A Modal-Based Partition of Unity Finite Element Method for Elastic Wave Propagation Problems in Layered Media

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] The time-harmonic propagation of elastic waves in layered media is simulated numerically by means of a modal-based Partition of Unity Finite Element Method (PUFEM). Instead of using the standard plane waves or the Bessel solutions of the Helmholtz equation to design the discretization basis, the proposed modal-based PUFEM explicitly uses the tensor-product expressions of the eigenmodes (the so-called Love and interior modes) of a spectral elastic transverse problem, which fulfil the coupling conditions among layers. This modal-based PUFEM approach does not introduce quadrature errors since the coefficients of the discrete matrices are computed in closed-form. A preliminary analysis of the high condition number suffered by the proposed method is also analyzed in terms of the mesh size and the number of eigenmodes involved in the discretization. The numerical methodology is validated through a number of test scenarios, where the reliability of the proposed PUFEM method is discussed by considering different modal basis and source terms. Finally, some indicators are introduced to select a convenient discrete PUFEM basis taking into account the observability of cracks located on a coupling boundary between two adjacent layers.This work has been supported by Xunta de Galicia project “Numerical simulation of high-frequency hydro-acoustic problems in coastal environments - SIMNUMAR” (EM2013/052), co-funded with European Regional Development Funds (ERDF). Moreover, the second and fifth authors have been supported by MICINN projects MTM2014-52876-R, MTM2017-82724-R, PID2019-108584RB-I00, and also by ED431C 2018/33 - M2NICA (Xunta de Galicia & ERDF) and ED431G 2019/01 - CITIC (Xunta de Galicia & ERDF). Additionally, the third author has been supported by Junta de Castilla y León under projects VA024P17 and VA105G18, co-financed by ERDF funds. This work has been funded for open access charge by Universidade da Coruña/CISUGXunta de Galicia; EM2013/052Xunta de Galicia; ED431C 2018/33Xunta de Galicia; ED431G 2019/01Junta de Castilla y León; VA024P17Junta de Castilla y León; VA105G1

Hard thermal loops and the entropy of supersymmetric Yang-Mills theories

We apply the previously proposed scheme of approximately self-consistent hard-thermal-loop resummations in the entropy of high-temperature QCD to N=4 supersymmetric Yang-Mills (SYM) theories and compare with a (uniquely determined) R[4,4] Pad\'e approximant that interpolates accurately between the known perturbative result and the next-to-leading order strong-coupling result obtained from AdS/CFT correspondence. We find good agreement up to couplings where the entropy has dropped to about 85% of the Stefan-Boltzmann value. This is precisely the regime which in purely gluonic QCD corresponds to temperatures above 2.5 times the deconfinement temperature and for which this method of hard-thermal-loop resummation has given similar good agreement with lattice QCD results. This suggests that in this regime the entropy of both QCD and N=4 SYM is dominated by effectively weakly coupled hard-thermal-loop quasiparticle degrees of freedom. In N=4 SYM, strong-coupling contributions to the thermodynamic potential take over when the entropy drops below 85% of the Stefan-Boltzmann value.Comment: 14 pages, 2 figures, JHEP3. v2: revised and expanded, with unchanged HTL results but corrected NLO strong-coupling result from AdS/CFT (which is incorrectly reproduced in almost all previous papers comparing weak and strong coupling results of N=4 SYM) and novel (unique) Pade approximant interpolating between weak and strong coupling result

A randomised open-label study of tiagabine given two or three times daily in refractory epilepsy

SummaryEfficacy and tolerability of tiagabine was evaluated in patients with non-controlled partial seizures in a multicentre, open-label, parallel group study. Tiagabine was administered either two (b.i.d.) or three times daily (t.i.d.) as adjunctive therapy and titrated stepwise to a target of 40mg/day during a 12-week, fixed-schedule titration period; this was followed by a 12-week flexible continuation period. The primary efficacy endpoint was the proportion of patients completing the fixed-schedule titration period. A total of 243 patients were randomised and received treatment, 123 to b.i.d. and 120 to t.i.d. dosing. Fewer patients in the b.i.d. (76 and 62%) than in the t.i.d. (87 and 72%) group completed the fixed-schedule titration period (OR: 0.562; 95% CI: 0.309–1.008; P=0.0532). The median percentage decrease in all types of seizure (excluding status epilepticus) during the fixed schedule titration period was 33.4% for the b.i.d. and 23.8% for the t.i.d. groups (P=0.9634; Van Elteren's test). The proportion of responders was similar for the b.i.d. and t.i.d. groups. There were no significant differences between dosage regimens in the change in median seizure rates from baseline. Adverse events were more frequent during the titration than the continuation period. Most events were mild and related to the central nervous system. Although their incidence was similar between treatment groups, severity was more frequent in the b.i.d. group. Our results suggest that during titration tiagabine is better tolerated with t.i.d. dosing, but during long-term maintenance, a t.i.d. schedule is as effective and well tolerated as b.i.d

Reliability of voluntary step execution behavior under single and dual task conditions

<p>Abstract</p> <p>Background</p> <p>The current study investigated the repeatability (test-retest reliability) of ground reaction force parameters recorded during a voluntary step execution under single (motor task) and dual task (motor and cognitive task) conditions for healthy adults and elderly individuals as well as the number of trials required to produce repeatable results.</p> <p>Methods</p> <p>Twenty-four healthy adults (21–63 years old) and 16 elderly adults (66–87 years) performed a voluntary rapid step execution following a tap on their heel while standing on a force platform under single and dual task conditions on three separate occasions. The first two tests were performed 30–60 minutes apart and the third test was performed a week later. Variables analyzed from the ground reaction force data included onset latency of step initiation (initiation phase), preparation and swing phases, foot-off and foot-contact times.</p> <p>Results</p> <p>Intraclass correlation coefficients (ICC(2,1)) were good to excellent across all parameters and test conditions for the pooled population and for elderly (0.74–0.92 and 0.62–0.88, respectively) except for the swing phase duration where lower values were seen (0.54–0.60 and 0.32–0.64 respectively). Values were similar under single and dual task conditions.</p> <p>Conclusion</p> <p>A voluntary step execution test, performed under single and dual task conditions especially foot-off and foot-contact times, is a reliable outcome measure that may be a useful tool to asses dynamic balance function for diagnostic purposes as well as clinical intervention trials.</p

Specific gene correction of the AGXT gene and direct cell reprogramming for the treatment of Primary Hyperoxaluria Type 1

P428 Primary Hyperoxaluria Type 1 (PH1) is an inherited rare metabolic liver disease caused by the deficiency in the alanine: glyoxylate aminotransferase enzyme (AGXT), involved in the glyoxylate metabolism. The only potentially curative treatment is organ transplantation. Thus, the development of new therapeutic approaches for the treatment of these patients appears as a priority.We propose the combination of site-specific gene correction and direct cell reprogramming for the generation of autologous phenotypically healthy induced hepatocytes (iHeps) from skin-derived fibroblast of PH1 patients. For the correction of AGXT mutations, we have designed specific gene editing tools to address gene correction by two different strategies, assisted by CRISPR/Cas9 system. Accurate specific point mutation correction (c.853T-C) has been achieved by homologydirected repair (HDR) with ssODN harbouring wild-type sequence. In the second strategy, an enhanced version ofAGXTcDNAhas been inserted near the transcription start codon of the endogenous gene, constituting an almost universal correction strategy for PH1 mutations. Direct reprogramming of fibroblasts has been conducted by overexpression of hepatic transcription factors and in vitro culture in defined media. In vitro characterization of healthy induced hepatocytes (iHeps) has demonstrated hepatic function of the reprogrammed cells. PH1 patient fibroblasts and , ,

CMOS Active Pixel Sensors as energy-range detectors for proton Computed Tomography

