Application of Sequential Quadratic Programming to Large-Scale Structural Design Problems

Large-scale structural optimization problems are often difficult to solve with reasonable efficiency and accuracy. Such problems are often characterized by constraint functions which are not explicitly defined. Constraint and gradient functions are usually expensive to evaluate. An optimization approach which uses the NLPQL sequential quadratic programming algorithm of Schittkowski, integrated with the Automated Structural Optimization System ASTROS is tested. The traditional solution approach involves the formulation and solution of an explicitly defined approximate problem during each iteration. This approach is replaced by a simpler approach in which the approximate problem is eliminated. In the simpler approach, each finite element analysis is followed by one iteration of the optimizer. To compensate for the cost of additional analyses incurred by the elimination of the approximate problem, a much more restrictive active set strategy is used. The approach is applied to three large structures problems, including one with constraints from multiple disciplines. Results and algorithm performance comparisons are given. Although not much computational efficiency is gained, the alternative approach gives accurate solutions. The largest of the three problems, which had 1527 design variables and 6124 constraints was solved with ASTROS for the first time using a direct method. The resulting design represents the lowest weight feasible design recorded to date

Computing Nash Equilibrium in Wireless Ad Hoc Networks: A Simulation-Based Approach

This paper studies the problem of computing Nash equilibrium in wireless networks modeled by Weighted Timed Automata. Such formalism comes together with a logic that can be used to describe complex features such as timed energy constraints. Our contribution is a method for solving this problem using Statistical Model Checking. The method has been implemented in UPPAAL model checker and has been applied to the analysis of Aloha CSMA/CD and IEEE 802.15.4 CSMA/CA protocols.Comment: In Proceedings IWIGP 2012, arXiv:1202.422

Evaluation Research and Institutional Pressures: Challenges in Public-Nonprofit Contracting

This article examines the connection between program evaluation research and decision-making by public managers. Drawing on neo-institutional theory, a framework is presented for diagnosing the pressures and conditions that lead alternatively toward or away the rational use of evaluation research. Three cases of public-nonprofit contracting for the delivery of major programs are presented to clarify the way coercive, mimetic, and normative pressures interfere with a sound connection being made between research and implementation. The article concludes by considering how public managers can respond to the isomorphic pressures in their environment that make it hard to act on data relating to program performance.This publication is Hauser Center Working Paper No. 23. The Hauser Center Working Paper Series was launched during the summer of 2000. The Series enables the Hauser Center to share with a broad audience important works-in-progress written by Hauser Center scholars and researchers

Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer

BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase. METHODS: We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients), included overall survival, progression-free survival among patients with brain metastases, confirmed objective response rate, and safety. RESULTS: Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively. Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P = 0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group. CONCLUSIONS: In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo; the risks of diarrhea and elevated aminotransferase levels were higher with tucatinib. (Funded by Seattle Genetics; HER2CLIMB ClinicalTrials.gov number, NCT02614794.)

“Super-deblended” dust emission in galaxies. I. The GOODS-North catalog and the cosmic star formation rate density out to redshift 6

We present a new technique to measure multi-wavelength “super-deblended” photometry from highly confused images, which we apply to Herschel and ground-based far-infrared (FIR) and (sub-)millimeter (mm) data in the northern field of the Great Observatories Origins Deep Survey. There are two key novelties. First, starting with a large database of deep Spitzer 24 μm and VLA 20 cm detections that are used to define prior positions for fitting the FIR/submm data, we perform an active selection of useful priors independently at each frequency band, moving from less to more confused bands. Exploiting knowledge of redshift and all available photometry, we identify hopelessly faint priors that we remove from the fitting pool. This approach significantly reduces blending degeneracies and allows reliable photometry to be obtained for galaxies in FIR+mm bands. Second, we obtain well-behaved, nearly Gaussian flux density uncertainties, individually tailored to all fitted priors for each band. This is done by exploiting extensive simulations that allow us to calibrate the conversion of formal fitting uncertainties to realistic uncertainties, depending on directly measurable quantities. We achieve deeper detection limits with high fidelity measurements and uncertainties at FIR+mm bands. As an illustration of the utility of these measurements, we identify 70 galaxies with z≥slant 3 and reliable FIR+mm detections. We present new constraints on the cosmic star formation rate density at 3< z< 6, finding a significant contribution from z≥slant 3 dusty galaxies that are missed by optical-to-near-infrared color selection. Photometric measurements for 3306 priors, including more than 1000 FIR+mm detections, are released publicly with our catalog

Cardiovascular inflammation in healthy women: multilevel associations with state-level prosperity, productivity and income inequality

<p>Abstract</p> <p>Background</p> <p>Cardiovascular inflammation is a key contributor to the development of atherosclerosis and the prediction of cardiovascular events among healthy women. An emerging literature suggests biomarkers of inflammation vary by geography of residence at the state-level, and are associated with individual-level socioeconomic status. Associations between cardiovascular inflammation and state-level socioeconomic conditions have not been evaluated. The study objective is to estimate whether there are independent associations between state-level socioeconomic conditions and individual-level biomarkers of inflammation, in excess of individual-level income and clinical covariates among healthy women.</p> <p>Methods</p> <p>The authors examined cross-sectional multilevel associations among state-level socioeconomic conditions, individual-level income, and biomarkers of inflammation among women (n = 26,029) in the Women's Health Study, a nation-wide cohort of healthy women free of cardiovascular diseases at enrollment. High sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1) and fibrinogen were measured between 1993 and 1996. Biomarker levels were examined among women within quartiles of state-level socioeconomic conditions and within categories of individual-level income.</p> <p>Results</p> <p>The authors found that favorable state-level socioeconomic conditions were correlated with lower hsCRP, in excess of individual-level income (e.g. state-level real per capital gross domestic product fixed effect standardized Βeta coefficient [Std B] -0.03, 95% CI -0.05, -0.004). Individual-level income was more closely associated with sICAM-1 (Std B -0.04, 95% CI -0.06, -0.03) and fibrinogen (Std B -0.05, 95% CI -0.06, -0.03) than state-level conditions.</p> <p>Conclusions</p> <p>We found associations between state-level socioeconomic conditions and hsCRP among healthy women. Personal household income was more closely associated with sICAM-1 and fibrinogen than state-level socioeconomic conditions. Additional research should examine these associations in other cohorts, and investigate what more-advantaged states do differently than less-advantaged states that may influence levels of cardiovascular inflammation among healthy women.</p

Speech Communication

Contains reports on five research projects.C.J. Lebel FellowshipNational Institutes of Health (Grant 5 T32 NSO7040)National Institutes of Health (Grant 5 R01 NS04332)National Institutes of Health (Grant 5 R01 NS21183)National Institutes of Health (Grant 5 P01 NS13126)National Institutes of Health (Grant 1 PO1-NS23734)National Science Foundation (Grant BNS 8418733)U.S. Navy - Naval Electronic Systems Command (Contract N00039-85-C-0254)U.S. Navy - Naval Electronic Systems Command (Contract N00039-85-C-0341)U.S. Navy - Naval Electronic Systems Command (Contract N00039-85-C-0290)National Institutes of Health (Grant RO1-NS21183), subcontract with Boston UniversityNational Institutes of Health (Grant 1 PO1-NS23734), subcontract with the Massachusetts Eye and Ear Infirmar