Autism spectrum disorders (ASDs) comprise a range of disorders that share a core of neurobehavioural deficits characterized by widespread abnormalities in social interactions, deficits in ...communication as well as restricted interests and repetitive behaviours. The neurological basis and circuitry mechanisms underlying these abnormal behaviours are poorly understood. SHANK3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for the development of 22q13 deletion syndrome (Phelan-McDermid syndrome) and other non-syndromic ASDs. Here we show that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction. Cellular, electrophysiological and biochemical analyses uncovered defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. Our findings demonstrate a critical role for SHANK3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic-like behaviours in mice.
The diagnosis of bipolar disorder in juveniles is controversial. This study was designed to compare proton magnetic resonance spectroscopy ((1)H MRS) in patients with bipolar disorder or intermittent ...explosive disorder, two groups with symptomatic overlap but categorical distinction. Children with intermittent explosive disorder designate patients whose illness clinically resembles pediatric bipolar disorder but does not satisfy DSM-IV criteria for mania. Based on the authors' previous report of higher levels of (1)H MRS cingulate myo-inositol/creatine in youngsters with bipolar disorder than in normal comparison subjects, they hypothesized that patients with bipolar disorder would have higher cingulate myo-inositol/creatine-phosphocreatine measurements than patients with intermittent explosive disorder and normal comparison subjects.
Myo-inositol levels were measured with a 2x2x2 cm(3) voxel placed in the anterior cingulate for acquisition of (1)H MRS in 10 patients with bipolar disorder, 10 patients with intermittent explosive disorder, and 13 normal comparison subjects. N-Acetylaspartate, choline moieties, creatine-phosphocreatine, and glutamate-glutamine metabolite levels were also measured.
The patients with bipolar disorder showed significantly higher anterior cingulate myo-inositol/creatine-phosphocreatine and myo-inositol (mmol/liter) levels than the patients with intermittent explosive disorder and the normal comparison subjects. No significant differences were found across groups for myo-inositol or other metabolites in the occipital cortex.
These data provide evidence that differences in the concentration of myo-inositol (mmol/liter) in the anterior cingulate cortex in (1)H MRS may differentiate these two populations. Follow-up studies involving larger samples may conclusively estimate the biological specificity between pediatric bipolar disorder and other disorders, which overlap clinically.
This commentary discusses the six articles that have been selected for publication in the Organizational Research Methods feature topic on ``Research Methods in Strategic Management: Opportunities ...and Challenges'' and lays out three directions to further our understanding of the centrality of methodological and measurement issues in strategy research.
Background Neurologic injury is common after cardiac surgery and disruption of the blood brain barrier (BBB) has been proposed as a contributing factor. We sought to study BBB characteristics in a ...rodent model of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Methods Adult rats were subjected to CPB/DHCA or to sham surgery. Analysis included Western blotting of relevant BBB proteins in addition to in vivo brain magnetic resonance imaging (MRI) with a clinically used low-molecular contrast agent. Results While quantitative analysis of BBB proteins revealed similar expression levels, MRI showed evidence of BBB disruption after CPB/DHCA compared to sham surgery. Conclusions Combining molecular BBB analysis and MRI technology in a rodent model is a highly translatable approach to study adverse neurologic outcomes following CPB/DHCA.
The governance of an organizational information technology (IT) infrastructure is steadily shifting away from pure hierarchical and market mechanisms toward hybrid and partnership modes that involve ...external vendors. In particular, IT outsourcing has recently emerged as a significant administrative innovation in an organization's IT strategy. This paper seeks to explore the sources of influence in the adoption of this innovation. For this purpose, we generated a comprehensive sample of outsourcing contracts in the US using an electronic bibliometric search process. Using diffusion modeling, our empirical analysis shows that the adoption of IT outsourcing is motivated more by internal influence (or imitative behavior) than by external influence amongst the user organizations. Subsequently, we considered the widely-publicized Eastman Kodak's outsourcing decision as a critical event to assess whether this internal influence is more pronounced in the post- Kodak regime than in the pre- Kodak regime. Our results show that internal influence is dominant in the post- Kodak regime but not in the pre- Kodak regime. Implications and directions for future research are discussed.
Abstract We utilized single-voxel1 H magnetic resonance spectroscopy (MRS) to investigate biochemical abnormalities related to late-life depression in the medial prefrontal cortex and medial temporal ...lobe. Fourteen elderly subjects whose depression responded to treatment and 12 nondepressed subjects were enrolled. Subjects were scanned using a GE 3.0 Tesla whole body MR scanner. Metabolite concentrations were quantified using the LC Model software and adjusted for CSF and ratio of gray to white matter. ANCOVA models tested for group differences while controlling for age and sex. Older previously depressed individuals showed significantly reduced concentrations of total N -acetyl aspartate (NAA), choline, and creatine in the prefrontal cortex and significantly elevated left medial temporal lobe concentrations of NAA and myo -inositol. There were no significant group differences in right temporal metabolite concentrations. The prefrontal cortex observations suggest that reduced neuronal, phospolipid, and energy metabolism is present even in clinically improved depression. In contrast, elevated NAA and myo -inositol concentrations in the left medial temporal lobe could be associated with neuronal and glial cell changes in the amygdala.
This paper develops a perspective of interorganizational relationships based on the concept of exploitation of expertise. Insights from marketing channel theory and resource-based views of the firm ...are integrated to test the effects of expertise exploitation capabilities in electronic channels. The distinctiveness of this study is based on the role of information and computer technology in creating advantage through differential expertise. A model of IT-induced quasi-integration was developed and tested on a sample of 117 travel agencies targeted by American Airlines using the Sabre system and SMARTS. We find that while the degree of quasi-integration is moderately explained by the Sabre link, it is more significantly explained by American Airlines' use of an expertise exploitation capability using SMARTS. These results show the necessity of extending the theoretical perspectives on IT-induced interorganizational relationships from an efficiency perspective to an expertise point of view.
This book discusses the rationale for, and design of, the first Business Education Jam. It reviews key challenges and articulates a vision for how the role and delivery of business education could be ...reimagined in a time when business schools struggle to identify the innovations necessary to meet the needs of a changing world.
A potential head ward retreat landslide area was identified in Munnar, a hill station in Western Ghats of Kerala, India. This imminent landslide was suspected to be formed in three different stages ...viz., evolution of plateau region, upliftment of the plateau region and the consequent slope modification which ultimately facilitated landslide occurrence. Geophysical study through vertical electrical sounding reveals that more than 11 m thick soil is still left in an overhanging position in the crown portion of the landslide and the thickness continues to the top of that ridge. In the event of high rainfall, the land can fail as there is no toe support, and the slope angle is >40º. This area is adjacent to a college building and in the event of any further landslide, the consequence will be high. Slope stability analysis using one-dimensional infinite slope stability model reveals that the entire area occupied by the college and the adjacent areas are unstable even in dry conditions. Rainfall threshold analysis shows that the landslide occurred due to very high amount of a 5-day antecedent rainfall rather than a daily rainfall during the monsoon. All these point towards a pressing requirement of landslide management practices in this area. This study also attempts to suggest a few management practices to minimize the effect of landslides.
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