Computational modelling of emboli travel trajectories in cerebral arteries: Influence of microembolic particle size and density

This article has been made available through the Brunel Open Access Publishing Fund.Ischaemic stroke is responsible for up to 80 % of stroke cases. Prevention of the reoccurrence of ischaemic attack or stroke for patients who survived the first symptoms is the major treatment target. Accurate diagnosis of the emboli source for a specific infarction lesion is very important for a better treatment for the patient. However, due to the complex blood flow patterns in the cerebral arterial network, little is known so far of the embolic particle flow trajectory and its behaviour in such a complex flow field. The present study aims to study the trajectories of embolic particles released from carotid arteries and basilar artery in a cerebral arterial network and the influence of particle size, mass and release location to the particle distributions, by computational modelling. The cerebral arterial network model, which includes major arteries in the circle of Willis and several generations of branches from them, was generated from MRI images. Particles with diameters of 200, 500 and 800 μ m and densities of 800, 1,030 and 1,300 kg/m 3 were released in the vessel's central and near-wall regions. A fully coupled scheme of particle and blood flow in a computational fluid dynamics software ANASYS CFX 13 was used in the simulations. The results show that heavy particles (density large than blood or a diameter larger than 500 μ m) normally have small travel speeds in arteries; larger or lighter embolic particles are more likely to travel to large branches in cerebral arteries. In certain cases, all large particles go to the middle cerebral arteries; large particles with higher travel speeds in large arteries are likely to travel at more complex and tortuous trajectories; emboli raised from the basilar artery will only exit the model from branches of basilar artery and posterior cerebral arteries. A modified Circle of Willis configuration can have significant influence on particle distributions. The local branch patterns of internal carotid artery to middle cerebral artery and anterior communicating artery can have large impact on such distributions. © 2014 The Author(s)

Clamp-on measurements of fluid flow in small-diameter metal pipes using ultrasonic guided waves

Clamp-on ultrasonic transit time difference is used extensively to calculate the volumetric flow rate of a fluid through a pipe. The operating principle is that waves traveling along a path that is generally against the flow direction take longer to travel the same path than waves traveling along the same path in the opposite direction. The transit time difference between the waves traveling in opposite directions can be used to calculate the flow rate through the pipe, by applying suitable mathematical correction factors. The approach is non-disruptive and noninvasive and can be retrospectively fit to pipes and easily relocated to different positions. When ultrasonic clamp-on transducers are attached to pipes with diameters of less than 30 mm and a wall thickness of less than a few millimeters, the resulting guided waves can appear confusing and produce very different signals to those observed on larger diameter pipes. The experimentally observed behavior of these guided waves in fluid-filled, small-diameter pipes is analyzed, modeled, and explained. Experiments are performed in copper pipes of sizes that are commonly used in buildings, and accurate measurements of water flow rates are taken down to a few milliliters per second. This technique presents new possibilities for smart metering of water supplies, where the positioning of the small clamp-on transducers is not sensitive to the variations in water temperature, and low-power electronics can be used

Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib

Objectives: In a phase Ib trial, afatinib plus cetuximab demonstrated promising clinical activity (objective response rate [ORR]: 29%; median progression-free survival [PFS]: 4.7 months) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with acquired resistance to erlotinib or gefitinib. Here, a separate cohort exploring afatinib plus cetuximab after progression on afatinib is reported. Materials and methods: Patients with EGFR mutation-positive NSCLC who progressed on erlotinib or gefitinib received afatinib 40 mg daily until progression, followed by afatinib daily plus cetuximab 500 mg/m(2) every 2 weeks until progression or intolerable adverse events (AEs). Endpoints included safety, ORR, and PFS. Results: Thirty-seven patients received afatinib monotherapy. Two (5%) patients responded; median PFS was 2.7 months. Thirty-six patients transitioned to afatinib plus cetuximab. Four (11%) patients responded; median PFS was 2.9 months. Median PFS with afatinib plus cetuximab for patients who received afatinib monotherapy for >= 12 versus <12 weeks was 4.9 versus 1.8 months (p = 0.0354), and for patients with T790M-positive versus T790M-negative tumors was 4.8 versus 1.8 months (p = 0.1306). Fifty percent of patients receiving afatinib plus cetuximab experienced drug-related grade 3/4 AEs. The most frequent drug-related AEs (any grade) were diarrhea (70%), rash (49%), and fatigue (35%) with afatinib monotherapy and rash (69%), paronychia (39%), and dry skin (36%) with afatinib plus cetuximab. Conclusion: Sequential EGFR blockade with afatinib followed by afatinib plus cetuximab had a predictable safety profile and demonstrated modest activity in patients with EGFR mutation-positive NSCLC with resistance to erlotinib or gefitinib

