Human-chimpanzee differences in a FZD8 enhancer alter cell-cycle dynamics in the developing neocortex.

The human neocortex differs from that of other great apes in several notable regards, including altered cell cycle, prolonged corticogenesis, and increased size [1-5]. Although these evolutionary changes most likely contributed to the origin of distinctively human cognitive faculties, their genetic basis remains almost entirely unknown. Highly conserved non-coding regions showing rapid sequence changes along the human lineage are candidate loci for the development and evolution of uniquely human traits. Several studies have identified human-accelerated enhancers [6-14], but none have linked an expression difference to a specific organismal trait. Here we report the discovery of a human-accelerated regulatory enhancer (HARE5) of FZD8, a receptor of the Wnt pathway implicated in brain development and size [15, 16]. Using transgenic mice, we demonstrate dramatic differences in human and chimpanzee HARE5 activity, with human HARE5 driving early and robust expression at the onset of corticogenesis. Similar to HARE5 activity, FZD8 is expressed in neural progenitors of the developing neocortex [17-19]. Chromosome conformation capture assays reveal that HARE5 physically and specifically contacts the core Fzd8 promoter in the mouse embryonic neocortex. To assess the phenotypic consequences of HARE5 activity, we generated transgenic mice in which Fzd8 expression is under control of orthologous enhancers (Pt-HARE5::Fzd8 and Hs-HARE5::Fzd8). In comparison to Pt-HARE5::Fzd8, Hs-HARE5::Fzd8 mice showed marked acceleration of neural progenitor cell cycle and increased brain size. Changes in HARE5 function unique to humans thus alter the cell-cycle dynamics of a critical population of stem cells during corticogenesis and may underlie some distinctive anatomical features of the human brain

Revising acute care systems and processes to improve breastfeeding and maternal postnatal health: a pre and post intervention study in one English maternity unit

Background Most women in the UK give birth in a hospital labour ward, following which they are transferred to a postnatal ward and discharged home within 24 to 48 hours of the birth. Despite policy and guideline recommendations to support planned, effective postnatal care, national surveys of women’s views of maternity care have consistently found in-patient postnatal care, including support for breastfeeding, is poorly rated. Methods Using a Continuous Quality Improvement approach, routine antenatal, intrapartum and postnatal care systems and processes were revised to support implementation of evidence based postnatal practice. To identify if implementation of a multi-faceted QI intervention impacted on outcomes, data on breastfeeding initiation and duration, maternal health and women’s views of care, were collected in a pre and post intervention longitudinal survey. Primary outcomes included initiation, overall duration and duration of exclusive breastfeeding. Secondary outcomes included maternal morbidity, experiences and satisfaction with care. As most outcomes of interest were measured on a nominal scale, these were compared pre and post intervention using logistic regression. Results Data were obtained on 741/1160 (64%) women at 10 days post-birth and 616 (54%) at 3 months post-birth pre-intervention, and 725/1153 (63%) and 575 (50%) respectively postintervention. Post intervention there were statistically significant differences in the initiation (p = 0.050), duration of any breastfeeding (p = 0.020) and duration of exclusive breastfeeding to 10 days (p = 0.038) and duration of any breastfeeding to three months (p = 0.016). Post intervention, women were less likely to report physical morbidity within the first 10 days of birth, and were more positive about their in-patient care. Conclusions It is possible to improve outcomes of routine in-patient care within current resources through continuous quality improvement

Ancient hydrothermal seafloor deposits in Eridania basin on Mars

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. The file attached is the Published/publisher’s pdf version of the article

What is the impact of a national postgraduate medical specialist education reform on the daily clinical training 3.5 years after implementation? A questionnaire survey

