On the Random Conjugate Spaces of a Random Locally Convex Module

Theoretically speaking, there are four kinds of possibilities to define the random conjugate space of a random locally convex module. The purpose of this paper is to prove that among the four kinds there are only two which are universally suitable for the current development of the theory of random conjugate spaces: in this process we also obtain a somewhat surprising and crucial result that for a random normed module with base $(\Omega,{\cal F},P)$ such that $(\Omega,{\cal F},P)$ is nonatomic then the random normed module is a totally disconnected topological space when it is endowed with the locally $L^{0}-$convex topology.Comment: 10 page

Sex‐specific activation of SK current by isoproterenol facilitates action potential triangulation and arrhythmogenesis in rabbit ventricles

Sex has a large influence on cardiac electrophysiological properties. Whether sex differences exist in apamin‐sensitive small conductance Ca2+‐activated K+ (SK) current (IKAS) remains unknown. We performed optical mapping, transmembrane potential, patch clamp, western blot and immunostaining in 62 normal rabbit ventricles, including 32 females and 30 males. IKAS blockade by apamin only minimally prolonged action potential (AP) duration (APD) in the basal condition for both sexes, but significantly prolonged APD in the presence of isoproterenol in females. Apamin prolonged APD at the level of 25% repolarization (APD25) more prominently than APD at the level of 80% repolarization (APD80), consequently reversing isoproterenol‐induced AP triangulation in females. In comparison, apamin prolonged APD to a significantly lesser extent in males and failed to restore the AP plateau during isoproterenol infusion. IKAS in males did not respond to the L‐type calcium current agonist BayK8644, but was amplified by the casein kinase 2 (CK2) inhibitor 4,5,6,7‐tetrabromobenzotriazole. In addition, whole‐cell outward IKAS densities in ventricular cardiomyocytes were significantly larger in females than in males. SK channel subtype 2 (SK2) protein expression was higher and the CK2/SK2 ratio was lower in females than in males. IKAS activation in females induced negative intracellular Ca2+–voltage coupling, promoted electromechanically discordant phase 2 repolarization alternans and facilitated ventricular fibrillation (VF). Apamin eliminated the negative Ca2+–voltage coupling, attenuated alternans and reduced VF inducibility, phase singularities and dominant frequencies in females, but not in males. We conclude that β‐adrenergic stimulation activates ventricular IKAS in females to a much greater extent than in males. IKAS activation plays an important role in ventricular arrhythmogenesis in females during sympathetic stimulation

The Effect of Lenalidomide on Health-Related Quality of Life in Patients With Lower-Risk non-del(5q) Myelodysplastic Syndromes: Results From the MDS-005 Study

Abstract Background The phase III MDS-005 study compared lenalidomide versus placebo in red blood cell transfusion-dependent (RBC-TD) patients with lower-risk non-del(5q) myelodysplastic syndromes (MDS), ineligible/refractory to erythropoiesis-stimulating agents. Lenalidomide-treated patients were more likely to achieve transfusion independence (TI) ≥ 8 weeks (26.9% vs. 2.5%; P Patients and Methods Patients were randomized 2:1 to oral lenalidomide 10 mg once daily or placebo once daily (both on 28-day cycles). Patients with creatinine clearance 40 to 60 mL/min were given lenalidomide 5 mg once daily. Health-related quality of life (HRQoL), a predefined secondary end point, was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 questionnaire at baseline, week 12, week 24, every 12 weeks thereafter, and at discontinuation. Results At week 24, lenalidomide was associated with benefit versus placebo across all 5 preselected questionnaire scales (fatigue, dyspnea, global quality of life, physical functioning, and emotional functioning). After adjustment for baseline scores, only emotional functioning achieved significance ( P = .047). Further improvement versus baseline was observed for patients who continued lenalidomide after week 24. In post hoc analyses, achievement of TI ≥ 8 weeks was associated with significant improvements across all scales ( P P Conclusion Lenalidomide did not adversely affect HRQoL in RBC-TD patients with lower-risk non-del(5q) MDS and response to lenalidomide was associated with significant improvements in HRQoL

Treatment Satisfaction and Convenience for Patients With Atrial Fibrillation on Edoxaban or Vitamin K Antagonists After Transcatheter Aortic Valve Replacement:A Post Hoc Analysis from the ENVISAGE-TAVI AF Trial

