Developmental divergence: motor trajectories in children with fragile X syndrome with and without co-occurring autism.

BackgroundAutism spectrum disorder (ASD) is highly prevalent in fragile X syndrome (FXS), affecting 50-70% of males. Motor impairments are a shared feature across autism and FXS that may help to better characterize autism in FXS. As motor skills provide a critical foundation for various language, cognitive, and social outcomes, they may serve an important mechanistic role for autism in FXS. As such, this study aimed to identify differences in motor trajectories across direct assessment and parent-report measures of fine and gross motor development between FXS with and without autism, and typical development, while controlling for cognitive functioning.MethodsThis prospective longitudinal study included 42 children with FXS, 24 of whom also had ASD (FXS + ASD), as well as 40 typically developing children. The Mullen Scales of Early Learning provided a direct measure of fine and gross motor skills, and the Vineland Adaptive Behavior Scales provided a measure of parent-reported fine and gross motor skills. Random slopes and random intercepts multilevel models were tested to determine divergence in developmental motor trajectories between groups when controlling for cognitive level.ResultsModel results indicated the children with FXS + ASD diverged from TD children by 9-months on all measures of gross and fine motor skills, even when controlling for cognitive level. Results also indicated an early divergence in motor trajectories of fine and gross motor skills between the FXS + ASD and FXS groups when controlling for cognitive level. This divergence was statistically significant by 18 months, with the FXS + ASD showing decelerated growth in motor skills across direct observation and parent-report measures.ConclusionsThis study is the first to examine longitudinal trends in motor development in children with FXS with and without comorbid ASD using both direct assessment and parent-report measures of fine and gross motor. Furthermore, it is among the first to account for nonverbal cognitive delays, a step towards elucidating the isolated role of motor impairments in FXS with and without ASD. Findings underscore the role of motor impairments as a possible signal representing greater underlying genetic liability, or as a potential catalyst or consequence, of co-occurring autism in FXS

Defect-unbinding transitions and inherent structures in two dimensions

We present a large-scale (36000-particle) computational study of the "inherent structures" (IS) associated with equilibrium, two-dimensional, one-component Lennard-Jones systems. Our results provide strong support both for the inherent-structures theory of classical fluids, and for the KTHNY theory of two-stage melting in two dimensions. This support comes from the observation of three qualitatively distinct "phases" of inherent structures: a crystal, a "hexatic glass", and a "liquid glass". We also directly observe, in the IS, analogs of the two defect-unbinding transitions (respectively, of dislocations, and disclinations) believed to mediate the two equilibrium phase transitions. Each transition shows up in the inherent structures---although the free disclinations in the "liquid glass" are embedded in a percolating network of grain boundaries. The bond-orientational correlation functions of the inherent structures show the same progressive loss of order as do the three equilibrium phases: long-range to quasi-long-range to short-range.Comment: RevTeX, 8 pages, 15 figure

Discourses on Fantasy: A Narrative Allegory

This project, though officially designated by the English Department as a creative thesis, is really a hybrid work that combines creative writing with literary criticism. The work is structured as a dream vision, a literary genre popular in the Middle Ages in which a narrator receives some form of instruction or wisdom through an allegorical dream. Examples include The Pearl, The Romance of the Rose, and Chaucer\u27s House of Fame. In this thesis, the allegorical space of the dream vision provides a platform for a series of essays structured as dialogues. These dialogues explore the aesthetics and politics of modern fantasy and supernatural literature, focusing particularly on the opposition of this literature, which often draws on ancient and medieval source material, to modern capitalist society. The discourses themselves are not strictly critical, but incorporate subjectivity, metaphor, and symbolism in their investigation of cultural texts

Theta Phase-dependent Modulation of Perception by Concurrent Transcranial Alternating Current Stimulation and Periodic Visual Stimulation

Background: Sensory perception can be modulated by the phase of neural oscillations, especially in the theta and alpha ranges. Oscillatory activity in the visual cortex can be entrained by transcranial alternating current stimulation (tACS) as well as periodic visual stimulation (i.e., flicker). Combined tACS and visual flicker stimulation modulates blood- oxygen-level-dependent (BOLD) responses and concurrent 4 Hz auditory click-trains and tACS modulates auditory perception in a phase-dependent way. Objective: In the present study, we investigated if phase synchrony between concurrent tACS and periodic visual stimulation (i.e., flicker) can modulate performance on a visual matching task. Methods: Participants completed a visual matching task on a flickering visual stimulus while receiving either in-phase (0°) or asynchronous (180°, 90°, or 270°) tACS at alpha or theta frequency. Stimulation was applied over either occipital cortex or dorsolateral prefrontal cortex (DLPFC). Results: Visual performance was significantly better during theta frequency tACS over the visual cortex when it was in-phase (0°) with visual stimulus flicker, compared to anti-phase (180°). This effect did not appear with alpha frequency flicker or with DLPFC stimulation. Furthermore, a control sham group showed no effect. There were no significant performance differences amongst the asynchronous (180°, 90°, and 270°) phase conditions. Conclusion: Extending previous studies on visual and auditory perception, our results support a crucial role of oscillatory phase in sensory perception and demonstrate a behaviourally relevant combination of visual flicker and tACS. The spatial and frequency specificity of our results have implications for research on the functional organisation of perception

