Sindbis virus (SINV) is an alphavirus that causes infection of neurons and encephalomyelitis inSindbis virus (SINV) is an arthropod-borne alphavirus of the family Togaviridae, related to eastern equine encephalitis and western equine encephalitis viruses. In humans, SINV infection results in diseases ranging from a self-limiting flu-like illness to fever, polyarthritis, and rash. In mice, SINV infects neurons of the central nervous system (CNS) (26, 27), resulting in a well-characterized encephalomyelitis (19). The severity of disease in infected mice is dependent on the viral strain and the age and genetic background of the mouse (26,27,51,55,58). While neonatal mice die within the first few days of infection, adult immunocompetent mice clear infectious virus within 8 days after infection without neurological sequelae. Although infectious virus has not been detected after clearance, viral RNA is not completely eliminated, and the independent contributions of various components of the immune response to long-term control of virus replication are not known (28,32,34,56). As a result, SINV-induced encephalomyelitis is an excellent model for identification of innate and adaptive immune responses critical for control and clearance of virus from the CNS and for prevention of reactivation.Because neurons are terminally differentiated cells with very limited capacity for regeneration, recovery from encephalomyelitis requires noncytolytic mechanisms for clearance of intracellular virus. Antiviral antibody is one important mechanism. Passive transfer of antibodies to persistently infected severe combined immunodeficiency (SCID) mice clears infectious SINV from all regions of the CNS, but virus production resumes as antibody levels decline (34, 35). However, mice unable to make antibodies can clear infectious virus from the brain stem and spinal cord, but not the brain, at least in part through the action of gamma interferon (IFN-␥) produced by CD4 ϩ and CD8 ϩ T cells (6). Furthermore, CD8 ϩ T-cell-deficient mice clear SINV from the CNS through the production of antibody, but clearance of viral RNA is delayed, suggesting an independent contribution of cellular immunity to noncytolytic virus clearance (29). In vitro, IFN-␥ treatment of differentiated neurons infected with SINV restores cellular protein synthesis and downregulates viral RNA transcription and protein synthesis, facilitating activation of cellular mechanisms that lead to neuron survival and virus clearance (7). These studies suggested that T cells play a synergistic role with the humoral response in virus clearance from the CNS.However, even in mice with normal antibody and T-cell responses, the innate immune response is essential for initial control of SINV replication and prevention of death. Mice deficient in either the type I IFN-␣/␤ receptor or the IFNactivated transcription factor Stat-1 succumb to alphavirus infection and die before mounting a virus-specific immune response (8, 61). In vitro, treatment of infected cells with antibody to the SINV E2 gly...

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Purpose The US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to enable patient reporting of symptomatic adverse events in oncology clinical research. This study was designed to assess the feasibility and resource requirements associated with implementing PRO-CTCAE in a multicenter trial. Methods Patients with locally advanced rectal cancer enrolled in the National Cancer Institute-sponsored North Central Cancer Treatment Group (Alliance) Preoperative Radiation or Selective Preoperative Radiation and Evaluation before Chemotherapy and Total Mesorectal Excision trial were asked to self-report 30 PRO-CTCAE items weekly from home during preoperative therapy, and every 6 months after surgery, via either the Web or an automated telephone system. If participants did not self-report within 3 days, a central coordinator called them to complete the items. Compliance was defined as the proportion of participants who completed PRO-CTCAE assessments at expected time points. Results The prespecified PRO-CTCAE analysis was conducted after the 500th patient completed the 6-month follow-up (median age, 56 years; 33% female; 12% nonwhite; 43% high school education or less; 5% Spanish speaking), across 165 sites. PRO-CTCAE was reported by participants at 4,491 of 4,882 expected preoperative time points (92.0% compliance), of which 3,771 (77.2%) were self-reported by participants and 720 (14.7%) were collected via central coordinator backup. Compliance at 6-month post-treatment follow-up was 333 of 468 (71.2%), with 122 (26.1%) via backup. Site research associates spent a median of 15 minutes on PRO-CTCAE work for each patient visit. Work by a central coordinator required a 50% time commitment. Conclusion Home-based reporting of PRO-CTCAE in a multicenter trial is feasible, with high patient compliance and low site administrative requirements. PRO-CTCAE data capture is improved through centralized backup calls.