El Conocimiento - su relación con el valor de las empresas

Desde hace más de 30 años que algo cambio a la hora de considerar los activos de las compañías, se empezaron a mirar muy de cerca los activos intangibles, generados por el conocimiento de las personas. Y los activos físicos pasaron a un segundo plano como motores del crecimiento de las empresas, y se fueron comoditizando con el correr del tiempo. Ha habido varias corrientes y enfoques acerca de cómo establecer la cuantificación de los activos intangibles para tratar de brindar información útil para la toma de decisiones a los gerentes, ya que su monetización rara vez aparece en los estados financieros de las empresas. Las normas contables de los países en general no consideran activos al capital intelectual (intangibles), sino que obligan a las compañías a registrarlo como gastos lo que distorsiona los periodos en los cuales se los registra, produciendo serios problemas a la hora de la valuación de las empresas, desviando la atención de los inversores, haciéndolos, a veces, tomar malas decisiones que alteran el valor de las compañías y sus planes de inversiones futuras en dichos activos

The Camino Verde intervention in Nicaragua, 2004-2012.

UNLABELLED: Camino Verde (the Green Way) is an evidence-based community mobilisation tool for prevention of dengue and other mosquito-borne viral diseases. Its effectiveness was demonstrated in a cluster-randomised controlled trial conducted in 2010-2013 in Nicaragua and Mexico. The Nicaraguan arm of the trial was preceded, from 2004 to 2008, by a feasibility study that provided valuable lessons and trained facilitators for the trial itself. Here, guided by the Template for Intervention Description and Replication (TIDieR), we describe the Camino Verde intervention in Nicaragua, presenting its rationale, its time and location, activities, materials used, the main actors, modes of delivery, how it was tailored to encourage community engagement, modifications made from the feasibility study to the trial itself, and how fidelity to the process originally designed was maintained. We also present information on costs and discuss the place of this study within the literature on implementation science. TRIAL REGISTRATION: ISRCTN27581154

Marcos discursivos de un movimiento ecologista emergente y su impacto virtual

El surgimiento de Fridays for Future (FfF) ha supuesto cambios en los discursos tradicionales en torno al cambio climático. Esto viene acompañado de nuevas estrategias comunicativas a través de las redes virtuales que han tenido bastante repercusión social, con un importante componente emocional basado en el concepto de emergencia climática. El objetivo de este artículo es el análisis de esta dimensión comunicativa a través de sus marcos discursivos y su uso en las redes, utilizando una metodología mixta basada en el trabajo etnográfico y un análisis de redes del movimiento (Twitter). Los resultados reflejan tres aspectos de su discurso que destacan respecto a lo que había recogido la literatura sobre marcos ecológicos anteriores: el énfasis en la emergencia climática frente a la sostenibilidad, el paso de las conductas individuales a la necesidad de transformación sistémica y, por último, su igualitarismo radical. Twitter se utiliza sobre todo para la información de movilizaciones recurriendo a los marcos del cambio de sistema y la emergencia climática, lo que consigue una repercusión menor que los mensajes sobre denuncia o divulgación de información ecológica. Estos últimos remiten con más frecuencia a marcos de justicia ecosocial, cambio climático y futuro en riesgo

Mobilising communities for Aedes aegypti control: the SEPA approach.

UNLABELLED: Camino Verde (the Green Way) is an evidence-based community mobilisation tool for prevention of dengue and other mosquito-borne viral diseases. Its effectiveness was demonstrated in a cluster-randomised controlled trial conducted in 2010-2013 in Nicaragua and Mexico. The common approach that brought functional consistency to the Camino Verde intervention in both Mexico and Nicaragua is Socialisation of Evidence for Participatory Action (SEPA). In this article, we explain the SEPA concept and its theoretical origins, giving examples of its previous application in different countries and contexts. We describe how the approach was used in the Camino Verde intervention, with details that show commonalities and differences in the application of the approach in Mexico and Nicaragua. We discuss issues of cost, replicability and sustainability, and comment on which components of the intervention were most important to its success. In complex interventions, multiple components act in synergy to produce change. Among key factors in the success of Camino Verde were the use of community volunteers called brigadistas, the house-to-house visits they conducted, the use of evidence derived from the communities themselves, and community ownership of the undertaking. Communities received the intervention by random assignment; dengue was not necessarily their greatest concern. The very nature of the dengue threat dictated many of the actions that needed to be taken at household and neighbourhood levels to control it. But within these parameters, communities exercised a large degree of control over the intervention and displayed considerable ingenuity in the process. TRIAL REGISTRATION: ISRCTN27581154

