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.
Abstract Background and objectives Mucinous cystic neoplasms and intraductal papillary mucinous tumours have greater malignant potential than serous cystic neoplasms. EUS alone is inadequate for ...characterising these lesions but the addition of FNA may significantly improve diagnostic accuracy. The performance of EUS-FNA is highly variable in published studies. Aim To determine the diagnostic accuracy of EUS-FNA to differentiate mucinous versus non-mucinous cystic lesions with cyst fluid analysis for cytology and carcinoembryonic antigen (CEA) by performing a meta-analysis of published studies. Methods Relevant studies were identified via structured database search and included if they used a reference standard of definitive surgical histology or clinical follow-up of at least 6 months. Data from selected studies were pooled to give summary sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio and Receiver Operating Characteristic (ROC) curve. Pre-defined subgroup analysis was performed. Results Eighteen studies (published 2002–2011) were included, with a total of 1438 patients. For cytology, pooled sensitivity was 54(95%CI 49–59)% and specificity 93(90–95)%. The diagnostic odds ratio (DOR) was 13.3 (4.37–49.43), with I2 of 77.1%. For CEA sensitivity was 63(59–67)% and specificity 88(83–91)%. The DOR was 10.76(6.29–18.41) with an I2 of 25.4%. The diagnostic accuracy of EUS-FNA was enhanced in prospective studies and studies of <36 months duration. No impact of publication bias on our results was demonstrated. Conclusions Fine-needle aspiration has moderate sensitivity but high specificity for mucinous lesions. EUS-FNA, when used in conjunction with cross sectional imaging, is a useful diagnostic tool for the correct identification of mucinous cysts.
Abstract Past studies highlight a narrowing gender gap and the existence of a shared etiology across substances of abuse; however, few have tested developmental models using longitudinal data. We ...present data on developmental trends of alcohol, tobacco, and marijuana use, abuse and dependence assessed during adolescence and young adulthood in a community-based Colorado twin sample of 1733 respondents through self-report questionnaires and structured psychiatric interviews. Additionally, we report on the rates of multiple substance use and disorders at each developmental stage, and the likelihood of a substance use disorder (SUD; i.e., abuse or dependence) diagnosis in young adulthood based on adolescent drug involvement. Most notably, we evaluate whether the pattern of multiple substance use and disorders and likelihood ratios across substances support a model of generalized risk. Lastly, we evaluate whether the ranked magnitudes of substance-specific risk match the addiction liability ranking. Substance use and SUDs are developmental phenomena, which increase from adolescence to young adulthood with few and inconsistent gender differences. Adolescents and young adults are not specialized users, but rather tend to use or abuse multiple substances increasingly with age. Risk analyses indicated that progression toward a SUD for any substance was increased with prior involvement with any of the three substances during adolescence. Despite the high prevalence of alcohol use, tobacco posed the greatest substance-specific risk for developing subsequent problems. Our data also confirm either a generalized risk or correlated risk factors for early onset substance use and subsequent development of SUDs.
ABSTRACT
We report on results of spectropolarimetry of the afterglow of the long gamma-ray burst GRB 191221B, obtained with SALT/RSS and VLT/FORS2, as well as photometry from two telescopes in the ...MASTER Global Robotic Network, at the MASTER-SAAO (South Africa) and MASTER-OAFA (Argentina) stations. Prompt optical emission was detected by MASTER-SAAO 38 s after the alert, which dimmed from a magnitude (white-light) of ∼10–16.2 mag over a period of ∼10 ks, followed by a plateau phase lasting ∼10 ks and then a decline to ∼18 mag after 80 ks. The light curve shows complex structure, with four or five distinct breaks in the power-law decline rate. SALT/RSS linear spectropolarimetry of the afterglow began ∼2.9 h after the burst, during the early part of the plateau phase of the light curve. Absorption lines seen at ∼6010 and 5490 Å are identified with the Mg ii 2799 Å line from the host galaxy at z = 1.15 and an intervening system located at z = 0.96. The mean linear polarization measured over 3400–8000 Å was ∼1.5 per cent and the mean equatorial position angle (θ) was ∼65°. VLT/FORS2 spectropolarimetry was obtained ∼10 h post-burst, during a period of slow decline (α = −0.44), and the polarization was measured to be p = 1.2 per cent and θ = 60°. Two observations with the MeerKAT radio telescope, taken 30 and 444 d after the GRB trigger, detected radio emission from the host galaxy only. We interpret the light curve and polarization of this long GRB in terms of a slow-cooling forward shock.
The new sea ice configuration GSI6.0, used in the Met Office global coupled configuration GC2.0, is described and the sea ice extent, thickness and volume are compared with the previous configuration ...and with observationally based data sets. In the Arctic, the sea ice is thicker in all seasons than in the previous configuration, and there is now better agreement of the modelled concentration and extent with the HadISST data set. In the Antarctic, a warm bias in the ocean model has been exacerbated at the higher resolution of GC2.0, leading to a large reduction in ice extent and volume; further work is required to rectify this in future configurations.
Treatment with estrogen in early menopausal women protects against development of hepatic steatosis and nonalcoholic fatty liver disease but estrogen has undesirable side effects, which negate its ...beneficial effects in premenopausal and postmenopausal women. Targeted therapies require better understanding of the target sites and mechanisms by which estrogen signaling exerts its protective effects in women. Estrogen receptor α (ERα) is thought to be the primary mediator for estrogen signaling to protect against hepatic steatosis. ERα has several mechanisms for signal transduction: (1) inducing gene transcription by direct binding to specific DNA sequences, (2) inducing tethered transcription with other DNA-binding factors, and (3) stimulating nongenomic action through membrane-associated ERα. However, it is still unclear which mechanisms mediate ERα-dependent protection against hepatic steatosis.
