Introduction Decision-making for T1 renal masses has become increasingly complex as more management options have become available. Most patients experience decisional conflict at some point in their decision-making process due to fear, uncertainty, and lack of understanding. Furthermore, decisional conflict may prompt patients to undergo a treatment that does not necessarily align with their priorities or values. For medical decisions, patients have a variety of unique support needs that impact their decision-making process, preferences, and treatment choice. To better support these patient needs, we sought to characterize support needs and coping mechanisms for patients presenting for small renal masses (SRM). Methods Forty patients previously enrolled onto the GRADE-SRM study, a prospective clinical trial examining cancer genomics and the impact of renal mass biopsy on decision-making, were recruited to participate in a follow-up qualitative study. Participants were purposely sampled based on high (21) vs. low (19) decisional conflict scores as well as diverse support needs and coping strategies. Trained qualitative researchers conducted semi-structured interviews asking participants questions related to decision-making support needs including factors that impacted their decision-making preferences and coping strategies. Qualitative researchers then conducted a coding-based thematic analysis to define pertinent themes regarding patient support needs that impact decision-making. Further post hoc analysis was conducted to synthesize and describe support needs and coping mechanisms across the cohort. Results Among the 40 interview participants, the mean age was 65.1, with 58% male and 72.5% White. A primary focus on either preparation/process or health outcomes tended to drive individual support needs. A focus on process entailed steps in management and the overall journey while a focus on outcomes encompassed impact on survival or other health effects. Patient support needs fell into three main categories that were identified in post hoc analysis: informational, emotional, and instrumental support. Within each category, patients desired support from both their healthcare team and personal support system. Informational supports included medical counseling from their urologist and advice externally. Patients required emotional support from both medical and social sources but mainly desired instrumental support from their social network. Patients described coping mechanisms employed from diagnosis through treatment. These fell into four categories: relying on faith, controlling outlook, depending on external support, and trusting in their urologist. Conclusions Patients display a diverse range of support needs and coping strategies during the process of diagnosis and decision-making for clinical T1 renal masses that we can overwhelmingly categorize into discrete subtypes. Further, patient support needs tend to be driven by either a focus on process or outcome. These findings provide further understanding and context for how support needs may be used to promote shared decision-making. Efforts to improve the decision-making process may consider support needs, drivers, and coping mechanisms during development.

You have accessJournal of UrologyHealth Services Research: Practice Patterns, Quality of Life and Shared Decision Making I (MP12)1 May 2024MP12-17 UNDERSTANDING PATIENT DECISION-MAKING FOR CLINICAL T1 RENAL MASSES Katherine E. Poulos, Allison Lazard, Lixin Song, Kathryn H. Gessner, Amir Feinberg, Deborah Usinger, Randall Teal, Debra Gottsleben, Marc Bjurlin, Eric Wallen, David Johnson, Mathew C. Raynor, and Hung-Jui Tan Katherine E. PoulosKatherine E. Poulos , Allison LazardAllison Lazard , Lixin SongLixin Song , Kathryn H. GessnerKathryn H. Gessner , Amir FeinbergAmir Feinberg , Deborah UsingerDeborah Usinger , Randall TealRandall Teal , Debra GottslebenDebra Gottsleben , Marc BjurlinMarc Bjurlin , Eric WallenEric Wallen , David JohnsonDavid Johnson , Mathew C. RaynorMathew C. Raynor , and Hung-Jui TanHung-Jui Tan View All Author Informationhttps://doi.org/10.1097/01.JU.0001009376.16371.fb.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients diagnosed with clinical T1 renal masses have multiple treatment options, especially those with a small renal mass (SRM). While numerous studies have examined clinical determinants of treatment choice, the patient perspective on treatment selection remains grossly understudied despite calls for shared decision-making. Accordingly, we sought to explore the decision-making process and experience in this patient population. METHODS: We purposefully recruited 40 participants from GRADE-SRM, a prospective clinical trial studying the impact of renal mass biopsy on decision-making, based on high (21) vs. low (19) levels of decisional conflict for interviews. Trained qualitative researchers asked participants about their decision-making experience including factors that affected their management choice. Using a coding-based approach, we identified themes related to the overlying process and facilitators and barriers of treatment selection. RESULTS: Of the 40 participants, mean age was 65.1, 27.5% were non-White, and 42% were female. Patients gave five primary reasons for selecting a treatment, with the majority describing the treatment was recommended by the urologist (N=14) or only one treatment was recommended (N=12) with other primary reasons being progressively less represented (Figure 1). Of the four primary options to consider, participants reported diverse facilitators and barriers behind their selection. Across all options, selection of treatment largely revolved around patients' perception of surgeon recommendation and communication. Barriers for choosing active surveillance (AS) and biopsy often involved fear and anxiety. Barriers for AS often revolved around anxiety and fear of living with a mass or desire to resolve treatment rather than prolong care. Uniquely, many patients who chose biopsy felt it was minimally invasive or could give confirmatory information, while other patients chose against biopsy because they felt uncomfortable due to negative past experiences. CONCLUSIONS: For patients, surgeon recommendation and the options provided largely shape treatment choice. In particular, patients may be more amendable to biopsy or active surveillance if their fears and concerns were alleviated. To improve decision-making, efforts may need to be directed toward these points. Download PPT Source of Funding: This work was supported by funding from the Department of Defense © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e207 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Katherine E. Poulos More articles by this author Allison Lazard More articles by this author Lixin Song More articles by this author Kathryn H. Gessner More articles by this author Amir Feinberg More articles by this author Deborah Usinger More articles by this author Randall Teal More articles by this author Debra Gottsleben More articles by this author Marc Bjurlin More articles by this author Eric Wallen More articles by this author David Johnson More articles by this author Mathew C. Raynor More articles by this author Hung-Jui Tan More articles by this author Expand All Advertisement PDF downloadLoading ...