Influence of cytogenetic and molecular findings on prognosis and response to treatment of patients with acute myeloid leukemia

La mayoría de las determinaciones moleculares detalladas según la ELN2017 resultan de difícil acceso en nuestro medio y el cariotipo mantiene su importancia al indicar el tratamiento de los pacientes con leucemia mieloide aguda. Nuestro objetivo fue evaluar la influencia del cariotipo y de los hallazgos moleculares disponibles en relación a la supervivencia global (SG) y respuesta al tratamiento. Se realizó un análisis retrospectivo de 688 pacientes (pertenecientes a 11 instituciones, diagnosticados entre ene-13/jun-19), de los cuales 592 (86%) fueron evaluables. Los 196 pacientes (p) con cariotipo alterado, 104 (55%) vinculables a síndromes mielodisplásicos, mostraron una distribución heterogénea según los nueve sistemas aplicados (adverso: rango 47%-CECOG-SWOG-MDACC hasta 99%-Keating). La mayoría de los sistemas fueron útiles para predecir SG, con superioridad para el definido por CECOG-SWOG-MDACC (intermedio 10 m vs adverso 6 m, HR1,6 p=0,007) y entre aquéllos que recibieron un trasplante de células progenitoras hematopoyéticas (TCPH) (intermedio no alcanzada-NA vs adverso 14,5 m, HR2,5 p=0,053). En cuanto al tratamiento con agentes hipometilantes en 1ª línea (N 41, a fin de homogeneizar), excluyendo o no a los que recibieron TCPH (N 4), ninguno fue útil para diferenciar SG (9 m), tasas de remisiones completas (RC) ni mejor respuesta. Al evaluar quimioterapia, los sistemas CECOG-SWOG-MDACC y ELN2010 fueron los mejores predictores censurando (13 vs 8 m, p=0,023 y 15 vs 8 m, p=0,018) o no hasta el TCPH (p=0,009 y p=0,005). Sin embargo, sólo el primero fue útil para diferenciar tasas de RC (51/70, 73% vs 28/54, 52%, p=0,023). Finalmente, se compararon los hallazgos frente a la t(15;17) (N 77, SG NA) tomando la categorización del CECOG-SWOG-MDACC para los cariotipos alterados: CBF (N 65, SG NA) HR1,6 p=0,184; cariotipo-normal/NPM1+/FLT3- (N 26, SG NA) HR2,3, p=0,057; cariotipo-normal/NPM1-/FLT3- (N 102, SG 14 m) HR4,2, p<0,001; cariotipo-alterado/intermedio (N 101, 10 m) HR5,6, p<0,001; cariotipo-normal/NPM1-/FLT3+ (N 21, 9 m) HR6,1, p<0,001; cariotipo-alterado/adverso (N 88, 6 m) HR8,2, p<0,001 y cariotipo-normal/NPM1+/FLT3+ (N 12, SG 7 m) HR9,9, p<0,001 (CEPBA disponible en N 62, no evaluable). La mayoría de los riesgos se incrementaron al excluir los TCPH. Los resultados obtenidos comprueban el buen pronóstico de los pacientes con t(15;17), rearreglos CBF y de NPM1+ con cariotipo normal. Mientras que la detección de FLT3+ se asoció con un pronóstico adverso, independiente de NPM1+. El sistema definido por el CECOG-SWOG-MDACC, el cual considera de mal pronóstico a los cariotipos complejos y -5/-7, es el que mejor refleja los parámetros evaluados. Sin embargo, las alteraciones recomendadas por la ELN2010 reord3q, 5q-, t(6;9); 11q23v y 17p-, también influirían en la SG frente al tratamiento con quimioterapia en 1ª línea.The ELN2017 stratification has proved useful in predicting the outcome for acute myeloid leukemia (AML). However, some molecular determinations detailed are limited in use in our media and the karyotype remains an important factor regarding therapy. Our aim was to evaluate the predictive capacity of different cytogenetic and molecular findings on the outcome of patients with AML. Data was informative