Epidemiological and Genomic Analysis of a Large SARS-CoV-2 Outbreak in a Long-Term Care Facility in Catalonia, Spain

9 páginas, 3 figuras, 1 tabla.Limiting outbreaks in long-term care facilities (LTCFs) is a cornerstone strategy to avoid an excess of COVID-19-related morbidity and mortality and to reduce its burden on the health system. We studied a large outbreak that occurred at an LTCF, combining methods of classical and genomic epidemiology analysis. The outbreak lasted for 31 days among residents, with an attack rate of 98% and 57% among residents and staff, respectively. The case fatality rate among residents was 16% (n = 15). Phylogenetic analysis of 59 SARS-CoV-2 isolates revealed the presence of two closely related viral variants in all cases (B.1.177 lineage), revealing a far more complex outbreak than initially thought and suggesting an initial spread driven by staff members. In turn, our results suggest that resident relocations to mitigate viral spread might have increased the risk of infection for staff members, creating secondary chains of transmission that were responsible for prolonging the outbreak. Our results highlight the importance of considering unnoticed chains of transmission early during an outbreak and making an adequate use and interpretation of diagnostic tests. Outbreak containment measures should be carefully tailored to each LTCF. IMPORTANCE The impact of COVID-19 on long-term care facilities (LTCFs) has been disproportionately large due to the high frailty of the residents. Here, we report epidemiological and genomic findings of a large outbreak that occurred at an LTCF, which ultimately affected almost all residents and nearly half of staff members. We found that the outbreak was initially driven by staff members; however, later resident relocation to limit the outbreak resulted in transmission from residents to staff members, evidencing the complexity and different phases of the outbreak. The phylogenetic analysis of SARS-CoV-2 isolates indicated that two closely related variants were responsible for the large outbreak. Our study highlights the importance of combining methods of classical and genomic epidemiology to take appropriate outbreak containment measures in LTCFsWe thank the CERCA Program/Generalitat de Catalunya for their support of the Germans Trias i Pujol Research Institute (IGTP). We thank the IGTP Translational Genomics Core Facility and staff for their contribution to this publication. Funding from the Instituto de Salud Carlos III project COV20/00140 (SeqCOVID consortium) and the European Commission—Next Generation EU (regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global).Peer reviewe

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The Gut Microbiome of an Indigenous Agropastoralist Population in a Remote Area of Colombia with High Rates of Gastrointestinal Infections and Dysbiosis

An Indigenous agropastoralist population called the Wiwa from the Sierra Nevada de Santa Marta, in North-East Colombia, shows high rates of gastrointestinal infections. Chronic gut inflammatory processes and dysbiosis could be a reason, suggesting an influence or predisposing potential of the gut microbiome composition. The latter was analyzed by 16S rRNA gene amplicon next generation sequencing from stool samples. Results of the Wiwa population microbiomes were associated with available epidemiological and morphometric data and compared to control samples from a local urban population. Indeed, locational-, age-, and gender-specific differences in the Firmicutes/Bacteriodetes ratio, core microbiome, and overall genera-level microbiome composition were shown. Alpha- and ß-diversity separated the urban site from the Indigenous locations. Urban microbiomes were dominated by Bacteriodetes, whereas Indigenous samples revealed a four times higher abundance of Proteobacteria. Even differences among the two Indigenous villages were noted. PICRUSt analysis identified several enriched location-specific bacterial pathways. Moreover, on a general comparative scale and with a high predictive accuracy, we found Sutterella associated with the abundance of enterohemorrhagic Escherichia coli (EHEC), Faecalibacteria associated with enteropathogenic Escherichia coli (EPEC) and helminth species Hymenolepsis nana and Enterobius vermicularis. Parabacteroides, Prevotella, and Butyrivibrio are enriched in cases of salmonellosis, EPEC, and helminth infections. Presence of Dialister was associated with gastrointestinal symptoms, whereas Clostridia were exclusively found in children under the age of 5 years. Odoribacter and Parabacteroides were exclusively identified in the microbiomes of the urban population of Valledupar. In summary, dysbiotic alterations in the gut microbiome in the Indigenous population with frequent episodes of self-reported gastrointestinal infections were confirmed with epidemiological and pathogen-specific associations. Our data provide strong hints of microbiome alterations associated with the clinical conditions of the Indigenous population

Reporte de las cláusulas de derecho internacional y política exterior de las constituciones Latinoamericanas 2021: Guía didáctica sobre la implementación, incorporación, eficacia y desarrollo del derecho internacional en las constituciones de América Latina