Since the first proof of concept in the early 70s, a number of technologies has been proposed to perform proton CT (pCT), as a means of mapping tissue stopping power for accurate treatment planning in proton therapy. Previous prototypes of energy-range detectors for pCT have been mainly based on the use of scintillator-based calorimeters, to measure proton residual energy after passing through the patient. However, such an approach is limited by the need for only a single proton passing through the energy-range detector in a read-out cycle. A novel approach to this problem could be the use of pixelated detectors, where the independent read-out of each pixel allows to measure simultaneously the residual energy of a number of protons in the same read-out cycle, facilitating a faster and more efficient pCT scan. This paper investigates the suitability of CMOS Active Pixel Sensors (APSs) to track indi- vidual protons as they go through a number of CMOS layers, forming an energy-range telescope. Measurements performed at the iThemba Laboratories will be presented and analysed in terms of correlation, to confirm capability of proton tracking for CMOS APSs

Exact solutions of the radial Schrodinger equation for some physical potentials

By using an ansatz for the eigenfunction, we have obtained the exact analytical solutions of the radial Schrodinger equation for the pseudoharmonic and Kratzer potentials in two dimensions. The energy levels of all the bound states are easily calculated from this eigenfunction ansatz. The normalized wavefunctions are also obtained.Comment: 13 page

Local wind speed forecasting based on WRF-HDWind coupling

[EN] Wind speed forecasts obtained by Numerical Weather Prediction models are limited for fine interpretation in heterogeneous terrain, in which different roughnesses and orographies occur. This limitation is derived from the use of low-resolution and grid-box averaged data. In this paper a dynamical downscaling method is presented to increase the local accuracy of wind speed forecasts. The proposed method divides the wind speed forecasting into two steps. In the first one, the mesoscale model WRF (Weather Research and Forecasting) is used for getting wind speed forecasts at specific points of the study domain. On a second stage, these values are used for feeding the HDWind microscale model. HDWind is a local model that provides both a high-resolution wind field that covers the entire study domain and values of wind speed and direction at very located points. As an example of use of the proposed method, we calculate a high-resolution wind field in an urban-interface area from Badajoz, a South-West Spanish city located near the Portugal border. The results obtained are compared with the values read by a weathervane tower of the Spanish State Meteorological Agency (AEMET) in order to prove that the microscale model improves the forecasts obtained by the mesoscale model

Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study).

It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the "in vivo" measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis. The goal of this project is to explore the relationship between the activity of drug-metabolizing enzymes (DME), assessed by a phenotypic approach, and the concentrations of Venlafaxine (VLX) + O-demethyl-venlafaxine (ODV), the efficacy and tolerance of VLX. This study is a multicentre prospective non-randomized open trial. Eligible patients present a major depressive episode, MADRS over or equal to 20, treatment with VLX regardless of the dose during at least 4 weeks. The Phenotype Visit includes VLX and ODV concentration measurement. Following the oral absorption of low doses of omeprazole, midazolam, dextromethorphan, and fexofenadine, drug metabolizing enzymes activity is assessed by specific metabolite/probe concentration ratios from a sample taken 2 h after cocktail administration for CYP2C19, CYP3A4, CYP2D6; and by the determination of the limited area under the curve from the capillary blood samples taken 2-3 and 6 h after cocktail administration for CYP2C19 and P-gp. Two follow-up visits will take place between 25 and 40 days and 50-70 days after inclusion. They include assessment of efficacy, tolerance and observance. Eleven french centres are involved in recruitment, expected to be completed within approximately 2 years with 205 patients. Metabolic ratios are determined in Geneva, Switzerland. By showing an association between drug metabolism and VLX concentrations, efficacy and tolerance, there is a hope that testing drug metabolism pathways with a phenotypical approach would help physicians in selecting and dosing antidepressants. The MARVEL study will provide an important contribution to increasing the knowledge of VLX variability and in optimizing the use of methods of personalized therapy in psychiatric settings. ClinicalTrials.gov NCT02590185 (10/27/2015). This study is currently recruiting participants

Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study

Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis