In vitro engineering of human stratified urothelium: analysis of its morphology and function.

PURPOSE: Gastric or intestinal patches, commonly used for reconstructive cystoplasty, may induce severe metabolic complications. The use of bladder tissues reconstructed in vitro could avoid these complications. We compared cellular differentiation and permeability characteristics of human native with in vitro cultured stratified urothelium. MATERIALS AND METHODS: Human stratified urothelium was induced in vitro. Morphology was studied with light and electron microscopy and expression of key cellular proteins was assessed using immunohistochemistry. Permeability coefficients were determined by measuring water, urea, ammonia and proton fluxes across the urothelium. RESULTS: As in native urothelium the stratified urothelial construct consisted of basal membrane and basal, intermediate and superficial cell layers. The apical membrane of superficial cells formed villi and glycocalices, and tight junctions and desmosomes were developed. Immunohistochemistry showed similarities and differences in the expression of cytokeratins, integrin and cellular adhesion proteins. In the cultured urothelium cytokeratin 20 and integrin subunits alpha6 and beta4 were absent, and symplekin was expressed diffusely in all layers. Uroplakins were clearly expressed in the superficial umbrella cells of the urothelial constructs, however, they were also present in intermediate and basal cells. Symplekin and uroplakins were expressed only in the superficial cells of native bladder tissue. The urothelial constructs showed excellent viability, and functionally their permeabilities for water, urea and ammonia were no different from those measured in native human urothelium. Proton permeability was even lower in the constructs compared to that of native urothelium. CONCLUSIONS: Although the in vitro cultured human stratified urothelium did not show complete terminal differentiation of its superficial cells, it retained the same barrier characteristics against the principal urine components. These results indicate that such in vitro cultured urothelium, after being grown on a compliant degradable support or in coculture with smooth muscle cells, is suitable for reconstructive cystoplasty.

Economic development and changes in car ownership patterns

The contributions of this paper are twofold: On the one hand, the paper analyses the factors determining the growth in car ownership in Spain over the last two decades, and, on the other, the paper provides empirical evidence for a controversial methodological issue. From a methodological point of view, the paper compares the two alternative decision mechanisms used for modelling car ownership: ordered-response versus unordered-response mechanisms. A discrete choice model is estimated at three points in time: 1980, 1990 and 2000. The study concludes that on the basis of forecasting performance, the multinomial logit model and the ordered probit model are almost undistinguishable. As for the empirical results, it can be emphasised that income elasticity is not constant and declines as car ownership increases. Besides, households living in rural areas are less sensitive than those living in urban areas. Car ownership is also sensitive to the quality of public transport for those living in the largest cities. The results also confirmed the existence of a generation effect, which will vanish around the year 2020, a weak life-cycle effect, and a positive effect of employment on the number of cars per household. Finally, the change in the estimated coefficients over time reflects an increase in mobility needs and, consequently, an increase in car ownership.

NAVA enhances tidal volume and diaphragmatic electro-myographic activity matching: a Range90 analysis of supply and demand.

Neurally adjusted ventilatory assist (NAVA) is a ventilation assist mode that delivers pressure in proportionality to electrical activity of the diaphragm (Eadi). Compared to pressure support ventilation (PS), it improves patient-ventilator synchrony and should allow a better expression of patient's intrinsic respiratory variability. We hypothesize that NAVA provides better matching in ventilator tidal volume (Vt) to patients inspiratory demand. 22 patients with acute respiratory failure, ventilated with PS were included in the study. A comparative study was carried out between PS and NAVA, with NAVA gain ensuring the same peak airway pressure as PS. Robust coefficients of variation (CVR) for Eadi and Vt were compared for each mode. The integral of Eadi (ʃEadi) was used to represent patient's inspiratory demand. To evaluate tidal volume and patient's demand matching, Range90 = 5-95 % range of the Vt/ʃEadi ratio was calculated, to normalize and compare differences in demand within and between patients and modes. In this study, peak Eadi and ʃEadi are correlated with median correlation of coefficients, R > 0.95. Median ʃEadi, Vt, neural inspiratory time (Ti_ ( Neural )), inspiratory time (Ti) and peak inspiratory pressure (PIP) were similar in PS and NAVA. However, it was found that individual patients have higher or smaller ʃEadi, Vt, Ti_ ( Neural ), Ti and PIP. CVR analysis showed greater Vt variability for NAVA (p < 0.005). Range90 was lower for NAVA than PS for 21 of 22 patients. NAVA provided better matching of Vt to ʃEadi for 21 of 22 patients, and provided greater variability Vt. These results were achieved regardless of differences in ventilatory demand (Eadi) between patients and modes.

