Psychiatric comorbidities in Asperger syndrome are related with polygenic overlap and differ from other Autism subtypes

There is great phenotypic heterogeneity within autism spectrum disorders (ASD), which has led to question their classification into a single diagnostic category. The study of the common genetic variation in ASD has suggested a greater contribution of other psychiatric conditions in Asperger syndrome (AS) than in the rest of the DSM-IV ASD subtypes (Non_AS). Here, using available genetic data from previously performed genome-wide association studies (GWAS), we aimed to study the genetic overlap between five of the most related disorders (schizophrenia (SCZ), major depression disorder (MDD), attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorders (OCD) and anxiety (ANX)), and AS, comparing it with the overlap in Non_AS subtypes. A Spanish cohort of autism trios (N = 371) was exome sequenced as part of the Autism Sequencing Consortium (ASC) and 241 trios were extensively characterized to be diagnosed with AS following DSM-IV and Gillberg's criteria (N = 39) or not (N = 202). Following exome imputation, polygenic risk scores (PRS) were calculated for ASD, SCZ, ADHD, MDD, ANX, and OCD (from available summary data from Psychiatric Genomic Consortium (PGC) repository) in the Spanish trios' cohort. By using polygenic transmission disequilibrium test (pTDT), we reported that risk for SCZ (Pscz = 0.008, corrected-PSCZ = 0.0409), ADHD (PADHD = 0.021, corrected-PADHD = 0.0301), and MDD (PMDD = 0.039, corrected-PMDD = 0.0501) is over-transmitted to children with AS but not to Non_AS. Indeed, agnostic clustering procedure with deviation values from pTDT tests suggested two differentiated clusters of subjects, one of which is significantly enriched in AS (P = 0.025). Subsequent analysis with S-Predixcan, a recently developed software to predict gene expression from genotype data, revealed a clear pattern of correlation between cortical gene expression in ADHD and AS (P < 0.001) and a similar strong correlation pattern between MDD and AS, but also extendable to another non-brain tissue such as lung (P < 0.001). Altogether, these results support the idea of AS being qualitatively distinct from Non_AS autism and consistently evidence the genetic overlap between AS and ADHD, MDD, or SCZ

Pharmaceutical companies information and antibiotic prescription patterns: A follow-up study in Spanish primary care

OBJECTIVES: To assess the impact of sources of drug information on antibiotic prescribing patterns (quantity and quality) among primary care physicians. METHODS: We conducted a cohort study on primary care physicians who were actively engaged in medical practice in 2010 in a region in north-west Spain (Galicia), fulfilling inclusion criteria (n = 2100). As the independent variable, we took the perceived utility of 6 sources of information on antibiotics, as measured by the validated KAAR-11 questionnaire. As dependent variables, we used: (1) a quality indicator (appropriate quality, defined as any case where 6 of the 12 indicators proposed by the European Surveillance of Antimicrobial Consumption Network [ESAC-Net] were better than the mean values for Spain); and, (2) a quantity indicator (high prescribing), defined as any case where defined daily doses (DDD) per 1 000 inhabitants per day of antibacterials for systemic use were higher than the mean values for Spain. The adjusted odds ratio for a change in the interquartile range (IqOR) for each sources of information on antibiotics was calculated using Generalized Linear Mixed Models. RESULTS: The questionnaire response rate was 68%. Greater perceived utility of pharmaceutical sales representatives increases the risk of having high prescribing (1/IqOR = 2.50 [95%CI: 1.63-3.66]) and reduces the probability of having appropriate quality (1/IqOR = 2.28 [95%CI: 1.77-3.01]). Greater perceived utility of clinical guidelines increases the probability of having appropriate quality (1/IqOR = 1.25 [95%CI: 1.02-1.54]) and reduces the probability of high prescribing (1/IqOR = 1.25 [95%CI: 1.02-1.54]). CONCLUSIONS: Sources of information on antibiotics are an important determinant of the quantity and quality of antibiotic prescribing in primary care. Commercial sources of information influence prescribing negatively, and clinical guidelines are associated with better indicators.Instituto de Salud Carlos IIIThe European Regional Development Fund (ERDF)Mutua Madrileñ

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

INTRODUCTION: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. METHODS: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. RESULTS: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. DISCUSSION: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Cu deficiency in multi stage co evaporated Cu In,Ga Se2 for solar cells applications Microstructure and Ga in depth alloying

The objective of this work is to study the influence of the maximum Cu content during the deposition of Cu In,Ga Se2 CIGSe by multi stage co evaporation on the phases present in the final film, the film structure and the electrical properties of resulting solar cell devices. The variation of the composition is controlled by the Cu content in stage 2 of the deposition process. The different phases are identified by Raman spectroscopy. The in depth Ga gradient distribution is investigated by in depth resolved Raman scattering and secondary neutral mass spectroscopy. The morphology of the devices is studied by scanning electron microscopy. Efficiencies of 9.2 are obtained for ordered vacancy compound based solar cells with a Cu In Ga 0.35, showing the system s flexibility. This work supports the current growth model a small amount of Cu excess during the absorber process is required to obtain a quality microstructure and high performances device

Raman scattering analysis of Cu poor Cu In,Ga Se2 cells fabricated on polyimide substrates Effect of Na content on microstructure and phase structure

This work reports the Raman scattering surface and in depth resolved analysis of Cu poor Cu In,Ga Se2 CIGS grown on polyimide substrates. In order to study the effect of Na on the formation and microstructure of the CIGS and the corresponding Cu poor ordered vacancy compound OVC phases, a NaF precursor layer with different thicknesses was deposited on the Mo coated substrates before growing of the samples. The Raman spectroscopy data are correlated with the analysis of the samples by Auger electron spectroscopy and scanning electron microscopy. These data corroborate the significant role of Na on the inhibition of Ga In interdiffusion and on the formation of the MoSe2 interfacial phase at the back region of the layers. Presence of Na also leads to an enhancement in the formation of the chalcopyrite CIGS phase and a decrease in the occurrence of the dominant OVC phase at the surface region. This study confirms the strong dependence of the microstructure and phase distribution in CIGS absorber layers on the Na available during their growt

Magnetic textures and singularities in ferri ferromagnetic multilayers

The stacking of ferrimagnetic and ferromagnetic films leads to a competition between magnetic interactions that can stabilize Bloch points and other singularities at the interfaces. In this work, GdxCo1 x NdCo5 GdyCo1 y tri layers, with different thicknesses, have been prepared. By tuning the stoichiometry of the Gd Co outer layers, the Co magnetic sublattice dominates in one layer, whereas the opposite side is Gd dominated. In this way, in depth magnetization domain walls can be created due to the balance between exchange and magnetostatic interactions. In addition, the weak perpendicular magnetic anisotropy of the Nd Co central layer induces a stripe domain pattern, supporting the formation of Bloch points, meron like textures, and vortex antivortex pairs. The interaction between both types of structures, in depth domain walls and magnetic singularities, has been studied by a combination of macroscopic Magneto Optical Kerr Effect and Vibrating Sample Magnetometry measurements with microscopic Magnetic Force Microscopy and element selective magnetic Transmission soft X ray Microscopy imaging. The results confirm marked changes in the magnetic properties of the trilayers, as compared with those single NdCo5 films, and the formation of complex magnetic textures, associated with partial magnetization reversal, where magnetic singularities are forme