in 592 patients (pt) (from a retrospective cohort of 688 pt diagnosed in 11 Argentine centers between Jan/13-Jun/19). The overall survival (OS) concerning genetic data was different: t(15;17), 77 pt, not reached (NR); CBF rearrangements, 65 pt, NR; normal karyotype, 254 pt, 13 m, and abnormal karyotype, 196 pt, 8 m; p<0.001. Regarding normal karyotype, combined data according to the ELN2010 showed differences in the outcome: NPM1+/FLT3-, 26 pt, NR; NPM1-/FLT3- , 102 pt, 14 m; NPM1-/FLT3+, 21 pt, 9 m; NPM1+/ FLT3+, 12 pt, 7 m; p=0.025 (CEPBA available 62 pt, no evaluable). Adverse karyotypes were heterogeneously distributed among 9 systems: 47% CECOG-SWOGMDACC to 99% Keating-classification, and 104 (55%) with changes related to myelodysplastic syndromes. The CECOG-SWOG-MDACC showed superiority to differentiate between intermediate vs adverse for OS (10 vs 6 m, p=0.004; HR1.6, p=0.007, Cox’s regression) and, in the limit, for those who undergone hematopoietic stem cell transplantation (HSCT) (NA vs 15 m, p=0.033; HR 2.5, p=0.053). Regarding hypomethylating agents (41 pt) as first line therapy none was useful to differentiate OS (9 m), complete remission (CR) or best response. When chemotherapy was evaluated, the CECOG-SWOG-MDACC and ELN2010 were similar censoring (13 vs 8 m, p=0.023 and 15 vs 8 m, p=0.018) or not censoring at HSCT (14 vs 8 m, p=0.009, and 16 vs 8 m, p=0.005). However, only the first one made a difference in CR rates (73% vs 52%, p=0.023), with a tendency for any therapy (p=0.057). Finally, all findings were compared, selecting t(15;17) as reference and applying the CECOGSWOG-MDACC: CBF HR1.6 p=0.184; normal karyotype NPM1+/FLT3- HR2.3, p=0.057; normal karyotype NPM1-/FLT3- HR4.2, p<0.001; intermediate HR5.6, p<0.001; normal karyotype NPM1-/ FLT3+ HR6.1, p<0.001; normal karyotype NPM1+/ FLT3+ HR9.9, p<0.001, and adverse HR8.2, p<0.001. These HRs increased when excluding HSCT, especially for FLT3+. Our results are in agreement with the favorable outcome of t(15;17), CBF rearrangement and NPM1+/FLT3- in those with normal karyotype, whereas FLT3+ was an adverse finding. Complex karyotypes, -5 and -7, according CECOG-SWOGMDACC, were associated with shorter OS and lower CR. However, when rearr3q, 5q-, t(6;9), 11q23v and 17p- were also included, according to ELN2010, they account for a shorter OS in those treated with chemotherapyFil: Belli, Carolina Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Correa, Walter A.. Hospital Italiano; Argentina. Hospital Italiano de La Plata; ArgentinaFil: Gonzalez, Natalia Jacqueline. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; ArgentinaFil: Ferrari, Luciana. Fundación Para Combatir la Leucemia; ArgentinaFil: Dick, Hernán. Hospital Italiano de La Plata; ArgentinaFil: Cranco, Santiago. Instituto Alexander Fleming.; Argentina. Hospital Pediatrico Alexander Fleming; ArgentinaFil: Moirano, María. Provincia de Buenos Aires. Hospital Interzonal General de Agudos Gral. San Martín; ArgentinaFil: Rapan, Leticia. Sanatorio “Sagrado Corazón”; ArgentinaFil: Oliveira, Natalia. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Kornblihtt, Laura Inés. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Suero, Alejandro. Unidad Asistencial "Dr. César Milstein"; ArgentinaFil: Navickas, Alicia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Gimenez Conca, Alberto. Hospital Italiano; Argentin