ENVISAGE-TAVI AF (Edoxaban versus Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation–Atrial Fibrillation; NCT02943785) was a prospective, randomized, open-label trial comparing non–vitamin K oral anticoagulant (NOAC) edoxaban with vitamin K antagonists (VKAs) in patients with atrial fibrillation after successful transcatheter aortic valve replacement (TAVR). The effect of edoxaban- or VKA-based therapy on patient-reported outcomes remains unknown, as most studies focus on efficacy and safety. Pre-TAVR patient-reported expectations and post-TAVR Treatment Satisfaction and Convenience with edoxaban or VKA treatment (at months 3 and 12) were analyzed using the Perception of Anticoagulation Treatment Questionnaire (PACT-Q). This analysis included randomized and dosed patients with an evaluable PACT-Q1 assessment at baseline and ≥1 postbaseline assessment (PACT-Q2). Subanalyses included patients stratified by pre-TAVR anticoagulant (NOAC, VKA, no NOAC/VKA). Edoxaban- (n = 585) and VKA-treated (n = 522) patients had similar baseline characteristics and treatment expectations. Pre-TAVR anticoagulant use did not affect treatment expectations. After TAVR, edoxaban-treated patients had significantly higher Treatment Satisfaction and Convenience scores compared with VKA-treated patients at all time points (p &lt;0.001 for all). Among edoxaban-treated patients, those who received VKAs pre-TAVR were significantly more satisfied with treatment than those who received NOACs (p &lt;0.001) or no NOACs/VKAs (p = 0.003); however, there was no significant difference in the perception of convenience (p = 0.927 and p = 0.092, respectively). Conversely, among VKA-treated patients, the type of anticoagulant used pre-TAVR did not affect Treatment Satisfaction or Convenience scores post-TAVR. In conclusion, patients with atrial fibrillation who received edoxaban post-TAVR reported significantly higher Treatment Satisfaction and Convenience scores compared with those who received VKAs, resulting in a clinically meaningful difference between treatment groups.</p

Exploration of growth conditions of TaAs Weyl semimetal thin film by pulsed laser deposition

TaAs, the first experimentally discovered Weyl semimetal material, has attracted a lot of attention due to its high carrier mobility, high anisotropy, nonmagnetic and strong interaction with light. These make it an ideal candidate for the study of Weyl fermions and the applications in quantum computation, thermoelectric devices, and photodetection. For further basic physics studies and potential applications, large-size and high-quality TaAs films are urgently needed. However, it is difficult to grow As-stoichiometry TaAs films due to the volatilization of As during the growth. To solve this problem, the TaAs films were attempted to grow on different substrates using targets with different As stoichiometric ratios by pulsed laser deposition (PLD). In this work, we have found that partial As ions of the GaAs substrate are likely to diffuse into the TaAs films during growth, which was preliminarily confirmed by the structural characterization, surface topography and composition analysis. As a result, the As content in the TaAs film is improved and the TaAs phase is achieved. Our work presents an effective method to fabricate the TaAs films by PLD, providing the possible use of the Weyl semimetal film for functional devices

Concomitant SK current activation and sodium current inhibition cause J wave syndrome

The mechanisms of J wave syndrome (JWS) are incompletely understood. Here, we showed that the concomitant activation of small-conductance calcium-activated potassium (SK) current (IKAS) and inhibition of sodium current by cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) recapitulate the phenotypes of JWS in Langendorff-perfused rabbit hearts. CyPPA induced significant J wave elevation and frequent spontaneous ventricular fibrillation (SVF), as well as sinus bradycardia, atrioventricular block, and intraventricular conduction delay. IKAS activation by CyPPA resulted in heterogeneous shortening of action potential (AP) duration (APD) and repolarization alternans. CyPPA inhibited cardiac sodium current (INa) and decelerated AP upstroke and intracellular calcium transient. SVFs were typically triggered by short-coupled premature ventricular contractions, initiated with phase 2 reentry and originated more frequently from the right than the left ventricles. Subsequent IKAS blockade by apamin reduced J wave elevation and eliminated SVF. β-Adrenergic stimulation was antiarrhythmic in CyPPA-induced electrical storm. Like CyPPA, hypothermia (32.0°C) also induced J wave elevation and SVF. It facilitated negative calcium-voltage coupling and phase 2 repolarization alternans with spatial and electromechanical discordance, which were ameliorated by apamin. These findings suggest that IKAS activation contributes to the development of JWS in rabbit ventricles