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Showing papers by "Pompeu Fabra University published in 2010"


Journal ArticleDOI
Thomas J. Hudson1, Thomas J. Hudson2, Warwick Anderson3, Axel Aretz4  +270 moreInstitutions (92)
15 Apr 2010
TL;DR: Systematic studies of more than 25,000 cancer genomes will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
Abstract: The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

2,041 citations


Journal ArticleDOI
TL;DR: In this paper, the authors examined joint associations of 12 childhood adversities with first onset of 20 DSM-IV disorders in World Mental Health Surveys in 21 countries and found strong associations with all classes of disorders at all life-course stages.
Abstract: Background Although significant associations of childhood adversities with adult mental disorders are widely documented, most studies focus on single childhood adversities predicting single disorders. Aims To examine joint associations of 12 childhood adversities with first onset of 20 DSM–IV disorders in World Mental Health (WMH) Surveys in 21 countries. Method Nationally or regionally representative surveys of 51 945 adults assessed childhood adversities and lifetime DSM–IV disorders with the WHO Composite International Diagnostic Interview (CIDI). Results Childhood adversities were highly prevalent and interrelated. Childhood adversities associated with maladaptive family functioning (e.g. parental mental illness, child abuse, neglect) were the strongest predictors of disorders. Co-occurring childhood adversities associated with maladaptive family functioning had significant subadditive predictive associations and little specificity across disorders. Childhood adversities account for 29.8% of all disorders across countries. Conclusions Childhood adversities have strong associations with all classes of disorders at all life-course stages in all groups of WMH countries. Long-term associations imply the existence of as-yet undetermined mediators.

1,837 citations


Journal ArticleDOI
TL;DR: In this paper, Neudecker et al. used the implicit function theorem to develop an improved scaling correction leading to a new scaled difference test statistic that avoids negative chi-square values.
Abstract: A scaled difference test statistic \(\tilde{T}{}_{d}\) that can be computed from standard software of structural equation models (SEM) by hand calculations was proposed in Satorra and Bentler (Psychometrika 66:507–514, 2001). The statistic \(\tilde{T}_{d}\) is asymptotically equivalent to the scaled difference test statistic \(\bar{T}_{d}\) introduced in Satorra (Innovations in Multivariate Statistical Analysis: A Festschrift for Heinz Neudecker, pp. 233–247, 2000), which requires more involved computations beyond standard output of SEM software. The test statistic \(\tilde{T}_{d}\) has been widely used in practice, but in some applications it is negative due to negativity of its associated scaling correction. Using the implicit function theorem, this note develops an improved scaling correction leading to a new scaled difference statistic \(\bar{T}_{d}\) that avoids negative chi-square values.

1,281 citations


Journal ArticleDOI
Stephen Richards1, Richard A. Gibbs1, Nicole M. Gerardo2, Nancy A. Moran3  +220 moreInstitutions (58)
TL;DR: The genome of the pea aphid shows remarkable levels of gene duplication and equally remarkable gene absences that shed light on aspects of aphid biology, most especially its symbiosis with Buchnera.
Abstract: Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.

1,271 citations


Journal ArticleDOI
25 Mar 2010-Nature
TL;DR: The data provide the first direct evidence for the source of proliferating cardiomyocytes during zebrafish heart regeneration and indicate that stem or progenitor cells are not significantly involved in this process.
Abstract: Although mammalian hearts show almost no ability to regenerate, there is a growing initiative to determine whether existing cardiomyocytes or progenitor cells can be coaxed into eliciting a regenerative response. In contrast to mammals, several non-mammalian vertebrate species are able to regenerate their hearts, including the zebrafish, which can fully regenerate its heart after amputation of up to 20% of the ventricle. To address directly the source of newly formed cardiomyocytes during zebrafish heart regeneration, we first established a genetic strategy to trace the lineage of cardiomyocytes in the adult fish, on the basis of the Cre/lox system widely used in the mouse. Here we use this system to show that regenerated heart muscle cells are derived from the proliferation of differentiated cardiomyocytes. Furthermore, we show that proliferating cardiomyocytes undergo limited dedifferentiation characterized by the disassembly of their sarcomeric structure, detachment from one another and the expression of regulators of cell-cycle progression. Specifically, we show that the gene product of polo-like kinase 1 (plk1) is an essential component of cardiomyocyte proliferation during heart regeneration. Our data provide the first direct evidence for the source of proliferating cardiomyocytes during zebrafish heart regeneration and indicate that stem or progenitor cells are not significantly involved in this process.

