While consensus regarding the return of secondary genomic findings in the clinical setting has been reached, debate about such findings in the research setting remains. We developed a hybrid, research-clinical translational genomics process for research exome data coupled with a CLIA-validated secondary findings analysis. Eleven intramural investigators from ten institutes at the National Institutes of Health piloted this process. Nearly 1,200 individuals were sequenced and 14 secondary findings were identified in 18 participants. Positive secondary findings were returned by a genetic counselor following a standardized protocol, including referrals for specialty follow-up care for the secondary finding local to the participants. Interviews were undertaken with 13 participants 4 months after receipt of a positive report. These participants reported minimal psychologic distress within a process to assimilate their results. Of the 13, 9 reported accessing the recommended health care services. A sample of 107 participants who received a negative findings report were surveyed 4 months after receiving it. They demonstrated good understanding of the negative secondary findings result and most expressed reassurance (64%) from that report. However, a notable minority (up to 17%) expressed confusion regarding the distinction of primary from secondary findings. This pilot shows it is feasible to couple CLIA-compliant secondary findings to research sequencing with minimal harms. Participants managed the surprise of a secondary finding with most following recommended follow up, yet some with negative findings conflated secondary and primary findings. Additional work is needed to understand barriers to follow-up care and help participants distinguish secondary from primary findings.

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This randomized, controlled study examined the initial efficacy of an executive function training program for children with autism spectrum disorder. Seventy 7- to 11 year-olds with autism spectrum disorder and intelligence quotients ⩾80 were randomly assigned to receive a web-based set of executive function training games combined with in-person metacognition coaching or to a waitlist. Primary outcomes were evaluated for neural responses related to executive function, lab-based executive function behavior, and generalization of executive function skills. Secondary outcomes included measures of social function. Post-testing and analyses were conducted by staff naïve to group assignment. Children exhibited a change in neural response following training relative to the waitlist group [Formula: see text]. Training effects were not detected via lab-based tasks [Formula: see text] or generalized to caregiver-reported executive function skills outside the lab [Formula: see text]. However, the training group demonstrated reduced symptoms of repetitive behavior [Formula: see text] following training. There were no adverse events or attrition from the training group. Findings suggest that brief, targeted computer-based training program accompanied by coaching is feasible and may improve neural responses and repetitive behaviors of school-aged children with autism spectrum disorder. Lay abstract Executive function, which is a set of thinking skills that includes stopping unwanted responses, being flexible, and remembering information needed to solve problems, is a challenge for many children on the autism spectrum. This study tested whether executive function could be improved with a computerized executive function training program under the guidance of a coach who reinforced the use of executive function skills. Seventy children with autism spectrum disorder from age 7 to 11 years of age participated in the study. They were randomly assigned to receive training or to a waiting group. The tests most likely to determine whether the training may be effective were chosen from a larger battery before the study started and included one task measuring brain responses, two measures of executive function in the lab, and a parent questionnaire. Changes in social functioning and repetitive behaviors were also explored. All children assigned to training completed the program and families generally reported the experience was positive. Brain responses of the training group changed following training, but not within the waiting group during a similar time period. Children who received training did not exhibit behavioral changes during the two the lab-based tasks. Parent report on questionnaires indicated that neither group showed a significant change in their broad use of executive function in other settings. Yet, children who received training were reported to have fewer restricted and repetitive behaviors following training. These initial findings suggest that short executive function training activities are feasible and may improve some functioning of school-aged children on the autism spectrum.

Vitamin E, along with other vitamins and micronutrients play a range of physiologic roles in the homeostasis of the body. Moreover, they also have postulated therapeutic roles that are often incompletely studied and understood. In this scoping review, we explored the recent randomized control trials (RCTs) of Vitamin E in the context of cancer, to investigate whether Vitamin E has a therapeutic role. We searched major bibliographic electronic databases to identify sixteen RCTs studying the role of Vitamin E in cancer management that have been published in the last ten years. These studies had different methodological qualities, including some that used Vitamin E in combination with other treatments. Furthermore, due to the heterogenous results, it is difficult to make a consensus statement on the effectiveness of Vitamin E in cancer therapeutics. In some cases, there were even suggestion of detriment with Vitamin E supplementation. Therefore, well designed, large, prospective RCTs are needed studying pure isoforms of Vitamin E to establish the safety and efficacy of this dietary supplement.