Exploratory Study of Executive Function Abilities Across the Adult Lifespan in Individuals Receiving an ASD Diagnosis in Adulthood

The few studies of autism spectrum disorder (ASD) across adulthood suggest different age-related associations in different aspects of executive function (EF). In this exploratory study we examined EF abilities and self-report autism traits in 134 adults (aged 18-75 years; mean=31 years) with abilities in the normal range, receiving a first diagnosis of ASD. Results suggest that in some EF relying on speed and sequencing (Trails A and B; Digit Symbol), late-diagnosed ASD individuals may demonstrate better performance than typical age-norms. On other EF (Digit Span, Hayling, Brixton tests) age-related correlations were similar to typical age-norms. Different domains of EF may demonstrate different trajectories for ageing with ASD, with patterns of slower, accelerated or equivalent age-related change observed across different measures

Exploratory Study of Executive Function Abilities Across the Adult Lifespan in Individuals Receiving an ASD Diagnosis in Adulthood

The few studies of autism spectrum disorder (ASD) across adulthood suggest different age-related associations in different aspects of executive function (EF). In this exploratory study we examined EF abilities and self-report autism traits in 134 adults (aged 18-75 years; mean=31 years) with abilities in the normal range, receiving a first diagnosis of ASD. Results suggest that in some EF relying on speed and sequencing (Trails A and B; Digit Symbol), late-diagnosed ASD individuals may demonstrate better performance than typical age-norms. On other EF (Digit Span, Hayling, Brixton tests) age-related correlations were similar to typical age-norms. Different domains of EF may demonstrate different trajectories for ageing with ASD, with patterns of slower, accelerated or equivalent age-related change observed across different measures

Ensemble Models of Neutrophil Trafficking in Severe Sepsis

A hallmark of severe sepsis is systemic inflammation which activates leukocytes and can result in their misdirection. This leads to both impaired migration to the locus of infection and increased infiltration into healthy tissues. In order to better understand the pathophysiologic mechanisms involved, we developed a coarse-grained phenomenological model of the acute inflammatory response in CLP (cecal ligation and puncture)-induced sepsis in rats. This model incorporates distinct neutrophil kinetic responses to the inflammatory stimulus and the dynamic interactions between components of a compartmentalized inflammatory response. Ensembles of model parameter sets consistent with experimental observations were statistically generated using a Markov-Chain Monte Carlo sampling. Prediction uncertainty in the model states was quantified over the resulting ensemble parameter sets. Forward simulation of the parameter ensembles successfully captured experimental features and predicted that systemically activated circulating neutrophils display impaired migration to the tissue and neutrophil sequestration in the lung, consequently contributing to tissue damage and mortality. Principal component and multiple regression analyses of the parameter ensembles estimated from survivor and non-survivor cohorts provide insight into pathologic mechanisms dictating outcome in sepsis. Furthermore, the model was extended to incorporate hypothetical mechanisms by which immune modulation using extracorporeal blood purification results in improved outcome in septic rats. Simulations identified a sub-population (about of the treated population) that benefited from blood purification. Survivors displayed enhanced neutrophil migration to tissue and reduced sequestration of lung neutrophils, contributing to improved outcome. The model ensemble presented herein provides a platform for generating and testing hypotheses in silico, as well as motivating further experimental studies to advance understanding of the complex biological response to severe infection, a problem of growing magnitude in humans

Pemphigus autoimmunity: Hypotheses and realities

The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients

Interpersonal memory-based guidance of attention is reduced for ingroup members.

Participants jointly engaged in common tasks with co-actors can be influenced in guiding their own attention by representations of what the co-actor also holds in memory (He et al. under review). This demonstrates an effect of interpersonal memory on attention. Here, we tested how this interpersonal memory effect is affected by the relationship between the actors. Participants searched for targets while maintaining images in working memory or after previewed images that co-actors had to memorise. We examined three groups: Caucasian strangers (low ingroup relations) and two other groups with likely higher ingroup relations (Caucasian friends and Chinese participants living in Britain). In all three groups, attention was directed to stimuli that matched the item the individual had to memorise. However, images that had to be memorised by co-actors only attracted the attention of Caucasian strangers but not the Caucasian friends and Chinese participants. We suggest that interpersonal memory-based guidance of attention is modulated by the nature of the relationship between individuals and reduces when individuals have higher ingroup relations