To understand the mechanisms of estrogen signaling for protection against hepatic steatosis in females, we analyzed the global ERα knockout mouse (αERKO), ERα DNA-binding domain mutant mouse (KIKO) and liver-specific ERα knockout mouse (LERKO) fed high-fat diets (HFD). The KIKO mouse disrupts the direct DNA-binding transcription activity but retains tethered transcription regulation and nongenomic action. Hepatic steatosis was evaluated by scoring the macrovesicular and microvesicular steatosis as well as serum alanine aminotransferase (ALT) levels. We analyzed serum testosterone to assess its correlation with hepatic steatosis.
Liver fat accumulation was far greater in HFD-fed αERKO and KIKO females than in HFD-fed wild-type (WT) controls. Conversely, HFD-fed LERKO females did not accumulate excess liver fat. HFD-fed αERKO and KIKO females showed higher microvesicular steatosis and ALT levels than WT controls that correlated with increased serum testosterone levels.
ERα-mediated direct transcription in non-hepatic tissues is essential for estrogen-mediated protection against hepatic steatosis in HFD-fed females. The balance between non-hepatic estrogen signaling and hepatic or non-hepatic testosterone action may control hepatic steatosis.
We describe the HadGEM2 family of climate configurations of the Met Office Unified Model, MetUM. The concept of a model "family" comprises a range of specific model configurations incorporating ...different levels of complexity but with a common physical framework. The HadGEM2 family of configurations includes atmosphere and ocean components, with and without a vertical extension to include a well-resolved stratosphere, and an Earth-System (ES) component which includes dynamic vegetation, ocean biology and atmospheric chemistry. The HadGEM2 physical model includes improvements designed to address specific systematic errors encountered in the previous climate configuration, HadGEM1, namely Northern Hemisphere continental temperature biases and tropical sea surface temperature biases and poor variability. Targeting these biases was crucial in order that the ES configuration could represent important biogeochemical climate feedbacks. Detailed descriptions and evaluations of particular HadGEM2 family members are included in a number of other publications, and the discussion here is limited to a summary of the overall performance using a set of model metrics which compare the way in which the various configurations simulate present-day climate and its variability.
We present data on the lifetime prevalence of substance use, abuse and dependence in adolescents obtained through structured psychiatric interviews and self-report questionnaires. Most notably, we ...evaluate symptom profiles based on DSM-IV abuse and dependence criteria for tobacco, alcohol and marijuana, including a gender comparison. Participants are 3072 adolescents (12–18 years) drawn from three community-based family samples in Colorado. Age trends suggest that substance use is a developmental phenomenon, which increases almost linearly from early to late adolescence. Substance use
disorders are less common than experimentation in adolescence, but approximately 1 in 4 adolescents in the oldest cohorts meets criteria for abuse for at least one substance, and 1 in 5 meets criteria for substance dependence. By age 18 nearly 1 in 3 adolescents report daily smoking and 8.6% meet criteria for tobacco dependence. Although alcohol is the most commonly
abused substance (10%), a slightly larger proportion of adolescents meet criteria for
dependence on marijuana (4.3%) than alcohol (3.5%). Gender differences in prevalence of use more often show greater use in males than females. Males more frequently meet criteria for dependence on alcohol and marijuana in late adolescence, while females are more often nicotine dependent. A comparison of abuse and dependence symptom profiles shows some interesting variability across substances, and suggests that manifestations of a subset of symptoms are gender specific.
Four high-resolution regional climate models (RCMs) have been set up for the area of Greenland, with the aim of providing future projections of Greenland ice sheet surface mass balance (SMB), and its ...contribution to sea level rise, with greater accuracy than is possible from coarser-resolution general circulation models (GCMs). This is the first time an intercomparison has been carried out of RCM results for Greenland climate and SMB. Output from RCM simulations for the recent past with the four RCMs is evaluated against available observations. The evaluation highlights the importance of using a detailed snow physics scheme, especially regarding the representations of albedo and meltwater refreezing. Simulations with three of the RCMs for the 21st century using SRES scenario A1B from two GCMs produce trends of between −5.5 and −1.1 Gt yr−2 in SMB (equivalent to +0.015 and +0.003 mm sea level equivalent yr−2), with trends of smaller magnitude for scenario E1, in which emissions are mitigated. Results from one of the RCMs whose present-day simulation is most realistic indicate that an annual mean near-surface air temperature increase over Greenland of ~ 2°C would be required for the mass loss to increase such that it exceeds accumulation, thereby causing the SMB to become negative, which has been suggested as a threshold beyond which the ice sheet would eventually be eliminated.
An extension to current maximum-likelihood variance-components procedures for mapping quantitative-trait loci in sib pairs that allows a simultaneous test of allelic association is proposed. The ...method involves modeling of the allelic means for a test of association, with simultaneous modeling of the sib-pair covariance structure for a test of linkage. By partitioning of the mean effect of a locus into between- and within-sibship components, the method controls for spurious associations due to population stratification and admixture. The power and efficacy of the method are illustrated through simulation of various models of both real and spurious association.
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