The diathesis-stress theory for depression states that the effects of stress on the depression risk are dependent on the diathesis or vulnerability, implying multiplicative interactive effects on the ...liability scale. We used polygenic risk scores for major depressive disorder (MDD) calculated from the results of the most recent analysis from the Psychiatric Genomics Consortium as a direct measure of the vulnerability for depression in a sample of 5221 individuals from 3083 families. In the same we also had measures of stressful life events and social support and a depression symptom score, as well as DSM-IV MDD diagnoses for most individuals. In order to estimate the variance in depression explained by the genetic vulnerability, the stressors and their interactions, we fitted linear mixed models controlling for relatedness for the whole sample as well as stratified by sex. We show a significant interaction of the polygenic risk scores with personal life events (0.12% of variance explained, P-value=0.0076) contributing positively to the risk of depression. Additionally, our results suggest possible differences in the aetiology of depression between women and men. In conclusion, our findings point to an extra risk for individuals with combined vulnerability and high number of reported personal life events beyond what would be expected from the additive contributions of these factors to the liability for depression, supporting the multiplicative diathesis-stress model for this disease.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Personality can be thought of as a set of characteristics that influence people's thoughts, feelings and behavior across a variety of settings. Variation in personality is predictive of many outcomes ...in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in 10 discovery samples (17,375 adults) and five in silico replication samples (3294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data of ≈ 2.4M single-nucleotide polymorphisms (SNPs; directly typed and imputed using HapMap data) were available. In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P=2.8 × 10(-8) and 3.1 × 10(-8)) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P=4.9 × 10(-8)). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The SuperCDMS experiment is designed to directly detect weakly interacting massive particles (WIMPs) that may constitute the dark matter in our Galaxy. During its operation at the Soudan Underground ...Laboratory, germanium detectors were run in the CDMSlite mode to gather data sets with sensitivity specifically for WIMPs with masses <10 GeV/c2. In this mode, a higher detector-bias voltage is applied to amplify the phonon signals produced by drifting charges. This paper presents studies of the experimental noise and its effect on the achievable energy threshold, which is demonstrated to be as low as 56 eVee (electron equivalent energy). The detector-biasing configuration is described in detail, with analysis corrections for voltage variations to the level of a few percent. Detailed studies of the electric-field geometry, and the resulting successful development of a fiducial parameter, eliminate poorly measured events, yielding an energy resolution ranging from ∼9 eVee at 0 keV to 101 eVee at ∼10 keVee. New results are derived for astrophysical uncertainties relevant to the WIMP-search limits, specifically examining how they are affected by variations in the most probable WIMP velocity and the Galactic escape velocity. These variations become more important for WIMP masses below 10 GeV/c2. Finally, new limits on spin-dependent low-mass WIMP-nucleon interactions are derived, with new parameter space excluded for WIMP masses ≲3 GeV/c2.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Although common sense suggests that environmental influences increasingly account for individual differences in behavior as experiences accumulate during the course of life, this hypothesis has not ...previously been tested, in part because of the large sample sizes needed for an adequately powered analysis. Here we show for general cognitive ability that, to the contrary, genetic influence increases with age. The heritability of general cognitive ability increases significantly and linearly from 41% in childhood (9 years) to 55% in adolescence (12 years) and to 66% in young adulthood (17 years) in a sample of 11 000 pairs of twins from four countries, a larger sample than all previous studies combined. In addition to its far-reaching implications for neuroscience and molecular genetics, this finding suggests new ways of thinking about the interface between nature and nurture during the school years. Why, despite life's 'slings and arrows of outrageous fortune', do genetically driven differences increasingly account for differences in general cognitive ability? We suggest that the answer lies with genotype-environment correlation: as children grow up, they increasingly select, modify and even create their own experiences in part based on their genetic propensities.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We present limits on spin-independent dark matter-nucleon interactions using a 10.6 g Si athermal phonon detector with a baseline energy resolution of σE = 3.86 ± 0.04 ( stat ) +0.19 −0.00 ( syst ) ...eV . This exclusion analysis sets the most stringent dark matter-nucleon scattering cross-section limits achieved by a cryogenic detector for dark matter particle masses from 93 to 140 MeV / c2 , with a raw exposure of 9.9 g d acquired at an above-ground facility. This work illustrates the scientific potential of detectors with athermal phonon sensors with eV-scale energy resolution for future dark matter searches.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Overview of the SPARC tokamak Creely, A. J.; Greenwald, M. J.; Ballinger, S. B. ...
Journal of plasma physics,
10/2020, Volume:
86, Issue:
5
Journal Article
Peer reviewed
Open access
The SPARC tokamak is a critical next step towards commercial fusion energy. SPARC is designed as a high-field ($B_0 = 12.2$ T), compact ($R_0 = 1.85$ m, $a = 0.57$ m), superconducting, D-T tokamak ...with the goal of producing fusion gain $Q>2$ from a magnetically confined fusion plasma for the first time. Currently under design, SPARC will continue the high-field path of the Alcator series of tokamaks, utilizing new magnets based on rare earth barium copper oxide high-temperature superconductors to achieve high performance in a compact device. The goal of $Q>2$ is achievable with conservative physics assumptions ($H_{98,y2} = 0.7$) and, with the nominal assumption of $H_{98,y2} = 1$, SPARC is projected to attain $Q \approx 11$ and $P_{\textrm {fusion}} \approx 140$ MW. SPARC will therefore constitute a unique platform for burning plasma physics research with high density ($\langle n_{e} \rangle \approx 3 \times 10^{20}\ \textrm {m}^{-3}$), high temperature ($\langle T_e \rangle \approx 7$ keV) and high power density ($P_{\textrm {fusion}}/V_{\textrm {plasma}} \approx 7\ \textrm {MW}\,\textrm {m}^{-3}$) relevant to fusion power plants. SPARC's place in the path to commercial fusion energy, its parameters and the current status of SPARC design work are presented. This work also describes the basis for global performance projections and summarizes some of the physics analysis that is presented in greater detail in the companion articles of this collection.
