Macmillandyhr0489

The Early Communication Indicator (ECI) was designed to measure expressive communication progress in young children. We evaluated using the 6-min ECI procedure for a new purpose-a sampling context for stable measures of vocal development of young children with autism spectrum disorder (ASD). We evaluated how many ECI sessions were required to adequately stabilize estimates of volubility, communicative use, and phonological complexity of vocalizations at two periods (average of 10 months apart). Participants included 83 young children with ASD (M age = 23.33 months). At study initiation, two phonological complexity variables required two sessions; other variables required three. At study endpoint, all variables required fewer sessions. Findings support the feasibility and stability of using the ECI for the new purpose.Children with autism spectrum disorder (ASD) are at risk for disrupted peer interactions. This study contributes to our understanding of how multiple foundational elements of emotional competence are related to children's prosocial behaviors with peers. Children with ASD demonstrated significantly lower non-stereotypical affective perspective taking, had lower ratings of emotion regulation, and showed differences from their typical peers in the use of discrete coping strategies during peer interactions. Children's emotion regulation and use of discrete coping strategies in the context of peers were associated with their prosocial behaviors one year later. The findings add to our understanding of how emotional development contributes to individual differences in the social-emotional behaviors of children with ASD. Implications for intervention are discussed.Early identification of behavioral risk markers for anxiety is essential to optimize long-term outcomes in children with neurodevelopmental disorders. This study analyzed attentional avoidance and its relation to anxiety and autism spectrum disorder (ASD) symptomatology during social and nonsocial fear conditions in toddlers with fragile X syndrome (FXS) and Down syndrome (DS). Toddlers with FXS and DS exhibited increased nonsocial attentional avoidance relative to typically developing (TD) toddlers. Attentional avoidance was not related to anxiety symptom severity in any group; however, higher ASD symptom severity was related to more social attentional avoidance in the FXS and TD groups. Findings suggest that there may be different underlying mechanisms driving attentional avoidance across neurodevelopmental disorders.Elevated salivary cortisol levels have been documented in individuals who engage in self-injurious behavior (SIB), indicating acute physiological stress. Less is known about the chronicity of stress and SIB. We analyzed the relationship between parent ratings of problem behavior and hair cortisol concentrations (an index of chronic adrenocortical activity) in 23 children with autism spectrum disorder (ASD). Parent ratings of problem behavior were not significantly correlated with hair cortisol concentrations. When children were categorized into groups based on the frequency and severity of SIB, participants with the greatest frequency and severity of SIB had higher hair cortisol concentrations compared to children without SIB. Frequent and severe SIB may be associated with altered hypothalamic-pituitary-adrenal (HPA) axis activity in children with ASD.The retinoic acid receptors (RARA, RARB, and RARG) are ligand-regulated nuclear receptors that act as transcriptional switches. These master genes drew significant interest in the 1990s because of their key roles in embryogenesis and involvement in a rare malignancy, acute promyelocytic leukemia (APL), in which the RARA (and very rarely, RARG or RARB) genes are rearranged, underscoring the central role of deregulated retinoid signaling in leukemogenesis. Several recent provocative observations have revived interest in the roles of retinoids in non-APL acute myeloid leukemia (AML), as well as in normal hematopoietic differentiation. We review the role of retinoids in hematopoiesis, as well as in the treatment of non-APL AMLs. From this perspective, broader uses of retinoids in the management of hematopoietic tumors are discussed.Adrenal chromaffin cells (CCs) in rodents express rapidly inactivating, tetrodotoxin (TTX)-sensitive sodium channels. The resulting current has generally been attributed to Nav1.7, although a possible role for Nav1.3 has also been suggested. Nav channels in rat CCs rapidly inactivate via two independent pathways which differ in their time course of recovery. One subpopulation recovers with time constants similar to traditional fast inactivation and the other ∼10-fold slower, but both pathways can act within a single homogenous population of channels. Here, we use Nav1.3 KO mice to probe the properties and molecular components of Nav current in CCs. We find that the absence of Nav1.3 abolishes all Nav current in about half of CCs examined, while a small, fast inactivating Nav current is still observed in the rest. Honokiol in vitro To probe possible molecular components underlying slow recovery from inactivation, we used mice null for fibroblast growth factor homology factor 14 (FGF14). In these cells, the slow component of recovery from fast inactivation is completely absent in most CCs, with no change in the time constant of fast recovery. The use dependence of Nav current reduction during trains of stimuli in WT cells is completely abolished in FGF14 KO mice, directly demonstrating a role for slow recovery from inactivation in determining Nav current availability. Our results indicate that FGF14-mediated inactivation is the major determinant defining use-dependent changes in Nav availability in CCs. These results establish that Nav1.3, like other Nav isoforms, can also partner with FGF subunits, strongly regulating Nav channel function.Autoimmune cytopenias (AIC) affect 5-9% of patients with chronic lymphocytic leukemia (CLL). Targeted drugs - ibrutinib, idelalisib and venetoclax - have a prominent role in the treatment of CLL, but their impact on CLL-associated AIC is largely unknown. In this study, we evaluated the characteristics and outcome of pre-existing AIC, and described the incidence, quality and management of treatment-emergent AIC during therapy with targeted drugs in patients with CLL. We collected data from 572 patients treated with ibrutinib (9% in combination with an anti-CD20 monoclonal antibody), 143 treated with idelalisib-rituximab and 100 treated with venetoclax (12% in combination with an anti-CD20 monoclonal antibody). A history of pre-existing AIC was reported in 104/815 patients (13%). Interestingly, 80% of patients whose AIC was not resolved at the time of targeted drug start experienced an improvement or a resolution during therapy. Treatment-emergent AIC occurred in 1% of patients during ibrutinib therapy, in 0.9% during idelalisib and in 7% during venetoclax, with an estimated incidence rate of 5, 6 and 69 episodes per 1000 patients per year of exposure in the three treatment groups, respectively.