Simple Examples of Estimating Causal Effects Using Targeted Maximum Likelihood Estimation

We present a brief overview of targeted maximum likelihood for estimating the causal effect of a single time point treatment and of a two time point treatment. We focus on simple examples demonstrating how to apply the methodology developed in (van der Laan and Rubin, 2006; Moore and van der Laan, 2007; van der Laan, 2010a,b). We include R code for the single time point case

Optimizing Randomized Trial Designs to Distinguish which Subpopulations Benefit from Treatment

It is a challenge to evaluate experimental treatments where it is suspected that the treatment effect may only be strong for certain subpopulations, such as those having a high initial severity of disease, or those having a particular gene variant. Standard randomized controlled trials can have low power in such situations. They also are not optimized to distinguish which subpopulations benefit from a treatment. With the goal of overcoming these limitations, we consider randomized trial designs in which the criteria for patient enrollment may be changed, in a preplanned manner, based on interim analyses. Since such designs allow data-dependent changes to the population sampled, care must be taken to ensure strong control of the familywise Type I error rate. Our main contribution is a general method for constructing randomized trial designs that (1) allow changes (based on a prespecified decision rule) to the population enrolled based on interim data, (2) make no parametric model assumptions, and (3) guarantee the asymptotic, familywise Type I error rate is strongly controlled at a specified level. As a demonstration of our method, we prove new, sharp results for a simple, two-stage enrichment design. We then compare this design to a fixed design, focusing on each design\u27s ability to determine overall and subpopulation specific treatment effects

Using Regression Models to Analyze Randomized Trials: Asymptotically Valid Hypothesis Tests Despite Incorrectly Specified Models

Regression models are often used to test for cause-effect relationships from data collected in randomized trials or experiments. This practice has deservedly come under heavy scrutiny, since commonly used models such as linear and logistic regression will often not capture the actual relationships between variables, and incorrectly specified models potentially lead to incorrect conclusions. In this paper, we focus on hypothesis test of whether the treatment given in a randomized trial has any effect on the mean of the primary outcome, within strata of baseline variables such as age, sex, and health status. Our primary concern is ensuring that such hypothesis tests have correct Type I error for large samples. Our main result is that for a surprisingly large class of commonly used regression models, standard regression-based hypothesis tests (but using robust variance estimators) are guaranteed to have correct Type I error for large samples, even when the models are incorrectly specified. To the best of our knowledge, this robustness of such model-based hypothesis tests to incorrectly specified models was previously unknown for Poisson regression models and for other commonly used models we consider. Our results have practical implications for understanding the reliability of commonly used, model-based tests for analyzing randomized trials

Fabrication of minority-carrier-limited n-Si/insulator/metal diodes

A photoelectrochemical anodization technique has been used to fabricate n-Si/insulator/metal (MIS) diodes with improved electrical properties. MIS structures fabricated with Au have provided the first experimental observation of a solid-state n-Si surface barrier device whose open circuit voltage Voc is controlled by minority-carrier bulk diffusion/recombination processes. For these diodes, variation of the minority-carrier diffusion length and majority-carrier dopant density produced changes in Voc that were in accord with bulk diffusion/recombination theory. Additionally, the variation in Voc in response to changes in the work function of the metal overlayer indicated that these MIS devices were not subject to the Fermi level pinning restrictions observed for n-Si Schottky structures. X-ray photoelectron spectroscopic characterization of the anodically grown insulator indicated 8.2±0.9 Å of a strained SiO2 layer as the interfacial insulator resulting from the photoanodization process

Neurocytoma in the cerebellum: Case report

A neurocytoma is a central nervous system tumor composed of small cells with features of neuronal differentiation; it typically occurs in the periventricular region, close to the septum pellucidum and the foramen of Monro. In this article, the authors report the case of a neurocytoma located in the cerebellum, which to their knowledge is the first reported case of its kind. The finding of a neurocytoma at a nonclassic location refutes the theory that this tumor has its origins in subependymal progenitor cells, unless an ectopic location of progenitor cells is invoked to explain the occurrence of a neurocytoma away from the ventricles. On the basis of this case, the authors suggest that neurocytomas should be added to the differential diagnosis of mass lesions in the supratentorial intraventricular regions as well as in the posterior fossa

Conus Medullaris Enterogenous Cyst

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147142/1/pmr2698.pd

Distance Traveled and Cross-State Commuting to Opioid Treatment Programs in the United States

This study examined commuting patterns among 23,141 methadone patients enrolling in 84 opioid treatment programs (OTPs) in the United States. Patients completed an anonymous one-page survey. A linear mixed model analysis was used to predict distance traveled to the OTP. More than half (60%) the patients traveled <10 miles and 6% travelled between 50 and 200 miles to attend an OTP; 8% travelled across a state border to attend an OTP. In the multivariate model (n = 17,792), factors significantly (P < .05) associated with distance were, residing in the Southeast or Midwest, low urbanicity, area of the patient's ZIP code, younger age, non-Hispanic white race/ethnicity, prescription opioid abuse, and no heroin use. A significant number of OTP patients travel considerable distances to access treatment. To reduce obstacles to OTP access, policy makers and treatment providers should be alert to patients' commuting patterns and to factors associated with them

Human Emotion Recognition from Motion Using a Radial Basis Function Network Architecture

(Also cross-referenced as CAR-TR-721) In this paper a radial basis function network architecture is developed that learns the correlation between facial feature motion patterns and human emotions. We describe a hierarchical approach which at the highest level identifies emotions, at the mid level determines motions of facial features, and at the low level recovers motion directions. Individual emotion networks were trained to recognize the 'smile" and "surprise" emotions. Each network was trained by viewing a set of sequences of one emotion for many subjects. The trained neural network was then tested for retention, extrapolation and rejection ability. Success rates were about 88% for retention, 73Wo for extrapolation, and 79% for rejection

Detailed Version: Analyzing Direct Effects in Randomized Trials with Secondary Interventions: An Application to HIV Prevention Trials

This is the detailed technical report that accompanies the paper “Analyzing Direct Effects in Randomized Trials with Secondary Interventions: An Application to HIV Prevention Trials” (an unpublished, technical report version of which is available online at http://www.bepress.com/ucbbiostat/paper223). The version here gives full details of the models for the time-dependent analysis, and presents further results in the data analysis section. The Methods for Improving Reproductive Health in Africa (MIRA) trial is a recently completed randomized trial that investigated the effect of diaphragm and lubricant gel use in reducing HIV infection among susceptible women. 5,045 women were randomly assigned to either the active treatment arm or not. Additionally, all subjects in both arms received intensive condom counselling and provision, the gold standard HIV prevention barrier method. There was much lower reported condom use in the intervention arm than in the control arm, making it difficult to answer important public health questions based solely on the intention-to-treat analysis. We adapt an analysis technique from causal inference to estimate the direct effects of assignment to the diaphragm arm, adjusting for condom use in an appropriate sense. Issues raised in the MIRA trial apply to other trials of HIV prevention methods, some of which are currently being conducted or designed