PURPOSE:Because multiple management options exist for clinical T1 renal masses, patients may experience a state of uncertainty about the course of action to pursue (ie, decisional conflict). To better support patients, we examined patient, clinical, and decision-making factors associated with decisional conflict among patients newly diagnosed with clinical T1 renal masses suspicious for kidney cancer. MATERIALS AND METHODS:From a prospective clinical trial, participants completed the Decisional Conflict Scale (DCS), scored 0 to 100 with < 25 associated with implementing decisions, at 2 time points during the initial decision-making period. The trial further characterized patient demographics, health status, tumor burden, and patient-centered communication, while a subcohort completed additional questionnaires on decision-making. Associations of patient, clinical, and decision-making factors with DCS scores were evaluated using generalized estimating equations to account for repeated measures per patient. RESULTS:Of 274 enrollees, 250 completed a DCS survey; 74% had masses ≤ 4 cm in size, while 11% had high-complexity tumors. Model-based estimated mean DCS score across both time points was 17.6 (95% CI 16.0-19.3), though 50% reported a DCS score ≥ 25 at least once. On multivariable analysis, DCS scores increased with age (+2.64, 95% CI 1.04-4.23), high- vs low-complexity tumors (+6.50, 95% CI 0.35-12.65), and cystic vs solid masses (+9.78, 95% CI 5.27-14.28). Among decision-making factors, DCS scores decreased with higher self-efficacy (-3.31, 95% CI -5.77 to -0.86]) and information-seeking behavior (-4.44, 95% CI -7.32 to -1.56). DCS scores decreased with higher patient-centered communication scores (-8.89, 95% CI -11.85 to -5.94). CONCLUSIONS:In addition to patient and clinical factors, decision-making factors and patient-centered communication relate with decisional conflict, highlighting potential avenues to better support patient decision-making for clinical T1 renal masses.

Introduction For patients with clinical T1 renal masses, active surveillance is becoming an increasingly popular management option instead of surgical resection or ablation. However, we lack effective prognostic biomarkers to identify patients with high-risk disease. Additionally, the presence of intratumoral heterogeneity in renal cell carcinoma (RCC) may impact our ability to use a genomic biomarker on renal mass biopsy (RMB) tissue. This study seeks to evaluate genomic and transcriptomic features associated with conversion from clinical T1 to pathologic T3 disease and characterize the extent of intratumoral heterogeneity. Methods From October 2018–June 2022, patients with new clinical T1 kidney tumors were enrolled onto GRADE-SRM (Genomic Risk Assessment and Decisional Evaluation for Small Renal Masses), a comparative, non-randomized hybrid trial assessing decision-making experience and cancer genomics. Tissue from surgery (including multifocal sampling), RMB, and germline DNA was obtained. Targeted exon sequencing was performed using UNCseq v10.2 platform and variants were filtered using standard criteria. Intratumoral heterogeneity was measured by mutation concordance, defined as percent of mutations in nephrectomy specimen also identified in multifocal sampling. RNA sequencing was performed using Illumina TruSeq Stranded mRNAseq with standard data processing. Results Of 70 patients with clear cell RCC who underwent surgery, 10 tumors converted from cT1b to pT3a based on surgical pathology and were compared to 16 cT1b tumors who remained pT1b. pT3a tumors demonstrated similar number of variants compared to pT1b tumors (7.4 vs 5.3, p=0.07) and similar levels of intratumoral heterogeneity (mutation concordance 66% vs 68%, p=0.89). However, pT3a tumors demonstrated a higher percentage with SETD2 mutations compared to pT1b tumors (30% vs 5%). Transcriptomic analysis identified 51 genes that were differentially expressed between pT1b and pT3a tumors. Conclusions This study identifies genomic and transcriptomic differences between cT1b tumors that remain pT1b versus those that convert to pT3a. These results highlight potential alterations for use as prognostic biomarkers to risk stratify patients and guide decisions regarding active surveillance vs treatment. Future research will focus on evaluating whether these alterations can be identified on prospectively collected standard-of-care RMB specimens.