Patterns and determinants of response to novel therapies in juvenile and adult-onset polyarthritis

Biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) have revolutionized the management of multiple rheumatic inflammatory conditions. Amongst these, polyarticular Juvenile-Idiopathic Arthritis (pJIA) and Rheumatoid Arthritis (RA) display similarities in terms of disease pathophysiology and response pattern to b/tsDMARDs. Indeed, therapeutic efficacy of novel targeted drugs is variable among individual patients, in both RA and pJIA. Mechanisms and determinants of this heterogeneous response are diverse and complex, such that development of true “precision”-medicine strategies has proven highly challenging. In this review, we will discuss pathophysiological, patient-specific, drug-specific and environmental factors contributing to individual therapeutic response in polyarticular JIA in comparison to what is known in RA. Although some biomarkers have been identified that stratify for the likelihood of either therapeutic response or non-response, few have proved useful in clinical practice so far, likely due to the complexity of treatment-response mechanisms. Consequently, we propose a pragmatic, patient-centered and clinically-based approach, i.e. personalized instead of biomarker-based precision medicine in JIA

Subdimensions of social-communication impairment in autism spectrum disorder

BACKGROUND: More refined dimensions of social-communication impairment are needed to elucidate the clinical and biological boundaries of autism spectrum disorders (ASD) and other childhood onset psychiatric disorders associated with social difficulties, as well as to facilitate investigations in treatment and long-term outcomes of these disorders. METHODS: The current study was intended to identify separable dimensions of clinician-observed, social-communication impairments by examining scores on a widely used autism diagnostic instrument. Participants included verbally fluent children ages 3 to 13 years, who were given a clinical diagnosis of ASD (n=120) or non-ASD (i.e., ADHD, language disorder, intellectual disability, mood or anxiety disorder; n=118) following a comprehensive diagnostic assessment. Exploratory and confirmatory factor analysis examined the factor structure of algorithm items from the Autism Diagnostic Observation Schedule (ADOS), Module 3. RESULTS: Results indicated that a three-factor model consisting of repetitive behaviors and two separate social-communication behavior factors had superior fit compared to a two-factor model that included repetitive behaviors and one social-communication behavior factor. In the three-factor model, impairments in ‘Basic Social-Communication’ behaviors (e.g., eye contact, facial expressions, gestures) were separated from impairments in ‘Interaction quality.’ Confirmatory factor analysis in an independent sample of children in the Simons Simplex Collection (SSC) further supported the division of social-communication impairments into these two factors. Scores in Interaction Quality were significantly associated with nonverbal IQ and male sex in the ASD group, and with age in the non-ASD group, while scores in basic social communication were not significantly associated with any of these child characteristics in either diagnostic group. CONCLUSIONS: Efforts to conceptualize level, or severity, of social-communication impairment in children with neurodevelopmental disorders might be facilitated by separating the most basic (or proximal) social-communication impairments, from those that could arise from a range of other phenotypic variables. Identification of social-communication subdimensions also highlights potential avenues for measuring different types of social-communication impairments for different purposes (e.g., for differential diagnosis vs. response to treatment)

Left ventricular diverticulum: incidental finding on dual source cardiac ct

The purpose of this retrospective study is to describe the prevalence, size and location of left ventricular (LV) diverticulum- diverticuli on cardiac dual source CT. Dual source computed tomography cardiac angiography (DS CTCA) was performed in 482 patients. Where literature states their rare occurrence, this retrospective study demonstrates the fairly common finding of incidental LV diverticulum on DS CTCA examinations. LV diverticuli were found incidentally in 20 out of 482 patients (4.1%), a substantially higher incidence than previously reported. Although diverticuli were most common along the inferoseptal wall (45%) they also occurred in all parts of the left ventricular wall. Multiple diverticuli were found in 30% of patients. Dimensions of the LV diverticuli varied enormously. LV diverticuli are reported to be frequently associated with other congenital anomalies. Complications ranging from sudden death and heart failure to embolic events have been described in literature. No relevant associated anomaly or complication was present in the studied 20 patients. Our data support the hypothesis that LV diverticuli, incidentally found in adulthood, follow a benign course and can be managed conservatively. More knowledge is however required to understand history and prognosis about this condition

Love is the triumph of the imagination: daydreams about significant others are associated with increased happiness, love and connection

Social relationships and interactions contribute to daily emotional well-being. The emotional benefits that come from engaging with others are known to arise from real events, but do they also come from the imagination during daydreaming activity? Using experience sampling methodology with 101 participants, we obtained 371 reports of naturally occurring daydreams with social and non-social content and self-reported feelings before and after daydreaming. Social, but not non-social, daydreams were associated with increased happiness, love and connection and this effect was not solely attributable to the emotional content of the daydreams. These effects were only present when participants were lacking in these feelings before daydreaming and when the daydream involved imagining others with whom the daydreamer had a high quality relationship. Findings are consistent with the idea that social daydreams may function to regulate emotion: imagining close others may serve the current emotional needs of daydreamers by increasing positive feelings towards themselves and others