714-6 Increased Action Potential Prolongation by Low Voltage Biphasic versus Monophasic Field Stimuli

In an in-vitro model for defibrillation, we compared action potential prolongation (APP) by monophasic (MONO) and biphasic (BI) field stimulus shocks in epicardial tissue strips from 10 dogs. Strips were paced at one end while cellular impalements were maintained in the center (cell A) to measure APP and at the other end (cell B) to determine if shocks produced propagated activations. Rectangular shocks (0.5 to 10V/cm) were delivered with MONO (8 ms) or BI (4.8/3.2 ms) waveforms at times ranging from 44% to 112% of the APD90 of cell A. Recordings were made during 3975 shocked and 2578 control action potentials. APP was the % increase in shocked repolarization time relative to the interlaced controls.While weaker MONO and BI shocks produced propagated activations, the threshold intensity ABOVEwhich shocks did NOTproduce activations was 25.9% lower (p<0.0005) for BI (2.78V/cm) versus MONO (3.75 V/cm). At most intensities and timings, MONO produced more APP than BI. However, for 2 to 4 V/cm shocks at 90% to 100% of APD90, BI produced more APP than MONO (36.9% versus 17.7%, P < 0.0001) shocks.Thus, increased defibrillation efficacy of BI waveforms may result from a greater APP by BI in the low-voltage gradient regions of the heart during defibrillation

Investment Behavior and the Small Firm Effect

Our purpose in this review is to develop one explanation of market behavior which is consistent with the many empirical findings that appear to be inconsistent with the market efficiency hypothesis. To date, researchers have attempted to reconcile their empirical results with market efficiency based on either measurement error or structural inefficiencies. We propose a different approach to market efficiency. We posit that the empirical findings previous researchers report are by their nature ex post, and are a direct result of a market which is best described as efficient. We develop a model and provide a simulation to support this explanation

Attribution of detected changes in streamflow using multiple working hypotheses

This paper revisits a widely cited study of the Boyne catchment in east Ireland that attributed greater streamflow from the mid-1970s to increased precipitation linked to a shift in the North Atlantic Oscillation. Using the method of multiple working hypotheses we explore a wider set of potential drivers of hydrological change. Rainfall-runoff models are used to reconstruct streamflow to isolate the effect of climate, taking account of both model structure and parameter uncertainty. The Mann-Kendall test for monotonic trend and Pettitt change point test are applied to explore signatures of change. Contrary to earlier work, arterial drainage and simultaneous onset of field drainage in the 1970s and early 1980s are now invoked as the predominant drivers of change in annual mean and high flows within the Boyne. However, a change in precipitation regime is also present in March, thereby amplifying the effect of drainage. This new explanation posits that multiple drivers acting simultaneously were responsible for the observed change, with the relative contribution of each driver dependant on the timescale investigated. This work demonstrates that valuable insights can be gained from a systematic application of the method of multiple working hypotheses in an effort to move towards more rigorous attribution, which is an important part of managing emerging impacts on hydrological systems. © Author(s) 2014

Improving Organ Procurement Travel Practices in the United States: Proceedings from the Michigan Donor Travel Forum

There are significant risks and inefficiencies associated with organ procurement travel. In an effort to identify, quantify, and define opportunities to mitigate these risks and inefficiencies, 25 experts from the transplantation, transportation and insurance fields were convened. The forum concluded that: on procurement travel practices are inadequate, there is wide variation in the quality of aero-medical transportation, current travel practices for organ procurement are inefficient and there is a lack of standards for organ procurement travel liability coverage. The forum concluded that the transplant community should require that air-craft vendors adhere to industry quality standards compatible with the degree of risk in their mission profiles. Within this context, a purchasing collaborative within the transplant community may offer opportunities for improved service and safety with lower costs. In addition, changes in travel practices should be considered with broader sharing of procurement duties across centers. Finally, best practice standards should be instituted for life insurance for transplant personnel and liability insurance for providers. Overall, the aims of these proposals are to raise procurement travel standards and in doing so, to improve the transplantation as a whole.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79257/1/j.1600-6143.2009.02964.x.pd

2003 Manifesto on the California Electricity Crisis

The authors, an ad-hocgroup of professionals with experience in regulatory and energy economics, share a common concern with the continuing turmoil facing the electricity industry ("the industry") in California. Most ofthe authorsendorsed the first California Electricity Manifesto issued on January 25, 2001. Almost two years have passed since that first Manifesto. While wholesale electric prices have moderated and California no longer faces the risk of blackouts, in many ways the industry is in worse shape now than it was at the start of 2001. As a result, the group of signatories continues to have a deep concern with the conflicting policy directions being pursued for the industry at both the State and Federal levels of government and the impact the uncertainties associated with these conflicting policies will have, long term, on the economy of California. Theauthorshave once again convened under the auspices of the Institute of Management, Innovation and Organization at the University of California, Berkeley, to put forward ourtheir ideas on a basic set of necessary policies to move the industry forward for the benefit of all Californians and the nation. The authors point out that theydo not pretend to be "representative." They do bring, however, a very diverse range of backgrounds and expertise.Technology and Industry, Regulatory Reform

Circulating Biomarkers to Identify Responders in Cardiac Cell therapy.

Bone marrow mononuclear cell (BM-MNC) therapy in ST-elevation acute myocardial infarction (STEMI) has no biological inclusion criteria. Here, we analyzed 63 biomarkers and cytokines in baseline plasma samples from 77 STEMI patients treated with BM-MNCs in the TIME and Late-TIME trials as well as 61 STEMI patients treated with placebo. Response to cell therapy was defined by changes in left ventricular ejection fraction, systolic/diastolic volumes, and wall motion indexes. We investigated the clinical value of circulating proteins in outcome prediction using significance testing, partial least squares discriminant analysis, and receiver operating characteristic (ROC) analysis. Responders had higher biomarker levels (76-94% elevated) than non-responders. Several biomarkers had values that differed significantly (P < 0.05) between responders and non-responders including stem cell factor, platelet-derived growth factor, and interleukin-15. We then used these lead candidates for ROC analysis and found multiple biomarkers with values areas under the curve >0.70 including interleukin 15. These biomarkers were not involved in the placebo-treated subjects suggesting that they may have predictive power. We conclude that plasma profiling after STEMI may help identify patients with a greater likelihood of response to cell-based treatment. Prospective trials are needed to assess the predictive value of the circulating biomarkers

TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup.

Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient\u27s progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. ©2017 AACR