Considerations of PoCUS vs Manual Pulse Check in Predicting ROSC for Patients Presenting in PEA

Background: Point of care ultrasound (PoCUS) has enabled providers to draw a contrast between true PEA (Pulseless Electrical Activity) and pseudo-PEA. The incorporation of PoCUS pulse checks in PEA and pseudo-PEA has been shown to more accurately predict Return of Spontaneous Circulation (ROSC) when compared to standard manual pulse checks. However, concerns have been raised in recent observational studies regarding increased duration of PoCUS pulse checks compared to manual pulse checks leading to suboptimal CPR and subsequent deterioration of ACLS protocol integrity. Objective: This clinical review aims to examine the utility and practical implementation of PoCUS versus manual pulse check in the prediction of ROSC for patients presenting to the hospital in PEA. Discussion: A PubMed, MEDLINE, Scopus, and CINAHL databases literature search was conducted with the following search terms: point of care ultrasound (PoCUS), pulseless electrical activity (PEA), Pseudo Pulseless Electrical Activity (Pseudo PEA), manual pulse check, Return of Spontaneous Circulation (ROSC) Conclusions: PoCUS plays in an important role in predicting ROSC for patients presenting in PEA. Given the importance of the distinction between true PEA and pseudo-PEA, the literature suggests implementation of training for providers in expedient and skillful use of PoCUS to identify pseudo-PEA may be beneficial provided that pauses in CPR are not prolonged

Financing Direct Democracy: Revisiting the Research on Campaign Spending and Citizen Initiatives

The conventional view in the direct democracy literature is that spending against a measure is more effective than spending in favor of a measure, but the empirical results underlying this conclusion have been questioned by recent research. We argue that the conventional finding is driven by the endogenous nature of campaign spending: initiative proponents spend more when their ballot measure is likely to fail. We address this endogeneity by using an instrumental variables approach to analyze a comprehensive dataset of ballot propositions in California from 1976 to 2004. We find that both support and opposition spending on citizen initiatives have strong, statistically significant, and countervailing effects. We confirm this finding by looking at time series data from early polling on a subset of these measures. Both analyses show that spending in favor of citizen initiatives substantially increases their chances of passage, just as opposition spending decreases this likelihood

Bipolar spintronics: From spin injection to spin-controlled logic

An impressive success of spintronic applications has been typically realized in metal-based structures which utilize magnetoresistive effects for substantial improvements in the performance of computer hard drives and magnetic random access memories. Correspondingly, the theoretical understanding of spin-polarized transport is usually limited to a metallic regime in a linear response, which, while providing a good description for data storage and magnetic memory devices, is not sufficient for signal processing and digital logic. In contrast, much less is known about possible applications of semiconductor-based spintronics and spin-polarized transport in related structures which could utilize strong intrinsic nonlinearities in current-voltage characteristics to implement spin-based logic. Here we discuss the challenges for realizing a particular class of structures in semiconductor spintronics: our proposal for bipolar spintronic devices in which carriers of both polarities (electrons and holes) contribute to spin-charge coupling. We formulate the theoretical framework for bipolar spin-polarized transport, and describe several novel effects in two- and three-terminal structures which arise from the interplay between nonequilibrium spin and equilibrium magnetization.Comment: 16 pages, 7 figure

Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies

Microphysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including 3D matrices and microperfusion. Here, we report an approach to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms that are compatible with the quantitative study of a range of compounds, including lipophilic drugs. We describe three different platform designs - "4-way", "7-way", and "10-way" - each accommodating a mixing chamber and up to 4, 7, or 10 MPSs. Platforms accommodate multiple different MPS flow configurations, each with internal re-circulation to enhance molecular exchange, and feature on-board pneumatically-driven pumps with independently programmable flow rates to provide precise control over both intra- and inter-MPS flow partitioning and drug distribution. We first developed a 4-MPS system, showing accurate prediction of secreted liver protein distribution and 2-week maintenance of phenotypic markers. We then developed 7-MPS and 10-MPS platforms, demonstrating reliable, robust operation and maintenance of MPS phenotypic function for 3 weeks (7-way) and 4 weeks (10-way) of continuous interaction, as well as PK analysis of diclofenac metabolism. This study illustrates several generalizable design and operational principles for implementing multi-MPS "physiome-on-a-chip" approaches in drug discovery.United States. Army Research Office (Grant W911NF-12-2-0039

Diversity Outbred Mice Identify Population-Based Exposure Thresholds and Genetic Factors that Influence Benzene-Induced Genotoxicity.

BACKGROUND: Inhalation of benzene at levels below the current exposure limit values leads to hematotoxicity in occupationally exposed workers. OBJECTIVE: We sought to evaluate Diversity Outbred (DO) mice as a tool for exposure threshold assessment and to identify genetic factors that influence benzene-induced genotoxicity. METHODS: We exposed male DO mice to benzene (0, 1, 10, or 100 ppm; 75 mice/exposure group) via inhalation for 28 days (6 hr/day for 5 days/week). The study was repeated using two independent cohorts of 300 animals each. We measured micronuclei frequency in reticulocytes from peripheral blood and bone marrow and applied benchmark concentration modeling to estimate exposure thresholds. We genotyped the mice and performed linkage analysis. RESULTS: We observed a dose-dependent increase in benzene-induced chromosomal damage and estimated a benchmark concentration limit of 0.205 ppm benzene using DO mice. This estimate is an order of magnitude below the value estimated using B6C3F1 mice. We identified a locus on Chr 10 (31.87 Mb) that contained a pair of overexpressed sulfotransferases that were inversely correlated with genotoxicity. CONCLUSIONS: The genetically diverse DO mice provided a reproducible response to benzene exposure. The DO mice display interindividual variation in toxicity response and, as such, may more accurately reflect the range of response that is observed in human populations. Studies using DO mice can localize genetic associations with high precision. The identification of sulfotransferases as candidate genes suggests that DO mice may provide additional insight into benzene-induced genotoxicity. CITATION: French JE, Gatti DM, Morgan DL, Kissling GE, Shockley KR, Knudsen GA, Shepard KG, Price HC, King D, Witt KL, Pedersen LC, Munger SC, Svenson KL, Churchill GA. 2015. Diversity Outbred mice identify population-based exposure thresholds and genetic factors that influence benzene-induced genotoxicity. Environ Health Perspect 123:237-245; http://dx.doi.org/10.1289/ehp.1408202