Suburban Poverty and the Health Care Safety Net

Examines trends in the number of suburban poor, their access to health care, and efforts to improve safety-net services in the suburbs of five cities. Explores causes of limited safety net capacity, community strategies, and policy implications

Community Efforts to Expand Dental Services for Low-Income People

Examines low-income patients' limited access to dental care, as well as state and community efforts to expand services, including changing Medicaid and State Children's Health Insurance Program reimbursement rates and licensing laws for preventive care

Recombinant Listeria promotes tumor rejection by CD8+ T cell-dependent remodeling of the tumor microenvironment.

Agents that remodel the tumor microenvironment (TME), prime functional tumor-specific T cells, and block inhibitory signaling pathways are essential components of effective immunotherapy. We are evaluating live-attenuated, double-deleted Listeria monocytogenes expressing tumor antigens (LADD-Ag) in the clinic. Here we show in numerous mouse models that while treatment with nonrecombinant LADD induced some changes in the TME, no antitumor efficacy was observed, even when combined with immune checkpoint blockade. In contrast, LADD-Ag promoted tumor rejection by priming tumor-specific KLRG1+PD1loCD62L- CD8+ T cells. These IFNγ-producing effector CD8+ T cells infiltrated the tumor and converted the tumor from an immunosuppressive to an inflamed microenvironment that was characterized by a decrease in regulatory T cells (Treg) levels, a proinflammatory cytokine milieu, and the shift of M2 macrophages to an inducible nitric oxide synthase (iNOS)+CD206- M1 phenotype. Remarkably, these LADD-Ag-induced tumor-specific T cells persisted for more than 2 months after primary tumor challenge and rapidly controlled secondary tumor challenge. Our results indicate that the striking antitumor efficacy observed in mice with LADD-based immunotherapy stems from TME remodeling which is a direct consequence of eliciting potent, systemic tumor-specific CD8+ T cells

A Potent and Effective Suicidal Listeria Vaccine Platform.

Live-attenuated Listeria monocytogenes has shown encouraging potential as an immunotherapy platform in preclinical and clinical settings. However, additional safety measures will enable application across malignant and infectious diseases. Here, we describe a new vaccine platform, termed Lm-RIID (L. monocytogenes recombinase-induced intracellular death), that induces the deletion of genes required for bacterial viability yet maintains potent T cell responses to encoded antigens. Lm-RIID grows normally in broth but commits suicide inside host cells by inducing Cre recombinase and deleting essential genes flanked by loxP sites, resulting in a self-limiting infection even in immunocompromised mice. Lm-RIID vaccination of mice induces potent CD8+ T cells and protects against virulent challenges, similar to live L. monocytogenes vaccines. When combined with α-PD-1, Lm-RIID is as effective as live-attenuated L. monocytogenes in a therapeutic tumor model. This impressive efficacy, together with the increased clearance rate, makes Lm-RIID ideal for prophylactic immunization against diseases that require T cells for protection

Modeling Concurrency in Parallel Debugging

We propose a description language, Data Path Expressions (DPEs), for modeling the behavior of parallel programs. We have designed DPEs as a high-level debugging language, where the debugging paradigm is for the programmer to describe the expected program behavior and for the debugger to compare the actual program behavior during execution to detect program errors. We classify DPEs into five subclasses according to syntactic criteria, and characterize their semantics in terms of a hierarchy of extended Petri Net models. The characterization demonstrates the power of DPEs for modeling (true) concurrency. We also present predecessor automata as a mechanism for implementing the third subclass of DPEs, which expresses bounded parallelism. Predecessor automata extend finite state automata to recognize or generate partial ordering graphs as well as strings, and provide efficient event recognizers for parallel debugging. We briefly describe the application of DPEs race conditions, deadlock and starvation

Renormalized spin coefficients in the accumulated orbital phase for unequal mass black hole binaries

We analyze galactic black hole mergers and their emitted gravitational waves. Such mergers have typically unequal masses with mass ratio of the order 1/10. The emitted gravitational waves carry the inprint of spins and mass quadrupoles of the binary components. Among these contributions, we consider here the quasi-precessional evolution of the spins. A method of taking into account these third post-Newtonian (3PN) effects by renormalizing (redefining) the 1.5 PN and 2PN accurate spin contributions to the accumulated orbital phase is developed.Comment: 10 pages, to appear in Class. Quantum Grav. GWDAW13 Proceedings Special Issue, v2: no typos conjectur

The Chandra Source Catalog

The Chandra Source Catalog (CSC) is a general purpose virtual X-ray astrophysics facility that provides access to a carefully selected set of generally useful quantities for individual X-ray sources, and is designed to satisfy the needs of a broad-based group of scientists, including those who may be less familiar with astronomical data analysis in the X-ray regime. The first release of the CSC includes information about 94,676 distinct X-ray sources detected in a subset of public ACIS imaging observations from roughly the first eight years of the Chandra mission. This release of the catalog includes point and compact sources with observed spatial extents <~ 30''. The catalog (1) provides access to the best estimates of the X-ray source properties for detected sources, with good scientific fidelity, and directly supports scientific analysis using the individual source data; (2) facilitates analysis of a wide range of statistical properties for classes of X-ray sources; and (3) provides efficient access to calibrated observational data and ancillary data products for individual X-ray sources, so that users can perform detailed further analysis using existing tools. The catalog includes real X-ray sources detected with flux estimates that are at least 3 times their estimated 1 sigma uncertainties in at least one energy band, while maintaining the number of spurious sources at a level of <~ 1 false source per field for a 100 ks observation. For each detected source, the CSC provides commonly tabulated quantities, including source position, extent, multi-band fluxes, hardness ratios, and variability statistics, derived from the observations in which the source is detected. In addition to these traditional catalog elements, for each X-ray source the CSC includes an extensive set of file-based data products that can be manipulated interactively.Comment: To appear in The Astrophysical Journal Supplement Series, 53 pages, 27 figure

