A near-stationary subspace for ridge approximation

Response surfaces are common surrogates for expensive computer simulations in engineering analysis. However, the cost of fitting an accurate response surface increases exponentially as the number of model inputs increases, which leaves response surface construction intractable for high-dimensional, nonlinear models. We describe ridge approximation for fitting response surfaces in several variables. A ridge function is constant along several directions in its domain, so fitting occurs on the coordinates of a low-dimensional subspace of the input space. We review essential theory for ridge approximation---e.g., the best mean-squared approximation and an optimal low-dimensional subspace---and we prove that the gradient-based active subspace is near-stationary for the least-squares problem that defines an optimal subspace. Motivated by the theory, we propose a computational heuristic that uses an estimated active subspace as an initial guess for a ridge approximation fitting problem. We show a simple example where the heuristic fails, which reveals a type of function for which the proposed approach is inappropriate. We then propose a simple alternating heuristic for fitting a ridge function, and we demonstrate the effectiveness of the active subspace initial guess applied to an airfoil model of drag as a function of its 18 shape parameters

Oxyradical mediated tissue injury

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26080/1/0000156.pd

Climate simulation of the latest Permian: Implications for mass extinction

This report presents the results of climate modeling research which indicates that elevated levels of carbon dioxide in the atmosphere at the end of the Permian period led to climatic conditions inhospitable to both marine and terrestrial life. The Permian-Triassic boundary (about 251 million years ago) was the time of the largest known mass extinction in Earth's history, when greater than ninety percent of all marine species, and approximately seventy percent of all terrestrial species, died out. The model, which used paleogeography and paleotopography correct for the time period, indicated that warm high-latitude surface air temperatures and elevated carbon dioxide levels may have resulted in slowed circulation and stagnant, anoxic conditions in Earth's oceans. The report also suggests that the excess carbon dioxide (and sulfur dioxide) may have originated from volcanic activity associated with eruption of the Siberian Trap flood basalts, which took place at the same time. Educational levels: Undergraduate lower division, Undergraduate upper division, Graduate or professional

Oxygen radicals, inflammation, and tissue injury

Inflammatory reactions often result in the activation and recruitment of phagocytic cells (e.g., neutrophils and/ or tissue macrophages) whose products result in injury to the tissue. In killing of endothelial cells by activated neutrophils as well as in lung injury produced by either activated neutrophils or activated macrophages there is evidence that H2O2 and iron play a role. HO[middle dot] may be a key oxygen product related to the process of injury. Endothelial cells in some vascular compartments may be susceptible to neutrophil mediated injury in a manner that is independent of oxygen radicals. On the basis of in vitro observations, a synergy exits between platelets and neutrophils, resulting in enhanced oxygen radical formation by the latter. Finally, the cytokines, interleukin 1 and tumor necrosis factor, released from macrophages have both direct stimulatory effects on oxygen radical formation in neutrophils and can "prime" macrophages for enhanced oxygen radical responses to other agonists. Cytokines may also alter endothelial cells rendering them more susceptible to oxygen radical mediated injury by neutrophils. This suggests a complex network of interactions between phagocytic cells and peptide mediators, the result of which is acute, oxygen radical mediated tissue injury.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27560/1/0000604.pd

Neutrophil Adhesion to Human Endothelial Cells is Induced by the Membrane Attack Complex: The Roles of P-Selectin and Platelet Activating Factor

A variety of inflammatory diseases are accompanied by activation of the complement system. We examined the role of the membrane attack complex (MAC) in mediating neutrophil adhesion to endothelial cells. To assemble the MAC in endothelial cell monolayers, a C5b-like molecule was created through the treatment of purified C5 with the oxidizing agent chloramine-T, followed by addition of the remaining components (C6-C9) that constitute the MAC. Use of this method abrogated potentially confounding effects mediated by other complement components (e.g., C5a). MAC assembly resulted in a rapid (30 min), concentration-dependent increase in neutrophil adherence. A monoclonal antibody directed against P-selectin inhibited MAC-mediated neutrophil adhesion. A whole cell EIA confirmed P-selectin expression after formation of the MAC. Incubation of neutrophils with the platelet-activating factor receptor antagonist, CF 3988, also significantly decreased adhesion, indicating that PAF plays a role in MAC-mediated adhesion. These results suggest that the MAC can promote neutrophil adhesion through P-selectin and PAF-mediated mechanisms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44521/1/10753_2004_Article_415305.pd

Pathophysiology of leukocyte-mediated tissue injury

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29292/1/0000353.pd

Prescription Opioid Use among Pregnant Women Enrolled in Rhode Island Medicaid

Objective: Our objective was to identify the patterns of opioid use among pregnant women enrolled in RI Medicaid. Methods: This study used linked RI Medicaid and RI Birth Certificate data from 01/01/2006 to 12/31/2016. We examined temporal trends of prescription opioid dispensings and identified risk factors associated with opioids use during pregnancy. Results: Among 25,500 RI Medicaid enrolled pregnant women who delivered a live baby from 2008 to 2016, 1,914 (7.5%) received at least one prescription for an opioid medication during pregnancy, 810 (3.2%) were during the first trimester, 633 (2.5%) during the second trimester, and 866 (3.4%) during the third trimester. Of these, 213 (0.8%) women received 3 or more opioids during pregnancy. The prevalence of prescription opioids dispensed in pregnant women increased from 4.9% in 2008 to 9.6% in 2015 (β SD: 0.66 0.28, P=0.05). Conclusions: Prescription opioid use during pregnancy has increased among women enrolled in RI Medicaid