Rapid molecular diagnosis of von Willebrand disease by direct sequencing. Detection of 12 novel putative mutations in VWF gene.

Molecular diagnosis of von Willebrand Disease (VWD) is particularly complex. The autosomal von Willebrand factor gene (VWF) is large and highly polymorphic, and there is a highly homologous (>96%) partial pseudogene in chromosome 22. Because of these difficulties, application of molecular study of VWD to the clinical routine has been considerably delayed. Recent advances in sequencing technology and bioinformatics could convert direct sequencing of the complete VWF into a routine diagnostic tool for VWD, which is especially desirable in types 1 and 3. This study describes a highly optimized procedure in which all the coding and intronic flanking regions of VWF are amplified under identical thermocycling parameters in a ready-to-use PCR plate format. The entire sequencing procedure, from blood extraction to mutation identification, can be done within 24 hours, resulting in a simple, versatile, cost-effective strategy with little hands-on time requirements. To validate the method, we performed full-length VWF sequencing of 21 index cases including seven of each VWD type. A total of 30 VWF genetic variations were identified. Twelve of these sequence variations are new, including four missense, one nonsense, one insertion, the first insertion-deletion described in VWF, and 5 potential splice site mutations. To our knowledge, this is the fastest and most efficient protocol designed to date for complete sequencing of the VWF coding region in the molecular diagnosis of VWD.

Approximate reduction of multiregional models with environmental stochasticity.

In this work we extend previous results regarding the use of approximate aggregation techniques to simplify the study of discrete time models for populations that live in an environment that changes randomly with time. Approximate aggregation techniques allow one to transform a complex system involving many coupled variables and in which there are processes with different time scales, by a simpler reduced model with a fewer number of 'global' variables, in such a way that the dynamics of the former can be approximated by that of the latter. We present the reduction of a stochastic multiregional model in which the population, structured by age and spatial location, lives in a random environment and in which migration is fast with respect to demography. However, the technique works in much more general settings as, for example, those of stage-structured populations living in a multipatch environment. By manipulating the original system and appropriately defining the global variables we obtain a simpler system. The paper concentrates on establishing relationships between the original and the reduced systems for a given separation of time scales between the two processes. In particular, we relate the original state variables and the global variables and, in the case the pattern of temporal variation is Markovian, we relate the presence of strong stochastic ergodicity for the original and reduced systems. Moreover, we relate different measures of asymptotic population growth for these systems.

Guía práctica para la constitución de IPS del primer nivel de atención en salud / Practical guide for a first level health care IPS constitution

Se ha realizado una monografía sobre los aspectos más importantes a tener en cuenta cuando se desee crear una Institución Prestadora de servicios de salud del primer nivel de atención de acuerdo con los lineamientos del nuevo sistema de Seguridad Social Integral creada en Colombia por la Ley 100 de 1993.La monografía analiza las aspectos más importantes a tener en cuenta por los gestores de una I.P.S del primer nivel de atención, como son: mercadeo en salud, planeación estratégica, sistemas de calidad, estructura orgánica, gerencia de la información, constitución legal y licenciamiento.En el desarrollo de los temas se utilizó un lenguaje de fácil comprensión para los que inician la idea. Quedan algunos contenidos sin analizar pero los expuestos representan los fundamentos que garantizan una gestión exitosa para cualquier empresa...