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Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Ionizing radiation can cause devastating injuries including hemorrhage, immune suppression, increased susceptibility to infection, and death. Medical countermeasures (MCMs) that address and mitigate radiation-induced injuries are the most important tools for countering the consequences of radiation exposure. Likewise, in matters of public health security, the development and advancement of radiological MCMs are fundamental for establishing an effective response to radiological and nuclear threats. United States Government agencies such as the Biomedical Advanced Research and Development Authority (BARDA), the National Institute of Allergy and Infectious Diseases (NIAID), and the National Aeronautics and Space Administration (NASA) have dedicated significant efforts to advance the development of MCMs to treat radiation injury and facilitate their introduction into the public sphere. Due to the severe nature of radiation injuries, clinical trials are unethical. Therefore, nonclinical models that accurately replicate clinical manifestations of ionizing radiation injury observed in humans are essential to MCM advancement. The most frequently used nonclinical models of radiation injury are rodents and non-human primates (NHPs). These species reproduce many aspects of human disease caused by ionizing radiation and have been pivotal for the development and licensure of radiological MCMs. Despite these successes, model drawbacks have prompted the exploration and development of additional nonclinical models. Minipigs and rabbits show promise as acceptable models of radiation injury and demonstrate the potential to contribute significantly to MCM advancement. This collection of research showcases the capabilities of minipigs and rabbits in mirroring clinically relevant aspects of radiation-induced disease and documents the potential value these models may hold for radiological and nuclear MCM research. Together, these government-funded studies represent advances in radiological MCM development that can facilitate the emergence of cutting-edge technologies.

Pericarditis is the most common inflammatory pericardial disease in both children and adults. Since the publication of the 2015 European Society of Cardiology Guidelines for the diagnosis and management of pericardial disease were published there have been significant updates to management. Pharmacotherapy has been historically reserved for idiopathic pericarditis (IP). However, there has been increasing use of pharmacotherapies such as anti-inflammatory therapies, colchicine and immunotherapies for other causes of pericarditis, such as post cardiac injury syndromes (PCIS). Nevertheless, the quality of data varies depending on PCIS or idiopathic etiologies, as well as the adult and pediatric population. High-dose anti-inflammatory therapies should be used to manage symptoms associated with either etiology of pericarditis in both adults and children, but do not ameliorate the inflammatory disease process. Choice of anti-inflammatory should be guided by drug-drug/disease interactions, cost, tolerability, patient age, and should be tapered accordingly over several weeks to months. Colchicine should be added as adjuvant therapy to anti-inflammatory therapies in adults and children with IP, as it has been shown to lower risk of recurrence, reduce pericarditis symptoms, and improve morbidity. Colchicine is also reasonable to add to adults and children with pericarditis secondary to PCIS. Systemic glucocorticoids increase risk of recurrence in adults and children with IP and are reserved for second-line treatment in acute and recurrent IP; they are generally avoided in PCIS. Immunotherapies are regarded as third-line for recurrent IP in adults and children. Limited evidence exists to support their use in patients with pericarditis from PCIS. Pharmacovigilance strategies such as C-reactive protein and adverse drug event monitoring are also important towards balancing efficacy and safety of the various strategies used to manage pericarditis in adults and children.

Healthcare clinical decision makers’ (CDMs) attitudes, beliefs, and biases can negatively contribute to both clinical conversations and subsequent inequitable management decisions in persistent mus...

As technological advancements and lowered costs make self-driving cars available to more people, it becomes important to understand the dynamics of human-automation interactions for safety and efficacy. We used a dynamical approach to examine data from a previous study on simulated driving with an automated driving assistant. To maximize effect size in this preliminary study, we focused the current analysis on the two lowest and two highest-performing participants. Our visual comparisons were the utilization of the automated system and the impact of perturbations. Low-performing participants toggled and maintained reliance either on automation or themselves for longer periods of time. Decision making of high-performing participants was using the automation briefly and consistently throughout the driving task. Participants who displayed an early understanding of automation capabilities opted for tactical use. Further exploration of individual differences and automation usage styles will help to understand the optimal human-automation-team dynamic and increase safety and efficacy.

Objective Chronic musculoskeletal pain (CMP) outcomes are affected by numerous variables, including the clinical conversation. When good therapeutic/working alliances are formed, congruent clinical conversations can lead to improved CMP outcomes. Identifying patient/provider attitudes, beliefs, and biases in CMP that can influence the clinical conversation, and thus clinical management decisions, is foundationally important. Design The aims of this systematic review were to 1) summarize the evidence of the attitudes and beliefs of patients and health care providers (HCPs) involved in the clinical conversation about CMP, and 2) examine whether and how these perceptions impacted the process of care. Methods A systematic search of CINAHL, PubMed, Scopus, Sociology Database in ProQuest, and Web of Science used the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Included studies were those investigating vulnerable adult populations with chronic pain. Study bias was examined with the Downs and Black tool. Results Seven retrospective studies were included. When making pharmaceutical management decisions, HCPs demonstrated negative implicit biases toward minorities and women. When making referrals to multidisciplinary care, HCPs demonstrated negative implicit biases toward women with lower educational attainment. Unmet patient expectations resulted in higher dropout rates at multidisciplinary pain management programs. Patients’ trust was influenced by the health care setting, and patients often had limited options secondary to health insurance type/status. Conclusion These findings suggest that patients with CMP may experience a marginalized process of care due to HCPs’ negative implicit biases, unmet patient expectations, and the health care setting. Results suggest several factors may contribute to inequitable care and the recalcitrant nature of CMP, particularly in vulnerable populations with limited health care choices.

Sensory processing necessitates discarding some information in service of preserving and reformatting more behaviorally relevant information. Sensory neurons seem to achieve this by responding selectively to particular combinations of features in their inputs, while averaging over or ignoring irrelevant combinations. Here, we expose the perceptual implications of this tradeoff between selectivity and invariance, using stimuli and tasks that explicitly reveal their opposing effects on discrimination performance. We generate texture stimuli with statistics derived from natural photographs, and ask observers to perform two different tasks: Discrimination between images drawn from families with different statistics, and discrimination between image samples with identical statistics. For both tasks, the performance of an ideal observer improves with stimulus size. In contrast, humans become better at family discrimination but worse at sample discrimination. We demonstrate through simulations that these behaviors arise naturally in an observer model that relies on a common set of physiologically plausible local statistical measurements for both tasks., Visual processing necessitates both extracting and discarding information. Here, the authors use a specialized set of stimuli and two complementary discrimination tasks to demonstrate the opposing perceptual implications of these two aspects of information processing.

