Cinemática rotacional del cabalgamiento basal surpirenaico en las Sierras Exteriores Aragonesas: Datos magnetotectónicos

The magnetotectonic analysis of 32 sites located along the External Sierras (mainly in Middle Eocene marls) shows the primary character of the magnetisation and pennits the differences between the paleovectors obtained to be interpreted as a result of the rotational kinematics of the southpyrenean floor thrust in the study area. The constancy of the directions of the defined unblocking intervals (300"-425°C for the thermal treatment) and the homogeneity of the magnetic carriers (these were always low coercitivity phases, probably sulphides andlor magnetite) prove the stability of the magnetisation. On the other hand, the primary character of the magnetisation (Middle Eocene) can be demonstrated by: a) the constancy of the magnetic inclination (47.3 +/- 1.7) and its similarity with the reference direction; b) the occurrence of reversals, and the positive result of the fold-test made in the Pico del Águila anticline; c) the consistency between the reference direction (DEC = 005", INC = 51°, a95=6 ") and the direction obtained for the authocthonous footwall (DEC = 005", INC = 38", a95= 8") which crops out in the western sector of the Sierras Exteriores thrust front. The interpretation of the paleomagnetic data within the External Sierras structural framework clearly shows that the kinematics of individual thrust sheets involves a clockwise component, at least during a period of their evolution. The maximum rotation values were found in the western and central sectors (42" and 30" respectively). The age of the rotation decreases towards the west along with the age of deformation of the cover rocks. Starting in late Priabonian the kinematics of the thrust front resulted in a lack of rotation in the central sector of the Sierras, while the western sector undenvent a clockwise rotation. The differential movement between both sectors gave rise to the development or reactivation of structures (i. e. Rasal-Anzáñigo anticlines) that articulated the deformation of adjacent zones with different rotational components

Cinemática rotacional del cabalgamiento basal surpirenaico en las Sierras Exteriores Aragonesas: Datos magnetotectónicos

The magnetotectonic analysis of 32 sites located along the External Sierras (mainly in Middle Eocene marls) shows the primary character of the magnetisation and pennits the differences between the paleovectors obtained to be interpreted as a result of the rotational kinematics of the southpyrenean floor thrust in the study area. The constancy of the directions of the defined unblocking intervals (300"-425°C for the thermal treatment) and the homogeneity of the magnetic carriers (these were always low coercitivity phases, probably sulphides andlor magnetite) prove the stability of the magnetisation. On the other hand, the primary character of the magnetisation (Middle Eocene) can be demonstrated by: a) the constancy of the magnetic inclination (47.3 +/- 1.7) and its similarity with the reference direction; b) the occurrence of reversals, and the positive result of the fold-test made in the Pico del Águila anticline; c) the consistency between the reference direction (DEC = 005", INC = 51°, a95=6 ") and the direction obtained for the authocthonous footwall (DEC = 005", INC = 38", a95= 8") which crops out in the western sector of the Sierras Exteriores thrust front. The interpretation of the paleomagnetic data within the External Sierras structural framework clearly shows that the kinematics of individual thrust sheets involves a clockwise component, at least during a period of their evolution. The maximum rotation values were found in the western and central sectors (42" and 30" respectively). The age of the rotation decreases towards the west along with the age of deformation of the cover rocks. Starting in late Priabonian the kinematics of the thrust front resulted in a lack of rotation in the central sector of the Sierras, while the western sector undenvent a clockwise rotation. The differential movement between both sectors gave rise to the development or reactivation of structures (i. e. Rasal-Anzáñigo anticlines) that articulated the deformation of adjacent zones with different rotational components

Wearable design requirements identification and evaluation

: Wearable electronics make it possible to monitor human activity and behavior. Most of these devices have not taken into account human factors and they have instead focused on technological issues. This fact could not only affect human–computer interaction and user experience but also the devices’ use cycle. Firstly, this paper presents a classification of wearable design requirements that have been carried out by combining a quantitative and a qualitative methodology. Secondly, we present some evaluation procedures based on design methodologies and human–computer interaction measurement tools. Thus, this contribution aims to provide a roadmap for wearable designers and researchers in order to help them to find more efficient processes by providing a classification of the design requirements and evaluation tools. These resources represent time and resource-saving contributions. Therefore designers and researchers do not have to review the literature. It will no be necessary to carry out exploratory studies for the purposes of identifying requirements or evaluation tools either

The wearable co-design domino: A user-centered methodology to co-design and co-evaluate wearables

This paper presents a user-centered methodology to co-design and co-evaluate wearables that has been developed following a research-through design methodology. It has been based on the principles of human–computer interaction and on an empirical case entitled “Design and Development of a Low-Cost Wearable Glove to Track Forces Exerted by Workers in Car Assembly Lines” published in Sensors. Insights from both studies have been used to develop the wearable co-design domino presented in this study. The methodology consists of different design stages composed of an ideation stage, digital service development and test stages, hardware development and test stage, and a final test stage. The main conclusions state that it is necessary to maintain a close relationship between human factors and technical factors when designing wearable. Additionally, through the several studies, it has been concluded that there is need of different field experts that should co-design and co-evaluate wearable iteratively and involving users from the beginning of the process

Evidence that exogenous but not endogenous norepinephrine activates the presynaptic alpha,-adrenoceptors on serotonergic nerve endings in the rat hypothalamus

ABSTRACT ABBREVIATiONS: NE, norepinephnne; 5-HT, 5-hydroxytryptamine; 6F-NE, 6-fluoronorepinephrine. 72

Whole-exome sequencing identifies genes associated with Tourette’s disorder in multiplex families

Tourette’s Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein–protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.This study was supported by a grant from the National Institute of Mental Health (R01MH092293 to GAH and JAT) and by a grant from the New Jersey Center for Tourette Syndrome (to GAH and JAT). This study was also supported by grants from the National Institute of Mental Health (K08MH099424 to TVF) and the National Institute for Environmental Health Science (R01 ES021462 for YSK and BLL). PM has received grants from the Instituto de Salud Carlos III (PI10/01674, PI13/01461), the Consejería de Economía, Innovación, Ciencia y Empresa de la Junta de Andalucía (CVI-02526, CTS-7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0741/2010, PI-0437-2012, PI-0471-2013), the Sociedad Andaluza de Neurología, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña, and the Jaques and Gloria Gossweiler Foundation. AM has received grants from the Fundacion Alicia Koplowitz and belongs to the research group of the Comissionat per Universitats i Recerca del Departmanent d’Innovacio (DIUE) 2009SGR1119. AM has received grants from the Deutsche Forschungsgemeinschaft (DFG: MU 1692/3-1, MU 1692/4-1, and FOR 2698). AJW received a Young Investigator Award from Tourette Association of America. IH declares that all research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre

Investigation of gene-environment interactions in relation to tic severity

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies

Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders

European Multicentre Tics in Children Studies (EMTICS): protocol for two cohort studies to assess risk factors for tic onset and exacerbation in children and adolescents

Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive-compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3-10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3-16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host's immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders