Variability in phenotype induced by the podocin variant R229Q plus a single pathogenic mutation.

BACKGROUND: Mutations in podocin (NPHS2) are the most common cause of childhood onset autosomal recessive steroid-resistant nephrotic syndrome (SRNS). The disease is characterized by early-onset proteinuria, resistance to immunosuppressive therapy and rapid progression to end-stage renal disease. Compound heterozygous changes involving the podocin variant R229Q combined with another pathogenic mutation have been associated with a mild phenotype with disease onset often in adulthood. METHODS: We screened 19 families with early-onset SRNS for mutations in NPHS2 and WT1 and identified four disease-causing mutations (three in NPHS2 and one in WT1) prior to planned whole-exome sequencing. RESULTS: We describe two families with three individuals presenting in childhood who are compound heterozygous for R229Q and one other pathogenic NPHS2 mutation, either L327F or A297V. One child presented at age 4 years (A297V plus R229Q) and the other two at age 13 (L327F plus R229Q), one with steadily deteriorating renal function. CONCLUSIONS: These cases highlight the phenotypic variability associated with the NPHS2 R229Q variant plus pathogenic mutation. Individuals may present with early aggressive disease.

Drug-drug interaction studies of cardiovascular drugs involving P-glycoprotein, an efflux transporter, on the pharmacokinetics of edoxaban, an oral factor Xa inhibitor.

BACKGROUND: Edoxaban, an oral direct factor Xa inhibitor, is in development for thromboprophylaxis, including prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). P-glycoprotein (P-gp), an efflux transporter, modulates absorption and excretion of xenobiotics. Edoxaban is a P-gp substrate, and several cardiovascular (CV) drugs have the potential to inhibit P-gp and increase drug exposure. OBJECTIVE: To assess the potential pharmacokinetic interactions of edoxaban and 6 cardiovascular drugs used in the management of AF and known P-gp substrates/inhibitors. METHODS: Drug-drug interaction studies with edoxaban and CV drugs with known P-gp substrate/inhibitor potential were conducted in healthy subjects. In 4 crossover, 2-period, 2-treatment studies, subjects received edoxaban 60 mg alone and coadministered with quinidine 300 mg (n = 42), verapamil 240 mg (n = 34), atorvastatin 80 mg (n = 32), or dronedarone 400 mg (n = 34). Additionally, edoxaban 60 mg alone and coadministered with amiodarone 400 mg (n = 30) or digoxin 0.25 mg (n = 48) was evaluated in a single-sequence study and 2-cohort study, respectively. RESULTS: Edoxaban exposure measured as area under the curve increased for concomitant administration of edoxaban with quinidine (76.7 %), verapamil (52.7 %), amiodarone (39.8 %), and dronedarone (84.5 %), and exposure measured as 24-h concentrations for quinidine (11.8 %), verapamil (29.1 %), and dronedarone (157.6 %) also increased. Administration of edoxaban with amiodarone decreased the 24-h concentration for edoxaban by 25.7 %. Concomitant administration with digoxin or atorvastatin had minimal effects on edoxaban exposure. CONCLUSION: Coadministration of the P-gp inhibitors quinidine, verapamil, and dronedarone increased edoxaban exposure. Modest/minimal effects were observed for amiodarone, atorvastatin, and digoxin.

Seroprotection against tetanus in patients of an an emergency department in Belgium and evaluation of a bedside immunotest (Tetanos Quick Stick R).

info:eu-repo/semantics/nonPublished

Seroprotection against tetanus in patients of an an emergency department in Belgium and evaluation of a bedside immunotest (Tetanos Quick Stick R). A prospective observational study

info:eu-repo/semantics/published

Seroprotection against tetanus in patients présenting to an emergency department in Belgium and evaluation of a bedside immunotest (Tetanos Quick Stick R): A prospective observational study