<p>Abstract</p> <p>Background</p> <p>Many countries have recently reformed their postgraduate medical education (PGME). New pedagogic initiatives and blueprints have been introduced to improve quality and effectiveness of the education. Yet it is unknown whether these changes improved the daily clinical training. The purpose was to examine the impact of a national PGME reform on the daily clinical training practice.</p> <p>Methods</p> <p>The Danish reform included change of content and format of specialist education in line with outcome-based education using the CanMEDS framework. We performed a questionnaire survey among all hospital doctors in the North Denmark Region. The questionnaire included items on educational appraisal meetings, individual learning plans, incorporating training issues into work routines, supervision and feedback, and interpersonal acquaintance. Data were collected before start and 31/2 years later. Mean score values were compared, and response variables were analysed by multiple regression to explore the relation between the ratings and seniority, type of hospital, type of specialty, and effect of attendance to courses in learning and teaching among respondents.</p> <p>Results</p> <p>Response rates were 2105/2817 (75%) and 1888/3284 (58%), respectively. We found limited impact on clinical training practice and learning environment. Variances in ratings were hardly affected by type of hospital, whereas belonging to the laboratory specialities compared to other specialties was related to higher ratings concerning all aspects.</p> <p>Conclusions</p> <p>The impact on daily clinical training practice of a national PGME reform was limited after 31/2 years. Future initiatives must focus on changing the pedagogical competences of the doctors participating in daily clinical training and on implementation strategies for changing educational culture.</p

High-Throughput Isolation and Mapping of C. elegans Mutants Susceptible to Pathogen Infection

We present a novel strategy that uses high-throughput methods of isolating and mapping C. elegans mutants susceptible to pathogen infection. We show that C. elegans mutants that exhibit an enhanced pathogen accumulation (epa) phenotype can be rapidly identified and isolated using a sorting system that allows automation of the analysis, sorting, and dispensing of C. elegans by measuring fluorescent bacteria inside the animals. Furthermore, we validate the use of Amplifluor® as a new single nucleotide polymorphism (SNP) mapping technique in C. elegans. We show that a set of 9 SNPs allows the linkage of C. elegans mutants to a 5–8 megabase sub-chromosomal region

Language Structure Is Partly Determined by Social Structure

BACKGROUND: Languages differ greatly both in their syntactic and morphological systems and in the social environments in which they exist. We challenge the view that language grammars are unrelated to social environments in which they are learned and used. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a statistical analysis of >2,000 languages using a combination of demographic sources and the World Atlas of Language Structures--a database of structural language properties. We found strong relationships between linguistic factors related to morphological complexity, and demographic/socio-historical factors such as the number of language users, geographic spread, and degree of language contact. The analyses suggest that languages spoken by large groups have simpler inflectional morphology than languages spoken by smaller groups as measured on a variety of factors such as case systems and complexity of conjugations. Additionally, languages spoken by large groups are much more likely to use lexical strategies in place of inflectional morphology to encode evidentiality, negation, aspect, and possession. Our findings indicate that just as biological organisms are shaped by ecological niches, language structures appear to adapt to the environment (niche) in which they are being learned and used. As adults learn a language, features that are difficult for them to acquire, are less likely to be passed on to subsequent learners. Languages used for communication in large groups that include adult learners appear to have been subjected to such selection. Conversely, the morphological complexity common to languages used in small groups increases redundancy which may facilitate language learning by infants. CONCLUSIONS/SIGNIFICANCE: We hypothesize that language structures are subjected to different evolutionary pressures in different social environments. Just as biological organisms are shaped by ecological niches, language structures appear to adapt to the environment (niche) in which they are being learned and used. The proposed Linguistic Niche Hypothesis has implications for answering the broad question of why languages differ in the way they do and makes empirical predictions regarding language acquisition capacities of children versus adults

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

Evidence for an excess of B -> D(*) Tau Nu decays

Based on the full BaBar data sample, we report improved measurements of the ratios R(D(*)) = B(B -> D(*) Tau Nu)/B(B -> D(*) l Nu), where l is either e or mu. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D) = 0.440 +- 0.058 +- 0.042 and R(D*) = 0.332 +- 0.024 +- 0.018, which exceed the Standard Model expectations by 2.0 sigma and 2.7 sigma, respectively. Taken together, our results disagree with these expectations at the 3.4 sigma level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model. We also report the observation of the decay B -> D Tau Nu, with a significance of 6.8 sigma.Comment: Expanded section on systematics, text corrections, improved the format of Figure 2 and included the effect of the change of the Tau polarization due to the charged Higg