Perceptual grouping and distance estimates in typical and atypical development: comparing performance across perception, drawing and construction tasks

Perceptual grouping is a pre-attentive process which serves to group local elements into global wholes, based on shared properties. One effect of perceptual grouping is to distort the ability to estimate the distance between two elements. In this study, biases in distance estimates, caused by four types of perceptual grouping, were measured across three tasks, a perception, a drawing and a construction task in both typical development (TD: Experiment 1) and in individuals with Williams syndrome (WS: Experiment 2). In Experiment 1, perceptual grouping distorted distance estimates across all three tasks. Interestingly, the effect of grouping by luminance was in the opposite direction to the effects of the remaining grouping types. We relate this to differences in the ability to inhibit perceptual grouping effects on distance estimates. Additive distorting influences were also observed in the drawing and the construction task, which are explained in terms of the points of reference employed in each task. Experiment 2 demonstrated that the above distortion effects are also observed in WS. Given the known deficit in the ability to use perceptual grouping in WS, this suggests a dissociation between the pre-attentive influence of and the attentive deployment of perceptual grouping in WS. The typical distortion in relation to drawing and construction points towards the presence of some typical location coding strategies in WS. The performance of the WS group differed from the TD participants on two counts. First, the pattern of overall distance estimates (averaged across interior and exterior distances) across the four perceptual grouping types, differed between groups. Second, the distorting influence of perceptual grouping was strongest for grouping by shape similarity in WS, which contrasts to a strength in grouping by proximity observed in the TD participants. (c) 2008 Elsevier Inc. All rights reserved.

Compulsive-Like Behaviors of Typical Development: A Question of Their Nature and Continuity with Obsessive-Compulsive Disorder

OBJECTIVE: To investigate compulsive-like behaviors (CLB) of typical development: how they relate to the obsessions and compulsions of obsessive-compulsive disorder (OCD); and the implication of their lingering past 6 years of age (i.e., past their normative, 2-to-5 year, drop). CONCLUSIONS: Findings suggest that normative CLB exist on a continuum (with regard to both symptomatology and functional difficulties) with clinical obsessions and compulsions. With normative repetitive behaviors predicting behavioral perseveration among typically developing individuals aged 6 to 17 years, the present study also suggests that, even in a non-clinical sample, some levels of CLB are maladaptive in middle childhood through adolescence. While studies to date have evaded investigation of high and low CLB in relation to OCD, this latter finding contributes to the growing emphasis upon continuity between typical and atypical development.

Avaliação assistida informatizada : indicadores do potencial cognitivo de crianças com deficiência

A identificação e a avaliação de crianças com desenvolvimento atípico configuram um processo muito importante para subsidiar as estratégias de ensino voltadas para a promoção do potencial de aprendizagem. O interesse em relação ao prognóstico de crianças com deficiência tem impulsionado o desenvolvimento de novas tecnologias e pesquisas relacionadas à avaliação, prevenção e intervenção. Nesse contexto, torna-se relevante verificar com instrumentos adequados indicadores linguísticos, cognitivos e comportamentais, para assim traçar metas a partir daquilo que as crianças podem aprender. Dessa forma, esta pesquisa teve por objetivo verificar se a avaliação assistida informatizada se apresenta como uma modalidade de diagnóstico mais prescritivo do desenvolvimento cognitivo, quando comparada à avaliação psicométrica, na aplicação em crianças com deficiência. Na modalidade assistida há ajuda do examinador para conduzir a criança a um melhor nível de desempenho cognitivo. Participaram 11 crianças que frequentam uma instituição de atendimento clínico, em saúde, para crianças com deficiência, na Grande Vitória. Na avaliação psicométrica foram utilizados a Escala de Maturidade Mental Colúmbia computadorizada – Colúmbiacomp e o Teste de Vocabulário por Imagens Peabody - TVIPcomp. Na avaliação assistida informatizada foram aplicadas três provas voltadas para as habilidades de classificação e raciocínio analógico: Exclusão de Objetos, Exclusão de Figuras Geométricas e Jogo de Analogia de Figuras, no ambiente informatizado SINDAPSI. Protocolos de registro de fatores afetivo-motivacionais e de operações cognitivas foram utilizados durante as tarefas assistidas. Na avaliação do comportamento, o Child Behavior Checklist – CBCL foi respondido pelas mães. Dados documentais e dos instrumentos foram submetidos à análise estatística descritiva para verificar o desempenho das crianças nas duas formas de avaliação informatizada (psicométrica e assistida). Nos testes psicométricos, 64% das crianças alcançaram índice “abaixo da média” no TVIPcomp, e 55% “médio-inferior” no Colúmbiacomp. Em relação ao perfil de desempenho cognitivo, na Prova de Exclusão de Objetos computadorizada 55% das crianças foram avaliadas como “não-mantenedoras”. Na Prova de Exclusão de Figuras Geométricas computadorizada 55% da amostra foi classificada no perfil “alto-escore”, e no Jogo de Analogias de Figuras computadorizado 45% apresentou o perfil “ganhador”. A amostra demonstrou níveis de dificuldade na realização dos testes,tanto na modalidade psicométrica quanto assistida. Contudo, o desempenho nos testes assistidos foi relativamente melhor, evidenciando que o grupo se beneficiou da mediação,implementada na fase de assistência, para melhorar as habilidades cognitivas. Além disso, a apresentação informatizada dos testes apresentou-se como fator motivador para a realização e persistência nas tarefas.

