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

A Review of Combination Antimicrobial Therapy for Enterococcus Faecalis Bloodstream Infections and Infective Endocarditis

Enterococci, one of the most common causes of hospital-associated infections, are responsible for substantial morbidity and mortality. Enterococcus faecalis, the more common and virulent species, cause serious high-inoculum infections, namely infective endocarditis, that are associated with cardiac surgery and mortality rates that remained unchanged for the last 30 years. The best cure for these infections are observed with combination antibiotic therapy; however, optimal treatment has not been fully elucidated. It is the purpose of this review to highlight treatment options, their limitations, and provide direction for future investigative efforts to aid in the treatment of these severe infections. While ampicillin plus ceftriaxone has emerged as a preferred treatment option, mortality rates continue to be high, and from a safety standpoint, ceftriaxone, unlike other cephalosporins, promotes colonization with vancomycin resistant-enterococci due to high biliary concentrations. More research is needed to improve patient outcomes from this high mortality disease

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

Diagnostic Stewardship: A Clinical Decision Rule for Blood Cultures in Community-Onset Methicillin-Resistant Staphylococcus aureus (MRSA) Skin and Soft Tissue Infections

INTRODUCTION: The emergence, spread and persistence of methicillin-resistant Staphylococcus aureus (MRSA) as a causative pathogen in community-onset (CO) skin and soft tissue infections (SSTIs) have resulted in substantial changes in the management of these infections. The indications for obtaining blood cultures in patients with CO-MRSA SSTIs remain poorly defined. The objectives of this study were to derive and validate a clinical decision rule that predicts the probability of MRSA bacteremia in CO-MRSA SSTIs and to identify a low-risk population for whom blood cultures may be safely omitted. METHODS: This was a retrospective, case-control study with an internal temporal validation cohort conducted at two large urban academic medical centers. Hospitalized adults with CO-MRSA SSTI between 2010 and 2018 were included. Independent predictors of MRSA bacteremia were identified through multivariable logistic regression. A decision rule was derived using weighted coefficient-based scoring. The decision rule was validated in an internal temporal validation cohort. RESULTS: A total of 307 patients (155 cases and 152 controls) were included in the derivation cohort. A decision rule was created with a major criterion defined as purulent cellulitis and minor criteria defined as abnormal temperature, intravenous drug use, leukocytosis, tachycardia, body mass index \u3c 25 kg/m CONCLUSION: The decision rule developed and validated in this study provides a standardized, evidenced-based approach to determine the need for blood cultures based on bacteremia risk

Begging and feeding responses vary with relatedness and sex of provisioners in a cooperative breeder

Begging behaviour can provide information on offspring hunger levels and be used by parents to adjust food provisioning efforts. In cooperative breeders, helpers also provide care by feeding the young. However, how helpers of different sex and relatedness to the offspring respond to begging behaviour has rarely been studied in cooperatively breeding species, which limits our understanding of the indirect and/or direct benefits that helpers may obtain by responding to offspring demand. Here, we used a cooperatively breeding bird, the sociable weaver, Philetairus socius, to investigate how nest intervisit intervals of breeders and different types of helpers, distinguished by sex and relatedness, varied with acoustic begging. Moreover, we tested whether these different classes of provisioners experienced distinct levels of begging. Our results show that only breeding males, but not breeding females or helpers of any sex and relatedness to the nestlings, returned faster to the nest to feed after experiencing more begging calls. When contrasted directly, we confirmed a statistically supported difference in responses to begging between male and female breeders. Surprisingly, second-order relatives experienced more begging calls than the other classes of more related helpers and breeders. These results show that we might find differences in how provisioners respond to begging levels when classifying group members according to their potential fitness gains. In sociable weavers, the benefits and costs of adjusting feeding efforts to begging seem to differ with sex and life history stage. Experimental and more detailed investigations on begging-feeding interactions are necessary to understand the origin and prevalence of these differences across cooperatively breeding systems. (c) 2021 The Author(s). Published by Elsevier Ltd on behalf of The Association for the Study of Animal Behaviour. This is an open access article under the CC BY license (http://creativecommons.org/licenses/ by/4.0/)

Patients\u27 perspectives of tuberculosis treatment challenges and barriers to treatment adherence in Ukraine: a qualitative study

OBJECTIVES: To understand the challenges faced by patients with tuberculosis (TB) and factors that influence TB treatment adherence in Ukraine. DESIGN: Qualitative study. SETTING: TB treatment facilities in Kyiv Oblast, Ukraine. PARTICIPANTS: Sixty adults who had undergone treatment for drug-sensitive TB between June 2012 and August 2015. METHODS: We conducted semistructured, in-depth, individual interviews among a purposively selected clinical sample of patients previously treated for drug-sensitive TB. Interview content encompassed WHO\u27s framework for barriers to adherence to long-term therapies and included questions about patient preferences and motivators concerning treatment adherence. We examined treatment experience across strata defined by previously identified risk correlates of non-adherence. RESULTS: Among 60 participants, 19 (32.8%) were HIV positive, 12 (20.3%) had substance use disorder and 9 (15.0%) had not completed TB treatment. Respondents discussed the psychological distress associated with hospital-based TB care, as well as perceived unsupportive, antagonistic interactions with TB providers as major challenges to treatment adherence. An additional barrier to successful treatment completion included the financial toll of lost income during TB treatment, which was exacerbated by the additional costs of ancillary medications and transportation to ambulatory TB clinics. The high pill burden of TB treatment also undermined adherence. These challenges were endorsed among participants with and without major risk factors for non-adherence. CONCLUSIONS: Our findings highlight important barriers to TB treatment adherence in this study population and suggest specific interventions that may be beneficial in mitigating high rates of poor treatment outcomes for TB in Ukraine

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