Whole-Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma

RATIONALE: Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response. OBJECTIVES: To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children. METHODS: We performed the first whole-genome sequencing pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR. MEASUREMENTS AND MAIN RESULTS: We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P \u3c 3.53 × 10 CONCLUSIONS: The lack of minority data, despite a collaboration of eight universities and 13 individual laboratories, highlights the urgent need for a dedicated national effort to prioritize diversity in research. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations

Whole-genome sequencing of pharmacogenetic drug response in racially diverse children with asthma

RATIONALE: Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response. OBJECTIVES: To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children. METHODS: We performed the first whole-genome sequencing pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR. MEASUREMENTS AND MAIN RESULTS: We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P \u3c 3.53 × 10-7) and suggestive (P \u3c 7.06 × 10-6) loci near genes previously associated with lung capacity (DNAH5), immunity (NFKB1 and PLCB1), and β-adrenergic signaling (ADAMTS3 and COX18). Functional analyses of the BDR-associated SNP in NFKB1 revealed potential regulatory function in bronchial smooth muscle cells. The SNP is also an expression quantitative trait locus for a neighboring gene, SLC39A8. The lack of other asthma study populations with BDR and whole-genome sequencing data on minority children makes it impossible to perform replication of our rare variant associations. Minority underrepresentation also poses significant challenges to identify age-matched and population-matched cohorts of sufficient sample size for replication of our common variant findings. CONCLUSIONS: The lack of minority data, despite a collaboration of eight universities and 13 individual laboratories, highlights the urgent need for a dedicated national effort to prioritize diversity in research. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations

La magia de tus pensamientos : poesías & cuentos

Recopilación de poesías y cuentos realizados por aprendices del SENA de los programas de Mantenimiento de Motores Diesel, Técnico en Sistemas, Automatización Industrial, Electricidad Industrial, Diseño e Integración de Automatismos Mecatrónicos, Mantenimiento de Equipo Biomédico, Animación 3D, Manejo Ambiental, Diseño e integración de Automatismos Mecatrónicos y Mantenimiento mecatrónico automotriz, entre 2015 y 2017.Poesías 2018 -- Dándome tu vida / Brayan Orlando Jaimes Chaparro -- Tierra infinita / Christian Ricardo Caballero Villamizar -- Lamento a la tierra / Jeferson Alexis Montoya Moreno -- Conciencia por favor / Daniel Rincón -- Salvar un hogar llamado tierra / William Gamboa Arguello -- Planeta tierra / Iván Arley jurado -- Salvemos nuestro planeta / Jonathan David Silva -- Tierra bella / Martin Santiago -- Mi planeta / Fabián Moreno -- Generando conciencia / José Alberto Lizarazo -- Añoranza / Javier Casanova -- Sin tierra… / Gustavo Andrés Rodríguez Mendoza -- Planeta vivo y limpio / Yesid Serrano -- Palabras del destino / Osneider David Hernández Otalvaro -- Planeta tierra / Luis Fernando Isidro -- Medio ambiente / Yorgin David Hernández -- Prevenir / Brayan Mauricio Sanmiguel Luengas -- Nada será cómo antes / Jaime Andres Rodriguez Parrado -- Yo…Sol / Jonathan Bautista -- Lamento / Héctor Mauricio Parra Cuesta -- Nuestro hogar / Juan José Amaya -- Te agradecemos / Edwin Andrés Navarro Rozo, Anderson Cardozo Villamizar -- HErmoso milagro / Jhonatan Jaimes Solano -- El creador / Ana Rosa Hernández Santana -- Cuentos 2015 -- Juventud en la zona azul / Jeniffer Solano Ardila -- Los Ucayali y los Cubeo / Oscar Ivan Rueda Quintero -- Vientos de armonía / Ever Edinson Monsalve Salcedo -- El nacimiento de una nueva era / Carlos Leonardo Ardila Alvarado -- Luz de sueños / Hugo Andrés Álvarez -- Sol de medio día / Claudia Ramírez Guarín -- Cuentos 2016 -- Mucha verraquera mano / Héctor Josué Amado Sandoval -- El viaje de irse y nunca volver / Dayana Marcela Fuentes Duran -- “Santander es hermosa” / Kelly Tatiana Pabón Blanco -- Los valores del SENA / Ana Rosa Hernandez Santana -- La fuerza del espiritu y el deseo de cambiar / Pablo Andrés Capera Rodríguez -- SENA, paz y reconciliación / Adrián Benítez R., Rubén Darío Martínez -- Cuentos 2017 -- Cartas a un pasado / Angelita Delgado Pérez -- ¿Por qué así? ¿por qué tan blanco? ¿por qué no de otra manera? / Cristian Felipe Vargas Buenahora -- El gato pacho pacho, el gato más pacho de todos los pachos / Edwin Matajira García -- Freeland “el paraíso perdido” / Dámaso Antonio Morales Palacin -- Un mundo al revés / Fabio Eduardo Contreras Piñeresna91 página

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

Análisis del término prescriptivo del Derecho a la valoración de la pérdida de capacidad laboral en el Régimen de Seguridad Social Colombiano.