Aumento da Linguagem: Um estudo de caso

Objetivo: O autismo é uma perturbação global do desenvolvimento infantil que se prolonga por toda a vida e evolui com a idade. Carateriza-se pela presença de um desenvolvimento acentuadamente atípico na interação social e na comunicação, por um repertório de atividades e interesses marcadamente restritos, por dificuldades de flexibilidade de pensamento e de comportamento, que se exibem em comportamentos estereotipados e rígidos, associados a dificuldades na aceitação de alterações de rotinas. Dentro da grande variação possível na severidade do autismo, encontram-se crianças sem linguagem verbal e com dificuldades na comunicação por qualquer outra via, assim como se encontram crianças que apresentam linguagem verbal com um vocabulário restrito, repetitivo e não comunicativo. O objetivo principal deste trabalho é analisar e potenciar o desenvolvimento da linguagem, a aquisição de palavras e frases na criança autista, tendo em vista a generalização dos resultados. Para isso, foi realizado um estudo de caso de uma criança de 4 anos de idade com comportamentos que sugerem uma Perturbação Pervasiva do Desenvolvimento. Utilizou-se o recurso aos instrumentos de observação e entrevistas, procedendo-se à sua análise e ao desenho da intervenção a realizar. Foi implementada a intervenção “Ensinar crianças com autismo a fazer perguntas sobre objetos escondidos” na qual são utilizados brinquedos de interesse para a criança, motivacionais para a concretização do objetivo do estudo.

A virtual reality approach to the study of visually driven postural control in developing and aging humans

