4,424 research outputs found

    Computing reconstructions from nonuniform Fourier samples: Universality of stability barriers and stable sampling rates

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    We study the problem of recovering an unknown compactly-supported multivariate function from samples of its Fourier transform that are acquired nonuniformly, i.e. not necessarily on a uniform Cartesian grid. Reconstruction problems of this kind arise in various imaging applications, where Fourier samples are taken along radial lines or spirals for example.Specifically, we consider finite-dimensional reconstructions, where a limited number of samples is available, and investigate the rate of convergence of such approximate solutions and their numerical stability. We show that the proportion of Fourier samples that allow for stable approximations of a given numerical accuracy is independent of the specific sampling geometry and is therefore universal for different sampling scenarios. This allows us to relate both sufficient and necessary conditions for different sampling setups and to exploit several results that were previously available only for very specific sampling geometries.The results are obtained by developing: (i) a transference argument for different measures of the concentration of the Fourier transform and Fourier samples; (ii) frame bounds valid up to the critical sampling density, which depend explicitly on the sampling set and the spectrum.As an application, we identify sufficient and necessary conditions for stable and accurate reconstruction of algebraic polynomials or wavelet coefficients from nonuniform Fourier data

    The phase difference between neural drives to antagonist muscles in essential tremor is associated with the relative strength of supraspinal and afferent input

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    The pathophysiology of essential tremor (ET), the most common movement disorder, is not fully understood. We investigated which factors determine the variability in the phase difference between neural drives to antagonist muscles, a long-standing observation yet unexplained. We used a computational model to simulate the effects of different levels of voluntary and tremulous synaptic input to antagonistic motoneuron pools on the tremor. We compared these simulations to data from 11 human ET patients. In both analyses, the neural drive to muscle was represented as the pooled spike trains of several motor units, which provides an accurate representation of the common synaptic input to motoneurons. The simulations showed that, for each voluntary input level, the phase difference between neural drives to antagonist muscles is determined by the relative strength of the supraspinal tremor input to the motoneuron pools. In addition, when the supraspinal tremor input to one muscle was weak or absent, Ia afferents provided significant common tremor input due to passive stretch. The simulations predicted that without a voluntary drive (rest tremor) the neural drives would be more likely in phase, while a concurrent voluntary input (postural tremor) would lead more frequently to an out-of-phase pattern. The experimental results matched these predictions, showing a significant change in phase difference between postural and rest tremor. They also indicated that the common tremor input is always shared by the antagonistic motoneuron pools, in agreement with the simulations. Our results highlight that the interplay between supraspinal input and spinal afferents is relevant for tremor generation

    Sedimentology, Provenance and Radiometric Dating of the Silante Formation: Implications for the Cenozoic Evolution of the Western Andes of Ecuador

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    The Silante Formation is a thick series of continental deposits, exposed along a trench-parallel distance of approximately 300 km within the Western Cordillera of Ecuador. The origin, tectonic setting, age and stratigraphic relationships are poorly known, although these are key to understand the Cenozoic evolution of the Ecuadorian Andes. We present new sedimentological, stratigraphic, petrographic, radiometric and provenance data from the Silante Formation and underlying rocks. The detailed stratigraphic analysis shows that the Silante Formation unconformably overlies Paleocene submarine fan deposits of the Pilalo Formation, which was coeval with submarine tholeiitic volcanism. The lithofacies of the Silante Formation suggest that the sediments were deposited in a debris flow dominated alluvial fan. Provenance analysis including heavy mineral assemblages and detrital zircon U-Pb ages indicate that sediments of the Silante Formation were derived from the erosion of a continental, calc-alkaline volcanic arc, pointing to the Oligocene to Miocene San Juan de Lachas volcanic arc. Thermochronological data and regional correlations suggest that deposition of the Silante Formation was coeval with regional rock and surface uplift of the Andean margin that deposited alluvial fans in intermontane and back-arc domains

    β-N-acetylglucosaminidase grafted on mesoporous silica nanoparticles. A bionanoantibiotic system against Staphylococcus aureus bacteria