Humans identify properties (e.g., the length or weight) of objects through touch using somatosensory perceptions in the limbs. Humans identify these properties by manipulating an object to access its inertial qualities. However, there is little work evidencing a unifying pattern of movements humans use to access these inertial properties. The current study examined if participants’ wielding movements followed a systematic distribution—specifically, a Levy-like distribution that is characterized by heavy-tails and is often seen in efficient foraging behavior. Participants wielded rods they could not see and were tasked to identify whether the rod they were wielding was the longer or shorter of two rods. While participants wielded the rod, the rod’s motion was captured. Results demonstrate that the sampling of angular accelerations produced heavy-tailed distributions. Since angular acceleration has a distinct physical–mathematical relationship with inertia, this finding is consistent with the interpretation that the haptic subsystems are sensitive to the inertial properties of an object. Angular acceleration from wielding motions appear to follow a similar distribution as optimal foraging strategies—perhaps it is the case that humans are foraging for information about the inertia of an object through changes in angular acceleration and wielding movements.

While SWI/SNF chromatin remodeling complex alterations occur in approximately 20% of cancer, the frequency and potential impact on clinical outcomes in meningiomas remains to be comprehensively elucidated. A large series of 255 meningiomas from a single institution that was enriched for high grade and recurrent lesions was identified. We performed next-generation targeted sequencing of known meningioma driver genes, including NF2, AKT1, PIK3CA, PIK3R1, and SMO and SWI/SNF chromatin remodeling complex genes, including ARID1A, SMARCA4, and SMARCB1 in all samples. Clinical correlates focused on clinical presentation and patient outcomes are presented. The series included 63 grade I meningiomas and 192 high-grade meningiomas, including 173 WHO grade II and 19 WHO grade III. Samples from recurrent surgeries comprised 37.3% of the series. A total of 41.6% meningiomas were from the skull base. NF2, AKT1, PIK3CA, PIK3R1, and SMO were mutated in 40.8, 7.1, 3.5, 3.9, and 2.4% of samples, respectively. ARID1A, SMARCA4, and SMARCB1 mutations were observed in 17.3, 3.5, and 5.1% of samples, respectively. A total of 68.2% of ARID1A-mutant meningiomas harbored a p.Gln1327del in-frame deletion. ARID1A mutations were seen in 19.1% of Grade I, 16.8% of Grade II, and 15.8% of Grade III meningiomas (P = 0.9, Fisher’s exact). Median overall survival was 16.3 years (95% CI 10.9, 16.8). With multivariable analysis, the presence of an ARID1A mutation was significantly associated with a 7.421-fold increased hazard of death (P = 0.04). ARID1A mutations occur with similar frequency between low and high-grade meningiomas, but ARID1A mutations are independently prognostic of worse prognosis beyond clinical and histopathologic features.

The density and distribution of the tumor immune microenvironment associated with brain metastases (BM) from gynecologic malignancies are unknown and have not been previously reported. We sought to describe the clinical features of a cohort of patients with BM from gynecologic malignancies and to characterize the tumor immune microenvironment from available archival surgical specimens. We performed a retrospective review of electronic medical records from 2002 to 2018 for patients with BM from gynecologic malignancies. Data on patient characteristics, treatment regimens, and clinical outcomes were procured. CD4, CD8, CD45RO, CD68, CD163, and FOXP3 immunohistochemistry were evaluated from available archival surgical specimens from primary disease site and neurosurgical resection. A cohort of 44 patients with BM from gynecologic malignancies was identified, 21 (47.7%) endometrial primaries and 23 (52.3%) ovarian primaries. Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) were evaluated in 13 primary cases and 15 BM cases. For the 13 primary cases, CD4+ TILs were evident in 76.9% of cases, CD8+ in 92.3%, CD45RO+ in 92.3%, and FOXP3+ in 46.2%, as well as CD68+ TAMs in 100% and CD163+ in 100%. For the 15 BM cases, CD4+ TILs were evident in 60.0% of cases, CD8+ in 93.3%, CD45RO+ in 73.3%, and FOXP3+ in 35.7%, as well as CD68+ TAMs in 86.7% and CD163+ in 100%. An active tumor immune microenvironment is present with similar distribution in the primary disease site and BM from patients with gynecologic malignancies.

Background The body of evidence on cutaneous mucormycosis is largely derived from case reports or single-centre databases. Objectives Our study aimed to describe incidence, predisposing factors and inpatient outcomes of cutaneous mucormycosis in the United States. Methods We conducted a population-based retrospective study using the National Inpatient Sample 2016-17 data. Fifty-six discharges had a diagnosis of cutaneous mucormycosis on the International Classification of Diseases, tenth revision. Descriptive analysis was performed for the demographics, predisposing factors, length of stay (LOS), cost and inpatient mortality. The NIS represents 20% of all discharges in the United States, which allowed us to estimate the national incidence of cutaneous mucormycosis. Results An estimated total of 280 admissions occurred between 2016 and 2017, indicating 3.9 cases per million admissions across the United States. The estimated incidence rate was 0.43 cases per million people per year. Median age was 49.5 (19-59) years, 44.6% were female, and 54.9% were Caucasian. We identified haematologic malignancies (48.2%) and solid organ transplantations (10.7%), often accompanied by skin/soft tissue or post-procedural infections, were the most common predisposing conditions. Median LOS was 15 (6-31) days, median total charges were 187,030 (65,962-446,265) USD, and in-hospital mortality rate was 16.1%. Conclusions In current clinical practice, physicians may encounter cutaneous mucormycosis most commonly in severely immunocompromised hosts with haematologic malignancies or transplantations, accompanied by skin/soft tissue or post-procedural infections. A high index of suspicion and prompt tissue sampling in at-risk groups is important to improve the outcomes.

Supplemental Digital Content is available in the text., Background: Rupture and erosion of advanced atherosclerotic lesions with a resultant myocardial infarction or stroke are the leading worldwide cause of death. However, we have a limited understanding of the identity, origin, and function of many cells that make up late-stage atherosclerotic lesions, as well as the mechanisms by which they control plaque stability. Methods: We conducted a comprehensive single-cell RNA sequencing of advanced human carotid endarterectomy samples and compared these with single-cell RNA sequencing from murine microdissected advanced atherosclerotic lesions with smooth muscle cell (SMC) and endothelial lineage tracing to survey all plaque cell types and rigorously determine their origin. We further used chromatin immunoprecipitation sequencing (ChIP-seq), bulk RNA sequencing, and an innovative dual lineage tracing mouse to understand the mechanism by which SMC phenotypic transitions affect lesion pathogenesis. Results: We provide evidence that SMC-specific Klf4- versus Oct4-knockout showed virtually opposite genomic signatures, and their putative target genes play an important role regulating SMC phenotypic changes. Single-cell RNA sequencing revealed remarkable similarity of transcriptomic clusters between mouse and human lesions and extensive plasticity of SMC- and endothelial cell-derived cells including 7 distinct clusters, most negative for traditional markers. In particular, SMC contributed to a Myh11-, Lgals3+ population with a chondrocyte-like gene signature that was markedly reduced with SMC-Klf4 knockout. We observed that SMCs that activate Lgals3 compose up to two thirds of all SMC in lesions. However, initial activation of Lgals3 in these cells does not represent conversion to a terminally differentiated state, but rather represents transition of these cells to a unique stem cell marker gene–positive, extracellular matrix-remodeling, “pioneer” cell phenotype that is the first to invest within lesions and subsequently gives rise to at least 3 other SMC phenotypes within advanced lesions, including Klf4-dependent osteogenic phenotypes likely to contribute to plaque calcification and plaque destabilization. Conclusions: Taken together, these results provide evidence that SMC-derived cells within advanced mouse and human atherosclerotic lesions exhibit far greater phenotypic plasticity than generally believed, with Klf4 regulating transition to multiple phenotypes including Lgals3+ osteogenic cells likely to be detrimental for late-stage atherosclerosis plaque pathogenesis.

