Phenotypic consequences of copy number variation: insights from Smith-Magenis and Potocki-Lupski syndrome mouse models.

A large fraction of genome variation between individuals is comprised of submicroscopic copy number variation of genomic DNA segments. We assessed the relative contribution of structural changes and gene dosage alterations on phenotypic outcomes with mouse models of Smith-Magenis and Potocki-Lupski syndromes. We phenotyped mice with 1n (Deletion/+), 2n (+/+), 3n (Duplication/+), and balanced 2n compound heterozygous (Deletion/Duplication) copies of the same region. Parallel to the observations made in humans, such variation in gene copy number was sufficient to generate phenotypic consequences: in a number of cases diametrically opposing phenotypes were associated with gain versus loss of gene content. Surprisingly, some neurobehavioral traits were not rescued by restoration of the normal gene copy number. Transcriptome profiling showed that a highly significant propensity of transcriptional changes map to the engineered interval in the five assessed tissues. A statistically significant overrepresentation of the genes mapping to the entire length of the engineered chromosome was also found in the top-ranked differentially expressed genes in the mice containing rearranged chromosomes, regardless of the nature of the rearrangement, an observation robust across different cell lineages of the central nervous system. Our data indicate that a structural change at a given position of the human genome may affect not only locus and adjacent gene expression but also "genome regulation." Furthermore, structural change can cause the same perturbation in particular pathways regardless of gene dosage. Thus, the presence of a genomic structural change, as well as gene dosage imbalance, contributes to the ultimate phenotype.

Divergent and convergent margins in the north-western Alps - Confrontation to actualistic models

Divergent and convergent margins actualistic models are reviewed and applied to the history of the western Alps. Tethyan rifting history and geometry are analyzed: the northern European margin is considered as an upper plate whereas the southern Apulian margin is a lower plate; the Breche basin is regarded as the former break-away trough; the internal Brianconnais domain represents the northern rift shoulder whilst the more external domains are regarded as the infill of a complex rim basin locally affected by important extension (Valaisan and Vocontain trough). The Schistes lustres and ophiolites of the Tsate nappe are compared to an accretionary prism: the imbrication of this nappe elements is regarded as a direct consequence of the accretionary phenomena already active in early Cretaceous; the Gets/Simme complex could orginate from a more internal part of the accretionary prism. Some eclogitic basements represent the former Apulian margin substratum (Sesia) others (Mont-Rose) are interpreted as the former edge of the European margin. The history of the closing Tethyan domain is analyzed and the remaining problems concerning the cinematics, the presence/absence of a volcanic arc and the eoalpine metamorphism are discussed.

Entrepreneurial intention, cognitive social capital and culture: empirical anaylisis for Spain and Taiwan

The main purpose of this paper is building a research model to integrate the socioeconomic concept of social capital within intentional models of new firm creation. Nevertheless, some researchers have found cultural differences between countries and regions to have an effect on economic development. Therefore, a second objective of this study is exploring whether those cultural differences affect entrepreneurial cognitions. Research design and methodology: Two samples of last year university students from Spain and Taiwan are studied through an Entrepreneurial Intention Questionnaire (EIQ). Structural equation models (Partial Least Squares) are used to test the hypotheses. The possible existence of differences between both sub-samples is also empirically explored through a multigroup analysis. Main outcomes and results: The proposed model explains 54.5% of the variance in entrepreneurial intention. Besides, there are some significant differences between both subsamples that could be attributed to cultural diversity. Conclusions: This paper has shown the relevance of cognitive social capital in shaping individuals’ entrepreneurial intentions across different countries. Furthermore, it suggests that national culture could be shaping entrepreneurial perceptions, but not cognitive social capital. Therefore, both cognitive social capital and culture (made up essentially of values and beliefs), may act together to reinforce the entrepreneurial intention.

A priori ratemaking using bivariate poisson regression models

In automobile insurance, it is useful to achieve a priori ratemaking by resorting to gene- ralized linear models, and here the Poisson regression model constitutes the most widely accepted basis. However, insurance companies distinguish between claims with or without bodily injuries, or claims with full or partial liability of the insured driver. This paper exa- mines an a priori ratemaking procedure when including two di®erent types of claim. When assuming independence between claim types, the premium can be obtained by summing the premiums for each type of guarantee and is dependent on the rating factors chosen. If the independence assumption is relaxed, then it is unclear as to how the tari® system might be a®ected. In order to answer this question, bivariate Poisson regression models, suitable for paired count data exhibiting correlation, are introduced. It is shown that the usual independence assumption is unrealistic here. These models are applied to an automobile insurance claims database containing 80,994 contracts belonging to a Spanish insurance company. Finally, the consequences for pure and loaded premiums when the independence assumption is relaxed by using a bivariate Poisson regression model are analysed.

Calculation of the variance in surveys of the economic climate

Public opinion surveys have become progressively incorporated into systems of official statistics. Surveys of the economic climate are usually qualitative because they collect opinions of businesspeople and/or experts about the long-term indicators described by a number of variables. In such cases the responses are expressed in ordinal numbers, that is, the respondents verbally report, for example, whether during a given trimester the sales or the new orders have increased, decreased or remained the same as in the previous trimester. These data allow to calculate the percent of respondents in the total population (results are extrapolated), who select every one of the three options. Data are often presented in the form of an index calculated as the difference between the percent of those who claim that a given variable has improved in value and of those who claim that it has deteriorated. As in any survey conducted on a sample the question of the measurement of the sample error of the results has to be addressed, since the error influences both the reliability of the results and the calculation of the sample size adequate for a desired confidence interval. The results presented here are based on data from the Survey of the Business Climate (Encuesta de Clima Empresarial) developed through the collaboration of the Statistical Institute of Catalonia (Institut d’Estadística de Catalunya) with the Chambers of Commerce (Cámaras de Comercio) of Sabadell and Terrassa.

Automatic Mallampati Classification Using Active Appearance Models

Difficult tracheal intubation assessment is an important research topic in anesthesia as failed intubations are important causes of mortality in anesthetic practice. The modified Mallampati score is widely used, alone or in conjunction with other criteria, to predict the difficulty of intubation. This work presents an automatic method to assess the modified Mallampati score from an image of a patient with the mouth wide open. For this purpose we propose an active appearance models (AAM) based method and use linear support vector machines (SVM) to select a subset of relevant features obtained using the AAM. This feature selection step proves to be essential as it improves drastically the performance of classification, which is obtained using SVM with RBF kernel and majority voting. We test our method on images of 100 patients undergoing elective surgery and achieve 97.9% accuracy in the leave-one-out crossvalidation test and provide a key element to an automatic difficult intubation assessment system.

Models i formes de la pintura catalana del Barroc: el mirall de l'art francès

Estudi elaborat a partir d’una estada a l’Institut National d'Histoire de l'Art- Bibliothèque Nationale de France entre l'1 i el 31 de juliol de 2007. S’ha treballat en la recerca documental sobre les relacions artístiques entre França i Catalunya a l’Època Moderna. Els materials o fons documentals d’interès han estat dos: els fons gràfics d’estampes i gravats de la Bibliothèque Nationale, no tant en el sentit de consulta dels originals –que en alguna ocasió també- com sí en el la visualització de les vastíssimes fototeques, que ha permès a l’autor aplegar un bon nombre d’imatges que en el futur serviran per posar en relació la cultura figurativa francesa –sobretot de la pintura i de l’escultura, però també de la tractadística arquitectònica- amb la catalana de l’època, ja sigui per constatar les semblances com per fer notar les diferències en els usos dels models figuratius. S’ha buidat material bibliogràfic difícil de localitzar a Catalunya. Són publicacions referides a gravat, d’una banda, i a patrimoni artístic. Aquest darrer aspecte s’ha treballat des de dos vessants: en seguir notícies de la presència d’artistes catalans a França i viceversa, i en buscar dades sobre l’espoli d’obres d’art portat a terme a Catalunya durant el període napoleònic.

Evaluation of cumulative PCB exposure estimated by a job exposure matrix versus PCB serum concentrations.

Although polychlorinated biphenyls (PCBs) have been banned in many countries for more than three decades, exposures to PCBs continue to be of concern due to their long half-lives and carcinogenic effects. In National Institute for Occupational Safety and Health studies, we are using semiquantitative plant-specific job exposure matrices (JEMs) to estimate historical PCB exposures for workers (n = 24,865) exposed to PCBs from 1938 to 1978 at three capacitor manufacturing plants. A subcohort of these workers (n = 410) employed in two of these plants had serum PCB concentrations measured at up to four times between 1976 and 1989. Our objectives were to evaluate the strength of association between an individual worker's measured serum PCB levels and the same worker's cumulative exposure estimated through 1977 with the (1) JEM and (2) duration of employment, and to calculate the explained variance the JEM provides for serum PCB levels using (3) simple linear regression. Consistent strong and statistically significant associations were observed between the cumulative exposures estimated with the JEM and serum PCB concentrations for all years. The strength of association between duration of employment and serum PCBs was good for highly chlorinated (Aroclor 1254/HPCB) but not less chlorinated (Aroclor 1242/LPCB) PCBs. In the simple regression models, cumulative occupational exposure estimated using the JEMs explained 14-24% of the variance of the Aroclor 1242/LPCB and 22-39% for Aroclor 1254/HPCB serum concentrations. We regard the cumulative exposure estimated with the JEM as a better estimate of PCB body burdens than serum concentrations quantified as Aroclor 1242/LPCB and Aroclor 1254/HPCB.

Can a Lucas model with habit generate realistic conditional volatility in exchange rate returns?

In this paper, we attempt to give a theoretical underpinning to the well established empirical stylized fact that asset returns in general and the spot FOREX returns in particular display predictable volatility characteristics. Adopting Moore and Roche s habit persistence version of Lucas model we nd that both the innovation in the spot FOREX return and the FOREX return itself follow "ARCH" style processes. Using the impulse response functions (IRFs) we show that the baseline simulated FOREX series has "ARCH" properties in the quarterly frequency that match well the "ARCH" properties of the empirical monthly estimations in that when we scale the x-axis to synchronize the monthly and quarterly responses we find similar impulse responses to one unit shock in variance. The IRFs for the ARCH processes we estimate "look the same" with an approximately monotonic decreasing fashion. The Lucas two-country monetary model with habit can generate realistic conditional volatility in spot FOREX return.

Bayesian Inference in the Time Varying Cointegration Model

There are both theoretical and empirical reasons for believing that the parameters of macroeconomic models may vary over time. However, work with time-varying parameter models has largely involved Vector autoregressions (VARs), ignoring cointegration. This is despite the fact that cointegration plays an important role in informing macroeconomists on a range of issues. In this paper we develop time varying parameter models which permit cointegration. Time-varying parameter VARs (TVP-VARs) typically use state space representations to model the evolution of parameters. In this paper, we show that it is not sensible to use straightforward extensions of TVP-VARs when allowing for cointegration. Instead we develop a specification which allows for the cointegrating space to evolve over time in a manner comparable to the random walk variation used with TVP-VARs. The properties of our approach are investigated before developing a method of posterior simulation. We use our methods in an empirical investigation involving a permanent/transitory variance decomposition for inflation.

The Estimation of Technical Efficiency Effects Models with an Example Applied to the Thai Manufacturing Sector

This paper does two things. First, it presents alternative approaches to the standard methods of estimating productive efficiency using a production function. It favours a parametric approach (viz. the stochastic production frontier approach) over a nonparametric approach (e.g. data envelopment analysis); and, further, one that provides a statistical explanation of efficiency, as well as an estimate of its magnitude. Second, it illustrates the favoured approach (i.e. the ‘single stage procedure’) with estimates of two models of explained inefficiency, using data from the Thai manufacturing sector, after the crisis of 1997. Technical efficiency is modelled as being dependent on capital investment in three major areas (viz. land, machinery and office appliances) where land is intended to proxy the effects of unproductive, speculative capital investment; and both machinery and office appliances are intended to proxy the effects of productive, non-speculative capital investment. The estimates from these models cast new light on the five-year long, post-1997 crisis period in Thailand, suggesting a structural shift from relatively labour intensive to relatively capital intensive production in manufactures from 1998 to 2002.

UK Macroeconomic Forecasting with Many Predictors: Which Models Forecast Best and When Do They Do So?

Block factor methods offer an attractive approach to forecasting with many predictors. These extract the information in these predictors into factors reflecting different blocks of variables (e.g. a price block, a housing block, a financial block, etc.). However, a forecasting model which simply includes all blocks as predictors risks being over-parameterized. Thus, it is desirable to use a methodology which allows for different parsimonious forecasting models to hold at different points in time. In this paper, we use dynamic model averaging and dynamic model selection to achieve this goal. These methods automatically alter the weights attached to different forecasting models as evidence comes in about which has forecast well in the recent past. In an empirical study involving forecasting output growth and inflation using 139 UK monthly time series variables, we find that the set of predictors changes substantially over time. Furthermore, our results show that dynamic model averaging and model selection can greatly improve forecast performance relative to traditional forecasting methods.