Lunar plume-surface interactions using rarefiedMultiphaseFoam

Understanding plume-surface interactions is essential to the design of lander modules and potential bases on bodies such as the Moon, as it is important to predict erosion patterns on the surface and the transport of the displaced regolith material. Experimentally, it is difficult to replicate the extra-terrestrial conditions (e.g. the effects of reduced gravity). Existing numerical tools have limited accessibility and different levels of sophistication in the modelling of regolith entrainment and subsequent transport. In this work, a fully transient open source code for solving rarefied multiphase flows, rarefiedMultiphaseFoam, is updated with models to account for solid-solid interactions and applied to rocket exhaust plume-lunar regolith interactions. Two different models to account for the solid-solid collisions are considered; at relatively low volume fractions, a stochastic collision model, and at higher volume fractions the higher fidelity multiphase particle-in-cell (MPPIC) method. Both methods are applied to a scaled down version of the Apollo era lunar module descent engine and comparisons are drawn between the transient simulation results. It is found that the transient effects are important for the gas phase, with the shock structure and stand-off height changing as the regolith is eroded by the plume. Both models predict cratering at early times and similar dispersion characteristics as the viscous erosion becomes dominant. In general, the erosion processes are slower with the multiphase particle-in-cell method because it accounts for more physical effects, such as enduring contacts and a maximum packing limit. It is found that even if the initial volume fraction is low, the stochastic collision method can become unreliable as the plume impinges on the surface and compresses the regolith particles, invalidating the method’s assumption of only binary collisions. Additionally, it is shown that the breakdown of the locally free-molecular flow assumption that is used to calculate the drag and heat transfer on the solid particles has a strong influence on the temperatures that the solid particles obtain

Enthesis tissue engineering: biological requirements meet at the interface

Tendon-to-bone interface (enthesis) exhibits a complex multiscale architectural and compositional organization maintained by a heterogeneous cellular environment. Orthopedic surgeons have been facing several challenges when treating tendon pullout or tear from the bony insertion due to unsatisfactory surgical outcomes and high retear rates. The limited understanding of enthesis hinders the development of new treatment options toward enhancing regeneration. Mimicking the natural tissue structure and composition is still a major challenge to be overcome. In this review, we critically assess current tendon-to-bone interface tissue engineering strategies through the use of biological, biochemical, or biophysical cues, which must be ultimately combined into sophisticated gradient systems. Cellular strategies are described, focusing on cell sources and cocultures to emulate a physiological heterotypic niche, as well as hypoxic environments, alongside with growth factor delivery and the use of platelet-rich hemoderivatives. Biomaterial design considerations are revisited, highlighting recent progresses in tendon-to-bone scaffolds. Mechanical loading is addressed to uncover prospective engineering advances. Finally, research challenges and translational aspects are considered. In summary, we highlight the importance of deeply investigating enthesis biology toward establishing foundational expertise and integrate cues from the native niche into novel biomaterial engineering, aiming at moving today's research advances into tomorrow's regenerative therapies.Authors thank the support from the European Union Framework Programme for Research and Innovation HORIZON2020 [TEAMING Grant agreement No 739572 - The Discoveries CTR]; FCT–Fundação para a Ciência e a Tecnologia for the PhD grant of IC [PD/BD/128088/2016]; the Project NORTE-01-0145-FEDER-000021:“Accelerating tissue engineering and personalized medicine discoveries by the integration of key enabling nanotechnologies, marine-derived biomaterials and stem cells”, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and the ERC Consolidator grant of ME [ERC-2017-CoG-772817]

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Real Time Measurement of PEG Shedding from Lipid Nanoparticles in Serum via NMR Spectroscopy

Small interfering RNA (siRNA) is a novel therapeutic modality that benefits from nanoparticle mediated delivery. The most clinically advanced siRNA-containing nanoparticles are polymer-coated supramolecular assemblies of siRNA and lipids (lipid nanoparticles or LNPs), which protect the siRNA from nucleases, modulate pharmacokinetics of the siRNA, and enable selective delivery of siRNA to target cells. Understanding the mechanisms of assembly and delivery of such systems is complicated by the complexity of the dynamic supramolecular assembly as well as by its subsequent interactions with the biological milieu. We have developed an ex vivo method that provides insight into how LNPs behave when contacted with biological fluids. Pulsed gradient spin echo (PGSE) NMR was used to directly measure the kinetics of poly(ethylene) glycol (PEG) shedding from siRNA encapsulated LNPs in rat serum. The method represents a molecularly specific, real-time, quantitative, and label-free way to monitor the behavior of a nanoparticle surface coating. We believe that this method has broad implications in gaining mechanistic insights into how nanoparticle-based drug delivery vehicles behave in biofluids and is versatile enough to be applied to a diversity of systems