instruction:
In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
question:
Context: Recent studies have identified MUC4 mucin as a ligand for activation of ErbB2, a receptor tyrosine kinase that modulates epithelial cell proliferation following epithelial damage in airways of asthmatics. In this study, we investigated the potential role of IL-4, one of the Th2 inflammatory cytokines persistent in asthmatic airways, in regulating MUC4 expression using a cell line NCI-H650.', 'Real time PCR analysis was performed to determine concentration and time dependent effects of IL-4 upon MUC4 expression. Nuclear run on experiments were carried out to explore potential transcriptional modulation. Western blotting experiments using a monoclonal antibody specific to ASGP-2 domain of MUC4 were performed to analyze MUC4 glycoprotein levels in plasma membrane fractions. To analyze potential signal transduction cascades, IL-4 treated confluent cultures were co-incubated, separately with a pan-JAK inhibitor, a JAK-3 selective inhibitor or a MEK-1, 2 (MAPK) inhibitor at various concentrations before MUC4 transcript analysis. Corresponding transcription factor activation was tested by western blotting using a monoclonal p-STAT-6 antibody.', 'MUC4 levels increased in a concentration and time specific fashion reaching peak expression at 2.5 ng/ml and 8 h. Nuclear run on experiments revealed transcriptional enhancement. Corresponding increases in MUC4 glycoprotein levels were observed in plasma membrane fractions. Pan-JAK inhibitor revealed marked reduction in IL-4 stimulated MUC4 levels and JAK3 selective inhibitor down-regulated MUC4 mRNA expression in a concentration-dependent fashion. In accordance with the above observations, STAT-6 activation was detected within 5 minutes of IL-4 stimulus. No effect in MUC4 levels was observed on using a MAPK inhibitor.\Question: Is iL-4 induced MUC4 enhancement in respiratory epithelial cells in vitro mediated through JAK-3 selective signaling?
answer:
These observations signify a potential role for IL-4 in MUC4 up-regulation in airway epithelia.

question:
Context: Trauma centers are currently benchmarked on mortality outcomes alone. However, pay-for-performance measures may financially penalize centers based on complications. Our objective was to determine whether the results would be similar to the current standard method of mortality-based benchmarking if trauma centers were profiled on complications.', 'We analyzed data from the National Trauma Data Bank from 2007 to 2010. Patients 16 years or older with blunt or penetrating injuries and an Injury Severity Score (ISS) of 9 or higher were included. Risk-adjusted observed-to-expected (O/E) mortality ratios for each center were generated and used to rank each facility as high, average, or low performing. We similarly ranked facilities on O/E morbidity ratios defined as occurrence of any major complication. Concordance between hospital performance rankings was evaluated using a weighted statistic. Correlation between morbidity- and mortality-based O/E ratios was assessed using Pearson coefficients. Sensitivity analyses were performed to mitigate the competing risk of death for the morbidity analyses.', 'A total of 449,743 patients from 248 facilities were analyzed. The unadjusted morbidity and mortality rates were 10.0% and 6.9%, respectively. No correlation was found between morbidity- and mortality-based O/E ratios (r = -0.01). Only 40% of the centers had similar performance rankings for both mortality and morbidity. Of the 31 high performers for mortality, only 11 centers were also high performers for morbidity. A total of 78 centers were ranked as average, and 11 ranked as low performers on both outcomes. Comparison of hospital performance status using mortality and morbidity outcomes demonstrated poor concordance (weighted = 0.03, p = 0.22).\Question: Does benchmarking trauma centers on mortality alone reflect quality of care : implications for pay-for-performance?
answer:
Mortality-based external benchmarking does not identify centers with high complication rates. This creates a dichotomy between current trauma center profiling standards and measures used for pay-for-performance. A benchmarking mechanism that reflects all measures of quality is needed.

question:
Context: Arteriogenesis represents the maturation of preformed vascular connections in response to flow changes and shear stress. These collateral vessels can restore up to 60% of the native blood flow. Shear stress and vascular injury can induce the release of nucleotides from vascular smooth muscle cells and platelets that can serve as signaling ligands, suggesting they may be involved in mediating arteriogenesis. The P2Y2 nucleotide receptor (P2Y2R) has also been shown to mediate smooth muscle migration and arterial remodeling. Thus, we hypothesize that P2Y2R mediates arteriogenesis in response to ischemia.', 'Hind limb ischemia was induced by femoral artery ligation (FAL) in C57Bl/6NJ or P2Y2R negative mice (P2Y2(-/-)). Hind limb perfusion was measured with laser Doppler perfusion imaging and compared with the sham-operated contralateral limb immediately and at 3, 7, 14, 21, and 28 days after ligation. Collateral vessel size was measured by Microfil casting. Muscle specimens were harvested and analyzed with immunohistochemistry for Ki67, vascular cell adhesion molecule, macrophages, and muscle viability by hematoxylin and essoin stain.', 'Hind limb ischemia induced by FAL in C57Bl/6NJ mice resulted in significant ischemia as measured by laser Doppler perfusion imaging. There was rapid recovery to nearly normal levels of perfusion by 2 weeks. FAL in P2Y2(-/-) mice resulted in severe ischemia with greater tissue loss. Recovery of perfusion was impaired, achieving only 40% compared with wild-type mice by 28 days. Collateral vessels in the P2Y2(-/-) mice were underdeveloped, with reduced vascular cell proliferation and smaller vessel size. The collaterals were 65% the size of wild-type collateral vessels (P = .011). Angiogenesis at 28 days in the ischemic muscle, however, was greater in the P2Y2(-/-) mice (P < .001), possibly related to persistent ischemia leading and angiogenic drive. Early macrophage recruitment was reduced by nearly 70% in P2Y2(-/-) despite significantly more myocyte necrosis. However, inflammation was greater at 28 days in the P2Y2(-/-) mice.\Question: Does p2Y2 nucleotide receptor mediate arteriogenesis in a murine model of hind limb ischemia?
answer:
P2Y2R deficiency does not alter baseline collateral vessel formation but does significantly impair collateral maturation, with resultant persistent limb ischemia despite enhanced angiogenesis. These findings reinforce the importance of arteriogenesis in the recovery of perfusion in ischemic tissues compared with angiogenesis. They also support the role of P2Y2R in mediating this process. The mechanism by which P2Y2R mediates arteriogenesis may involve the recruitment of inflammatory cells to the ischemic tissues, which is essential to arteriogenesis. Approaches to target P2Y2R may yield new therapeutic strategies for the treatment of arterial occlusive disease.