Patients diagnosed with acute PE in U.S. EDs have high functional status, and their mortality rate is low. These registry data suggest that appropriate initial medical management of ED patients with severe PE with anticoagulation is poorly standardized and indicate a need for research to determine the appropriate threshold for empiric treatment when PE is suspected before diagnostic confirmation.
A procedure for lowering the mean square error (MSE) of the minimum variance unbiased linear estimator (MVULE) of the mean of a population is considered. The technique employed is shrinkage of the MVULE towards a natural origin, po, in the parameter space. The suggested estimator is:The case where Po= 0 is given special consideration. This is the general case for the normal distribution. When jp/uz I is small, shrinkage buys decreased MSE at the expense of increased MSE for jp/uz jlarge.
Hepatocellular carcinoma (HCC) is often diagnosed at an advanced stage for which there are limited treatment options. Two recently identified human heparin-degrading endosulfatases, named sulfatase 1 (SULF1) and sulfatase 2 (SULF2), have been found to be involved in liver carcinogenesis. SULF1 and SULF2 desulfate cell surface and extracellular matrix heparan sulfate proteoglycans (HSPGs) and modulate heparin-binding growth factor signaling in multiple cancers, including HCCs. SULF1 inhibits HCC tumor cell growth in vitro and in nude mice in vivo, partially through effects on gene expression mediated through histone H4 acetylation. While SULF1 is downregulated in the majority of HCC cell lines and approximately 30% of primary HCCs, SULF2 is up regulated in almost all HCC cell lines and in 60% of primary HCCs. In contrast to the tumor suppressor effect of SULF1, expression of SULF2 activates mitogen activated protein kinase (MAPK) and Akt pathways, promotes HCC cell growth in vitro and in vivo, and is associated with decreased survival of HCC patients. Targeting SULF2 or the interaction between SULF2 and SULF1 may lead to novel therapeutics for the treatment of HCCs.
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