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    A bionanoantibiotic system based on beta-N-acetylglucosaminidase (Ami) and Lysozyme (Lyz) enzymes grafted on the external surface of amino functionalized mesoporous silica nanoparticles, having a radial arrangement of pores (MSNr-NH2), was prepared and fully characterized. Before the enzyme grafting the nanoparticles were also loaded with the antibiotic drug levofloxacin (Levo) to explore the possible synergic effect with the enzymes. MSNr-NH2-Lyz-Levo and MSNr-NH2-Ami-Levo did not show any activity against S. aureus. On the contrary, in the absence of the antibiotic, both Lyz and Ami immobilized on MSNr were able to destroy S. aureus cells, suggesting an inhibiting action of the antibiotic on the enzymes. Although the loading of immobilized Lyz was higher than that of Ami (76 vs. 20 mg/g, respectively), the highest antibacterial efficacy was found for MSNr-NH2-Ami nanoantibiotic. Moreover, MSNr-NH2-Ami was active against S. aureus even at very low concentration (12.5 mu g/ mL) with a bactericidal activity (79%), higher than that determined for MSNr-NH2 loaded with levofloxacin (54%). These results suggest the possibility of using enzyme grafted MSNr as a bionanoantibiotic drug with high efficiency even at low nanoparticles concentration

    Quantum Non-Demolition Detection of Strongly Correlated Systems

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    Preparation, manipulation, and detection of strongly correlated states of quantum many body systems are among the most important goals and challenges of modern physics. Ultracold atoms offer an unprecedented playground for realization of these goals. Here we show how strongly correlated states of ultracold atoms can be detected in a quantum non-demolition scheme, that is, in the fundamentally least destructive way permitted by quantum mechanics. In our method, spatially resolved components of atomic spins couple to quantum polarization degrees of freedom of light. In this way quantum correlations of matter are faithfully mapped on those of light; the latter can then be efficiently measured using homodyne detection. We illustrate the power of such spatially resolved quantum noise limited polarization measurement by applying it to detect various standard and "exotic" types of antiferromagnetic order in lattice systems and by indicating the feasibility of detection of superfluid order in Fermi liquids.Comment: Published versio

    Estudio del efecto solvatocrómico en derivados fenólicos naturales

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    Se describen las características espectrofluorimétricas de dos derivados de quercetina aislados de las hojas deFlaveria bidentis, un derivado de 6-prenilpinocembrina, aislado de las raíces de Dalea elegans y un compuesto deestructura antraquinónica aislado de las hojas de Heterophyllaea pustulata. Todos ellos presentan espectros deabsorción con máximos en la región UV-visible acordes con los grupos cromóforos presentes en su estructura. Loscuatro compuestos estudiados presentan fluorescencia nativa. La posición de los máximos de emisión de fluorescenciase modifica en función del disolvente. Los desplazamientos producidos están relacionados con el diferente gradode solvatación de las moléculas en estado excitado según la polaridad del disolvente. La adición de ácidos mineralesprovoca desplazamientos en los máximos de fluorescencia concordantes con los ya descritos para compuestos deestructura similar. Estas modificaciones espectrales tienen un gran interés analítico desde el punto de vista de laidentificación y caracterización de productos naturales de estructura fenólica

    Cost-utility model of brivaracetam in the adjunctive treatment of patients with epilepsy in Spain

