Paleogenomic Evidence for Multi-generational Mixing between Neolithic Farmers and Mesolithic Hunter-Gatherers in the Lower Danube Basin

The transition from hunting and gathering to farming involved profound cultural and technological changes. In Western and Central Europe, these changes occurred rapidly and synchronously after the arrival of early farmers of Anatolian origin [1-3], who largely replaced the local Mesolithic hunter-gatherers [1, 4-6]. Further east, in the Baltic region, the transition was gradual, with little or no genetic input from incoming farmers [7]. Here we use ancient DNA to investigate the relationship between hunter-gatherers and farmers in the Lower Danube basin, a geographically intermediate area that is characterized by a rapid Neolithic transition but also by the presence of archaeological evidence that points to cultural exchange, and thus possible admixture, between hunter-gatherers and farmers. We recovered four human paleogenomes (1.1× to 4.1× coverage) from Romania spanning a time transect between 8.8 thousand years ago (kya) and 5.4 kya and supplemented them with two Mesolithic genomes (1.7× and 5.3×) from Spain to provide further context on the genetic background of Mesolithic Europe. Our results show major Western hunter-gatherer (WHG) ancestry in a Romanian Eneolithic sample with a minor, but sizeable, contribution from Anatolian farmers, suggesting multiple admixture events between hunter-gatherers and farmers. Dietary stable-isotope analysis of this sample suggests a mixed terrestrial/aquatic diet. Our results provide support for complex interactions among hunter-gatherers and farmers in the Danube basin, demonstrating that in some regions, demic and cultural diffusion were not mutually exclusive, but merely the ends of a continuum for the process of Neolithization.This research was supported by a European Research Council (ERC) Starting Grant (ERC-2010-StG 263441) to R.P. G.G.-F. was also supported by MSC Individual Fellowship (NeoGenHeritage, grant no. 655478). E.R.J. was supported by a Herchel Smith Research Fellowship. M.H. and A.M. were supported by ERC consolidator grants 310763 GeneFlow and 647797 LocalAdaptation, respectively. V.S. was supported by the Gates Cambridge Trust. The work of C.L. was undertaken through the Partnerships in Priority Areas Program PN II, developed with the support of MEN-UEFISCDI (project no. PN-II-PTPCCA-2013-4-2302). A.G.-D. is supported by the research project BIOGEOS (CGL2014-57209-P) of the Spanish MINECO. The research of P.A., M.D.G., and L.D. on Los Canes is currently supported by the project CoChange (HAR2014-51830-P) of the Spanish State Plan for R+D+i (MINECO)

Evaluation of sleep, puberty and mental health in children with long-term melatonin treatment for chronic idiopathic childhood sleep onset insomnia

OBJECTIVES: To establish whether long-term use of melatonin influences pubertal development, sleep quality and mental health development in children as compared with the normal Dutch population of the same age. METHODS: This follow-up research study was conducted in children included in a previous melatonin dose-finding trial. Outcomes were measured using questionnaires (Strength and Difficulties Questionnaire (SDQ), Children's Sleep Habits Questionnaire (CSHQ) and Tanner Stages) adopted for Dutch children. Mean duration of therapy, persistence of effect, adverse events and (other) reasons leading to cessation of therapy were additional objectives of this study. RESULTS: Mean years of usage (n = 51) was 3.1 years (min 1.0 year, max 4.6 years), mean dose 2.69 mg (min 0.3 mg, max 10 mg). Mean SDQ score, mean CSHQ score and Tanner Stages standard deviation scores did not differ in a statistically significant way from published scores of the general Dutch population of the same age and sex. CONCLUSIONS: This follow-up study demonstrates that melatonin treatment in children can be sustained over a long period of time without substantial deviation of the development of children with respect to sleep quality, puberty development and mental health scores, as compared with the general Dutch population

