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Balanced truncation is an attractive method for reducing the dimension of medium-scale dynamical systems. Research in recent years has brought approximate balanced truncation to the large-scale setting. At the heart of this technique are alternating direction implicit (ADI) methods for solving large Lyapunov and Sylvester equations. This work concerns the convergence of these methods. Our primary objective is the practical solution of very large Lyapunov equations. Uncertainty in the selection of shifts for the ADI method and its variants has prevented the widespread adoption of an otherwise promising variant, the block modified Smith method. We examine in detail the role of shift selection, the fundamental minimax problem, and the often startling influence of nonnormality. Our analysis is tied intimately to the decay rate of the singular values of the solutions to these equations. We improve upon past bounds and develop new ones, including bounds based on pseudospectra. In the end, we provide simple yet effective schemes for finding shifts that outperform those produced by conventional selection strategies. To make effective use of these shifts, we provide insights that allow the block modified Smith method to be applied to very large equations in a practical setting. First, we give an error bound in terms of the drop tolerance that substantially improves upon ad hoc choices that could fail or demand excessive memory. Next, we improve the residual calculation in the method, which can be a surprisingly expensive computation. Finally, we provide guidance on the use of complex shifts, when to update the singular value decomposition, and the number of shifts to use. We have succeeded in providing a practical implementation of the block modified Smith method. The success of the algorithm is demonstrated in numerous experiments, culminating in the rapid solution of some of the largest known Lyapunov equations attempted on a workstation.

Borrelia burgdorferi is an extracellular bacterium that causes Lyme disease, an inflammatory, multi-systemic ailment. Interferon-γ (IFNγ) is present in lesions of human Lyme disease and positively correlates with severity of illness. Endothelial cells, which line the vasculature, mediate recruitment of immune cells to sites of infection and inflammation. To determine whether IFNγ contributes to development of Lyme disease through its actions on endothelium, cultured human umbilical vein endothelial cells (HUVEC) were exposed to B. burgdorferi, IFNγ, or the two stimuli together. Treatment of HUVEC with both stimuli enhanced the transendothelial migration of monocytes and diminished that of natural killer cells, compared to each stimulus alone. Adhesion molecules on endothelium are integral to guiding movement of leukocytes into infected tissues. Concurrent stimulation of HUVEC with IFNγ and B. burgdorferi increased expression of two such adhesion molecules, compared to each stimulus singly, and caused a third to disperse from its usual junctional location. Macrophages secrete chemoattractant cytokines (chemokines) that recruit immune cells, which could contribute to accumulation of leukocytes in lesions of Lyme disease. In studies of cultured human and murine macrophages, IFNγ and B. burgdorferi synergistically induced several chemokines for T cells and monocytes, while synergistically downregulating others that attract neutrophils. To investigate the role of IFNγ in the development of Lyme carditis, wild-type and IFNγ-deficient mice were infected with B. burgdorferi. Histological analysis of infected mice revealed no difference in severity of carditis between wild-type and IFNγ-deficient mice at 14, 21, 25, and 28 days post-infection. However, a shift in the types of leukocytes within the hearts of IFNγ-deficient mice was observed at 25 days. In the absence of IFNγ, the number of neutrophils in the heart was increased, while T cells were decreased. Bacterial loads within these hearts were similar to those in wild-type mice. Thus, both in vitro and in vivo studies show that IFNγ and B. burgdorferi cooperate to enhance recruitment of monocytes and T cells, which typify chronic inflammation, and suppress that of neutrophils and natural killer cells, which accumulate during acute inflammation. These results support the hypothesis that IFNγ promotes a shift from acute to chronic inflammation in Lyme disease.

Lyapunov equations with low-rank right-hand sides often have solutions whose singular values decay rapidly, enabling iterative methods that produce low-rank approximate solutions. All previously known bounds on this decay involve quantities that depend quadratically on the departure of the coefficient matrix from normality: these bounds suggest that the larger the departure from normality, the slower the singular values will decay. We show this is only true up to a threshold, beyond which a larger departure from normality can actually correspond to faster decay of singular values: if the singular values decay slowly, the numerical range cannot extend far into the right-half plane.

Background: With the current climate change crisis and its influence on infectious disease transmission there is an increased desire to understand its impact on infectious diseases globally. Hantaviruses are found worldwide, causing infectious diseases such as haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS)/hantavirus pulmonary syndrome (HPS) in tropical regions such as Latin America and the Caribbean (LAC). These regions are inherently vulnerable to climate change impacts, infectious disease outbreaks and natural disasters. Hantaviruses are zoonotic viruses present in multiple rodent hosts resident in Neotropical ecosystems within LAC and are involved in hantavirus transmission. Methods: We conducted a systematic review to assess the association of climatic factors with human hantavirus infections in the LAC region. Literature searches were conducted on MEDLINE and Web of Science databases for published studies according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria. The inclusion criteria included at least eight human hantavirus cases, at least one climatic factor and study from > 1 LAC geographical location. Results: In total, 383 papers were identified within the search criteria, but 13 studies met the inclusion criteria ranging from Brazil, Chile, Argentina, Bolivia and Panama in Latin America and a single study from Barbados in the Caribbean. Multiple mathematical models were utilized in the selected studies with varying power to generate robust risk and case estimates of human hantavirus infections linked to climatic factors. Strong evidence of hantavirus disease association with precipitation and habitat type factors were observed, but mixed evidence was observed for temperature and humidity. Conclusions: The interaction of climate and hantavirus diseases in LAC is likely complex due to the unknown identity of all vertebrate host reservoirs, circulation of multiple hantavirus strains, agricultural practices, climatic changes and challenged public health systems. There is an increasing need for more detailed systematic research on the influence of climate and other co-related social, abiotic, and biotic factors on infectious diseases in LAC to understand the complexity of vector-borne disease transmission in the Neotropics.