L'être humain utilise trois systèmes sensoriels distincts pour réguler le maintien de la station debout: la somesthésie, le système vestibulaire, et le système visuel. Le rôle de la vision dans la régulation posturale demeure peu connu, notamment sa variabilité en fonction de l'âge, du type développemental, et des atteintes neurologiques. Dans notre travail, la régulation posturale induite visuellement a été évaluée chez des participants au développement et vieillissement normaux âgés de 5-85 ans, chez des individus autistes (développement atypique) âgés de 12-33 ans, ainsi que chez des enfants entre 9-18 ans ayant subi un TCC léger. À cet effet, la réactivité posturale des participants en réponse à un tunnel virtuel entièrement immersif, se mouvant à trois niveaux de vélocité, a été mesurée; des conditions contrôles, où le tunnel était statique ou absent, ont été incluses. Les résultats montrent que la réactivité (i.e. instabilité) posturale induite visuellement est plus élevée chez les jeunes enfants; ensuite, elle s'atténue pour rejoindre des valeurs adultes vers 16-19 ans et augmente de façon linéaire en fonction de l'âge après 45 ans jusqu'à redevenir élevée vers 60 ans. De plus, à la plus haute vélocité du tunnel, les plus jeunes participants autistes ont manifesté significativement moins de réactivité posturale comparativement à leurs contrôles; cette différence n'était pas présente chez des participants plus âgés (16-33 ans). Enfin, les enfants ayant subi un TCC léger, et qui étaient initialement modérément symptomatiques, ont montré un niveau plus élevé d'instabilité posturale induite visuellement que les contrôles, et ce jusqu'à 12 semaines post-trauma malgré le fait que la majorité d'entre eux (89%) n'étaient plus symptomatiques à ce stade. En somme, cela suggère la présence d'une importante période de transition dans la maturation des systèmes sous-tendant l'intégration sensorimotrice impliquée dans le contrôle postural vers l'âge de 16 ans, et d'autres changements sensorimoteurs vers l'âge de 60 ans; cette sur-dépendance visuelle pour la régulation posturale chez les enfants et les aînés pourrait guider l'aménagement d'espaces et l'élaboration d'activités ajustés à l'âge des individus. De plus, le fait que l'hypo-réactivité posturale aux informations visuelles chez les autistes dépende des caractéristiques de l'environnement visuel et de l'âge chronologique, affine notre compréhension des anomalies sensorielles propres à l'autisme. Par ailleurs, le fait que les enfants ayant subi un TCC léger montrent des anomalies posturales jusqu'à 3 mois post-trauma, malgré une diminution significative des symptômes rapportés, pourrait être relié à une altération du traitement de l'information visuelle dynamique et pourrait avoir des implications quant à la gestion clinique des patients aux prises avec un TCC léger, puisque la résolution des symptômes est actuellement le principal critère utilisé pour la prise de décision quant au retour aux activités. Enfin, les résultats obtenus chez une population à développement atypique (autisme) et une population avec atteinte neurologique dite transitoire (TCC léger), contribuent non seulement à une meilleure compréhension des mécanismes d'intégration sensorimotrice sous-tendant le contrôle postural mais pourraient aussi servir comme marqueurs sensibles et spécifiques de dysfonction chez ces populations. Mots-clés : posture, équilibre, vision, développement/vieillissement sensorimoteur, autisme, TCC léger symptomatique, réalité virtuelle.

Fetal programming effects of testosterone on the reward system and behavioral approach tendencies in humans

BACKGROUND: Sex differences are present in many neuropsychiatric conditions that affect emotion and approach-avoidance behavior. One potential mechanism underlying such observations is testosterone in early development. Although much is known about the effects of testosterone in adolescence and adulthood, little is known in humans about how testosterone in fetal development influences later neural sensitivity to valenced facial cues and approach-avoidance behavioral tendencies. METHODS: With functional magnetic resonance imaging we scanned 25 8-11-year-old children while viewing happy, fear, neutral, or scrambled faces. Fetal testosterone (FT) was measured via amniotic fluid sampled between 13 and 20 weeks gestation. Behavioral approach-avoidance tendencies were measured via parental report on the Sensitivity to Punishment and Sensitivity to Rewards questionnaire. RESULTS: Increasing FT predicted enhanced selectivity for positive compared with negatively valenced facial cues in reward-related regions such as caudate, putamen, and nucleus accumbens but not the amygdala. Statistical mediation analyses showed that increasing FT predicts increased behavioral approach tendencies by biasing caudate, putamen, and nucleus accumbens but not amygdala to be more responsive to positive compared with negatively valenced cues. In contrast, FT was not predictive of behavioral avoidance tendencies, either through direct or neurally mediated paths. CONCLUSIONS: This work suggests that testosterone in humans acts as a fetal programming mechanism on the reward system and influences behavioral approach tendencies later in life. As a mechanism influencing atypical development, FT might be important across a range of neuropsychiatric conditions that asymmetrically affect the sexes, the reward system, emotion processing, and approach behavior.

Early influence of auditory stimuli on upper-limb movements in young human infants: an overview

Given that the auditory system is rather well developed at the end of the third trimester of pregnancy, it is likely that couplings between acoustics and motor activity can be integrated as early as at the beginning of postnatal life. The aim of the present mini-review was to summarize and discuss studies on early auditory-motor integration, focusing particularly on upper-limb movements (one of the most crucial means to interact with the environment) in association with auditory stimuli, to develop further understanding of their significance with regard to early infant development. Many studies have investigated the relationship between various infant behaviors (e.g., sucking, visual fixation, head turning) and auditory stimuli, and established that human infants can be observed displaying couplings between action and environmental sensory stimulation already from just after birth, clearly indicating a propensity for intentional behavior. Surprisingly few studies, however, have investigated the associations between upper-limb movements and different auditory stimuli in newborns and young infants, infants born at risk for developmental disorders/delays in particular. Findings from studies of early auditory-motor interaction support that the developing integration of sensory and motor systems is a fundamental part of the process guiding the development of goal-directed action in infancy, of great importance for continued motor, perceptual, and cognitive development. At-risk infants (e.g., those born preterm) may display increasing central auditory processing disorders, negatively affecting early sensorymotor integration, and resulting in long-term consequences on gesturing, language development, and social communication. Consequently, there is a need for more studies on such implications.

L’abilità di perspective taking : un training per bambini in età prescolare in differenti contesti

Elemento centrale della presente tesi dottorale è il costrutto di perspective taking, definibile come l’abilità, emergente nei bambini intorno a 4-5 anni, di assumere la prospettiva altrui secondo tre differenti dimensioni: emotiva, cognitiva e percettiva (Bonino, Lo Coco, Tani, 1998; Moll e Meltzoff, 2011). Dalla letteratura emerge come il perspective taking, in quanto abilità di comprensione sociale, rivesta un ruolo adattivo e sia fondamentale per lo sviluppo, non solo intellettivo, ma anche per la formazione di adeguate capacità relazionali e sociali (Jenkins e Astington, 2000; Weil et al., 2011). Sulla base di tali considerazioni, alcuni ricercatori si sono interrogati sulla possibilità di insegnare questa abilità, elaborando specifiche e differenti procedure di intervento finalizzate ad incrementare l’abilità di perspective taking sia in bambini a sviluppo normativo (Cigala e Mori, 2015), sia in gruppi di bambini a sviluppo atipico (Fisher e Happé, 2005; Heagle e Rehfeldt, 2006; Paynter e Peterson, 2012). A partire da una prospettiva teorica socio-costruzionista, secondo cui l’acquisizione del perspective taking si configura come un’impresa di co-costruzione continua, all’interno di interazioni quotidiane con figure significative per il bambino, si è deciso di analizzare il perspective taking non solo in relazione a variabili individuali (genere, età del bambino, regolazione emotiva, abilità sociali) ma anche e soprattutto a variabili contestuali quali le caratteristiche del contesto familiare (caratteristiche disposizionali e stili genitoriali di socializzazione emotiva, presenza di fratelli). Sono stati in particolare indagati un contesto familiare normativo ed uno caratterizzato da maltrattamento psicologico, contrassegnato dalla reiterazione di comportamenti inadeguati (critiche svalutanti, denigrazione, umiliazione, minacce verbali, indifferenza) nei confronti del minore, che convogliano sul bambino l’idea di non essere amato e di avere poco valore. Con i termini “a sviluppo tipico” si intendono i bambini per i quali non sussista una diagnosi clinica e con quelli di “famiglie normative” ci si riferisce a nuclei per i quali non ci siano state segnalazioni da parte dei Servizi Educativi e Sociali di riferimento, indipendentemente dalle caratteristiche della composizione del nucleo familiare (nucleare, estesa, multipla, ricostituita o ricomposta). Tale studio rientra in un ampio progetto di ricerca e formazione che ha coinvolto più di 250 prescolari frequentanti 8 scuole dell’infanzia e 15 comunità terapeutiche e di accoglienza mamma-bambino, situate in differenti province del Nord Italia. Il gruppo dei partecipanti alla ricerca si è composto di 256 bambini in età prescolare, compresa quindi tra 3 e 5 anni (M=54,39; DS=5,705): 128 maschi (M=54,08; DS=5,551) e 128 femmine (M=54,70; DS=5,860). In particolare, 213 bambini appartenevano a famiglie normative e 43 a nuclei familiari caratterizzati dalla presenza di maltrattamento psicologico. Oltre ai bambini, la ricerca ha previsto il coinvolgimento di 155 coppie di genitori, 43 madri ospitate in comunità, 18 insegnanti e 30 operatori. Obiettivo centrale è stato l’indagine della possibilità di poter promuovere il perspective taking in bambini di età prescolare a sviluppo tipico appartenenti a due differenti tipologie di contesto familiare (normativo e psicologicamente maltrattante), attraverso l’applicazione di uno specifico percorso di training di natura “ecologica” all’interno della scuola dell’infanzia e della comunità, assimilabile a quelli di tipo evidence based. In particolare è stata prevista una procedura quasi sperimentale di tipo pre-test, training, post-test e follow-up. Dopo una preliminare valutazione dello sviluppo del perspective taking nelle sue tre componenti, in bambini appartenenti ad entrambi i contesti, si è voluto verificare l’esistenza di eventuali relazioni tra questa abilità ed alcune capacità socio-emotive dei bambini, con particolare riferimento alla disposizione prosociale, rilevate nel contesto scolastico attraverso differenti metodologie (osservazioni dirette non partecipanti, questionari self report compilati dalle insegnanti). Inoltre, data l’importanza del contesto familiare per lo sviluppo di tale abilità, la ricerca ha avuto lo scopo di verificare l’esistenza di eventuali relazioni tra le abilità di perspective taking mostrate dai bambini e gli stili di socializzazione emotiva delle figure familiari, caratteristiche di entrambi i contesti (maltrattante e non maltrattante). È stato inoltre previsto uno studio di confronto tra i due campioni rispetto alle dimensioni indagate. I risultati ottenuti sono stati particolarmente interessanti. Innanzitutto, le esperienze di training hanno determinato, in entrambi i contesti, miglioramenti nell’abilità dei prescolari di mettersi nei panni altrui. Tale training ha inoltre dimostrato effetti positivi sulla competenza sociale dei bambini, che, a seguito del percorso, hanno manifestato un incremento dei comportamenti prosociali ed una diminuzione di quelli aggressivi. Per lo studio in contesto normativo, è stato inoltre dimostrato un mantenimento delle abilità acquisite a seguito del training attraverso un follow-up a distanza di 4 mesi dal termine dell’intervento. Il positivo esito di tale percorso sembra quindi rappresentare un’importante risorsa per i prescolari, soprattutto in caso di situazioni in cui l’abilità di perspective taking risulti deficitaria. Il confronto dei due gruppi a seguito del training ha evidenziato come non siano emerse differenze significative, rispetto al perspective taking, ad eccezione della dimensione emotiva, in cui le prestazioni dei prescolari maltrattati sono risultate inferiori, come già evidenziato prima del training. Tali risultati non giungono però inaspettati, poiché, sebbene il percorso abbia agito significativamente sull’abilità di comprensione delle emozioni altrui di questi bambini, non si configura come sufficiente a ristrutturare così profondamente le problematiche presentate. Interessanti sono stati altresì i risultati ottenuti dall’analisi degli stili di socializzazione emotiva, dei genitori (madri e padri) dei prescolari non maltrattati e delle mamme dei bambini residenti in comunità. In particolare è emerso come, stili accettanti e di tipo coaching nei confronti delle emozioni negative dei bambini, siano positivamente correlati con il perspective taking dei figli, e come all’opposto, stili rifiutanti rispetto alle espressioni emotive negative dei propri bambini, mostrino correlazioni negative con le abilità di perspective taking dei figli. Oltre ad interessi di ordine teorico e metodologico, è possibile quindi affermare come, il presente lavoro di tesi, sia stato guidato da fini applicativi, affinché la ricerca scientifica possa tradursi in pratiche educative quotidiane da applicare ai contesti di vita significativi per i bambini.

