Improved convergence and stability properties in a three-dimensional higher-order ice sheet model

We present a finite difference implementation of a three-dimensional higher-order ice sheet model. In comparison to a conventional centred difference discretisation it enhances both numerical stability and convergence. In order to achieve these benefits the discretisation of the governing force balance equation makes extensive use of information on staggered grid points. Using the same iterative solver, a centred difference discretisation that operates exclusively on the regular grid serves as a reference. The reprise of the ISMIP-HOM experiments indicates that both discretisations are capable of reproducing the higher-order model inter-comparison results. This setup allows a direct comparison of the two numerical implementations also with respect to their convergence behaviour. First and foremost, the new finite difference scheme facilitates convergence by a factor of up to 7 and 2.6 in average. In addition to this decrease in computational costs, the accuracy for the resultant velocity field can be chosen higher in the novel finite difference implementation. Changing the discretisation also prevents build-up of local field irregularites that occasionally cause divergence of the solution for the reference discretisation. <br><br> The improved behaviour makes the new discretisation more reliable for extensive application to real ice geometries. Higher accuracy and robust numerics are crucial in time dependent applications since numerical oscillations in the velocity field of subsequent time steps are attenuated and divergence of the solution is prevented

Chemoreception and neuroplasticity in respiratory circuits

The respiratory central pattern generator must respond to chemosensory cues to maintain oxygen (O2) and carbon dioxide (CO2) homeostasis in the blood and tissues. To do this, sensorial cells located in the periphery and central nervous system monitor the arterial partial pressure of O2 and CO2 and initiate respiratory and autonomic reflex adjustments in conditions of hypoxia and hypercapnia. In conditions of chronic intermittent hypoxia (CIH), repeated peripheral chemoreceptor input mediated by the nucleus of the solitary tract induces plastic changes in respiratory circuits that alter baseline respiratory and sympathetic motor outputs and result in chemoreflex sensitization, active expiration, and arterial hypertension. Herein, we explored the hypothesis that the CIH-induced neuroplasticity primarily consists of increased excitability of pre-inspiratory/inspiratory neurons in the pre-Bötzinger complex. To evaluate this hypothesis and elucidate neural mechanisms for the emergence of active expiration and sympathetic overactivity in CIH-treated animals, we extended a previously developed computational model of the brainstem respiratory-sympathetic network to reproduce experimental data on peripheral and central chemoreflexes post-CIH. The model incorporated neuronal connections between the 2nd-order NTS neurons and peripheral chemoreceptors afferents, the respiratory pattern generator, and sympathetic neurons in the rostral ventrolateral medulla in order to capture key features of sympathetic and respiratory responses to peripheral chemoreflex stimulation. Our model identifies the potential neuronal groups recruited during peripheral chemoreflex stimulation that may be required for the development of inspiratory, expiratory and sympathetic reflex responses. Moreover, our model predicts that pre-inspiratory neurons in the pre-Bötzinger complex experience plasticity of channel expression due to excessive excitation during peripheral chemoreflex. Simulations also show that, due to positive interactions between pre-inspiratory neurons in the pre-Bötzinger complex and expiratory neurons in the retrotrapezoid nucleus, increased excitability of the former may lead to the emergence of the active expiratory pattern at normal CO2 levels found after CIH exposure. We conclude that neuronal type specific neuroplasticity in the pre-Bötzinger complex induced by repetitive episodes of peripheral chemoreceptor activation by hypoxia may contribute to the development of sympathetic over-activity and hypertension

Stretching and Kibble scaling regimes for Hubble-damped defect networks

The cosmological evolution of topological defect networks can broadly be divided into two stages. At early times they are friction dominated due to particle scattering and therefore nonrelativistic and may either be conformally stretched or evolve in the Kibble regime. At late times they are relativistic and evolve in the well-known linear scaling regime. In this work we show that a sufficiently large Hubble damping (that is a sufficiently fast expansion rate) leads to a linear scaling regime where the network is nonrelativistic. This is therefore another realization of a Kibble scaling regime and also has a conformal stretching regime counterpart which we characterize for the first time. We describe these regimes using analytic arguments in the context of the velocity-dependent one-scale model, and we confirm them using high-resolution 4096[superscript]3 field-theory simulations of domain wall networks. We also use these simulations to improve the calibration of this analytic model for the case of domain walls

Comparative Analysis of Super-Kamiokande and SNO Solar-Neutrino Data and the Photospheric Magnetic Field

We analyze Super-Kamiokande, SNO, and photospheric magnetic-field data for the common time interval, namely the SNO D2O phase. Concerning rotational modulation, the magnetic-field power spectrum shows the strongest peaks at the second and sixth harmonics of the solar synodic rotation frequency [3 nu(rot) and 7 nu(rot)]. The restricted Super-Kamiokande dataset shows strong modulation at the second harmonic. The SNO D2O dataset shows weak modulation at that frequency, but strong modulation in the sixth-harmonic frequency band. We estimate the significance level of the correspondence of the Super-Kamiokande second-harmonic peak with the corresponding magnetic-field peak to be 0.0004, and the significance level of the correspondence of the SNO D2O sixth-harmonic peak with the corresponding magnetic-field peak to be 0.009. By estimating the amplitude of the modulation of the solar neutrino flux at the second harmonic from the restricted Super-Kamiokande dataset, we find that the weak power at that frequency in the SNO D2O power spectrum is not particularly surprising. Concerning 9.43 yr-1, we find no peak at this frequency in the power spectrum formed from the restricted Super-Kamiokande dataset, so it is no surprise that this peak does not show up in the SNO D2O dataset, either.Comment: 32 pages, 8 tables, 16 figure