The head-tail radio galaxy and revived fossil plasma in Abell 1775

Context. Head-tail radio galaxies are characterized by a head, corresponding to an elliptical galaxy, and two radio jets sweeping back from the head, forming an extended structure behind the host galaxy that is moving through the intracluster medium (ICM). This morphology arises from the interaction between the diffuse radio-emitting plasma and the surrounding environment. Sometimes, in galaxy clusters, revived fossil plasma can be found, and it traces old active galactic nucleus ejecta with a very steep spectrum that has been re-energized through processes in the ICM, unrelated to the progenitor radio galaxy. Aims. We focus on the study of the central region of Abell 1775, a galaxy cluster in an unclear dynamical state at a redshift of z = 0.07203. It hosts two giant radio-loud elliptical galaxies, the head-tail radio galaxy that ‘breaks’ at the position of a cold front detected in the X-rays, filamentary revived fossil plasma, and central diffuse emission. This study aims to investigate and constrain the spectral properties and trends along the head-tail, as well as the revived fossil plasma, to better understand the formation process of the non-thermal phenomena in A1775. Methods. We make use of observations at three frequencies performed with LOFAR at 144 MHz, and new deep uGMRT observations at 400 MHz and at 650 MHz. Results. We observe an overall steepening along the tail of the head-tail radio galaxy. In the radio colour-colour diagram, ageing models reproduce the emission of the head-tail. An unexpected brightness increase at the head of the tail suggests a complex bending of the jets. We derived the equipartition magnetic field and minimum pressure along the tail. We recovered the structure of the revived fossil plasma, which appears as thin filaments with ultra-steep spectra. Conclusions. We show that high-sensitivity, high-resolution observations at low frequencies are essential for detecting the full extent of the tail, enabling a deeper spectral analysis and resolving the structure and spectral properties of revived fossil plasma

Use of the Cascade expandable net to treat cerebral vasospasm – initial clinical experience from a single centre with in vitro benchside tests

Abstract Background The use of self-expanding stents to treat post-hemorrhagic cerebral vasospasm was recently described. We sought to determine the clinical efficacy of the Cascade device to treat delayed cerebral vasospasm (DCV). We performed benchside tests to determine the chronic outward force exerted by the Cascade in comparison to the Solitaire. Methods The chronic outward force (COF) of the Cascade M agile and Cascade L Agile was tested with equivalent tests of the Solitaire 4x20mm. Further tests to determine the forces generated in pre-formed tubes of 1.5–6 mm were performed using both fully and partially unsheathed Cascades. A retrospective review to identify all patients with aSAH and DCV treated with a Cascade device between January 2020 and July 2021. We recorded the treatment arterial vessel diameters and hemorrhagic or ischemic complications. Results In vitro the Cascade generated greater radial force than the Solitaire. The force generated by the Cascade M Agile at 1.5 mm was approximately 64% higher than the Solitaire 6x40mm and approximately 350% higher than the Solitaire 4x20mm. 4 patients with DCV were identified all of whom were treated with a cascade device. In all cases there was a significant improvement in the diameter of the vasospastic vessels treated with an average diameter increase of approximately 300%. There were no complications from the Cascade. Delayed CT angiography showed persistent dilatation of the segments treated with the Cascade at 24 h. Conclusion The Cascade is a safe and effective device when used to treat DCV secondary to aSAH. Larger studies are required to validate our initial results. </jats:sec

Dual Inhibition of EGFR with Afatinib and Cetuximab in Kinase Inhibitor-Resistant EGFR-Mutant Lung Cancer with and without T790M Mutations

EGFR-mutant lung cancers responsive to reversible EGFR inhibitors (gefitinib/erlotinib) develop acquired resistance, mediated by second-site EGFR T790M mutation in >50% of cases. Preclinically, afatinib (irreversible ErbB family blocker) plus cetuximab (anti-EGFR monoclonal antibody) overcomes T790M-mediated resistance. This phase lb study combining afatinib and cetuximab enrolled heavily pretreated patients with advanced EGFR-mutant lung cancer and acquired resistance to erlotinib/gefitinib. Patients provided post-acquired-resistance tumor samples for profiling EGFR mutations. Among 126 patients, objective response rate (overall 29%) was comparable in T790M-positive and T790M-negative tumors (32% vs. 25%; P = 0.341). Median progression-free survival was 4.7 months (95% confidence interval, 4.3-6.4), and the median duration of confirmed objective response was 5.7 months (range, 1.8-24.4). Therapy-related grade 3/4 adverse events occurred in 44%/2% of patients. Afatinib-cetuximab demonstrated robust clinical activity and a manageable safety profile in EGFR-mutant lung cancers with acquired resistance to gefitinibor erlotinib, both with and without T790M mutations, warranting further investigation. SIGNIFICANCE: This article reports the results of a trial combining afatinib and cetuximab in patients with acquired resistance and details the first clinical proof-of-concept for the preclinical hypothesis that a significant proportion of tumors in patients with acquired resistance to gefitinib/erlotinib remain dependent on EGFR signaling for survival. (C) 2014 AACR