How pharmacoepidemiology networks can manage distributed analyses to improve replicability and transparency and minimize bias

Several pharmacoepidemiology networks have been developed over the past decade that use a distributed approach, implementing the same analysis at multiple data sites, to preserve privacy and minimize data sharing. Distributed networks are efficient, by interrogating data on very large populations. The structure of these networks can also be leveraged to improve replicability, increase transparency, and reduce bias. We describe some features of distributed networks using, as examples, the Canadian Network for Observational Drug Effect Studies, the Sentinel System in the USA, and the European Research Network of Pharmacovigilance and Pharmacoepidemiology. Common protocols, analysis plans, and data models, with policies on amendments and protocol violations, are key features. These tools ensure that studies can be audited and repeated as necessary. Blinding and strict conflict of interest policies reduce the potential for bias in analyses and interpretation. These developments should improve the timeliness and accuracy of information used to support both clinical and regulatory decisions

Effect of breastfeeding on gastrointestinal infection in infants: A targeted maximum likelihood approach for clustered longitudinal data

The PROmotion of Breastfeeding Intervention Trial (PROBIT) cluster-randomized a program encouraging breastfeeding to new mothers in hospital centers. The original studies indicated that this intervention successfully increased duration of breastfeeding and lowered rates of gastrointestinal tract infections in newborns. Additional scientific and popular interest lies in determining the causal effect of longer breastfeeding on gastrointestinal infection. In this study, we estimate the expected infection count under various lengths of breastfeeding in order to estimate the effect of breastfeeding duration on infection. Due to the presence of baseline and time-dependent confounding, specialized "causal" estimation methods are required. We demonstrate the double-robust method of Targeted Maximum Likelihood Estimation (TMLE) in the context of this application and review some related methods and the adjustments required to account for clustering. We compare TMLE (implemented both parametrically and using a data-adaptive algorithm) to other causal methods for this example. In addition, we conduct a simulation study to determine (1) the effectiveness of controlling for clustering indicators when cluster-specific confounders are unmeasured and (2) the importance of using data-adaptive TMLE.Comment: Published in at http://dx.doi.org/10.1214/14-AOAS727 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Method and apparatus for calibrating multi-axis load cells in a dexterous robot

A robotic system includes a dexterous robot having robotic joints, angle sensors adapted for measuring joint angles at a corresponding one of the joints, load cells for measuring a set of strain values imparted to a corresponding one of the load cells during a predetermined pose of the robot, and a host machine. The host machine is electrically connected to the load cells and angle sensors, and receives the joint angle values and strain values during the predetermined pose. The robot presses together mating pairs of load cells to form the poses. The host machine executes an algorithm to process the joint angles and strain values, and from the set of all calibration matrices that minimize error in force balance equations, selects the set of calibration matrices that is closest in a value to a pre-specified value. A method for calibrating the load cells via the algorithm is also provided

Stability and Localization of Rapid Shear in Fluid-Saturated Fault Gouge: 2. Localized Zone Width and Strength Evolution

Field and laboratory observations indicate that at seismic slip rates most shearing is confined to a very narrow zone, just a few tens to hundreds of microns wide, and sometimes as small as a few microns. Rice et al. (2014) analyzed the stability of uniform shear in a fluid-saturated gouge material. They considered two distinct mechanisms to limit localization to a finite thickness zone, rate-strengthening friction, and dilatancy. In this paper we use numerical simulations to extend beyond the linearized perturbation context in Rice et al. (2014), and study the behavior after the loss of stability. Neglecting dilatancy we find that straining localizes to a width that is almost independent of the gouge layer width, suggesting that the localized zone width is set by the physical properties of the gouge material. Choosing parameters thought to be representative of a crustal depth of 7 km, this predicts that deformation should be confined to a zone between 4 and 44 μm wide. Next, considering dilatancy alone we again find a localized zone thickness that is independent of gouge layer thickness. For dilatancy alone we predict localized zone thicknesses between 1 and 2 μm wide for a depth of 7 km. Finally, we study the impact of localization on the shear strength and temperature evolution of the gouge material. Strain rate localization focuses frictional heating into a narrower zone, leading to a much faster temperature rise than that predicted when localization is not accounted for. Since the dynamic weakening mechanism considered here is thermally driven, this leads to accelerated dynamic weakening.Earth and Planetary SciencesEngineering and Applied Science

Stability and Localization of Rapid Shear in Fluid-Saturated Fault Gouge: 1. Linearized Stability Analysis

Field observations of major earthquake fault zones show that shear deformation is often confined to principal slipping zones that may be of order 1–100 μm wide, located within a broader gouge layer of order 10–100 mm wide. This paper examines the possibility that the extreme strain localization observed may be due to the coupling of shear heating, thermal pressurization, and diffusion. In the absence of a stabilizing mechanism shear deformation in a continuum analysis will collapse to an infinitesimally thin zone. Two possible stabilizing mechanisms, studied in this paper, are rate-strengthening friction and dilatancy. For rate-strengthening friction alone, a linear stability analysis shows that uniform shear of a gouge layer is unstable for perturbations exceeding a critical wavelength. Using this critical wavelength we predict a width for the localized zone as a function of the gouge properties. Taking representative parameters for fault gouge at typical centroidal depths of crustal seismogenic zones, we predict localized zones of order 5–40 μm wide, roughly consistent with field and experimental observations. For dilatancy alone, linearized strain rate perturbations with a sufficiently large wavelength will undergo transient exponential growth before decaying back to uniform shear. The total perturbation strain accumulated during this transient strain rate localization is shown to be largely controlled by a single dimensionless parameter E, which is a measure of the dilatancy of the gouge material due to an increase in strain rate.Earth and Planetary SciencesEngineering and Applied Science

