Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Measurement of the W-boson mass in pp collisions at √s=7 TeV with the ATLAS detector

A measurement of the mass of the W boson is presented based on proton–proton collision data recorded in 2011 at a centre-of-mass energy of 7 TeV with the ATLAS detector at the LHC, and corresponding to 4.6 fb−1 of integrated luminosity. The selected data sample consists of 7.8×106 candidates in the W→μν channel and 5.9×106 candidates in the W→eν channel. The W-boson mass is obtained from template fits to the reconstructed distributions of the charged lepton transverse momentum and of the W boson transverse mass in the electron and muon decay channels, yielding mW=80370±7 (stat.)±11(exp. syst.) ±14(mod. syst.) MeV =80370±19MeV, where the first uncertainty is statistical, the second corresponds to the experimental systematic uncertainty, and the third to the physics-modelling systematic uncertainty. A measurement of the mass difference between the W+ and W−bosons yields mW+−mW−=−29±28 MeV

Creación de una empresa prestadora de servicios de asesorías financieras y jurídicas, soportada en estrategias digitales para las Pymes en la ciudad de Montería

Nombre: A&A DIGICONSULTING S.A.S Oportunidad de negocio: La evolución del mundo empresarial demanda la reinvención de los procesos empresariales, la adopción de tecnologías y políticas de innovación que aumenten la eficiencia y agilidad de los negocios. Dos áreas que han sufrido bastantes transformaciones y, por tanto, son cruciales para el proceso de transformación digital, son la financiera y jurídica, sus actividades han pasado de métodos manuales a procesos digitales, para dar lugar a una mejora en la eficiencia, la precisión y la agilidad en el manejo de información, elemento esencial para toda empresa. Sin embargo, las empresas monterianas se encuentran en un proceso incipiente de innovación tecnológica, por lo que requieren asesoría y acompañamiento especializado para alcanzar sus objetivos estratégicos y fomentar el éxito empresarial. En razón a lo expuesto, en el siguiente proyecto se desarrolló un estudio de creación de empresa, que analiza elementos del mercado como la oferta, demanda, precios, canales de comercialización, entre otros; los aspectos técnicos que interfieren en la operación de la empresa; los componentes organizacionales que promueven el desempeño eficiente del personal; el impacto económico, social y ambiental que la empresa generaría en el municipio de Montería; y la proyección y evaluación de los elementos financieros necesarios para la ejecución del proyecto empresarial. Servicio: se ofrece el servicio de asesorías financieras y jurídicas, soportadas en estrategias digitales; para transformar estas áreas dentro de las empresas monterianas, promoviendo la agilidad, eficiencia, productividad y competitividad en todas las actividades y operaciones asociadas. Competidores: partiendo de la premisa, de que no se habla de un servicio de asesoría en materia jurídica y financiera, sino de la adopción de la tecnología para dichos procesos, es posible afirmar que no existe en el mercado ninguna empresa que sea competencia directa. Inversión inicial: $182.022.741 VPN:$ 27.781.799 TIR: 37,73% RBC: 2,98Introducción ...................................................................................................................... 14Resumen Ejecutivo ........................................................................................................... 171 Referente Teórico y Conceptual................................................................................. 191.1 Marco Teórico..................................................................................................... 191.1.1 Transformación digital .................................................................................. 191.1.2 Evolución de las Operaciones Financieras y Jurídicas.................................. 251.2 Marco Conceptual ............................................................................................... 271.2.1 Algoritmo ...................................................................................................... 271.2.2 Big Data......................................................................................................... 281.2.3 Blokchain ...................................................................................................... 281.2.4 Dinero Digital................................................................................................ 281.2.5 Contratos Inteligentes.................................................................................... 291.2.6 Data Protection.............................................................................................. 301.2.7 Firma Electrónica .......................................................................................... 301.2.8 Smart Working .............................................................................................. 312 Módulo de Mercado.................................................................................................... 322.1 Servicio................................................................................................................ 322.1.1 Características del Servicio ........................................................................... 322.1.2 Usos del Servicio........................................................................................... 332.1.3 Beneficios del Servicio.................................................................................. 332.1.4 Servicios Sustitutos y/o Complementarios.................................................... 342.2 Usuarios del Servicio .......................................................................................... 352.2.1 Segmentación del Mercado ........................................................................... 352.2.2 Características Socioculturales...................................................................... 362.3 Delimitación Geográfica ..................................................................................... 372.4 Análisis de la Demanda....................................................................................... 372.4.1 Diseño Muestral ............................................................................................ 372.4.2 Validación del Instrumento ........................................................................... 402.4.3 Análisis de los Resultados............................................................................. 402.4.4 Cálculo de la demanda actual........................................................................ 532.4.5 Proyección de la Demanda............................................................................ 542.5 Análisis de la Oferta............................................................................................ 552.6 Delimitación del Tipo de Demanda .................................................................... 552.6.1 Proyección de la Demanda Insatisfecha........................................................ 562.7 Análisis de Precios.............................................................................................. 562.8 Canales de Comercialización .............................................................................. 572.9 Imagen Corporativa............................................................................................. 582.10 Estrategia Publicitaria...................................................................................... 593 Módulo Técnico y Organizacional ............................................................................. 613.1 Tamaño del Proyecto........................................................................................... 613.2 Localización ........................................................................................................ 623.2.1 Macrolocalización ......................................................................................... 623.2.2 Microlocalización.......................................................................................... 643.3 Distribución en Planta ......................................................................................... 653.4 Proceso de Prestación del Servicio...................................................................... 673.5 Naturaleza Jurídica.............................................................................................. 693.6 Misión.................................................................................................................. 703.7 Visión .................................................................................................................. 713.8 Principios............................................................................................................. 713.9 Organigrama........................................................................................................ 733.10 Manual de Funciones....................................................................................... 744 Módulo de Impacto Social, Económico y Ambiental................................................. 824.1 Impacto Social..................................................................................................... 824.2 Impacto Económico............................................................................................. 844.3 Impacto Ambiental.............................................................................................. 865 Módulo Financiero ..................................................................................................... 895.1 Inversiones Fijas.................................................................................................. 895.2 Inversiones Diferidas........................................................................................... 905.3 Distribución de Costos........................................................................................ 915.4 Punto de Equilibrio.............................................................................................. 975.5 Capital de Trabajo ............................................................................................... 985.6 Flujo Neto de Inversión..................................................................................... 1005.7 Proyecciones Financieras.................................................................................. 1015.8 Flujo Neto de Operación ................................................................................... 1045.9 Flujo Neto del Plan de Negocios....................................................................... 1055.10 Evaluación Financiera: VPN, TIR, RB/C...................................................... 1065.10.1 Valor Presente Neto (VPN)....................................................................... 1065.10.2 Tasa Interna de Retorno (TIR) .................................................................. 1065.10.3 Relación Beneficio - Costo (RBC)............................................................ 1086 Fuentes de financiación ............................................................................................ 1107 Conclusiones............................................................................................................. 1118 Recomendaciones..................................................................................................... 1149 Referencias ............................................................................................................... 11610 Anexos .................................................................................................................. 124PregradoAdministrador(a) en Finanzas y Negocios InternacionalesCreación de Empres