Herpes simplex virus (HSV) and varicella zoster virus (VZV) rely on transport of virus particles in neuronal axons to spread from sites of viral latency in sensory ganglia to peripheral tissues then on to other hosts. This process of anterograde axonal transport involves kinesin motors that move virus particles rapidly along microtubules. α-herpesvirus anterograde transport has been extensively studied by characterizing the porcine pseudorabies virus (PRV) and HSV, with most studies focused on two membrane proteins: gE/gI and US9. It was reported that PRV and HSV US9 proteins bind to kinesin motors, promoting tethering of virus particles on the motors, and furthering anterograde transport within axons. Alternatively, other models have argued that HSV and PRV US9 and gE/gI function in the cytoplasm and not in neuronal axons. Specifically, HSV gE/gI and US9 mutants are defective in the assembly of virus particles in the cytoplasm of neurons and the subsequent sorting of virus particles to cell surfaces and into axons. However, PRV US9 and gE/gI mutants have not been characterized for these cytoplasmic defects. We examined neurons infected with PRV mutants, one lacking both gE/gI and US9 and the other lacking just US9, by electron microscopy. Both PRV mutants exhibited similar defects in virus assembly and cytoplasmic sorting of virus particles to cell surfaces. As well, the mutants exhibited reduced quantities of infectious virus in neurons and in cell culture supernatants. We concluded that PRV US9 primarily functions in neurons to promote cytoplasmic steps in anterograde transport.

