Causal exposure-response curve estimation with surrogate confounders: a study of air pollution and children's health in Medicaid claims data

In this paper, we undertake a case study in which interest lies in estimating a causal exposure-response function (ERF) for long-term exposure to fine particulate matter (PM$_{2.5}$) and respiratory hospitalizations in socioeconomically disadvantaged children using nationwide Medicaid claims data. New methods are needed to address the specific challenges the Medicaid data present. First, Medicaid eligibility criteria, which are largely based on family income for children, differ by state, creating socioeconomically distinct populations and leading to clustered data, where zip codes (our units of analysis) are nested within states. Second, Medicaid enrollees' individual-level socioeconomic status, which is known to be a confounder and an effect modifier of the exposure-response relationships under study, is not available. However, two useful surrogates are available: median household income of each enrollee's zip code of residence and state-level Medicaid family income eligibility thresholds for children. In this paper, we introduce a customized approach, called \textit{MedMatch}, that builds on generalized propensity score matching methods for estimating causal ERFs, adapting these approaches to leverage our two surrogate variables to account for potential confounding and/or effect modification by socioeconomic status. We conduct extensive simulation studies, consistently demonstrating the strong performance of \textit{MedMatch} relative to conventional approaches to handling the surrogate variables. We apply \textit{MedMatch} to estimate the causal ERF between long-term PM$_{2.5}$ exposure and first respiratory hospitalization among children in Medicaid from 2000 to 2012. We find a positive association, with a steeper curve at PM$_{2.5} \le 8$ $\mu$g/m$^3$ that levels off at higher concentrations.Comment: 38 pages,5 figure

Cosmicflows-2: The Data

Cosmicflows-2 is a compilation of distances and peculiar velocities for over 8000 galaxies. Numerically the largest contributions come from the luminosity-linewidth correlation for spirals, the TFR, and the related Fundamental Plane relation for E/S0 systems, but over 1000 distances are contributed by methods that provide more accurate individual distances: Cepheid, Tip of the Red Giant Branch, Surface Brightness Fluctuation, SNIa, and several miscellaneous but accurate procedures. Our collaboration is making important contributions to two of these inputs: Tip of the Red Giant Branch and TFR. A large body of new distance material is presented. In addition, an effort is made to assure that all the contributions, our own and those from the literature, are on the same scale. Overall, the distances are found to be compatible with a Hubble Constant H_0 = 74.4 +-3.0 km/s/Mpc. The great interest going forward with this data set will be with velocity field studies. Cosmicflows-2 is characterized by a great density and high accuracy of distance measures locally, falling to sparse and coarse sampling extending to z=0.1.Comment: To be published in Astronomical Journal. Two extensive tables to be available on-line. Table 1 available at http://edd.ifa.hawaii.edu select catalog `Cosmicflows-2 Distances

The discontinuous Galerkin method for fractional degenerate convection-diffusion equations

We propose and study discontinuous Galerkin methods for strongly degenerate convection-diffusion equations perturbed by a fractional diffusion (L\'evy) operator. We prove various stability estimates along with convergence results toward properly defined (entropy) solutions of linear and nonlinear equations. Finally, the qualitative behavior of solutions of such equations are illustrated through numerical experiments

Dissipative preparation of W states in trapped ion systems

We present protocols for dissipative entanglement of three trapped-ion qubits and discuss a scheme that uses sympathetic cooling as the dissipation mechanism. This scheme relies on tailored destructive interference to generate any one of six entangled W states in a three-ion qubit space. Using a beryllium-magnesium ion crystal as an example system, we theoretically investigate the protocol's performance and the effects of likely error sources, including thermal secular motion of the ion crystal, calibration imperfections, and spontaneous photon scattering. We estimate that a fidelity of $\sim$ 98 % may be achieved in typical trapped ion experiments with $\sim$ 1 ms interaction time. These protocols avoid timescale hierarchies for faster preparation of entangled states

Optimal cDNA microarray design using expressed sequence tags for organisms with limited genomic information

BACKGROUND: Expression microarrays are increasingly used to characterize environmental responses and host-parasite interactions for many different organisms. Probe selection for cDNA microarrays using expressed sequence tags (ESTs) is challenging due to high sequence redundancy and potential cross-hybridization between paralogous genes. In organisms with limited genomic information, like marine organisms, this challenge is even greater due to annotation uncertainty. No general tool is available for cDNA microarray probe selection for these organisms. Therefore, the goal of the design procedure described here is to select a subset of ESTs that will minimize sequence redundancy and characterize potential cross-hybridization while providing functionally representative probes. RESULTS: Sequence similarity between ESTs, quantified by the E-value of pair-wise alignment, was used as a surrogate for expected hybridization between corresponding sequences. Using this value as a measure of dissimilarity, sequence redundancy reduction was performed by hierarchical cluster analyses. The choice of how many microarray probes to retain was made based on an index developed for this research: a sequence diversity index (SDI) within a sequence diversity plot (SDP). This index tracked the decreasing within-cluster sequence diversity as the number of clusters increased. For a given stage in the agglomeration procedure, the EST having the highest similarity to all the other sequences within each cluster, the centroid EST, was selected as a microarray probe. A small dataset of ESTs from Atlantic white shrimp (Litopenaeus setiferus) was used to test this algorithm so that the detailed results could be examined. The functional representative level of the selected probes was quantified using Gene Ontology (GO) annotations. CONCLUSIONS: For organisms with limited genomic information, combining hierarchical clustering methods to analyze ESTs can yield an optimal cDNA microarray design. If biomarker discovery is the goal of the microarray experiments, the average linkage method is more effective, while single linkage is more suitable if identification of physiological mechanisms is more of interest. This general design procedure is not limited to designing single-species cDNA microarrays for marine organisms, and it can equally be applied to multiple-species microarrays of any organisms with limited genomic information

Regulation of Tcf7l1 DNA Binding and Protein Stability as Principal Mechanisms of Wnt/β-Catenin Signaling

SummaryWnt/β-catenin signal transduction requires direct binding of β-catenin to Tcf/Lef proteins, an event that is classically associated with stimulating transcription by recruiting coactivators. This molecular cascade plays critical roles throughout embryonic development and normal postnatal life by affecting stem cell characteristics and tumor formation. Here, we show that this pathway utilizes a fundamentally different mechanism to regulate Tcf7l1 (formerly named Tcf3) activity. β-catenin inactivates Tcf7l1 without a switch to a coactivator complex by removing it from DNA, which leads to Tcf7l1 protein degradation. Mouse genetic experiments demonstrate that Tcf7l1 inactivation is the only required effect of the Tcf7l1-β-catenin interaction. Given the expression of Tcf7l1 in pluripotent embryonic and adult stem cells, as well as in poorly differentiated breast cancer, these findings provide mechanistic insights into the regulation of pluripotency and the role of Wnt/β-catenin in breast cancer

Multichannel phase-sensitive amplification in a low-loss CMOS-compatible spiral waveguide

We investigate single-channel and multichannel phase-sensitive amplification (PSA) in a highly nonlinear, CMOS-compatible spiral waveguide with ultralow linear and negligible nonlinear losses. We achieve a net gain of 10.4 dB and an extinction ratio of 24.6 dB for single-channel operation, as well as a 5 dB gain and a 15 dB extinction ratio spanning over a bandwidth of 24 nm for multiple-channel operation. In addition, we derive a simple analytic solution that enables calculating the maximum phase-sensitive gain in any Kerr medium featuring linear and nonlinear losses. These results not only give a clear guideline for designing PSA-based amplifiers but also show that it is possible to implement both optical regeneration and amplification in a single on-chip device