1,195 citations


Journal ArticleDOI
01 Apr 2010-Nature
TL;DR: This analysis shows that high throughput sequencing technologies reveal new properties of Genetic effects on the transcriptome and allow the exploration of genetic effects in cellular processes.
Abstract: Gene expression is an important phenotype that informs about genetic and environmental effects on cellular state. Many studies have previously identified genetic variants for gene expression phenotypes using custom and commercially available microarrays. Second generation sequencing technologies are now providing unprecedented access to the fine structure of the transcriptome. We have sequenced the mRNA fraction of the transcriptome in 60 extended HapMap individuals of European descent and have combined these data with genetic variants from the HapMap3 project. We have quantified exon abundance based on read depth and have also developed methods to quantify whole transcript abundance. We have found that approximately 10 million reads of sequencing can provide access to the same dynamic range as arrays with better quantification of alternative and highly abundant transcripts. Correlation with SNPs (small nucleotide polymorphisms) leads to a larger discovery of eQTLs (expression quantitative trait loci) than with arrays. We also detect a substantial number of variants that influence the structure of mature transcripts indicating variants responsible for alternative splicing. Finally, measures of allele-specific expression allowed the identification of rare eQTLs and allelic differences in transcript structure. This analysis shows that high throughput sequencing technologies reveal new properties of genetic effects on the transcriptome and allow the exploration of genetic effects in cellular processes.

861 citations


Journal ArticleDOI
TL;DR: NPTs emerge as a useful, versatile and potentially cost-effective approach to improve outcomes and QoL in ADRD for both the PWD and CG.
Abstract: Introduction: Nonpharmacological therapies (NPTs) can improve the quality of life (QoL) of people with Alzheimer’s disease (AD) and their carers. The objective of this study was to evaluate the best evidence on the effects of NPTs in AD and related disorders (ADRD) by performing a systematic review and meta-analysis of the entire field. Methods: Existing reviews and major electronic databases were searched for randomized controlled trials (RCTs). The deadline for study inclusion was September 15, 2008. Intervention categories and outcome domains were predefined by consensus. Two researchers working together detected 1,313 candidate studies of which 179 RCTs belonging to 26 intervention categories were selected. Cognitive deterioration had to be documented in all participants, and degenerative etiology

834 citations


Posted Content
TL;DR: In this article, the authors provide a model of competition among credit ratings Agencies (CRAs) in which there are three possible sources of conflicts: 1) the CRA conflict of interest of understating credit risk to attract more business; 2) the ability of issuers to purchase only the most favorable ratings; and 3) the trusting nature of some investor clienteles who may take ratings at face value.
Abstract: The collapse of so many AAA-rated structured finance products in 2007-2008 has brought renewed attention to the causes of ratings failures and the conflicts of interest in the Credit Ratings Industry. We provide a model of competition among Credit Ratings Agencies (CRAs) in which there are three possible sources of conflicts: 1) the CRA conflict of interest of understating credit risk to attract more business; 2) the ability of issuers to purchase only the most favorable ratings; and 3) the trusting nature of some investor clienteles who may take ratings at face value. We show that when combined, these give rise to three fundamental equilibrium distortions. First, competition among CRAs can reduce market efficiency, as competition facilitates ratings shopping by issuers. Second, CRAs are more prone to inflate ratings in boom times, when there are more trusting investors, and when the risks of failure which could damage CRA reputation are lower. Third, the industry practice of tranching of structured products distorts market efficiency as its role is to deceive trusting investors. We argue that regulatory intervention requiring: i) upfront payments for rating services (before CRAs propose a rating to the issuer), ii) mandatory disclosure of any rating produced by CRAs, and iii) oversight of ratings methodology can substantially mitigate ratings inflation and promote efficiency.

749 citations


Journal ArticleDOI
TL;DR: These findings point to a more intimate and multifaceted interplay between attention and multisensory integration than was previously thought, and propose a framework that unifies previous, apparently discordant, findings.

