Capillary interactions between soft capsules protruding through thin fluid films

When a suspension dries, the suspending fluid evaporates, leaving behind a dry film composed of the suspended particles. During the final stages of drying, the height of the fluid film on the substrate drops below the particle size, inducing local interface deformations that lead to strong capillary interactions among the particles. Although capillary interactions between rigid particles are well studied, much is still to be understood about the behaviour of soft particles and the role of their softness during the final stages of film drying. Here, we use our recently-introduced numerical method that couples a fluid described using the lattice Boltzmann approach to a finite element description of deformable objects to investigate the drying process of a film with suspended soft particles. Our measured menisci deformations and lateral capillary forces, which agree well with previous theoretical and experimental works in case of rigid particles, show the deformations become smaller with increasing particles softness, resulting in weaker lateral interaction forces. At large interparticle distances, the force approaches that of rigid particles. Finally, we investigate the time dependent formation of particle clusters at the late stages of the film drying

Mesoscale simulation of soft particles with tunable contact angle in multicomponent fluids

Soft particles at fluid interfaces play an important role in many aspects of our daily life, such as the food industry, paints and coatings, and medical applications. Analytical methods are not capable of describing the emergent effects of the complex dynamics of suspensions of many soft particles, whereas experiments typically either only capture bulk properties or require invasive methods. Computational methods are therefore a great tool to complement experimental work. However, an efficient and versatile numerical method is needed to model dense suspensions of many soft particles. In this article we propose a method to simulate soft particles in a multi-component fluid, both at and near fluid-fluid interfaces, based on the lattice Boltzmann method, and characterize the error stemming from the fluid-structure coupling for the particle equilibrium shape when adsorbed onto a fluid-fluid interface. Furthermore, we characterize the influence of the preferential contact angle of the particle surface and the particle softness on the vertical displacement of the center of mass relative to the fluid interface. Finally, we demonstrate the capability of our model by simulating a soft capsule adsorbing onto a fluid-fluid interface with a shear flow parallel to the interface, and the covering of a droplet suspended in another fluid by soft particles with different wettability.Comment: 16 pages, 14 figure

Green Tea catechins modulate skeletal development with effects dependent on dose, time, and structure in a Down syndrome mouse model

Altered skeletal development in Down syndrome (DS) results in a brachycephalic skull, flattened face, shorter mandibular ramus, shorter limbs, and reduced bone mineral density (BMD). Our previous study showed that low doses of green tea extract enriched in epigallocatechin-3-gallate (GTE-EGCG), administered continuously from embryonic day 9 to postnatal day 29, reduced facial dysmorphologies in the Ts65Dn (TS) mouse model of DS, but high doses could exacerbate them. Here, we extended the analyses to other skeletal structures and systematically evaluated the effects of high and low doses of GTE-EGCG treatment over postnatal development in wild-type (WT) and TS mice using in vivo µCT and geometric morphometrics. TS mice developed shorter and wider faces, skulls, and mandibles, together with shorter and narrower humerus and scapula, and reduced BMD dynamically over time. Besides facial morphology, GTE-EGCG did not rescue any other skeletal phenotype in TS treated mice. In WT mice, GTE-EGCG significantly altered the shape of the skull and mandible, reduced the length and width of the long bones, and lowered the BMD. The disparate effects of GTE-EGCG depended on the dose, developmental timepoint, and anatomical structure analyzed, emphasizing the complex nature of DS and the need to further investigate the simultaneous effects of GTE-EGCG supplementation

Current Anesthetic Care of Patients Undergoing Transcatheter Aortic Valve Replacement in Europe:Results of an Online Survey

Objectives: Transcatheter aortic valve replacement (TAVR) has become an alternative treatment for patients with symptomatic aortic stenosis not eligible for surgical valve replacement due to a high periprocedural risk or comorbidities. However, there are several areas of debate concerning the pre-, intra- and post-procedural management. The standards and management for these topics may vary widely among different institutions and countries in Europe. Design: Structured web-based, anonymized, voluntary survey. Setting: Distribution of the survey via email among members of the European Association of Cardiothoracic Anaesthesiology working in European centers performing TAVR between September and December 2018. Participants: Physicians. Measurements and main results: The survey consisted of 25 questions, including inquiries regarding number of TAVR procedures, technical aspects of TAVR, medical specialities present, preoperative evaluation of TAVR candidates, anesthesia regimen, as well as postoperative management. Seventy members participated in the survey. Reporting members mostly performed 151-to-300 TAVR procedures per year. In 90% of the responses, a cardiologist, cardiac surgeon, cardiothoracic anesthesiologist, and perfusionist always were available. Sixty-six percent of the members had a national curriculum for cardiothoracic anesthesia. Among 60% of responders, the decision for TAVR was made preoperatively by an interdisciplinary heart team with a cardiothoracic anesthesiologist, yet in 5 countries an anesthesiologist was not part of the decision-making. General anesthesia was employed in 40% of the responses, monitored anesthesia care in 44%, local anesthesia in 23%, and in 49% all techniques were offered to the patients. In cases of general anesthesia, endotracheal intubation almost always was performed (91%). It was stated that norepinephrine was the vasopressor of choice (63% of centers). Transesophageal echocardiography guiding, whether performed by an anesthesiologist or cardiologist, was used only Conclusion: The results indicated that requirements and quality indicators (eg, periprocedural anesthetic management, involvement of the anesthesiologist in the heart team, etc) for TAVR procedures as published within the European guideline are largely, yet still not fully implemented in daily routine. In addition, anesthetic TAVR management also is performed heterogeneously throughout Europe. (C) 2020 Elsevier Inc. All rights reserved

Characterization of a preclinical PET insert in a 7 tesla MRI scanner: beyond NEMA testing

