Background: Following initial evaluation and management, youth requiring inpatient psychiatric care often experience boarding, defined as being held in the emergency department or another location while awaiting inpatient care. Although mental health boarding is common, little research has examined the quality of healthcare delivery during the boarding period. Objective: This study aimed to explore the perspectives and experiences of multidisciplinary clinicians and parents regarding mental health boarding and to develop a conceptual model to inform quality improvement efforts. Design, Setting, & Participants: We conducted semistructured interviews with clinicians and parents of youth experiencing boarding. Interviews focused on experiences of care and perceived opportunities for improvement were continued until thematic saturation was reached. Interviews were recorded, transcribed, and analyzed to identify emergent themes using a general inductive approach. Axial coding was used to inform conceptual framework development. Results: Interviews were conducted with 19 clinicians and 11 parents. Building on the Donabedian structure-process-outcome model of quality evaluation, emergent domains, and associated themes included: (1) infrastructure for healthcare delivery, including clinician training, healthcare team composition, and the physical environment; (2) processes of healthcare delivery, including clinician roles and responsibilities, goals of care, communication with families, policies/procedures, and logistics of inter-facility transfer; and (3) measurable outcomes, including patient safety, family experience, mental health status, timeliness of care, and clinician moral distress. Conclusion: This qualitative study summarizes clinician and family perspectives about care for youth experiencing boarding. The conceptual model resulting from this analysis can be applied to implement and evaluate quality improvement endeavors to support this vulnerable population.

Reovirus attachment protein σ1 is a trimeric molecule containing tail, body, and head domains. During infection, σ1 engages sialylated glycans and junctional adhesion molecule-A (JAM-A), triggering uptake into the endocytic compartment, where virions are proteolytically converted to infectious subvirion particles (ISVPs). Further disassembly allows σ1 release and escape of transcriptionally active reovirus cores into the cytosol. Electron microscopy has revealed a distinct conformational change in σ1 from a compact form on virions to an extended form on ISVPs. To determine the importance of σ1 conformational mobility, we used reverse genetics to introduce cysteine mutations that can crosslink σ1 by establishing disulfide bonds between structurally adjacent sites in the tail, body, and head domains. We detected phenotypic differences among the engineered viruses. A mutant with a cysteine pair in the head domain replicates with enhanced kinetics, forms large plaques, and displays increased avidity for JAM-A relative to the parental virus, mimicking properties of ISVPs. However, unlike ISVPs, particles containing cysteine mutations that crosslink the head domain uncoat and transcribe viral positive-sense RNA with kinetics similar to the parental virus and are sensitive to ammonium chloride, which blocks virion-to-ISVP conversion. Together, these data suggest that σ1 conformational flexibility modulates the efficiency of reovirus host cell attachment. IMPORTANCE Nonenveloped virus entry is an incompletely understood process. For reovirus, the functional significance of conformational rearrangements in the attachment protein, σ1, that occur during entry and particle uncoating are unknown. We engineered and characterized reoviruses containing cysteine mutations that crosslink σ1 monomers in non-reducing conditions. We found that the introduction of a cysteine pair in the receptor-binding domain of σ1 yielded a virus that replicates with faster kinetics than the parental virus and forms larger plaques. Using functional assays, we found that crosslinking the σ1 receptor-binding domain modulates reovirus attachment but not uncoating or transcription. These data suggest that σ1 conformational rearrangements mediate the efficiency of reovirus host cell binding.

Lung cancer screening (LCS) is severely under-utilized by eligible individuals living in rural areas. The purpose of this study is to increase LCS in a rural population by applying a combined systems and design approach to identify needed health system-level changes and to proactively identify potential facilitators and roadblocks for the changes across multiple levels in an academic medical center. Data to identify system-level processes and gaps included LCS referral and screening data, 26 stakeholder interviews with providers, clinical staff and potential eligible patients, review of health record fields for smoking history, and LCS process mapping, including potential pathways of referral and notification of eligibility. Design thinking was applied by assessing potential facilitators and roadblocks across different levels for changes, including higher-level institution commitment, financial implications of increased LCS (i.e., return on investment), gaps in process-level resources (e.g., accredited scanners, time for shared decision making), and overall stigma related to smoking. Results indicated overall support for LCS by all stakeholders but a lack of knowledge about LCS among potential patients and challenges to easily identify eligible patients and finding time for shared-decision making and smoking cessation required for LCS referrals among providers. Further investigation showed lack of full EHR documentation of smoking history due partially to insufficient fields in the EHR to document full smoking history or to calculate pack years which led to largely inaccurate automated LCS eligibility notifications. Targeted interventions based on the system findings include adding smoking history fields and calculators in the EHR to adequately document smoking history and identify eligible patients, creating an education and question-based pamphlet for patients visiting primary care to prompt accurate history documentation and LCS conversation, provider letters to highlight an existing Lung Health Center resource for SDM and smoking cessation, avoiding stigmatizing language (e.g., “smoker”), and highlighting health versus cancer (Lung Health Check versus Lung Cancer Screening) in patient-facing materials. Application of design thinking led to identifying sustainable interventions within existing processes and arranging leadership meetings to establish LCS ROI and personnel/equipment justifications to support and sustain increased LCS referrals. Models of healthcare improvement, such as those promoted by the Institute for Healthcare Improvement, focus largely on system-level analyses without adequate attention to design thinking which may lead to interventions that are limited in scope or subject to obstacles that limit success. This study demonstrates that using wider and multiple lens for improving LCS in a rural population allows for human-centered and system-centered approaches that may better address gaps in care for individuals at high risk for inadequate care and provide them services that they deserve. Citation Format: Rian M. Hasson, Karen E. Schifferdecker, Shaun A. Golding, Shani Bardach, Linda M. Kinney, Maureen B. Boardman, Ellie Kyung, Sean R. Halloran, Samuel L. Youkilis, Amanda N. Perry, Vrushabh P. Ladage, Tom Bird. Use of a combined systems and design framework to assess and improve lung cancer screening for underserved rural population [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A103.

23Reovirus attachment protein σ1 is a trimeric molecule containing tail, body, and head 24 domains. During infection, σ1 engages sialylated glycans and junctional adhesion 25 molecule-A (JAM-A), triggering uptake into the endocytic compartment, where virions 26 are proteolytically converted to infectious subvirion particles (ISVPs). Further 27 disassembly allows σ1 release and escape of transcriptionally active reovirus cores into 28 the cytosol. Electron microscopy has revealed a distinct conformational change in σ1 29 from a compact form on virions to an extended form on ISVPs. To determine the 30 importance of σ1 conformational mobility, we used reverse genetics to introduce 31 cysteine mutations that can crosslink σ1 by establishing disulfide bonds between 32 structurally adjacent sites in the tail, body, and head domains. We detected phenotypic 33 differences among the engineered viruses. A mutant with a cysteine pair in the head 34 domain replicates with enhanced kinetics, forms large plaques, and displays increased 35 avidity for JAM-A relative to the parental virus, mimicking properties of ISVPs. However, 36 unlike ISVPs, particles containing cysteine mutations that crosslink the head domain 37 uncoat and transcribe viral positive-sense RNA with kinetics similar to the parental virus 38 and are sensitive to ammonium chloride. Together, these data suggest that σ1 39 conformational flexibility modulates the efficiency of reovirus host cell attachment. 40 1 (NgR1) (4, 5, 10-12). Virion binding is followed by uptake into the endocytic 71 compartment of some types of cells via clathrin-dependent endocytosis (13-15). The σ1 72 head engages JAM-A within a conserved binding region, and for prototype strain type 1 73 Lang (T1L) σ1, the head also engages sialic acid (SA) (4, 16). For prototype strain type 74 5 3 Dearing (T3D) σ1, the body domain contains the SA-binding region (5). Reovirus 75 attaches to cells using an adhesion-strengthening mechanism, wherein initial low-avidity 76 σ1 interactions with SA permit lateral particle diffusion across the cell surface, which is 77 followed by high-avidity binding to JAM-A (17). For T3D reovirus, SA binding enhances 78 JAM-A binding capacity, possibly by triggering conformational changes in σ1 (18). 79Within the endocytic compartment, reovirus virions are proteolytically converted 80 to infectious subvirion particles (ISVPs). This conversion involves a stepwise, acid-81 dependent disassembly process catalyzed by cathepsin proteases (19). The first 82 disassembly intermediate, the infectious subvirion particle (ISVP), is characterized by 83 proteolytic removal of σ3, cleavage of µ1, and a conformational change in the σ1 protein 84 (3, 20). Conversion from the ISVP to ISVP* involves a conformational rearrangement of 85 the particle and μ1 autocleavage, releasing μ1 fragments that mediate formation of 86 pores in the endosomal membrane (21-24). Additional conformational rearrangements 87 result in σ1 release from icosahedral vertices and delivery of the transcriptionally ac...