Gaia Early Data Release 3: Gaia photometric science alerts

Context. Since July 2014, the Gaia mission has been engaged in a high-spatial-resolution, time-resolved, precise, accurate astrometric, and photometric survey of the entire sky. Aims. We present the Gaia Science Alerts project, which has been in operation since 1 June 2016. We describe the system which has been developed to enable the discovery and publication of transient photometric events as seen by Gaia. Methods. We outline the data handling, timings, and performances, and we describe the transient detection algorithms and filtering procedures needed to manage the high false alarm rate. We identify two classes of events: (1) sources which are new to Gaia and (2) Gaia sources which have undergone a significant brightening or fading. Validation of the Gaia transit astrometry and photometry was performed, followed by testing of the source environment to minimise contamination from Solar System objects, bright stars, and fainter near-neighbours. Results. We show that the Gaia Science Alerts project suffers from very low contamination, that is there are very few false-positives. We find that the external completeness for supernovae, CE = 0.46, is dominated by the Gaia scanning law and the requirement of detections from both fields-of-view. Where we have two or more scans the internal completeness is CI = 0.79 at 3 arcsec or larger from the centres of galaxies, but it drops closer in, especially within 1 arcsec. Conclusions. The per-transit photometry for Gaia transients is precise to 1% at G = 13, and 3% at G = 19. The per-transit astrometry is accurate to 55 mas when compared to Gaia DR2. The Gaia Science Alerts project is one of the most homogeneous and productive transient surveys in operation, and it is the only survey which covers the whole sky at high spatial resolution (subarcsecond), including the Galactic plane and bulge

Stress hormones and posttraumatic stress symptoms following paediatric critical illness: an exploratory sudy

In t his exploratory case - control study we investigated basal cortisol regulation in 5 - 16 year - old children, 3 - 6 months following PICU (paediatric intensive care) admi ssion . This was nested within a study of child psych ological and cognitive function; 47 children were assessed alongside 56 healthy controls. Saliva samples were collected three times per day (immediately after waking, waking +30 min, and waking +12h) over two consecutive weekdays. In addition, data on posttraumatic stress symptoms were ascertained from 33 PICU admitted children using the Impact of Events Scale - 8 (IES - 8) . Primary analysis revealed no significant differences in basal cortisol concentrations between PICU discharged children and healthy controls (p > 0.05). Secondary analysis in the PICU group identified a significant positive association between posttraumatic stress symptoms and evening (waking +12h) cortisol concentrations (p = 0.004). Howev er when subject to multivariate analysis , evening cortisol was a modest independent predictor of IES - 8 scores, relative to the presence of septic illness and poor pre - morbid health. We conclude that paediatric critical illness does not appear to result in marked perturbations to basal cortisol at 3 - 6 month following discharge. T here was evidence of a link between evening cortisol and symptoms of PTSD, but this was not a robust effect and requ ires further elucidation

Chronology of a Quina type mousterian site of Les Pradelles (Marillac-le-Franc, Charente)

This paper presents a chronological framework for the site of Les Pradelles (Marillac-le-Franc, Charente, France). In the East locus of the site, four meters of sediments preserve late Middle Paleolithic archaeological materials with Quina Mousterian lithics associated with abundant reindeer-dominated faunal remains. During the most recent excavations conducted by B. Maureille and A. Mann between 2001 et 2013, only two dates were obtained in this locus: one was a single burnt flint dated by thermoluminescence (TL) and the second, was a single speleothem located at the base of the sequence dated using uranium-series disequilibrium (U-Th). The top layers fell beyond the radiocarbon limit. Owing to the scarcity of datable material, only a relative chronology was proposed for the site (Maureille et al., 2008). As part of a multidisciplinary project that aims to define a reliable chronological framework for understanding the variability of Neandertal cultures in the SW France, we dated the sedimentary deposits of the Les Pradelles site using Optically Stimulated Luminescence (OSL) techniques. The results of these techniques applied on various materials (quartz and feldspars), as well as previously obtained radiometric datasets improve the chronostratigraphy of the site. They constrain the age of the Neandertal remains and the Quina occupations between the end of Marine Isotope Stage (MIS) 4 and during MIS 3, up to 50 ka BP

Articles Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study

Summary Background We report clinical safety and biochemical effi cacy from a dose-ranging study of intravenously administered AVI-4658 phosphorodiamidate morpholino oligomer (PMO) in patients with Duchenne muscular dystrophy

Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet 378

Summary Background We report clinical safety and biochemical effi cacy from a dose-ranging study of intravenously administered AVI-4658 phosphorodiamidate morpholino oligomer (PMO) in patients with Duchenne muscular dystrophy