Purpose: To report the observation of iris atrophy with the use of Dexycu in cataract surgery and describe a possible mechanism for this complication. Observations: Between 2020 and 2021, 2 patients underwent cataract surgery procedures with the use of Dexycu and experienced iris atrophy. The first case of iris atrophy was discovered by 6-month follow-up and the second case by 2-month follow-up. The timing and nature of this complication possibly represent more than steroid-induced hypopigmentation. Conclusions and importance: This publication adds further evidence of iris atrophy and a proposed mechanism associated with the use of Dexycu. Surgeons should be aware of this complication, especially when operating on eyes with dark irides.
This study showcases the electromechanical impedance (EMI) technique for extracting and promoting zero-group velocity (ZGV) and cutoff frequency resonances in a waveguide structure. We identify the mechanisms of multiple resonances in the EMI spectra via a wave propagation perspective. Both simulation and experiments reveal the fact that sharp resonances in the conductance spectra are associated with either ZGV or cutoff frequency points. Consequently, we design four test configurations to enhance local resonances by aligning induced motions with considered mode shapes. Reasonable agreement between simulation and experiment results is observed. We evaluate the performance of considered configurations in terms of mode enhancement, and configurations that can selectively promote certain mode families are summarized. This study also shines the light on the EMI technique for quantitative non-destructive evaluation (NDE) by potentially supporting the inverse characterization of mechanical properties of host structures.
We use ultrasound directed self-assembly (DSA) to organize filler dispersed in a viscous medium into concentric circle patterns during continuous flow through an extruder nozzle for additive manufacturing. The ability to organize and orient filler dispersed in a viscous medium into specific patterns is useful in the context of manufacturing engineered polymer matrix composite materials that derive their function from the spatial organization of the filler (particles) in the matrix. We implement an experimental methodology based on time-frequency analysis of video images of a viscous medium with a concentric circle pattern of particles flowing through an extruder nozzle, and quantify the spacing between concentric circles of particles. Using this methodology, we characterize the effect of material properties, particle volume fraction, flow rate, and nozzle design parameters on the organization of the particles at the inlet and outlet of the extruder nozzle. The experiments show that the ratio of the distance between adjacent concentric circles of particles in the extruder nozzle (outlet) and in the cylindrical ultrasound transducer (inlet) is almost independent of the acoustic contrast factor (material properties), particle volume fraction (viscosity), and flow rate, but strongly depends on the diameter of the throat section of the nozzle. The results of this work are relevant to integrating ultrasound DSA with fused filament fabrication and direct ink writing for additive manufacturing of polymer matrix composite materials with tailored properties.
Latin America has seen vast improvements in gender educational and health equality. Favorable supply-side conditions, however, have not translated into greater gender economic equality, a process that also depends on structural economic change and global macroeconomic conditions. In this paper, we assess the role of a variety of macro-level policies and structures in influencing trends in women’s access to high-quality jobs for a sample of 15 countries in Latin America over the period 1990–2018. Using micro-level data, we first evaluate women’s relative share of good jobs, defined in terms of women’s weekly earnings in an industry or occupation relative to the national median wage. Further, we econometrically estimate the association between a variety of macro-level variables and the relative quality of women’s jobs. Results indicate that the most significant and robust positive correlate of women’s relative access to good jobs is public social spending as a share of GDP. Other important macro-covariates include measures of labor market regulation, monetary and fiscal policy, and macroeconomic structure and global orientation, including financial openness. The results suggest that macro-level structures and policies related to globalization that hamper the achievement of greater gender equality can be offset by appropriately targeted government policies.
Existing research has found that women who use opioids (WWUO) experience challenges to hormonal and long-acting reversible contraception (HC-LARC) access and use. Facilitators of such use are unclear. We conducted a scoping review to comprehensively map the literature on barriers to and facilitators of HC-LARC access and use in the United States among reproductive-aged WWUO. In accordance with the JBI Manual of Evidence Synthesis, we conducted literature searches for empirical articles published from 1990 to 2021. Independent reviewers screened references, first by titles and abstracts, then by full-text, and charted data of eligible articles. We coded and organized HC-LARC barriers and facilitators according to a four-level social-ecological model (SEM) and categorized findings within each SEM level into domains. We screened 4,617 records, of which 28 articles focusing on HC-LARC (n = 18), LARC only (n = 6), or testing an intervention to increase HC-LARC uptake (n = 4) met inclusion criteria. We identified 13 domains of barriers and 11 domains of facilitators across four SEM levels (individual, relationship, community, societal). The most frequently cited barriers and facilitators were methods characteristics, partner and provider relations, transportation, healthcare availability and accessibility, cost, insurance, and stigma. Future studies would benefit from recruiting participants and collecting data in community settings, targeting more diverse populations, and identifying neighborhood, social, and policy barriers and facilitators. Reducing barriers and improving equity in HC-LARC access and use among WWUO is a complex, multifaceted issue that will require targeting factors simultaneously at multiple levels of the social-ecological hierarchy to effect change.
Background and objective: Computer simulations of joint contact mechanics have great merit to improve our current understanding of articular ankle pathology. Owed to its computational simplicity, discrete element analysis (DEA) is an encouraging alternative to finite element analysis (FEA). However, previous DEA models lack subject-specific anatomy and may oversimplify the biomechanics of the ankle. The objective of this study was to develop and validate a personalized DEA framework that permits movement of the fibula and incorporates personalized cartilage thickness as well as ligamentous constraints. Methods: A linear and non-linear DEA framework, representing cartilage as compressive springs, was established, verified, and validated. Three-dimensional (3D) bony ankle models were constructed from cadaveric lower limb CT scans imaged during application of weight (85 kg) and/or torque (10 Nm). These 3D models were used to generate cartilage thickness and ligament insertion sites based on a previously validated statistical shape model. Ligaments were modelled as non-linear tension-only springs. Validation of contact stress prediction was performed using a simple, axially constrained tibiotalar DEA model against an equivalent FEA model. Validation of ligamentous constraints compared the final position of the ankle mortise to that of the cadaver after application of torque and sequential ligament sectioning. Finally, a combined ligamentous-constraining DEA model was validated for predicted contact stress against an equivalent ligament-constraining FEA model. Results: The linear and non-linear DEA model reproduced a mean articular contact stress within 0.36 MPa and 0.39 MPa of the FEA calculated stress, respectively. With respect to the ligamentous validation, the DEA ligament-balancing algorithm could reproduce the position of the distal fibula within the ankle mortise to within 0.97 mm of the experimental observed distal fibula. When combining the ligament-constraining and contact stress algorithm, DEA was able to reproduce a mean articular contact stress to within 0.50 MPa of the FEA calculated contact stress. Conclusion: The DEA framework presented herein offers a computationally efficient alternative to FEA for the prediction of contact stress in the ankle joint, manifesting its potential to enhance the mechanical understanding of articular ankle pathologies on both a patient-specific and population-wide level. The novelty of this model lies in its personalized nature, inclusion of the distal tibiofibular joint and the use of non-linear ligament balancing to maintain the physiological ankle joint articulation.
This paper proposes a model for hierarchical combination of deep reinforcement learning (DRL) with quadratic programming for distribution system restoration after major outages. In the proposed model, optimal power dispatch of a collection of distributed energy resources, called integrated hybrid resources (IHRs), is determined by a DRL-trained controller, while a grid-level quadratic programming problem checks grid constraints and performs critical restoration operation. DRL is implemented using Soft Actor-Critic (SAC) algorithm, which is shown to outperform the common Deep Deterministic Policy Gradient in continuous action spaces. The numerical studies, performed on the 123-bus test distribution system, demonstrates that the hierarchical combination of DRL and quadratic programming not only speeds up the local operation of multiple IHRs, but also ensures that the network constraints are satisfied during the restoration operation.
Purpose: Rates of mutilating hand injuries are increasing from accidents caused by all-terrain vehicles (ATVs) and the recently popularized side-by-side utility-terrain vehicles (UTVs). Increasing surgeon familiarity with upper extremity (UE) injury patterns, severity, and outcomes following ATV and UTV accidents may improve patient care and advocacy. Methods: Retrospective comparisons of UE injury patterns, severity, hospital and intensive care unit (ICU) admission lengths, and number of surgeries were made between ATVs and UTVs. Findings were analyzed with Fisher's exact tests, MANOVA, ANOVAs with post hoc analyses, and multiple linear regressions. Results: A total of 154 cases were identified for inclusion (ATV=87; UTV=67). Patient ages ranged from 4-89 years. The UTV group contained significantly more hand and finger injuries, and more of the fractures were open (p=0.005, p<0.001, p<0.001, respectively). Riders of UTVs had nearly three times as many mutilating hand injuries and a near ninefold increase in amputations compared to ATV riders (p<0.001 and p<0.001, respectively). On average, the UTV group spent 2.5 additional days in the hospital, 0.91 additional days in an ICU, and had 1.3 additional surgeries (p=0.001, p=0.007, p<0.001, respectively). Vehicle type was the only variable significantly correlated with days in the hospital, ICU, and number of UE surgeries (p=0.002, p=0.008, p<0.001, respectively). Conclusions: Hand surgeons are in a unique position to serve as forerunners for increasing public awareness of off-road vehicle risks and promoting rider safety. Collaborating with manufacturers, emergency care providers, and directing teaching initiatives may improve patient outcomes.
Introduction: The diagnosis and management of metopic craniosynostosis involves subjective decision-making at the point of care. The purpose of this work is to describe a quantitative severity metric and point-of-care user interface to aid clinicians in the management of metopic craniosynostosis and to provide a platform for future research through deep phenotyping. Methods: Two machine-learning algorithms were developed that quantify the severity of craniosynostosis - a supervised model specific to metopic craniosynostosis (Metopic Severity Score) and an unsupervised model used for cranial morphology in general (Cranial Morphology Deviation). CT imaging from multiple institutions were compiled to establish the spectrum of severity and a point-of-care tool was developed and validated. Results: Over the study period (2019-2021), 254 patients with metopic craniosynostosis and 92 control patients who underwent CT scan between the ages of 6 and 18 months were included. Scans were processed using an unsupervised machine-learning based dysmorphology quantification tool, CranioRate TM. The average Metopic severity score (MSS) for normal controls was 0.0±1.0 and for metopic synostosis was 4.9±2.3 (p<0.001). The average Cranial Morphology Deviation (CMD) for normal controls was 85.2±19.2 and for metopic synostosis was 189.9±43.4 (p<0.001). A point-of-care user interface (craniorate.org) has processed 46 CT images from 10 institutions. Conclusion: The resulting quantification of severity using MSS and CMD has shown an improved capacity, relative to conventional measures, to automatically classify normal controls versus patients with metopic synostosis. We have mathematically described, in an objective and quantifiable manner, the distribution of phenotypes in metopic craniosynostosis.
Ongoing urbanization and land transformation drive profound changes in ecosystems worldwide, with wildlife responding in myriad ways. Particularly, functional homogenization of wildlife communities due to these widespread changes may reduce biodiversity and urban ecosystem resilience. However, there are benefits of urbanization (e.g., increased resources and survival) for some mammal species, likely supported by corresponding traits that facilitate the exploitation of human-dominated landscapes. Using data collected simultaneously from 107 sites throughout the contiguous United States, we explored how urban development, agricultural development, and environmental factors affected mammalian functional diversity (i.e., richness, evenness, and divergence of effect traits) and mean species' traits at two spatial scales. Although we expected that urbanization would lead to mammal community functional homogenization, we found that urban development was positively associated with functional richness at the camera-site and all three functional metrics at the camera-array scales, whereas environmental variables (i.e., primary productivity, temperature) were not associated with any functional diversity metric. Sampling locations with greater urban development were associated with mammals that had smaller average home ranges, smaller average body sizes, and decreased mean rates of carnivory and scavenging. Identifying the effects of anthropogenic development on ecosystem functioning, as mediated by species' traits, is crucial as urban landscapes continue to expand globally.
Introduction: Rumination, or repetitive and habitual negative thinking, is associated with psychopathology and related behaviors in adolescents, including non-suicidal self-injury (NSSI). Despite the link between self-reported rumination and NSSI, there is limited understanding of how rumination is represented at the neurobiological level among youth with NSSI. Method: We collected neuroimaging and rumination data from 39 adolescents with current or past NSSI and remitted major depression. Participants completed a rumination induction fMRI task, consisting of both rumination and distraction blocks. We examined brain activation associated with total lifetime NSSI in the context of the rumination versus distraction contrast. Results: Lifetime NSSI was associated with a greater discrepancy in activation during rumination relative to distraction conditions in clusters including the precuneus, posterior cingulate, superior, and middle frontal gyrus, and cerebellum. Conclusion: Difficulties associated with rumination in adolescents with NSSI may be related to requiring greater cognitive effort to distract from ruminative content in addition to increased attention in the context of ruminative content. Increasing knowledge of neurobiological circuits and nodes associated with rumination and their relationship with NSSI may enable us to better tailor interventions that can facilitate lasting well-being and neurobiological change.
Background: Caffeine consumption is common during pregnancy, but published associations with birth defects are mixed. We updated estimates of associations between prepregnancy caffeine consumption and 48 specific birth defects from the National Birth Defects Prevention Study (NBDPS) for deliveries from 1997 to 2011. Methods: NBDPS was a large population-based case-control study conducted in 10 U.S. states. We categorized self-reported total dietary caffeine consumption (mg/day) from coffee, tea, soda, and chocolate as: <10, 10 to <100, 100 to <200, 200 to <300, and ≥ 300. We used logistic regression to estimate adjusted odds ratios (aORs [95% confidence intervals]). Analyses for defects with ≥5 exposed case children were adjusted for maternal race/ethnicity, age at delivery, body mass index, early pregnancy cigarette smoking and alcohol use, and study site. Results: Our analysis included 30,285 case and 11,502 control children, with mothers of 52% and 54%, respectively, reporting consuming <100 mg caffeine, and 11% of mothers of both cases and controls reported consuming ≥300 mg per day. Low (10 to <100 mg/day) levels of prepregnancy caffeine consumption were associated with statistically significant increases in aORs (1.2-1.7) for 10 defects. Associations with high (≥300 mg/day) levels of caffeine were generally weaker, except for craniosynostosis and aortic stenosis (aORs = 1.3 [1.1-1.6], 1.6 [1.1-2.3]). Conclusions: Given the large number of estimates generated, some of the statistically significant results may be due to chance and thus the weakly increased aORs should be interpreted cautiously. This study supports previous observations suggesting lack of evidence for meaningful associations between caffeine consumption and the studied birth defects.
Background: Acute kidney injury (AKI) in children has serious short-term and long-term consequences. We sought 1) to prospectively describe NSAID-associated AKI in hospitalized children; 2) to determine if NSAID-associated AKI was more severe in younger children < 5 years; and 3) to follow outcomes after hospitalization for NSAID-associated AKI. Methods: This was a prospective, multi-center study in hospitalized children 1 month to 18 years. Parents/guardians were given a brief questionnaire to determine the dosing, duration, and type of NSAIDs given. Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria were used to stage AKI severity. Patients with other causes of AKI were excluded (e.g., other nephrotoxins, sepsis, malignancy, etc.). Results: We identified 25 patients with NSAID-associated AKI, accounting for 3.1% of AKI. All 25 had AKI upon hospital presentation. The median age was 15.5 years, and 20/25 (80%) had volume depletion. Median duration of NSAID use was 2 days, and 63% of patients took the normal recommended NSAID dose. Median hospital length of stay was 4 days, and none required dialysis. At the most recent estimated glomerular filtration rate (eGFR) after discharge (available in 17/25 patients), only 4/17 (24%) had eGFR ≥ 90 ml/min/1.73 m2, and 13/17 (76%) had eGFR 60 to < 90 ml/min/1.73 m2, indicative of abnormal kidney function. Conclusions: NSAID-associated AKI usually occurs with recommended NSAID dosing in the setting of dehydration. Follow-up after AKI showed a substantial rate of CKD. Therefore, we recommend that NSAIDs should not be used in dehydrated children. A higher resolution version of the Graphical abstract is available as Supplementary information.
Objective: The novel Coronavirus (COVID-19) has continued to present a significant burden to global public health efforts. The purpose of this study was to estimate the health-related quality of life, disability, and health status of individuals with self-reported long COVID at various lengths of recovery. Methods: We conducted a cross-sectional online survey of individuals with self-reported long COVID. Participants were asked to complete the five-item EuroQOL EQ-5D-5L and EQ visual analog scale, the 12-item World Health Organization Disability Assessment Schedule (WHODAS) 2.0 and the 10-item Patient Reported Outcome Measurement Information System (PROMIS) Global Health v1.2 short form. Descriptive and inferential statistics were used to characterize the responses and differences across groups. Results: Eighty-two participants from 13 countries completed the EQ-5D-5L, 73 completed the WHODAS 2.0 and 80 participants completed the PROMIS. The mean EQ-5D-5L utility score was 0.51. The mean WHODAS score was 49.0. In the previous 30 days, participants reported their symptoms affected them for a mean of 24 days, they were totally unable to carry out usual activities for 15 days, and they cut back or reduced activities for 26 days. The mean PROMIS physical health and mental health scores were 10.7 and 8.6, respectively, corresponding to below-average health. No significant differences were detected across time or according to severity of acute infection. Conclusions: Long COVID presents a significant chronic health burden to adults in the US and abroad. This health burden may persist for many months post-acute infection.
Given a set of pairwise disjoint polygonal obstacles in the plane, finding an obstacle-avoiding Euclidean shortest path between two points is a classical problem in computational geometry and has been studied extensively. Previously, Hershberger and Suri (in SIAM Journal on Computing , 1999) gave an algorithm of O(n log n ) time and O(n log n ) space, where n is the total number of vertices of all obstacles. Recently, by modifying Hershberger and Suri’s algorithm, Wang (in SODA’21) reduced the space to O(n) while the runtime of the algorithm is still O(n log n ). In this article, we present a new algorithm of O(n+h log h ) time and O(n) space, provided that a triangulation of the free space is given, where h is the number of obstacles. The algorithm is better than the previous work when h is relatively small. Our algorithm builds a shortest path map for a source point s so that given any query point t , the shortest path length from s to t can be computed in O (log n ) time and a shortest s - t path can be produced in additional time linear in the number of edges of the path.
The major determinant of disease severity in Duchenne muscular dystrophy (DMD) or milder Becker muscular dystrophy (BMD) is whether the dystrophin gene (DMD) mutation truncates the mRNA reading frame or allows expression of a partially functional protein. However, even in the complete absence of dystrophin, variability in disease severity is observed, and candidate gene studies have implicated several genes as modifiers. Here we present the largest genome-wide search to date for loci influencing severity in N = 419 DMD patients. Availability of subjects for such studies is quite limited, leading to modest sample sizes, which present a challenge for GWAS design. We have therefore taken special steps to minimize heterogeneity within our dataset at the DMD locus itself, taking a novel approach to mutation classification to effectively exclude the possibility of residual dystrophin expression, and utilized statistical methods that are well adapted to smaller sample sizes, including the use of a novel linear regression-like residual for time to ambulatory loss and the application of evidential statistics for the GWAS approach. Finally, we applied an unbiased in silico pipeline, utilizing functional genomic datasets to explore the potential impact of the best supported SNPs. In all, we obtained eight SNPs (out of 1,385,356 total) with posterior probability of trait-marker association (PPLD) ≥ 0.4, representing six distinct loci. Our analysis prioritized likely non-coding SNP regulatory effects on six genes (ETAA1, PARD6G, GALNTL6, MAN1A1, ADAMTS19, and NCALD), each with plausibility as a DMD modifier. These results support both recurrent and potentially new pathways for intervention in the dystrophinopathies.
Objectives: Everyday listening environments are filled with competing noise and distractors. Although significant research has examined the effect of competing noise on speech recognition and listening effort, little is understood about the effect of distraction. The framework for understanding effortful listening recognizes the importance of attention-related processes in speech recognition and listening effort; however, it underspecifies the role that they play, particularly with respect to distraction. The load theory of attention predicts that resources will be automatically allocated to processing a distractor, but only if perceptual load in the listening task is low enough. If perceptual load is high (i.e., listening in noise), then resources that would otherwise be allocated to processing a distractor are used to overcome the increased perceptual load and are unavailable for distractor processing. Although there is ample evidence for this theory in the visual domain, there has been little research investigating how the load theory of attention may apply to speech processing. In this study, we sought to measure the effect of distractors on speech recognition and listening effort and to evaluate whether the load theory of attention can be used to understand a listener's resource allocation in the presence of distractors. Design: Fifteen adult listeners participated in a monosyllabic words repetition task. Test stimuli were presented in quiet or in competing speech (+5 dB signal-to-noise ratio) and in distractor or no distractor conditions. In conditions with distractors, auditory distractors were presented before the target words on 24% of the trials in quiet and in noise. Percent-correct was recorded as speech recognition, and verbal response time (VRT) was recorded as a measure of listening effort. Results: A significant interaction was present for speech recognition, showing reduced speech recognition when distractors were presented in the quiet condition but no effect of distractors when noise was present. VRTs were significantly longer when distractors were present, regardless of listening condition. Conclusions: Consistent with the load theory of attention, distractors significantly reduced speech recognition in the low-perceptual load condition (i.e., listening in quiet) but did not impact speech recognition scores in conditions of high perceptual load (i.e., listening in noise). The increases in VRTs in the presence of distractors in both low- and high-perceptual load conditions (i.e., quiet and noise) suggest that the load theory of attention may not apply to listening effort. However, the large effect of distractors on VRT in both conditions is consistent with the previous work demonstrating that distraction-related shifts of attention can delay processing of the target task. These findings also fit within the framework for understanding effortful listening, which proposes that involuntary attentional shifts result in a depletion of cognitive resources, leaving less resources readily available to process the signal of interest; resulting in increased listening effort (i.e., elongated VRT).
Background The reactivation of genetic programs from early development is a common mechanism for injury-induced organ regeneration. T-box 3 (TBX3) is a member of the T-box family of transcription factors previously shown to regulate pluripotency and subsequent lineage commitment in a number of tissues, including limb and lung. TBX3 is also involved in lung and heart organogenesis. Here, we provide a comprehensive and thorough characterization of TBX3 and its role during pancreatic organogenesis and regeneration. Results We interrogated the level and cell specificity of TBX3 in the developing and adult pancreas at mRNA and protein levels at multiple developmental stages in mouse and human pancreas. We employed conditional mutagenesis to determine its role in murine pancreatic development and in regeneration after the induction of acute pancreatitis. We found that Tbx3 is dynamically expressed in the pancreatic mesenchyme and epithelium. While Tbx3 is expressed in the developing pancreas, its absence is likely compensated by other factors after ablation from either the mesenchymal or epithelial compartments. In an adult model of acute pancreatitis, we found that a lack of Tbx3 resulted in increased proliferation and fibrosis as well as an enhanced inflammatory gene programs, indicating that Tbx3 has a role in tissue homeostasis and regeneration. Conclusions TBX3 demonstrates dynamic expression patterns in the pancreas. Although TBX3 is dispensable for proper pancreatic development, its absence leads to altered organ regeneration after induction of acute pancreatitis.
Aging coincides with the accumulation of senescent cells within skeletal muscle that produce inflammatory products, known as the senescence-associated secretory phenotype, but the relationship of senescent cells to muscle atrophy is unclear. Previously, we found that a metformin + leucine (MET+LEU) treatment had synergistic effects in aged mice to improve skeletal muscle structure and function during disuse atrophy. Therefore, the study's purpose was to determine the mechanisms by which MET+LEU exhibits muscle atrophy protection in vitro and if this occurs through cellular senescence. C2C12 myoblasts differentiated into myotubes were used to determine MET+LEU mechanisms during atrophy. Additionally, aged mouse single myofibers and older human donor primary myoblasts were individually isolated to determine the translational potential of MET+LEU on muscle cells. MET+LEU (25 + 125 μM) treatment increased myotube differentiation and prevented myotube atrophy. Low concentration (0.1 + 0.5 μM) MET+LEU had unique effects to prevent muscle atrophy and increase transcripts related to protein synthesis and decrease transcripts related to protein breakdown. Myotube atrophy resulted in dysregulated proteostasis that was reversed with MET+LEU and individually with proteasome inhibition (MG-132). Inflammatory and cellular senescence transcriptional pathways and respective transcripts were increased following myotube atrophy yet reversed with MET+LEU treatment. Dasatinib + quercetin (D+Q) senolytic prevented myotube atrophy similar to MET+LEU. Finally, MET+LEU prevented loss in myotube size in alternate in vitro models of muscle atrophy as well as in aged myofibers while, in human primary myotubes, MET+LEU prevented reductions in myonuclei fusion. These data support that MET+LEU has skeletal muscle cell-autonomous properties to prevent atrophy by reversing senescence and improving proteostasis.
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Salt Lake City, Utah, United States
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University of Utah