Self-regulated learning:Validating a task-specific questionnaire for children in elementary school

This paper describes the development and initial validation of the Cognition and Emotion/Motivation Regulation (CEMOR) questionnaire, a task-specific questionnaire for upper elementary school students that measures self-regulated learning (SRL). Using a multistep procedure, 22 items were developed, divided over five theory-informed dimensions (Planning, Monitoring, Cognition Control, Emotion/Motivation Control, and Reflecting). The CEMOR was applied in a math context. Children from grades 3–6 (N = 547, 54.7 % females) completed the CEMOR. Confirmatory factor analyses indicated that the five proposed scales have adequate to good model fit, with factor loadings ranging from .54 to .83, and acceptable to good composite reliability (ρ range = .75–.85). To find further validity support, the SRL scales were correlated with students’ performance on a math task, experienced emotions, and level of motivation during the task. Most correlations were statistically significant and in the expected direction. Hence, the CEMOR questionnaire shows promise as a new SRL instrument for elementary education

Visuospatial working memory and mathematical ability at different ages throughout primary school.

a b s t r a c t a r t i c l e i n f o In this study, three aims were addressed: (1) validating a visuospatial working memory task in Math Garden, an adaptive online tool in which item difficulty and person ability are determined on the fly, (2) investigating the contribution of different item characteristics to the difficulty of the visuospatial working memory items, and (3) investigating relations between visuospatial working memory and various math domains at different ages. The method was validated by showing that item ratings were stable and grade differences in ability were significant. Regression analyses on the item level showed that not only sequence length, but also other characteristics, such as type of task (forward or backward), explained variance in item difficulty. Finally, regression analyses on the child level showed that visuospatial working memory and mathematics were significantly related: especially for addition and subtraction in the lower grades. For multiplication and division this relationship was weaker and without age trend

TREASUREHUNT: Transients and Variability Discovered with HST in the JWST North Ecliptic Pole Time-domain Field

The James Webb Space Telescope (JWST) North Ecliptic Pole (NEP) Time-domain Field (TDF) is a >14′ diameter field optimized for multiwavelength time-domain science with JWST. It has been observed across the electromagnetic spectrum both from the ground and from space, including with the Hubble Space Telescope (HST). As part of HST observations over three cycles (the “TREASUREHUNT” program), deep images were obtained with the Wide Field Camera on the Advanced Camera for Surveys in F435W and F606W that cover almost the entire JWST NEP TDF. Many of the individual pointings of these programs partially overlap, allowing an initial assessment of the potential of this field for time-domain science with HST and JWST. The cumulative area of overlapping pointings is ∼88 arcmin2, with time intervals between individual epochs that range between 1 day and 4+ yr. To a depth of m AB ≃ 29.5 mag (F606W), we present the discovery of 12 transients and 190 variable candidates. For the variable candidates, we demonstrate that Gaussian statistics are applicable and estimate that ∼80 are false positives. The majority of the transients will be supernovae, although at least two are likely quasars. Most variable candidates are active galactic nuclei (AGNs), where we find 0.42% of the general z ≲ 6 field galaxy population to vary at the ∼3σ level. Based on a 5 yr time frame, this translates into a random supernova areal density of up to ∼0.07 transients arcmin−2 (∼245 deg−2) per epoch and a variable AGN areal density of ∼1.25 variables arcmin−2 (∼4500 deg−2) to these depths

Identification of Common Genetic Variants Influencing Spontaneous Dizygotic Twinning and Female Fertility.

