Persistent thinness and anorexia nervosa differ on a genomic level

Thinness and anorexia nervosa are both characterised by persistent low weight. Individuals with anorexia nervosa concurrently report distorted perceptions of their body and engage in weight-loss behaviours, whereas individuals with thinness often wish to gain weight. Both conditions are heritable and share genomics with BMI, but are not genetically correlated with each other. Based on their pattern of genetic associations with other traits, we explored differences between thinness and anorexia nervosa on a genomic level. In Part 1, using publicly available data, we compared genetic correlations of persistent thinness/anorexia nervosa with eleven psychiatric disorders. In Part 2, we identified individuals with adolescent persistent thinness in the Avon Longitudinal Study of Parents and Children (ALSPAC) by latent class growth analysis of measured BMI from 10 to 24 years (n = 6594) and evaluated associations with psychiatric and anthropometric polygenic scores. In Part 1, in contrast to the positive genetic correlations of anorexia nervosa with various psychiatric disorders, persistent thinness showed negative genetic correlations with attention deficit hyperactivity disorder (r gAN = 0.08 vs. r gPT = −0.30), alcohol dependence (r gAN = 0.07 vs. r gPT = −0.44), major depressive disorder (rgAN = 0.27 vs. rgPT = −0.18) and post-traumatic stress disorder (rgAN = 0.26 vs. rgPT = −0.20). In Part 2, individuals with adolescent persistent thinness in the ALSPAC had lower borderline personality disorder polygenic scores (OR = 0.77; Q = 0.01). Overall, results suggest that genetic variants associated with thinness are negatively associated with psychiatric disorders and therefore thinness may be differentiable from anorexia nervosa on a genomic level

Discovery of six new class II methanol maser transitions, including the unambiguous detection of three torsionally excited lines toward G 358.931-0.030

We present the unambiguous discovery of six new class II methanol maser transitions, three of which are torsionally excited (vt = 1). The newly discovered 6.18 GHz 17−2 → 18−3 E (vt = 1), 7.68 GHz 124 → 133 A− (vt = 0), 7.83 GHz 124 → 133 A+ (vt = 0), 20.9 GHz 101 → 112 A+ (vt = 1), 44.9 GHz 20 → 31 E (vt = 1), and 45.8 GHz 93 → 102 E (vt = 0) methanol masers were detected toward G 358.931-0.030, where the known 6.68 GHz maser has recently been reported to be undergoing a period flaring. The detection of the vt = 1 torsionally excited lines corroborates one of the missing puzzle pieces in class II maser pumping, but the intensity of the detected emission provides an additional challenge, especially in the case of the very highly excited 6.18 GHz line. Together with the newly detected vt = 0 lines, these observations provide significant new information that can be utilized to improve class II methanol maser modeling. We additionally present detections of 6.68, 19.9, 23.1, and 37.7 GHz class II masers, as well as 36.2 and 44.1 GHz class I methanol masers, and provide upper limits for the 38.3 and 38.5 GHz class II lines. Near simultaneous Australia Telescope Compact Array observations confirm that all 10 of the class II methanol maser detections are co-spatial to ∼0.2 arcsec, which is within the uncertainty of the observations. We find significant levels of linearly polarized emission in the 6.18, 6.67, 7.68, 7.83, 20.9, 37.7, 44.9, and 45.8 GHz transitions, and low levels of circular polarization in the 6.68, 37.7, and 45.8 GHz transitions

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD

Selling lottery products to minors: factors affecting retailer compliance

Illegal gambling by adolescent minors has become a major issue in many societies and lottery gambling is often considered a "gateway" to gambling more generally among this age group. The purpose of this study was to identify the influencing factors that affect retailer compliance concerning the selling of lottery products to minors. The research team received the original data (i) directly from the sales agents of the Austrian Lotteries after their responsible gambling training of the retailer in 2014/2015 (Round 1: n = 5032), (ii) directly from a third-party agency carrying out test purchases (i.e., "mystery shopping") in 2014 (Round 2: n = 1421), and (iii) retailers’ responses to their attitudes to youth protection issues (through direct interface with the research team) in 2015 (Round 3: n = 4516). The data from a total of 1036 participants who had taken part in all three rounds was analyzed in the present study. Results showed that in 13.1% of mystery shopping checks (n = 1421), lottery products were sold to a test purchaser under the age of 16 years. The analysis also showed that the older the test purchaser, the greater the likelihood that a lottery product was sold. Under-age lottery sales to girls were over three times more prevalent than sales to boys. Finally, the analysis showed that the higher the number of responsible gambling training sessions completed in the past and the more positive the attitude towards mystery shopping, the higher the compliance rate not to sell a lottery product to young mystery shoppers. Recommendations to increase compliance and raise the awareness among retailers are presented

Developmental Transcriptional Networks Are Required to Maintain Neuronal Subtype Identity in the Mature Nervous System

