Health Reform: The Cost of Failure

Estimates the intermediate and long-term implications of not enacting healthcare reform. Simulates the effects on employer-sponsored insurance, private non-group coverage, and Medicaid and State Children's Health Insurance Programs under three scenarios

The Coverage and Cost Impacts of Expanding Medicaid

Estimates the drop in the number of uninsured and the rise in government costs from not limiting Medicaid eligibility for adults to the disabled and those with dependent children but basing it on income level, under two scenarios. Discusses implications

APOBEC-related mutagenesis and neo-peptide hydrophobicity: implications for response to immunotherapy.

Tumor-associated neo-antigens are mutated peptides that allow the immune system to recognize the affected cell as foreign. Cells carrying excessive mutation load often develop mechanisms of tolerance. PD-L1/PD-1 checkpoint immunotherapy is a highly promising approach to overcome these protective signals and induce tumor shrinkage. Yet, the nature of the neo-antigens driving those beneficial responses remains unclear. Here, we show that APOBEC-related mutagenesis - a mechanism at the crossroads between anti-viral immunity and endogenous nucleic acid editing - increases neo-peptide hydrophobicity (a feature of immunogenicity), as demonstrated by in silico computation and in the TCGA pan-cancer cohort, where APOBEC-related mutagenesis was also strongly associated with immune marker expression. Moreover, APOBEC-related mutagenesis correlated with immunotherapy response in a cohort of 99 patients with diverse cancers, and this correlation was independent of the tumor mutation burden (TMB). Combining APOBEC-related mutagenesis estimate and TMB resulted in greater predictive ability than either parameter alone. Based on these results, further investigation of APOBEC-related mutagenesis as a marker of response to anti-cancer checkpoint blockade is warranted

Petrology and Geochemistry of Volcanic Rocks from the South Kauaʻi Swell Volcano, Hawaiʻi: Implications for the Lithology and Composition of the Hawaiian Mantle Plume

The South Kauaʻi Swell (SKS) volcano was sampled during four JASON dives and three dredge hauls recovering rocks that range from fresh pillow lavas to altered volcanic breccias. Two geochemical groups were identified: shield-stage tholeiites (5·4–3·9 Ma) and rejuvenation-stage alkalic lavas (1·9–0·1 Ma). The young SKS ages and the coeval rejuvenated volcanism along a 400km segment of the Hawaiian Islands (Maui to Niʻihau) are inconsistent with the timing and duration predictions by the flexure and secondary plume melting models for renewed volcanism. The SKS tholeiites are geochemically heterogeneous but similar to lavas from nearby Kauaʻi, Niʻihau and Waiʻanae volcanoes, indicating that their source regions within the Hawaiian mantle plume sampled a well-mixed zone. Most SKS tholeiitic lavas exhibit radiogenic Pb isotope ratios (208Pb*/206Pb*) that are characteristic of Loa compositions (>0·9475), consistent with the volcano’s location on the west side of the Hawaiian Islands. These results document the existence of the Loa component within the Hawaiian mantle plume prior to 5 Ma. Loa trend volcanoes are thought to have a major pyroxenite component in their source. Calculations of the pyroxenitic component in the parental melts for SKS tholeiites using high-precision olivine analyses and modeling of trace element ratios indicate a large pyroxenite proportion (≥50%), which was predicted by recent numerical models. Rejuvenation-stage lavas were also found to have a significant pyroxenite component based on olivine analyses (40–60%). The abundance of pyroxenite in the source for SKS lavas may be the cause of this volcano’s extended period of magmatism (>5 Myr). The broad distribution of the Loa component in the northern Hawaiian Island lavas coincides with the start of a dramatic magma flux increase (300%) along the Hawaiian Chain, which may reflect a major structural change in the source of the Hawaiian mantle plume

Development of X-TOOLSS: Preliminary Design of Space Systems Using Evolutionary Computation

Evolutionary computational (EC) techniques such as genetic algorithms (GA) have been identified as promising methods to explore the design space of mechanical and electrical systems at the earliest stages of design. In this paper the authors summarize their research in the use of evolutionary computation to develop preliminary designs for various space systems. An evolutionary computational solver developed over the course of the research, X-TOOLSS (Exploration Toolset for the Optimization of Launch and Space Systems) is discussed. With the success of early, low-fidelity example problems, an outline of work involving more computationally complex models is discussed

Scalable Tuning of Building Models to Hourly Data

Energy models of existing buildings are unreliable unless calibrated so that they correlate well with actual energy usage. Manual tuning requires a skilled professional and is prohibitively expensive for small projects, imperfect, nonrepeatable, and not scalable to the dozens of sensor channels that smart meters, smart appliances, and sensors are making available. A scalable, automated methodology is needed to quickly, intelligently calibrate building energy models to all available data, increase the usefulness of those models, and facilitate speed-and-scale penetration of simulation-based capabilities into the marketplace for actualized energy savings. The Autotune project is a novel, model-agnostic methodology that leverages supercomputing, large simulation ensembles, and big data mining with multiple machine learning algorithms to allow automatic calibration of simulations that match measured experimental data in a way that is deployable on commodity hardware. This paper shares several methodologies employed to reduce the combinatorial complexity to a computationally tractable search problem for hundreds of input parameters. Accuracy metrics are provided that quantify model error to measured data for either monthly or hourly electrical usage from a highly instrumented, emulated-occupancy research home

Constraints on H_0 from the Central Velocity Dispersions of Lens Galaxies

We employ Schwarzschild's method of orbit modeling to constrain the mass profiles of the central lens galaxies in Q0957+561 and PG 1115+080. We combine the measured central projected stellar velocity dispersions of these galaxies with the self-similar radial profiles of the rms velocity and of the Gauss-Hermite moment h_4 observed in nearby galaxies for 0 < R < 2 R_eff. For Q0957+561, we find a 16% uncertainty in the galaxy mass, and formal 2-sigma limits on the Hubble constant of H_0 = (61 +13/-15) km/s/Mpc. For PG 1115+080, we find that none of the viable lens models can be ruled out, so that H_0 is not yet strongly constrained by this system.Comment: Revised version accepted by ApJ: slightly modified results for both lens sytems. 18 pages, with 7 inline Postscript figures, LaTeX, aaspp4.sty; postscript paper w/figs (490 kb) also available at http://cfa-www.harvard.edu/~romanow/orbit.post.v2.ps.g