You have accessJournal of UrologyCME1 Apr 2023PD32-10 DECISIONAL CONFLICT AMONG PATIENTS NEWLY DIAGNOSED WITH CLINICAL T1 RENAL MASSES Amir Feinberg, Kathryn Gessner, Shannon Myers, Hillary Heiling, Allison Deal, Sara Wobker, Allison Lazard, Marc Bjurlin, Mathew Raynor, Matthew Nielsen, Angela Smith, Eric Wallen, David Johnson, William Kim, and Hung-Jui Tan Amir FeinbergAmir Feinberg More articles by this author , Kathryn GessnerKathryn Gessner More articles by this author , Shannon MyersShannon Myers More articles by this author , Hillary HeilingHillary Heiling More articles by this author , Allison DealAllison Deal More articles by this author , Sara WobkerSara Wobker More articles by this author , Allison LazardAllison Lazard More articles by this author , Marc BjurlinMarc Bjurlin More articles by this author , Mathew RaynorMathew Raynor More articles by this author , Matthew NielsenMatthew Nielsen More articles by this author , Angela SmithAngela Smith More articles by this author , Eric WallenEric Wallen More articles by this author , David JohnsonDavid Johnson More articles by this author , William KimWilliam Kim More articles by this author , and Hung-Jui TanHung-Jui Tan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003325.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Increasingly, the management of clinical T1 renal masses has become a complex, preference-sensitive decision due to their favorable prognosis and multitude of management options. However, having multiple options can also generate significant decisional conflict and ultimately regret. Accordingly, we sought to evaluate factors driving decisional conflict among patients with clinical T1 renal masses suspicious for kidney cancer. METHODS: From October 2018–June 2022, we prospectively enrolled patients with new clinical T1 renal masses onto GRADE-SRM, a non-randomized hybrid trial investigating the decision-making experience and cancer genomics. Participants completed surveys on their demographics, health status, and patient-centered communication. Beginning in June 2019, participants also completed surveys on their health status and decision-making traits (e.g., self-efficacy, maximizer-minimizer, autonomy preference, literacy, numeracy). For this analysis, decisional conflict served as the primary outcome as measured by the decisional conflict scale (DCS). We compared DCS score by patient and clinical factors using bivariable linear regression analyses. RESULTS: Overall, 236 of 265 enrollees completed a baseline DCS survey. Mean age was 62.4 years (SD 11.2), 61.4% were male, and 31.3% were non-White. While 74.9% had masses ≤4cm in size, 10.7% had high complexity tumors, 5.9% had bilateral masses, and 6.4% had multifocal masses. Overall, mean DCS score was 16.8 (SD 14.1) though 38.1% had a high DCS score (≥25). DCS scores increased with age (p=0.003). Patients with high complexity (p=0.032), cystic (p=0.043), or multifocal (p=0.037) masses had higher DCS scores compared to their counterparts. DCS scores increased with lower self-efficacy (p<0.001) but did not differ based on maximizer-minimizer tendency or numeracy. Patients with less information-seeking behavior and worse perceived communication experienced more decisional conflict (p<0.001). CONCLUSIONS: Over a third of patients with newly diagnosed clinical T1 renal masses suspicious for kidney cancer experience significant decisional conflict. High scores seemed to be driven by tumor complexity, self-efficacy, information-seeking, and perceived communication, perhaps relating to both the potential risks of treatment and the importance of patient-provider communication. Efforts to improve the decision-making experience will need to focus on the collaborative aspects of shared decision-making. Source of Funding: This work was supported by funding from the National Institutes of Health (UNC Integrated Translational Oncology Program T32-CA244125 to UNC/khg) and UNC Lineberger Comprehensive Cancer Center UNCseq v2 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e911 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amir Feinberg More articles by this author Kathryn Gessner More articles by this author Shannon Myers More articles by this author Hillary Heiling More articles by this author Allison Deal More articles by this author Sara Wobker More articles by this author Allison Lazard More articles by this author Marc Bjurlin More articles by this author Mathew Raynor More articles by this author Matthew Nielsen More articles by this author Angela Smith More articles by this author Eric Wallen More articles by this author David Johnson More articles by this author William Kim More articles by this author Hung-Jui Tan More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyCME1 Apr 2023PD32-04 CLINICAL AND DECISION-MAKING FACTORS IMPACTING PATIENT-CENTERED COMMUNICATION IN PATIENTS WITH CLINICAL T1 RENAL MASSES Kathryn Gessner, Amir Feinberg, Shannon Myers, Hillary Heiling, Allison Deal, Sara Wobker, Allison Lazard, Marc Bjurlin, Mathew Raynor, Matthew Nielsen, Angela Smith, Eric Wallen, David Johnson, William Kim, and Hung-Jui Tan Kathryn GessnerKathryn Gessner More articles by this author , Amir FeinbergAmir Feinberg More articles by this author , Shannon MyersShannon Myers More articles by this author , Hillary HeilingHillary Heiling More articles by this author , Allison DealAllison Deal More articles by this author , Sara WobkerSara Wobker More articles by this author , Allison LazardAllison Lazard More articles by this author , Marc BjurlinMarc Bjurlin More articles by this author , Mathew RaynorMathew Raynor More articles by this author , Matthew NielsenMatthew Nielsen More articles by this author , Angela SmithAngela Smith More articles by this author , Eric WallenEric Wallen More articles by this author , David JohnsonDavid Johnson More articles by this author , William KimWilliam Kim More articles by this author , and Hung-Jui TanHung-Jui Tan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003325.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Management of clinical T1 renal masses has become a complex, preference-sensitive decision. In a previous study, 30% of patients with SRMs reported decisional conflict. More patient-centered communication that could reduce decisional conflict, but its determinants remain unknown. Therefore, we sought to evaluate the clinical and decision-making factors impacting patient-centered communication in patients with clinical T1 renal masses. METHODS: From October 2018–June 2022, we enrolled patients with new clinical T1 kidney tumors onto GRADE-SRM, a comparative, non-randomized hybrid trial investigating the decision-making experience and cancer genomics. Upon study entry (T0) and 2-4 weeks later (T1), participants completed surveys to characterize their decision-making and communication preferences in addition to demographic, health, and tumor characteristics. Patient-centered communication served as the primary outcome and measured by the validated Patient-Centered Communication in Cancer Care (PCC) Instrument. We examined the relationship between PCC and patient/tumor characteristics through repeated measures bivariable linear regression analyses using generalized estimating equations. RESULTS: Among 265 enrollees, 229 completed a T0 PCC survey and 195 enrollees completed a T1PCC survey. Mean age was 62.3 years (SD 11.2), 61.4% were male, and 31.8% were non-White. Overall, mean PCC score was 4.40 (SD 0.62) at T0 and 4.31 (SD 0.69) at T1. Patients with higher levels of education (p=0.047), previous history of kidney cancer (p=0.0001), and previous abdominal surgery (p=0.011) reported better communication scores. Worse communication scores were associated with seeing an outside urologist prior to UNC evaluation (p=0.022) and higher perceived risk of metastasis (p=0.015). Better communication scores were associated with higher self-efficacy (p=0.003), numeracy (p=0.019) and information seeking behavior (p=0.011), while worse communication scores were associated with increased worry (p=0.021). CONCLUSIONS: For patients with SRMs, more patient-centered communication is reported by those with similar past healthcare experiences, more self-efficacy, and information seeking behavior. These findings highlight the importance of both lived experiences and patient learning ability on their perception of communication. Efforts to improve communication and decision-making may need to be directed toward these action points. Source of Funding: This work was supported by funding from the National Institutes of Health (UNC Integrated Translational Oncology Program T32-CA244125 to UNC/khg) and UNC Lineberger Comprehensive Cancer Center UNCseq v2 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e908 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kathryn Gessner More articles by this author Amir Feinberg More articles by this author Shannon Myers More articles by this author Hillary Heiling More articles by this author Allison Deal More articles by this author Sara Wobker More articles by this author Allison Lazard More articles by this author Marc Bjurlin More articles by this author Mathew Raynor More articles by this author Matthew Nielsen More articles by this author Angela Smith More articles by this author Eric Wallen More articles by this author David Johnson More articles by this author William Kim More articles by this author Hung-Jui Tan More articles by this author Expand All Advertisement PDF downloadLoading ...

