Evaluation of the ADOS Revised Algorithm: The Applicability in 558 Dutch Children and Adolescents

The revised ADOS algorithms, proposed by Gotham et al. (J Autism Dev Disord 37:613–627, 2007), were investigated in an independent sample of 558 Dutch children (modules 1, 2 and 3). The revised algorithms lead to better balanced sensitivity and specificity for modules 2 and 3, without losing efficiency of the classification. Including the restricted repetitive behaviour domain in the algorithm contributes to a clinical ASD classification in modules 2 and 3. For module 1, the results indicate less improvement, probably due to the low-functioning population. In most groups, the advantages of the revised algorithms are achieved without losing the strength of the original algorithm

IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes.

GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach

Naphthenic acid fraction compounds, produced by the extraction of bitumen from oil sands, alter survival and behaviour of juvenile yellow perch (Perca flavescens)

We evaluated whether naphthenic acid fraction compounds (NAFCs) extracted from oil sand tailings adversely affect fish survival and behaviour. Following a before–after-control-impact design, we housed wild-caught juvenile yellow perch (Perca flavescens) in outdoor mesocosms to assess survival and behaviour under baseline conditions, then exposed fish to one of three treatments: negative control, 2 mg/L NAFC, or 15 mg/L NAFC. We performed behavioural assays (no-stimulus activity, food stimulus, and predator stimulus using a model bird) and assessed a comprehensive suite of endpoints (equilibrium losses, activity, shoaling, burst swimming, freezing, and space use). We found that exposure to 15 mg/L NAFCs substantially reduced fish survival and impaired fish equilibrium in all three behavioural tests. Furthermore, exposure to NAFCs impaired anti-predator behaviour: while the activity of control fish increased by two-fold in response to a predator stimulus, fish exposed to 2 or 15 mg/L NAFC did not change their activity levels after stimulation. No significant changes were observed in other behavioural endpoints. Overall, our findings suggest that a week-long exposure to NAFCs at concentrations commonly found in tailings ponds, constructed wetlands, and other mining-impacted waters may affect multiple facets of fish behaviour that could ultimately lead to reduced fitness in fish populations

The super-soft source phase of the recurrent nova V3890 Sgr

Context. The 30-yr recurrent symbiotic nova V3890 Sgr exploded on 2019 August 28 and was observed with multiple X-ray telescopes. Swift and AstroSat monitoring revealed slowly declining hard X-ray emission from shocks between the nova ejecta and the stellar wind of the companion. Later, highly variable super-soft-source (SSS) emission was seen. An XMM-Newton observation during the SSS phase captured the high degree of X-ray variability in terms of a deep dip in the middle of the observation. Aims. This observation adds to the growing sample of diverse SSS spectra and allows spectral comparison of low- and high-state emission to identify the origin of variations and subsequent effects of such dips, all leading to new insights into how the nova ejecta evolve. Methods. Based on an initial visual inspection, quantitative modelling approaches were conceptualised to test hypotheses of interpretation. The light curve was analysed with a power spectrum analysis before and after the dip and with an eclipse model to test the hypothesis of occulting clumps as in U Sco. A phenomenological spectral model (SPEX) was used to fit the complex Reflection Grating Spectrometer (RGS) spectrum accounting for all known atomic physics. A blackbody source function was assumed, as in all atmosphere radiation transport models, while the complex radiation transport processes were not modelled. Instead, one or multiple absorbing layers were used to model the absorption lines and edges, taking into account all state-of-the-art knowledge of atomic physics. Results. In addition to the central deep dip, there is an initial rise of similar depth and shape, and, after the deep dip, there are smaller dips of ~10% amplitude, which might be periodic over 18.1-min. Our eclipse model of the dips yields clump sizes and orbital radii of 0.5–8 and 5–150 white dwarf radii, respectively. The simultaneous XMM-Newton UV light curve shows no significant variations beyond slow fading. The RGS spectrum contains both residual shock emission at short wavelengths and the SSS emission at longer wavelengths. The shock temperature has clearly decreased compared to an earlier Chandra observation (day 6). The dip spectrum is dominated by emission lines as in U Sco. The intensity of underlying blackbody-like emission is much lower with the blackbody normalisation yielding a similar radius to that of the brighter phases, while the lower bolometric luminosity is ascribed to lower Teff. This would be inconsistent with clump occultations unless Compton scattering of the continuum emission reduces the photon energies to mimic a lower effective temperature. However, systematic uncertainties are high. The absorption lines in the bright SSS spectrum are blueshifted by 870 ± 10 km s−1 before the dip and are slightly faster, 900 ± 10 km s−1, after the dip. The reproduction of the observed spectrum is astonishing, especially that only a single absorbing layer is necessary while three such layers are needed to reproduce the RGS spectrum of V2491 Cyg. The ejecta of V3890 Sgr are thus more homogeneous than many other SSS spectra indicate. Abundance determination is in principle possible but highly uncertain. Generally, solar abundances are found, except for N and possibly O, which are higher by an order of magnitude. Conclusions. High-amplitude variability of SSS emission can be explained in several ways without having to give up the concept of constant bolometric luminosity. Variations in the photospheric radius can expose deeper lying plasma that could pulse with 18.1 min and that would yield a higher outflow velocity. Also, clump occultations are consistent with the observations

