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

Explaining efficient search for conjunctions of motion and form: Evidence from negative color effects

Dent, Humphreys, and Braithwaite (2011) showed substantial costs to search when a moving target shared its color with a group of ignored static distractors. The present study further explored the conditions under which such costs to performance occur. Experiment 1 tested whether the negative color-sharing effect was specific to cases in which search showed a highly serial pattern. The results showed that the negative color-sharing effect persisted in the case of a target defined as a conjunction of movement and form, even when search was highly efficient. In Experiment 2, the ease with which participants could find an odd-colored target amongst a moving group was examined. Participants searched for a moving target amongst moving and stationary distractors. In Experiment 2A, participants performed a highly serial search through a group of similarly shaped moving letters. Performance was much slower when the target shared its color with a set of ignored static distractors. The exact same displays were used in Experiment 2B; however, participants now responded "present" for targets that shared the color of the static distractors. The same targets that had previously been difficult to find were now found efficiently. The results are interpreted in a flexible framework for attentional control. Targets that are linked with irrelevant distractors by color tend to be ignored. However, this cost can be overridden by top-down control settings. © 2014 Psychonomic Society, Inc

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

Protocol for the saMS trial (supportive adjustment for multiple sclerosis): a randomized controlled trial comparing cognitive behavioral therapy to supportive listening for adjustment to multiple sclerosis

BackgroundMultiple Sclerosis (MS) is an incurable, chronic, potentially progressive and unpredictable disease of the central nervous system. The disease produces a range of unpleasant and debilitating symptoms, which can have a profound impact including disrupting activities of daily living, employment, income, relationships, social and leisure activities, and life goals. Adjusting to the illness is therefore particularly challenging. This trial tests the effectiveness of a cognitive behavioural intervention compared to supportive listening to assist adjustment in the early stages of MS.MethodsThis is a two arm randomized multi-centre parallel group controlled trial. 122 consenting participants who meet eligibility criteria will be randomly allocated to receive either Cognitive Behavioral Therapy or Supportive Listening. Eight one hour sessions of therapy (delivered over a period of 10 weeks) will be delivered by general nurses trained in both treatments. Self-report questionnaire data will be collected at baseline (0 weeks), mid-therapy (week 5 of therapy), post-therapy (15 weeks) and at six months (26 weeks) and twelve months (52 weeks) follow-up. Primary outcomes are distress and MS-related social and role impairment at twelve month follow-up. Analysis will also consider predictors and mechanisms of change during therapy. In-depth interviews to examine participants’ experiences of the interventions will be conducted with a purposively sampled sub-set of the trial participants. An economic analysis will also take place. DiscussionThis trial is distinctive in its aims in that it aids adjustment to MS in a broad sense. It is not a treatment specifically for depression. Use of nurses as therapists makes the interventions potentially viable in terms of being rolled out in the NHS. The trial benefits from incorporating patient input in the development and evaluation stages. The trial will provide important information about the efficacy, cost-effectiveness and acceptability of the interventions as well as mechanisms of psychosocial adjustment.Trial registrationCurrent Controlled Trials ISRCTN91377356<br/

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

"Do I really want to do this?" Longitudinal cohort study participants' perspectives on postal survey design: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Randomised controlled trials have investigated aspects of postal survey design yet cannot elaborate on reasons behind participants' decision making and survey behaviour. This paper reports participants' perspectives of the design of, and participation in, a longitudinal postal cohort survey. It describes strengths and weaknesses in study design from the perspectives of study participants and aims to contribute to the: 1) design of future cohort surveys and questionnaires generally and, 2) design of cohort surveys for people with musculoskeletal disorders (MSDs) specifically.</p> <p>Methods</p> <p>In-depth interviews explored the design of postal surveys previously completed by participants. Interviews used open ended questioning with a topic guide for prompts if areas of interest were not covered spontaneously. Thematic data analysis was undertaken based on the framework method. A second researcher verified all coding.</p> <p>Results</p> <p>Data from fourteen interviews were analysed within three main themes; participation, survey design and survey content. One of the main findings was the importance of clear communication aimed at the correct audience both when inviting potential participants to take part and within the survey itself. Providing enough information about the study, having a topic of interest and an explanation of likely benefits of the study were important when inviting people to participate. The neutrality of the survey and origination from a reputable source were both important; as was an explanation about why information was being collected within the survey itself. Study findings included participants' impressions when invited to take part, why they participated, the acceptability of follow-up of non-responders and why participants completed the follow-up postal survey. Also discussed were participants' first impression of the survey, its length, presentation and participants' views about specific questions within the survey.</p> <p>Conclusions</p> <p>Ideas generated in this study provide an insight into participants' decision making and survey behaviour and may enhance the acceptability of future surveys to potential participants. As well as clear communication, participants valued incentives and survey questions that were relevant to them. However, opinions varied as to the preferred format for responses with some advising more opportunity for open-ended feedback. We also found that some standard format questions can raise quandaries for individual participants.</p

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