Search

This paper studies the seismic response of structure-elevator systems. Dynamic models are developed to represent the structure and elevator counterweight subsystems, with nonlinear contact elements between the counterweight and the guide rails. The computational output is given in terms of maximum rail stresses, relative elastic deflections, and interaction forces between counterweight and guide rails. Numerical methods are developed and analysis is performed to study the seismic response of the combined system. The structure subsystem is represented by six flexural modes (i.e., three for each of two horizontal axes), while the counterweight subsystem is modeled with four degrees of freedom. A nonlinear contact element with air gaps, viscous damper, Coulomb friction, and variable stiffness of guide rail is developed to model the dynamic interaction between structure and counterweight subsystems. Nonlinear time-history dynamic analysis was carried out using step-by-step integration of the 20 first-order differential equations using the Runge-Kutta fifth-order method. It was observed that contact forces and rail stresses depend on the mass of the counterweight, width of gaps, cross-sectional properties of rails, vertical motion velocity, and intensities of earthquake excitations. Dynamic contact between the counterweight and guide rails introduces large forces that may endanger the elevator system.

Clinical presentations of COVID-19 are highly variable, yet the precise mechanisms that govern the pathophysiology of different disease courses remain poorly defined. Across the spectrum of disease severity, COVID-19 impairs both innate and adaptive host immune responses by activating innate immune cell recruitment, while resulting in low lymphocyte counts. Recently, several reports have shown that patients with severe COVID-19 exhibit a dysregulated myeloid cell compartment, with increased myeloid-derived suppressor cells (MDSCs) correlating with disease severity. MDSCs, in turn, promote virus survival by suppressing T-cell responses and driving a highly pro-inflammatory state through the secretion of various mediators of immune activation. Here, we summarize the evidence on MDSCs and myeloid cell dysregulation in COVID-19 infection and discuss the potential of MDSCs as biomarkers and therapeutic targets in COVID-19 pneumonia and associated disease., Competing Interests: Authors MR, FS and DH were employed by the company Novartis., (Copyright © 2021 Rowlands, Segal and Hartl.)

We describe a physics-based learning model for predicting the immunogenicity of cytotoxic T lymphocyte (CTL) epitopes derived from diverse pathogens including SARS-CoV-2. The model was trained and optimized on the relative immunodominance of CTL epitopes in human immunodeficiency virus infection. Its accuracy was tested against experimental data from patients with COVID-19. Our model predicts that only some SARS-CoV-2 epitopes predicted to bind to HLA molecules are immunogenic. The immunogenic CTL epitopes across all SARS-CoV-2 proteins are predicted to provide broad population coverage, but those from the SARS-CoV-2 spike protein alone are unlikely to do so. Our model also predicts that several immunogenic SARS-CoV-2 CTL epitopes are identical to seasonal coronaviruses circulating in the population and such cross-reactive CD8 + T cells can indeed be detected in prepandemic blood donors, suggesting that some level of CTL immunity against COVID-19 may be present in some individuals before SARS-CoV-2 infection., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Human cytomegalovirus (HCMV) can cause significant disease in immunocompromised patients, and treatment options are limited by toxicities. CSJ148 is a combination of two anti-HCMV human monoclonal antibodies (LJP538 and LJP539) that bind to and inhibit the functions of viral HCMV glycoprotein B (gB) and the pentameric complex, consisting of glycoproteins gH, gL, UL128, UL130, and UL131. In this phase 2, randomized, placebo-controlled trial, we evaluated the safety and efficacy of CSJ148 for prophylaxis of HCMV in patients undergoing allogeneic hematopoietic stem cell transplantation. As would be expected in the study population, all the patients (100%) reported at least one treatment-emergent adverse event. There were 22 deaths during this study, and over 80% of the patients receiving placebo or CSJ148 developed at least one adverse event of grade 3 or higher severity. No subject who received antibody developed a hypersensitivity- or infusion-related reaction. CSJ148-treated patients showed trends toward decreased viral load, shorter median duration of preemptive therapy, and fewer courses of preemptive therapy. However, the estimated probability that CSJ148 decreases the need for preemptive therapy compared to placebo was 69%, with a risk ratio of 0.89 and a 90% credible interval of 0.61 to 1.31. The primary efficacy endpoint was therefore not met, indicating that CSJ148 did not prevent clinically significant HCMV reactivation in recipients of allogeneic hematopoietic cell transplants. (This study has been registered at ClinicalTrials.gov under identifier NCT02268526 and at EudraCT under number 2017-002047-15.)., (Copyright © 2020 Maertens et al.)

Infections caused by antibiotic-resistant Gram-negative bacteria expressing extended-spectrum β-lactamases and carbapenemases are a growing global problem resulting in increased morbidity and mortality with limited treatment options. LYS228 is a novel intravenous monobactam antibiotic targeting penicillin binding protein 3 with potent activity against Enterobacteriaceae , including multidrug-resistant clinical isolates expressing serine and metallo-β-lactamases. In this study, we evaluated the safety, tolerability, and pharmacokinetics of single and multiple intravenous doses of LYS228 in healthy volunteers. LYS228 was safe: no serious adverse events were reported. Adverse events, with the exception of catheter-related events, occurred sporadically, with similar incidences between LYS228 and placebo groups. No apparent adverse event-dose relationship was identified. LYS228 was not associated with any clinically significant dose-related hematologic, hepatic, or renal laboratory abnormalities. The most frequently observed adverse events were local injection site reactions, noted in 91.7% and 75.0% of subjects administered multiple doses of LYS228 and placebo, respectively. LYS228 demonstrated pharmacokinetic properties consistent with those of other β-lactam antibiotics, with systemic exposures slightly greater than dose proportional, short terminal half-lives (between 1.0 and 1.6 h) with no significant accumulation, and rapid clearance predominantly through urinary excretion., (Copyright © 2019 Osborn et al.)