Disordered connectivity in the autistic brain:challenges for the 'new psychophysiology'

In 2002, we published a paper [Brock, J., Brown, C., Boucher, J., Rippon, G., 2002. The temporal binding deficit hypothesis of autism. Development and Psychopathology 142, 209-224] highlighting the parallels between the psychological model of 'central coherence' in information processing [Frith, U., 1989. Autism: Explaining the Enigma. Blackwell, Oxford] and the neuroscience model of neural integration or 'temporal binding'. We proposed that autism is associated with abnormalities of information integration that is caused by a reduction in the connectivity between specialised local neural networks in the brain and possible overconnectivity within the isolated individual neural assemblies. The current paper updates this model, providing a summary of theoretical and empirical advances in research implicating disordered connectivity in autism. This is in the context of changes in the approach to the core psychological deficits in autism, of greater emphasis on 'interactive specialisation' and the resultant stress on early and/or low-level deficits and their cascading effects on the developing brain [Johnson, M.H., Halit, H., Grice, S.J., Karmiloff-Smith, A., 2002. Neuroimaging of typical and atypical development: a perspective from multiple levels of analysis. Development and Psychopathology 14, 521-536].We also highlight recent developments in the measurement and modelling of connectivity, particularly in the emerging ability to track the temporal dynamics of the brain using electroencephalography (EEG) and magnetoencephalography (MEG) and to investigate the signal characteristics of this activity. This advance could be particularly pertinent in testing an emerging model of effective connectivity based on the balance between excitatory and inhibitory cortical activity [Rubenstein, J.L., Merzenich M.M., 2003. Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes, Brain and Behavior 2, 255-267; Brown, C., Gruber, T., Rippon, G., Brock, J., Boucher, J., 2005. Gamma abnormalities during perception of illusory figures in autism. Cortex 41, 364-376]. Finally, we note that the consequence of this convergence of research developments not only enables a greater understanding of autism but also has implications for prevention and remediation. © 2006.

Probing the neurocognitive trajectories of children's reading skills

Emerging evidence of the high variability in the cognitive skills and deficits associated with reading achievement and dysfunction promotes both a more dimensional view of the risk factors involved, and the importance of discriminating between trajectories of impairment. Here we examined reading and component orthographic and phonological skills alongside measures of cognitive ability and auditory and visual sensory processing in a large group of primary school children between the ages of 7 and 12 years. We identified clusters of children with pseudoword or exception word reading scores at the 10th percentile or below relative to their age group, and a group with poor skills on both tasks. Compared to age-matched and reading-level controls, groups of children with more impaired exception word reading were best described by a trajectory of developmental delay, whereas readers with more impaired pseudoword reading or combined deficits corresponded more with a pattern of atypical development. Sensory processing deficits clustered within both of the groups with putative atypical development: auditory discrimination deficits with poor phonological awareness skills; impairments of visual motion processing in readers with broader and more severe patterns of reading and cognitive impairments. Sensory deficits have been variably associated with developmental impairments of literacy and language; these results suggest that such deficits are also likely to cluster in children with particular patterns of reading difficulty. © 2012 Elsevier Ltd.

Developing multidimensional metrics for evaluating paediatric neurodevelopmental disorders

Healthy brain functioning depends on efficient communication of information between brain regions, forming complex networks. By quantifying synchronisation between brain regions, a functionally connected brain network can be articulated. In neurodevelopmental disorders, where diagnosis is based on measures of behaviour and tasks, a measure of the underlying biological mechanisms holds promise as a potential clinical tool. Graph theory provides a tool for investigating the neural correlates of neuropsychiatric disorders, where there is disruption of efficient communication within and between brain networks. This research aimed to use recent conceptualisation of graph theory, along with measures of behaviour and cognitive functioning, to increase understanding of the neurobiological risk factors of atypical development. Using magnetoencephalography to investigate frequency-specific temporal dynamics at rest, the research aimed to identify potential biological markers derived from sensor-level whole-brain functional connectivity. Whilst graph theory has proved valuable for insight into network efficiency, its application is hampered by two limitations. First, its measures have hardly been validated in MEG studies, and second, graph measures have been shown to depend on methodological assumptions that restrict direct network comparisons. The first experimental study (Chapter 3) addressed the first limitation by examining the reproducibility of graph-based functional connectivity and network parameters in healthy adult volunteers. Subsequent chapters addressed the second limitation through adapted minimum spanning tree (a network analysis approach that allows for unbiased group comparisons) along with graph network tools that had been shown in Chapter 3 to be highly reproducible. Network topologies were modelled in healthy development (Chapter 4), and atypical neurodevelopment (Chapters 5 and 6). The results provided support to the proposition that measures of network organisation, derived from sensor-space MEG data, offer insights helping to unravel the biological basis of typical brain maturation and neurodevelopmental conditions, with the possibility of future clinical utility.

