Computational models predict that experience-driven clustering of coactive synapses is a mechanism for information storage. This prediction has remained untested, because it is difficult to approach through time-lapse analysis. Here, we exploit a unique feature of the barn owl auditory localization pathway that permits retrospective analysis of prelearned and postlearned circuitry: owls reared wearing prismatic spectacles develop an adaptive microcircuit that coexists with the native one but can be analyzed independently based on topographic location. To visualize the clustering of axodendritic contacts (potential synapses) within these zones, coactive axons were labeled by focal injection of fluorescent tracer and their target dendrites labeled with an antibody directed against CaMKII (calcium/ calmodulin-dependent protein kinase type II, ␣ subunit). Using high-resolution confocal imaging, we measured the distance from each contact to its nearest neighbor on the same branch of dendrite. We found that the distribution of intercontact distances for the adaptive zone was shifted dramatically toward smaller values compared with distributions for either the maladaptive zone of the same animals or the adaptive zone of normal juveniles, which indicates that a dynamic clustering of contacts had occurred. Moreover, clustering in the normal zone was greater in normal juveniles than in prism-adapted owls, indicative of declustering. These data demonstrate that clustering is bidirectionally adjustable and tuned by behaviorally relevant experience. The microanatomical configurations in all zones of both experimental groups matched the functional circuit strengths that were assessed by in vivo electrophysiological mapping. Thus, the observed changes in clustering are appropriately positioned to contribute to the adaptive strengthening and weakening of auditorydriven responses.

NCT01171898.

PE is neither highly sensitive nor specific for identifying active synovitis when compared to US, and screening with US can identify subclinical disease. In joints with both non-bony swelling and limitation of motion with pain on motion or tenderness, and in the knee joint, little additional information is gained by US. This has implications for classification and treatment of JIA.

PurposeAbiraterone is the active metabolite of the pro-drug abiraterone acetate (AA) and a selective inhibitor of CYP17, a key enzyme in testosterone synthesis, and improves overall survival in postdocetaxel metastatic castration-resistant prostate cancer (mCRPC). This open-label, single-arm phase 1b study was conducted to assess the effect of AA and abiraterone on the QT interval.MethodsThe study was conducted in 33 patients with mCRPC. Patients received AA 1,000 mg orally once daily + prednisone 5 mg orally twice daily. Electrocardiograms (ECGs) were collected in triplicate using 12-lead Holter monitoring. Baseline ECGs were obtained on Cycle 1 Day-1. Serial ECG recordings and time-matched pharmacokinetic (PK) blood samples were collected over 24 h on Cycle 1 Day 1 and Cycle 2 Day 1. Serial PK blood samples were also collected over 24 h on Cycle 1 Day 8.ResultsAfter AA administration, the upper bound of the 2-sided 90 % confidence interval (CI) for the mean baseline-adjusted QTcF change was <10 ms; no patients discontinued due to QTc prolongation or adverse events. No apparent relationship between change in QTcF and abiraterone plasma concentrations was observed [estimated slope (90 % CI): 0.0031 (−0.0040, 0.0102)].ConclusionsThere is no significant effect of AA plus prednisone on the QT/QTc interval in patients with mCRPC.

Values of distal femoral epiphyseal cartilage thickness measured by sonography of the femorotibial joint are similar to those reported at the patellofemoral joint. We propose that femoral epiphyseal cartilage thickness be measured on the basis of a coronal image at the medial femorotibial joint. This technique requires less knee flexion, which may prove advantageous when evaluating cartilage in patients with joint inflammation and a limited range of motion. It also allows concurrent measurement of tibial epiphyseal cartilage and thus provides another parameter for assessing cartilage loss.