ABSTRACT
The academy form competences to work in the routine, without worries, without unknown hazards. The rules and objectives in routine activities are clear and require operational discipline to control the cost of production and product quality. The current educational model does not prepare society and groups for an emergency or even for decisions in a crisis, where resources are scarce mainly because the necessary knowledge about danger and its mechanism of action is lacking. What really happens in the chain event scenario when the danger is unknown? What are the typical models of action of the emergency leader and his team? What are the required actions in crisis management required for a BS type event considering the scarce resources, the high level of stress and the direction of the danger energy? Which models are indicated for the situation of unknown danger and its intense energy flow with high impacts during these events? What is the appropriate mind map of those who lead and execute the actions considering the low level of visibility in the events and the dynamic of geopolitics in the BS scenario where, depending on the preparation for emergency, in case of intense demand for attention and action, possible modifications may occur in the map mental for decisions? This work intends to review the discussions already performed about new concepts and tools to be used in the crisis prevention area. Between this works we will understand the effect of the stress level on emergency decisions valuating human error and observing team response using LODA tool. The Human elements designed in the organizational culture, can stop the high danger energy that can flow from some industries. The principal aspects to be constructed and monitored are technology (risk and complexity);management (leadership and stress);and behavior (cooperation, commitment, competence, and communication). By the other hand, human factors are analyzed to avoid situations which hazard energy carriers during top events, as the effect of cultural aspects to chain reaction until the occurrence of disaster. Decision models for the emergency brigade (leader and team) indicate the motor and cognitive gaps that cause lack of control during contingencies. Finally, the analysis of simulation types, by rotating observation of field simulation allow find the deficiencies of the emergency team in a real situation in the future. The methodology divided in following steps are dynamic: first, rescue the discussions about stress and the BS events and, in second step, recognize the intense hazard energy flow through failure events, antecedents, elements and human factors. In third step, we try to locate the gaps and environmental conflicts influencing losses from accidents. Finally, we assess the current event of covid-19 pandemics to suggest correct emergency preparedness actions in the preparation of leaders and their teams regarding cognitive and motor characteristics in situations of high demand. When comparing the characteristics already described by TALEB about BS with the event COVID-19, we intend to carry out a case study to indicate the possible causes this global impact crisis, or even, understand the technological disaster causes where uncontrolled events from chemical, nuclear, and oil industry begins chain reactions until the disaster. Unfortunately, a Crisis situation can be caused from several intricated dimensions, making difficult the contingency and mitigation actions. © 36th Center for Chemical Process Safety International Conference, CCPS 2021 - Topical Conference at the 2021 AIChE Spring Meeting and 17th Global Congress on Process Safety.
ABSTRACT
Introduction: Patients with hematologic malignancies are at an increased risk of morbid/mortality from COVID-19. Our prospective clinical study evaluated immune responses to COVID-19 mRNA vaccines in patients with B-cell lymphoma who had received CD19-directed chimeric antigen receptor (CAR) T cell therapy. Methods: We measured SARS-CoV-2 neutralizing activity of plasma from 18 patients and 4 healthy controls (HC) and antibody titers against viral spike proteins (S1, S2, RBD) including their delta variants using an enzyme-linked immunoassay (ELISA). We measured B cell subpopulations in the patients' blood using flow cytometry. Results: We found that the peripheral blood plasma from 3/4 HCs showed substantial SARS-CoV-2 neutralizing activity already at 4 weeks after the first dose of COVID-19 mRNA vaccine while none of the CD19 CART patients evidenced any antibody-mediated neutralizing activity at the same point in time. At 4 weeks after receiving the second dose of the vaccine, all 4 HCs showed complete neutralizing activity. In marked contrast, only 1 of 14 CART patients evidenced any relevant antibody-mediated SARS-CoV-2 neutralizing activity. Assessing whether a globally insufficient antibody-mediated immunity was the underlying cause of the lack of a response to the COVID-19 vaccine in our CART patients, we found that IgG antibody levels against common microbial and viral antigens like influenza, Epstein-Barr virus (EBV), Cytomegalovirus (CMV), and tetanus toxoid, were comparable to those observed in HCs. However, while at 4 weeks post second dose of the vaccine the HCs showed high levels of vaccine-induced IgG antibody titers against all the viral spike proteins (S1, S2, RBD), including the delta variants of the S1 and RBD proteins, the vast majority of our CART patients did not evidence any SARS-CoV-2-specific antibodies. Importantly, a third booster vaccination did not lead to an improvement in the antiviral immunity in the 4 CART patients analyzed. When we assessed B cell subpopulations in the blood of patients and HCs, we found that prior treatments had completely eradicated all CD19+/CD20+ B cells in the patients while numbers of long-lived memory plasma cells were comparable to those of HCs. Conclusions: In this study, 17 of 18 patients with lymphoma who received CD19 CART therapy had very poor immunoreactivity to 1-3 doses of mRNA-based COVID-19 vaccines. Importantly, antibody responses to common recall antigens were preserved, suggesting impaired immune response primarily against novel antigens like SARS-COV-2. This lack of immunoreactivity against novel antigens was probably based on the eradication of earlier-stage B cell subpopulations after treatment with anti-CD19 and anti-CD20 immunotherapies.
