Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients

Background Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive. Methods We report on visuospatial cognition in two individuals with contrasting partial deletions in the WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted. Results Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JB’s atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion. Conclusions Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed

A computational study on altered theta-gamma coupling during learning and phase coding

There is considerable interest in the role of coupling between theta and gamma oscillations in the brain in the context of learning and memory. Here we have used a neural network model which is capable of producing coupling of theta phase to gamma amplitude firstly to explore its ability to reproduce reported learning changes and secondly to memory-span and phase coding effects. The spiking neural network incorporates two kinetically different GABAA receptor-mediated currents to generate both theta and gamma rhythms and we have found that by selective alteration of both NMDA receptors and GABAA,slow receptors it can reproduce learning-related changes in the strength of coupling between theta and gamma either with or without coincident changes in theta amplitude. When the model was used to explore the relationship between theta and gamma oscillations, working memory capacity and phase coding it showed that the potential storage capacity of short term memories, in terms of nested gamma-subcycles, coincides with the maximal theta power. Increasing theta power is also related to the precision of theta phase which functions as a potential timing clock for neuronal firing in the cortex or hippocampus

Diffuse Gamma Rays: Galactic and Extragalactic Diffuse Emission

"Diffuse" gamma rays consist of several components: truly diffuse emission from the interstellar medium, the extragalactic background, whose origin is not firmly established yet, and the contribution from unresolved and faint Galactic point sources. One approach to unravel these components is to study the diffuse emission from the interstellar medium, which traces the interactions of high energy particles with interstellar gas and radiation fields. Because of its origin such emission is potentially able to reveal much about the sources and propagation of cosmic rays. The extragalactic background, if reliably determined, can be used in cosmological and blazar studies. Studying the derived "average" spectrum of faint Galactic sources may be able to give a clue to the nature of the emitting objects.Comment: 32 pages, 28 figures, kapproc.cls. Chapter to the book "Cosmic Gamma-Ray Sources," to be published by Kluwer ASSL Series, Edited by K. S. Cheng and G. E. Romero. More details can be found at http://www.gamma.mpe-garching.mpg.de/~aws/aws.htm

Why are we not flooded by involuntary thoughts about the past and future? Testing the cognitive inhibition dependency hypothesis

© The Author(s) 2018In everyday life, involuntary thoughts about future plans and events occur as often as involuntary thoughts about the past. However, compared to involuntary autobiographical memories (IAMs), such episodic involuntary future thoughts (IFTs) have become a focus of study only recently. The aim of the present investigation was to examine why we are not constantly flooded by IFTs and IAMs given that they are often triggered by incidental cues while performing undemanding activities. One possibility is that activated thoughts are suppressed by the inhibitory control mechanism, and therefore depleting inhibitory control should enhance the frequency of both IFTs and IAMs. We report an experiment with a between-subjects design, in which participants in the depleted inhibition condition performed a 60-min high-conflict Stroop task before completing a laboratory vigilance task measuring the frequency of IFTs and IAMs. Participants in the intact inhibition condition performed a version of the Stroop task that did not deplete inhibitory control. To control for physical and mental fatigue resulting from performing the 60-min Stroop tasks in experimental conditions, participants in the control condition completed only the vigilance task. Contrary to predictions, the number of IFTs and IAMs reported during the vigilance task, using the probe-caught method, did not differ across conditions. However, manipulation checks showed that participants’ inhibitory resources were reduced in the depleted inhibition condition, and participants were more tired in the experimental than in the control conditions. These initial findings suggest that neither inhibitory control nor physical and mental fatigue affect the frequency of IFTs and IAMs.Peer reviewedFinal Published versio

Polysomnographic evaluation of obstructive sleep apnea syndrome in children, before and after adenotonsillectomy

Introduction: In the last years the Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS) has much interested because it has not been completed established. Many criteria defined for OSAS in adults and children are different. We know that patient's clinical story is not sufficient for the diagnosis of OSAHS. In childhood, the most common cause of OSAHS is adenotonsillar hypertrophy, clinically characterised by snoring, apnea episodes, restless sleep, mouth breathing and daytime somnolence. Aim: This study has the purpose of comprovating, by objective way, the OSAS improving in children who underwent adenotonsillectomy. Study design: Clinical prospective. Material and method: For that, 23 children, among 2 and 13 years old, with adenotonsillar hypertrophy, were analysed. After endoscopy and polysomnography, they were submitted to adenotonsillectomy. Results: The polysomnography was repeated 2 months after surgery. The polysomnographic findings were compared through statistic study. Conclusion: All the patients had an important improve after adenotonsillectomy. Only two children (8.69%) persisted with light OSAHS, but they had moderate and important OSAHS before. We concluded that OSAHS is a precise indication for adenotonsillectomy in children.Introdução: Nos últimos anos a Síndrome da Apnéia/Hipopnéia Obstrutiva do Sono (SAHOS) tem despertado muito interesse por tratar-se de uma condição não totalmente estabelecida. Muitos critérios usados para definir SAHOS em adultos e crianças são diferentes entre si. Em 1995 Sabe-se que a história clínica do paciente não era suficiente para estabelecer o diagnóstico de SAHOS. Na criança a causa mais comum de SAOS é a hipertrofia adenoamigdaliana, normalmente caracterizada clinicamente pela presença de roncos noturnos, episódios de apnéia, sono agitado, respiração bucal e hipersonolência diurna4. Objetivo: Este estudo tem o intuito de comprovar de forma objetiva a melhora da SAHOS em crianças submetidas a adenoamigdalectomia. Forma de estudo: Clínico prospectivo. Material e método: Para isso, foram avaliadas 23 crianças entre 2 e 13 anos (1999-2001), com hipertrofia adenoamigdaliana, que após nasofibroscopia e polissonografia foram submetidas a cirurgia de adenoamigdalectomia. A polissonografia foi repetida após 2 meses de pós-operatório. Foi então realizado estudo estatístico dos dados obtidos na polissonografia pré- e pós-operatória. Resultado: Observamos que todos os pacientes tiveram melhora importante após adenoamigdalectomia. Duas crianças (8,69%) persistiram com SAOS leve, que anteriormente eram de grau moderado e acentuado. Conclusão: Concluímos assim que SAOS é uma indicação precisa para cirurgia de adenoamigdalectomia em crianças.UNIFESP-EPM Disciplina de Otorrinolaringologia PediátricaUNIFESP, EPM, Disciplina de Otorrinolaringologia PediátricaSciEL

Horizontally acquired glycosyltransferase operons drive salmonellae lipopolysaccharide diversity.

The immunodominant lipopolysaccharide is a key antigenic factor for Gram-negative pathogens such as salmonellae where it plays key roles in host adaptation, virulence, immune evasion, and persistence. Variation in the lipopolysaccharide is also the major differentiating factor that is used to classify Salmonella into over 2600 serovars as part of the Kaufmann-White scheme. While lipopolysaccharide diversity is generally associated with sequence variation in the lipopolysaccharide biosynthesis operon, extraneous genetic factors such as those encoded by the glucosyltransferase (gtr) operons provide further structural heterogeneity by adding additional sugars onto the O-antigen component of the lipopolysaccharide. Here we identify and examine the O-antigen modifying glucosyltransferase genes from the genomes of Salmonella enterica and Salmonella bongori serovars. We show that Salmonella generally carries between 1 and 4 gtr operons that we have classified into 10 families on the basis of gtrC sequence with apparent O-antigen modification detected for five of these families. The gtr operons localize to bacteriophage-associated genomic regions and exhibit a dynamic evolutionary history driven by recombination and gene shuffling events leading to new gene combinations. Furthermore, evidence of Dam- and OxyR-dependent phase variation of gtr gene expression was identified within eight gtr families. Thus, as O-antigen modification generates significant intra- and inter-strain phenotypic diversity, gtr-mediated modification is fundamental in assessing Salmonella strain variability. This will inform appropriate vaccine and diagnostic approaches, in addition to contributing to our understanding of host-pathogen interactions

Flows of granular material in two-dimensional channels

Secondary cone-type crushing machines are an important part of the aggregate production process. These devices process roughly crushed material into aggregate of greater consistency and homogeneity. We apply a continuum model for granular materials (`A Constitutive Law For Dense Granular Flows', Nature 441, p727-730, 2006) to flows of granular material in representative two-dimensional channels, applying a cyclic applied crushing stress in lieu of a moving boundary. Using finite element methods we solve a sequence of quasi-steady fluid problems within the framework of a pressure dependent particle size problem in time. Upon approximating output quantity and particle size we adjust the frequency and strength of the crushing stroke to assess their impact on the output

HABIT-an early phase study to explore an oral health intervention delivered by health visitors to parents with young children aged 9-12 months: study protocol.