A conservação do papagaio-da-cara-roxa (Amazona brasiliensis) no estado do Paraná: uma experiência de Educação Ambiental no ensino formal Conservation of the red-tailed-parrot (Amazona brasiliensis) in the northern coast of Paraná State: an Environmental Education experience for formal school

No presente trabalho, avaliou-se a experiência de Educação Ambiental do "Projeto de Conservação do Papagaio-da-Cara-Roxa (Amazona brasiliensis)", no ensinoformal, realizado pela Sociedade de Pesquisa em Vida Selvagem e Educação Ambiental (SPVS), no litoral norte do Estado do Paraná. A experiência teve o intuito de fomentar, tanto no corpo docente quando no corpo discente, a discussão sobre valores e princípios que norteiam as relações homem/natureza, desenvolvendo-se, assim, uma interação mais responsável com o meio ambiente. Foram desenvolvidos módulos-educativos sobre o papagaio-da-cara-roxa e seu ambiente, direcionados a 795 estudantes do ensino fundamental, nos Municípios de Paranaguá e Guaraqueçaba. Para analisar a eficácia das atividades, os estudantes responderam a testes antes e depois do processo educativo que mediram mudanças obtidas com relação ao incremento de conhecimento, postura e valorização do papagaio-da-cara-roxa e de seu ambiente. Os resultados indicaram que a utilização do exemplo de uma espécie, ameaçada de extinção e que ocorre próximo às comunidades envolvidas no processo de conservação, serviu de base para a associação do tema específico para com uma realidade ambiental mais ampla e contextualizada localmente.<br>The utilization of a flag-species in environmental education can be an important strategy to discuss the interrelations between the species, their habitats, and man. The red-tailed-parrot (Amazona brasiliensis), is endemic in the Atlantic Rainforest and is threatened with extinction. This work aims to analyze the environmental education experience of the project "Conservation of the red-tailed-parrot (Amazona brasiliensis)", together with formal teaching, held by the Society for Wildlife Research and Environmental Education (SPVS), in the northern coast of Paraná State. The objective of this work was to promote a teaching method among students and teachers that contextualizes the local environment and its problems. Discussions on the values and principles of man/nature relations were also promoted, developing a more environmentally-responsible interaction. Educative modules on the red-tailed-parrot and its habitat were developed for 795 students from the municipalities of Paranaguá and Guaraqueçaba. In order to analyze the efficiency of the activities, tests, before and after the process, were developed for the students. This analysis enabled a measurement of changes with respect to an increase in knowledge, posture, and valuation of the red-tailed-parrot and its habitat