642 citations


Book ChapterDOI
01 Jan 2010
TL;DR: The purpose here is to give an accessible description of the underlying principles of iterated local search and a discussion of the main aspects that need to be taken into account for a successful application of it.
Abstract: The key idea underlying iterated local search is to focus the search not on the full space of all candidate solutions but on the solutions that are returned by some underlying algorithm, typically a local search heuristic. The resulting search behavior can be characterized as iteratively building a chain of solutions of this embedded algorithm. The result is also a conceptually simple metaheuristic that nevertheless has led to state-of-the-art algorithms for many computationally hard problems. In fact, very good performance is often already obtained by rather straightforward implementations of the metaheuristic. In addition, the modular architecture of iterated local search makes it very suitable for an algorithm engineering approach where, progressively, the algorithms’ performance can be further optimized. Our purpose here is to give an accessible description of the underlying principles of iterated local search and a discussion of the main aspects that need to be taken into account for a successful application of it. In addition, we review the most important applications of this method and discuss its relationship to other metaheuristics.

589 citations


Posted Content
TL;DR: The authors found that low monetary policy short-term interest rates soften standards, especially for mortgages, for household and corporate loans, and that this softening is amplified by securitization activity, weak supervision for bank capital and too low for too long monetary policy rates.
Abstract: Using a unique dataset of the Euro area and the U.S. bank lending standards, we find that low (monetary policy) short-term interest rates soften standards, for household and corporate loans. This softening – especially for mortgages – is amplified by securitization activity, weak supervision for bank capital and too low for too long monetary policy rates. Conversely, low long-term interest rates do not soften lending standards. Finally, countries with softer lending standards before the crisis related to negative Taylor-rule residuals experienced a worse economic performance afterwards. These results help shed light on the origins of the crisis and have important policy implications.

Journal ArticleDOI
TL;DR: This article provided a comparative study of a number of outcomes (education, earnings and employment) of both first and second-generation immigrants of different origins in the three largest European economies: France, Germany and the UK.
Abstract: A central concern about immigration is the integration into the labour market, not only of the first generation but also of subsequent generations. Little comparative work exists for Europe’s largest economies. France, Germany and the UK have all become, perhaps unwittingly, countries with large immigrant populations albeit with very different ethnic compositions. Today, the descendants of these immigrants live and work in their parents destination countries. This article presents and discusses comparative evidence on the performance of first and second-generation immigrants in these countries in terms of education, earnings and employment. It is widely believed that many European countries have a serious problem with the integration of immigrants and their children (LEED, 2006). Many Northern European countries have accumulated sizeable populations of immigrants but the lack of longterm strategies and policies to integrate these into societal structures and the labour market is often cited as one reason for social and economic exclusion of the children of these immigrants. In the past decade, Southern European countries such as Spain and Italy have experienced similar, if not larger, immigrations than the large Northern European economies France, Germany and the UK in the late 1950s to early 1970s. Again, it seems that there is little thought devoted to long-term strategies for immigrants and their descendants. The experience of those countries that had large-scale immigration in the last half of the twentieth century should be of importance for devising future immigration and integration policies. However, there is rather little hard evidence in the literature about the relative position of immigrants and their descendants in these countries, in a manner that allows comparisons to be made. In this article, we aim to provide a comparative study of a number of outcomes (education, earnings and employment) of both first and second-generation immigrants of different origins in the three largest European economies: France, Germany and the UK.

Journal ArticleDOI
TL;DR: Nonnodal presentation, predominantly hypermutated IGVH, lack of genomic complexity, and absence of SOX11 expression are defined as qualities of a specific subtype of iMCL with excellent outcomes that might be managed more conservatively than cMCL.
Abstract: Mantle cell lymphoma (MCL) is typically a very aggressive disease with poor outcomes, but some cases display an indolent behavior that might not necessitate treatment at diagnosis. To define molecular criteria that might permit recognition of such cases, we compared the clinicopathologic features, gene expression, and genomic profile of patients who had indolent or conventional disease (iMCL or cMCL). Patients with iMCL displayed nonnodal leukemic disease with predominantly hypermutated IGVH and noncomplex karyotypes. iMCL and cMCL shared a common gene expression profile that differed from other leukemic lymphoid neoplasms. However, we identified a signature of 13 genes that was highly expressed in cMCL but underexpressed in iMCL. SOX11 was notable in this signature and we confirmed a restriction of SOX11 protein expression to cMCL. To validate the potential use of SOX11 as a biomarker for cMCL, we evaluated SOX11 protein expression in an independent series of 112 cases of MCL. Fifteen patients with SOX11-negative tumors exhibited more frequent nonnodal presentation and better survival compared with 97 patients with SOX11-positive MCL (5-year overall survival of 78% versus 36%, respectively; P = 0.001). In conclusion, we defined nonnodal presentation, predominantly hypermutated IGVH, lack of genomic complexity, and absence of SOX11 expression as qualities of a specific subtype of iMCL with excellent outcomes that might be managed more conservatively than cMCL.

Journal ArticleDOI
17 Jun 2010-Oncogene
TL;DR: ZEB1/BRG1 is identified as a new transcriptional mechanism regulating E-cadherin expression and epithelial-to-mesenchymal transdifferentiation that may be involved during the initial stages of tumor invasion.
Abstract: Loss of E-cadherin is a key initial step in the transdifferentiation of epithelial cells to a mesenchymal phenotype, which occurs when tumor epithelial cells invade into surrounding tissues. Expression of the nuclear factor ZEB1 induces an epithelial-to-mesenchymal transition and confers a metastatic phenotype on carcinomas by repressing the E-cadherin gene at the transcriptional level. In this study, we show that ZEB1 interacts with the SWI/SNF chromatin-remodeling protein BRG1 to regulate E-cadherin independently of CtBP, its traditional co-repressor. Blocking the interaction between ZEB1 and BRG1 induces expression of E-cadherin and downregulation of the mesenchymal marker vimentin. ZEB1 and BRG1 colocalize in E-cadherin-negative cells from cancer lines and in the stroma of normal colon. Colocalization of ZEB1 and BRG1 in epithelial cells is only found in those de-differentiated cells characterized by nuclear β-catenin staining at the invasive edge of the tumor. Our results identify ZEB1/BRG1 as a new transcriptional mechanism regulating E-cadherin expression and epithelial-to-mesenchymal transdifferentiation that may be involved during the initial stages of tumor invasion.

Journal ArticleDOI
Nathaniel Rothman, Montserrat Garcia-Closas, Nilanjan Chatterjee, Núria Malats, Xifeng Wu1, Jonine D. Figueroa, Francisco X. Real2, David Van Den Berg3, Giuseppe Matullo4, Dalsu Baris, Michael J. Thun5, Lambertus A. Kiemeney6, Paolo Vineis7, Immaculata De Vivo8, Demetrius Albanes, Mark P. Purdue, Thorunn Rafnar9, Michelle A.T. Hildebrandt1, Anne E. Kiltie10, Olivier Cussenot, Klaus Golka, Rajesh Kumar11, Jack A. Taylor12, Jose I. Mayordomo13, Kevin B. Jacobs14, Manolis Kogevinas, Amy Hutchinson14, Zhaoming Wang14, Yi-Ping Fu, Ludmila Prokunina-Olsson, Laurie Burdett14, Meredith Yeager14, William Wheeler, Adonina Tardón15, Consol Serra2, Alfredo Carrato, Reina García-Closas16, Josep Lloreta2, Alison Johnson, Molly Schwenn, Margaret R. Karagas17, Alan R. Schned17, Gerald L. Andriole18, Robert L. Grubb18, Amanda Black, Eric J. Jacobs5, W. Ryan Diver5, Susan M. Gapstur5, Stephanie J. Weinstein, Jarmo Virtamo12, Victoria K. Cortessis3, Manuela Gago-Dominguez3, Malcolm C. Pike19, Malcolm C. Pike3, Mariana C. Stern3, Jian-Min Yuan20, David J. Hunter21, Monica McGrath21, Colin P.N. Dinney1, Bogdan Czerniak1, Meng Chen1, Hushan Yang1, Sita H. Vermeulen6, Katja K.H. Aben6, J. Alfred Witjes6, Remco R. R. Makkinje6, Patrick Sulem9, Søren Besenbacher9, Kari Stefansson9, Kari Stefansson22, Elio Riboli7, Paul Brennan23, Salvatore Panico, Carmen Navarro, Naomi E. Allen24, H. Bas Bueno-de-Mesquita, Dimitrios Trichopoulos25, Dimitrios Trichopoulos21, Neil E. Caporaso, Maria Teresa Landi, Federico Canzian11, Börje Ljungberg26, Anne Tjønneland, Françoise Clavel-Chapelon27, D T Bishop28, Mark Teo28, Margaret A. Knowles28, Simonetta Guarrera, Silvia Polidoro, Fulvio Ricceri4, Carlotta Sacerdote4, Alessandra Allione, Geraldine Cancel-Tassin, Silvia Selinski, Jan G. Hengstler, Holger Dietrich29, Tony Fletcher, Peter Rudnai12, Eugen Gurzau30, Kvetoslava Koppova, Sophia C.E. Bolick12, Ashley C. Godfrey12, Zongli Xu12, José I Sanz-Velez, Maria D. Garcia-Prats, Manuel Sanchez13, Gabriel Valdivia13, Stefano Porru31, Simone Benhamou32, Simone Benhamou33, Robert N. Hoover, Joseph F. Fraumeni, Debra T. Silverman, Stephen J. Chanock 
TL;DR: Two new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1 are identified and previous candidate associations for the GSTM1 deletion and a tag SNP for NAT2 acetylation status are validated, and interactions with smoking in both regions are found.
Abstract: We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q131, 19q12 and 2q371: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q131, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q371 We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p163, 8q2421 and 8q243, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Book
26 Mar 2010
TL;DR: It is shown how computations can be performed through stochastic dynamical effects, including the role of noise in enabling probabilistic jumping across barriers in the energy landscape describing the flow of the dynamics in attractor networks.
Abstract: 1 Introduction: neuronal, cortical, and network foundations 2 Stochastic neurodynamics 3 Short-term memory and stochastic dynamics 4 Attention and stochastic dynamics 5 Probabilistic decision-making 6 Confidence and decision-making 7 Perceptual detection and stochastic dynamics 8 Applications of this stochastic dynamical theory to brain function A Mean-field analyses, and stochastic dynamics References Index B Colour Plates

Journal ArticleDOI
TL;DR: Naïve Bayes appears as the most robust algorithm, and SMO the least, relative to the other two techniques, however, the underlying empirical behavior of the techniques is more complex, and varies depending on the noise type and the specific data set being processed.
Abstract: Machine learning techniques often have to deal with noisy data, which may affect the accuracy of the resulting data models. Therefore, effectively dealing with noise is a key aspect in supervised learning to obtain reliable models from data. Although several authors have studied the effect of noise for some particular learners, comparisons of its effect among different learners are lacking. In this paper, we address this issue by systematically comparing how different degrees of noise affect four supervised learners that belong to different paradigms. Specifically, we consider the Naive Bayes probabilistic classifier, the C4.5 decision tree, the IBk instance-based learner and the SMO support vector machine. We have selected four methods which enable us to contrast different learning paradigms, and which are considered to be four of the top ten algorithms in data mining (Yu et al. 2007). We test them on a collection of data sets that are perturbed with noise in the input attributes and noise in the output class. As an initial hypothesis, we assign the techniques to two groups, NB with C4.5 and IBk with SMO, based on their proposed sensitivity to noise, the first group being the least sensitive. The analysis enables us to extract key observations about the effect of different types and degrees of noise on these learning techniques. In general, we find that Naive Bayes appears as the most robust algorithm, and SMO the least, relative to the other two techniques. However, we find that the underlying empirical behavior of the techniques is more complex, and varies depending on the noise type and the specific data set being processed. In general, noise in the training data set is found to give the most difficulty to the learners.

Journal ArticleDOI
TL;DR: Re-examine theoretical predictions and revisit different sources of data to question some previous predictions and suggest new empirical and theoretical approaches to understanding the relevance of rearrangements in the origin of species.
Abstract: The suggestion that chromosomal rearrangements play a role in speciation resulted from the observation that heterokaryotypes are often infertile. However, the first chromosomal speciation models were unsatisfactory and data available to test them was scarce. Recently, large amounts of data have become available and new theoretical models have been developed explaining how rearrangements facilitate speciation in the face of gene flow. Here, we re-examine theoretical predictions and revisit different sources of data. Although rearrangements are often associated with increased levels of divergence, unequivocal demonstration that their role in suppressing recombination results in speciation is often lacking. Finally, we question some previous predictions and suggest new empirical and theoretical approaches to understanding the relevance of rearrangements in the origin of species.