A Multicenter Evaluation of Vancomycin-Associated Acute Kidney Injury in Hospitalized Patients with Acute Bacterial Skin and Skin Structure Infections

BACKGROUND: We sought to determine the real-world incidence of and risk factors for vancomycin-associated acute kidney injury (V-AKI) in hospitalized adults with acute bacterial skin and skin structure infections (ABSSSI). METHODS: Retrospective, observational, cohort study at ten U.S. medical centers between 2015 and 2019. Hospitalized patients treated with vancomycin (≥ 72 h) for ABSSSI and ≥ one baseline AKI risk factor were eligible. Patients with end-stage kidney disease, on renal replacement therapy or AKI at baseline, were excluded. The primary outcome was V-AKI by the vancomycin guidelines criteria. RESULTS: In total, 415 patients were included. V-AKI occurred in 39 (9.4%) patients. Independent risk factors for V-AKI were: chronic alcohol abuse (aOR 4.710, 95% CI 1.929-11.499), no medical insurance (aOR 3.451, 95% CI 1.310-9.090), ICU residence (aOR 4.398, 95% CI 1.676-11.541), Gram-negative coverage (aOR 2.926, 95% CI 1.158-7.392) and vancomycin duration (aOR 1.143, 95% CI 1.037-1.260). Based on infection severity and comorbidities, 34.7% of patients were candidates for oral antibiotics at baseline and 39.3% had non-purulent cellulitis which could have been more appropriately treated with a beta-lactam. Patients with V-AKI had significantly longer hospital lengths of stay (9 vs. 6 days, p = 0.001), higher 30-day readmission rates (30.8 vs. 9.0%, p \u3c 0.001) and increased all-cause 30-day mortality (5.1 vs. 0.3%, p = 0.024) CONCLUSIONS: V-AKI occurred in approximately one in ten ABSSSI patients and may be largely prevented by preferential use of oral antibiotics whenever possible, using beta-lactams for non-purulent cellulitis and limiting durations of vancomycin therapy

The study of vancomycin use and its adverse reactions associated to patients of a brazilian university hospital

<p>Abstract</p> <p>Background</p> <p>Vancomycin is an antibiotic of growing importance in the treatment of hospital infections, with particular emphasis on its value in the fight against methicillin-resistant <it>Staphylococcus aureus</it>. However its usage profile must be evaluated to assure maximum benefit and minimum risk.</p> <p>Findings</p> <p>A cross-sectional retrospective study was carried out among inpatients that received vancomycin in a Brazilian quaternary hospital. The occurrence of adverse reactions reported was evaluated in medical records relating to patients taking vancomycin during a one year period. Males comprised 52% (95% CI: 41.7-60.2%) of the sample population, with a mean age of 50.6 (95% CI: 47.2-54.0) years and mean treatment period of 9.7 (95% CI: 8.0-11.5) Days. It was verified that nephrotoxicity occurred in 18.4% (95% CI: 11.3-27.5) of patients, Red man syndrome occurred in 2% (95% CI 0.2-7.2), while the occurrence of thrombocytopenia was 7.1% (95% CI: 2.9-14.2).</p> <p>Conclusions</p> <p>It may be noted that even after 50 years of use, adverse reactions associated with vancomycin continue with high frequency, presenting a public health problem, especially considering its current use in cases of multidrug resistant infections. In this context, we emphasize the importance of intensive pharmacovigilance in hospital as a surveillance tool after drug approval by the sanitary authority.</p

Opinion dynamics: models, extensions and external effects

Recently, social phenomena have received a lot of attention not only from social scientists, but also from physicists, mathematicians and computer scientists, in the emerging interdisciplinary field of complex system science. Opinion dynamics is one of the processes studied, since opinions are the drivers of human behaviour, and play a crucial role in many global challenges that our complex world and societies are facing: global financial crises, global pandemics, growth of cities, urbanisation and migration patterns, and last but not least important, climate change and environmental sustainability and protection. Opinion formation is a complex process affected by the interplay of different elements, including the individual predisposition, the influence of positive and negative peer interaction (social networks playing a crucial role in this respect), the information each individual is exposed to, and many others. Several models inspired from those in use in physics have been developed to encompass many of these elements, and to allow for the identification of the mechanisms involved in the opinion formation process and the understanding of their role, with the practical aim of simulating opinion formation and spreading under various conditions. These modelling schemes range from binary simple models such as the voter model, to multi-dimensional continuous approaches. Here, we provide a review of recent methods, focusing on models employing both peer interaction and external information, and emphasising the role that less studied mechanisms, such as disagreement, has in driving the opinion dynamics. [...]Comment: 42 pages, 6 figure

Mechanisms for Tuning Engineered Nanomaterials to Enhance Radiation Therapy of Cancer.

Engineered nanomaterials that produce reactive oxygen species on exposure to X- and gamma-rays used in radiation therapy offer promise of novel cancer treatment strategies. Similar to photodynamic therapy but suitable for large and deep tumors, this new approach where nanomaterials acting as sensitizing agents are combined with clinical radiation can be effective at well-tolerated low radiation doses. Suitably engineered nanomaterials can enhance cancer radiotherapy by increasing the tumor selectivity and decreasing side effects. Additionally, the nanomaterial platform offers therapeutically valuable functionalities, including molecular targeting, drug/gene delivery, and adaptive responses to trigger drug release. The potential of such nanomaterials to be combined with radiotherapy is widely recognized. In order for further breakthroughs to be made, and to facilitate clinical translation, the applicable principles and fundamentals should be articulated. This review focuses on mechanisms underpinning rational nanomaterial design to enhance radiation therapy, the understanding of which will enable novel ways to optimize its therapeutic efficacy. A roadmap for designing nanomaterials with optimized anticancer performance is also shown and the potential clinical significance and future translation are discussed