El reporte 2021 realizado por los estudiantes del curso “constitución, convencionalidad y derecho internacional” del pregrado en Derecho de la Facultad de Jurisprudencia de la Universidad del Rosario, presenta el estudio de la relación entre la constitución y el derecho internacional, a través de las cláusulas constitucionales de veintiséis (26) países de América Latina, especialmente en lo que respecta a su cláusula de supremacía constitucional; seguido de un ejemplo analizado de una cláusula en su correspondiente constitución que desarrolle la noción de “constitución internacional” y “constitución exterior”. Igualmente, el reporte presenta dos listados que enumeran el total de los artículos de la constitución que hacen referencia expresa al derecho internacional, y todas aquellas clausulas relevantes para las relaciones internacionales que desarrollen conceptos de política exterior en la constitución de cada Estado

Monismo y dualismo: Apuntes de jurisprudencia sobre el control constitucional de los tratados en Colombia

Entre las principales teorías del derecho internacional encontramos el dualismo y el monismo. La primera, entiende el derecho interno (nacional) y el derecho internacional como dos sistemas jurídicos que coexisten de manera separada, por lo que no se relacionan entre sí. Por otro lado, el monismo parte de la idea que los sistemas se cruzan. Al hacer parte de un mismo sistema, hay dos variantes de esta teoría. El monismo moderado con primacía del derecho internacional considera que este es superior que el derecho nacional. Por otro lado, el monismo moderado interno plantea lo opuesto. Cuales quiera que sea la teoría monista adoptada, busca que el "inferior" se adecue a sus principios. A partir del estudio del fenómeno de control constitucional en Colombia se evidencia la aplicación de las distintas teorías. En ese sentido, la obligatoriedad y eficacia del derecho internacional es cuestionada al ser contrastado con el derecho interno, particularmente con la Constitución de 1991. En Colombia, los tratados son incorporados mediante las leyes. Gracias al artículo 241 de la Constitución, la Corte Constitucional está facultada para analizar las leyes aprobatorias de tratado y contrastarlos con la Constitución. Aunque hoy en día el control constitucional es posterior a la ley aprobatoria y previo a que el ejecutivo ratifique un tratado, en los orígenes de esta figura surgió la polémica de los tratados con inconstitucionalidad sobreviniente. En ese sentido, los compromisos internacionales adoptados por Colombia antes del 91 pueden ser contrarios a la Constitución. Tal situación pone en entre dicho el principio de pacta sunt servanda. Sin embargo, como se estudiará a continuación, han sido diversos escenarios en los cuales se estudió la constitucionalidad de los tratados internacionales variando entre el dualismo y el monismo moderado. Con eso presente, en este documento, encontrarán nueve sentencias hito de control constitucional de los tratados. En cada una de ellas se analizará cómo llego la norma a ser estudiada por la Corte, los argumentos para su inconstitucionalidad, las consideraciones de la Corte, la teoría que aplicó y un breve comentario sobre la decisión y sus implicaciones

CONSULTORIAS EMPRESARIALES Y NEGOCIOS INTERNACIONALES

The purpose of this document is to present the analysis of the negotiating profileof the employees of the sales area of a hardware store in the city of Valledupar inwhich 31 salespeople were surveyed according to the criteria of the profile of thenegotiator of the Marrero and Ortiz model. It was possible to identify through anexploratory and confirmatory factorial analysis that the orientation of the employeesof the company was directed to the collaboration and satisfaction of the collectiveneeds of the individuals involved, in the same way it was established that in theemployees of this union the Compliance with duty with responsibility and ethicsplays a very important role when it comes to establishing negotiations.El prop´osito del presente documento es el de exponer el an´alisis del perfil negociadorde los empleados del ´area de ventas de una ferreter´ıa en la ciudad de Valleduparen la que se encuestaron a 31 vendedores de acuerdo a los criterios del perfil delnegociador del modelo de Marrero y Ortiz (2016). Se logr´o identificar mediante unan´alisis factorial exploratorio y confirmatorio que la orientaci´on de los empleadosde la empresa estaba dirigida a la colaboraci´on y a la satisfacci´on de las necesidadescolectivas de los individuos involucrados, de la misma manera se estableci´o que enlos empleados de este gremio el cumplimiento del deber con responsabilidad y ´eticajuega un papel muy importante a la hora de establecer negociaciones