233 research outputs found

    Quantifying Between-Cohort and Between-Sex Genetic Heterogeneity in Major Depressive Disorder

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    Major depressive disorder (MDD) is clinically heterogeneous with prevalence rates twice as high in women as in men. There are many possible sources of heterogeneity in MDD most of which are not measured in a sufficiently comparable way across study samples. Here, we assess genetic heterogeneity based on two fundamental measures, between-cohort and between-sex heterogeneity. First, we used genome-wide association study (GWAS) summary statistics to investigate between-cohort genetic heterogeneity using the 29 research cohorts of the Psychiatric Genomics Consortium (PGC; N cases = 16,823, N controls = 25,632) and found that some of the cohort heterogeneity can be attributed to ascertainment differences (such as recruitment of cases from hospital vs community sources). Second, we evaluated between-sex genetic heterogeneity using GWAS summary statistics from the PGC, Kaiser Permanente GERA, UK Biobank and the Danish iPSYCH studies but did not find convincing evidence for genetic differences between the sexes. We conclude that there is no evidence that the heterogeneity between MDD data sets and between sexes reflects genetic heterogeneity. Larger sample sizes with detailed phenotypic records and genomic data remain the key to overcome heterogeneity inherent in assessment of MDD

    Quantifying between-cohort and between-sex genetic heterogeneity in major depressive disorder

    Get PDF
    Major depressive disorder (MDD) is clinically heterogeneous with prevalence rates twice as high in women as in men. There are many possible sources of heterogeneity in MDD most of which are not measured in a sufficiently comparable way across study samples. Here, we assess genetic heterogeneity based on two fundamental measures, between-cohort and between-sex heterogeneity. First, we used genome-wide association study (GWAS) summary statistics to investigate between-cohort genetic heterogeneity using the 29 research cohorts of the Psychiatric Genomics Consortium (PGC; N cases = 16,823, N controls = 25,632) and found that some of the cohort heterogeneity can be attributed to ascertainment differences (such as recruitment of cases from hospital vs. community sources). Second, we evaluated between-sex genetic heterogeneity using GWAS summary statistics from the PGC, Kaiser Permanente GERA, UK Biobank, and the Danish iPSYCH studies but did not find convincing evidence for genetic differences between the sexes. We conclude that there is no evidence that the heterogeneity between MDD data sets and between sexes reflects genetic heterogeneity. Larger sample sizes with detailed phenotypic records and genomic data remain the key to overcome heterogeneity inherent in assessment of MDD

    Diatreta Cups, Light in Roman Dining Spaces

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    Cage cups or Diatreta are ancient Roman glass vessels produced by creating a thick blown blank of glass that, once cooled down, is taken to a glass cutter or diatretarii. The latter would cut and carve away most of the glass leaving a transparent vessel inside and an open-work decoration separated through thin posts of glass. The work is very delicate and exclusive, produced within limited space in time with no record of similar vessels until the late 1800 (Donald B. Harden & Toynbee 1959, p.181). Many of these glass objects have good-will inscriptions or decorations that express the importance of drinking. As for their provenance, most –when found in context- have been found in pagan burials. Nevertheless some fragments have been found in Christian environments or with Christian motifs like the Szekszárd cup. The location of these finds is mostly in the Rhine area –northern Empire, when Milan was one of its capitals (Aquaro 2004)- but the actual extent of finds expand throughout the 4th century extent of the Roman Empire. Considering their typological analysis there are basically two types, beaker and bowl. Beakers are considered drinking vessels as they either display a legend or a mythological reference to drink or wine. Whereas a general consensus agrees that open bowl-form cups were hanging lamps (Whitehouse 1988, p.28) since the 1986 find of a diatreta bowl with copper alloy hanging attachments. It is clear these were luxury objects to be used in special occasions and spaces. The aim of this paper is to understand the space were socialisation and drinking took place and the importance of luxurious objects to adorn, display and use. The paper will also put forward the idea that the beaker shaped diatreta vessels, usually considered for drinking, could have been lamps that encouraged drinking and good will to the guests. This paper is structured to first consider an introduction to late luxury Roman glass and then analysing the typological shape of all, or most of the diatreta currently known; secondly, through assessment by the means of comparison, analyse the writings or decorations the vessels were endowed with. Thirdly, by describing and understanding the people and the space were these vessels would have been used, emphasise the beauty of illuminating such spaces with these vessels. According to Herodotus in his historical investigation –5th century-, dress habits and food regime are elements of extreme importance to understand a people (Caporusso et al. 2011, p.12). This idea is not only valid for Herodotus’ time but it is something anthropology uses time and again to explain different aspects in people’s way of life. Through food and its environment, the dining space, this paper will aim to put the cage cups into a social context in order to give emphasis to the hypothesis of light versus wine