Alveolar echinococcosis of the liver: Diffusion-weighted MRI findings and potential role in lesion characterisation

PURPOSE: To report the diffusion-weighted MRI findings in alveolar echinococcosis (AE) of the liver and evaluate the potential role of apparent diffusion coefficients (ADCs) in the characterisation of lesions. MATERIALS AND METHODS: We retrospectively included 22 patients with 63 AE liver lesions (≥1cm), examined with 3-T liver MRI, including a free-breathing diffusion-weighted single-shot echo-planar imaging sequence (b-values=50, 300 and 600s/mm(2)). Two radiologists jointly assessed the following lesion features: size, location, presence of cystic and/or solid components (according to Kodama's classification system), relative contrast enhancement, and calcifications (on CT). The ADCtotal, ADCmin and ADCmax were measured in each lesion and the surrounding liver parenchyma. RESULTS: Three type 1, 19 type 2, 17 type 3, three type 4 and 21 type 5 lesions were identified. The mean (±SD) ADCtotal, ADCmin and ADCmax for all lesions were 1.73±0.50, 0.76±0.38 and 2.63±0.76×10(-3)mm(2)/s, respectively. The mean ADCtotal for type 1, type 2, type 3, type 4 and type 5 lesions were 1.97±1.01, 1.76±0.53, 1.73±0.41, 1.15±0.42 and 1.76±0.44×10(-3)mm(2)/s, respectively. No significant differences were found between the five lesion types, except for type 4 (p=0.0363). There was a significant correlation between the presence of a solid component and low ADCmin (r=0.39, p=0.0016), whereas an inverse correlation was found between the relative contrast enhancement and ADCtotal (r=-0.34, p=0.0072). CONCLUSION: The ADCs of AE lesions are relatively low compared to other cystic liver lesions, which may help in the differential diagnosis. Although ADCs are of little use to distinguish between the five lesion types, their low value reflects the underlying solid component.

Testing for Proportional Hazards with Unrestricted Univariate Unobserved Heterogeneity

We develop tests of the proportional hazards assumption, with respect to a continuous covariate, in the presence of unobserved heterogeneity with unknown distribution at the individual observation level. The proposed tests are specially powerful against ordered alternatives useful for modeling non-proportional hazards situations. By contrast to the case when the heterogeneity distribution is known up to …nite dimensional parameters, the null hypothesis for the current problem is similar to a test for absence of covariate dependence. However, the two testing problems di¤er in the nature of relevant alternative hypotheses. We develop tests for both the problems against ordered alternatives. Small sample performance and an application to real data highlight the usefulness of the framework and methodology.

Simulating Wages and House Prices Using the NEG

The paper incorporates house prices within an NEG framework leading to the spatial distributions of wages, prices and income. The model assumes that all expenditure goes to firms under a monopolistic competition market structure, that labour efficiency units are appropriate, and that spatial equilibrium exists. The house price model coefficients are estimated outside the NEG model, allowing an econometric analysis of the significance of relevant covariates. The paper illustrates the methodology by estimating wages, income and prices for small administrative areas in Great Britain, and uses the model to simulate the effects of an exogenous employment shock.

Dépistage et traitement de l'infection tuberculeuse latente chez les requérants d'asile récemment arrivés dans le canton de Vaud Dépistage et traitement de l'infection tuberculeuse latente chez les requérants d'asile récemment arrivés dans le canton de Vaud