Spontaneous dizygotic (DZ) twinning occurs in 1%-4% of women, with familial clustering and unknown physiological pathways and genetic origin. DZ twinning might index increased fertility and has distinct health implications for mother and child. We performed a GWAS in 1,980 mothers of spontaneous DZ twins and 12,953 control subjects. Findings were replicated in a large Icelandic cohort and tested for association across a broad range of fertility traits in women. Two SNPs were identified (rs11031006 near FSHB, p = 1.54 × 10(-9), and rs17293443 in SMAD3, p = 1.57 × 10(-8)) and replicated (p = 3 × 10(-3) and p = 1.44 × 10(-4), respectively). Based on ∼90,000 births in Iceland, the risk of a mother delivering twins increased by 18% for each copy of allele rs11031006-G and 9% for rs17293443-C. A higher polygenic risk score (PRS) for DZ twinning, calculated based on the results of the DZ twinning GWAS, was significantly associated with DZ twinning in Iceland (p = 0.001). A higher PRS was also associated with having children (p = 0.01), greater lifetime parity (p = 0.03), and earlier age at first child (p = 0.02). Allele rs11031006-G was associated with higher serum FSH levels, earlier age at menarche, earlier age at first child, higher lifetime parity, lower PCOS risk, and earlier age at menopause. Conversely, rs17293443-C was associated with later age at last child. We identified robust genetic risk variants for DZ twinning: one near FSHB and a second within SMAD3, the product of which plays an important role in gonadal responsiveness to FSH. These loci contribute to crucial aspects of reproductive capacity and health.Support for the Netherlands Twin Register was obtained from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organization for Health Research and Development (ZonMW) grants, 904-61-193,480-04-004, 400-05-717, Addiction-31160008, 911-09-032, Biobanking and Biomolecular Resources Research Infrastructure (BBMRI –NL, 184.021.007); Royal Netherlands Academy of Science Professor Award (PAH/6635) to DIB; European Research Council (ERC-230374 and ERC-284167); Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute, Sioux Falls, South Dakota (USA) and the National Institutes of Health (NIH R01 HD042157-01A1). Part of the genotyping was funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health and Grand Opportunity grants 1RC2 MH089951). We acknowledge support from VU Amsterdam and the Institute for Health and Care Research (EMGO+). The Berghofer Medical Research Institute (QIMR) study was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485, 552498, 1050208, 1075175). Dale R. Nyholt was supported by the Australian Research Council (ARC) Future Fellowship (FT0991022), NHMRC Research Fellowship (APP0613674) Schemes and by the Visiting Professors Programme (VPP) of the Royal Netherlands Academy of Arts and Sciences (KNAW). Allan F. McRae was supported by an NRMRC Career Development Fellowship (APP1083656). Grant W. Montgomery was supported by NIH grant (HD042157, a collaborative study of the genetics of DZ twinning) and NHMRC Fellowship (GNT1078399). The Minnesota Center for Twin and Family Research (MCTFR) was supported in part by USPHS Grants from the National Institute on Alcohol Abuse and Alcoholism (AA09367 and AA11886), and the National Institute on Drug Abuse (DA05147, DA13240, and DA024417). We would like to thank also 23andMe's consented research participants for contributing data on age at menarche for the FSHB gene locus and the Twinning Gwas Consortium (TGC). Co-authors from: Finland (Anu Loukola, Juho Wedenoja, Emmi Tikkanen, Beenish Qaiser), Sweden (Nancy Pedersen, Andrea Ganna), United kingdom King's College London (Department of Twin Research & Genetic Epidemiology: Pirro Hysi, Massimo Mangino), Institute of Psychiatry, Psychology & Neuroscience, Medical Research Council Social, Genetic and Developmental Psychiatry Centre (Eva Krapohl, Andrew McMillan).This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.ajhg.2016.03.00

Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes

Type 2 diabetes (T2D) is a very common disease in humans. Here we conduct a meta-analysis of genome-wide association studies (GWAS) with ~16 million genetic variants in 62,892 T2D cases and 596,424 controls of European ancestry. We identify 139 common and 4 rare variants associated with T2D, 42 of which (39 common and 3 rare variants) are independent of the known variants. Integration of the gene expression data from blood (n = 14,115 and 2765) with the GWAS results identifies 33 putative functional genes for T2D, 3 of which were targeted by approved drugs. A further integration of DNA methylation (n = 1980) and epigenomic annotation data highlight 3 genes (CAMK1D, TP53INP1, and ATP5G1) with plausible regulatory mechanisms, whereby a genetic variant exerts an effect on T2D through epigenetic regulation of gene expression. Our study uncovers additional loci, proposes putative genetic regulatory mechanisms for T2D, and provides evidence of purifying selection for T2D-associated variants

Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus

: Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success

Gene-based analysis of regulatory variants identifies 4 putative novel asthma risk genes related to nucleotide synthesis and signaling

Background Hundreds of genetic variants are thought to contribute to variation in asthma risk by modulating gene expression. Methods that increase the power of genome-wide association studies (GWASs) to identify risk-associated variants are needed. Objective We sought to develop a method that aggregates the evidence for association with disease risk across expression quantitative trait loci (eQTLs) of a gene and use this approach to identify asthma risk genes. Methods We developed a gene-based test and software package called EUGENE that (1) is applicable to GWAS summary statistics; (2) considers both cis- and trans-eQTLs; (3) incorporates eQTLs identified in different tissues; and (4) uses simulations to account for multiple testing. We applied this approach to 2 published asthma GWASs (combined n\ua0=\ua046,044) and used mouse studies to provide initial functional insights into 2 genes with novel genetic associations. Results We tested the association between asthma and 17,190 genes that were found to have cis- and/or trans-eQTLs across 16 published eQTL studies. At an empirical FDR of 5%, 48 genes were associated with asthma risk. Of these, for 37, the association was driven by eQTLs located in established risk loci for allergic disease, including 6 genes not previously implicated in disease cause (eg, LIMS1, TINF2, and SAFB). The remaining 11 significant genes represent potential novel genetic associations with asthma. The association with 4 of these replicated in an independent GWAS: B4GALT3, USMG5, P2RY13, and P2RY14, which are genes involved in nucleotide synthesis or nucleotide-dependent cell activation. In mouse studies, P2ry13 and P2ry14—purinergic receptors activated by adenosine 5-diphosphate and UDP-sugars, respectively—were upregulated after allergen challenge, notably in airway epithelial cells, eosinophils, and neutrophils. Intranasal exposure with receptor agonists induced the release of IL-33 and subsequent eosinophil infiltration into the lungs. Conclusion We identified novel associations between asthma and eQTLs for 4 genes related to nucleotide synthesis/signaling and demonstrated the power of gene-based analyses of GWASs

White matter disturbances in major depressive disorder : a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group

Altres ajuts: The ENIGMA-Major Depressive Disorder working group gratefully acknowledges support from the NIH Big Data to Knowledge (BD2K) award (U54 EB020403 to PMT) and NIH grant R01 MH116147 (PMT). LS is supported by an NHMRC MRFF Career Development Fellowship (APP1140764). We wish to acknowledge the patients and control subjects that have particiaped int the study. We thank Rosa Schirmer, Elke Schreiter, Reinhold Borschke and Ines Eidner for image acquisition and data preparation, and Anna Oliynyk for quality checks. We thank Dorothee P. Auer and F. Holsboer for initiation of the RUD study. We wish to acknowledge the patients and control subjects that have particiaped int the study. We thank Rosa Schirmer, Elke Schreiter, Reinhold Borschke and Ines Eidner for image acquisition and data preparation, and Anna Oliynyk for quality checks. We thank Dorothee P. Auer and F. Holsboer for initiation of the RUD study. NESDA: The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-Mw, grant number 10-000-1002) and is supported by participating universities (VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen) and mental health care organizations, see www.nesda.nl. M-JvT was supported by a VENI grant (NWO grant number 016.156.077). UCSF: This work was supported by the Brain and Behavior Research Foundation (formerly NARSAD) to TTY; the National Institute of Mental Health (R01MH085734 to TTY; K01MH117442 to TCH) and by the American Foundation for Suicide Prevention (PDF-1-064-13) to TCH. Stanford: This work was supported by NIMH Grants R01MH59259 and R37101495 to IHG. MS is partially supported by an award funded by the Phyllis and Jerome Lyle Rappaport Foundation. Muenster: This work was funded by the German Research Foundation (SFB-TRR58, Projects C09 and Z02 to UD) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/012/17 to UD). Marburg: This work was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 to UD; KI 588/ 14-1, KI 588/14-2 to TK; KR 3822/7-1, KR 3822/7-2 to AK; JA 1890/ 7-1, JA 1890/7-2 to AJ). IMH-MDD: This work was supported by the National Healthcare Group Research Grant (SIG/15012) awarded to KS. Barcelona: This study was funded by two grants of the Fondo de Investigación Sanitaria from the Instituto de Salud Carlos III, by the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). The author is funded through 'Miguel Servet' research contract (CP16-0020), co-financed by the European Regional Development Fund (ERDF) (2016-2019). QTIM: We thank the twins and singleton siblings who gave generously of their time to participate in the QTIM study. We also thank the many research assistants, radiographers, and IT support staff for data acquisition and DNA sample preparation. This study was funded by White matter disturbances in major depressive disorder: a coordinated analysis across 20 international. . . 1521 the National Institute of Child Health & Human Development (RO1 HD050735); National Institute of Biomedical Imaging and Bioengineering (Award 1U54EB020403-01, Subaward 56929223); National Health and Medical Research Council, Australia (Project Grants 496682, 1009064). NIH ENIGMA-BD2K U54 EB020403 (Thompson); R01 MH117601 (Jahanshad/Schmaal). Magdeburg: M.L. and M.W. are funded by SFB 779. Bipolar Family Study: This study has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013). This paper reflects only the author's views and the European Union is not liable for any use that may be made of the information contained therein. This work was also supported by a Wellcome Trust Strategic Award (104036/Z/14/Z). Minnesota Adolescent Depression Study: The study was funded by the National Institute of Mental Health (K23MH090421), the National Alliance for Research on Schizophrenia and Depression, the University of Minnesota Graduate School, the Minnesota Medical Foundation, and the Biotechnology Research Center (P41 RR008079 to the Center for Magnetic Resonance Research), University of Minnesota, and the Deborah E. Powell Center for Women's Health Seed Grant, University of Minnesota. Dublin: This study was supported by Science Foundation Ireland through a Stokes Professorhip grant to TF. MPIP: The MPIP Sample comprises patients included in the Recurrent Unipolar Depression (RUD) Case-Control study at the clinic of the Max Planck Institute of Psychiatry, Munich, German. The RUD study was supported by GlaxoSmithKline.Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen's d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen's d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD

JWST’s PEARLS: A new lens model for ACT-CL J0102−4915, “El Gordo,” and the first red supergiant star at cosmological distances discovered by JWST

The first James Webb Space Telescope (JWST) data on the massive colliding cluster El Gordo allow for 23 known families of multiply lensed images to be confirmed and for eight new members of these families to be identified. Based on these families, which have been confirmed spectroscopically by MUSE, we derived an initial lens model. This model guided the identification of 37 additional families of multiply lensed galaxies, among which 28 are entirely new systems, and nine were previously known. The initial lens model determined geometric redshifts for the 37 new systems. The geometric redshifts agree reasonably well with spectroscopic or photometric redshifts when those are available. The geometric redshifts enable two additional models that include all 60 families of multiply lensed galaxies spanning a redshift range 2  0.8 and has an estimated virial mass close the maximum mass allowed by standard cosmological models. The JWST images also reveal the presence of small-mass perturbers that produce small lensing distortions. The smallest of these is consistent with being a dwarf galaxy at z = 0.87 and has an estimated mass of 3.8 × 109 M⊙, making it the smallest substructure found at z > 0.5. The JWST images also show several candidate caustic-crossing events. One of them is detected at high significance at the expected position of the critical curve and is likely a red supergiant star at z = 2.1878. This would be the first red supergiant found at cosmological distances. The cluster lensing should magnify background objects at z > 6, making more of them visible than in blank fields of a similar size, but there appears to be a deficiency of such objects.J.M.D. acknowledges the support of project PGC2018-101814-B-100 (MCIU/AEI/MINECO/FEDER, UE) Ministerio de Ciencia, Investigación y Universidades. This project was funded by the Agencia Estatal de Investigación, Unidad de Excelencia María de Maeztu, ref. MDM-2017-0765. AZ and AKM acknowledge support by Grant No. 2020750 from the United States-Israel Binational Science Foundation (BSF) and Grant No. 2109066 from the United States National Science Foundation (NSF), and by the Ministry of Science & Technology, Israel. RAW, SHC, and RAJ acknowledge support from NASA JWST Interdisciplinary Scientist grants NAG5-12460, NNX14AN10G and 80NSSC18K0200 from GSFC. EZ acknowledges funding from the Swedish National Space Agency. Work by CJC acknowledges support from the European Research Council (ERC) Advanced Investigator Grant EPOCHS (788113). LD acknowledges the research grant support from the Alfred P. Sloan Foundation (Award Number FG-2021-16495). BLF thanks the Berkeley Center for Theoretical Physics for their hospitality during the writing of this paper. MAM acknowledges the support of a National Research Council of Canada Plaskett Fellowship, and the Australian Research Council Centre of Excellence for All Sky Astrophysics in 3 Dimensions (ASTRO 3D), through project number CE17010001. CNAW acknowledges funding from the JWST/NIRCam contract NASS-0215 to the University of Arizona. GBC acknowledges the Max Planck Society for financial support through the Max Planck Research Group for S. H. Suyu and the academic support from the German Centre for Cosmological Lensing.Peer reviewe