Structure-Based Analysis of Five Novel Disease-Causing Mutations in 21-Hydroxylase-Deficient Patients

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most frequent inborn error of metabolism, and accounts for 90–95% of CAH cases. The affected enzyme, P450C21, is encoded by the CYP21A2 gene, located together with a 98% nucleotide sequence identity CYP21A1P pseudogene, on chromosome 6p21.3. Even though most patients carry CYP21A1P-derived mutations, an increasing number of novel and rare mutations in disease causing alleles were found in the last years. In the present work, we describe five CYP21A2 novel mutations, p.R132C, p.149C, p.M283V, p.E431K and a frameshift g.2511_2512delGG, in four non-classical and one salt wasting patients from Argentina. All novel point mutations are located in CYP21 protein residues that are conserved throughout mammalian species, and none of them were found in control individuals. The putative pathogenic mechanisms of the novel variants were analyzed in silico. A three-dimensional CYP21 structure was generated by homology modeling and the protein design algorithm FoldX was used to calculate changes in stability of CYP21A2 protein. Our analysis revealed changes in protein stability or in the surface charge of the mutant enzymes, which could be related to the clinical manifestation found in patients

Leucemias Agudas

Sobre: Leucemia linfoblástica aguda; Linfoma linfoblástico; Leucemia mieloide aguda; Leucemia promielocítica aguda y situaciones especiales.Fil: Agriello, Evangelina Edith. No especifíca;Fil: Belli, Carolina Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bullorsky, Laura. No especifíca;Fil: Cazap, Nicolás. No especifíca;Fil: Cranco, Santiago. No especifíca;Fil: Dick, Hernán. No especifíca;Fil: Fernandez, Isolda. No especifíca;Fil: Fischman, Laura. No especifíca;Fil: Funes, María Eugenia. No especifíca;Fil: Gimenez Conca, Alberto. No especifíca;Fil: González, Jacqueline. No especifíca;Fil: Lang, Cecilia. No especifíca;Fil: Mela Osorio, María José. No especifíca;Fil: Navickas, Alicia. No especifíca;Fil: Oliveira, Natalia. No especifíca;Fil: Rey, Irene. No especifíca;Fil: Rivas, Marta. No especifíca;Fil: Suero, Alejandro. No especifíca;Fil: Zanella, Lorena. No especifíca

Mobilising communities for Aedes aegypti control: the SEPA approach

Abstract Camino Verde (the Green Way) is an evidence-based community mobilisation tool for prevention of dengue and other mosquito-borne viral diseases. Its effectiveness was demonstrated in a cluster-randomised controlled trial conducted in 2010–2013 in Nicaragua and Mexico. The common approach that brought functional consistency to the Camino Verde intervention in both Mexico and Nicaragua is Socialisation of Evidence for Participatory Action (SEPA). In this article, we explain the SEPA concept and its theoretical origins, giving examples of its previous application in different countries and contexts. We describe how the approach was used in the Camino Verde intervention, with details that show commonalities and differences in the application of the approach in Mexico and Nicaragua. We discuss issues of cost, replicability and sustainability, and comment on which components of the intervention were most important to its success. In complex interventions, multiple components act in synergy to produce change. Among key factors in the success of Camino Verde were the use of community volunteers called brigadistas, the house-to-house visits they conducted, the use of evidence derived from the communities themselves, and community ownership of the undertaking. Communities received the intervention by random assignment; dengue was not necessarily their greatest concern. The very nature of the dengue threat dictated many of the actions that needed to be taken at household and neighbourhood levels to control it. But within these parameters, communities exercised a large degree of control over the intervention and displayed considerable ingenuity in the process. Trial registration ISRCTN27581154

Serological response and breakthrough infection after COVID-19 vaccination in patients with cirrhosis and post-liver transplant

BACKGROUND: Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection. METHODS: COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4-10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected. RESULTS: After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level. CONCLUSIONS: LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level

Serological response and breakthrough infection after COVID-19 vaccination in patients with cirrhosis and post-liver transplant

Background: Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection.Methods: COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4-10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected.Results: After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p &lt; 0.0001), AILD (p &lt; 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-alpha levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level.Conclusions: LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level