The interplay between charge transfer and electronic disorder in transition-metal dichalcogenide multilayers gives rise to superconductive coupling driven by proximity enhancement, tunneling and superconducting fluctuations, of a yet unwieldy variety. Artificial spacer layers introduced with atomic precision change the density of states by charge transfer. Here, we tune the superconductive coupling betweenNbSe2monolayers from proximity-enhanced to tunneling-dominated. We correlate normal and superconducting properties inSnSe1+δmNbSe21tailored multilayers with varying SnSe layer thickness (m=1-15). From high-field magnetotransport the critical fields yield Ginzburg-Landau coherence lengths with an increase of140%cross-plane (m=1-9), trending towards two-dimensional superconductivity form>9. We show cross-overs between three regimes: metallic with proximity-enhanced coupling (m=1-4), disordered-metallic with intermediate coupling (m=5-9) and insulating with Josephson tunneling (m>9). Our results demonstrate that stacking metal mono- and dichalcogenides allows to convert a metal/superconductor into an insulator/superconductor system, prospecting the control of two-dimensional superconductivity in embedded layers.

Background: Acute viral bronchiolitis is among the most common illnesses seen in the emergency department (ED) and is the leading cause of infant hospitalization in Canada. Practice guidelines do not recommend routine use of certain diagnostic tests and medications in managing bronchiolitis, yet prior studies suggest that low-value interventions are routinely administered to patients with bronchiolitis. Successful implementation of quality improvement at the Alberta Children’s Hospital suggested that low-value interventions and tests can be improved. Yet, practice variation and potential opportunities to improve bronchiolitis management are likely present in EDs in urban and rural settings. Implementation: The project is a collaboration between the Maternal Newborn Child and Youth Strategic Clinical Network (MNCY SCN), the Improving Health Outcomes Together Team (IHOT), and Physician Learning Program (PLP) under the umbrella of the AHS Ernst & Young Clinical Appropriateness Theme recommendations to expand and scale initiatives to reduce unnecessary tests to improve patient safety. A provincial Bronchiolitis Steering Committee, led by two Physician Initiative Leads, was formed to guide the project and implementation at 16 facilities across Alberta. Site implementation includes two key aspects: Audit & Feedback (A&F) – review practice data, facilitated discussion with clinicians, and identify enablers and barriers to practice change Site Specific Implementation Plan – options for sites include use of posters, tools, resources; utilization of ConnectCare (order sets); and staff and physician education Qualitative interviews with site-champions will provide perspectives and feedback on enablers and barriers to change. Discussions from the A&F sessions, in addition to the qualitative interviews will be coded and analyzed based on the Consolidated Framework for Implementation Research and Theoretical Domains Framework. Resources required included clinical leads, project management, data/dashboards, educational posters, updated order sets, and a central location for staff and physician to access bronchiolitis materials (via SharePoint). Evaluation Methods: The primary objective of the study is a reduction of chest x-ray utilization. Chest x-rays utilization can be readily obtained from administrative data at all sites in the project. Secondary measures include medications (PIN) and respiratory viral testing. There is strong evidence to support that medications and respiratory viral testing do not impact bronchiolitis management. The project addresses patient safety and outcomes by reducing the use of low-value interventions and tests in the ED and enables resources to be directed towards evidence-based care. As ConnectCare is phased into all facilities across Alberta, additional metrics will be incorporated into reports and updates to participating sites. Results: The first phase of the project took place from September to November 2021, with rollout to six facilities (four EDs and two inpatient units). A total of 151 physicians attended the audit and group feedback sessions. Site-specific planning sessions and qualitative interviews with site-champions are planned, and the next phase of the project will continue with spread and scale to regional EDs (n=5), urban (n=2) and rural (n=4) locations in fall 2022. Advice and Lessons Learned: The partnership with MNCY SCN, PLP, IHOT, and two Clinician Leads has been beneficial for establishing a team-based multi-disciplinary approach to address needs as they arise and the ability to work together with site champions. Identifying and collaborating with site champions is necessary for establishing relationships and trust prior to conducting audit and feedback sessions and addressing practice change. Site champions understand the contextual factors of their facility and how to best utilize enablers or address barriers for practice change. Initiation of these working relationships need to take place months before implementation and ideally develop through existing networks. Timing and flexibility are crucial for successful implementation. Rescheduling launch dates, adjusting session time, validating data, and adjusting to external factors such as delays in ConnectCare rollouts and pressures on the healthcare system brought on by the COVID-19 pandemic were experienced in the planning and initiating phases of the project. These lessons will be carried forward as we plan for the second part of spread and scale in Fall 2022.

Background: Exposure-based therapy is an effective first-line treatment for anxiety-, obsessive-compulsive, and trauma- and stressor-related disorders; however, many patients do not improve, resulting in prolonged suffering and poorly used resources. Basic research on fear extinction may inform the development of a biomarker for the selection of exposure-based therapy. Growing evidence links orexin system activity to deficits in fear extinction and we have demonstrated that reactivity to an inhaled carbon dioxide (CO2) challenge-a safe, affordable, and easy-to-implement procedure-can serve as a proxy for orexin system activity and predicts fear extinction deficits in rodents. Building upon this basic research, the goal for the proposed study is to validate CO2 reactivity as a biomarker of exposure-based therapy non-response. Methods: We will assess CO2 reactivity in 600 adults meeting criteria for one or more fear- or anxiety-related disorders prior to providing open exposure-based therapy. By incorporating CO2 reactivity into a multivariate model predicting treatment non-response that also includes reactivity to hyperventilation as well as a number of related predictor variables, we will establish the mechanistic specificity and the additive predictive utility of the potential CO2 reactivity biomarker. By developing models independently within two study sites (University of Texas at Austin and Boston University) and predicting the other site's data, we will validate that the results are likely to generalize to future clinical samples. Discussion: Representing a necessary stage in translating basic research, this investigation addresses an important public health issue by testing an accessible clinical assessment strategy that may lead to a more effective treatment selection (personalized medicine) for patients with anxiety- and fear-related disorders, and enhanced understanding of the mechanisms governing exposure-based therapy.

Caribbean small island developing states are highly exposed to climate change impacts. Incorporating weather and climate information into public health decisions can promote resilience to climate change’s adverse health effects, but regionally it is not common practice. We implemented a project to enhance dialogue between climate and public health specialists in Puerto Rico and Dominica. First, we conducted environmental scans of public health vulnerability in the context of weather and climate for both islands. Then, we convened stakeholders to discuss the scan results and identify priorities for climate and health. A shared priority was increasing climate and health knowledge; thus, we developed several educational initiatives. In this viewpoint, we discuss our process for conducting environmental scans, building capacity and partnerships, and translating knowledge-to-action around climate and health.

Human cytomegalovirus (HCMV) entry involves trimer (gH/gL/gO) that interacts with PDGFRα in fibroblasts. Entry into epithelial and endothelial cells requires trimer, which binds unidentified receptors, and pentamer (gH/gL/UL128-131), which binds neuropilin-2. To identify functionally important domains in trimer, we screened an overlapping 20-mer gO peptide library and identified two sets of peptides: 19/20 (a.a. 235-267) and 32/33 (a.a. 404-436) that could block virus entry. Soluble trimer containing wild type gO blocked HCMV entry, whereas soluble trimers with the 19/20 or 32/33 sequences mutated did not block entry. Interestingly, the mutant trimers retained the capacity to bind to cellular receptors including PDGFRα. Peptide 19/20 and 32/33 sequences formed a lobe extending from the surface of gO and an adjacent concave structure, respectively. Neither of these sets of sequences contacted PDGFRα. Instead, our data support a model in which the 19/20 and 32/33 trimer sequences function downstream of receptor binding, e.g. trafficking of HCMV into endosomes or binding to gB for entry fusion. We also screened for peptides that bound antibodies (Abs) in human sera, observing that peptides 20 and 26 bound Abs. These peptides engendered neutralizing Abs (NAbs) after immunization of rabbits and could pull out NAbs from human sera. Peptides 20 and 26 sequences represent the first NAb epitopes identified in trimer. These studies describe two important surfaces on gO defined by: i) peptides 19/20 and 32/33, which apparently act downstream of receptor binding and ii) peptide 26 that interacts with PDGFRα. Both these surfaces are targets of NAbs.

Alpha-herpes viruses such as herpes simplex virus (HSV) and pseudorabies virus (PRV) rely on anterograde transport from sensory ganglia, down neuronal axons, to reach epithelial tissues and spread Transport is achieved by tethering the alpha-herpes virus to kinesin motors which move along microtubule tracks in the axon The role of two viral proteins, gE/gI and US9, in this mechanism is still unclear. One model indicates that the gE/gI and US9 proteins promote tethering of PRV virus particles onto kinesin motors [2]. Another model argues that gE/gI and US9 do not participate in transport and are instead active in viral assembly and sorting within the cytoplasm [3,4]. Since PRV gE/gI and US9 mutants have yet to be screened for cytoplasmic defects, one PRV mutant lacking gE/gI and US9 and another only lacking US9 were characterized via transmission electron microscopy (TEM). We observe that PRV mutants for gE/gI and US9 exhibit defective viral assembly and sorting which may indicate that the main function of the gE/gI and US9 proteins is in the cytoplasmic steps of anterograde transport, rather than kinesin-mediated axonal transport. Two cell lines were infected with wild type PRV and PRV mutants for gE/gI and US9. Differentiated CAD cells which are a derivative of mouse catecholaminergic central nervous systems cells their Around 10% of the

Spurred by recent discoveries of high-temperature superconductivity in Fe-Se-based materials, the magnetic, electronic, and catalytic properties of iron chalcogenides have drawn significant attention. However, much remains to be understood about the sequence of phase formation in these systems. Here, we shed light on this issue by preparing a series of binary Fe-Se ultrathin diffusion couples via designed thin-film precursors and investigating their structural evolution as a function of composition and annealing temperature. Two previously unreported Fe-Se phases crystallized during the deposition process on a nominally room-temperature Si substrate in the 27-33 and 37-47% Fe (atomic percent) composition regimes. Both phases completely decompose after annealing to 200 degrees C in a nitrogen glovebox. At higher temperatures, the sequence of phase formation is governed by Se loss in the annealing process, consistent with what would be expected from the phase diagram. Films rich in Fe (53-59% Fe) crystalized during deposition as beta-FeSe (P4/nmm) with preferred c-axis orientation to the amorphous SiO2 substrate surface, providing a means to nonepitaxial self-assembly of crystallographically aligned, iron-rich beta-FeSe for future research. Our findings suggest that the crystallization of binary Fe-Se compounds at room temperature via near diffusionless transformations should be a significant consideration in future attempts to prepare metastable ternary and higher-order compounds containing Fe and Se.

Thin films of (Ge 1– x Sn x ) 8 Sb 2 Te 11 are prepared to study the impact of Sn‐substitution on properties relevant for application in phase‐change memory, a next‐generation electronic data storage technology. It is expected that substitution decreases the crystallization temperature, but it is not known how the maximum crystallization rate is affected. Ge 8 Sb 2 Te 11 is chosen from the (GeTe) y (Sb 2 Te 3 ) 1– y system of phase‐change materials as a starting point due to its higher crystallization temperature as compared to the common material Ge 2 Sb 2 Te 5 . In situ X‐ray diffraction at 5 K min −1 heating rate is performed to determine the crystallization temperature and the resulting structure. To measure the maximum crystallization rate, femtosecond optical pulses that heat the material repetitively and monitor the resulting increase of optical reflectance are used. Glasses over the entire composition range are prepared using a melt‐quenching process. While at x = 0, 97, subsequent pulses are required for crystallization, one single pulse is enough to achieve the same effect at x = 0.5. The samples are further characterized by optical ellipsometry and calorimetry. The combined electrical and optical contrast and the ability to cycle between states with single femtosecond pulses renders Ge 4 Sn 4 Sb 2 Te 11 promising for photonics applications.

Human cytomegalovirus (HCMV) is a herpesvirus that produces disease in transplant patients and newborn children. Entry of HCMV into cells relies on gH/gL trimer (gHgLgO) and pentamer (gHgLUL128-131) complexes that bind cellular receptors. Here, we studied the structure and interactions of the HCMV trimer, formed by AD169 strain gH and gL and TR strain gO proteins, with the human platelet-derived growth factor receptor alpha (PDGFRα). Three trimer surfaces make extensive contacts with three PDGFRα N-terminal domains, causing PDGFRα to wrap around gO in a structure similar to a human hand, explaining the high-affinity interaction. gO is among the least conserved HCMV proteins, with 8 distinct genotypes. We observed high conservation of residues mediating gO-gL interactions but more extensive gO variability in the PDGFRα interface. Comparisons between our trimer structure and a previously determined structure composed of different subunit genotypes indicate that gO variability is accommodated by adjustments in the gO-PDGFRα interface. We identified two loops within gO that were disordered and apparently glycosylated, which could be deleted without disrupting PDGFRα binding. We also identified four gO residues that contact PDGFRα, which when mutated produced markedly reduced receptor binding. These residues fall within conserved contact sites of gO with PDGFRα and may represent key targets for anti-trimer neutralizing antibodies and HCMV vaccines. Finally, we observe that gO mutations distant from the gL interaction site impact trimer expression, suggesting that the intrinsic folding or stability of gO can impact the efficiency of trimer assembly. IMPORTANCE HCMV is a herpesvirus that infects a large percentage of the adult population and causes significant levels of disease in immunocompromised individuals and birth defects in the developing fetus. The virus encodes a complex protein machinery that coordinates infection of different cell types in the body, including a trimer formed of gH, gL, and gO subunits. Here, we studied the interactions of the HCMV trimer with its receptor on cells, the platelet derived growth factor receptor α (PDGFRα), to better understand how HCMV coordinates virus entry into cells. Our results add to our understanding of HCMV strain-specific differences and identify sites on the trimer that represent potential targets for therapeutic antibodies or vaccine development.

The dramatic 50% improvement in energy density that Li-metal anodes offer in comparison to graphite anodes in conventional lithium (Li)-ion batteries cannot be realized with current cell designs because of cell failure after a few cycles. Often, failure is caused by Li dendrites that grow through the separator, leading to short circuits. Here, we used a new characterization technique, cryogenic femtosecond laser cross sectioning and subsequent scanning electron microscopy, to observe the electroplated Li-metal morphology and the accompanying solid electrolyte interphase (SEI) into and through the intact coin cell battery's separator, gradually opening pathways for soft-short circuits that cause failure. We found that separator penetration by the SEI guided the growth of Li dendrites through the cell. A short-circuit mechanism via SEI growth at high current density within the separator is provided. These results will inform future efforts for separator and electrolyte design for Li-metal anodes.

Herpesvirus capsids are assembled in the nucleus and undergo a two-step process to cross the nuclear envelope. Capsids bud into the inner nuclear membrane (INM) aided by the nuclear egress complex (NEC) proteins UL31/34. At that stage of egress, enveloped virions are found for a short time in the perinuclear space. In the second step of nuclear egress, perinuclear enveloped virions (PEVs) fuse with the outer nuclear membrane (ONM) delivering capsids into the cytoplasm. Once in the cytoplasm, capsids undergo re-envelopment in the Golgi/trans-Golgi apparatus producing mature virions. This second step of nuclear egress is known as de-envelopment and is the focus of this review. Compared with herpesvirus envelopment at the INM, much less is known about de-envelopment. We propose a model in which de-envelopment involves two phases: (i) fusion of the PEV membrane with the ONM and (ii) expansion of the fusion pore leading to release of the viral capsid into the cytoplasm. The first phase of de-envelopment, membrane fusion, involves four herpes simplex virus (HSV) proteins: gB, gH/gL, gK and UL20. gB is the viral fusion protein and appears to act to perturb membranes and promote fusion. gH/gL may also have similar properties and appears to be able to act in de-envelopment without gB. gK and UL20 negatively regulate these fusion proteins. In the second phase of de-envelopment (pore expansion and capsid release), an alpha-herpesvirus protein kinase, US3, acts to phosphorylate NEC proteins, which normally produce membrane curvature during envelopment. Phosphorylation of NEC proteins reverses tight membrane curvature, causing expansion of the membrane fusion pore and promoting release of capsids into the cytoplasm.

JADPRO Live Virtual kicked off with the opening panel on advanced practitioner leadership during the COVID-19 pandemic. The group discussed their institutional emergency protocols, how they leveraged advanced practitioners (APs) to provide care during the crisis peak, and how they responded to the personal issues and anxieties of their AP colleagues.