Autism spectrum disorders in extremely preterm children

Objectives To investigate the prevalence, correlates, and antecedents of autism spectrum disorders (ASD) in extremely preterm children. Study design We conducted a prospective study of all births <26 weeks gestation in the United Kingdom and Ireland in 1995. Of 307 survivors at 11 years, 219 (71%) were assessed and compared with 153 term-born classmates. Parents completed the Social Communication Questionnaire (SCQ) to assess autism spectrum symptoms, and ASD were diagnosed by using a psychiatric evaluation. An IQ test and clinical evaluation were also administered. Longitudinal outcome data were available for extremely preterm children. Results Extremely preterm children had significantly higher SCQ scores than classmates (mean difference, 4.6 points; 95% CI, 3.4-5.8). Sixteen extremely preterm children (8%) were assigned an ASD diagnosis, compared with none of the classmates. By hospital discharge, male sex, lower gestation, vaginal breech delivery, abnormal cerebral ultrasound scanning results, and not having had breast milk were independently associated with autism spectrum symptoms. By 6 years, independent associates were cognitive impairment, inattention and peer problems, withdrawn behavior at 2.5 years, and not having had breast milk. Conclusions Extremely preterm children are at increased risk for autism spectrum symptoms and ASD in middle childhood. These symptoms and disorders were associated with neurocognitive outcomes, suggesting that ASD may result from abnormal brain development in this population

Repetitive Behavior in Rubinstein–Taybi Syndrome:Parallels with Autism Spectrum Phenomenology

Syndrome specific repetitive behavior profiles have been described previously. A detailed profile is absent for Rubinstein–Taybi syndrome (RTS). The Repetitive Behaviour Questionnaire and Social Communication Questionnaire were completed for children and adults with RTS (N = 87), Fragile-X (N = 196) and Down (N = 132) syndromes, and individuals reaching cut-off for autism spectrum disorder (N = 228). Total and matched group analyses were conducted. A phenotypic profile of repetitive behavior was found in RTS. The majority of behaviors in RTS were not associated with social-communication deficits or degree of disability. Repetitive behavior should be studied at a fine-grained level. A dissociation of the triad of impairments might be evident in RTS

Pharmacological activation of Nur77 enhances BMP signalling and inhibits vascular remodelling in pulmonary arterial hypertension

Therapeutic cell differentiatio

Cognitive Neuroscience NeuroReport The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans

AUTISM is a biological disorder which affects social cognition, and understanding brain abnormalities of the former will elucidate the brain basis of the latter. We report structural MRI data on 15 high-functioning individuals with autistic disorder. A voxel-based whole brain analysis identi®ed grey matter differences in an amygdala centered system relative to 15 age-and IQmatched controls. Decreases of grey matter were found in anterior parts of this system (right paracingulate sulcus, left inferior frontal gyrus). Increases were found in posterior parts (amygdala/peri-amygdaloid cortex, middle temporal gyrus, inferior temporal gyrus), and in regions of the cerebellum. These structures are implicated in social cognition by animal, imaging and histopathological studies. This study therefore provides converging evidence of the physiological basis of social cognition

Regional impacts of abolishing direct payments: An integrated analysis in four European regions

The direct payment system of the Common Agricultural Policy (CAP) provides income transfers to European farmers. Recently, several countries including England and Sweden have advocated the elimination of direct payments after 2013. The extent to which an elimination of direct payments would affect the land use dynamics in Europe including impacts on structural change and the environment has not been addressed in the existing literature. In this paper, we combine participatory methods, to analyze regional preferences for functions and effects of agriculture, and farm-level modeling, to assess the impacts of such a policy change on farm structures and land use intensities in four European regions located in Germany, Denmark, Italy and Poland, each with different socio-economic and biophysical characteristics. In each region, the entire farm population consisting of different farm types with different production orientations and land management types was modeled under the presence and absence of direct payments using a combination of agent-based and bio-economic modeling. We found that the initial characteristics of the regions, such as the historical farm structure and regional site conditions, greatly influence the impact of direct support elimination and cause regionally different development trends. The results for the four regions were summarized in four specific storylines that emphasize how much the diversity of European regions matters for future policy decisions. An explicitly regional focus is, therefore, argued to be crucial to complement future policy analysis

Delayed Microvascular Shear Adaptation in Pulmonary Arterial Hypertension.:Role of Platelet Endothelial Cell Adhesion Molecule-1 Cleavage

Rationale: Altered pulmonary hemodynamics and fluid flow-induced high shear stress (HSS) are characteristic hallmarks in the pathogenesis of pulmonary arterial hypertension (PAH). However, the contribution of HSS to cellular and vascular alterations in PAH is unclear.Objectives: We hypothesize that failing shear adaptation is an essential part of the endothelial dysfunction in all forms of PAH and tested whether microvascular endothelial cells (MVECs) or pulmonary arterial endothelial cells (PAECs) from lungs of patients with PAH adapt to HSS and if the shear defect partakes in vascular remodeling in vivo.Methods: PAH MVEC (n = 7) and PAH PAEC (n = 3) morphology, function, protein, and gene expressions were compared with control MVEC (n = 8) under static culture conditions and after 24, 72, and 120 hours of HSS.Measurements and Main Results: PAH MVEC showed a significantly delayed morphological shear adaptation (P = 0.03) and evidence of cell injury at sites of nonuniform shear profiles that are critical loci for vascular remodeling in PAH. In clear contrast, PAEC isolated from the same PAH lungs showed no impairments. PAH MVEC gene expression and transcriptional shear activation were not altered but showed significant decreased protein levels (P = 0.02) and disturbed interendothelial localization of the shear sensor platelet endothelial cell adhesion molecule-1 (PECAM-1). The decreased PECAM-1 levels were caused by caspase-mediated cytoplasmic cleavage but not increased cell apoptosis. Caspase blockade stabilized PECAM-1 levels, restored endothelial shear responsiveness in vitro, and attenuated occlusive vascular remodeling in chronically hypoxic Sugen5416-treated rats modeling severe PAH.Conclusions: Delayed shear adaptation, which promotes shear-induced endothelial injury, is a newly identified dysfunction specific to the microvascular endothelium in PAH. The shear response is normalized on stabilization of PECAM-1, which reverses intimal remodeling in vivo.</p