Despite osteoarthritis (OA) and rheumatoid arthritis (RA) being typically age-related, their underlying etiologies are markedly different. We used 1H nuclear magnetic resonance (NMR) spectroscopy to ...identify differences in metabolite profiles in low volumes of OA and RA synovial fluid (SF). SF was aspirated from knee joints of 10 OA and 14 RA patients. 100 μL SF was analyzed using a 700 MHz Avance IIIHD Bruker NMR spectrometer with a TCI cryoprobe. Spectra were analyzed by Chenomx, Bruker TopSpin and AMIX software. Statistical analysis was undertaken using Metaboanalyst. 50 metabolites were annotated, including amino acids, saccharides, nucleotides and soluble lipids. Discriminant analysis identified group separation between OA and RA cohorts, with 32 metabolites significantly different between OA and RA SF (false discovery rate (FDR) < 0.05). Metabolites of glycolysis and the tricarboxylic acid cycle were lower in RA compared to OA; these results concur with higher levels of inflammation, synovial proliferation and hypoxia found in RA compared to OA. Elevated taurine in OA may indicate increased subchondral bone sclerosis. We demonstrate that quantifiable differences in metabolite abundance can be measured in low volumes of SF by 1H NMR spectroscopy, which may be clinically useful to aid diagnosis and improve understanding of disease pathogenesis.
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IJS, KILJ, NUK, PNG, UL, UM
We present a robust calibration of the 1.4 GHz radio continuum star formation rate (SFR) using a combination of the Galaxy And Mass Assembly (GAMA) survey and the Faint Images of the Radio Sky at ...Twenty-cm (FIRST) survey. We identify individually detected 1.4 GHz GAMA-FIRST sources and use a late-type, non-active galactic nucleus, volume-limited sample from GAMA to produce stellar mass-selected samples. The latter are then combined to produce FIRST-stacked images. This extends the robust parametrization of the 1.4 GHz-SFR relation to faint luminosities. For both the individually detected galaxies and our stacked samples, we compare 1.4 GHz luminosity to SFRs derived from GAMA to determine a new 1.4 GHz luminosity-to-SFR relation with well-constrained slope and normalization. For the first time, we produce the radio SFR-M* relation over 2 decades in stellar mass, and find that our new calibration is robust, and produces a SFR-M* relation which is consistent with all other GAMA SFR methods. Finally, using our new 1.4 GHz luminosity-to-SFR calibration we make predictions for the number of star-forming GAMA sources which are likely to be detected in the upcoming Australian Square Kilometre Array Pathfinder surveys, Evolutionary Map of the Universe and Deep Investigation of Neutral Gas Origins.
Achieving the ability to identify individuals who are susceptible to drug‐induced liver injury (DILI) would represent a major advance in personalized medicine. Clayton et al. demonstrated that the ...pattern of endogenous metabolites in urine could predict susceptibility to acetaminophen‐induced liver injury in rats. We designed a clinical study to test this approach in healthy adults who received 4 g of acetaminophen per day for 7 days. Urine metabolite profiles obtained before the start of treatment were not sufficient to distinguish which of the subjects would develop mild liver injury, as indicated by a rise in alanine aminotransferase (ALT) to a level more than twice the baseline value (responders). However, profiles obtained shortly after the start of treatment, but prior to ALT elevation, could distinguish responders from nonresponders. Statistical analyses revealed that predictive metabolites included those derived from the toxic metabolite N‐acetyl paraquinone imine (NAPQI), but that the inclusion of endogenous metabolites was required for significant prediction. This “early‐intervention pharmaco‐metabonomics” approach should now be tested in clinical trials of other potentially hepatotoxic drugs.
Clinical Pharmacology & Therapeutics (2010) 88 1, 45–51. doi: 10.1038/clpt.2009.240
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
BACKGROUND AND PURPOSE
The novel cathinone derivative 4‐methylmethcathinone (4‐MMC; mephedrone) is increasingly popular with recreational users. Little scientific information is available but users ...report both entactogen‐like and classic stimulant‐like subjective properties. A recent study in humans reported psychomotor speed improvement after intranasal 4‐MMC suggesting classic stimulant properties. Limitations of the user group (which was impaired on some tasks) prompt controlled laboratory investigation.
EXPERIMENTAL APPROACH
Adult male rhesus monkeys were trained to perform tasks from the non‐human primate Cambridge Neuropsychological Test Automated Battery, which assess spatial working memory, visuospatial associative memory, learning and motivation for food reward. Test of bimanual motor coordination and manual tracking were also included. The subjects were challenged with 0.178–0.56 mg·kg−1 4‐MMC and 0.056–0.56 mg·kg−1 d‐methamphetamine (MA), i.m., in randomized order for behavioural evaluation.
KEY RESULTS
A pronounced improvement in visuospatial memory and learning was observed after the 0.32 mg·kg−1 dose of each compound, this effect was confirmed with subsequent repetition of these conditions. Spatial working memory was not improved by either drug, and the progressive ratio, bimanual motor and rotating turntable tasks were all disrupted in a dose‐dependent manner.
CONCLUSIONS AND IMPLICATIONS
These studies show that 4‐MMC produces behavioural effects, including improvements in complex spatial memory and learning that are in large part similar to those of MA in non‐human primates. Thus, the data suggest that the effects of 4‐MMC in monkeys can be classified with classical psychomotor stimulants.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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