206 research outputs found

    Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia

    Get PDF
    Abstract The antipsychotic clozapine is uniquely effective in the management of schizophrenia; however, its use is limited by its potential to induce agranulocytosis. The causes of this, and of its precursor neutropenia, are largely unknown, although genetic factors have an important role. We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide association study (GWAS), imputed human leukocyte antigen (HLA) alleles, exome array and copy-number variation (CNV) analyses. We then combined associated variants in a meta-analysis with data from the Clozapine-Induced Agranulocytosis Consortium (up to 163 cases and 7970 controls). In the largest combined sample to date, we identified a novel association with rs149104283 (odds ratio (OR)=4.32, P=1.79 × 10−8), intronic to transcripts of SLCO1B3 and SLCO1B7, members of a family of hepatic transporter genes previously implicated in adverse drug reactions including simvastatin-induced myopathy and docetaxel-induced neutropenia. Exome array analysis identified gene-wide associations of uncommon non-synonymous variants within UBAP2 and STARD9. We additionally provide independent replication of a previously identified variant in HLA-DQB1 (OR=15.6, P=0.015, positive predictive value=35.1%). These results implicate biological pathways through which clozapine may act to cause this serious adverse effect.</jats:p

    Physical activity, cardiorespiratory fitness, and metabolic syndrome in adolescents: A cross-sectional study

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>In adults, there is a substantial body of evidence that physical inactivity or low cardiorespiratory fitness levels are strongly associated with the development of metabolic syndrome. Although this association has been studied extensively in adults, little is known regarding this association in adolescents. The aim of this study was to analyze the association between physical activity and cardiorespiratory fitness levels with metabolic syndrome in Brazilian adolescents.</p> <p>Methods</p> <p>A random sample of 223 girls (mean age, 14.4 ± 1.6 years) and 233 boys (mean age, 14.6 ± 1.6 years) was selected for the study. The level of physical activity was determined by the Bouchard three-day physical activity record. Cardiorespiratory fitness was estimated by the Leger 20-meter shuttle run test. The metabolic syndrome components assessed included waist circumference, blood pressure, HDL-cholesterol, triglycerides, and fasting plasma glucose levels. Independent Student <it>t</it>-tests were used to assess gender differences. The associations between physical activity and cardiorespiratory fitness with the presence of metabolic syndrome were calculated using logistic regression models adjusted for age and gender.</p> <p>Results</p> <p>A high prevalence of metabolic syndrome was observed in inactive adolescents (males, 11.4%; females, 7.2%) and adolescents with low cardiorespiratory fitness levels (males, 13.9%; females, 8.6%). A significant relationship existed between metabolic syndrome and low cardiorespiratory fitness (OR, 3.0 [1.13-7.94]).</p> <p>Conclusion</p> <p>The prevalence of metabolic syndrome is high among adolescents who are inactive and those with low cardiorespiratory fitness. Prevention strategies for metabolic syndrome should concentrate on enhancing fitness levels early in life.</p

    Abrasive, Silica Phytoliths and the Evolution of Thick Molar Enamel in Primates, with Implications for the Diet of Paranthropus boisei

    Get PDF
    Background: Primates—including fossil species of apes and hominins—show variation in their degree of molar enamel thickness, a trait long thought to reflect a diet of hard or tough foods. The early hominins demonstrated molar enamel thickness of moderate to extreme degrees, which suggested to most researchers that they ate hard foods obtained on or near the ground, such as nuts, seeds, tubers, and roots. We propose an alternative hypothesis—that the amount of phytoliths in foods correlates with the evolution of thick molar enamel in primates, although this effect is constrained by a species ’ degree of folivory. Methodology/Principal Findings: From a combination of dietary data and evidence for the levels of phytoliths in plant families in the literature, we calculated the percentage of plant foods rich in phytoliths in the diets of twelve extant primates with wide variation in their molar enamel thickness. Additional dietary data from the literature provided the percentage of each primate’s diet made up of plants and of leaves. A statistical analysis of these variables showed that the amount of abrasive silica phytoliths in the diets of our sample primates correlated positively with the thickness of their molar enamel, constrained by the amount of leaves in their diet (R 2 = 0.875; p,.0006). Conclusions/Significance: The need to resist abrasion from phytoliths appears to be a key selective force behind the evolution of thick molar enamel in primates. The extreme molar enamel thickness of the teeth of the East African homini

