Discrete Optimization for Interpretable Study Populations and Randomization Inference in an Observational Study of Severe Sepsis Mortality

Motivated by an observational study of the effect of hospital ward versus intensive care unit admission on severe sepsis mortality, we develop methods to address two common problems in observational studies: (1) when there is a lack of covariate overlap between the treated and control groups, how to define an interpretable study population wherein inference can be conducted without extrapolating with respect to important variables; and (2) how to use randomization inference to form confidence intervals for the average treatment effect with binary outcomes. Our solution to problem (1) incorporates existing suggestions in the literature while yielding a study population that is easily understood in terms of the covariates themselves, and can be solved using an efficient branch-and-bound algorithm. We address problem (2) by solving a linear integer program to utilize the worst case variance of the average treatment effect among values for unobserved potential outcomes that are compatible with the null hypothesis. Our analysis finds no evidence for a difference between the sixty day mortality rates if all individuals were admitted to the ICU and if all patients were admitted to the hospital ward among less severely ill patients and among patients with cryptic septic shock. We implement our methodology in R, providing scripts in the supplementary material

Stabilizing the Retromer Complex in a Human Stem Cell Model of Alzheimer's Disease Reduces TAU Phosphorylation Independently of Amyloid Precursor Protein.

Developing effective therapeutics for complex diseases such as late-onset, sporadic Alzheimer's disease (SAD) is difficult due to genetic and environmental heterogeneity in the human population and the limitations of existing animal models. Here, we used hiPSC-derived neurons to test a compound that stabilizes the retromer, a highly conserved multiprotein assembly that plays a pivotal role in trafficking molecules through the endosomal network. Using this human-specific system, we have confirmed previous data generated in murine models and show that retromer stabilization has a potentially beneficial effect on amyloid beta generation from human stem cell-derived neurons. We further demonstrate that manipulation of retromer complex levels within neurons affects pathogenic TAU phosphorylation in an amyloid-independent manner. Taken together, our work demonstrates that retromer stabilization is a promising candidate for therapeutic development in AD and highlights the advantages of testing novel compounds in a human-specific, neuronal system

Transgenic crops : new weed problems for Canada?

Over 25 000 transgenic field trials were conducted globally from 1986-1997, and many transgenic crops, including soybean (Glycine max), maize (Zea mays), tobacco (Nicotiana tabaccum), cotton (Gossypium hirsutum), canola (Brassica napus, B. rapa), tomato (Lycopersicon esculentum) and potato (Solarium tuberosum) have been commercially released. There has been a high adoption rate, with at least 28 million ha reported for 1998, with herbicide- and insect-resistant plants occupying 71 and 28% of the releases, respectively. The current status of commercial production of transgenic crops in Canada is summarized. Transgenic crops have the potential to change weed communities/populations in three principal ways, via: 1 ) escape and proliferation of the transgenic plants as 'weedy' volunteers with subsequent displacement of the crop, weed and/or natural vegetation; 2) hybridization with and transgene infiltration into related weedy and/or wild species, resulting in invigorated weeds and/or alteration of natural gene frequencies in these species; and 3) genetic changes in populations of unrelated species, as a result of changes to the environment, in particular herbicide-resistant (HR) transgenic crops and the development of HR weeds. Potential risk can be estimated a priori using knowledge of the systematics of crop/wild/weed complexes. Risk must be assessed on a case-by-case basis for each crop, each country/ecological region, and for each trait. Potential weed risks will be greater if crop volunteers are predisposed to becoming weedy, are well adapted to the Canadian climate and if sexually compatible wild species are present

Common adversaries form alliances: modelling complex networks via anti-transitivity

Anti-transitivity captures the notion that enemies of enemies are friends, and arises naturally in the study of adversaries in social networks and in the study of conflicting nation states or organizations. We present a simplified, evolutionary model for anti-transitivity influencing link formation in complex networks, and analyze the model's network dynamics. The Iterated Local Anti-Transitivity (or ILAT) model creates anti-clone nodes in each time-step, and joins anti-clones to the parent node's non-neighbor set. The graphs generated by ILAT exhibit familiar properties of complex networks such as densification, short distances (bounded by absolute constants), and bad spectral expansion. We determine the cop and domination number for graphs generated by ILAT, and finish with an analysis of their clustering coefficients. We interpret these results within the context of real-world complex networks and present open problems

Multi-Player Diffusion Games on Graph Classes

We study competitive diffusion games on graphs introduced by Alon et al. [1] to model the spread of influence in social networks. Extending results of Roshanbin [8] for two players, we investigate the existence of pure Nash equilibria for at least three players on different classes of graphs including paths, cycles, grid graphs and hypercubes; as a main contribution, we answer an open question proving that there is no Nash equilibrium for three players on (m x n) grids with min(m, n) >= 5. Further, extending results of Etesami and Basar [3] for two players, we prove the existence of pure Nash equilibria for four players on every d-dimensional hypercube.Comment: Extended version of the TAMC 2015 conference version now discussing hypercube results (added details for the proof of Proposition 1

A revised radiometric normalisation standard for SAR

Improved geometric accuracy in SAR sensors implies that more complex models of the Earth may be used not only to geometrically rectify imagery, but also to more robustly calibrate their radiometry. Current beta, sigma, and gamma nought SAR radiometry conventions all assume a simple “flat as Kansas” Earth ellipsoid model. We complement these simple models with improved radiometric calibration that accounts for local terrain variations. In the era of ERS-1 and RADARSAT-1, image geolocation accuracy was in the order of multiple samples, and tiepointfree establishment of the relationship between radar and map geometries was not possible. Newer sensors such as ASAR, PALSAR, and TerraSAR-X all support accurate geolocation based on product annotations alone. We show that high geolocation accuracy, combined with availability of high-resolution accurate elevation models, enables a more robust radiometric calibration standard for modern SAR sensors that is based on gamma nought normalised using an Earth terrain-model

Orbital Support of Fast and Slow Inner Bars in Double Barred Galaxies

We analyze how the orbital support of the inner bar in a double-barred galaxy (nested bars) depends on the angular velocity (i.e. pattern speed) of this bar. We study orbits in seven models of double bars using the method of invariant loops. The range of pattern speed is covered exhaustively. We find that not all pattern speeds are allowed when the inner bar rotates in the same direction as the outer bar. Below a certain minimum pattern speed orbital support for the inner bar abruptly disappears, while at high values of this speed the orbits indicate an increasingly round bar that looks more like a twist in the nuclear isophotes than a dynamically independent component. For values between these two extremes, orbits supporting the inner bar extend further out as the bar's pattern speed decreases, their corresponding loops become more eccentric, pulsate more, and their rotation becomes increasingly non-uniform, as they speed up and slow down in their motion. Lower pattern speeds also lead to a less coherent bar, as the pulsation and acceleration increasingly varies among the loops supporting the inner bar. The morphologies of fast and slow inner bars expected from the orbital structure studied here are recently recovered observationally by decomposition of double barred galaxies. Our findings allow us to link the observed morphology to the dynamics of the inner bar.Comment: ApJ accepte