I. Facteurs associés avec l'infection tuberculose latent chez les requérants d'asile entrant dans le canton de Vaud : Une étude transversale dans le canton de Vaud. Objectifs : Les objectifs de cette étude étaient l'identification des facteurs associés à l'infection tuberculeuse latente (ITBL) chez les requérants d'asile récemment arrivés au Canton de Vaud et leur utilisation pondérée pour l'élaboration d'un score prédictif qui pourrait permettre la meilleure sélection des individus à dépister avec les Interferon Gamma Release Assays (IGRA). Méthode : Le protocole de l'étude prévoyait l'inclusion des requérants d'asile de plus de 16 ans, récemment arrivés dans deux centre de requérant du canton de Vaud ceux de Sainte-Croix et de Crissier. De septembre 2009 à juillet 2010 les requérants d'asile ont bénéficié lors des visites au centre de soins infirmier (CSI) d'informations sur l'ITBL et le protocole et les enjeux de l'étude. Les requérants d'asile ont d'emblée été informées que leur participation à l'étude n'aurait pas d'impact sur le débouché de leur dossier d'asile et qu'il n'y aurait pas de compensation financière à leur participation. Après avoir signé le consentement éclairé les requérants d'asile bénéficiaient d'une entrevue avec l'infirmière du centre où un questionnaire démographique et médical était remplit. 10cc de sang étaient prélevés à la fin de l'entrevue pour l'examen IGRA. Les patients présentant des symptômes évocateurs de tuberculose active ou un anamnèse de traitement pour une tuberculose active étaient exclus de l'étude et adressés au médecin référant du centre pour une visite médicale. Selon les résultats du test T-SPOT.TB (IGRA), les requérants étaient classés en deux groupes : positifs et négatifs. Le groupe IGRA positif était adressé au médecin référant. L'analyse statistique des données de l'étude a été réalisée par le logiciel STATA 11.2. Les coefficients de l'analyse multivariée ont été combinées pour la création d'un score pronostic dont la puissance de discrimination a été évaluée par une courbe ROC. Le protocole de l'étude avait reçu l'aval de la commission d'éthique de l'Université de Lausanne. Résultats : Durant la période de l'étude, 788 requérants d'asile ont été hébergés dans les deux centres de l'étude. 639 avaient plus de 16 ans et 393 d'entre eux ont participé à l'étude (61.50%). 295 (75.06%) avaient un IGRA négatif et 98 (24.93%) étaient positifs. A noter que parmi les 98 positifs, 5 avaient une tuberculose active non détecté précédemment. Les analyses univarié et multivarié ont permis d'identifier 6 facteurs associées à l'ITBL : Région d'origine, moyen de transport, état civil, âge, toux et antécédent d'exposition à la tuberculose. Le score élaboré en combinant ces 6 facteurs présente un AUC de 81% avec une sensibilité de 80%, une spécificité de 70% et des valeurs prédictive positive et négative respectivement de 45% et 92% quant un seuil de 13 est utilisé. Conclusion : Les requérants d'asile qui immigrent en Suisse proviennent de pays où l'incidence de la tuberculose est supérieure à celle des pays de l'Europe occidentale et présentent un risque élevé pour l'infection tuberculose latente (ITBL). L'origine comme seul facteur n'est pas suffisant pour stratifier le risque d'ITBL et ne peut pas justifier la prescription d'un traitement préventif d'ITBL. L'introduction des tests de détection, hautement spécifiques de l'infection au M. tuberculosis tel que les IGRA ainsi que le taux élevé de réussite des traitements préventifs de l'infection latente ont ouvert la voie à un dépistage précoce de l'ITBL qui compléterait le dépistage de la tuberculose active actuellement effectué à la frontière. Afin de mieux cibler le dépistage par ces tests une meilleure sélection des individus à dépister est impérative. Elle pourrait se faire en évaluant le score individuel de risque ITBL par requérant. -- II. Taux élevé d'adhérence au traitement préventif de l'infection tuberculeuse latente prescrit à un collectif de requérants d'asile dans un canton suisse. Objectifs: L'efficacité du traitement préventif de l'infection tuberculeuse latente dépend de l'adherence du sujet au traitement. Un traitement bien conduit pour une duré prévue est en mesure de prévenir l'activation des cas d'infection tuberculeuse latente (ITBL). Le plus grand enjeu dans un programme préventif pour la tuberculose est, outre de cibler la détection des individus les plus à risque pour l'ITBL, de pouvoir traiter efficacement le collectif dépisté positif. Cette étude évaluait la faisabilité d'un traitement préventif court parmi un collectif de requérants d'asile porteurs d'une ITBL dans le canton de Vaud. Méthode: Nous avons effectué une étude prospective de cohorte parmi des requérants d'asile récemment attribués dans le canton de Vaud, âgés de plus de 16 ans et qui avaient été dépistés positifs par IGRA. L'ensemble du collectif selon le protocole de l'étude était adressé au médecin référant afin d'exclure une tuberculose active et pour discuter du traitement préventif si le diagnostic d'ITBL était confirmé. Lors de la première visite médicale, outre l'examen clinique, un bilan radiologique avec une radiographie du thorax et un bilan de la biologie hépatique ainsi qu'un test de dépistage HIV était proposé à l'ensemble du collectif. En cas de suspicion clinique ou d'image radiologique suspecte de tuberculose active le sujet était adressé pour des examens complémentaires. Les sujets porteurs d'ITBL se voyaient proposés, en l'absence de contre indications, un traitement de rifampicine de quatre mois. En acceptant de participer à l'étude ils s'engageaient de se présenter à leur contrôle médical mensuel où était évaluée l'adhérence au traitement et l'apparition d'effets indésirable ou de complications. Si l'adhérence était jugée correcte l'ordonnance du traitement était renouvelée d'un mois et le requérant recevait son prochain rendez-vous de contrôle. L'adhérence était considéré satisfaisante si le patient était adhérent à son schéma de visites médicales et demandait le renouvellement de son ordonnance. Si le requérant d'asile ne se présentait pas à deux contrôles il était considéré comme non adhérent et son traitement est suspendu. Résultats : Notre collectif comptait 98 sujet présument atteint de ITBL sur la base du test T-SPOT.TB ce qui représentait 24.9% du collectif initial. L'âge moyen était de 26.7 ans, 74% était des hommes. La majorité étaient des africains: 66 %, 17% étaient asiatiques et les populations balkaniques et de l'exunion soviétique étaient représentés à part égale d'huit pourcent. Parmi notre collectif nous n'avions pas de sujet immunodéficient notamment HIV positif. Des 98 sujets, 11 ne se sont pas présenté à leur visite médicale initiale. La visite médicale initiale a permis la détection de 8 patients porteurs d'une tuberculose active, dont cinq ont reçu un traitement antituberculeux, ou d'une autre affection pulmonaire non tuberculeuse. Chez deux patients il y avait une contre-indication au traitement préventif et deux avaient un anamnèse positif de traitement antituberculeux non précédemment déclaré. Le traitement préventif a été prescrit à 74 requérants d'asile. Durant le suivi mensuel trois requérants ne se sont pas présentés lors de la première visite de suivi, trois lors de la seconde et sept lors de la troisième pour un total de 13 sujets. Chez deux sujets le traitement préventif a du être suspendu à cause d'une adhérence problématique secondaire à des abus de substances illégales. Durant le suivi, nous n'avons pas eu de sérieuses complications ni d'effets indésirables au traitement qui auraient nécessité son arrêt. En final 60/75 des sujets ont achevé leur traitement soit 80% du collectif. Conclusion: Malgré la vulnérabilité et la volatilité inhérente à cette population qui est d'ailleurs la plus à risqué de réactivation d'une ITBL, cette étude montre que il est possible d'obtenir de taux d'adhérence très élevés au traitement préventif. Nous considérons que les conditions qui ont permis ces résultats sont la prescription d'un schéma de traitement préventif court, un suivi médico-soignant régulier et l'hébergement contrôlée et stable où résidait notre collectif.