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    [EN] Objective This study aims to assess the cost utility of Brivaracetam compared with the third-generation anti-epileptic drugs used as standard care. Methods A cost utility analysis of Brivaracetam was carried out with other third-generation comparators. The treatment pathway of a hypothetical cohort over a period of 2 years was simulated using the Markov model. Data for effectiveness and the QALYs of each health status for epilepsy, as well as for the disutilities of adverse events of treatments, were analyzed through a studies review. The cost of the anti-epileptics and the use of medical resources linked to the different health statuses were taken into consideration. A probabilistic sensitivity analysis was performed using a Monte Carlo simulation. Results Brivaracetam was shown to be the dominant alternative, with Incremental Cost Utility Ratio (ICUR) values from -11,318 for Lacosamide to -128,482 for Zonisamide. The probabilistic sensitivity analysis validates these results. The ICUR sensitivity is greater for increases in the price of Brivaracetam than for decreases, and for Eslicarbizapine over the other adjunctives considered in the analysis. Conclusions Treatment with Brivaracetam resulted in cost effective and incremental quality adjusted life years come at an acceptable cost.Barrachina Martínez, I.; Vivas-Consuelo, D.; Reyes-Santias, F. (2020). Cost-utility model of brivaracetam in the adjunctive treatment of patients with epilepsy in Spain. Expert review of pharmacoeconomics & outcomes research (Online). 1-10. https://doi.org/10.1080/14737167.2021.1838899S110WHO | Epilepsy: aISBN public health imperative. ISBN 978-92-4-151593-1. World Health Organization. 2019. Printed in Thailand.Ngugi, A. K., Kariuki, S. M., Bottomley, C., Kleinschmidt, I., Sander, J. W., & Newton, C. R. (2011). Incidence of epilepsy: A systematic review and meta-analysis. Neurology, 77(10), 1005-1012. doi:10.1212/wnl.0b013e31822cfc90Henning, O., Landmark, C. J., Henning, D., Nakken, K. O., & Lossius, M. I. (2019). Challenges in epilepsy—The perspective of Norwegian epilepsy patients. Acta Neurologica Scandinavica, 140(1), 40-47. doi:10.1111/ane.13098Brodie, M. J. (2005). Diagnosing and predicting refractory epilepsy. Acta Neurologica Scandinavica, 112(s181), 36-39. doi:10.1111/j.1600-0404.2005.00507.xGarcía-Ramos, R., Pastor, A. G., Masjuan, J., Sánchez, C., & Gil, A. (2011). FEEN: Informe sociosantario FEEN sobre la epilepsia en España. Neurología, 26(9), 548-555. doi:10.1016/j.nrl.2011.04.002Kwan, P., & Brodie, M. J. (2000). Early Identification of Refractory Epilepsy. New England Journal of Medicine, 342(5), 314-319. doi:10.1056/nejm200002033420503Brodie, M. J. (2008). Epilepsy: randomised trials and genetic tribulations. The Lancet Neurology, 7(1), 7-8. doi:10.1016/s1474-4422(07)70301-0French, J. A. (2006). Refractory Epilepsy: One Size Does Not Fit All. Epilepsy Currents, 6(6), 177-180. doi:10.1111/j.1535-7511.2006.00137.xLaxer, K. D., Trinka, E., Hirsch, L. J., Cendes, F., Langfitt, J., Delanty, N., … Benbadis, S. R. (2014). The consequences of refractory epilepsy and its treatment. Epilepsy & Behavior, 37, 59-70. doi:10.1016/j.yebeh.2014.05.031Giordano, C., Marchiò, M., Timofeeva, E., & Biagini, G. (2014). Neuroactive Peptides as Putative Mediators of Antiepileptic Ketogenic Diets. Frontiers in Neurology, 5. doi:10.3389/fneur.2014.00063European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP). Briviact brivaracetam. Assessment Report EMA/CHMP/822086/2015 Nov.Markham, A. (2016). Brivaracetam: First Global Approval. Drugs, 76(4), 517-522. doi:10.1007/s40265-016-0555-6Willems, L. M., Bauer, S., Rosenow, F., & Strzelczyk, A. (2019). Recent advances in the pharmacotherapy of epilepsy: brivaracetam and perampanel as broad-spectrum antiseizure drugs for the treatment of epilepsies and status epilepticus. Expert Opinion on Pharmacotherapy, 20(14), 1755-1765. doi:10.1080/14656566.2019.1637420Craig, D., Rice, S., Paton, F., Fox, D., & Woolacott, N. (2013). Retigabine for the Adjunctive Treatment of Adults with Partial-Onset Seizures in Epilepsy with and without Secondary Generalization. PharmacoEconomics, 31(2), 101-110. doi:10.1007/s40273-012-0018-1Charokopou, M., Harvey, R., Srivastava, K., Brandt, C., & Borghs, S. (2019). Relative performance of brivaracetam as adjunctive treatment of focal seizures in adults: a network meta-analysis. Current Medical Research and Opinion, 35(8), 1345-1354. doi:10.1080/03007995.2019.1584501Chhatwal J. Changing cycle lengths in state-transition models: doing it the right way; [cited 2018 Jan 23]. Available from: https://www.ispor.org/News/Connections_methodology_state-transition-models.PDFMulhern, B., Rowen, D., Snape, D., Jacoby, A., Marson, T., Hughes, D., … Brazier, J. (2014). Valuations of epilepsy-specific health states: a comparison of patients with epilepsy and the general population. Epilepsy & Behavior, 36, 12-17. doi:10.1016/j.yebeh.2014.04.011Kristian, B., Wachtmeister, K., Stefan, F., & Forsgren, L. (2013). Retigabine as add-on treatment of refractory epilepsy - a cost-utility study in a Swedish setting. Acta Neurologica Scandinavica, 127(6), 419-426. doi:10.1111/ane.12077Vera-Llonch, M., Brandenburg, N. A., & Oster, G. (2008). Cost-effectiveness of Add-on Therapy with Pregabalin in Patients with Refractory Partial Epilepsy. Epilepsia, 49(3), 431-437. doi:10.1111/j.1528-1167.2007.01279.xSimoens, S. (2010). Pharmacoeconomics of anti-epileptic drugs as adjunctive therapy for refractory epilepsy. Expert Review of Pharmacoeconomics & Outcomes Research, 10(3), 309-315. doi:10.1586/erp.10.18Wijnen, B. F. M., van Mastrigt, G. A. P. G., Evers, S. M. A. A., Gershuni, O., Lambrechts, D. A. J. E., Majoie, M. H. J. M., … de Kinderen, R. J. A. (2017). A systematic review of economic evaluations of treatments for patients with epilepsy. Epilepsia, 58(5), 706-726. doi:10.1111/epi.13655Boeck, J. D., Verpoorten, K., Luyten, K., & Coninx, K. (2007). A Comparison between Decision Trees and Markov Models to Support Proactive Interfaces. 18th International Conference on Database and Expert Systems Applications (DEXA 2007). doi:10.1109/dexa.2007.94Zhang, Y., Wu, H., Denton, B. T., Wilson, J. R., & Lobo, J. M. (2017). Probabilistic sensitivity analysis on Markov models with uncertain transition probabilities: an application in evaluating treatment decisions for type 2 diabetes. Health Care Management Science, 22(1), 34-52. doi:10.1007/s10729-017-9420-8Swallow, E., Fang, A., Signorovitch, J., Plumb, J., & Borghs, S. (2017). Can Matching-Adjusted Indirect Comparison Methods Mitigate Placebo Response Differences Among Patient Populations in Adjunctive Trials of Brivaracetam and Levetiracetam? CNS Drugs, 31(10), 899-910. doi:10.1007/s40263-017-0462-8Malyshkina NV, Mannering FL. Markov switching multinomial logit model: an application to accident injury severities; 2008 [cited 2019 Sep 25]. Available from: http://arxiv.org/abs/0811.3644Hawkins, N., Epstein, D., Drummond, M., Wilby, J., Kainth, A., Chadwick, D., & Sculpher, M. (2005). Assessing the Cost-Effectiveness of New Pharmaceuticals in Epilepsy in Adults: The Results of a Probabilistic Decision Model. Medical Decision Making, 25(5), 493-510. doi:10.1177/0272989x05280559Agencia Española del Medicamento. Utilización de medicamentos antiepilépticos en España durante el periodo 2008–2016 [Internet]; 2017 [cited 2019 Sep 25]. Available from: https://www.aemps.gob.es/medicamentosUsoHumano/observatorio/docs/antiepilepticos-periodo-2008-2016.pdfMegiddo, I., Colson, A., Chisholm, D., Dua, T., Nandi, A., & Laxminarayan, R. (2016). Health and economic benefits of public financing of epilepsy treatment in India: An agent‐based simulation model. Epilepsia, 57(3), 464-474. doi:10.1111/epi.13294De Andrés-Nogales, F., Oyagüez, I., Álvarez-Sala, L. A., García-Bragado, F., Navarro, A., González, P., … Soto, J. (2017). Análisis coste-efectividad y coste-utilidad de apixaban frente a dabigatrán y rivaroxaban en el tratamiento y prevención secundaria del tromboembolismo venoso. PharmacoEconomics Spanish Research Articles, 14(1), 7-18. doi:10.1007/s40277-016-0064-8Fricke-Galindo, I., Jung-Cook, H., LLerena, A., & López-López, M. (2018). Farmacogenética de reacciones adversas a fármacos antiepilépticos. 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    COVID-19 pandemic on coronary artery and cerebrovascular diseases in Southern Spain: interrupted time series analysis