Gender discrimination continues to plague organizations. While the advent of the Internet and the digitization of commerce have provided both a mechanism by which goods and services can be exchanged, as well as an efficient way for consumers to voice their opinions about retailers (i.e., via online rating systems), recent work has begun to uncover significant biases that manifest during the review process. In particular, it has been suggested that the gig-economy’s elimination of previously anonymous arm’s-length transactions may re-introduce bias into perceptions of quality. In this work, we build upon research that has identified biases based on ascriptive characteristics in rating systems of ridesharing platforms. In doing so, we conduct an online experiment using a series of factorial vignettes to consider not only willingness to transact but post-transaction perceptions of quality. Findings suggest that female drivers are not penalized ex ante for taking on gender incongruent roles, i.e., driving, and experience no penalty when a rider reports a high-quality experience. However, conditional upon a lower quality experience, there is a disproportionate penalty for female drivers. Strikingly, we also observe that historic high quality does not serve as a buffer against such penalties, as prior literature would suggest. These findings underscore the challenges platforms face in ensuring their participants are being evaluated in a fair and impartial way, and highlight the difficulties present when non-employees (customers) are rating non-employees (drivers) of the firm.

The optical extinction spectra arising from localized surface plasmon resonance in doped semiconductor nanocrystals (NCs) have intensities and lineshapes determined by free charge carrier concentrations and the various mechanisms for damping the oscillation of those free carriers. However, these intrinsic properties are convoluted by heterogeneous broadening when measuring spectra of ensembles. We reveal that the traditional Drude approximation is not equipped to fit spectra from a heterogeneous ensemble of doped semiconductor NCs and produces fit results that violate Mie scattering theory. The heterogeneous ensemble Drude approximation (HEDA) model rectifies this issue by accounting for ensemble heterogeneity and near-surface depletion. The HEDA model is applied to tin-doped indium oxide NCs for a range of sizes and doping levels but we expect it can be employed for any isotropic plasmonic particles in the quasistatic regime. It captures individual NC optical properties and their contributions to the ensemble spectra thereby enabling the analysis of intrinsic NC properties from an ensemble measurement. Quality factors for the average NC in each ensemble are quantified and found to be notably higher than those of the ensemble. Carrier mobility and conductivity derived from HEDA fits matches that measured in the bulk thin film literature.

When aliovalent dopants are sufficiently segregated to the core or near the surface of semiconductor nanocrystals, charge carriers donated by the dopants are also segregated to the core or near the surface, respectively. In Sn-doped indium oxide nanocrystals, we find that this contrast in free charge carrier concentration creates a core and shell with differing dielectric properties and results in two distinctly observable plasmonic extinction peaks. The trends in this dual-mode optical response with shell growth differ from core/shell nanoparticles composed of traditional plasmonic metals such as Au and Ag. We developed a model employing a core/shell effective medium approximation that can fit the dual-mode spectra and explain the trends in the extinction response. Lastly, we show that dopant segregation can improve sensitivity of plasmon spectra to changes in refractive index of the surrounding environment.

Summary Background Voluntary individual quarantine and voluntary active monitoring of contacts are core disease control strategies for emerging infectious diseases such as COVID-19. Given the impact of quarantine on resources and individual liberty, it is vital to assess under what conditions individual quarantine can more effectively control COVID-19 than active monitoring. As an epidemic grows, it is also important to consider when these interventions are no longer feasible and broader mitigation measures must be implemented. Methods To estimate the comparative efficacy of individual quarantine and active monitoring of contacts to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we fit a stochastic branching model to reported parameters for the dynamics of the disease. Specifically, we fit a model to the incubation period distribution (mean 5·2 days) and to two estimates of the serial interval distribution: a shorter one with a mean serial interval of 4·8 days and a longer one with a mean of 7·5 days. To assess variable resource settings, we considered two feasibility settings: a high-feasibility setting with 90% of contacts traced, a half-day average delay in tracing and symptom recognition, and 90% effective isolation; and a low-feasibility setting with 50% of contacts traced, a 2-day average delay, and 50% effective isolation. Findings Model fitting by sequential Monte Carlo resulted in a mean time of infectiousness onset before symptom onset of 0·77 days (95% CI −1·98 to 0·29) for the shorter serial interval, and for the longer serial interval it resulted in a mean time of infectiousness onset after symptom onset of 0·51 days (95% CI −0·77 to 1·50). Individual quarantine in high-feasibility settings, where at least 75% of infected contacts are individually quarantined, contains an outbreak of SARS-CoV-2 with a short serial interval (4·8 days) 84% of the time. However, in settings where the outbreak continues to grow (eg, low-feasibility settings), so too will the burden of the number of contacts traced for active monitoring or quarantine, particularly uninfected contacts (who never develop symptoms). When resources are prioritised for scalable interventions such as physical distancing, we show active monitoring or individual quarantine of high-risk contacts can contribute synergistically to mitigation efforts. Even under the shorter serial interval, if physical distancing reduces the reproductive number to 1·25, active monitoring of 50% of contacts can result in overall outbreak control (ie, effective reproductive number Interpretation Our model highlights the urgent need for more data on the serial interval and the extent of presymptomatic transmission to make data-driven policy decisions regarding the cost–benefit comparisons of individual quarantine versus active monitoring of contacts. To the extent that these interventions can be implemented, they can help mitigate the spread of SARS-CoV-2. Funding National Institute of General Medical Sciences, National Institutes of Health.

Meningiomas are the most common primary central nervous system tumor. Emerging data supports that higher mutational burden portends worse clinical outcomes in meningiomas. However, there is a lack of imaging biomarkers that are associated with tumor genomics in meningiomas. We performed next-generation targeted sequencing in a cohort of 75 primary meningiomas and assessed preoperative imaging for tumor volume and peritumoral brain edema (PTBE). An Edema Index was calculated. Meningiomas that were high grade (WHO grade II or grade III) had significantly larger tumor volume and were more likely to present with PTBE. Moreover, PTBE was associated with brain invasion on histopathology and reduced overall survival. There was a direct association between Edema Index and mutational burden. For every one increase in Edema Index, the number of single nucleotide variants increased by 1.09-fold (95% CI: 1.02, 1.2) (P = 0.01). These data support that Edema Index may serve as a novel imaging biomarker that can inform underlying mutational burden in patients with meningiomas.

The tumor microenvironment is an emerging biomarker of underlying genomic heterogeneity and response to immunotherapy-based treatment regimens in solid malignancies. How tumor mutational burden influences the density, distribution, and presence of a localized immune response in meningiomas is unknown. Representative hematoxylin and eosin slides were reviewed at 40X to assess for the density of inflammatory cells. Lymphocytes and macrophages were quantified in the following ordinal manner: 0 = not present, 1 = 1–25 cells present, and 2 = greater than 26 cells present. Immune cell infiltrate grade was scored for both scattered and aggregated distributions. Next generation targeted sequencing was performed on all meningiomas included in this study. One hundred and forty-five meningiomas were evaluated in this study. Lymphocytes were observed in both scattered (95.9%) and aggregated (21.4%) distributions. A total of 115 (79.3%) meningiomas had 1–25 scattered lymphocytes, and 24 (16.6%) had > 25 scattered lymphocytes, and 6 (4.1%) had no scattered lymphocytes. Twenty (13.8%) meningiomas had 1–25 aggregated lymphocytes. Eleven (7.6%) had > 25 aggregated lymphocytes and 114 (78.6%) had no aggregated lymphocytes. Six (4.1%) meningiomas had 1–25 aggregated macrophages, 5 (3.4%) had > 25 aggregated macrophages, and 134 (92.4%) had no aggregated macrophages. Density of aggregated lymphocytes and aggregated macrophages were associated with higher tumor grade, P = 0.0071 and P = 0.0068, respectively. Scattered lymphocyte density was not associated with meningioma grade. The presence of scattered lymphocytes was associated with increased tumor mutational burden. Meningiomas that did not have scattered lymphocytes had a mean number of single mutations of 2.3 ± 2.9, compared with meningiomas that had scattered lymphocytes, 6.9 ± 20.3, P = 0.03. NF2 mutations were identified in 59 (40.7%) meningiomas and were associated with increased density of scattered lymphocytes. NF2 mutations were seen in 0 (0%) meningiomas that did not have scattered lymphocytes, 46 (40.0%) meningiomas that had 1–25 scattered lymphocytes, and 13 (54.2%) meningiomas that had > 25 scattered lymphocytes, P = 0.046. Our findings suggest that distribution of immune cell infiltration in meningiomas is associated with tumor mutational burden. NF2 mutational status was associated with an increasing density of scattered lymphocytes. As the role of immunotherapy in meningiomas continues to be elucidated with clinical trials that are currently underway, these results may serve as a novel biomarker of tumor mutational burden in meningiomas.

Tropical splenomegaly is often associated with malaria and schistosomiasis. In 2014 and 2015, 145 Congolese refugees in western Uganda diagnosed with splenomegaly during predeparture medical examinations underwent enhanced screening for various etiologies. After anecdotal reports of unresolved splenomegaly and complications after U.S. arrival, patients were reassessed to describe long-term clinical progression after arrival in the United States. Post-arrival medical information was obtained through medical chart abstraction in collaboration with state health partners in nine participating states. We evaluated observed splenomegaly duration and associated clinical sequelae between 130 case patients from eastern Congo and 102 controls through adjusted hierarchical Poisson models, accounting for familial clustering. Of the 130 case patients, 95 (73.1%) had detectable splenomegaly after arrival. Of the 85 patients with records beyond 6 months, 45 (52.9%) had persistent splenomegaly, with a median persistence of 14.7 months (range 6.0–27.9 months). Of the 112 patients with available results, 65 (58.0%) patients had evidence of malaria infection, and the mean splenomegaly duration did not differ by Plasmodium species. Refugees with splenomegaly on arrival were 43% more likely to have anemia (adjusted relative risk [aRR]: 1.43, 95% CI: 1.04–1.97). Those with persistent splenomegaly were 60% more likely (adjusted relative risk [aRR]: 1.60, 95% CI: 1.15–2.23) to have a hematologic abnormality, particularly thrombocytopenia (aRR: 5.53, 95% CI: 1.73–17.62), and elevated alkaline phosphatase (aRR: 1.57, 95% CI: 1.03–2.40). Many patients experienced persistent splenomegaly, contradicting literature describing resolution after treatment and removal from an endemic setting. Other possible etiologies should be investigated and effective treatment, beyond treatment for malaria and schistosomiasis, explored.

Uncertainty is intrinsic to perception. Neural circuits which process sensory information must therefore also represent the reliability of this information. How they do so is a topic of debate. We propose a model of visual cortex in which average neural response strength encodes stimulus features, while cross-neuron variability in response gain encodes the uncertainty of these features. To test this model, we studied spiking activity of neurons in macaque V1 and V2 elicited by repeated presentations of stimuli whose uncertainty was manipulated in distinct ways. We show that gain variability of individual neurons is tuned to stimulus uncertainty, that this tuning is specific to the features encoded by these neurons and largely invariant to the source of uncertainty. We demonstrate that this behavior naturally arises from known gain-control mechanisms, and illustrate how downstream circuits can jointly decode stimulus features and their uncertainty from sensory population activity., How does the brain represent sensory uncertainty? The authors find that neural gain variability tracks stimulus uncertainty across the visual hierarchy and explain their findings with a simple generalization of canonical models of neural computation.

Context After knee-joint injury, pain, effusion, and mechanoreceptor damage alter afferent signaling, which can result in quadriceps inhibition and subsequent weakness. The individual contributions of each factor to inhibition remain unclear due to confounding knee-joint injuries and indirect experimental models. Objective To characterize the influence of naturally occurring knee damage and pain on quadriceps neuromuscular function in individuals with patellar tendinopathy. Design Cross-sectional study. Setting Research laboratory. Patients or Other Participants Twenty participants who self-reported patellar tendinopathy (PT) and 10 healthy control individuals underwent ultrasonic tendon assessment. Injured participants were dichotomized by an orthopaedic surgeon into groups with (1) pain and structural tendon abnormality and (2) regional pain alone. Main Outcome Measure(s) Quadriceps inhibition was assessed with the Hoffman reflex and the central activation ratio via the superimposed-burst technique. Normally distributed measures were analyzed using a 1-way analysis of variance and post hoc independent t tests. Kruskal-Wallis tests with post hoc Mann-Whitney U tests were used to analyze nonnormally distributed data. An a priori α level of P ≤ .05 was set. Results Control participants presented with more spinal-reflex excitability (0.37 ± 0.23) than the PT (0.10 ± 0.06; P = .03) and regional-pain (0.18 ± 0.05; P = .02) groups. Knee-extension strength was greater in the control (3.37 ± 0.59 Nm/kg) than in the PT (2.41 ± 0.67 Nm/kg; P = .01) group but not the regional-pain group (3.05 ± 0.66 Nm/kg; P = .24). Control individuals presented with more quadriceps activation (97.93% ± 3.12) than the PT (84.44% ± 16.98; P < .01) and regional-pain (91.17% ± 10.56; P = .01) groups. No differences were present for any measures between the PT and regional-pain groups (P values > .05). Conclusions Deficits in spinal-reflex excitability, quadriceps activation, and strength were present in both the PT and regional-pain groups. A combination of pain and structural damage appeared to have the greatest negative effect on quadriceps function, as only the PT group presented with neuromuscular outcomes that failed to meet clinical thresholds.