Understanding Interactions in Social Networks and Committees

While much of the literature on cross section dependence has focused mainly on estimation of the regression coefficients in the underlying model, estimation and inferences on the magnitude and strength of spill-overs and interactions has been largely ignored. At the same time, such inferences are important in many applications, not least because they have structural interpretations and provide useful interpretation and structural explanation for the strength of any interactions. In this paper we propose GMM methods designed to uncover underlying (hidden) interactions in social networks and committees. Special attention is paid to the interval censored regression model. Our methods are applied to a study of committee decision making within the Bank of England’s monetary policy committee.

Responsibility for regional waste generation: A single region extended input-output analysis with uni-directional trade flows

The paper uses a regional input-output (IO) framework and data derived on waste generation by industry to examine regional accountability for waste generation. In addition to estimating a series of industry output-waste coefficients, the paper considers two methods for waste attribution but focuses first on one (trade endogenised linear attribution system (TELAS)) that permits a greater focus on private and public final consumption as the main exogenous driver of waste generation. Second, the paper uses a domestic technology assumption (DTA) to consider a regional ‘waste footprint’ where local consumption requirements are assumed to be met through domestic production.

A Panel Data Investigation of Real Exchange Rate Misalignment and Growth

The paper investigates the role of real exchange rate misalignment on long-run growth for a set of ninety countries using time series data from 1980 to 2004. We first estimate a panel data model (using fixed and random effects) for the real exchange rate, with different model specifications, in order to produce estimates of the equilibrium real exchange rate and this is then used to construct measures of real exchange rate misalignment. We also provide an alternative set of estimates of real exchange rate misalignment using panel cointegration methods. The variables used in our real exchange rate models are: real per capita GDP; net foreign assets; terms of trade and government consumption. The results for the two-step System GMM panel growth models indicate that the coefficients for real exchange rate misalignment are positive for different model specification and samples, which means that a more depreciated (appreciated) real exchange rate helps (harms) long-run growth. The estimated coefficients are higher for developing and emerging countries.

