U-Shaped Relation between Plasma Oxytocin Levels and Behavior in the Trust Game

10.1371/journal.pone.0051095PLoS ONE712

Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity

Efficient transcriptional programming promises to open new frontiers in regenerative medicine. However, mechanisms by which programming factors transform cell fate are unknown, preventing more rational selection of factors to generate desirable cell types. Three transcription factors, Ngn2, Isl1 and Lhx3, were sufficient to program rapidly and efficiently spinal motor neuron identity when expressed in differentiating mouse embryonic stem cells. Replacement of Lhx3 by Phox2a led to specification of cranial, rather than spinal, motor neurons. Chromatin immunoprecipitation–sequencing analysis of Isl1, Lhx3 and Phox2a binding sites revealed that the two cell fates were programmed by the recruitment of Isl1-Lhx3 and Isl1-Phox2a complexes to distinct genomic locations characterized by a unique grammar of homeodomain binding motifs. Our findings suggest that synergistic interactions among transcription factors determine the specificity of their recruitment to cell type–specific binding sites and illustrate how a single transcription factor can be repurposed to program different cell types.Project ALS FoundationNational Institutes of Health (U.S.) (Grant P01 NS055923

Mistakes and Pitfalls Associated with Two-Point Compression Ultrasound for Deep Vein Thrombosis

Introduction: Two-point compression ultrasound is purportedly a simple and accurate means to diagnose proximal lower extremity deep vein thrombosis (DVT), but the pitfalls of this technique have not been fully elucidated. The objective of this study is to determine the accuracy of emergency medicine resident-performed two-point compression ultrasound, and to determine what technical errors are commonly made by novice ultrasonographers using this technique. Methods: This was a prospective diagnostic test assessment of a convenience sample of adult emergency department (ED) patients suspected of having a lower extremity DVT. After brief training on the technique, residents performed two-point compression ultrasounds on enrolled patients. Subsequently a radiology department ultrasound was performed and used as the gold standard. Residents were instructed to save videos of their ultrasounds for technical analysis. Results: Overall, 288 two-point compression ultrasound studies were performed. There were 28 cases that were deemed to be positive for DVT by radiology ultrasound. Among these 28, 16 were identified by the residents with two-point compression. Among the 260 cases deemed to be negative for DVT by radiology ultrasound, 10 were thought to be positive by the residents using two-point compression. This led to a sensitivity of 57.1% (95% CI [38.8-75.5]) and a specificity of 96.1% (95% CI [93.8-98.5]) for resident-performed two-point compression ultrasound. This corresponds to a positive predictive value of 61.5% (95% CI [42.8-80.2]) and a negative predictive value of 95.4% (95% CI [92.9-98.0]). The positive likelihood ratio is 14.9 (95% CI [7.5-29.5]) and the negative likelihood ratio is 0.45 (95% CI [0.29-0.68]). Video analysis revealed that in four cases the resident did not identify a DVT because the thrombus was isolated to the superior femoral vein (SFV), which is not evaluated by two-point compression. Moreover, the video analysis revealed that the most common mistake made by the residents was inadequate visualization of the popliteal vein. Conclusion: Two-point compression ultrasound does not identify isolated SFV thrombi, which reduces its sensitivity. Moreover, this technique may be more difficult than previously reported, in part because novice ultrasonographers have difficulty properly assessing the popliteal vein