Background: Parental supervised brushing (PSB) when initiated in infancy can lead to long-term protective home-based oral health habits thereby reducing the risk of dental caries. However, PSB is a complex behaviour with many barriers reported by parents hindering its effective implementation. Within the UK, oral health advice is delivered universally to parents by health visitors and their wider teams when children are aged between 9 and 12 months. Nevertheless, there is no standardised intervention or training upon which health visitors can base this advice, and they often lack the specialised knowledge needed to help parents overcome barriers to performing PSB and limiting sugary foods and drinks.Working with health visitors and parents of children aged 9-24 months, we have co-designed oral health training and resources (Health Visitors delivering Advice in Britain on Infant Toothbrushing (HABIT) intervention) to be used by health visitors and their wider teams when providing parents of children aged 9-12 months with oral health advice.The aim of the study is to explore the acceptability of the HABIT intervention to parents and health visitors, to examine the mechanism of action and develop suitable objective measures of PSB. Methods/design: Six health visitors working in a deprived city in the UK will be provided with training on how to use the HABIT intervention. Health visitors will then each deliver the intervention to five parents of children aged 9-12 months. The research team will collect measures of PSB and dietary behaviours before and at 2 weeks and 3 months after the HABIT intervention. Acceptability of the HABIT intervention to health visitors will be explored through semi-structured diaries completed after each visit and a focus group discussion after delivery to all parents. Acceptability of the HABIT intervention and mechanism of action will be explored briefly during each home visit with parents and in greater details in 20-25 qualitative interviews after the completion of data collection. The utility of three objective measures of PSB will be compared with each other and with parental-self reports. Discussion: This study will provide essential information to inform the design of a definitive cluster randomised controlled trial. Trial registration: There is no database for early phase studies such as ours

Why Robots Should Be Social: Enhancing Machine Learning through Social Human-Robot Interaction.

Social learning is a powerful method for cultural propagation of knowledge and skills relying on a complex interplay of learning strategies, social ecology and the human propensity for both learning and tutoring. Social learning has the potential to be an equally potent learning strategy for artificial systems and robots in specific. However, given the complexity and unstructured nature of social learning, implementing social machine learning proves to be a challenging problem. We study one particular aspect of social machine learning: that of offering social cues during the learning interaction. Specifically, we study whether people are sensitive to social cues offered by a learning robot, in a similar way to children's social bids for tutoring. We use a child-like social robot and a task in which the robot has to learn the meaning of words. For this a simple turn-based interaction is used, based on language games. Two conditions are tested: one in which the robot uses social means to invite a human teacher to provide information based on what the robot requires to fill gaps in its knowledge (i.e. expression of a learning preference); the other in which the robot does not provide social cues to communicate a learning preference. We observe that conveying a learning preference through the use of social cues results in better and faster learning by the robot. People also seem to form a "mental model" of the robot, tailoring the tutoring to the robot's performance as opposed to using simply random teaching. In addition, the social learning shows a clear gender effect with female participants being responsive to the robot's bids, while male teachers appear to be less receptive. This work shows how additional social cues in social machine learning can result in people offering better quality learning input to artificial systems, resulting in improved learning performance

Cardiac T1 Mapping and Extracellular Volume (ECV) in clinical practice: a comprehensive review.

Cardiovascular Magnetic Resonance is increasingly used to differentiate the aetiology of cardiomyopathies. Late Gadolinium Enhancement (LGE) is the reference standard for non-invasive imaging of myocardial scar and focal fibrosis and is valuable in the differential diagnosis of ischaemic versus non-ischaemic cardiomyopathy. Diffuse fibrosis may go undetected on LGE imaging. Tissue characterisation with parametric mapping methods has the potential to detect and quantify both focal and diffuse alterations in myocardial structure not assessable by LGE. Native and post-contrast T1 mapping in particular has shown promise as a novel biomarker to support diagnostic, therapeutic and prognostic decision making in ischaemic and non-ischaemic cardiomyopathies as well as in patients with acute chest pain syndromes. Furthermore, changes in the myocardium over time may be assessed longitudinally with this non-invasive tissue characterisation method