Background Non-syndromic hearing loss (NSHL) is the most common sensory impairment in humans. Until recently its extreme genetic heterogeneity precluded comprehensive genetic testing. Using a platform that couples targeted genomic enrichment (TGE) and massively parallel sequencing (MPS) to sequence all exons of all genes implicated in NSHL, we test 100 persons with presumed genetic NSHL and in so doing establish sequencing requirements for maximum sensitivity and define MPS quality score metrics that obviate Sanger validation of variants. Methods We examined DNA from 100 sequentially collected probands with presumed genetic NSHL without exclusions due to inheritance, previous genetic testing, or type of hearing loss. We performed TGE using post-capture multiplexing in variable pool sizes followed by Illumina sequencing. We developed a local Galaxy installation on a high performance-computing cluster for bioinformatics analysis. Results To obtain maximum variant sensitivity with this platform 3.2–6.3 million total mapped sequencing reads per sample are required. Quality score analysis showed that Sanger validation is not required for 95% of variants. Our overall diagnostic rate was 42% but varied by clinical features from 0% for persons with asymmetric hearing loss to 56% for persons with bilateral autosomal recessive NSHL. Conclusions These findings will direct the use of TGE and MPS strategies for genetic diagnosis for NSHL. Our diagnostic rate highlights the need for further research on genetic deafness focused on novel gene identification and an improved understanding of the role of non-exonic mutations. The unsolved families we have identified provide a valuable resource to address these areas.

BACKGROUND: Transgender people and racial/ethnic minorities separately report poor healthcare experiences. However, little is known about the healthcare experiences of transgender people of color (TPOC), who are both transgender and racial/ethnic minorities. OBJECTIVE: To investigate how TPOC healthcare experiences are shaped by both race/ethnicity and gender identity. DESIGN AND PARTICIPANTS: Semi-structured, indepth individual interviews (n = 22) and focus groups (2; n = 17 total); all taken from a sample of TPOC from the Chicago area. All participants completed a quantitative survey (n = 39). APPROACH: Interviews and focus groups covered healthcare experiences, and how these were shaped by gender identity and/or race/ethnicity. The interviews and focus groups were audio recorded, transcribed verbatim, and imported into HyperRESEARCH software. At least two reviewers independently coded each transcript using a codebook of themes created following grounded theory methodology. The quantitative survey data captured participants' demographics and past healthcare experiences, and were analyzed with descriptive statistics. KEY RESULTS: All participants described healthcare experiences where providers responded negatively to their race/ethnicity and/or gender identity. A majority of participants believed they would be treated better if they were cisgender or white. Participants commonly cited providers' assumptions about TPOC as a pivotal factor in negative experiences. A majority of participants sought out healthcare locations designated as lesbian, gay, bisexual, and transgender (LGBT)-friendly in an effort to avoid discrimination, but feared experiencing racism there. A minority of participants expressed a preference for providers of color; but a few reported reluctance to reveal their gender identity to providers of their own race due to fear of transphobia. When describing positive healthcare experiences, participants were most likely to highlight providers' respect for their gender identity. CONCLUSIONS: TPOC have different experiences compared with white transgender or cisgender racial/ethnic minorities. Providers must improve understanding of intersectional experiences of TPOC to improve quality of care.

OBJECTIVERevascularization of a symptomatic, medically refractory, cervical chronically occluded internal carotid artery (COICA) using endovascular techniques (ETs) has surfaced as a viable alternative to extracranial-intracranial bypass. The authors aimed to assess the safety, success, and neurocognitive outcomes of recanalization of COICA using ETs or hybrid treatment (ET plus carotid endarterectomy) and to identify candidate radiological markers that could predict success.METHODSThe authors performed a retrospective analysis of their prospectively collected institutional database and used their previously published COICA classification to assess the potential benefits of ETs or hybrid surgery to revascularize symptomatic patients with COICA. Subjects who had undergone CT perfusion (CTP) imaging and Montreal Cognitive Assessment (MoCA) testing, both pre- and postprocedure, were included. The authors then performed a review of the literature on patients with COICA to further evaluate the success and safety of these treatment alternatives.RESULTSThe single-center study revealed 28 subjects who had undergone revascularization of symptomatic COICA. Five subjects had CTP imaging and MoCA testing pre- and postrevascularization and thus were included in the study. All 5 patients had very large penumbra involving the entire hemisphere supplied by the ipsilateral COICA, which resolved postoperatively. Significant improvement in neurocognitive outcome was demonstrated by MoCA testing after treatment (preprocedure: 19.8 ± 2.4, postprocedure: 27 ± 1.6; p = 0.0038). Moreover, successful revascularization of COICA led to full restoration of cerebral hemodynamics in all cases. Review of the literature identified a total of 333 patients with COICA. Of these, 232 (70%) showed successful recanalization after ETs or hybrid surgery, with low major and minor complication rates (3.9% and 2.7%, respectively).CONCLUSIONSETs and hybrid surgery are safe and effective alternatives to revascularize patients with symptomatic COICA. CTP imaging could be used as a radiological marker to assess cerebral hemodynamics and predict the success of revascularization. Improvement in CTP parameters is associated with significant improvement in neurocognitive functions.

Created Out of Mind is an interdisciplinary project, comprised of individuals from arts, social sciences, music, biomedical sciences, humanities and operational disciplines. Collaboratively we are working to shape perceptions of dementias through the arts and sciences, from a position within the Wellcome Collection. The Collection is a public building, above objects and archives, with a porous relationship between research, museum artefacts, and the public.  This pre-planning framework will act as an introduction to Created Out of Mind. The framework explains the rationale and aims of the project, outlines our focus for the project, and explores a number of challenges we have encountered by virtue of working in this way.