[EN] This study evaluates the performance of the Bruker positron emission tomograph (PET) insert combined with a BioSpec 70/30 USR magnetic resonance imaging (MRI) scanner using the manufacturer acceptance protocol and the NEMA NU 4-2008 for small animal PET. The PET insert is made of 3 rings of 8 monolithic LYSO crystals (50 x 50 x 10 mm(3)) coupled to silicon photomultipliers (SiPM) arrays, conferring an axial and transaxial FOV of 15 cm and 8 cm. The MRI performance was evaluated with and without the insert for the following radiofrequency noise, magnetic field homogeneity and image quality. For the PET performance, we extended the NEMA protocol featuring system sensitivity, count rates, spatial resolution and image quality to homogeneity and accuracy for quantification using several MRI sequences (RARE, FLASH, EPI and UTE). The PET insert does not show any adverse effect on the MRI performances. The MR field homogeneity is well preserved (Diameter Spherical Volume, for 20 mm of 1.98 +/- 4.78 without and -0.96 +/- 5.16 Hz with the PET insert). The PET insert has no major effect on the radiofrequency field. The signal-to-noise ratio measurements also do not show major differences. Image ghosting is well within the manufacturer specifications (<2.5%) and no RF noise is visible. Maximum sensitivity of the PET insert is 11.0% at the center of the FOV even with simultaneous acquisition of EPI and RARE. PET MLEM resolution is 0.87 mm (FWHM) at 5 mm off-center of the FOV and 0.97 mm at 25 mm radial offset. The peaks for true/noise equivalent count rates are 410/240 and 628/486 kcps for the rat and mouse phantoms, and are reached at 30.34/22.85 and 27.94/22.58 MBq. PET image quality is minimally altered by the different MRI sequences. The Bruker PET insert shows no adverse effect on the MRI performance and demonstrated a high sensitivity, sub-millimeter resolution and good image quality even during simultaneous MRI acquisition.We acknowledge the KU Leuven core facility, Molecular Small Animal Imaging Center (MoSAIC), for their support with obtaining scientific data presented in this paper. This work was supported by Stichting tegen Kanker (2015-145, Christophe M. Deroose) and Hercules foundation (AKUL/13/029, Uwe Himmelreich) for the purchase of the PET and MRI equipment respectively. The work was supported by the following funding organizations: European Commission for the PANA project (H2020-NMP-2015-two-stage, grant 686009) and the European ERA-NET project 'CryptoView' (3rd call of the FP7 program Infect-ERA).Gsell, W.; Molinos, C.; Correcher, C.; Belderbos, S.; Wouters, J.; Junge, S.; Heidenreich, M.... (2020). Characterization of a preclinical PET insert in a 7 tesla MRI scanner: beyond NEMA testing. 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Seminars in Nuclear Medicine, 48(4), 332-347. doi:10.1053/j.semnuclmed.2018.02.011Maramraju, S. H., Smith, S. D., Junnarkar, S. S., Schulz, D., Stoll, S., Ravindranath, B., … Schlyer, D. J. (2011). Small animal simultaneous PET/MRI: initial experiences in a 9.4 T microMRI. Physics in Medicine and Biology, 56(8), 2459-2480. doi:10.1088/0031-9155/56/8/009Molinos, C., Sasser, T., Salmon, P., Gsell, W., Viertl, D., Massey, J. C., … Heidenreich, M. (2019). Low-Dose Imaging in a New Preclinical Total-Body PET/CT Scanner. Frontiers in Medicine, 6. doi:10.3389/fmed.2019.00088Nagy, K., Tóth, M., Major, P., Patay, G., Egri, G., Häggkvist, J., … Gulyás, B. (2013). Performance Evaluation of the Small-Animal nanoScan PET/MRI System. Journal of Nuclear Medicine, 54(10), 1825-1832. doi:10.2967/jnumed.112.119065Nanni, C., & Torigian, D. A. (2008). Applications of Small Animal Imaging with PET, PET/CT, and PET/MR Imaging. PET Clinics, 3(3), 243-250. doi:10.1016/j.cpet.2009.01.002Omidvari, N., Cabello, J., Topping, G., Schneider, F. R., Paul, S., Schwaiger, M., & Ziegler, S. I. (2017). PET performance evaluation of MADPET4: a small animal PET insert for a 7 T MRI scanner. Physics in Medicine & Biology, 62(22), 8671-8692. doi:10.1088/1361-6560/aa910dOmidvari, N., Topping, G., Cabello, J., Paul, S., Schwaiger, M., & Ziegler, S. I. (2018). MR-compatibility assessment of MADPET4: a study of interferences between an SiPM-based PET insert and a 7 T MRI system. Physics in Medicine & Biology, 63(9), 095002. doi:10.1088/1361-6560/aab9d1Raylman, R. R., Majewski, S., Lemieux, S. K., Velan, S. S., Kross, B., Popov, V., … Marano, G. D. (2006). Simultaneous MRI and PET imaging of a rat brain. Physics in Medicine and Biology, 51(24), 6371-6379. doi:10.1088/0031-9155/51/24/006Roncali, E., & Cherry, S. R. (2011). Application of Silicon Photomultipliers to Positron Emission Tomography. Annals of Biomedical Engineering, 39(4), 1358-1377. doi:10.1007/s10439-011-0266-9Schug, D., Lerche, C., Weissler, B., Gebhardt, P., Goldschmidt, B., Wehner, J., … Schulz, V. (2016). Initial PET performance evaluation of a preclinical insert for PET/MRI with digital SiPM technology. Physics in Medicine and Biology, 61(7), 2851-2878. doi:10.1088/0031-9155/61/7/2851Shao, Y., Cherry, S. R., Farahani, K., Meadors, K., Siegel, S., Silverman, R. W., & Marsden, P. K. (1997). Simultaneous PET and MR imaging. Physics in Medicine and Biology, 42(10), 1965-1970. doi:10.1088/0031-9155/42/10/010Steinert, H. C., & von Schulthess, G. K. (2002). Initial clinical experience using a new integrated in-line PET/CT system. The British Journal of Radiology, 75(suppl_9), S36-S38. doi:10.1259/bjr.75.suppl_9.750036Stortz, G., Thiessen, J. D., Bishop, D., Khan, M. S., Kozlowski, P., Retière, F., … Sossi, V. (2017). Performance of a PET Insert for High-Resolution Small-Animal PET/MRI at 7 Tesla. Journal of Nuclear Medicine, 59(3), 536-542. doi:10.2967/jnumed.116.187666Townsend, D. W. (2008). Combined Positron Emission Tomography–Computed Tomography: The Historical Perspective. Seminars in Ultrasound, CT and MRI, 29(4), 232-235. doi:10.1053/j.sult.2008.05.006Vandenberghe, S., & Marsden, P. K. (2015). PET-MRI: a review of challenges and solutions in the development of integrated multimodality imaging. Physics in Medicine and Biology, 60(4), R115-R154. doi:10.1088/0031-9155/60/4/r115Vaquero, J. J., & Kinahan, P. (2015). Positron Emission Tomography: Current Challenges and Opportunities for Technological Advances in Clinical and Preclinical Imaging Systems. Annual Review of Biomedical Engineering, 17(1), 385-414. doi:10.1146/annurev-bioeng-071114-040723Von Schulthess, G. K., & Schlemmer, H.-P. W. (2008). A look ahead: PET/MR versus PET/CT. 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Microbiome-based interventions to modulate gut ecology and the immune system