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    Objective: Healthcare systems have been put under intense pressure by the COVID-19 pandemic, although some studies have shown a decline in hospital admissions for cardiovascular and cerebrovascular diseases during the first and second wave of the pandemic. In addition, studies analyzing gender and procedural differences are scarce. The present study aimed to determine the impact of the pandemic on hospital admissions for acute myocardial infarction (AMI) and cerebrovascular disease (CVD) in Andalusia (Spain) and analyzed differences by gender and by percutaneous coronary interventions performed. Patients and methods: An interrupted time series analysis of AMI and CVD hospital admissions in Andalusia (Spain) was carried out to measure the impact of the COVID-19 outbreak. AMI and CVD cases admitted daily in public hospitals of Andalusia between January 2018 and December 2020 were included. Results: During the pandemic, significant reductions in AMI [-19%; 95% confidence interval (CI): (-29%, -9%), p<0.001] and CVD [-17%; 95% CI: (-26%, -9%); p<0.01] in daily hospital admissions were observed. Differences were also produced according to the diagnosis (ST-Elevation Myocardial Infarction, Non-ST-Elevation Myocardial Infarction, other AMI and stroke), with a greater reduction in females for AMI and in males for CVD. Although there were more percutaneous coronary interventions during the pandemic, no significant reductions were observed. Conclusions: A decline in AMI and CVD daily hospital admissions during the first and second wave of COVID-19 pandemic was noted. Gender differences were observed, but no clear impact was observed in percutaneous interventions