Barrett's esophagus (BE) is a complication of gastroesophageal reflux disease, and a premalignant lesion for esophageal adenocarcinoma (EAC). Observational studies suggest that endoscopic surveillance is associated with the detection of dysplasia and EAC at an early stage along with improved survival, but controversies still remain. The management of patients with BE involves endoscopic surveillance, preventive and clinical measures for cancer, and endoscopic and surgical approaches to treatment. Deciding upon the most appropriate treatment is a challenge. This study presents the results and the effectiveness of these practices.

Protein p53 is the tumor suppressor involved in cell cycle control and apoptosis. There are several polymorphisms reported for p53 which can affect important regions involved in protein tumor suppressor activity. Amongst the polymorphisms described, R213R and 13949 g-->a are rarely studied, with an estimate frequency not yet available for the Brazilian population. The purpose of this study was to investigate the genotype and allele frequencies and associations of these polymorphisms in a group of patients with altered esophageal tissue from South Brazil and compare with the frequency observed for a control population. A total of 35 patients for R213R and 45 for 13494 g-->a polymorphisms analysis with gastroesophageal reflux disease (GERD) symptoms diagnosed by upper digestive endoscopy and confirmed by biopsy were studied. For both groups, 100 controls were used for comparison. Loss of heterozygosity (LOH) was also analyzed for a selected group of patients where normal and affected tissue was available. There was one patient with Barrett's Esophagus (BE) showing LOH for R213R out of two heterozygous samples analyzed and two patients (esophagitis and BE) for 13494 g-->a polymorphism. We also aimed to build a haplotype for both polymorphisms collectively analyzed with R27P polymorphism, previously reported by our group. There were no significant differences in allele and genotype distribution between patients and controls. Although using esophagitis, intestinal metaplasia of the cardia and BE samples, all non-neoplastic lesions, we can conclude that these sites do not represent genetic susceptibility markers for the development and early progression of GERD to BE and esophageal cancer. Additional studies are required in order to investigate other determiners of early premalignant lesions known to predispose to esophageal cancer.

Background: Bleeding ulcers are a major problem in public health and represent approximately half of all the cases of upper gastrointestinal hemorrhage in the United States. This study aims to determine the prognostic value of factors such as clinical history, laboratory and endoscopic findings in the occurrence of new episodes of bleeding in patients who have upper gastrointestinal hemorrhage caused by gastric or duodenal peptic ulcer., Methods: A cohort study with 94 patients was designed to investigate prognostic factors to the occurrence of new episodes of bleeding., Results: From the 94 patients studied, 88 did not present a new bleeding episode in the 7 days following hospital admission. The incidence of rebleeding was significantly higher in those patients with hemoglobin < 6 g/dL at the admission (P = 0.03, RR = 6.2). The localization of the ulcers in bulb was positively associated to rebleeding (P = 0.003). The rebleeding group needed a greater number of units transfunded (P = 0.03) and the time of hospitalization was longer than the time of the hemostasia group (P = 0.0349)., Conclusions: The identification of patients with risk of death by bleeding peptic ulcer remains as a challenge, once few factors are capable of predicting the severity of the evolution. The identification of such factors will allow the choice of the better therapeutic conduct improving the diagnosis and decreasing the rate of rebleeding and the mortality.

A case of a middle-aged Black woman with maturity-on-set diabetes is described. The patient had had a cerebrovascular accident and subsequently developed thrombosis of the descending thoracic aorta, with extension into the left subclavian artery and emboli in the right femoral and left brachial arteries. Occlusive large-vessel disease rarely occurs in Black diabetics. Vascular disorders and haemostatic factors in Black and White diabetics are discussed.

We report on a patient with polymyositis which caused a malabsorption syndrome. The radiological findings included marked dilatation of the oesophagus and small intestine. The malabsorption syndrome appears to arise from bacterial overgrowth associated with intestinal stasis. The literature is reviewed. Polymyositis or dermatomyositis, like scleroderma, may involve the small bowel and cause the malabsorption syndrome.

Three patients presenting in the postpartum period with veno-occlusive disease not related to the ingestion of pyrrolizidine alkaloids are described. The patients were treated by intravenous reinfusion of the ascitic fluid. This form of therapy has, to our knowledge, not previously been reported in the management of this condition.

Seven patients with inferior vena-caval obstruction associated with cirrhosis of the liver are described. Inferior vena-caval obstruction is suggested when an enlarged azygous vein is seen on chest radiography, or when superficial collateral veins draining upwards are visible on the abdomen and chest. When a short obstruction or 'web' is present, this should be treated surgically. Venous thrombosis below the obstruction may result in occlusion of a long segment of the vena cava. Chronic suprahepatic venous obstruction may cause macronodular cirrhosis and predispose to the development of hepatocellular carcinoma.

During the period August 1977 to April 1978, 14 Black patients in Johannesburg area had systemic infections caused by Listeria monocytogenes. Nine of these patients were neonates who presented with septicaemia (5 cases) or septicaemia and meningitis (4 cases) and 5 were adults, all of whom had meningitis. The mortality rate was 43% (6/14), with 4 neonatal and 2 adult deaths. All isolates of L. monocytogenes were type 4b. Only sporadic cases of human listeriosis have previously been reported in South Africa, and the cases reported here constitute the first epidemic in this country.