Gene fusions and their products (RNA and protein) were once thought to be unique features to cancer. However, chimeric RNAs can also be found in normal cells. Here, we performed, curated and analyzed nearly 300 RNA-Seq libraries covering 30 different non-neoplastic human tissues and cells as well as 15 mouse tissues. A large number of fusion transcripts were found. Most fusions were detected only once, while 291 were seen in more than one sample. We focused on the recurrent fusions and performed RNA and protein level validations on a subset. We characterized these fusions based on various features of the fusions, and their parental genes. They tend to be expressed at higher levels relative to their parental genes than the non-recurrent ones. Over half of the recurrent fusions involve neighboring genes transcribing in the same direction. A few sequence motifs were found enriched close to the fusion junction sites. We performed functional analyses on a few widely expressed fusions, and found that silencing them resulted in dramatic reduction in normal cell growth and/or motility. Most chimeras use canonical splicing sites, thus are likely products of ‘intergenic splicing’. We also explored the implications of these non-pathological fusions in cancer and in evolution.

Objectives Age-related decline of the five classical senses (vision, smell, hearing, touch, and taste) poses significant burdens on older adults. The co-occurrence of multiple sensory deficits in older adults is not well characterized and may reflect a common mechanism resulting in global sensory impairment. Design, Setting, and Participants The National Social Life, Health, and Aging Project, a representative, population-based study of community dwelling older US adults (57-85 years of age), collected biomarkers, social and health history, and other physiological measures, including sensory function. Measurements We estimated the frequency with which impairment co-occurred across the five senses as an integrated measure of sensory aging. We hypothesized that multisensory deficits would be common and reflect global sensory impairment which would largely explain the effects of age, gender, and race on sensory dysfunction. Results Two thirds (67%) of the older US population suffer from two or more sensory deficits, 27% from just one, and only 6% had none. Impairment of the sense of taste was the most common (74%); 70% had a poor sense of touch; 22% had poor sense of smell; 20% had impaired corrected vision; and 18% had poor corrected hearing. Older adults, men, African Americans, and Hispanics had greater multisensory impairment (all P<0.01). Global sensory impairment largely accounted for the effects of age, gender, and race on the likelihood of impairment of each of the five senses. Conclusion Multisensory impairment is prevalent in older US adults. These data support the concept of a common process that underlies sensory aging across the five senses. Clinicians assessing patients with a sensory deficit should consider further evaluation for additional cooccurring sensory deficits.

OBJECTIVES:To evaluate global sensory impairment (GSI, an integrated measure of sensory dysfunction) as a predictor of physical function, cognition, overall health, and mortality. DESIGN: Prospective study. SETTING: The National Social Life, Health, and Aging Project. PARTICIPANTS: A national probability sample of 3,005 home-dwelling older U.S. adults assessed at baseline and 5-year follow-up (2010-11). MEASUREMENTS: Gait speed, activity, disability, cognition, overall health, 5-year mortality. RESULTS: At baseline, older adults with worse GSI were slower (Timed Up and Go times: odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.17-1.50) and had more activity of daily living deficits (≥2: OR = 1.26, 95% CI = 1.10-1.46). Five years later, they were still slower (timed walk: OR = 1.22, 95% CI = 1.05-1.42), had more disabilities (≥2 instrumental activities of daily living; OR = 1.45, 95% CI = 1.23-1.70), were less active (daytime activity according to accelerometry: b = À2.7, 95% CI = À5.2 to À0.2), had worse cognitive function (Montreal Cognitive Assessment; b = À0.64, 95% CI = À0.84 to À0.44), more likely to have poorer overall health (OR = 1.16, 95% CI = 1.03-1.31) and lose weight (>10%: OR = 1.31, 95% CI = 1.04-1.64), and have died (OR = 1.45, 95% CI = 1.19-1.76). All analyses were adjusted for relevant confounders at baseline, including age, sex, race and ethnicity, education, smoking, problem drinking, body mass index, comorbidities, and cognitive function. CONCLUSION: GSI predicts impaired physical function, cognitive dysfunction, significant weight loss, and mortality 5 years later in older U.S. adults. Multisensory evaluation may identify vulnerable individuals, offering the opportunity for early intervention to mitigate adverse outcomes.

Context:Current information-rich electronic health record (EHR) interfaces require large, high-resolution screens running on desktop computers. This interface compromises the provider’s already limited time at the bedside by physically separating the patient from the doctor. The case study presented here describes a patient-centered clinical decision support (CDS) design process that aims to bring the physician back to the bedside by integrating a patient decision aid with CDS for shared use by the patient and provider on a touchscreen tablet computer for deciding whether or not to obtain a CT scan for minor head injury in the emergency department, a clinical scenario that could benefit from CDS but has failed previous implementation attempts.Case Description:This case study follows the user-centered design (UCD) approach to build a bedside aid that is useful and usable, and that promotes shared decision-making between patients and their providers using a tablet computer at the bedside. The patient-centered decision support design process focuses on the prototype build using agile software development, but also describes the following: (1) the requirement gathering phase including triangulated qualitative research (focus groups and cognitive task analysis) to understand current challenges, (2) features for patient education, the physician, and shared decision-making, (3) system architecture and technical requirements, and (4) future plans for formative usability testing and field testing.Lessons Learned:We share specific lessons learned and general recommendations from critical insights gained in the patient-centered decision support design process about early stakeholder engagement, EHR integration, external expert feedback, challenges to two users on a single device, project management, and accessibility.Conclusions:Successful implementation of this tool will require seamless integration into the provider’s workflow. This protocol can create an effective interface for shared decision-making and safe resource reduction at the bedside in the austere and dynamic clinical environment of the ED and is generalizable for these purposes in other clinical environments as well.

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