Extragenital Chlamydia and Gonorrhea Among Community Venue–Attending Men Who Have Sex with Men — Five Cities, United States, 2017

Sexually transmitted diseases (STDs) disproportionately affect gay, bisexual, and other men who have sex with men (MSM) in the United States ( 1 ). Because chlamydia and gonorrhea at extragenital (rectal and pharyngeal) anatomic sites are often asymptomatic, these anatomic sites serve as a reservoir of infection, which might contribute to gonococcal antimicrobial resistance ( 2 ) and increased risk for human immunodeficiency virus (HIV) transmission and acquisition ( 3 ). To ascertain prevalence of extragenital STDs, MSM attending community venues were recruited in five U.S. cities to provide self-collected swabs for chlamydia and gonorrhea screening as part of National HIV Behavioral Surveillance (NHBS). Overall, 2,075 MSM provided specimens with valid results, and 13.3% of participants were infected with at least one of the two pathogens in at least one of these two extragenital anatomic sites. Approximately one third of participating MSM had not been screened for STDs in the previous 12 months. MSM attending community venues had a high prevalence of asymptomatic extragenital STDs. The findings underscore the importance of sexually active MSM following current recommendations for STD screening at all exposed anatomic sites at least annually ( 4 )

Military-related risk factors for dementia

Introduction: In recent years, there has been growing discussion to better understand the pathophysiological mechanisms of traumatic brain injury and post-traumatic stress disorder and how they may be linked to an increased risk of neurodegenerative diseases including Alzheimer's disease in veterans. Methods: Building on that discussion, and subsequent to a special issue of Alzheimer's &amp; Dementia published in June 2014, which focused on military risk factors, the Alzheimer's Association convened a continued discussion of the scientific community on December 1, 2016. Results: During this meeting, participants presented and evaluated progress made since 2012 and identified outstanding knowledge gaps regarding factors that may impact veterans' risk for later life dementia. Discussion: The following is a summary of the invited presentations and moderated discussions of both the review of scientific understanding and identification of gaps to inform further investigations.</p

Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19.

BackgroundStudies quantifying SARS-CoV-2 have focused on upper respiratory tract or plasma viral RNA with inconsistent association with clinical outcomes. The association between plasma viral antigen levels and clinical outcomes has not been previously studied. Our aim was to investigate the relationship between plasma SARS-CoV-2 nucleocapsid antigen (N-antigen) concentration and both markers of host response and clinical outcomes.MethodsSARS-CoV-2&nbsp;N-antigen concentrations were measured in the first study plasma sample (D0), collected within 72&nbsp;h of hospital admission, from 256 subjects admitted between March 2020 and August 2021 in a prospective observational cohort of hospitalized patients with COVID-19. The rank correlations between plasma N-antigen and plasma biomarkers of tissue damage, coagulation, and inflammation were assessed. Multiple ordinal regression was used to test the association between enrollment N-antigen plasma concentration and the primary outcome of clinical deterioration at one week as measured by a modified World Health Organization (WHO) ordinal scale. Multiple logistic regression was used to test the association between enrollment plasma N-antigen concentration and the secondary outcomes of ICU admission, mechanical ventilation at 28&nbsp;days, and death at 28&nbsp;days. The prognostic discrimination of an externally derived "high antigen" cutoff of N-antigen ≥ 1000&nbsp;pg/mL was also tested.ResultsN-antigen on D0 was detectable in 84% of study participants. Plasma N-antigen levels significantly correlated with RAGE (r = 0.61), IL-10 (r = 0.59), and IP-10 (r = 0.59, adjusted p = 0.01 for all correlations). For the primary outcome of clinical status at one week, each 500&nbsp;pg/mL increase in plasma N-antigen level was associated with an adjusted OR of 1.05 (95% CI 1.03-1.08) for worse WHO ordinal status. D0 plasma N-antigen ≥ 1000&nbsp;pg/mL was 77% sensitive and 59% specific (AUROC 0.68) with a positive predictive value of 23% and a negative predictive value of 93% for a worse WHO ordinal scale at day 7 compared to baseline. D0 N-antigen concentration was independently associated with ICU admission and 28-day mechanical ventilation, but not with death at 28&nbsp;days.ConclusionsPlasma N-antigen levels are readily measured and provide important insight into the pathogenesis and prognosis of COVID-19. The measurement of N-antigen levels early in-hospital course may improve risk stratification, especially for identifying patients who are unlikely to progress to severe disease