Cloze tests prepared both from general interest reading materials and from materials drawn from college texts were administered to 66 international students enrolled in reading classes at the English Language Institute at Texas A&M University. Each student took both an academic and a general cloze test with either every fifth word deleted or every tenth word deleted. There were several purposes for this study: (1) to examine correlational relationships between the general cloze test and standard placement test scores; (2) to examine the correlational relationship between the academic cloze test and an oral proficiency examination; (3) to examine mean scores relative to the deletion scheme to determine whether deletion scheme is a critical factor in either the test construction process or in test score results. Findings with this sample support previous research studies which show the cloze to be significantly correlated with standardized language proficiency measures used for placement and with other integrative language measures as well. Deletion scheme was found to be an irrelevant factor when the difficulty of the material was beyond the student's comprehension level. Practical implications address the issues of placement (the use of cloze as an alternative to or supplement to standardized proficiency measures); instruction (for diagnosis and remediation, for student self-diagnosis, for individualized instruction); and the use of cloze in other educational settings (adult literacy, adult basic education, staff development).

BackgroundHepatic artery infusion (HAI) combined with systemic chemotherapy is a treatment strategy for patients with unresectable liver-only or liver-dominant colorectal liver metastases (CRLM). Although HAI has previously been performed in only a few centers, this study aimed to describe patient selection and initial perioperative outcomes during implementation of a new HAI program.MethodsThe study enrolled patients with CRLM selected for HAI after multi-disciplinary review November 2018–January 2020. Demographics, prior treatment, and perioperative outcomes were assessed. Objective hepatic response was calculated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.ResultsDuring a 14-month period, 21 patients with CRLM underwent HAI pump placement. Of these 21 patients, 20 (95%) had unresectable disease. Most of the patients had synchronous disease (n = 18, 86%) and had received prior chemotherapy (n = 20, 95%) with extended treatment cycles (median 16; interquartile range, 8–22; range, 0–66). The median number of CRLMs was 7 (range, 2–40). Operations often were performed with combined hepatectomy (n = 4, 19%) and/or colectomy/proctectomy (n = 11, 52%). The study had no 90-day mortality. The overall surgical morbidity was 19%. The HAI-specific complications included pump pocket seroma (n = 2), hematoma (n = 1), surgical-site infection (n = 1), and extrahepatic perfusion (n = 1). HAI was initiated in 20 patients (95%). The hepatic response rates at 3 months included partial response (n = 4, 24%), stable disease (n = 9, 53%), and progression of disease (n = 4, 24%), yielding a 3-month hepatic disease control rate (DCR) of 76%.ConclusionImplementation of a new HAI program is feasible, and HAI can be delivered safely to selected patients with CRLM. The initial response and DCR are promising, even for patients heavily pretreated with chemotherapy.

Although most of cases of dengue infections are asymptomatic or mild symptomatic some individuals present warning signs progressing to severe dengue in which plasma leakage is a hallmark. The present study used Electric Cell-substrate Impedance Sensing (ECIS®) which allows for electrical monitoring of cellular barrier function measuring changes in Transendothelial Electric Resistance (TEER) to investigate the parameters associated with dengue induced leakage. Three groups of individuals were tested: dengue-positives with plasma leakage (leakage), dengue-positives without plasma leakage (no leakage), and dengue-negatives (control). Data show that TEER values of human umbilical vein endothelial cells (HUVECs) was significantly lower after incubation with serum from subjects of the leakage group in comparison to the no leakage or control groups. The serum levels of CXCL1, EGF, eotaxin, IFN-γ, sCD40L, and platelets were significantly decreased in the leakage group, while IL-10, IL-6, and IP-10 levels were significantly increased. We also found a strong correlation between TEER values and augmented levels of IP-10, GM-CSF, IL-1α, and IL-8, as well as decreased levels of CXCL1 and platelets. The present work shows that the magnitude of the immune response contributes to the adverse plasma leakage outcomes in patients and that serum components are important mediators of changes in endothelial homeostasis during dengue infections. In particular, the increased levels of IP-10 and the decreased levels of CXCL1 and platelets seem to play a significant role in the disruption of vascular endothelium associated with leakage outcomes after DENV infection. These findings may have important implications for both diagnostic and therapeutic approaches to predict and mitigate vascular permeabilization in those experiencing the most severe clinical disease outcomes after dengue infection.