The gut microbiome lies at the intersection between the environment and the host, with the ability to modify host responses to disease-relevant exposures and stimuli. This is evident in how enteric microbes interact with the immune system, e.g., supporting immune maturation in early life, affecting drug efficacy via modulation of immune responses, or influencing development of immune cell populations and their mediators. Many factors modulate gut ecosystem dynamics during daily life and we are just beginning to realise the therapeutic and prophylactic potential of microbiome-based interventions. These approaches vary in application, goal, and mechanisms of action. Some modify the entire community, such as nutritional approaches or faecal microbiota transplantation, while others, such as phage therapy, probiotics, and prebiotics, target specific taxa or strains. In this review, we assessed the experimental evidence for microbiome-based interventions, with a particular focus on their clinical relevance, ecological effects, and modulation of the immune system

Extent of FLAIR Hyperintense Vessels May Modify Treatment Effect of Thrombolysis: A Post hoc Analysis of the WAKE-UP Trial

Background and Aims: Fluid-attenuated inversion recovery (FLAIR) hyperintense vessels (FHVs) on MRI are a radiological marker of vessel occlusion and indirect sign of collateral circulation. However, the clinical relevance is uncertain. We explored whether the extent of FHVs is associated with outcome and how FHVs modify treatment effect of thrombolysis in a subgroup of patients with confirmed unilateral vessel occlusion from the randomized controlled WAKE-UP trial. Methods: One hundred sixty-five patients were analyzed. Two blinded raters independently assessed the presence and extent of FHVs (defined as the number of slices with visible FHV multiplied by FLAIR slice thickness). Patients were then separated into two groups to distinguish between few and extensive FHVs (dichotomization at the median <30 or ≥30). Results: Here, 85% of all patients (n = 140) and 95% of middle cerebral artery (MCA) occlusion patients (n = 127) showed FHVs at baseline. Between MCA occlusion patients with few and extensive FHVs, no differences were identified in relative lesion growth (p = 0.971) and short-term [follow-up National Institutes of Health Stroke Scale (NIHSS) score; p = 0.342] or long-term functional recovery [modified Rankin Scale (mRS) p = 0.607]. In linear regression analysis, baseline extent of FHV (defined as a continuous variable) was highly associated with volume of hypoperfused tissue (β = 2.161; 95% CI 0.96-3.36; p = 0.001). In multivariable regression analysis adjusted for treatment group, stroke severity, lesion volume, occlusion site, and recanalization, FHV did not modify functional recovery. However, in patients with few FHVs, the odds for good functional outcome (mRS) were increased in recombinant tissue plasminogen activator (rtPA) patients compared to those who received placebo [odds ratio (OR) = 5.3; 95% CI 1.2-24.0], whereas no apparent benefit was observed in patients with extensive FHVs (OR = 1.1; 95% CI 0.3-3.8), p-value for interaction was 0.11. Conclusion: While the extent of FHVs on baseline did not alter the evolution of stroke in terms of lesion progression or functional recovery, it may modify treatment effect and should therefore be considered relevant additional information in those patients who are eligible for intravenous thrombolysis. Clinical Trial Registration: Main trial (WAKE-UP): ClinicalTrials.gov, NCT01525290; and EudraCT, 2011-005906-32. Registered February 2, 2012