Development of advanced tools and methods for the assessment and management of risk due to atypical major accident scenarios

Proper hazard identification has become progressively more difficult to achieve, as witnessed by several major accidents that took place in Europe, such as the Ammonium Nitrate explosion at Toulouse (2001) and the vapour cloud explosion at Buncefield (2005), whose accident scenarios were not considered by their site safety case. Furthermore, the rapid renewal in the industrial technology has brought about the need to upgrade hazard identification methodologies. Accident scenarios of emerging technologies, which are not still properly identified, may remain unidentified until they take place for the first time. The consideration of atypical scenarios deviating from normal expectations of unwanted events or worst case reference scenarios is thus extremely challenging. A specific method named Dynamic Procedure for Atypical Scenarios Identification (DyPASI) was developed as a complementary tool to bow-tie identification techniques. The main aim of the methodology is to provide an easier but comprehensive hazard identification of the industrial process analysed, by systematizing information from early signals of risk related to past events, near misses and inherent studies. DyPASI was validated on the two examples of new and emerging technologies: Liquefied Natural Gas regasification and Carbon Capture and Storage. The study broadened the knowledge on the related emerging risks and, at the same time, demonstrated that DyPASI is a valuable tool to obtain a complete and updated overview of potential hazards. Moreover, in order to tackle underlying accident causes of atypical events, three methods for the development of early warning indicators were assessed: the Resilience-based Early Warning Indicator (REWI) method, the Dual Assurance method and the Emerging Risk Key Performance Indicator method. REWI was found to be the most complementary and effective of the three, demonstrating that its synergy with DyPASI would be an adequate strategy to improve hazard identification methodologies towards the capture of atypical accident scenarios.

High-resolution Transcript Profiling Of The Atypical Biotrophic Interaction Between Theobroma Cacao And The Fungal Pathogen Moniliophthora Perniciosa.

Witches' broom disease (WBD), caused by the hemibiotrophic fungus Moniliophthora perniciosa, is one of the most devastating diseases of Theobroma cacao, the chocolate tree. In contrast to other hemibiotrophic interactions, the WBD biotrophic stage lasts for months and is responsible for the most distinctive symptoms of the disease, which comprise drastic morphological changes in the infected shoots. Here, we used the dual RNA-seq approach to simultaneously assess the transcriptomes of cacao and M. perniciosa during their peculiar biotrophic interaction. Infection with M. perniciosa triggers massive metabolic reprogramming in the diseased tissues. Although apparently vigorous, the infected shoots are energetically expensive structures characterized by the induction of ineffective defense responses and by a clear carbon deprivation signature. Remarkably, the infection culminates in the establishment of a senescence process in the host, which signals the end of the WBD biotrophic stage. We analyzed the pathogen's transcriptome in unprecedented detail and thereby characterized the fungal nutritional and infection strategies during WBD and identified putative virulence effectors. Interestingly, M. perniciosa biotrophic mycelia develop as long-term parasites that orchestrate changes in plant metabolism to increase the availability of soluble nutrients before plant death. Collectively, our results provide unique insight into an intriguing tropical disease and advance our understanding of the development of (hemi)biotrophic plant-pathogen interactions.

46,XY disorders of sex development (DSD)

The term disorders of sex development (DSD) includes congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical. Mutations in genes present in X, Y or autosomal chromosomes can cause abnormalities of testis determination or disorders of sex differentiation leading to 46,XY DSD. Detailed clinical phenotypes allow the identification of new factors that can alter the expression or function of mutated proteins helping to understand new undisclosed biochemical pathways. In this review we present an update on 46,XY DSD aetiology, diagnosis and treatment based on extensive review of the literature and our three decades of experience with these patients.