The Role of Institutions in Cross-Section Income and Panel Data Growth Models: A Deeper Investigation on the Weakness and Proliferation of Instruments

This paper investigates the role of institutions in determining per capita income levels and growth. It contributes to the empirical literature by using different variables as proxies for institutions and by developing a deeper analysis of the issues arising from the use of weak and too many instruments in per capita income and growth regressions. The cross-section estimation suggests that institutions seem to matter, regardless if they are the only explanatory variable or are combined with geographical and integration variables, although most models suffer from the issue of weak instruments. The results from the growth models provides some interesting results: there is mixed evidence on the role of institutions and such evidence is more likely to be associated with law and order and investment profile; government spending is an important policy variable; collapsing the number of instruments results in fewer significant coefficients for institutions.

Forecasting the European Carbon Market

In an effort to meet its obligations under the Kyoto Protocol, in 2005 the European Union introduced a cap-and-trade scheme where mandated installations are allocated permits to emit CO2. Financial markets have developed that allow companies to trade these carbon permits. For the EU to achieve reductions in CO2 emissions at a minimum cost, it is necessary that companies make appropriate investments and policymakers design optimal policies. In an effort to clarify the workings of the carbon market, several recent papers have attempted to statistically model it. However, the European carbon market (EU ETS) has many institutional features that potentially impact on daily carbon prices (and associated nancial futures). As a consequence, the carbon market has properties that are quite different from conventional financial assets traded in mature markets. In this paper, we use dynamic model averaging (DMA) in order to forecast in this newly-developing market. DMA is a recently-developed statistical method which has three advantages over conventional approaches. First, it allows the coefficients on the predictors in a forecasting model to change over time. Second, it allows for the entire fore- casting model to change over time. Third, it surmounts statistical problems which arise from the large number of potential predictors that can explain carbon prices. Our empirical results indicate that there are both important policy and statistical bene ts with our approach. Statistically, we present strong evidence that there is substantial turbulence and change in the EU ETS market, and that DMA can model these features and forecast accurately compared to conventional approaches. From a policy perspective, we discuss the relative and changing role of different price drivers in the EU ETS. Finally, we document the forecast performance of DMA and discuss how this relates to the efficiency and maturity of this market.

Large Time-Varying Parameter VARs

In this paper we develop methods for estimation and forecasting in large timevarying parameter vector autoregressive models (TVP-VARs). To overcome computational constraints with likelihood-based estimation of large systems, we rely on Kalman filter estimation with forgetting factors. We also draw on ideas from the dynamic model averaging literature and extend the TVP-VAR so that its dimension can change over time. A final extension lies in the development of a new method for estimating, in a time-varying manner, the parameter(s) of the shrinkage priors commonly-used with large VARs. These extensions are operationalized through the use of forgetting factor methods and are, thus, computationally simple. An empirical application involving forecasting inflation, real output, and interest rates demonstrates the feasibility and usefulness of our approach.

Extending contingency: the impact of strategy, technology, size and business environment on the organisational form of small Chinese firms

This paper is inspired by articles in the last decade or so that have argued for more attention to theory, and to empirical analysis, within the well-known, and long-lasting, contingency framework for explaining the organisational form of the firm. Its contribution is to extend contingency analysis in three ways: (a) by empirically testing it, using explicit econometric modelling (rather than case study evidence) involving estimation by ordered probit analysis; (b) by extending its scope from large firms to SMEs; (c) by extending its applications from Western economic contexts, to an emerging economy context, using field work evidence from China. It calibrates organizational form in a new way, as an ordinal dependent variable, and also utilises new measures of familiar contingency factors from the literature (i.e. Environment, Strategy, Size and Technology) as the independent variables. An ordered probit model of contingency was constructed, and estimated by maximum likelihood, using a cross section of 83 private Chinese firms. The probit was found to be a good fit to the data, and displayed significant coefficients with plausible interpretations for key variables under all the four categories of contingency analysis, namely Environment, Strategy, Size and Technology. Thus we have generalised the contingency model, in terms of specification, interpretation and applications area.

Bayesian forecasting with highly correlated predictors

This paper considers Bayesian variable selection in regressions with a large number of possibly highly correlated macroeconomic predictors. I show that by acknowledging the correlation structure in the predictors can improve forecasts over existing popular Bayesian variable selection algorithms.