ABSTRACT
The academy form competences to work in the routine, without worries, without unknown hazards. The rules and objectives in routine activities are clear and require operational discipline to control the cost of production and product quality. The current educational model does not prepare society and groups for an emergency or even for decisions in a crisis, where resources are scarce mainly because the necessary knowledge about danger and its mechanism of action is lacking. What really happens in the chain event scenario when the danger is unknown? What are the typical models of action of the emergency leader and his team? What are the required actions in crisis management required for a BS type event considering the scarce resources, the high level of stress and the direction of the danger energy? Which models are indicated for the situation of unknown danger and its intense energy flow with high impacts during these events? What is the appropriate mind map of those who lead and execute the actions considering the low level of visibility in the events and the dynamic of geopolitics in the BS scenario where, depending on the preparation for emergency, in case of intense demand for attention and action, possible modifications may occur in the map mental for decisions? This work intends to review the discussions already performed about new concepts and tools to be used in the crisis prevention area. Between this works we will understand the effect of the stress level on emergency decisions valuating human error and observing team response using LODA tool. The Human elements designed in the organizational culture, can stop the high danger energy that can flow from some industries. The principal aspects to be constructed and monitored are technology (risk and complexity);management (leadership and stress);and behavior (cooperation, commitment, competence, and communication). By the other hand, human factors are analyzed to avoid situations which hazard energy carriers during top events, as the effect of cultural aspects to chain reaction until the occurrence of disaster. Decision models for the emergency brigade (leader and team) indicate the motor and cognitive gaps that cause lack of control during contingencies. Finally, the analysis of simulation types, by rotating observation of field simulation allow find the deficiencies of the emergency team in a real situation in the future. The methodology divided in following steps are dynamic: first, rescue the discussions about stress and the BS events and, in second step, recognize the intense hazard energy flow through failure events, antecedents, elements and human factors. In third step, we try to locate the gaps and environmental conflicts influencing losses from accidents. Finally, we assess the current event of covid-19 pandemics to suggest correct emergency preparedness actions in the preparation of leaders and their teams regarding cognitive and motor characteristics in situations of high demand. When comparing the characteristics already described by TALEB about BS with the event COVID-19, we intend to carry out a case study to indicate the possible causes this global impact crisis, or even, understand the technological disaster causes where uncontrolled events from chemical, nuclear, and oil industry begins chain reactions until the disaster. Unfortunately, a Crisis situation can be caused from several intricated dimensions, making difficult the contingency and mitigation actions. © 2021 American Institute of Chemical Engineers. All rights reserved.
ABSTRACT
Introduction: Patients with hematologic malignancies are at an increased risk of morbidity and mortality from COVID-19 disease (Vijenthira, Blood 2020). This is likely a result of combination of immunodeficiency conferred by the disease and the therapeutics. The immunogenicity of the COVID-19 vaccines in patients with exposure to CD19 directed Chimeric Antigen Receptor (CAR)-T cell therapy is not established. CD19 CAR-T cell therapies cause B-cell aplasia, which in turn can affect humoral immune response against novel antigens. Herein, we present results from our prospectively conducted clinical study to evaluate immune responses against mRNA based COVID-19 vaccines in patients with lymphoma who have received CD19 directed CAR-T cell therapy. Methods: All patients and healthy controls were enrolled in a prospective clinical study evaluating immune responses against commercial COVID-19 RNA vaccines in patients with hematologic malignancies. Plasma samples were generated from heparinized peripheral blood of 4 heathy controls (HCs) receiving the same vaccines and 19 B cell lymphoma patients treated with CD19 CAR- T cells. Samples from ~4 weeks post second dose of the vaccine (d56) were available for 14 CAR-T patients, for 5 CAR-T patients samples were available from ~4 weeks after the first dose (d28). Plasma samples were analyzed in an enzyme-linked immunosorbent assay (ELISA) using different full-length recombinant SARS-CoV-2 proteins and control proteins. Neutralizing activity was measured using the cPass Neutralization Antibody