Estudi de l'estat de Salut autopercebut: Modelització de l'índex d'utilitat EQ-5D mitjançant un model tobit

Objective: Health status measures usually have an asymmetric distribution and present a highpercentage of respondents with the best possible score (ceiling effect), specially when they areassessed in the overall population. Different methods to model this type of variables have beenproposed that take into account the ceiling effect: the tobit models, the Censored Least AbsoluteDeviations (CLAD) models or the two-part models, among others. The objective of this workwas to describe the tobit model, and compare it with the Ordinary Least Squares (OLS) model,that ignores the ceiling effect.Methods: Two different data sets have been used in order to compare both models: a) real datacomming from the European Study of Mental Disorders (ESEMeD), in order to model theEQ5D index, one of the measures of utilities most commonly used for the evaluation of healthstatus; and b) data obtained from simulation. Cross-validation was used to compare thepredicted values of the tobit model and the OLS models. The following estimators werecompared: the percentage of absolute error (R1), the percentage of squared error (R2), the MeanSquared Error (MSE) and the Mean Absolute Prediction Error (MAPE). Different datasets werecreated for different values of the error variance and different percentages of individuals withceiling effect. The estimations of the coefficients, the percentage of explained variance and theplots of residuals versus predicted values obtained under each model were compared.Results: With regard to the results of the ESEMeD study, the predicted values obtained with theOLS model and those obtained with the tobit models were very similar. The regressioncoefficients of the linear model were consistently smaller than those from the tobit model. In thesimulation study, we observed that when the error variance was small (s=1), the tobit modelpresented unbiased estimations of the coefficients and accurate predicted values, specially whenthe percentage of individuals wiht the highest possible score was small. However, when theerrror variance was greater (s=10 or s=20), the percentage of explained variance for the tobitmodel and the predicted values were more similar to those obtained with an OLS model.Conclusions: The proportion of variability accounted for the models and the percentage ofindividuals with the highest possible score have an important effect in the performance of thetobit model in comparison with the linear model.

Combined loss of the BH3-only proteins Bim and Bmf restores B-cell development and function in TACI-Ig transgenic mice.

Terminal differentiation of B cells depends on two interconnected survival pathways, elicited by the B-cell receptor (BCR) and the BAFF receptor (BAFF-R), respectively. Loss of either signaling pathway arrests B-cell development. Although BCR-dependent survival depends mainly on the activation of the v-AKT murine thymoma viral oncogene homolog 1 (AKT)/PI3-kinase network, BAFF/BAFF-R-mediated survival engages non-canonical NF-κB signaling as well as MAPK/extracellular-signal regulated kinase and AKT/PI3-kinase modules to allow proper B-cell development. Plasma cell survival, however, is independent of BAFF-R and regulated by APRIL that signals NF-κB activation via alternative receptors, that is, transmembrane activator and CAML interactor (TACI) or B-cell maturation (BCMA). All these complex signaling events are believed to secure survival by increased expression of anti-apoptotic B-cell lymphoma 2 (Bcl2) family proteins in developing and mature B cells. Curiously, how lack of BAFF- or APRIL-mediated signaling triggers B-cell apoptosis remains largely unexplored. Here, we show that two pro-apoptotic members of the 'Bcl2 homology domain 3-only' subgroup of the Bcl2 family, Bcl2 interacting mediator of cell death (Bim) and Bcl2 modifying factor (Bmf), mediate apoptosis in the context of TACI-Ig overexpression that effectively neutralizes BAFF as well as APRIL. Surprisingly, although Bcl2 overexpression triggers B-cell hyperplasia exceeding the one observed in Bim(-/-)Bmf(-/-) mice, Bcl2 transgenic B cells remain susceptible to the effects of TACI-Ig expression in vivo, leading to ameliorated pathology in Vav-Bcl2 transgenic mice. Together, our findings shed new light on the molecular machinery restricting B-cell survival during development, normal homeostasis and under pathological conditions. Our data further suggest that Bcl2 antagonists might improve the potency of BAFF/APRIL-depletion strategies in B-cell-driven pathologies.

Les polymorphismes des gènes encodant les protéines apoptotiques Bim et Bax : leur rôle dans la réponse thérapeutique chez les enfants ayant la leucémie lymphoblastique aiguë

INTRODUCTION Des réponses thérapeutiques variables aux glucocorticoïdes (GCs) sont observées parmi les patients atteints de la leucémie lymphoblastique aiguë (LLA). Les protéines Bax et Bim ont déjà montré un rôle important dans l’apoptose des cellules leucémiques. L’expression de Bax était plus basse chez les patients leucémiques résistants au médicament, de même une sensibilité diminuée aux GCs a été associée avec une expression réduite de Bim. La différence dans l’expression pourrait être due à des polymorphismes présents dans ces gènes et donc être associés avec la résistance aux GCs. MÉTHODE Dix-huit polymorphismes en régions régulatrices, 2 polymorphismes exoniques et 7 polymorphismes en région 3’UTR de ces gènes ont été analysés chez les témoins (n=50) et ont permis de déterminer un nombre minimal de polymorphismes suffisants pour définir les haplotypes (tagSNPs). Ces 8 polymorphismes ont ensuite été génotypés chez 286 enfants atteints de la LLA et ont été testés pour l’issue de la maladie par l’analyse de survie. RÉSULTATS Une survie sans évènement et une survie sans rechute diminuées ont été observées pour l’haplotype 3 (p=0,03 et p=0,02). Une survie globale diminuée a été associée avec l’homozygotie pour l’allèle exonique T298C>T (p=0,03), de même que pour les haplotypes 1 et 4 (p=0,04 et p=0,02) du gène Bim. CONCLUSION Les polymorphismes ont été associés avec une survie diminuée chez des enfants atteints de LLA. Il reste à tester d’autres polymorphismes présents dans ces deux gènes ainsi qu’à définir leurs fonctions afin de comprendre leurs rôles dans la réponse aux GCs.

Análisis de la evolución en las prácticas de Mejoramiento Integral de Barrios (BIM) en la Gestión Urbana de Bogotá entre 1995-2011

La ciudad informal en las periferias urbanas ha sido una de las mayores preocupaciones de las grandes ciudades latinoamericanas. Distintos enfoques a este problema han derivado en distintas formas de abordarlo a partir de la política pública. En el caso de Bogotá, los Programas de Mejoramiento Integral han permitido visibilizar, intervenir e integrar grandes porciones de suelo objeto de procesos de urbanizaciones incompletas, dando solución a miles de familias que han tenido que asentarse de forma emergente y bajo condiciones urbanas muy precarias. De hecho, Bogotá se ha convertido en una referencia nacional e internacional sobre la forma en que se ha implementado este tipo de programa. Sin embargo, al hacer un repaso sobre las enseñanzas que ha dejado esta experiencia, se encuentra información pública limitada y se evidencia una pérdida de la memoria institucional sobre su operación y resultados.

Implementing ‘Site BIM’: a case study of ICT innovation on a large hospital project

Numerous Building Information Modelling (BIM) tools are well established and potentially beneficial in certain uses. However, issues of adoption and implementation persist, particularly for on-site use of BIM tools in the construction phase. We describe an empirical case-study of the implementation of an innovative ‘Site BIM’ system on a major hospital construction project. The main contractor on the project developed BIM-enabled tools to allow site workers using mobile tablet personal computers to access design information and to capture work quality and progress data on-site. Accounts show that ‘Site BIM’, while judged to be successful and actively supporting users, was delivered through an exploratory and emergent development process of informal prototyping. Technical IT skills were adopted into the construction project through personal relationships and arrangements rather than formal processes. Implementation was driven by construction project employees rather than controlled centrally by the corporate IT function.

BIM: innovation in design management, influence and challenges of implementation

The construction industry is widely being criticised as a fragmented industry. There are mounting calls for the industry to change. The espoused change calls for collaboration as well as embracing innovation in the process of design, construction and across the supply chain. Innovation and the application of emerging technologies are seen as enablers for integrating the processes ‘integrating the team’ such as building information modelling (BIM). A questionnaire survey was conducted to ascertain change in construction with regard to design management, innovation and the application of BIM as cutting edge pathways for collaboration. The respondents to the survey were from an array of designations across the construction industry such as construction managers, designers, engineers, design coordinators, design managers, architects, architectural technologists and surveyors. There was a general agreement by most respondents that the design team was responsible for design management in their organisation. There is a perception that the design manager and the client are the catalyst for advancing innovation. The current state of industry in terms of incorporating BIM technologies is posing a challenge as well as providing an opportunity for accomplishment. BIM technologies provide a new paradigm shift in the way buildings are designed, constructed and maintained. This paradigm shift calls for rethinking the curriculum for educating building professionals, collectively.

Interactive learning in UK construction practice: examining the role of BIM process standards

From a construction innovation systems perspective, firms acquire knowledge from suppliers, clients, universities and institutional environment. Building information modelling (BIM) involves these firms using new process standards. To understand the implications on interactive learning using BIM process standards, a case study is conducted with the UK operations of a multinational construction firm. Data is drawn from: a) two workshops involving the firm and a wider industry group, b) observations of practice in the BIM core team and in three ongoing projects, c) 12 semi-structured interviews; and d) secondary publications. The firm uses a set of BIM process standards (IFC, PAS 1192, Uniclass, COBie) in its construction activities. It is also involved in a pilot to implement the COBie standard, supported by technical and management standards for BIM, such as Uniclass and PAS1192. Analyses suggest that such BIM process standards unconsciously shapes the firm's internal and external interactive learning processes. Internally standards allow engineers to learn from each through visualising 3D information and talking around designs with operatives to address problems during construction. Externally, the firm participates in trial and pilot projects involving other construction firms, government agencies, universities and suppliers to learn about the standard and access knowledge to solve its specific design problems. Through its BIM manager, the firm provides feedback to standards developers and information technology suppliers. The research contributes by articulating how BIM process standards unconsciously change interactive learning processes in construction practice. Further research could investigate these findings in the wider UK construction innovation system.