Emerging evidence suggests that STK11 mutations may influence clinical outcome and response to immunotherapy in cancer. Next-generation targeted sequencing of STK11 mutation status in a large cohort of 188 meningiomas. STK11 loss-of-function mutations were identified in 3.7% of meningiomas. STK11 mutations were found in both low- and high-grade lesions and samples from primary and recurrent disease. There was a 2.8-fold increased risk of death for patients whose meningioma harbored an STK11 mutation, after controlling for lesion grade and occurrence status. The median overall survival for patients with STK11-mutated meningiomas was 4.4 years compared with 16.8 years. These data identify recurrent STK11 mutations in a subset of meningiomas. Genotyping of STK11 is encouraged for meningioma patients undergoing immunotherapy-based therapy.

BACKGROUND Asthma is a heterogenous disease that can be classified into eosinophilic (type 2-high) and noneosinophilic (type 2-low) endotypes. The type 2-low endotype of asthma can be characterized by the presence of neutrophilic airway inflammation that is poorly responsive to corticosteroids. Dysregulated innate immune responses to microbial products including Toll-like receptor (TLR) ligands have been associated with the pathogenesis of neutrophilic asthma. The key molecules that regulate inflammatory responses in individuals with neutrophilic asthma remain unclear. We previously reported that the immunoregulatory receptor neuropilin-2 (NRP2) is expressed by murine and human alveolar macrophage (AM) and suppresses lipopolysaccharide (LPS)-induced neutrophilic airway inflammation. METHODS Here, we investigated the immunoregulatory role of NRP2 in a mouse model of neutrophilic asthma. RESULTS We found that TLR ligands, but not T helper 2 (Th2)-promoting adjuvants, induced NRP2 expression by AM. Using an LPS-mediated model of neutrophilic asthma, we demonstrate that NRP2 was increased in AM and other lung antigen-presenting cells following airway challenge with antigen. Conditional deletion of NRP2 in myeloid cells exacerbated airway inflammation in a neutrophilic asthma model. In contrast, myeloid-specific ablation of NRP2 did not affect airway inflammation in a Th2-mediated eosinophilic asthma model. Myeloid-specific ablation of NRP2 did not affect Th1/Th17 responses to inhaled antigens or expression of neutrophil chemokines but rather resulted in impaired efferocytosis by AM, which is necessary for effective resolution of airway inflammation. CONCLUSION Our findings suggest that NRP2 is a negative regulator of airway inflammation associated with neutrophilic asthma.

Coloration efficiency is an important figure of merit in electrochromic windows. Though it is thought to be an intrinsic material property, we tune optical modulation by effective utilization of ion intercalation sites. Specifically, we enhance the coloration efficiency of m-WO

Objective This article aims to characterize 14 patients who underwent purely endoscopic surgical debridement of acute invasive skull base fungal rhinosinusitis, and to evaluate postoperative outcomes and risk for recurrence.Design Retrospective cohort study.Setting Tertiary single-institution neurosurgery department.Participants We performed a retrospective analysis of all patients with skull base fungal infections treated with a purely endoscopic surgical approach at Mount Sinai Hospital from 1998 to 2018.Main Outcome Measures Clinical presentation, number of recurrences, and mortality rate.Results The most common underlying medical comorbidities were hematologic malignancy in 8 (57.1%) patients and poorly controlled diabetes mellitus in 7 (50%) patients. Presenting symptoms included headache (50%), eye pain (35.7%), facial pain (28.6%), visual changes (21.4%), and nasal congestion (14.3%). The fungal organisms identified on culture were Aspergillus (42.9%), Mucorales (28.6%), Fusarium (14.3%), Penicillium (7.1%), and unspecified (7.1%). Eight (57.1%) patients developed recurrence and required multiple surgical debridements. Patients who had only a hematologic malignancy were more likely to require multiple surgical debridements compared with those who did not have a hematologic malignancy or those who had both hematologic malignancy and underlying diabetes mellitus (p = 0.03). The mortality rate from surgery was 42.9%.Conclusion Surgical endoscopic intervention is an option for definitive management of acute invasive skull base fungal rhinosinusitis; however, postoperative mortality and risk of recurrence requiring additional surgical interventions remains high. Patients with hematologic malignancy may be more susceptible to recurrent infection requiring multiple surgical debridements. We recommend early aggressive multimodal treatment. Multiple debridements may be warranted in most cases; close clinical surveillance is needed during neurosurgical intervention.

CONTEXT State health officials (SHOs), the executive and administrative leaders of state public health, play a key role in policy development, must be versed in the relevant/current evidence, and provide expertise about health issues to the legislature and the governor. OBJECTIVE To provide an empirical examination of SHO backgrounds and qualifications over time. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional survey of current/former SHOs. MAIN OUTCOME MEASURES State health official educational backgrounds; public health experience; previous employment setting. RESULTS Two-thirds of respondents (64.6%) reported having a medical degree, approximately half (48.3%) a formal public health degree, and almost one-quarter (21.8%) a management degree. The majority had governmental public health experience at some prior point in their career (70.0%). Almost two-thirds worked in governmental public health immediately before becoming an SHO. The proportion that was female increased significantly by decade from 5.6% in the 1970s/80s to 46.4% in the 2010s (P = .02). CONCLUSIONS The main finding from this study shows that more than two-thirds of SHOs have had governmental public health experience at some point in their career. This is not a new trend as there were no statistical differences in public health experience by decade. More than half of the SHOs were appointed to the role directly from governmental public health, indicating that their public health experience is timely and likely germane to their appointment as SHO. Findings also indicate improvements in gender diversity among one of the most influential leadership roles in governmental public health whereas significant changes in racial and ethnic diversity were not identified. Women are increasingly being appointed as SHOs, indicating increasing gender diversity in this influential position. Given that governmental public health employees are predominantly women, there is still room for gender equity improvements in executive leadership roles. This is coupled with the need for further racial and ethnic diversity improvements as well.

Lay Responder Care in Out-of-Hospital Cardiac Arrest Lay responders play a major role in the resuscitation of persons with out-of-hospital cardiac arrest. Crucial steps include recognition of cardi...

The purpose of our study was to determine the role of brown adipose tissue (BAT) in cancer progression. Our study was approved by our institutional review board and Health Insurance Portability and Accountability Act–compliant. Our study group comprised 132 cancer patients (116 f, 16 m; mean age 50 ± 16 years) who underwent F18-FDG PET/CT per standard clinical protocol, for staging or surveillance of cancer. We included patients who were BAT-positive on PET/CT and had clinical follow-up data available for at least 12 months or until tumor recurrence or tumor-related death, whichever occurred first. BAT volume by PET/CT was quantified by PET-CT Viewer shareware. Clinical information including tumor type, tumor recurrence, survival, and outside temperature at time of scan were recorded. Cox proportional hazard models were used to determine longitudinal associations between BAT volume and tumor recurrence/mortality. There were 55 tumor recurrences/tumor-related deaths over a median follow-up period of 71 (33; 110 interquartile range) months. Higher BAT volume was associated with an increased likelihood of tumor recurrence/tumor-associated mortality after adjustment for covariates (p = 0.03). BAT volume, assessed using routine PET/CT, is a predictor of tumor recurrence/mortality in patients with cancer, independent of other factors that can influence BAT activity, such as sex, age, BMI, or tumor type.

BACKGROUND: A fundamental responsibility of aerospace medicine is the analysis and mitigation of the human component's risk to the aviation system. Medications are part of this risk mitigation process and are present within a multitude of work environments, including aviation. For example, during fiscal year (FY) 2013-2015, the Army Aeromedical Activity (AAMA) received 8596 medication waiver requests. During this same time period the U.S. Army Medical Department's Patient Administration Systems and Biostatistics Activity reported the organization prescribed over 187,668 prescriptions for opioids, 133,475 prescriptions for SSRIs, 116,649 prescriptions for muscle relaxants, and 71,723 prescriptions for hypnotics to its active duty soldiers in the outpatient setting.METHODS: A conceptual model to mitigate the risk of adverse reactions to medications by severity score was developed based off the methodology published by Prudhomme et al.RESULTS: The mean severity score of the 50 historically safe medications in the Army aviation community is 7346. The standard deviation of the population is 7300. The difference between safe and unsafe drugs determined by subject matter experts (SME) is highly significant when tested with the nonparametric Wilcoxon rank sum test.CONCLUSION: The visual representation of the data from this conceptual model clearly demonstrates room for improvement from current methods. Historically, utilizing SME opinion has created a system with deficiencies related to high variance, inconsistencies, and perceived ambiguity. There is need for a model addressing adverse drug reactions that has concrete strengths of transparency, simplicity, and speed of use.Cronrath CM, Klick MP, Merfeld CM, Gaydos SJ. Medication Adverse Reaction, Risk Stratification (MAR2S) model. Aerosp Med Hum Perform. 2019; 90(10):896-900.

CONTEXT Public health agencies will likely struggle to staff at necessary levels, given ongoing workforce shortages, the potential for mass retirement, and expanding responsibility. Although the majority of public health workers are satisfied with their jobs overall, it is critical to understand the degree to which they are satisfied and identify factors that contribute to any dissatisfaction that occurs. OBJECTIVE This study identified opportunities for public health agencies to improve work environments and, in turn, improve employee satisfaction and retention. DESIGN Using data from the 2014 Public Health Workforce Interest and Needs Survey, we analyze responses to the survey question, "If you wish, you may provide comments below about your level of job satisfaction." The 2966 responses (2389 from state and 542 from local public health agencies) that indicated a negative disposition were examined to understand employee dissatisfaction. SETTING The survey was administered to a representative sample of state health departments and convenience samples of local health departments. PARTICIPANTS Responses from employees of state and local health departments are considered. MAIN OUTCOME MEASURES The most frequently occurring themes overall were identified. In addition, responses describing weaknesses in organizational support (specifically training, communication, workload, and innovation) were summarized. RESULTS The most frequently occurring themes were as follows: (1) salary, specifically in relation to the merit system, performance evaluation, and workload; (2) job security with emphasis on funding, organizational transformation, and politics/government; and (3) career development related to the merit system, performance evaluation, and management. Respondents also reported opportunities in the areas of training, communication, workload, and innovation to improve satisfaction levels. CONCLUSIONS These findings serve as a call to action for leaders in health departments as well as national public health leaders to remedy the concerns raised in their responses. Some of the solutions are within the realm of public health agency leadership, but some may fall within the realm of governors and public health leaders at the federal level. It is important to share these findings so that appropriate decision makers can address public health workforce retention and recruitment issues in the interest of retaining valuable employees.

Chordomas are rare primary malignant tumors of the bones that occur along the skull base, spine, and sacrum. Long-term survival and neurological outcome continue to be challenging with continued low percentages of long-term survival. Recent studies have used genome, exome, transcriptome, and proteome sequencing to assess the mutational profile of chordomas. Most notably, Brachyury, or T-protein, has been shown to be an early mutational event in chordoma evolution. Clinically actionable mutations, including in the PI3K pathway, were identified. Preliminary evidence suggests that there may be mutational differences associated with primary tumor location. In this study, we review the therapeutic landscape of chordomas and discuss emerging targets in the genomic era.

Background Women with a previous neural tube defect (NTD)-affected pregnancy are recommended to consume 4,000 μg daily folic acid (FA) for prevention (10 times the general-population recommendation). Protection from doses between 400 and 4,000 μg for this and other higher risk groups is unclear. Methods In the case-control Slone Birth Defects Study (1988-2015), we examined the associations between periconceptional FA doses and NTDs among four higher risk groups: NTD family history, periconceptional antiepileptic drug exposure (AED), pregestational diabetes, and prepregnancy obesity. Mothers completed standardized interviews about pregnancy events and exposures. FA categorizations were based on (a) supplements only and (b) supplements and diet ("total folate"). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) (adjusted for age and study center) using logistic regression. Results Cases and controls included: 45 and 119 with family history, 25 and 108 with AED exposure, 12 and 63 with pregestational diabetes, 111 and 1,243 with obesity. Daily FA supplementation was associated with lower NTD risk compared to no supplementation (adjusted ORs were 0.33 [95% CI 0.13, 0.76] for family history, 0.31 [0.09, 0.95] for AED exposure, 0.25 [0.04, 1.05] for pregestational diabetes, 0.65 [0.40, 1.04] for obesity). Though estimates were imprecise, as total folate increased stronger point estimates were observed, notably among family history. No mothers with a prior NTD-affected pregnancy supplemented with 4,000 μg. Conclusions Our findings reinforce that all women of childbearing potential should consume at least 400 μg FA/day to protect against NTDs. Higher risk groups may benefit from higher doses.

Strong infrared (IR) light-matter interaction and spectral tunability combine to make plasmonic metal oxide nanocrystals (NCs) a compelling choice for IR applications. In particular, visible transparency paired with strong, dynamically tunable IR absorption has motivated their implementation in electrochromic smart windows, but these NCs hold promise for a far broader range of plasmonically driven processes such as surface-enhanced infrared sensing, photothermal therapy, and enhanced photocatalysis. These unique properties result from localized surface plasmon resonance (LSPR) sustained by a relatively low free charge carrier concentration, which in turn requires consideration of distinct materials physics relative to traditional plasmonic materials (i.e., metals). Particularly important is the formation of insulating shells devoid of charge carriers (depletion layers) near the NC surface. Surface states as well as applied surface potentials can give rise to a potential difference between the NC surface and its core that depletes free charge carriers from the surface, forming an insulating shell that reduces the conductivity in NC films, lowers the dielectric sensitivity of the LSPR, and diminishes the incident electric field enhancement. In this Account, we report recent investigations of depletion layers in plasmonic metal oxide NCs that have advanced understanding of the semiconductor physics underlying the optoelectronic properties of these NCs and the electrochemical modulation of their LSPR, establishing a conceptual framework with which to broaden their applicability and optimize their performance. As a result of surface depletion, larger, highly doped NCs have improved dielectric sensitivity compared with their smaller, lightly doped counterparts. Concentrating dopants near the NC surface compresses the depletion layer, resulting in improved conductivity of NC films. Moreover, atomic layer deposition of alumina to infill NC films enhances the film conductivity by more than 2 orders of magnitude, ascribed to the elimination of depletion effects by reactive removal of surface water species. At the conclusion, we reflect on how our newfound understanding of surface depletion in plasmonic metal oxide NCs is quickly leading to rational material design. This insight is already resulting in significant performance improvements, and the same principles can be applied to new, exciting opportunities in hot carrier extraction and resonant IR energy transduction.

