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We conducted a phase I clinical trial of H3B-8800, an oral small molecule that binds Splicing Factor 3B1 (SF3B1), in patients with MDS, CMML, or AML. Among 84 enrolled patients (42 MDS, 4 CMML and 38 AML), 62 were red blood cell (RBC) transfusion dependent at study entry. Dose escalation cohorts examined two once-daily dosing regimens: schedule I (5 days on/9 days off, range of doses studied 1-40 mg, n = 65) and schedule II (21 days on/7 days off, 7-20 mg, n = 19); 27 patients received treatment for ≥180 days. The most common treatment-related, treatment-emergent adverse events included diarrhea, nausea, fatigue, and vomiting. No complete or partial responses meeting IWG criteria were observed; however, RBC transfusion free intervals >56 days were observed in nine patients who were transfusion dependent at study entry (15%). Of 15 MDS patients with missense SF3B1 mutations, five experienced RBC transfusion independence (TI). Elevated pre-treatment expression of aberrant transcripts of Transmembrane Protein 14C (TMEM14C), an SF3B1 splicing target encoding a mitochondrial porphyrin transporter, was observed in MDS patients experiencing RBC TI. In summary, H3B-8800 treatment was associated with mostly low-grade TAEs and induced RBC TI in a biomarker-defined subset of MDS.

To study the stern vibration characteristics of the ship sailing in still water under the action of propeller induced pressure fluctuation, the propeller self-propulsion numerical simulation was conducted based on the Reynolds-averaged Navier-Stokes (RANS) method, in combination with the shear-stress transport (SST) k-ω model. Taking the obtained fluctuating pressure on the hull surface as the external excitation, the acoustic-structure coupling calculation was performed through the structural finite element model coupled with the flow field boundary element model, and a numerical prediction method for the stern vibration of the self-propulsion ship excited by the propeller surface force was established. By analyzing the fluctuating pressure characteristics in the time domain and frequency domain, it is found that the amplitude of the blade frequency component is much larger than that of other frequency components. For the right-handed propeller, the starboard side pressure amplitude above the propeller is higher than that on the port side. The analysis of the corresponding relationship between the propeller fluctuating pressure, the structural inherent characteristics, and the vibration response shows that the coupled mode natural frequency should be far away from the propeller excitation force frequency to reduce the vibration response. The exploration of the effect of modifying stern structure on the vibration response at the same excitation indicates that increasing the plate thickness or installing stiffeners can change the inherent characteristics of the structure, thus avoiding resonance and achieving the vibration reduction effect.

By solving Reynolds-Averaged Navier–Stokes equations with the shear stress transport k–ω turbulence model, the two-dimensional wake of a flapping hydrofoil turbine near a wall was studied, including evolution of vortices, spatial distribution of velocity, time-averaged and time-varying characteristics of the flow field. A custom adaptive mesh refinement approach was used for vortex simulations. Unlike the double-row configuration wake behind a flapping hydrofoil turbine in no near-wall situation, the wake of a flapping hydrofoil turbine near a wall shows an approximate single-row vortex pattern, which makes the wake energy more concentrated and beneficial for recovery by downstream turbines. As the near-wall spacing decreases, the intensity of vortices gradually increases, but the change in the degree of vortex diffusion toward the side is non-monotonic. Especially, due to the continuous diffusion of vortices to the side, several equally spaced velocity recovery zones are formed near the centerline, which improves the conditions for energy recovering. As the pitching amplitude increases, the degree of vortex diffusion to the side monotonically decreases; the intensity of vortices increases, which exacerbates the unevenness of velocity field. As the motion frequency increases, the degree of vortex diffusion monotonically increases, the velocity attenuation is more severe, and the trajectories of all vortices become increasingly consistent. Anyway, the velocity intensification stabilization and fluctuation zones in the wake are the top two choices for installing downstream turbines. The study expands our understanding of the wake of a flapping hydrofoil turbine and can provide reference for improving the power of downstream turbines. [ABSTRACT FROM AUTHOR]

Author(s): Michael Seiler [1]; Akihide Yoshimi [2]; Rachel Darman [1]; Betty Chan [1]; Gregg Keaney [1]; Michael Thomas [1]; Anant A Agrawal [1]; Benjamin Caleb [1]; Alfredo Csibi [1]; Eckley [...]

Aim: To evaluate the level of diabetes knowledge and related influencing factors among Chinese orthopaedic nurses. Design: A cross‐sectional observational study. The STROBE checklist was followed. Methods: A convenience sampling method was adopted by using the Questionnaire Star application to publish online questionnaire. The nurses' diabetes knowledge levels were assessed, including a total of 34 items from the "Orthopaedic Nurses Diabetes Knowledge Mastery Questionnaire" and the "Orthopaedic Nurses General Information Questionnaire" between July 2020 and September 2020. Results: Altogether, 363 nurses participated in the survey. Their levels of diabetes‐related knowledge were moderate or lower (16.51 ± 2.96 out of 25 points). The knowledge level was closely related to five factors: professional title, education level, whether the hospital employed diabetes specialist nurses or treated outpatients, type of diabetes‐related training received and whether the individual was familiar with and adhered to current treatment guidelines. The knowledge level can be improved by providing additional training that accounts for these factors. [ABSTRACT FROM AUTHOR]