    What the egg can tell about its hen: embryo development on the basis of Dynamic Energy Budgets.

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    The energy cost of offspring is important in the conversion of resources allocated to reproduction to numbers of offspring, and in obtaining energy budget parameters from quantities that are easy to measure. An efficient numerical procedure is presented to obtain this cost for eggs and foetusses in the context of the dynamic energy budget theory, which specifies that birth occurs when maturity exceeds a threshold value and maternal effects determine the reserve density at birth. This paper extends previous work to arbitrary values of the ratio of the maturity and somatic maintenance costs. I discuss the body size scaling implications for the relative size and age at birth and conclude that the size at birth, contrary to the age at birth, covaries with the maintenance ratio. Apart from evolutionary adaptation of the maturity at birth, this covariation might explain some of the observed scatter in the relative length at birth. The theory can be used to evaluate the effects of the separation of cells in e.g. the two-cell stage of embryonic development, and of the removal of initial egg mass. If cell separation hardly affects energy parameters, body size scaling relationships imply that cell separation can only occur successfully in species with sufficiently large maximum body length (as adult); i.e. some two times that of Daphnia magna. Toxic compounds that increase the cost of synthesis of structure, decrease the allocation to reproduction indirectly via the life cycle, because food uptake is linked to size. They can also decrease the egg size, however, such that the reproduction rate is stimulated at low concentrations. The present theory offers a possible explanation for this well-known phenomenon. © 2008 Springer-Verlag

    Identification of common genetic risk variants for autism spectrum disorder

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    Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

    Solar parameters for modeling interplanetary background

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    The goal of the Fully Online Datacenter of Ultraviolet Emissions (FONDUE) Working Team of the International Space Science Institute in Bern, Switzerland, was to establish a common calibration of various UV and EUV heliospheric observations, both spectroscopic and photometric. Realization of this goal required an up-to-date model of spatial distribution of neutral interstellar hydrogen in the heliosphere, and to that end, a credible model of the radiation pressure and ionization processes was needed. This chapter describes the solar factors shaping the distribution of neutral interstellar H in the heliosphere. Presented are the solar Lyman-alpha flux and the solar Lyman-alpha resonant radiation pressure force acting on neutral H atoms in the heliosphere, solar EUV radiation and the photoionization of heliospheric hydrogen, and their evolution in time and the still hypothetical variation with heliolatitude. Further, solar wind and its evolution with solar activity is presented in the context of the charge exchange ionization of heliospheric hydrogen, and in the context of dynamic pressure variations. Also the electron ionization and its variation with time, heliolatitude, and solar distance is presented. After a review of all of those topics, we present an interim model of solar wind and the other solar factors based on up-to-date in situ and remote sensing observations of solar wind. Results of this effort will further be utilised to improve on the model of solar wind evolution, which will be an invaluable asset in all heliospheric measurements, including, among others, the observations of Energetic Neutral Atoms by the Interstellar Boundary Explorer (IBEX).Comment: Chapter 2 in the planned "Cross-Calibration of Past and Present Far UV Spectra of Solar System Objects and the Heliosphere", ISSI Scientific Report No 12, ed. R.M. Bonnet, E. Quemerais, M. Snow, Springe
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