sites in 14 countries, including 12 European countries, Canada, and Japan. Participants were randomly assigned (1:1:1) to a treatment group using an interactive web response system, with randomisation stratified by whether patients were receiving a direct-acting oral anticoagulant before the study start. Masking was achieved using a double-dummy design, with participants receiving both the assigned treatment and a placebo that resembled the non-assigned treatment. The primary endpoint was the composite of major or clinically relevant non-major bleeding according to International Society on Thrombosis and Haemostasis criteria, assessed in all patients who took at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT04218266, and EudraCT, 2019-002365-35. Findings: Between Jan 30, 2020, and June 21, 2021, 862 patients were enrolled. 755 patients were randomly assigned to treatment. Two patients (assigned to asundexian 20 mg) never took any study medication, resulting in 753 patients being included in the analysis (249 received asundexian 20 mg, 254 received asundexian 50 g, and 250 received apixaban). The mean age of participants was 73·7 years (SD 8·3), 309 (41%) were women, 216 (29%) had chronic kidney disease, and mean CHA2DS2-VASc score was 3·9 (1·3). Asundexian 20 mg resulted in 81% inhibition of FXIa activity at trough concentrations and 90% inhibition at peak concentrations; asundexian 50 mg resulted in 92% inhibition at trough concentrations and 94% inhibition at peak concentrations. Ratios of incidence proportions for the primary endpoint were 0·50 (90% CI 0·14–1·68) for asundexian 20 mg (three events), 0·16 (0·01–0·99) for asundexian 50 mg (one event), and 0·33 (0·09–0·97) for pooled asundexian (four events) versus apixaban (six events). The rate of any adverse event occurring was similar in the three treatment groups: 118 (47%) with asundexian 20 mg, 120 (47%) with asundexian 50 mg, and 122 (49%) with apixaban. Interpretation: The FXIa inhibitor asundexian at doses of 20 mg and 50 mg once daily resulted in lower rates of bleeding compared with standard dosing of apixaban, with near-complete in-vivo FXIa inhibition, in patients with atrial fibrillation. Funding: Bayer