Journal ArticleDOI
TL;DR: It is suggested that FGR induces primary cardiac and vascular changes that could explain the increased predisposition to cardiovascular disease in adult life and the impact of strategies with beneficial effects on cardiac remodeling should be explored in children with FGR.
Abstract: Background—Fetal growth restriction (FGR) affects 5% to 10% of newborns and is associated with increased cardiovascular mortality in adulthood. The most commonly accepted hypothesis is that fetal metabolic programming leads secondarily to diseases associated with cardiovascular disease, such as obesity, diabetes mellitus, and hypertension. Our main objective was to evaluate the alternative hypothesis that FGR induces primary cardiac changes that persist into childhood. Methods and Results—Within a cohort of fetuses with growth restriction identified in fetal life and followed up into childhood, we randomly selected 80 subjects with FGR and compared them with 120 normally grown fetuses, matched for gender, birth date, and gestational age at birth. Cardiovascular assessment was performed in childhood (mean age of 5 years). Compared with control subjects, children with FGR had a different cardiac shape, with increased transversal diameters and more globular cardiac ventricles. Although left ejection fraction was similar among the study groups, stroke volume was reduced significantly, which was compensated for by an increased heart rate to maintain output in severe FGR. This was associated with subclinical longitudinal systolic dysfunction (decreased myocardial peak velocities) and diastolic changes (increased E/E ratio and E deceleration time). Children with FGR also had higher blood pressure and increased intima-media thickness. For all parameters evaluated, there was a linear increase with the severity of growth restriction. Conclusions—These findings suggest that FGR induces primary cardiac and vascular changes that could explain the increased predisposition to cardiovascular disease in adult life. If these results are confirmed, the impact of strategies with beneficial effects on cardiac remodeling should be explored in children with FGR. (Circulation. 2010;121:2427-2436.)

Proceedings ArticleDOI
13 Jun 2010
TL;DR: A method based on a combination of Support Vector Regression and Markov Random Fields to drastically reduce the time needed to search for a point's location and increase the accuracy and robustness of the algorithm.
Abstract: Finding fiducial facial points in any frame of a video showing rich naturalistic facial behaviour is an unsolved problem. Yet this is a crucial step for geometric-feature-based facial expression analysis, and methods that use appearance-based features extracted at fiducial facial point locations. In this paper we present a method based on a combination of Support Vector Regression and Markov Random Fields to drastically reduce the time needed to search for a point's location and increase the accuracy and robustness of the algorithm. Using Markov Random Fields allows us to constrain the search space by exploiting the constellations that facial points can form. The regressors on the other hand learn a mapping between the appearance of the area surrounding a point and the positions of these points, which makes detection of the points very fast and can make the algorithm robust to variations of appearance due to facial expression and moderate changes in head pose. The proposed point detection algorithm was tested on 1855 images, the results of which showed we outperform current state of the art point detectors.

Journal ArticleDOI
TL;DR: A model of judgment under uncertainty is presented, in which an agent combines data received from the external world with information retrieved from memory to evaluate a hypothesis, which can account for some of the evidence on heuristics and biases presented by Kahneman and Tversky.
Abstract: We present a model of intuitive inference, called “local thinking,” in which an agent combines data received from the external world with information retrieved from memory to evaluate a hypothesis. In this model, selected and limited recall of information follows a version of the respresentativeness heuristic. The model can account for some of the evidence on judgment biases, including conjunction and disjunction fallacies, but also for several anomalies related to demand for insurance.

Journal ArticleDOI
02 Feb 2010-PLOS ONE
TL;DR: The remarkable inverse miRNA profile revealed for human pre-adipocytes and mature adipocytes hints at a closely crosstalk between miRNAs and adipogenesis.
Abstract: Background Potential regulators of adipogenesis include microRNAs (miRNAs), small non-coding RNAs that have been recently shown related to adiposity and differentially expressed in fat depots. However, to date no study is available, to our knowledge, regarding miRNAs expression profile during human adipogenesis. Thereby, the aim of this study was to investigate whether miRNA pattern in human fat cells and subcutaneous adipose tissue is associated to obesity and co-morbidities and whether miRNA expression profile in adipocytes is linked to adipogenesis.

