The effect of transmucosal 0.2mg/kg Midazolam premedication on dental anxiety, anaesthetic induction and psychological morbidity in children undergoing general anaesthesia for tooth extraction

<b>Background:</b> The project aims were to evaluate the benefit of transmucosal Midazolam 0.2mg/kg pre-medication on anxiety, induction behaviour and psychological morbidity in children undergoing general anaesthesia (GA) extractions. <b>Method:</b> 179 children aged 5-10 years (mean 6.53 years) participated in this randomised, double blind, placebo controlled trial. Ninety children had Midazolam placed in the buccal pouch. Dental anxiety was recorded pre operatively and 48 hours later using a child reported MCDAS-FIS scale. Behaviour at anaesthetic induction was recorded and psychological morbidity was scored by the parent using the Rutter Scale pre-operatively and again one-week later. Subsequent dental attendance was recorded at one, three and six months after GA. <b>Results:</b> Whilst levels of mental anxiety did not reduce overall, the most anxious patients demonstrated a reduction in anxiety after receiving midazolam premedicationmay (p=0.01). Neither induction behaviour nor psychological morbidity improved. Irrespective of group, parents reported less hyperactive (p= 0.002) and more prosocial behaviour (p=0.002) after the procedure:;, older children improved most (p=0.048), Post GA Dental attendance was poor and unrelated to after the procedure and unaffected by premedication. <b>Conclusion:</b> 0.2mg/kg buccal Midazolam provided some evidence for reducing anxiety in the most dentally anxious patients. However, induction behaviour, psychological morbidity and subsequent dental attendance were not found to alter between the premedication groups

Influence of the Environment on Participation in Social Roles for Young Adults with Down Syndrome

Background: The concept of disability is now understood as a result of the interaction between the individual, features related to impairment, and the physical and social environment. It is important to understand these environmental influences and how they affect social participation. The purpose of this study is to describe the social participation of young adults with Down syndrome and examine its relationship with the physical and social environment. Methods: Families ascertained from the Down syndrome ‘Needs Opinion Wishes’ database completed questionnaires during 2011. The questionnaires contained two parts, young person characteristics and family characteristics. Young adults’ social participation was measured using the Assessment of Life Habits (LIFE-H) and the influences of environmental factors were measured by the Measure of the Quality of the Environment (MQE). The analysis involved descriptive statistics and linear and logistic regression. Results: Overall, participation in daily activities was higher (mean 6.45) than in social roles (mean 5.17) (range 0 to 9). When the physical and/or social environment was reported as a facilitator, compared to being no influence or a barrier, participation in social roles was greater (coef 0.89, 95%CI 0.28, 1.52, coef 0.83, 95%CI 0.17, 1.49, respectively). The relationships between participation and both the physical (coef 0.60, 95% CI -0.40, 1.24) and social (coef 0.20, 95%CI -0.47, 0.87) environments were reduced when age, gender, behavior and functioning in ADL were taken into account. Conclusion: We found that young adults’ participation in social roles was influenced more by the physical environment than by the social environment, providing a potentially modifiable avenue for intervention

Cell-based screen for altered nuclear phenotypes reveals senescence progression in polyploid cells after Aurora kinase B inhibition.

Cellular senescence is a widespread stress response and is widely considered to be an alternative cancer therapeutic goal. Unlike apoptosis, senescence is composed of a diverse set of subphenotypes, depending on which of its associated effector programs are engaged. Here we establish a simple and sensitive cell-based prosenescence screen with detailed validation assays. We characterize the screen using a focused tool compound kinase inhibitor library. We identify a series of compounds that induce different types of senescence, including a unique phenotype associated with irregularly shaped nuclei and the progressive accumulation of G1 tetraploidy in human diploid fibroblasts. Downstream analyses show that all of the compounds that induce tetraploid senescence inhibit Aurora kinase B (AURKB). AURKB is the catalytic component of the chromosome passenger complex, which is involved in correct chromosome alignment and segregation, the spindle assembly checkpoint, and cytokinesis. Although aberrant mitosis and senescence have been linked, a specific characterization of AURKB in the context of senescence is still required. This proof-of-principle study suggests that our protocol is capable of amplifying tetraploid senescence, which can be observed in only a small population of oncogenic RAS-induced senescence, and provides additional justification for AURKB as a cancer therapeutic target.This work was supported by the University of Cambridge, Cancer Research UK, Hutchison Whampoa; Cancer Research UK grants A6691 and A9892 (M.N., N.K., C.J.T., D.C.B., C.J.C., L.S.G, and M.S.); a fellowship from the Uehara Memorial Foundation (M.S.).This is the author accepted manuscript. The final version is available from the American Society for Cell Biology via http://dx.doi.org/10.1091/mbc.E15-01-000

Palaeoclimatic events, dispersal and migratory losses along the Afro-European axis as drivers of biogeographic distribution in Sylvia warblers

<p>Abstract</p> <p>Background</p> <p>The Old World warbler genus <it>Sylvia </it>has been used extensively as a model system in a variety of ecological, genetic, and morphological studies. The genus is comprised of about 25 species, and 70% of these species have distributions at or near the Mediterranean Sea. This distribution pattern suggests a possible role for the Messinian Salinity Crisis (from 5.96-5.33 Ma) as a driving force in lineage diversification. Other species distributions suggest that Late Miocene to Pliocene Afro-tropical forest dynamics have also been important in the evolution of <it>Sylvia </it>lineages. Using a molecular phylogenetic hypothesis and other methods, we seek to develop a biogeographic hypothesis for <it>Sylvia </it>and to explicitly assess the roles of these climate-driven events.</p> <p>Results</p> <p>We present the first strongly supported molecular phylogeny for <it>Sylvia</it>. With one exception, species fall into one of three strongly supported clades: one small clade of species distributed mainly in Africa and Europe, one large clade of species distributed mainly in Africa and Asia, and another large clade with primarily a circum-Mediterranean distribution. Asia is reconstructed as the ancestral area for <it>Sylvia</it>. Long-distance migration is reconstructed as the ancestral character state for the genus, and sedentary behavior subsequently evolved seven times.</p> <p>Conclusion</p> <p>Molecular clock calibration suggests that <it>Sylvia </it>arose in the early Miocene and diverged into three main clades by 12.6 Ma. Divergence estimates indicate that the Messinian Salinity Crisis had a minor impact on <it>Sylvia</it>. Instead, over-water dispersals, repeated loss of long-distance migration, and palaeo-climatic events in Africa played primary roles in <it>Sylvia </it>divergence and distribution.</p

Global urban environmental change drives adaptation in white clover.

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale