An initial reaction among many observers of urban America to recently released data showing a net migration out of its metropolitan areas is that this phenomenon must reflect nothing more than an accelerated expansion of these areas beyond their conventionally defined borders. This paper tests this hypothesis by tracing out the behavior of the Hoover index for five levels of areal disaggregation in the US. In Statistical Geography, Duncan and his collaborators found that for the period 1900–1950 there was dispersal at the finest and coarsest grains of areal disaggregation (reflecting city—suburb and East—West dispersal, respectively) and concentration at intermediate grains (reflecting rural-urban migration). We find that, by 1970, dispersal was occurring at all levels of areal disaggregation. That is, using the county as our basic unit of analysis, and building up increasingly more aggregated regions based on these units, we are unable to find an increase in concentration at any level of areal aggregation. We conclude that dispersal is more than a statistical artifact of the way in which metropolitan areas are defined.
Previous studies of Drosophila flight muscle neuromuscular synapses have revealed their tripartite architecture and established an attractive experimental model for genetic analysis of glial function in synaptic transmission. Here we extend these findings by defining a new Drosophila glial cell type, designated peripheral perisynaptic glia (PPG), which resides in the periphery and interacts specifically with fine motor axon branches forming neuromuscular synapses. Identification and specific labeling of PPG was achieved through cell type-specific RNAi-mediated knockdown (KD) of a glial marker, Glutamine Synthetase 2 (GS2). In addition, comparison among different Drosophila neuromuscular synapse models from adult and larval developmental stages indicated the presence of tripartite synapses on several different muscle types in the adult. In contrast, PPG appear to be absent from larval body wall neuromuscular synapses, which do not exhibit a tripartite architecture but rather are imbedded in the muscle plasma membrane. Evolutionary conservation of tripartite synapse architecture and peripheral perisynaptic glia in vertebrates and Drosophila suggests ancient and conserved roles for glia-synapse interactions in synaptic transmission.
Purpose of reviewManagement for patients with refractory eosinophilic esophagitis (EoE) remains a clinical challenge. This review aims to define refractory EoE, explore rates and reasons for nonresponse, and discuss the evidence that informs the approach to these patients.Recent findingsMany patients will fail first-line therapies for EoE. Longer duration of therapy can increase response rates, and initial nonresponders may respond to alternative first-line therapies. There are ongoing clinical trials evaluating novel therapeutics that hold promise for the future of EoE management. Increasingly, there is recognition of the contribution of oesophageal hypervigilance, symptom-specific anxiety, abnormal motility and oesophageal remodelling to ongoing clinical symptoms in patients with EoE.SummaryFor refractory EoE, clinicians should first assess for adherence to treatment, adequate dosing and correct administration. Extending initial trials of therapy or switching to an alternative first-line therapy can increase rates of remission. Patients who are refractory to first-line therapy can consider elemental diets, combination therapy or clinical trials of new therapeutic agents. Patients with histologic remission but ongoing symptoms should be evaluated for fibrostenotic disease with EGD, barium esophagram or the functional luminal imaging probe (FLIP) and should be assessed for the possibility of oesophageal hypervigilance.
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