Statistical Characterization of the Chandra Source Catalog

The first release of the Chandra Source Catalog (CSC) contains ~95,000 X-ray sources in a total area of ~0.75% of the entire sky, using data from ~3,900 separate ACIS observations of a multitude of different types of X-ray sources. In order to maximize the scientific benefit of such a large, heterogeneous data-set, careful characterization of the statistical properties of the catalog, i.e., completeness, sensitivity, false source rate, and accuracy of source properties, is required. Characterization efforts of other, large Chandra catalogs, such as the ChaMP Point Source Catalog (Kim et al. 2007) or the 2 Mega-second Deep Field Surveys (Alexander et al. 2003), while informative, cannot serve this purpose, since the CSC analysis procedures are significantly different and the range of allowable data is much less restrictive. We describe here the characterization process for the CSC. This process includes both a comparison of real CSC results with those of other, deeper Chandra catalogs of the same targets and extensive simulations of blank-sky and point source populations.Comment: To be published in the Astrophysical Journal Supplement Series (Fig. 52 replaced with a version which astro-ph can convert to PDF without issues.

Logical Analysis of Data (LAD) model for the early diagnosis of acute ischemic stroke

<p>Abstract</p> <p>Background</p> <p>Strokes are a leading cause of morbidity and the first cause of adult disability in the United States. Currently, no biomarkers are being used clinically to diagnose acute ischemic stroke. A diagnostic test using a blood sample from a patient would potentially be beneficial in treating the disease.</p> <p>Results</p> <p>A classification approach is described for differentiating between proteomic samples of stroke patients and controls, and a second novel predictive model is developed for predicting the severity of stroke as measured by the National Institutes of Health Stroke Scale (NIHSS). The models were constructed by applying the Logical Analysis of Data (LAD) methodology to the mass peak profiles of 48 stroke patients and 32 controls. The classification model was shown to have an accuracy of 75% when tested on an independent validation set of 35 stroke patients and 25 controls, while the predictive model exhibited superior performance when compared to alternative algorithms. In spite of their high accuracy, both models are extremely simple and were developed using a common set consisting of only 3 peaks.</p> <p>Conclusion</p> <p>We have successfully identified 3 biomarkers that can detect ischemic stroke with an accuracy of 75%. The performance of the classification model on the validation set and on cross-validation does not deteriorate significantly when compared to that on the training set, indicating the robustness of the model. As in the case of the LAD classification model, the results of the predictive model validate the function constructed on our support-set for approximating the severity scores of stroke patients. The correlation and root mean absolute error of the LAD predictive model are consistently superior to those of the other algorithms used (Support vector machines, C4.5 decision trees, Logistic regression and Multilayer perceptron).</p

A highly magnified candidate for a young galaxy seen when the Universe was 500 Myrs old

The early Universe at redshift z\sim6-11 marks the reionization of the intergalactic medium, following the formation of the first generation of stars. However, those young galaxies at a cosmic age of \lesssim 500 million years (Myr, at z \gtrsim 10) remain largely unexplored as they are at or beyond the sensitivity limits of current large telescopes. Gravitational lensing by galaxy clusters enables the detection of high-redshift galaxies that are fainter than what otherwise could be found in the deepest images of the sky. We report the discovery of an object found in the multi-band observations of the cluster MACS1149+22 that has a high probability of being a gravitationally magnified object from the early universe. The object is firmly detected (12 sigma) in the two reddest bands of HST/WFC3, and not detected below 1.2 {\mu}m, matching the characteristics of z\sim9 objects. We derive a robust photometric redshift of z = 9.6 \pm 0.2, corresponding to a cosmic age of 490 \pm 15Myr (i.e., 3.6% of the age of the Universe). The large number of bands used to derive the redshift estimate make it one of the most accurate estimates ever obtained for such a distant object. The significant magnification by cluster lensing (a factor of \sim15) allows us to analyze the object's ultra-violet and optical luminosity in its rest-frame, thus enabling us to constrain on its stellar mass, star-formation rate and age. If the galaxy is indeed at such a large redshift, then its age is less than 200 Myr (at the 95% confidence level), implying a formation redshift of zf \lesssim 14. The object is the first z>9 candidate that is bright enough for detailed spectroscopic studies with JWST, demonstrating the unique potential of galaxy cluster fields for finding highly magnified, intrinsically faint galaxies at the highest redshifts.Comment: Submitted to the Nature Journal. 39 Pages, 13 figure