    Inhibition of α9α10 nicotinic acetylcholine receptors prevents chemotherapy-induced neuropathic pain

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    Opioids are first-line drugs for moderate to severe acute pain and cancer pain. However, these medications are associated with severe side effects, and whether they are efficacious in treatment of chronic nonmalignant pain remains controversial. Medications that act through alternative molecular mechanisms are critically needed. Antagonists of α9α10 nicotinic acetylcholine receptors (nAChRs) have been proposed as an important nonopioid mechanism based on studies demonstrating prevention of neuropathology after trauma-induced nerve injury. However, the key α9α10 ligands characterized to date are at least two orders of magnitude less potent on human vs. rodent nAChRs, limiting their translational application. Furthermore, an alternative proposal that these ligands achieve their beneficial effects by acting as agonists of GABA(B) receptors has caused confusion over whether blockade of α9α10 nAChRs is the fundamental underlying mechanism. To address these issues definitively, we developed RgIA4, a peptide that exhibits high potency for both human and rodent α9α10 nAChRs, and was at least 1,000-fold more selective for α9α10 nAChRs vs. all other molecular targets tested, including opioid and GABA(B) receptors. A daily s.c. dose of RgIA4 prevented chemotherapy-induced neuropathic pain in rats. In wild-type mice, oxaliplatin treatment produced cold allodynia that could be prevented by RgIA4. Additionally, in α9 KO mice, chemotherapy-induced development of cold allodynia was attenuated and the milder, temporary cold allodynia was not relieved by RgIA4. These findings establish blockade of α9-containing nAChRs as the basis for the efficacy of RgIA4, and that α9-containing nAChRs are a critical target for prevention of chronic cancer chemotherapy-induced neuropathic pain
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