Modelling Curved and Non-Aligned Surfaces using the Finite-Difference Time-Domain Method

The finite-difference time-domain (FDTD) method is widely used for computational electromagnetic simulations due to its efficiency and ease of implementation. However, due to its reliance on an orthogonal grid, it is difficult to represent curved and non-aligned planar surfaces. A common method of dealing with this is to use stair-cased meshes that align with the stair-cased grid as close as possible to the surface being meshed. This work explores the errors that arise from using stair-cased meshes of cavities for shielding and scattering problems. It is determined that the increased surface area of a stair-cased mesh alters the transmission and reflection of incident waves. A method of altering the boundary properties is presented to counteract the errors in transmission and reflection. This method is shown to reduce the error in the magnitude of shielding effectiveness (SE) of stair-cased cavities. However, as this method does not change the geometry of the mesh itself, errors in resonant frequency and the presence of spurious resonances is not affected. A second method is proposed to locally deform FDTD cells to conform to a curved or non-aligned planar surface. This method incorporates a thin layer model to vastly increase the efficiency of the algorithm when compared to bulk material alternatives. The method is shown to improve errors in the magnitude of SE, resonant frequency and spurious resonances when compared to stair-cased models

Serelaxin Elicits Bronchodilation and Enhances β-Adrenoceptor-Mediated Airway Relaxation.

Treatment with β-adrenoceptor agonists does not fully overcome the symptoms associated with severe asthma. Serelaxin elicits potent uterine and vascular relaxation via its cognate receptor, RXFP1, and nitric oxide (NO) signaling, and is being clinically evaluated for the treatment of acute heart failure. However, its direct bronchodilator efficacy has yet to be explored. Tracheal rings were prepared from male Sprague-Dawley rats (250-350 g) and tricolor guinea pigs, and precision cut lung slices (PCLSs) containing intrapulmonary airways were prepared from rats only. Recombinant human serelaxin (rhRLX) alone and in combination with rosiglitazone (PPARγ agonist; recently described as a novel dilator) or β-adrenoceptor agonists (isoprenaline, salbutamol) were added either to pre-contracted airways, or before contraction with methacholine or endothelin-1. Regulation of rhRLX responses by epithelial removal, indomethacin (cyclooxygenase inhibitor), L-NAME (nitric oxide synthase inhibitor), SQ22536 (adenylate cyclase inhibitor) and ODQ (guanylate cyclase inhibitor) were also evaluated. Immunohistochemistry was used to localize RXFP1 to airway epithelium and smooth muscle. rhRLX elicited relaxation in rat trachea and PCLS, more slowly than rosiglitazone or isoprenaline, but potentiated relaxation to both these dilators. It markedly increased β-adrenoceptor agonist potency in guinea pig trachea. rhRLX, rosiglitazone, and isoprenaline pretreatment also inhibited the development of rat tracheal contraction. Bronchoprotection by rhRLX increased with longer pre-incubation time, and was partially reduced by epithelial removal, indomethacin and/or L-NAME. SQ22536 and ODQ also partially inhibited rhRLX-mediated relaxation in both intact and epithelial-denuded trachea. RXFP1 expression in the airways was at higher levels in epithelium than smooth muscle. In summary, rhRLX elicits large and small airway relaxation via epithelial-dependent and -independent mechanisms, likely via RXFP1 activation and generation of NO, prostaglandins and cAMP/cGMP. rhRLX also enhanced responsiveness to other dilators, suggesting its potential as an alternative or add-on therapy for severe asthma

Pulmonary myeloid cell uptake of biodegradable nanoparticles conjugated with an anti-fibrotic agent provides a novel strategy for treating chronic allergic airways disease

Asthma (chronic allergic airways disease, AAD) is characterized by airway inflammation (AI), airway remodeling (AWR) and airway hyperresponsiveness (AHR). Current treatments for AAD mainly focus on targeting AI and its contribution AHR, with the use of corticosteroids. However, there are no therapies for the direct treatment of AWR, which can contribute to airway obstruction, AHR and corticosteroid resistance independently of AI. The acute heart failure drug, serelaxin (recombinant human gene-2 relaxin, RLX), has potential anti-remodeling and anti-fibrotic effects but only when continuously infused or injected to overcome its short half-life. To alleviate this limitation, we conjugated serelaxin to biodegradable and noninflammatory nanoparticles (NP-RLX) and evaluated their therapeutic potential on measures of AI, AWR and AHR, when intranasally delivered to a preclinical rodent model of chronic AAD and TGF-β1-stimulated collagen gel contraction from asthma patient-derived myofibroblasts. NP-RLX was preferentially taken-up by CD206+-infiltrating and CD68+-tissue resident alveolar macrophages. Furthermore, NP-RLX ameliorated the chronic AAD-induced AI, pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), chemokines (CCL2, CCL11) and the pro-fibrotic TGF-β1/IL-1β axis on AWR and resulting AHR, as well as human myofibroblast-induced collagen gel contraction, to a similar extent as unconjugated RLX. Hence, NP-RLX represents a novel strategy for treating the central features of asthma

Different hierarchical reconfigurations in the brain by psilocybin and escitalopram for depression

Effective interventions for neuropsychiatric disorders may work by rebalancing the brain’s functional hierarchical organization. Here we directly investigated the effects of two different serotonergic pharmacological interventions on functional brain hierarchy in major depressive disorder in a two-arm double-blind phase II randomized controlled trial comparing psilocybin therapy (22 patients) with escitalopram (20 patients). Patients with major depressive disorder received either 2 × 25 mg of oral psilocybin, three weeks apart, plus six weeks of daily placebo (‘psilocybin arm’) or 2 × 1 mg of oral psilocybin, three weeks apart, plus six weeks of daily escitalopram (10–20 mg; ‘escitalopram arm’). Resting-state functional magnetic resonance imaging scans were acquired at baseline and three weeks after the second psilocybin dose (NCT03429075). The brain mechanisms were captured by generative effective connectivity, estimated from whole-brain modeling of resting state for each session and patient. Hierarchy was determined for each of these sessions using measures of directedness and trophic levels on the effective connectivity, which captures cycle structure, stability and percolation. The results showed that the two pharmacological interventions created significantly different hierarchical reconfigurations of whole-brain dynamics with differential, opposite statistical effect responses. Furthermore, the use of machine learning revealed significant differential reorganization of brain hierarchy before and after the two treatments. Machine learning was also able to predict treatment response with an accuracy of 0.85 ± 0.04. Overall, the results demonstrate that psilocybin and escitalopram work in different ways for rebalancing brain dynamics in depression. This suggests the hypothesis that neuropsychiatric disorders could be closely linked to the breakdown in regions orchestrating brain dynamics from the top of the hierarchy

A Conformal Thin Boundary Model for FDTD

Thin layer models are widely used in the finitedifference time-domain (FDTD) technique to efficiently model boundaries in multi-scale simulations as they significantly reduce simulation run-times and memory requirements. These models often utilise surface impedance boundary conditions (SIBCs) to represent the material of the boundary. Conformal meshes are a popular method of representing curved and non-aligned surfaces in FDTD. These meshes deform cells in the FDTD grid around the boundary between bulk materials so as to more accurately represent the shape of the material. Here we present an algorithm that combines the efficiency of a thin layer model with the accuracy of a conformal mesh. The algorithm is applied to three resonant cavity models and the accuracy verified using comparisons to non-conformal meshes and analytic solutions. Improvements are shown in the accuracy of the resonant frequencies and magnitude of the shielding effectiveness (SE) of the cavities. It is also shown to reduce the prevalence of extraneous features in the frequency response of the SE that are apparent when using a stair-cased mesh

Ramucirumab plus FOLFIRI or irinotecan as second-line treatment for patients with gastroesophageal adenocarcinoma: a review and meta-analysis of an emerging option.

INTRODUCTION: The aim of this study was to provide a review of the clinical evidence for use of ramucirumab (RAM) plus folinic acid (leucovorin), fluorouracil (5-FU), and irinotecan (FOLFIRI) or irinotecan as second-line treatment in gastroesophageal adenocarcinoma (GEA). METHODS: A systematic and comprehensive search of PubMed was performed to identify phase 2 clinical trials or retrospective studies using RAM plus FOLFIRI or irinotecan in GEA, including abstracts from major congresses, in addition to published manuscripts. An aggregated review and meta-analysis was performed to assess the effectiveness (overall response rate [ORR] as primary outcome) and safety data of RAM plus FOLFIRI or irinotecan. ORR for each study was calculated with 95% confidence interval estimated from normal approximation. To generate the combined ORR with 95% confidence interval, random-effects meta-analysis was conducted to synthesize response data from available studies. RESULTS: Six studies were identified with non-overlapping populations, 3 phase 2 clinical trials and 3 retrospective studies. Across these studies the ORR ranged from 22% to 38%, and pooled ORR was 25.4%. Two of the 3 studies reported better ORR in patients pretreated with taxanes followed by RAM plus FOLFIRI. Treatment with RAM plus FOLFIRI or irinotecan was well tolerated. Neutropenia and diarrhea were the most common adverse events reported across studies. CONCLUSION: The studies examined in this review suggest that RAM plus FOLFIRI or irinotecan have activity in previously treated GEA irrespective of prior-taxane use. Overall, RAM plus FOLFIRI or irinotecan was well tolerated with no new safety concerns identified beyond established profiles for these regimens

A hybrid Crank-Nicolson FDTD subgridding boundary condition for lossy thin-layer modelling

The inclusion of thin lossy, material layers, such as carbon based composites, is essential for many practical applications modeling the propagation of electromagnetic energy through composite structures such as those found in vehicles and electronic equipment enclosures. Many existing schemes suffer problems of late time instability, inaccuracy at low frequency, and/or large computational costs. This work presents a novel technique for the modeling of thin-layer lossy materials in FDTD schemes which overcomes the instability problem at low computational cost. For this, a 1D-subgrid is used for the spatial discretization of the thin layer material. To overcome the additional time-step constraint posed by the reduction in the spatial cell size, a Crank-Nicolson time-integration scheme is used locally in the subgridded zone, and hybridized with the usual 3D Yee-FDTD method, which is used for the rest of the computational domain. Several numerical experiments demonstrating the accuracy of this approach are shown and discussed. Results comparing the proposed technique with classical alternatives based on impedance boundary condition approaches are also presented. The new technique is shown to have better accuracy at low frequencies, and late time stability than existing techniques with low computational cost

Computer simulations show that Neanderthal facial morphology represents adaptation to cold and high energy demands, but not heavy biting

Three adaptive hypotheses have been forwarded to explain the distinctive Neanderthal face: (i) an improved ability to accommodate high anterior bite forces, (ii) more effective conditioning of cold and/or dry air and, (iii) adaptation to facilitate greater ventilatory demands. We test these hypotheses using three-dimensional models of Neanderthals, modern humans, and a close outgroup (Homo heidelbergensis), applying finite-element analysis (FEA) and computational fluid dynamics (CFD). This is the most comprehensive application of either approach applied to date and the first to include both. FEA reveals few differences between H. heidelbergensis, modern humans, and Neanderthals in their capacities to sustain high anterior tooth loadings. CFD shows that the nasal cavities of Neanderthals and especially modern humans condition air more efficiently than does that of H. heidelbergensis, suggesting that both evolved to better withstand cold and/or dry climates than less derived Homo. We further find that Neanderthals could move considerably more air through the nasal pathway than could H. heidelbergensis or modern humans, consistent with the propositions that, relative to our outgroup Homo, Neanderthal facial morphology evolved to reflect improved capacities to better condition cold, dry air, and, to move greater air volumes in response to higher energetic requirements

Christian Correspondence: Being A Collection Of Letters Written By The Late Rev. John Wesley And Several Methodists Preachers, In Connection With Him. To The Late Mrs. Eliza Bennis, With Her Answers

Facsimile Reproductionhttps://place.asburyseminary.edu/bennisbooks/1000/thumbnail.jp

The Small Politics of Everyday Life: Local History Society Archives and the Production of Public Histories

Thousands of small, private archives sit in attics, cupboard, church halls and computer hard drives around the country; they are the archives of local history societies. Simultaneously freed from the control of archives sector and government initiatives, and yet saturated with local peculiarities and biases, local history society archives can seem to be the very antithesis of the wider archives movement, apparently private and parochial, undemocratic and uncatalogued. Consequently, local history society archives are rarely included in ‘the politics of the archive’ discussions. But if the activity of archiving is to be understood as a political act, what are the politics and meanings of local history and their archives? In this article, I suggest that certain types of local history society archive collections can help us paint a picture of the everyday lives of working-class people in Britain in the twentieth century. They detail the small politics of people’s lives – family, work, leisure, and beliefs. They give ordinary people a name, a face, and a life lived. Moreover, the workings of local history society archives raise important questions about historical production, for these groups play a significant role in rescuing and preserving archival collections, and in creating and curating their own histories