Food Habits of Juvenile American Alligators in the Upper Lake Pontchartrain Estuary

Food habits of juvenile (0.49-1.21 m total length) American alligators (Alligator mississippiensis) from an area in southeastern Louisiana were investigated. One-hundred and one stomach samples were obtained by stomach-pumping. Crustaceans (crayfish; blue crabs, Callinectes sapidus; grass shrimp, Palaemonetes sp.), insects (hemipterans, coleopterans), and small fish (least killifish, Heterandria formosa; mosquitofish, Gambusia affinis) constituted the majority of prey items taken. Fish consumption was significantly more frequent during April and May than during June through September (P\u3c0.025). This differential use of prey species may be due to seasonally fluctuating water levels in the study area. Comparisons of juvenile alligator food habits revealed dietary differences between Louisiana and Florida (P\u3c0.001), possibly due to the different prey available at the two areas. Prey utilization was not significantly different between larger alligators (0.9-1.2 m total length) and smaller alligators (0.3·0.9 m total length) (P\u3e0.25)

Comparison of nested case-control and survival analysis methodologies for analysis of time-dependent exposure

BACKGROUND: Epidemiological studies of exposures that vary with time require an additional level of methodological complexity to account for the time-dependence of exposure. This study compares a nested case-control approach for the study of time-dependent exposure with cohort analysis using Cox regression including time-dependent covariates. METHODS: A cohort of 1340 subjects with four fixed and seven time-dependent covariates was used for this study. Nested case-control analyses were repeated 100 times for each of 4, 8, 16, 32, and 64 controls per case, and point estimates were compared to those obtained using Cox regression on the full cohort. Computational efficiencies were evaluated by comparing central processing unit times required for analysis of the cohort at sizes 1, 2, 4, 8, 16, and 32 times its initial size. RESULTS: Nested case-control analyses yielded results that were similar to results of Cox regression on the full cohort. Cox regression was found to be 125 times slower than the nested case-control approach (using four controls per case). CONCLUSIONS: The nested case-control approach is a useful alternative for cohort analysis when studying time-dependent exposures. Its superior computational efficiency may be particularly useful when studying rare outcomes in databases, where the ability to analyze larger sample sizes can improve the power of the study

Hierarchical Robot Control System and Method for Controlling Select Degrees of Freedom of an Object Using Multiple Manipulators

A robotic system includes a robot having manipulators for grasping an object using one of a plurality of grasp types during a primary task, and a controller. The controller controls the manipulators during the primary task using a multiple-task control hierarchy, and automatically parameterizes the internal forces of the system for each grasp type in response to an input signal. The primary task is defined at an object-level of control, e.g., using a closed-chain transformation, such that only select degrees of freedom are commanded for the object. A control system for the robotic system has a host machine and algorithm for controlling the manipulators using the above hierarchy. A method for controlling the system includes receiving and processing the input signal using the host machine, including defining the primary task at the object-level of control, e.g., using a closed-chain definition, and parameterizing the internal forces for each of grasp type

Tension Distribution in a Tendon-Driven Robotic Finger

A method is provided for distributing tension among tendons of a tendon-driven finger in a robotic system, wherein the finger characterized by n degrees of freedom and n+1 tendons. The method includes determining a maximum functional tension and a minimum functional tension of each tendon of the finger, and then using a controller to distribute tension among the tendons, such that each tendon is assigned a tension value less than the maximum functional tension and greater than or equal to the minimum functional tension. The method satisfies the minimum functional tension while minimizing the internal tension in the robotic system, and satisfies the maximum functional tension without introducing a coupled disturbance to the joint torques. A robotic system includes a robot having at least one tendon-driven finger characterized by n degrees of freedom and n+1 tendons, and a controller having an algorithm for controlling the tendons as set forth above

Five-year predictors of physical activity decline among adults in low-income communities: a prospective study

BACKGROUND: Obesity in North America is now endemic, and increased understanding of the determinants of physical inactivity is critical. This analysis identified predictors of declines in physical activity over 5 years among adults in low-income, inner-city neighbourhoods. METHODS: Data on leisure time physical activity were collected in telephone interviews in 1992 and 1997 from 765 adults (47% of baseline respondents), as part of the evaluation of a community-based cardiovascular disease risk reduction program. RESULTS: One-third of 527 participants who were physically active at baseline, were inactive in 1997. Predictors of becoming inactive included female sex (OR = 1.63 95% CI (1.09, 2.43)), older age (1.02 (1.01, 1.04)), higher BMI (1.57 (1.03, 2.40)), poor self-rated health (1.39 (1.05, 1.84)), lower self-efficacy for physical activity (1.46 (1.00, 2.14)), and not using a neighborhood facility for physical activity (1.61 (1.02, 2.14)). CONCLUSION: These results highlight the fact that a variety of variables play a role in determining activity level, from demographic variables such as age and sex, to psychosocial and environmental variables. In addition, these results highlight the important role that other health-related variables may play in predicting physical activity level, in particular the observed association between baseline BMI and the increased risk of becoming inactive over time. Lastly, these results demonstrate the need for multi-component interventions in low-income communities, which target a range of issues, from psychosocial factors, to features of the physical environment