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A series of 3-(2,4-dichlorophenyl)-N-alkyl-N-fluoroalkyl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amines were synthesized and evaluated as potential positron emission tomography (PET) tracers for the corticotropin-releasing factor type-1 (CRF1) receptor. Compounds 27, 28, 29, and 30 all displayed high binding affinity (⩽1.2 nM) to the CRF1 receptor when assessed by in vitro competition binding assays at 23 °C, whereas a decrease in affinity (⩾10-fold) was observed with compound 26. The logP7.4 values of [(18)F]26-[(18)F]29 were in the range of ∼2.2-2.8 and microPET evaluation of [(18)F]26-[(18)F]29 in an anesthetized male cynomolgus monkey demonstrated brain penetrance, but specific binding was not sufficient enough to differentiate regions of high CRF1 receptor density from regions of low CRF1 receptor density. Radioactivity uptake in the skull, and sphenoid bone and/or sphenoid sinus during studies with [(18)F]28, [(18)F]28-d8, and [(18)F]29 was attributed to a combination of [(18)F]fluoride generated by metabolic defluorination of the radiotracer and binding of intact radiotracer to CRF1 receptors expressed on mast cells in the bone marrow. Uptake of [(18)F]26 and [(18)F]27 in the skull and sphenoid region was rapid but then steadily washed out which suggests that this behavior was the result of binding to CRF1 receptors expressed on mast cells in the bone marrow with no contribution from [(18)F]fluoride., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Kornell and Bjork (Psychological science 19:585-592, 2008) found that interleaving exemplars of different categories enhanced inductive learning of the concepts based on those exemplars. They hypothesized that the benefit of mixing exemplars from different categories is that doing so highlights differences between the categories. Kang and Pashler (Applied cognitive psychology 26:97-103, 2012) obtained results consistent with this discriminative-contrast hypothesis: Interleaving enhanced inductive learning, but temporal spacing, which does not highlight category differences, did not. We further tested the discriminative-contrast hypothesis by examining the effects of interleaving and spacing, as well as their combined effects. In three experiments, using photographs of butterflies and birds as the stimuli, temporal spacing was harmful when it interrupted the juxtaposition of interleaved categories, even when total spacing was held constant, supporting the discriminative-contrast hypothesis. Temporal spacing also had value, however, when it did not interrupt discrimination processing.

Objectives: The present study was designed to characterize Arizona schools with high rates of permanent PBE among kindergartners, and to determine the degree to which they aggregate across the state., Methods: Data for permanent personal belief exemptions (PBE) were accessed through the 2010-2011 kindergarten Immunization Data Report (IDR) from the Arizona Department of Health Services (AZDHS), and were linked to the 2009-2010 data from the National Center of Education Statistics (NCES). Incidence rate ratios (IRR) were calculated using negative binomial regression, and hotspots were identified using Getis-Ord Gi*., Results: Schools with highest proportion of white students compared to the lowest had the highest exemption rates (IRR=14.11; 95% confidence interval [CI], 9.47-21.03); furthermore charter schools and those with low prevalence of free and reduced lunches had significantly higher rates of PBE. Statewide analyses of PBE identified higher rates of permanent PBE in northern vs. southern Arizona, while a more focused examination of the central Arizona region demonstrated a pattern of increased PBE from west to east., Conclusion: In Arizona, the profile of a high PBE school is that of a charter school attended by predominantly white, higher-income students. The local and statewide hotspots serve as a challenge that requires a multi-faceted approach that calls upon all healthcare professionals. It is important that both local and statewide pockets be targeted by local and state officials either to improve vaccination uptake or to employ careful monitoring to identify outbreaks at their onset., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We previously showed that when rats were trained to fear an auditory conditioned stimulus (CS) by pairing it with a mild unilateral shock to the eyelid (the unconditioned stimulus, or US), conditioned freezing depended upon the amygdala contralateral but not ipsilateral from the US. It was proposed that convergent activation of amygdala neurons by the CS and US occurred mainly in the amygdala contralateral from US delivery, causing memories of the CS-US association to be stored primarily by that hemisphere. In the present study, we further tested this interpretation by administering unilateral infusions of U0126 (in 50% dimethyl sulfoxide (DMSO) vehicle) to block phosphorylation of extracellular signal-responsive kinase (ERK) in the amygdala prior to CS-US pairings. Conditioned freezing was impaired 24 h after training when U0126 was infused contralaterally-but not ipsilaterally-from the US, suggesting that fear memories were consolidated mainly by the contralateral amygdala. However, immunostaining experiments revealed that ERK phosphorylation was elevated in both hemispheres of the amygdale's lateral (LA) and centrolateral (CeL) nuclei after paired (but not unpaired (UNP)) presentations of the CS and US. Thus, fear acquisition induced ERK phosphorylation bilaterally in the amygdala, even though the ipsilateral hemisphere did not appear to participate in conditioned freezing. These findings suggest that associative plasticity may occur in both amygdala hemispheres even when only one hemisphere is involved in freezing behavior. Conditioning-induced ERK phosphorylation was identical in both hemispheres of LA, but was slightly greater in the contralateral than ipsilateral hemisphere of CeL. Hence, asymmetric induction of plasticity in CeL might help to explain why conditioned freezing depends preferentially upon the amygdala contralateral from the US in our fear conditioning paradigm.