Status Report and Beam Time Request for Experiment AD-4

Summary of current status and plans for October 200

Polypharmacy, functional outcome, and treatment effect of intravenous alteplase for acute ischemic stroke

Background: Polypharmacy is an important challenge in clinical practice. We aimed at determining the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischemic stroke. Methods: Post‐hoc analysis of the randomized, placebo‐controlled WAKE‐UP trial of MRI‐guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as intake of ≥5 medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favorable outcome defined by a score of 0‐1 on the modified Rankin Scale at 90 days. We used logistic regression analysis to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis. Results: Polypharmacy was present in 133/503 (26%) patients. Patients with polypharmacy were older (mean age 70 vs 64 years; P&lt;0.0001) and had a higher score on the National Institutes of Health Stroke Scale at baseline (median 7 vs 5; P=0.0007). A comorbidity load defined by a CCI score ≥2 was more frequent in patients with polypharmacy (48% vs 8%; P&lt;0.001). Polypharmacy was associated with lower odds of favorable outcome (adjusted odds ratio 0.50, 95% CI, 0.30‐0.85; P=0.0099), while the CCI score was not. Treatment with alteplase was associated with higher odds of favorable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, P=0.29). Conclusion: In stroke patients, polypharmacy is associated with worse functional outcome after intravenous thrombolysis independent of comorbidities. However, polypharmacy does not interact with the beneficial effect of alteplase

Clinical characteristics and outcome of patients with lacunar infarcts and concurrent embolic ischemic lesions

Purpose: Lacunar infarcts are thought to result from occlusion of small penetrating arteries due to microatheroma and lipohyalinosis, pathognomonic for cerebral small vessel disease (CSVD). Concurrent embolic ischemic lesions indicate a different stroke mechanism. The purpose of this study was to examine the clinical characteristics and outcome of patients with lacunar infarcts and concurrent embolic infarcts on diffusion-weighted imaging (DWI). Methods: All patients screened for the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290) were reviewed for acute lacunar infarcts and concurrent embolic lesions on baseline DWI. Clinical characteristics and outcome were compared between lacunar infarct patients with and without concurrent embolic lesions. Results: Of 244 patients with an acute lacunar infarct, 20 (8.2%) had concurrent acute embolic infarcts. Compared to patients with a lacunar infarct only, patients with concurrent embolic infarcts were older (mean age 69 years vs. 63 years; p = 0.031), more severely affected (median National Institutes of Health Stroke Scale [NIHSS] score 5 vs. 4; p = 0.046), and—among those randomized—had worse functional outcome at 90 days (median modified Rankin Scale [mRS] 3 vs. 1; p = 0.011). Conclusion: Approximately 8% of lacunar infarct patients show concurrent embolic lesions suggesting a stroke etiology other than CSVD. These patients are more severely affected and have a worse functional outcome illustrating the need for a thorough diagnostic work-up of possible embolic sources even in patients with an imaging-defined diagnosis of lacunar infarcts