Journal ArticleDOI
TL;DR: A novel VR based paradigm for neurorehabilitation, RGS, which combines specific rehabilitative principles with a psychometric evaluation to provide a personalized and automated training is introduced.
Abstract: Stroke is a frequent cause of adult disability that can lead to enduring impairments. However, given the life-long plasticity of the brain one could assume that recovery could be facilitated by the harnessing of mechanisms underlying neuronal reorganization. Currently it is not clear how this reorganization can be mobilized. Novel technology based neurorehabilitation techniques hold promise to address this issue. Here we describe a Virtual Reality (VR) based system, the Rehabilitation Gaming System (RGS) that is based on a number of hypotheses on the neuronal mechanisms underlying recovery, the structure of training and the role of individualization. We investigate the psychometrics of the RGS in stroke patients and healthy controls. We describe the key components of the RGS and the psychometrics of one rehabilitation scenario called Spheroids. We performed trials with 21 acute/subacute stroke patients and 20 healthy controls to study the effect of the training parameters on task performance. This allowed us to develop a Personalized Training Module (PTM) for online adjustment of task difficulty. In addition, we studied task transfer between physical and virtual environments. Finally, we assessed the usability and acceptance of the RGS as a rehabilitation tool. We show that the PTM implemented in RGS allows us to effectively adjust the difficulty and the parameters of the task to the user by capturing specific features of the movements of the arms. The results reported here also show a consistent transfer of movement kinematics between physical and virtual tasks. Moreover, our usability assessment shows that the RGS is highly accepted by stroke patients as a rehabilitation tool. We introduce a novel VR based paradigm for neurorehabilitation, RGS, which combines specific rehabilitative principles with a psychometric evaluation to provide a personalized and automated training. Our results show that the RGS effectively adjusts to the individual features of the user, allowing for an unsupervised deployment of individualized rehabilitation protocols.

Journal ArticleDOI
TL;DR: In this article, a stylized model of economic growth with bubbles is presented, which views asset price bubbles as a market-generated device to moderate the effects of frictions in financial markets, improving the allocation of investments and raising the capital stock and welfare.
Abstract: This paper presents a stylized model of economic growth with bubbles. This model views asset price bubbles as a market-generated device to moderate the effects of frictions in financial markets, improving the allocation of investments and raising the capital stock and welfare. The model illustrates various channels through which asset price bubbles affect the incentives for innovation and economic reforms, and therefore, the rate of economic growth. The model also offers a new perspective on the effects of financial development on asset price bubbles and economic growth.


Journal ArticleDOI
TL;DR: Two new loci showing strong evidence for association with intracranial aneurysms are identified and several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.
Abstract: Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with approximately 832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.2 (odds ratio (OR) = 1.22, P = 1.1 x 10(-12)), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 x 10(-9)) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 x 10(-9)). We also confirmed prior associations near SOX17 (8q11.23-q12.1; OR = 1.28, P = 1.3 x 10(-12)) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 x 10(-22)). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.

Journal ArticleDOI
TL;DR: The findings on immigrants from Spain highlight the transitory nature of the 'healthy immigrant effect', and that action on inequality in socio-economic determinants affecting migrant groups should not be deferred.

Proceedings Article
11 Jul 2010
TL;DR: This work shows that the problem of probabilistic plan recognition can be solved efficiently using classical planners provided that the probability of a partially observed execution given a goal is defined in terms of the cost difference of achieving the goal under two conditions: complying with the observations, and not complying with them.
Abstract: Plan recognition is the problem of inferring the goals and plans of an agent after observing its behavior. Recently, it has been shown that this problem can be solved efficiently, without the need of a plan library, using slightly modified planning algorithms. In this work, we extend this approach to the more general problem of probabilistic plan recognition where a probability distribution over the set of goals is sought under the assumptions that actions have deterministic effects and both agent and observer have complete information about the initial state. We show that this problem can be solved efficiently using classical planners provided that the probability of a partially observed execution given a goal is defined in terms of the cost difference of achieving the goal under two conditions: complying with the observations, and not complying with them. This cost, and hence the posterior goal probabilities, are computed by means of two calls to a classical planner that no longer has to be modified in any way. A number of examples is considered to illustrate the quality, flexibility, and scalability of the approach.

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TL;DR: In this article, the authors provide guidelines and recommendations for producing first-rate economic evaluations of health technologies and provide a commentary, providing a justification and comparing and contrasting the proposal with other available alternatives.

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TL;DR: The hypothesis that bilinguals' early training in switching back and forth between their languages leads to the recruitment of brain regions involved in language control when performing non-linguistic cognitive tasks is supported.