    An ultrahot Neptune in the Neptune desert

    Get PDF
    About one out of 200 Sun-like stars has a planet with an orbital period shorter than one day: an ultra-short-period planet (Sanchis-ojeda et al. 2014; Winn et al. 2018). All of the previously known ultra-short-period planets are either hot Jupiters, with sizes above 10 Earth radii (Re), or apparently rocky planets smaller than 2 Re. Such lack of planets of intermediate size (the "hot Neptune desert") has been interpreted as the inability of low-mass planets to retain any hydrogen/helium (H/He) envelope in the face of strong stellar irradiation. Here, we report the discovery of an ultra-short-period planet with a radius of 4.6 Re and a mass of 29 Me, firmly in the hot Neptune desert. Data from the Transiting Exoplanet Survey Satellite (Ricker et al. 2015) revealed transits of the bright Sun-like star \starname\, every 0.79 days. The planet's mean density is similar to that of Neptune, and according to thermal evolution models, it has a H/He-rich envelope constituting 9.0^(+2.7)_(-2.9)% of the total mass. With an equilibrium temperature around 2000 K, it is unclear how this "ultra-hot Neptune" managed to retain such an envelope. Follow-up observations of the planet's atmosphere to better understand its origin and physical nature will be facilitated by the star's brightness (Vmag=9.8)

    Neural Network Development in Late Adolescents during Observation of Risk-Taking Action

    Get PDF
    Emotional maturity and social awareness are important for adolescents, particularly college students beginning to face the challenges and risks of the adult world. However, there has been relatively little research into personality maturation and psychological development during late adolescence and the neural changes underlying this development. We investigated the correlation between psychological properties (neuroticism, extraversion, anxiety, and depression) and age among late adolescents (n = 25, from 18 years and 1 month to 22 years and 8 months). The results revealed that late adolescents became less neurotic, less anxious, less depressive and more extraverted as they aged. Participants then observed video clips depicting hand movements with and without a risk of harm (risk-taking or safe actions) during functional magnetic resonance imaging (fMRI). The results revealed that risk-taking actions elicited significantly stronger activation in the bilateral inferior parietal lobule, temporal visual regions (superior/middle temporal areas), and parieto-occipital visual areas (cuneus, middle occipital gyri, precuneus). We found positive correlations of age and extraversion with neural activation in the insula, middle temporal gyrus, lingual gyrus, and precuneus. We also found a negative correlation of age and anxiety with activation in the angular gyrus, precentral gyrus, and red nucleus/substantia nigra. Moreover, we found that insula activation mediated the relationship between age and extraversion. Overall, our results indicate that late adolescents become less anxious and more extraverted with age, a process involving functional neural changes in brain networks related to social cognition and emotional processing. The possible neural mechanisms of psychological and social maturation during late adolescence are discussed

    Societal-level versus individual-level predictions of ethical behavior: a 48-society study of collectivism and individualism

    Get PDF
    Is the societal-level of analysis sufficient today to understand the values of those in the global workforce? Or are individual-level analyses more appropriate for assessing the influence of values on ethical behaviors across country workforces? Using multi-level analyses for a 48-society sample, we test the utility of both the societal-level and individual-level dimensions of collectivism and individualism values for predicting ethical behaviors of business professionals. Our values-based behavioral analysis indicates that values at the individual-level make a more significant contribution to explaining variance in ethical behaviors than do values at the societal-level. Implicitly, our findings question the soundness of using societal-level values measures. Implications for international business research are discussed
    corecore