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

Performance of an emergency cold weld repair on a 2.25Cr-1Mo longitudinally seam-welded pressure vessel.

This is an overview of a current three-year project for the Cooperative Research Centre for Welded Structures entitled “Integrity of High Energy Piping”. The results of a performance evaluation conducted on an emergency cold weld (controlled deposition temperbead, TB) repair applied to a 2.25Cr-1Mo steel header using the manual metal arc welding (MMAW) process are described. With repair rather than replace being a far more viable option, welding is increasingly used for performing repairs, replacements, retrofits and modifications to elevated temperature plants. However, with the considerable cost and time involved with performing conventional post weld heat-treatment (PWHT) repairs, in today’s economic environment utility owners are increasingly forced to turn toward other alternatives, such as cold weld repairs. These require no PWHT and rely on a controlled deposition process – precise weld bead placement and heat inputs etc to achieve tempering of the HAZ. However, much of the research conducted on these repair techniques has used accelerated high temperature creep testing to demonstrate their integrity. How well this reflects their real-life performance is unknown. Therefore this study provides an opportunity to evaluate the effects of service exposure on the performance of an emergency cold weld repair. © 2003, The Institute of Materials Engineering Australasia Ltd

Electric Field Modulation of Galvanomagnetic Properties of Mesoscopic Graphite

Electric field effect devices based on mesoscopic graphite are fabricated for galvanomagnetic measurements. Strong modulation of magneto-resistance and Hall resistance as a function of gate voltage is observed as sample thickness approaches the screening length. Electric field dependent Landau level formation is detected from Shubnikov de Haas oscillations in magneto-resistance. The effective mass of electron and hole carriers has been measured from the temperature dependant behavior of these oscillations.Comment: 4 pages, 4 figures included, submitted to Phys. Rev. Let

Embryonic Pattern Scaling Achieved by Oppositely Directed Morphogen Gradients

Morphogens are proteins, often produced in a localised region, whose concentrations spatially demarcate regions of differing gene expression in developing embryos. The boundaries of expression must be set accurately and in proportion to the size of the one-dimensional developing field; this cannot be accomplished by a single gradient. Here, we show how a pair of morphogens produced at opposite ends of a developing field can solve the pattern-scaling problem. In the most promising scenario, the morphogens effectively interact according to the annihilation reaction $A+B\to\emptyset$ and the switch occurs according to the absolute concentration of $A$ or $B$. In this case embryonic markers across the entire developing field scale approximately with system size; this cannot be achieved with a pair of non-interacting gradients that combinatorially regulate downstream genes. This scaling occurs in a window of developing-field sizes centred at a few times the morphogen decay length.Comment: 24 pages; 11 figures; uses iopar

Randomization Inference and Sensitivity Analysis for Composite Null Hypotheses With Binary Outcomes in Matched Observational Studies

We present methods for conducting hypothesis testing and sensitivity analyses for composite null hypotheses in matched observational studies when outcomes are binary. Causal estimands discussed include the causal risk difference, causal risk ratio, and the effect ratio. We show that inference under the assumption of no unmeasured confounding can be performed by solving an integer linear program, while inference allowing for unmeasured confounding of a given strength requires solving an integer quadratic program. Through simulation studies and data examples, we demonstrate that our formulation allows these problems to be solved in an expedient manner even for large datasets and for large strata. We further exhibit that through our formulation, one can assess the impact of various assumptions about the potential outcomes on the performed inference. R scripts are provided that implement our methods. Supplementary materials for this article are available online. Keywords: Causal inference; Causal risk; Effect ratio; Integer programming; Sensitivity analysi

The Fall of the Quasar Population

We derive quantitative predictions of the optical and X-ray luminosity functions (LF) for QSs in the redshift range $z<3$. Based on BH paradigm, we investigate how the accretion is controlled by the surrounding structures, as these grow hierarchically. We argue that for $z < 3$ efficient black hole fueling is triggered by the encounters of a gas-rich host with its companions in a group. The dispersion of the dynamical parameters in the encounters produces a double power-law LF. Strong luminosity evolution (LE) is produced as these encounters deplete the gas supply in the host; an additional, milder density evolution obtains since the interactions become progressively rarer as the groups grow richer but less dense. From the agreement with the optical and the X-ray data, we conclude that the evolution of the bright quasars is articulated in two ways. Earlier than $z~3$ the gas-rich protogalaxies grow by merging, which also induces parallel growth of central holes accreting at Eddington rates. In the later era of group assemblage the host encounters with companions drive onto already existing holes further but meager accretion; these consume the gas in the hosts, and cause supply-limited emissions which are intermittent, go progressively sub-Eddington and peter out. Then other fueling processes come to the foreground; we discuss the faint emissions, especially noticeable in X-rays, which are expected when hosts in the field cannibalize satellite galaxies with their meager gas contents.Comment: 12 pages Latex + 3 EPS figures, ApJ in press, we have corrected the previous printing problems with the style \ca

Cryoultramicrotomy and Immunocytochemistry in the Analysis of Muscle Fine Structure

Cryoultramicrotomy, which avoids the use of harsh fixation procedures, deleterious dehydration and plastic embedding can be combined with immunocytochemis try to determine the ultra-structural localization of cellular proteins. Our attempts to use the cryosectioning technique in combination with immunolabelling to bridge the gap between light and electron microscopic analysis of muscle morphology have enabled us to obtain new information on fibre typing at the ultrastructural level. Furthermore, we have obtained a marked improvement in the resolution of myofibrillar structures by using semithin cryosections for fluorescence microscopy. Data are also presented on correlated light and electron microscope immunocytochemistry of myocardial intermediate filaments confirming the presence of longitudinally oriented intermediate filaments of desmin in the region of the intercalated discs of mammalian cardiac myocytes, whereas elsewhere in the myocyte the bulk of intermediate filaments of desmin is concentrated in the intermyofibrillar space at the level of the Z disc