info:eu-repo/semantics/published

Análisis de la Corporación J.R Lindley S.A. : caso Inca Kola

Inca Kola es una bebida gasificada del Perú y elaborada por la Corporación Lindley, que ha conservado el liderazgo en el mercado peruano desde su creación, a pesar del ingreso de bebidas internacionales y de bebidas que tienen un menor precio. Desde su creación, la corporación se enfocó en vincular la bebida con la identidad peruana; estrategia que ha sido efectiva y se pueden comprobar por el liderazgo que presenta en el mercado. En los noventa, la corporación Lindley tuvo que enfrentar un escenario turbulento debido al ingreso de Coca Cola y Pepsi, sin embargo, estas no desplazaron a Inca Kola a pesar del poder de marketing que cuentan. En este sentido, el objetivo del presente trabajo es estudiar cómo la Corporación Lindley mantiene su bebida "Inca Kola" como una especialidad en el Perú, por medio de la metodología de las tres vías propuesto por Joskow. Los resultados indican que existen leyes que salvaguardan la marca Inca Kola, tanto en el ámbito nacional como internacional y que gracias a la alianza entre la corporación Lindley y Coca Cola Company, se puso fin a la competencia, aumentando las barreras de ingreso en el sector de bebidas, y como resultado la corporación pudo enfocar sus esfuerzos en seguir vinculando la bebida con la cultura peruana y modernizar sus diferentes plantas de envasado. Las conclusiones más resaltantes indican que la corporación Lindley se apalancó en el Entorno Institucional informal para captar las preferencia de los peruanos, en otras palabras vinculó una bebida aprovechando las características que tienen los consumidores peruano, los cuales tienen lazos muy fuertes con productos que asocian con la identidad nacional. En la vía de la Moderna Organización Industrial se observa que la bebida sigue liderando las ventas con un precio mayor que los competidores, indicando que la corporación tiene una estrategia de diferenciación. Respecto a la vía de la estructura de gobernaza, la corporación pudo alinear sus transacciones con los proveedores de insumos y distribuidores para garantizar la calidad, precio y a asegurando su activo especifico más importante, la marca "Inca Kola". Estas características son propias de las Especialidades.

Preliminary studies on the effect of the increased biodiversity on the population dynamics of Caliroa cerasi L. (Hymenoptera: Tenthredinidae), and its natural enemy Trichogramma minutum R. (Hymenoptera: Trichogrammatidae) in a sweet cherry (Prunus avium L.) orchard in Virch (Southern Patagonia Argentina)

p.25-36

Una propuesta para predecir el factor de erosividad R para el centro y norte de la Argentina

p.133-138

Efecto del 2,4 - DP sobre el tamaño de frutos de kiwi, Actinidia deliciosa (Chevalier) - C.F. Liang - A.R.Ferguson

p.161-165

Preliminary studies on the effect of the increased biodiversity on the population dynamics of Caliroa cerasi L. (Hymenoptera: Tenthredinidae), and its natural enemy Trichogramma minutum R. (Hymenoptera: Trichogrammatidae) in a sweet cherry (Prunus avium L.) orchard in Virch (Southern Patagonia Argentina)

p.25-36

Introducción a la Estadística con R

Generalmente, los estudiantes de bachillerato y universitarios tienen dificultades para comprender los conceptos más elementales de probabilidad y estadística. La presentación de conceptos abstractos de una forma visual y dinámica puede ayudar a comprenderlos mejor. La simulación de experimentos aleatorios ayudará a conseguirlo. Presentamos a continuación algunas de las actividades preparadas para ello.

Implementación del análisis en componentes principales con el software estadístico R

El Análisis en Componentes Principales (ACP) constituye la técnica base para el Análisis Multivariado de Datos. Su objetivo principal es reducir la cantidad de variables, manteniendo la máxima cantidad de información, presente en una tabla de datos de variables cuantitativas. En el presente artículo se expone un panorama general sobre la estructura que fundamenta un ACP y se implementa un caso concreto en el software estadístico R. Para ello es necesario un conocimiento básico de este software.

[1H,15N] N.M.R. Kinetic Studies of Reactions of cis- and trans-[PtCl2(15NH3)(c-C6H1115NH2)] with Guanosine 5'-Monophosphate

cis-[PtCl2(15NH3)(c-C6H11NH2)] is an active metabolite of the oral platinum(IV) anticancer drug cis,trans,cis-[PtCl2(CH3CO2)2(NH2)(c-C6H11NH2)]. Since it is likely that guanine bases on DNA are targets for this drug, we have analysed the kinetics of reaction of this platinum(II) metabolite with guanosine 5′-monophosphate (5′-GMP) at 310 K, pH 7, using [1H, 15N] n.m.r. methods. Reactions of the trans isomer are reported for comparison. The reactions proceed via aquated intermediates, and, for the cis isomer, the rates of aquation and substitution of H2O by 5′-GMP are 2-5 times faster trans to the amine ligand (c-C6H11NH2) compared to trans to NH3 for both the first and second steps. For the trans complex, the first aquation step is c. 3 times faster than for the cis complex, as expected from the higher trans influence of Cl¯, whereas the rate of the second aquation step (trans to N7 of 5′-GMP) is comparable to that trans to NH3. These findings have implications for the courses of reactions with DNA.

Methodologies employed in the collection, retrieval and storage of human factors information derived from first hand accounts of survivors of the WTC disaster of 11 September 2001

This article provides a broad overview of project HEED (High-rise Evacuation Evaluation Database) and the methodologies employed in the collection and storage of first-hand accounts of evacuation experiences derived from face-to-face interviews of evacuees from the World Trade Center (WTC) Twin Towers complex on September 11, 2001. In particular, the article describes the development of the HEED database. This is a flexible research tool which contains qualitative type data in the form of coded evacuee experiences along with the full interview transcripts. The data and information captured and stored in the HEED database is not only unique, but provides a means to address current and emerging issues relating to human factors associated with the evacuation of high-rise buildings