Spatial Cluster Detection for Weighted Outcomes Using Cumulative Geographic Residuals

Spatial cluster detection is an important methodology for identifying regions with excessive numbers of adverse health events without making strong model assumptions on the underlying spatial dependence structure. Previous work has focused on point or individual-level outcome data and few advances have been made when the outcome data are reported at an aggregated level, e.g. at the county- or census tract-level. This paper proposes a new class of spatial cluster detecion methods for point or aggregate data, comprising of continuous, binary, and count data. Compared with the existing spatial cluster detection methods it has the following advantages. First, it readily incorporates region-specific weights, for example, based on a region’s population or a region’s outcome variance, which is key for aggregate data. Second, the established general framework allows for area-level and individual-level covariate adjustment. A simulation study is conducted to evaluate the performance of the method. The proposed method is then applied to assess spatial clustering of high Body Mass Index in a HMO population in the Seattle, Washington USA area

Pareto optimality in multilayer network growth

We model the formation of multi-layer transportation networks as a multi-objective optimization process, where service providers compete for passengers, and the creation of routes is determined by a multi-objective cost function encoding a trade-off between efficiency and competition. The resulting model reproduces well real-world systems as diverse as airplane, train and bus networks, thus suggesting that such systems are indeed compatible with the proposed local optimization mechanisms. In the specific case of airline transportation systems, we show that the networks of routes operated by each company are placed very close to the theoretical Pareto front in the efficiency-competition plane, and that most of the largest carriers of a continent belong to the corresponding Pareto front. Our results shed light on the fundamental role played by multi-objective optimization principles in shaping the structure of large-scale multilayer transportation systems, and provide novel insights to service providers on the strategies for the smart selection of novel routes

The Phase Diagram of 1-in-3 Satisfiability Problem

We study the typical case properties of the 1-in-3 satisfiability problem, the boolean satisfaction problem where a clause is satisfied by exactly one literal, in an enlarged random ensemble parametrized by average connectivity and probability of negation of a variable in a clause. Random 1-in-3 Satisfiability and Exact 3-Cover are special cases of this ensemble. We interpolate between these cases from a region where satisfiability can be typically decided for all connectivities in polynomial time to a region where deciding satisfiability is hard, in some interval of connectivities. We derive several rigorous results in the first region, and develop the one-step--replica-symmetry-breaking cavity analysis in the second one. We discuss the prediction for the transition between the almost surely satisfiable and the almost surely unsatisfiable phase, and other structural properties of the phase diagram, in light of cavity method results.Comment: 30 pages, 12 figure

¹⁸F FDG PET/CT and Novel Molecular Imaging for Directing Immunotherapy in Cancer

Immunotherapy has transformed the treatment landscape of many cancers, with durable responses in disease previously associated with a poor prognosis. Patient selection remains a challenge, with predictive biomarkers an urgent unmet clinical need. Current predictive biomarkers, including programmed death-ligand 1 (PD-L1) (measured with immunohistochemistry), are imperfect. Promising biomarkers, including tumor mutation burden and tumor infiltrating lymphocyte density, fail to consistently predict response and have yet to translate to routine clinical practice. Heterogeneity of immune response within and between lesions presents a further challenge where fluorine 18 fluorodeoxyglucose PET/CT has a potential role in assessing response, stratifying treatment, and detecting and monitoring immune-related toxicities. Novel radiopharmaceuticals also present a unique opportunity to define the immune tumor microenvironment to better predict which patients may respond to therapy, for example by means of in vivo whole-body PD-L1 and CD8+ T cell expression imaging. In addition, longitudinal molecular imaging may help further define dynamic changes, particularly in cases of immunotherapy resistance, helping to direct a more personalized therapeutic approach. This review highlights current and emerging applications of molecular imaging to stratify, predict, and monitor molecular dynamics and treatment response in areas of clinical need

Taming open/closed string duality with a Losev trick

A target space string field theory formulation for open and closed B-model is provided by giving a Batalin-Vilkovisky quantization of the holomorphic Chern-Simons theory with off-shell gravity background. The target space expression for the coefficients of the holomorphic anomaly equation for open strings are obtained. Furthermore, open/closed string duality is proved from a judicious integration over the open string fields. In particular, by restriction to the case of independence on continuous open moduli, the shift formulas of [7] are reproduced and shown therefore to encode the data of a closed string dual.Comment: 22 pages, no figures; v.2 Refs. and a comment added

Hydroclimate Variability and Change in the Prairie Pothole Region, the “Duck Factory” of North America

The Prairie Pothole Region (PPR) of the northern Great Plains is a vital ecosystem responsible each year for producing 50%–80% of new recruits to the North American duck population. Climate variability and change can impact the hydrology and ecology of the region with implications for waterfowl populations. The historical relationship between PPR wetlands, duck populations, and seasonal hydroclimate are explored. Model experiments from phase 5 of the Coupled Model Intercomparison Project are used to determine whether a recent wetting trend is due to natural variability or changing climate and how PPR hydroclimate will change into the future. Year-to-year variations in May duck populations, pond numbers, and the Palmer drought severity index are well correlated over past decades. Pond and duck numbers tend to increase in spring following La Niña events, but the correlation is not strong. Model simulations suggest that the strengthening of the precipitation gradient across the PPR over the past century is predominantly due to natural variability and therefore could reverse. Model projections of future climate indicate precipitation will increase across the PPR in all seasons except summer, but this gain for surface moisture is largely offset by increased evapotranspiration because of higher temperatures and increased atmospheric evaporative demand. In summer, the combined effects of warming and precipitation changes indicate seasonal surface drying in the future. The presented hydroclimate analyses produce potential inputs to ecological and hydrological simulations of PPR wetlands to inform risk analysis of how this North American waterfowl habitat will evolve in the future, providing guidance to land managers facing conservation decisions

Decoupling A and B model in open string theory -- Topological adventures in the world of tadpoles

In this paper we analyze the problem of tadpole cancellation in open topological strings. We prove that the inclusion of unorientable worldsheet diagrams guarantees a consistent decoupling of A and B model for open superstring amplitudes at all genera. This is proven by direct microscopic computation in Super Conformal Field Theory. For the B-model we explicitly calculate one loop amplitudes in terms of analytic Ray-Singer torsions of appropriate vector bundles and obtain that the decoupling corresponds to the cancellation of D-brane and orientifold charges. Local tadpole cancellation on the worldsheet then guarantees the decoupling at all loops. The holomorphic anomaly equations for open topological strings at one loop are also obtained and compared with the results of the Quillen formula

Human Adipose-Derived Stem Cells Suppress Elastase-Induced Murine Abdominal Aortic Inflammation and Aneurysm Expansion Through Paracrine Factors

Abdominal aortic aneurysm (AAA) is a potentially lethal disease associated with immune activation-induced aortic degradation. We hypothesized that xenotransplantation of human adipose-derived stem cells (hADSCs) would reduce aortic inflammation and attenuate expansion in a murine AAA model. Modulatory effects of ADSCs on immune cell subtypes associated with AAA progression were investigated using human peripheral blood mononuclear cells (hPBMNCs) cocultured with ADSCs. Murine AAA was induced through elastase application to the abdominal aorta in C57BL/6 mice. ADSCs were administered intravenously, and aortic changes were determined by ultrasonography and videomicrometry. Circulating monocytes, aortic neutrophils, CD28− T cells, FoxP3+ regulatory T cells (Tregs), and CD206+ M2 macrophages were assessed at multiple terminal time points. In vitro, ADSCs induced M2 macrophage and Treg phenotypes while inhibiting neutrophil transmigration and lymphocyte activation without cellular contact. Intravenous ADSC delivery reduced aneurysmal expansion starting from day 4 [from baseline: 54.8% (saline) vs. 16.9% (ADSCs), n = 10 at baseline, n = 4 at day 4, p < 0.001], and the therapeutic effect persists through day 14 (from baseline: 64.1% saline vs. 24.6% ADSCs, n = 4, p < 0.01). ADSC administration increased aortic Tregs by 20-fold (n = 5, p < 0.01), while decreasing CD4+CD28− (-28%), CD8+CD28− T cells (-61%), and Ly6G/C+ neutrophils (-43%, n = 5, p < 0.05). Circulating CD115+CXCR1−LY6C+-activated monocytes decreased in the ADSC-treated group by day 7 (-60%, n = 10, p < 0.05), paralleled by an increase in aortic CD206+ M2 macrophages by 2.4-fold (n = 5, p < 0.05). Intravenously injected ADSCs transiently engrafted in the lung on day 1 without aortic engraftment at any time point. In conclusion, ADSCs exhibit pleiotropic immunomodulatory effects in vitro as well as in vivo during the development of AAA. The temporal evolution of these effects systemically as well as in aortic tissue suggests that ADSCs induce a sequence of anti-inflammatory cellular events mediated by paracrine factors, which leads to amelioration of AAA progression