The instrumental variable method consistently estimates the effect of a treatment when there is unmeasured confounding and a valid instrumental variable. A valid instrumental variable is a variable that is independent of unmeasured confounders and affects the treatment but does not have a direct effect on the outcome beyond its effect on the treatment. Two commonly used estimators for using an instrumental variable to estimate a treatment effect are the two stage least squares estimator and the control function estimator. For linear causal effect models, these two estimators are equivalent, but for nonlinear causal effect models, the estimators are different. We provide a systematic comparison of these two estimators for nonlinear causal effect models and develop an approach to combing the two estimators that generally performs better than either one alone. We show that the control function estimator is a two stage least squares estimator with an augmented set of instrumental variables. If these augmented instrumental variables are valid, then the control function estimator can be much more efficient than usual two stage least squares without the augmented instrumental variables while if the augmented instrumental variables are not valid, then the control function estimator may be inconsistent while the usual two stage least squares remains consistent. We apply the Hausman test to test whether the augmented instrumental variables are valid and construct a pretest estimator based on this test. The pretest estimator is shown to work well in a simulation study. An application to the effect of exposure to violence on time preference is considered.

With increasing urbanization vector-borne diseases are quickly developing in cities, and urban control strategies are needed. If streets are shown to be barriers to disease vectors, city blocks could be used as a convenient and relevant spatial unit of study and control. Unfortunately, existing spatial analysis tools do not allow for assessment of the impact of an urban grid on the presence of disease agents. Here, we first propose a method to test for the significance of the impact of streets on vector infestation based on a decomposition of Moran's spatial autocorrelation index; and second, develop a Gaussian Field Latent Class model to finely describe the effect of streets while controlling for cofactors and imperfect detection of vectors. We apply these methods to cross-sectional data of infestation by the Chagas disease vector Triatoma infestans in the city of Arequipa, Peru. Our Moran's decomposition test reveals that the distribution of T. infestans in this urban environment is significantly constrained by streets (p<0.05). With the Gaussian Field Latent Class model we confirm that streets provide a barrier against infestation and further show that greater than 90% of the spatial component of the probability of vector presence is explained by the correlation among houses within city blocks. The city block is thus likely to be an appropriate spatial unit to describe and control T. infestans in an urban context. Characteristics of the urban grid can influence the spatial dynamics of vector borne disease and should be considered when designing public health policies.

Vector-borne transmission of Chagas disease has become an urban problem in the city of Arequipa, Peru, yet the debilitating symptoms that can occur in the chronic stage of the disease are rarely seen in hospitals in the city. The lack of obvious clinical disease in Arequipa has led to speculation that the local strain of the etiologic agent, Trypanosoma cruzi, has low chronic pathogenicity. The long asymptomatic period of Chagas disease leads us to an alternative hypothesis for the absence of clinical cases in Arequipa: transmission in the city may be so recent that most infected individuals have yet to progress to late stage disease. Here we describe a new method, epicenter regression, that allows us to infer the spatial and temporal history of disease transmission from a snapshot of a population's infection status. We show that in a community of Arequipa, transmission of T. cruzi by the insect vector Triatoma infestans occurred as a series of focal micro-epidemics, the oldest of which began only around 20 years ago. These micro-epidemics infected nearly 5% of the community before transmission of the parasite was disrupted through insecticide application in 2004. Most extant human infections in our study community arose over a brief period of time immediately prior to vector control. According to our findings, the symptoms of chronic Chagas disease are expected to be absent, even if the strain is pathogenic in the chronic phase of disease, given the long asymptomatic period of the disease and short history of intense transmission. Traducción al español disponible en Alternative Language Text S1/A Spanish translation of this article is available in Alternative Language Text S1.

MOTIVATION: We address the problem of identifying differentially expressed genes between two conditions in the scenario where the data arise from an observational study, in which confounding factors are likely to be present. RESULTS: We suggest to use matching methods to balance two groups of observed cases on measured covariates, and to identify differentially expressed genes using a test suited to matched data. We illustrate this approach on two microarray studies: the first study consists of data from patients with two cancer subtypes, and the second study consists of data from AMKL patients with and without Down syndrome. AVAILABILITY: R code (www.r-project.org) for implementing our approach is included as Supplementary Material. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.