Increasing emphasis on the use of real-world evidence (RWE) to support clinical policy and regulatory decision-making has led to a proliferation of guidance, advice, and frameworks from regulatory agencies, academia, professional societies, and industry. A broad spectrum of studies use real-world data (RWD) to produce RWE, ranging from randomized trials with outcomes assessed using RWD to fully observational studies. Yet, many proposals for generating RWE lack sufficient detail, and many analyses of RWD suffer from implausible assumptions, other methodological flaws, or inappropriate interpretations. The Causal Roadmap is an explicit, itemized, iterative process that guides investigators to prespecify study design and analysis plans; it addresses a wide range of guidance within a single framework. By supporting the transparent evaluation of causal assumptions and facilitating objective comparisons of design and analysis choices based on prespecified criteria, the Roadmap can help investigators to evaluate the quality of evidence that a given study is likely to produce, specify a study to generate high-quality RWE, and communicate effectively with regulatory agencies and other stakeholders. This paper aims to disseminate and extend the Causal Roadmap framework for use by clinical and translational researchers; three companion papers demonstrate applications of the Causal Roadmap for specific use cases.

Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.

We present the observed “continuum” levels of polarization as a function of time for four well-observed Type II-Plateau supernovae (SNe II-P; Fig. 1), the class of SNe decisively determined to arise from red supergiant stars (Smartt 2009). All four objects show temporally increasing degrees of polarization through the end of the photospheric phase, with some exhibiting early-time polarization that challenge existing models (e.g., Dessart and Hillier 2011) to reproduce. A fundamental ejecta asymmetry is present in this photometrically diverse sample of type II SNe, and it probably takes different forms (e.g., 56Ni blobs/fingers, large scale deformation). We acknowledge support from NSF grants AST-1009571 and AST-1210311.

This paper describes a project that addressed teaching a miniature robotic manipulator to play chess. This task was accomplished by interfacing a Microbot Minimover 5 robot and its Radio Shack TRS-80 control computer to a set of chessboard contacts and a Fidelity Electronics Chess Challenger 7 microcomputer. An extensive control program and interface circuitry were designed to enable each of the major components of the system to electronically communicate with one another.

The P300 event-related potential (ERP) was elicited in left- and right-handed young adult male and female participants (n = 20/group) with both auditory and visual stimulus discrimination tasks that varied systematically in difficulty. P300 amplitude was larger across all task conditions for left- than for right-handed participants at anterior and central electrode sites. P300 latency was shorter across all task conditions for left- than for right-handers. Task difficulty did not affect the ERP handedness differences. Male and female subjects demonstrated comparable ERP handedness effects, although smaller P300 components were obtained for males than for females. When considered in the context of corpus callosal size differences for left- versus right-handed and male versus female participants, the findings suggest that the P300 reflects callosal size and interhemispheric transmission efficacy.