During neurogenesis, transcription factors combinatorially specify neuronal fates and then differentiate subtype identities by inducing subtype-specific gene expression profiles. But how is neuronal subtype identity maintained in mature neurons? Modeling this question in two Drosophila neuronal subtypes (Tv1 and Tv4), we test whether the subtype transcription factor networks that direct differentiation during development are required persistently for long-term maintenance of subtype identity. By conditional transcription factor knockdown in adult Tv neurons after normal development, we find that most transcription factors within the Tv1/Tv4 subtype transcription networks are indeed required to maintain Tv1/Tv4 subtype-specific gene expression in adults. Thus, gene expression profiles are not simply “locked-in,” but must be actively maintained by persistent developmental transcription factor networks. We also examined the cross-regulatory relationships between all transcription factors that persisted in adult Tv1/Tv4 neurons. We show that certain critical cross-regulatory relationships that had existed between these transcription factors during development were no longer present in the mature adult neuron. This points to key differences between developmental and maintenance transcriptional regulatory networks in individual neurons. Together, our results provide novel insight showing that the maintenance of subtype identity is an active process underpinned by persistently active, combinatorially-acting, developmental transcription factors. These findings have implications for understanding the maintenance of all long-lived cell types and the functional degeneration of neurons in the aging brain

Impact of organised programs on colorectal cancer screening

<p>Abstract</p> <p>Purpose</p> <p>Colorectal cancer (CRC) screening has been shown to decrease CRC mortality. Organised mass screening programs are being implemented in France. Its perception in the general population and by general practitioners is not well known.</p> <p>Methods</p> <p>Two nationwide observational telephone surveys were conducted in early 2005. First among a representative sample of subjects living in France and aged between 50 and 74 years that covered both geographical departments with and without implemented screening services. Second among General Practionners (Gps). Descriptive and multiple logistic regression was carried out.</p> <p>Results</p> <p>Twenty-five percent of the persons(N = 1509) reported having undergone at least one CRC screening, 18% of the 600 interviewed GPs reported recommending a screening test for CRC systematically to their patients aged 50–74 years. The odds ratio (OR) of having undergone a screening test using FOBT was 3.91 (95% CI: 2.49–6.16) for those living in organised departments (referent group living in departments without organised screening), almost twice as high as impact educational level (OR = 2.03; 95% CI: 1.19–3.47).</p> <p>Conclusion</p> <p>CRC screening is improved in geographical departments where it is organised by health authorities. In France, an organised screening programs decrease inequalities for CRC screening.</p

Adrenocorticotropic Hormone Suppresses Gonadotropin-Stimulated Estradiol Release from Zebrafish Ovarian Follicles

While stress is known to impact reproductive performance, the pathways involved are not entirely understood. Corticosteroid effects on the functioning of the hypothalamus-pituitary-gonadal axis are thought to be a key aspect of stress-mediated reproductive dysfunction. A vital component of the stress response is the pituitary secretion of adrenocorticotropic hormone (ACTH), which binds to the melanocortin 2 receptor (MC2R) in the adrenal glands and activates cortisol biosynthesis. We recently reported MC2R mRNA abundance in fish gonads leading to the hypothesis that ACTH may be directly involved in gonadal steroid modulation. Using zebrafish (Danio rerio) ovarian follicles, we tested the hypothesis that acute ACTH stimulation modulates cortisol and estradiol (E2) secretion. ACTH neither affected cortisol nor unstimulated E2 release from ovarian follicles. However, ACTH suppressed human chorionic gonadotropin (hCG)-stimulated E2 secretion in a dose-related manner, with a maximum decrease of 62% observed at 1 I.U. ACTH mL−1. This effect of ACTH on E2 release was not observed in the presence of either 8-bromo-cAMP or forskolin, suggesting that the mechanism(s) involved in steroid attenuation was upstream of adenylyl cyclase activation. Overall, our results suggest that a stress-induced rise in plasma ACTH levels may initiate a rapid down-regulation of acute stimulated E2 biosynthesis in the zebrafish ovary, underscoring a novel physiological role for this pituitary peptide in modulating reproductive activity

Computed tomography segmental calcium score (SCS) to predict stenosis severity of calcified coronary lesions

To estimate the probability of ≥50 % coronary stenoses based on computed tomography (CT) segmental calcium score (SCS) and clinical factors. The Institutional Review Board approved the study. A training sample of 201 patients underwent CT calcium scoring and conventional coronary angiography (CCA). All patients consented to undergo CT before CCA after being informed of the additional radiation dose. SCS and calcification morphology were assessed in individual coronary segments. We explored the predictive value of patient’s symptoms, clinical history, SCS and calcification morphology. We developed a prediction model in the training sample based on these variables then tested it in an independent test sample. The odds ratio (OR) for ≥50 % coronary stenosis was 1.8-fold greater (p = 0.006) in patients with typical chest pain, twofold (p = 0.014) greater in patients with acute coronary syndromes, twofold greater (p < 0.001) in patients with prior myocardial infarction. Spotty calcifications had an OR for ≥50 % stenosis 2.3-fold (p < 0.001) greater than the absence of calcifications, wide calcifications 2.7-fold (p < 0.001) greater, diffuse calcifications 4.6-fold (p < 0.001) greater. In middle segments, each unit of SCS had an OR 1.2-fold (p < 0.001) greater than in distal segments; in proximal segments the OR was 1.1-fold greater (p = 0.021). The ROC curve area of the prediction model was 0.795 (0.95 confidence interval 0.602–0.843). Validation in a test sample of 201 independent patients showed consistent diagnostic performance. In conjunction with calcification morphology, anatomical location, patient’s symptoms and clinical history, SCS can be helpful to estimate the probability of ≥50 % coronary stenosis