Neurocardiac risk stratification 6 hours after resuscitation from cardiac arrest

Introduction: • An increasing number of patients are resuscitated from out-ofhospital cardiac arrest. Triage to optimal treatment pathways could improve and increase the efficacy of post-resuscition care. • Despite great variability in etiology, duration, and patterns of injury from cardiac arrest, post-resuscitation treatment guidelines emphasize standard treatments. We hypothesize that by categorizing competing risks very early after resuscitation, it may be possible to improve the efficacy and efficiency of care. • When measured very early after resuscitation, suppression ratio (SR, the percentage of suppressed EEG), correlates with severity of brain injury and the likelihood of poor neurological outcome. • The CREST score2 is a validated model to predict circulatoryetiology death (CED) based on: Coronary artery disease, initial nonshockable Rhythm, Ejection fraction25 minutes

Assessing the authority of political office-holders: the leadership capital index

This article argues that the extent to which political office-holders can effectively attain and wield authority is a function of the stock of ‘leadership capital.’ Drawing on the concept of political capital, we define leadership capital as aggregate authority composed of three dimensions: skills; relations; and reputation of a leader. Leadership capital ebbs and flows over time within a trajectory of acquisition, expenditure and inevitable depreciation. We present a Leadership Capital Index (LCI) that systematically maps out the three broad areas combining concrete measures with interpretive aspects. This can be used as a tool for systematically tracking and comparing the political fortunes of leaders in a way that is both more nuanced and robust than exclusive reliance on the latest approval ratings. We offer an illustrative case study of Tony Blair demonstrating the LCI. We conclude by discerning several promising paths for future development of the LCI

Cystatin E/M suppresses legumain activity and invasion of human melanoma

<p>Abstract</p> <p>Background</p> <p>High activity of cysteine proteases such as legumain and the cathepsins have been shown to facilitate growth and invasion of a variety of tumor types. In breast cancer, several recent studies have indicated that loss of the cysteine protease inhibitor cystatin E/M leads to increased growth and metastasis. Although cystatin E/M is normally expressed in the skin, its role in cysteine protease regulation and progression of malignant melanoma has not been studied.</p> <p>Methods</p> <p>A panel of various non-melanoma and melanoma cell lines was used. Cystatin E/M and C were analyzed in cell media by immunoblotting and ELISA. Legumain, cathepsin B and L were analyzed in cell lysates by immunoblotting and their enzymatic activities were analyzed by peptide substrates. Two melanoma cell lines lacking detectable secretion of cystatin E/M were transfected with a cystatin E/M expression plasmid (pCST6), and migration and invasiveness were studied by a Matrigel invasion assay.</p> <p>Results</p> <p>Cystatin E/M was undetectable in media from all established melanoma cell lines examined, whereas strong immunobands were detected in two of five primary melanoma lines and in two of six lines derived from patients with metastatic disease. Among the four melanoma lines secreting cystatin E/M, the glycosylated form (17 kD) was predominant compared to the non-glycosylated form (14 kD). Legumain, cathepsin B and L were expressed and active in most of the cell lines, although at low levels in the melanomas expressing cystatin E/M. In the melanoma lines where cystatin E/M was secreted, cystatin C was generally absent or expressed at a very low level. When melanoma cells lacking secretion of cystatin E/M were transfected with pCST6, their intracellular legumain activity was significantly inhibited. In contrast, cathepsin B activity was not affected. Furthermore, invasion was suppressed in cystatin E/M over-expressing melanoma cell lines as measured by the transwell Matrigel assay.</p> <p>Conclusions</p> <p>These results suggest that the level of cystatin E/M regulates legumain activity and hence the invasive potential of human melanoma cells.</p