Detection Kit (GenScript Biotech). Results: Results from 4 healthy controls and 19 patients (12 males and 7 females) with lymphoma are reported. Median age for the lymphoma patients is 65 years. Eleven patients had large B cell lymphoma, 5 had follicular lymphoma and 3 had mantle cell lymphoma as primary diagnoses. Seventeen patients had advance stage disease (III/IV stage) and had received a median of 3 prior lines of therapy. All patients received CD19 directed CAR-T cell therapy. Ten patients received Moderna vaccine and 9 received Pfizer vaccine. Median time between CAR-T infusion and first COVID-19 vaccine was 258 days. While the peripheral blood plasma from 3/4 HCs already showed substantial SARS-CoV-2 neutralizing activity at ~4 weeks after the first dose of COVID-19 mRNA vaccine, none of the 5 CD19 CAR-T patients analyzed evidenced any antibody-mediated neutralizing activity in their blood at the same point in time (Figure 1A). Around 4 weeks after receiving the second dose of the vaccine, all 4 HCs tested evidenced complete or almost complete neutralizing activity (Figure 1B). In marked contrast, only 1 out of 14 CAR-T patients analyzed evidenced any relevant antibody-mediated SARS-CoV-2 neutralizing activity in their blood (Figure 1B). Interestingly, when we asked whether a globally insufficient antibody-mediated immunity was the underlying cause of the lack of a response to the COVID-19 vaccine in our CAR-T patients, we found that that was clearly not the case since anti-Flu, -TT, and -EBV responses were equivalent to the ones observed in HCs (Figure 2A). However, while at ~4 weeks post second dose of the vaccine the HCs showed marked antibody titers against all the viral spike proteins including their “delta” variants (Figure 2B), that was not the case for our CAR-T patients. The vast majority of our CAR-T patients did not evidence IgG antibody responses against any of the SARS-CoV-2 proteins analyzed such as S1, S1 delta, RBD, RBD delta, or S2 (Figure 2B). Conclusion: In this prospectively conducted clinical study, 18 of 19 patients with lymphoma who have received CD19 CAR-T therapy had poor immunogenicity against mRNA based COVID-19 vaccines as measured by neutralization assays and antibody titers. The antibody titers against B.1.617.2 (delta variant, S1 and RBD protein) were also demonstrably poor. The antibody response to common pathogens (flu, EBV, TT) were preserved, suggesting impaired immune response against novel antigens. Long-term follow-up of this study is ongoin . APR and DJ contributed equally [Formula presented] Disclosures: Dahiya: Kite, a Gilead Company: Consultancy;Atara Biotherapeutics: Consultancy;BMS: Consultancy;Jazz Pharmaceuticals: Research Funding;Miltenyi Biotech: Research Funding. Hardy: American Gene Technologies, International: Membership on an entity's Board of Directors or advisory committees;InCyte: Membership on an entity's Board of Directors or advisory committees;Kite/Gilead: Membership on an entity's Board of Directors or advisory committees.
ABSTRACT
The current conditions of the pandemic, as a result of Covid-19, have led university teachers to look for ways to improve the learning process and the generation of knowledge, taking advantage of the use of information technologies. This research paper proposes a model to support the learning process and knowledge generation using collaborative tools considering two aspects of importance: the management of the learning activity and the implementation using specifically the collaborative wall Padlet to facilitate student participation, team collaboration and the corresponding feedback, reinforcing the generation of knowledge. The results obtained are quite encouraging, identifying based on a satisfaction survey that students build their knowledge based on collaborative learning. © 2021 IEEE.
ABSTRACT
With the present review, we propose recognizing and analyzing some fundamental aspects recently reported in the literature, which relate the oral cavity to SARS CoV-2 infection. A literature search was performed in Pubmed, Scopus, Scielo and the medRivx preprint server. There, articles published during 2019 and 2020 were selected from research associated with oral cavity, COVID 19, SARS-CoV-2, viral diagnosis in saliva and the use of mouth rinses as a possible mechanism to reduce viral load. A total of 33 articles related to oral cavity;SARS-CoV-2 infection;oral manifestations of COVID 19;symptomatology, saliva diagnosis, and the use of mouth rinses to minimize the risk of infection were selected. The oral manifestations of COVID 19 were recognized among the findings;also, the potential of the oral cavity as a site of infection and viral dissemination to other organs was evidenced and the role of saliva as a diagnostic tool for SARS-CoV-2. Knowledge about the oral cavity and the relationship with SARS-CoV-2 is limited, making necessary a better understanding the oral manifestations during COVID-19, symptoms and possible complications in the mouth. The need for the establishment of infection prevention strategies during dental practice is identified.