El objetivo de esta monografía era establecer un criterio jurídico, sobre la legalidad de los términos de prescripción para la reclamación de las prestaciones económicas y asistenciales por accidente de trabajo o por enfermedad laboral en Colombia. Para lograrlo, se realizó una investigación documental en materia de seguridad social, derecho laboral y constitucional. Se trata de una investigación aplicada, porque se recurre a la normatividad que versa sobre los riesgos laborales. En primer lugar se aborda el sistema general de riesgos laborales como componente del sistema de seguridad social, para luego adentrarnos a los riesgos laborales y la calificación de la pérdida de capacidad laboral y finalmente, dedicarnos a la prescripción de la calificación de la pérdida de la capacidad laboral. De lo anterior, se puede anticipar que el derecho a la calificación de la pérdida de la capacidad laboral es imprescriptible, pero no será sino pasado algunos años, que algunos actores del sistema general de riesgos laborales dejarán de negar o dilatar tal valoración, que a todas luces, eluden por la carga económica que de él se desprende, en detrimento de los derechos fundamentales del trabajador.Universidad Libre de Colombia--Facultad de Derecho -- Derech

Los saberes múltiples y las ciencias sociales y políticas

Este libro debe comprenderse como un intento de formalización por escrito de las razones y emociones que animaron el Coloquio Internacional sobre Saberes Múltiples, Ciencias Sociales y Políticas, realizado en la Sede Bogotá de la Universidad Nacional de Colombia (18-21 de octubre de 2016). Este evento contó con la colaboración de la Universidade Nova de Lisboa (CICS - Centro Interdisciplinar de Ciências Sociais), la Universität Freiburg (Suiza), la Unievrsidade Estadual de Montes Claros (Brasil), la Université catholique de Louvain (Bélgica) y la Association internationale des sociologues de langue française (AISLF) en el marco de las actividades del Comité de recherche 30 (CR30) (Inégalités, identités et liens sociaux). Los textos reunidos aquí son testimonios de los debates alrededor de dos perspectivas metodológicas y epistemológicas que con frecuencia se confrontan en el campo de las ciencias sociales y políticas: la monista y la pluralista. Los grandes temas que animaron las discusiones fueron: 1) los movimientos sociales o las sociedades y comunidades en movimiento; 2) los saberes sociales: indígenas, populares y ancestrales; 3) los estudios sobre el género y la diversidad sexual; 4) el ambientalismo, el ecologismo, los estudios sobre el territorio, el desarrollo y el animalismo; 5) la investigación acción participativa, la intervención sociológica y la educación popular; y 6) el debate epistemológico

A genome-wide association study of bronchodilator response in Latinos implicates rare variants.

BackgroundThe primary rescue medication to treat acute asthma exacerbation is the short-acting β₂-adrenergic receptor agonist; however, there is variation in how well a patient responds to treatment. Although these differences might be due to environmental factors, there is mounting evidence for a genetic contribution to variability in bronchodilator response (BDR).ObjectiveTo identify genetic variation associated with bronchodilator drug response in Latino children with asthma.MethodsWe performed a genome-wide association study (GWAS) for BDR in 1782 Latino children with asthma using standard linear regression, adjusting for genetic ancestry and ethnicity, and performed replication studies in an additional 531 Latinos. We also performed admixture mapping across the genome by testing for an association between local European, African, and Native American ancestry and BDR, adjusting for genomic ancestry and ethnicity.ResultsWe identified 7 genetic variants associated with BDR at a genome-wide significant threshold (P &lt; 5 × 10(-8)), all of which had frequencies of less than 5%. Furthermore, we observed an excess of small P values driven by rare variants (frequency, &lt;5%) and by variants in the proximity of solute carrier (SLC) genes. Admixture mapping identified 5 significant peaks; fine mapping within these peaks identified 2 rare variants in SLC22A15 as being associated with increased BDR in Mexicans. Quantitative PCR and immunohistochemistry identified SLC22A15 as being expressed in the lung and bronchial epithelial cells.ConclusionOur results suggest that rare variation contributes to individual differences in response to albuterol in Latinos, notably in SLC genes that include membrane transport proteins involved in the transport of endogenous metabolites and xenobiotics. Resequencing in larger, multiethnic population samples and additional functional studies are required to further understand the role of rare variation in BDR

The genetics of Mexico recapitulates Native American substructure and affects biomedical traits

Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide

A genome-wide association and admixture mapping study of bronchodilator drug response in African Americans with asthma

Short-acting β2-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the United States. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma. To identify genetic variants that may contribute to differences in BDR in African Americans with asthma, we performed a genome-wide association study (GWAS) of BDR in 949 African-American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase III genotypes. We used linear regression models adjusting for age, sex, body mass index (BMI) and genetic ancestry to test for an association between BDR and genotype at single-nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1830 Latinos (total = 2779). Finally, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. We identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p = 7.69 × 10-9). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958 and rs7081864, p ≤ 5 × 10-8). Our results failed to replicate in three additional populations of 416 Latinos and 1615 African Americans. Our findings indicate that both population-specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups