Recalibration of the Local Magnitude (ML) Scale for Earthquakes in the Yellowstone Volcanic Region

ABSTRACT The Yellowstone volcanic region is one of the most seismically active areas in the western United States. Assigning magnitudes (M) to Yellowstone earthquakes is a critical component of monitoring this geologically dynamic zone. The University of Utah Seismograph Stations (UUSS) has assigned M to 46,767 earthquakes in Yellowstone that occurred between 1 January 1984 and 31 December 2020. Here, we recalibrate the local magnitude (ML) distance and station corrections for the Yellowstone volcanic region. This revision takes advantage of the large catalog of earthquakes and an increase in broadband stations installed by the UUSS since the last ML update in 2007. Using a nonparametric method, we invert 7728 high-quality, analyst-reviewed amplitude measurements from 1383 spatially distributed earthquakes for 39 distance corrections and 20 station corrections. The inversion is constrained with four moment magnitude (Mw) values determined from time-domain inversion of regional-distance broadband waveforms by the UUSS. Overall, the new distance corrections indicate relatively high attenuation of amplitudes with distance. The distance corrections decrease with hypocentral distance from 3 km to a local minimum at 80 km, rise to a broad peak at 110 km, and then decrease again out to 180 km. The broad peak may result from superposition of direct arrivals with near-critical Moho reflections. Our ML inversion doubles the number of stations with ML corrections in and near the Yellowstone volcanic region. We estimate that the additional station corrections will nearly triple the number of Yellowstone earthquakes that can be assigned an ML. The new ML distance and station corrections will also reduce uncertainties in the mean MLs for Yellowstone earthquakes. The new MLs are ∼0.07 (±0.18) magnitude units smaller than the previous MLs and have better agreement with 12 Mws (3.15–4.49) determined by the UUSS and Saint Louis University.

A Decade of Teaching the Course Aging & the Arts: Reflecting on Opportunities and Challenges

In 2010, the University of Utah Gerontology Interdisciplinary Program first offered GERON 5240/6240: Aging and the Arts. This course was developed to enrich program curricula by addressing a gap in content specific to the arts and humanities. The purpose of this presentation is to focus on identifying the opportunities and challenges experienced teaching this course over the past decade. Opportunities will highlight competency mapping, internal and external partnerships, the benefits of bridging disciplines, and innovation in teaching and problem-solving. Challenges experienced include addressing various needs (online learning, undergraduate and graduate levels, multiple disciplines), tuition differentials, and varying levels of enrollment. A stand-alone course is one method of increasing humanities, arts, and cultural gerontology within curricula. It has the potential of enhancing student interest in gerontology while also demonstrating how the arts and humanities can improve work across disciplines.

Implementing Age-Friendly University Principles: Institutional Supports, Barriers, and Outcomes

The University of Utah Gerontology Interdisciplinary Program received an Age-Friendly University (AFU) seed grant through GSA’s Academy of Gerontology in Higher Education, funded by AARP, to develop a model for promoting lifelong learning in partnership with university and community stakeholders. We designed and instituted a targeting marketing campaign that supported our goals: 1) to implement AFU principles; 2) to promote awareness of HB60, a legislative bill allowing people 62+ to audit courses at public universities for a minimal cost; 3) to enhance HB 60 enrollment through increased communication of online course options and tuition waiver support; and 4) to improve university and community stakeholder engagement. This presentation describes project benefits, including increased awareness of AFU initiatives, promoting age diversity, safe participation through online coursework, and enhanced community partnerships. The initiative garnered strong departmental support for marketing, communications, and structure for the post-award process. Barriers occurred due to a lack of HB60 infrastructure at the university level, which inadvertently obstructs organizational engagement. This initiative targeted AFU principles while supporting the university’s strategic goal of engaging communities and preparing to pursue membership in the AFU Global Network. Future AFU goals include developing advocacy channels within the university to improve organizational support.

Does Autoimmunity in Family Members of Children with Immune Thrombocytopenia Help Identify Patients at Higher Risk of Chronic Immune Thrombocytopenia?

Background Immune thrombocytopenia (ITP) is the most common cause of thrombocytopenia during childhood. Approximately 10-30% of pediatric patients will develop chronic ITP (cITP), which is defined as thrombocytopenia lasting over 12 months, and constitutes a significant burden for patients and their caregivers. Patients with cITP may require ongoing medications to treat symptomatic thrombocytopenia, may have asymptomatic thrombocytopenia not requiring medical interventions, or may experience complete resolution of their ITP. There are not specific patient nor disease characteristics that can help us predict how cITP may progress, and which patients are more likely to require ongoing treatments. ITP can be a manifestation of immune dysregulation in patients with other autoimmune conditions or primary immunodeficiency disorders (PIDDs). We aimed to assess the characteristics of patients with cITP including the presence of autoimmune or allergic disorders in the patients and in first-, second-, and third-degree family members. We hypothesized that patients with cITP may have a higher incidence of immune dysregulation in family members in contrast to patients with acute aITP. Methods The study was approved by the institutional review and ethics boards at the University of Utah. We queried the Primary Children's Hospital database for cases of "immune thrombocytopenia" from January 1 st, 2001 to January 1 st,2021. Retrospective chart review was done to confirm the diagnosis. Patient demographics, clinical presentation, and family history of patients were reviewed. Data was collected in RedCap at the University of Utah. Descriptive summaries of data were done. Results Medical charts from 266 ITP patients diagnosed during the study period were reviewed; 182/266 (68.5%) had acute ITP (aITP) and 84/266 (31.5%) patients had cITP, defined as platelet count <150 K/µl for >12 months. Resolution of ITP occurred in 28/84 (33.3%) patients with cITP (resolved cITP), while 56/84 (66.7%) had ongoing thrombocytopenia (unresolved cITP). Mean duration of ITP in patients with resolved cITP was 2.9 years, and 4.6 years in patients with unresolved cITP at the time of the last known platelet count. Mean age at diagnosis was 7.4 years in the cITP group and 5.1 years in the aITP group. Concurrent allergic conditions were identified in 10/84 (12%) of patients with cITP and 5/182 (2.7%) of patients with aITP. Autoimmune conditions were identified in 3 patients (3.5%) with cITP, and 4 patients (2.2%) with aITP. First-degree family members of cITP patients were more likely to be reported with an autoimmune condition than first-degree family members of aITP patients (15.5% vs. 5.5%, p=0.007 using Chi-square test); this effect was not seen amongst second- or third-degree relatives. The most common autoimmune condition reported in family members was autoimmune thyroid disease in both cohorts (2.7% in aITP and 9.5% in cITP). Common variable immunodeficiency (CVID) was reported in second degree relatives of 3/84 (3.6%) patients with cITP; no relatives of patients with aITP had a report of PIDD. Additionally, we identified 14 patients with Evans syndrome (ES), all with chronic immune thrombocytopenia and all patients had been followed for over a year at the time of the chart review. Four ES patients were previously diagnosed with 22q11.2 deletion, and one with CVID. In patients with ES, 4/14 (28.6%) and 5/14 (35.7%) had first- and second-degree family members with a reported autoimmune condition, respectively. No PIDDs were identified in first, second-, or third-degree relatives of patients with ES. Conclusions There is increasing evidence that patients with chronic ITP may exhibit polyautoimmunity or other signs of immune dysregulation, suggesting that ITP may be the initial manifestation of another autoimmune process or PIDD. We evaluated medical histories of patients with ITP and their family members. Patients with cITP have a history of autoimmunity in their family stronger than in patients with aITP. This association was even stronger in patients with ES. Disclosures No relevant conflicts of interest to declare.

1161. Increasing incidence of Sinogenic Intracranial Infections in Utah Children 2004-2019

Background Intracranial extension of sinusitis is a rare complication. Non-specific presentations are a diagnostic challenge, and complications include long-term neurologic sequelae. Early recognition is critical, although optimal management remains poorly characterized. Methods We conducted a retrospective chart review of 123 patients admitted to Primary Children’s Hospital between 2004-2019 with ICD9 and ICD10 codes for sinusitis and intracranial suppurative infection. Chart review confirmed cases in patients < 18 years with evidence of sinusitis and intracranial extension. Variables collected included: demographic data, clinical presentation, microbial profile, clinical management, and outcomes. Results We observed 84 pediatric sinogenic intracranial infections between 2004-2019. Incidence significantly increased over the interval. Median patient age was 12.8 years (IQR 10.5-14.7 years); most were male (n=52). The most common presenting symptoms were headache and fever. Most patients (n=80) required surgical management; 62 required neurosurgery. All but one patient survived. Most infections were polymicrobial (n=47). Streptococcus anginous group were most frequently identified (n=32). All patients were started on vancomycin empirically; only 10 required use for definitive management. Most patients were treated with a carbapenem (n=42) or ceftriaxone plus metronidazole (n=32). Average duration of antibiotics was 44 days (IQR 38-55 days). The most common complication was epilepsy (n=11). Patients with Streptococcus sp. infections were more likely to experience adverse outcomes (p= 0.04). We observed significantly decreased carbapenem use following introduction of an antimicrobial stewardship program in 2012, with no change in clinical outcomes. Annual incidence of Sinogenic Intracranial Infections Shown is the increasing incidence of sinogenic intracranial infections annually in the state of Utah/100,000 children. Conclusion Sinogenic intracranial infections are increasingly frequent severe pediatric infections with associated long term neurologic sequelae. Most patients require both surgical and long-term IV antibiotic treatment. Most infections are polymicrobial. Streptococcus sp. are commonly identified. Antibiotic resistant bacteria are rare. The combination ceftriaxone and metronidazole is appropriate for treatment of most infections. Disclosures Anne Bonkowsky, MD/PhD, BioFire Diagnostics (Consultant, Grant/Research Support, Other Financial or Material Support, I have intellectual property through the University of Utah in BioFire Diagnostics and the FilmArray and receive royalties through the University of Utah.)Merck (Advisor or Review Panel member)

493. Incidence and Characterization of Chronic Active COVID Among Patients Infected with the Novel Coronavirus (COVID-19) Receiving B-cell Depleting Therapies (BCDTs)

Background There have been reports of COVID-19 infection characterized by prolonged viral replication [chronic active COVID-19 (CAC)] among immunocompromised patients, including those receiving B-cell depleting therapies (BCDTs). We aimed to characterize the severity and incidence of CAC among patients on BCDTs with COVID-19, and to identify associated risk factors. Methods We retrospectively reviewed all patients who received an anti-CD20 BCDT within 1 year of a positive COVID test at University of Utah Health. Demographics, comorbidities, indications, and timing of BCDT were documented. Chart review was performed to characterize the clinical course, including need for hospitalization, COVID-specific therapies, need for ICU and ventilatory support, and mortality. We defined CAC as: (1) despite initial clinical improvement, progression of illness extending beyond 14 days, characterized by ongoing fevers or progressive respiratory failure; or (2) ongoing symptoms with demonstration of absent seroconversion ≥ 14 days into illness. In some patients the diagnosis of CAC was supported by low viral PCR crossing thresholds that occurred ≥ 14 days into illness. Logistic models were used to identify risk factors for CAC among the cohort of patients who survived through the initial period of infection. Results We identified 66 individuals who received a BCDT within 1 year of a positive COVID test; 29 (44%) were hospitalized, 4 (6%) required ventilation, and 7 (11%) died within 60 days. Among 63 patients who survived their initial COVID course, 16 (25%) had courses compatible with CAC. Nine (56%) who received a BCDT within 1 month before or 2 weeks after their COVID diagnosis developed CAC; OR 7.4 (95% CI 1.7, 31.6, p=0.002). Conclusion We clinically observed COVID-19 infection lasting longer than the typical course and propose a definition for CAC. Incidence of CAC was highest among patients who received BCDT within 30 days before or 2 weeks after COVID-19 diagnosis. High suspicion for CAC is warranted among patients receiving these therapies. Additional study is needed to better define risk for CAC among varying immunosuppressed populations and determine whether COVID-specific treatments early in disease may benefit these patients. Disclosures Hannah Imlay, MD, MS, Gilead Sciences, Inc. (Scientific Research Study Investigator)

77. Opportunity for Improved Use of a Commercially Available Meningitis/Encephalitis Panel in Pediatric Patients

Background The BioFire® FilmArray Meningitis/Encephalitis (ME) panel delivers timely CSF analysis when meningitis or encephalitis is suspected and has the potential for earlier optimization of patient care. It is unclear if the M/E panel provides incremental benefit over standard microbiologic methods such as culture and cell counts, especially in the absence of significant pleocytosis. We evaluated the clinical utility of the ME panel with respect to CSF white blood cell count per high power field (WBC/hpf) and patient age. Methods We identified paired CSF ME panels and CSF cultures collected throughout a large healthcare system from 2016–May 2021 in children < 18 years of age. CSF results from the same calendar day were included in the dataset. We reviewed standalone HSV and Enterovirus (EV) CSF studies to determine frequency of duplicative testing. Results were stratified by CSF WBC/hpf and patient age (< 14 days, 14–60 days, > 60 days and < 5 years, and > 5 years). Results 1045 paired cultures and ME panels were identified. Of those, 921 (88%) ME panels were negative, but 5 of those cultures grew bacteria. Of 124 (12%) positive ME panel results, 66% were viral: 46 (37%) EV, 22 (18%) HHV-6 and 6 (5%) parechovirus. In 498 cases, ME panels were sent when CSF had < 10 WBC/hpf, resulting in only 2 (0.4%) PCRs positive for bacteria, one which was gram stain positive and the other was considered a false positive (Table 1). In addition to a ME panel, standalone PCRs for enterovirus and HSV were sent in 134 (13%) and 213 (20%) of cases, respectively, with < 2% discordance. Pathogen distribution by ME panel did not vary with age (Table 2). Meningitis and encephalitis panel, standalone PCR and culture results overall and by age group. Conclusion In our cohort, the ME panels were overwhelmingly negative. Only 12% of ME panels were positive, mostly with self-limited viral pathogens (e.g., EV, parechovirus). Performance was worse when samples had < 10 WBC/hpf. Duplicative testing was common and had no benefit. Performance was similar across age groups. More targeted use of the ME panel could improve the utility and efficacy of this test. Disclosures Anne Bonkowsky, MD/PhD, BioFire Diagnostics (Consultant, Grant/Research Support, Other Financial or Material Support, I have intellectual property through the University of Utah in BioFire Diagnostics and the FilmArray and receive royalties through the University of Utah.)Merck (Advisor or Review Panel member)

MFN2 Influences Amyotrophic Lateral Sclerosis Pathology

Objective: To better understand the pathology of amyotrophic lateral sclerosis, we used sequence data from patients seen at the University of Utah to identify novel disease-associated loci. We utilized both in vitro and in vivo studies to determine the biological effect of patient mutations in MFN2. Methods: Sequence data for a total of 140 patients were run through VAAST and Phevor to determine genes that were more burdened with rare, nonsynonymous variants compared to control longevity cohort. Variants identified in MFN2 were expressed in Mfn2 knockout cells to determine if mutant MFN2 could rescue mitochondrial morphology defects. We identified additional rare, nonsynonymous variants in MFN2 in ALSdb that were expressed in knockout mouse embryonic fibroblasts (MEFs). Membrane potential was measured to quantify mitochondrial health upon mutant MFN2 expression. mfn2 knockout zebrafish were used to examine movement compared to wildtype and protein aggregation in brain. Results: MFN2 mutations identified in ALS patients from our University of Utah cohort and ALSdb were defective in rescuing morphological defects in Mfn2 knockout MEFs. Selected mutants showed decreased membrane potential compared to wildtype MFN2 expression. Zebrafish heterozygous and homozygous for loss of mfn2 showed increased TDP-43 levels in their hindbrain and cerebellum. Conclusion: In total, 21 rare, deleterious mutations in MFN2 were tested in Mfn2 knockout MEFs. Mutant MFN2 expression was not able to rescue the knockout phenotype, though at differing degrees of severity. Decreased membrane potential also argues for inhibited mitochondrial function. Increased TDP-43 levels in mutant zebrafish illustrates MFN2's function in ALS pathology. MFN2 variants influence ALS pathology and highlight the importance of mitochondria in neurodegeneration.