Background Hepatitis A is a vaccine-preventable viral disease transmitted by the fecal-oral route. During 2016–2018, the County of San Diego investigated an outbreak of hepatitis A infections primarily among people experiencing homelessness (PEH) to identify risk factors and support control measures. At the time of the outbreak, homelessness was not recognized as an independent risk factor for the disease. Methods We tested the association between homelessness and infection with hepatitis A virus (HAV) using a test-negative study design comparing patients with laboratory-confirmed hepatitis A with control subjects who tested negative for HAV infection. We assessed risk factors for severe hepatitis A disease outcomes, including hospitalization and death, using multivariable logistic regression. We measured the frequency of indications for hepatitis A vaccination according to Advisory Committee on Immunization Practices (ACIP) guidelines. Results Among 589 outbreak-associated cases reported, 291 (49%) occurred among PEH. Compared with those who were not homeless, PEH had 3.3 (95% confidence interval [CI], 1.5–7.9) times higher odds of HAV infection, 2.5 (95% CI, 1.7–3.9) times higher odds of hospitalization, and 3.9 (95% CI, 1.1–16.9) times higher odds of death associated with hepatitis A. Among PEH, 212 (73%) patients recorded other ACIP indications for hepatitis A vaccination. Conclusions PEH were at higher risk of infection with HAV and of severe hepatitis A disease outcomes compared with those not experiencing homelessness. Approximately one-fourth of PEH had no other ACIP indication for hepatitis A vaccination. These findings support the recent ACIP recommendation to add homelessness as an indication for hepatitis A vaccination.

Purpose In an increasingly budget-constrained environment, the Department of Defense (DoD) must maximize the value of fiscal resources obligated on service contracts. Over half of DoD procurement spending between 2008 and 2012 was obligated on service contracts (GAO, 2013). Many services are common across the enterprise and recurring in nature; however, they are treated as unique and procured individually at the base level, year after year, rather than collectively in accordance with a larger, enterprise-wide category management strategy. The purpose of this paper is to focus on creating a methodology that treats common, recurring service requirements in a more strategic manner. Design/methodology/approach The authors develop a standardized, repeatable methodology that uses relevant cost drivers to analyze service requirements to identify more efficient procurement strategies. Furthermore, they create a clustering continuum to organize services based on proximity between the customer-supplier bases. This paper uses a commercial business mapping software to analyze cost driver data, produce visualizations and illustrate strategic opportunities for category management initiatives. DoD requirements for Integrated Solid Waste Management (ISWM) within the Los Angeles area are evaluated using the software and methodology to demonstrate a model for practical application. Findings The authors find that commercial software can be used to cluster requiring activities needing common, recurring services. This standardized, repeatable method can be applied to any category of services with any number of cost drivers. By identifying optimal requiring activity clusters, procurement agencies can more effectively implement category management strategies for service requirements. Research limitations/implications The initial approach of this paper was to develop a macro-level, one-size-fits-all model to centralize procurement. The authors found this approach inadequate as they tried to group service requirements of wildly differing characteristics. They experienced other significant limiting factors related to data availability and data collection. Social implications Clustering common and recurring DoD service requirements would result in standardized levels of service at all installations. The demand savings from clustering would promote the implementation of best practices for that service requirement across the DoD, which would eliminate non-value-added activities currently performed at some installations, or gold-plating of requirements, which is also likely occurring. Originality/value This paper is the first to use an analytics-based methodology to cluster common, recurring public services. It is the first method that offers a standardized, repeatable approach to implementing category management of service requirements to achieve cost savings.

Although significant research has examined the effect of enterprise information systems on the behavior and careers of employees, the majority of this work has been devoted to the study of blue- and gray-collar workers, with little attention paid to the transformative effect information technology may have on high-status professionals. In this paper, we begin to bridge this gap by examining how highly skilled professionals react to the increasing presence of enterprise systems within their organizations. Specifically, we investigate how the implementation of enterprise systems—in the form of electronic health records—affects the decision of physicians to continue practicing at their current hospital. Results suggest that when enterprise systems create complementarities for professionals, their duration of practice at the organization increases significantly. However, when technologies are disruptive and force professionals to alter their routines, there is a pronounced exodus from the organization. Interestingly, these effects are strongly moderated by individual and organizational characteristics, such as the degree of firm-specific human capital, local competition, and the prevalence of past disruptions, but are not associated with accelerated retirement or the strategic poaching of talent by competing organizations.

Key Points Question What do adolescents and young adults with cancer, their families, and clinicians find important in end-of-life care? Findings This qualitative study of interviews with 23 adolescents and young adults, 28 family caregivers, and 29 clinicians identified 7 distinct end-of-life priority domains: attention to physical symptoms, attention to quality of life, psychosocial and spiritual care, communication and decision-making, relationships with clinicians, care and treatment, and independence. Although some domains reflected existing quality domains for adults, some domains were unique or had distinct manifestations for this young population. Meaning The priority domains identified in this study as relevant to adolescents and young adults with advanced cancer may be used for quality measurement., Importance End-of-life care quality indicators specific to adolescents and young adults (AYAs) aged 12 to 39 years with cancer have not been developed. Objective To identify priority domains for end-of-life care from the perspectives of AYAs, family caregivers, and clinicians, and to propose candidate quality indicators reflecting priorities. Design, Setting, and Participants This qualitative study was conducted from December 6, 2018, to January 5, 2021, with no additional follow-up. In-depth interviews were conducted with patients, family caregivers, and clinicians and included a content analysis of resulting transcripts. A multidisciplinary advisory group translated priorities into proposed quality indicators. Interviews were conducted at the Dana-Farber Cancer Institute, Kaiser Permanente Northern California, Kaiser Permanente Southern California, and an AYA cancer support community (lacunaloft.org). Participants included 23 AYAs, 28 caregivers, and 29 clinicians. Exposure Stage IV or recurrent cancer. Main Outcomes and Measures Care priorities. Results Interviews were conducted with 23 patients (mean [SD] age, 29.3 [7.3] years; 12 men [52%]; 18 White participants [78%]), 28 family caregivers (23 women [82%]; 14 White participants [50%]), and 29 clinicians (20 women [69%]; 13 White participants [45%]). Caregivers included 22 parents (79%), 5 spouses or partners (18%), and 1 other family member (4%); the 29 clinicians included 15 physicians (52%), 6 nurses or nurse practitioners (21%), and 8 social workers or psychologists (28%). Interviews identified 7 end-of-life priority domains: attention to physical symptoms, attention to quality of life, psychosocial and spiritual care, communication and decision-making, relationships with clinicians, care and treatment, and independence. Themes were consistent across the AYA age range and participant type. Although some domains were represented in quality indicators developed for adults, unique domains were identified, as well as AYA-specific manifestations of existing domains. For example, quality of life included global quality of life; attainment of life goals, legacy, and meaning; support of personal relationships; and normalcy. Within communication and decision-making, domains included communication early in the disease course, addressing prognosis and what to expect at the end of life, and opportunity for AYAs to hold desired roles in decision-making. Care and treatment domains relevant to cancer therapy, use of life-prolonging measures, and location of death emphasized the need for preference sensitivity rather than a standard path. This finding differs from existing adult indicators that propose that late-life chemotherapy, intensive measures, and hospital death should be rare. Conclusions and Relevance The findings of this qualitative study suggest that AYAs with cancer have priorities for care at the end of life that are not fully encompassed in existing indicators for adults. Use of new indicators for this young population may better reflect patient- and family-centered experiences of quality care., This qualitative study assesses patient, family, and clinician perspectives on priority domains for end-of-life care for adolescents and young adults with cancer.