Growth hormone supplementation and psychosocial functioning to adult height in Turner syndrome: A questionnaire study of participants in the Canadian randomized trial

Despite the long-held belief that growth hormone supplementation provides psychosocial benefits to patients with Turner syndrome (TS), this assumption has never been rigorously tested in a randomized control trial. As a sub-study of the Canadian growth-hormone trial, parent-, and patient-completed standardized questionnaires were used to compare 70 girls with TS who received injections (GH group) and 61 similarly followed untreated TS controls (C) on multiple facets of psychosocial functioning. Questionnaires were given (i) at baseline (session 1, mean age = 10.4 y), (ii) before estrogen therapy for puberty induction (session 2, mean age = 13.0 y), (iii) after 1 year of estrogen therapy (session 3, mean age = 14.4 y), and (iv) when growth stopped (session 4, mean age = 16.3 y). Groups were compared for multiple facets of psychosocial function within social, behavioral, self-esteem, and academic domains. Results were also correlated with indices of adult height. We found no global (i.e., across-session) group differences on any scales or subscales of the four domains. In both GH and C groups, age-related improvements were seen for social problems, externalizing behavior problems, and school functioning and age-related declines for social competence and social relations. Both parents and patients claimed GH received less teasing than C but C had more friends than GH. Results from analyses conducted within individual sessions showed that while GH at early sessions claimed to be more popular, more socially engaged, better adapted, and to have higher self-esteem than C, C was reported to be less anxious, depressed, and withdrawn than GH at adult height. The correlation analyses revealed different effects of adult height and height gain on outcome for the two groups. In GH, both height parameters were correlated with multiple parent- and/or self-reported indices from the four psychosocial domains, whereas in C, only adult height and two indices (viz., total self-concept and school functioning), were correlated. The observed modest gains in psychosocial functioning for patients with TS treated with GH highlight the need for alternative approaches to assist them in coping with the challenges of their condition

PRECISION: the Belgian molecular profiling program of metastatic cancer for clinical decision and treatment assignment.

PRECISION is an initiative from the Belgian Society of Medical Oncology (BSMO) in collaboration with several stakeholders, encompassing four programs that aim to boost genomic and clinical knowledge with the ultimate goal to offer patients with metastatic solid tumors molecularly guided treatments. The PRECISION 1 study has led to the creation of a clinico-genomic database. The Belgian Approach for Local Laboratory Extensive Tumor Testing (BALLETT) and GeNeo studies will increase the number of patients with advanced cancer that have comprehensive genotyping of their cancer. The PRECISION 2 project consists of investigator-initiated phase II studies aiming to provide access to a targeted drug for patients whose tumors harbor actionable mutations in case the matched drug is not available through reimbursement or clinical trials in Belgium

Isothermal Titration Calorimetry: Assisted Crystallization of RNA–Ligand Complexes

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