T he pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to >1.5 million infections in the United States (30% of global cases) and >90,000 deaths as of May 20, 2020 (1). Coronavirus disease (COVID-19, the clinical syndrome associated with SARS-Cov-2) is most commonly characterized by respiratory illness and viral pneumonia with fever, cough, and shortness of breath, and progression to acute respiratory distress syndrome in severe cases (2). Although neurologic complications have been noted in previous human coronavirus infections (3-5), there are few in-depth investigations for neurologic syndromes associated with SARS-CoV-2 infection (6). This deficiency can result from the need to reduce unnecessary staff exposure and difficulties in establishing preillness neurologic status without regular family visitors. It is known that neurons and glia express the putative SARS-CoV-2 receptor angiotensin converting enzyme 2 (7), and that the related coronavirus SARS-CoV (responsible for the 2003 SARS outbreak) can inoculate the mouse olfactory bulb (8). If SARS-CoV-2 can enter the central nervous system (CNS) directly or through hematogenous spread, cerebrospinal fluid (CSF) changes, including viral RNA, IgM, or cytokine levels, might support CNS infection as a cause for neurologic symptoms. We report clinical, blood, neuroimaging, and CSF findings for 3 patients with laboratory-confirmed COVID-19 and a range of neurologic outcomes (neuro-COVID). We also show the presence of SARS-CoV-2 antibodies in the blood and CSF of these patients, consistent with CNS penetration of disease. Methods We describe the clinical, laboratory and radiologic findings for 3 patients with respiratory failure and neurologic complications caused by COVID-19. This case series was reviewed and exempted from Emory Institutional Review Board approval. Medical records were reviewed by 4 of the coauthors (K.B., A.A., M.E.M., and W.T.H.). CSF Serologic Analysis, Cytokines, and Molecular Testing We assessed CSF IgM by using an in-house ELISA against SARS-CoV-2 S1 or envelope (E) protein. This ELISA was modified from an in-house blood-based Encephalopathy and Encephalitis Associated with Cerebrospinal Fluid Cytokine Alterations and Coronavirus Disease,

Ethanol ingestion, via glutathione depletion, increased sepsis-mediated lung dysfunction, and these effects could contribute to the increased risk of ARDS seen in alcoholic patients.

We employed a bile duct ligation (BDL) model of cholestatic liver injury to test the hypothesis that this form of preexisting hepatic dysfunction alters the kinetics of circulating TNF-alpha and IL-6 after Escherichia coli endotoxemia, thereby augmenting mortality and lung injury by a TNF-alpha:leukotriene (LT) axis of inflammation. Male rats were catheterized 13 d after BDL or sham surgery and studied while awake 18 to 24 h later. Cholestasis after BDL was confirmed by baseline serum bilirubin (BDL = 7.34 +/- 0.72 mg/dl, mean +/- SEM, n = 17 versus Sham = 0.25 +/- 0.07, n = 20; p < 0.005) and histopathology. Sham and BDL animals received E. coli lipopolysaccharide serotype O55:B5 (LPS, 5 mg/kg i.v.) or 0.9% NaCl (NS) ending at t = 0 and were monitored over 24 h for vital signs and hemodynamics. In parallel studies, lipoxygenase inhibition was performed using diethylcarbamazine or the 5-lipoxygenase activating-protein inhibitor MK-886. Blood was collected at baseline and at t = 1.5, 3.5, and 24 h for formed elements and for serum endotoxin, TNF-alpha, IL-6, bilirubin, and alanine aminotransferase (ALT). Organs were evaluated at 24 h for histopathology, including neutrophil (PMN) densities and wet/dry weight (W/D) ratios. Cholestasis reduced survival after otherwise nonlethal endotoxemia, with seven of 11 BDL + LPS rats dying within 24 h versus no deaths in BDL + NS (n = 6), Sham + LPS (n = 14), or Sham + NS (n = 6) animals (p < 0.01). Despite equivalent serum endotoxin between groups, circulating TNF-alpha was 8-fold higher in BDL + LPS than in Sham + LPS rats at 1.5 and 3.5 h (p < 0.001), whereas serum TNF-alpha did not differ between BDL + NS and Sham + NS rats. IL-6 likewise was increased differentially by 1.5 h in BDL + LPS animals (11.98 +/- 2.42 ng/ml) versus Sham + LPS rats (3.05 +/- 0.58 ng/ml, p < 0.05). Hypothermia, bradycardic hypotension, and leukopenia were most severe and prolonged in BDL + LPS rats, which also had significantly higher ALT values, W/D ratios, and organ PMN counts. LT inhibition failed to reduce BDL-related differences in serum cytokines or survival after endotoxemia. Thus, cholestasis augments inflammatory responses to gram-negative endotoxemia, sensitizing the host to enhanced fluid flux in multiple organs and to mortality by a LT-independent mechanism.

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Ethanol ingestion, via glutathione depletion, increased sepsis-mediated lung dysfunction, and these effects could contribute to the increased risk of ARDS seen in alcoholic patients.

In this paper, we introduce the Steady-State Policy Synthesis (SSPS) problem which consists of finding a stochastic decision-making policy that maximizes expected rewards while satisfying a set of asymptotic behavioral specifications. These specifications are determined by the steady-state probability distribution resulting from the Markov chain induced by a given policy. Since such distributions necessitate recurrence, we propose a solution which finds policies that induce recurrent Markov chains within possibly non-recurrent Markov Decision Processes (MDPs). The SSPS problem functions as a generalization of steady-state control, which has been shown to be in PSPACE. We improve upon this result by showing that SSPS is in P via linear programming. Our results are validated using CPLEX simulations on MDPs with over 10000 states. We also prove that the deterministic variant of SSPS is NP-hard.

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Samples of magnetite, both pure and doped with divalent copper, Fe 3−x Cu x O 4 , with x = 0, 0.05, 0.10 and 0.20 atm.%, were synthesized hydrothermally. The samples were characterized by Atomic Absorption Spectroscopy, Mössbauer Spectroscopy, X-ray diffraction, Scanning Electron Microscopy and SQUID magnetometry. The analyses made by the above techniques showed that as the Cu 2+ concentration increases, a simultaneous reduction in the magnetic and structural parameters takes place, namely: magnetic hyperfine interactions at octahedral sites, particle size and lattice constant. Degradation in the particles morphology as well as a distribution of their size were also observed. Our study points two important effects of Cu 2+ in magnetite, the first one is its incorporation within the structure, replacing Fe 2+ ions and decreasing both the magnetic hyperfine interactions at octahedral sites and the bulk magnetization, the second one is the contraction of the crystalline lattice of magnetite, because incorporation of Cu 2+ within the structure, generation of vacancies or both simultaneous effects.