Sophisticated three-dimensional microstructures fabricated using the negative tone SU-8 photoresist are used in many biomedical and microfluidic applications. Scanning electron microscopy (SEM) and profilometry are commonly used metrological techniques for the dimensional characterization of fabricated SU-8 microstructures but are not viable for non-destructive measurements and characterization of subsurface features like hidden microchannels. In this study, we report a unique methodology for the non-destructive dimensional characterization of SU-8 microstructures using the emitted autofluorescence radiation from fabricated SU-8 microstructures to generate depth profiles. The relationship between autofluorescence emission intensities and the thicknesses of the microstructures measured using SEM was determined and used to characterize the dimensions of unknown SU-8 microstructures based on their autofluorescence intensities. Lateral dimensions were also measured. This relationship was used to create highly accurate depth profiles for different types of microstructures including hidden subsurface features. These results were validated by comparison with SEM. The results suggest a feasible and accurate non-destructive, low cost, metrological technique to characterize SU-8 surface and subsurface microstructures using autofluorescence emission intensities.

Universal Design for Learning (UDL) is a pedagogical design theory that accounts for variability across and within learners, both in physical classrooms and with online learning materials. Librarians at Washington State University implemented elements reflective of specific UDL checkpoints in a heavily-used LibGuide for a required undergraduate course. Online learning objects create opportunities for meeting UDL’s goals of not only multiple means of representation, but also engagement and action and expression extending beyond the baseline obligation to meet standard accessibility guidelines. We discuss our implementation of UDL elements, changes in LibGuide use before and after the introduction of UDL features, and usability study results, focusing on how students who face learning barriers view UDL. We explain considerations for successfully implementing UDL in online materials and the potential benefits.

Objective: To quantify the occurrence rate of abnormal electrocardiographic (ECG) findings and symptoms following coronavirus disease 2019 (COVID-19) infection. Patients and Methods: In this retrospective analysis, we studied adult patients (>18 years old) who were participating in collegiate athletics and previously tested positive for COVID-19 between August 1, 2020, and December 30, 2020. The athletes underwent general examinations and ECG screening prior to being medically cleared for a return to sports following their COVID-19 diagnosis. Predetermined predictors were grouped into categorical variables including (1) sex, (2) symptom severity, and (3) body mass index (normal vs overweight [≥24 kg/m2]). These variables were used to examine differences of abnormal rates that occurred between different predictor categories. Results: Of the 170 athletes screened, 6 (3.5%) presented with abnormal ECG findings and were referred to cardiologists. We found no evidence that sex, symptom severity, and body mass index category were associated with a higher rate of abnormal ECG findings (all P>.05). Greater severity of COVID-19 symptoms was associated with a higher percentage of ST depression, T-wave inversion, ST-T changes, and the presence of fragmented QRS complex. Loss of smell, loss of taste, headache, and fatigue were the most prevalent symptoms, with 38.8% (66), 36.5% (62), 32.9% (56), and 25.3% (43), respectively, of the 170 athletes reporting each symptom. Conclusion: Preliminary findings indicate a low risk of myocardial injury secondary to COVID-19 infection, with less than 4% of the 170 patients in our study presenting with abnormal ECG findings and a total of 16 patients (9.4%) requiring referral to a cardiologist. Although viral myocarditis was not detected in any athlete referred for cardiological assessment, 2 patients experienced effusive viral pericarditis.

We have developed a novel microfabrication and assembly strategy for the realization of 3D Microelectrode Arrays (3D MEAs) which allows for simultaneous optical and electrical probing of a Nerve-on-a-Chip® construct. Specific microfabrication and assembly process innovations include "edge-wrapped" metal interconnects and custom Digital Light Processing (DLP) 3D printed transition rigs respectively. A Nerve-on-a-Chip® construct consisting of primary rat Dorsal Root Ganglion (DRG) cells are further seeded and grown atop the 3D MEA for 28 Days in vitro (DIV). Herein, we present results of the fabrication technology including AFM profilometry of interconnects, in addition to Impedance Spectroscopy, Root Mean Square (RMS) noise characterization, mechanical stability of the MEAs and long-term culture viability of the integrated tissue chip (Nerve-on-a-Chip® construct on the 3D MEAs) with fluorescence imaging.

During the COVID-19 pandemic, social distancing measures have made in-person mutual help groups inaccessible to many individuals struggling with substance use disorders (SUDs). Prior to the pandemic, stakeholders in our community had sponsored a program to train volunteers to facilitate local Self-Management and Recovery Training (SMART Recovery) groups. As a result, the community established seven weekly SMART Recovery groups, which more than 200 community members attended. In March 2020, the community discontinued these groups due to the COVID-19 pandemic. To provide SMART Recovery during social distancing, we developed a one-on-one phone-in service for people with SUDs and addictions: the SMART Recovery Line (SMARTline). In this paper, we share our experience training volunteers to facilitate SMART Recovery groups and SMARTline. As a result of our experience, we have learned to: (1) establish plans in advance to migrate services from face-to-face settings to remote platforms; (2) consider remote platforms that are easily accessible to the greatest number of individuals; (3) include as many stakeholders in the planning process as possible; (4) consider recruiting volunteers to help in the provision of services, especially since many people want to help fellow community members during crises; and (5) anticipate and prepare for crises well before they occur., Highlights • People with addictions rely on mutual help groups (e.g., AA, NA, SMART Recovery). • We have developed a program to train volunteers to facilitate SMART Recovery groups. • SMART Recovery groups were established, but were discontinued due to COVID-19. • In response we developed a novel phone adaptation of SMART Recovery (SMARTline). • We share recommendations for providing remote addiction services during COVID-19.