Aggregate Boid behaviour to aid in artificial autopoietic organization.

Analyzing carbon-based life on earth can lead to biased inferences on the nature of life as might exist in elsewhere in the universe in alternative forms, therefore, scientists have looked into either abstracting life into constituent systems it is comprised of, or logics of life, or lists of essential criteria, or essential dynamic patterning that characterizes the living. A system-level characterization that is and referred to as a general pattern of minimal life is autopoiesis (Varela et al., 1974) including production, maintenance and replacement of required constituents for setting up and maintaining an internal environment with self/other separation that regulates and is constitutive of processes that produce the environment and components for processes that comprise this ongoing activity of self-production in 'recursively', i.e., in a manner that allows the organizational pattern to continually reconstitute the conditions, components and processes required for its own perpetuation. This seminal concept of an autopoiesis is instantiated in life as we know it, but might also be instantiated in different media and in unforeseen ways. Other researchers have argued life is more than autopoiesis and that it is a co-emergent property of autopoiesis and cognition. Life produces many emergent properties such as synchronization and patterns as seen in flocks and herds of different animal species. The mechanics of this synchrony displayed in flocks and herd animals has been extracted by Craig Reynolds into a generative model referred to as "Boids". With these concepts in mind, we address the following research question: How can the synchronous maneuvers and aggregate behaviour of Boids contribute to constitutive subsystems in realizing an autopoietic system? Can such a system exhibit minimal cognition? This work attempts to answer these questions with a bottom-up approach to constructing an artificial life system. We exhibit a computational model of autopoiesis and a minimal level of cognition in the sense of M. Bitbol and P. Luigi Luisi, whereby an autopoietic entity engages in active assimilation of external components as part of its activity of self-production.

Priorities for HIV and chronic pain research: results from a survey of individuals with lived experience.

The Global Task Force on Chronic Pain in HIV published seven research priorities in the field of HIV-associated chronic pain in 2019: (1) causes; (2) management; (3) treatment individualization and integration with addiction treatment; (4) mental and social health factors; (5) prevalence; (6) treatment cost effectiveness; and (7) prevention. The current study used a web-based survey to determine whether the research topics were aligned with the priorities of adults with lived experiences of HIV and chronic pain. We also collected information about respondents' own pain and treatment experiences. We received 311 survey responses from mostly US-based respondents. Most respondents reported longstanding, moderate to severe, multisite pain, commonly accompanied by symptoms of anxiety and/or depression. The median number of pain treatments tried was 10 (IQR = 8, 13), with medications and exercise being the most common modalities, and opioids being viewed as the most helpful. Over 80% of respondents considered all research topics either "extremely important" or "very important". Research topic #2, which focused on optimizing management of pain in people with HIV, was accorded the greatest importance by respondents. These findings suggest good alignment between the priorities of researchers and US-based people with lived experience of HIV-associated chronic pain.

Neighborhood-Level Socioeconomic Status and Prescription Fill Patterns Among Patients With Heart Failure.

Importance: Medication nonadherence is common among patients with heart failure with reduced ejection fraction (HFrEF) and can lead to increased hospitalization and mortality. Patients living in socioeconomically disadvantaged areas may be at greater risk for medication nonadherence due to barriers such as lower access to transportation or pharmacies. Objective: To examine the association between neighborhood-level socioeconomic status (nSES) and medication nonadherence among patients with HFrEF and to assess the mediating roles of access to transportation, walkability, and pharmacy density. Design, Setting, and Participants: This retrospective cohort study was conducted between June 30, 2020, and December 31, 2021, at a large health system based primarily in New York City and surrounding areas. Adult patients with a diagnosis of HF, reduced EF on echocardiogram, and a prescription of at least 1 guideline-directed medical therapy (GDMT) for HFrEF were included. Exposure: Patient addresses were geocoded, and nSES was calculated using the Agency for Healthcare Research and Quality SES index, which combines census-tract level measures of poverty, rent burden, unemployment, crowding, home value, and education, with higher values indicating higher nSES. Main Outcomes and Measures: Medication nonadherence was obtained through linkage of health record prescription data with pharmacy fill data and was defined as proportion of days covered (PDC) of less than 80% over 6 months, averaged across GDMT medications. Results: Among 6247 patients, the mean (SD) age was 73 (14) years, and majority were male (4340 [69.5%]). There were 1011 (16.2%) Black participants, 735 (11.8%) Hispanic/Latinx participants, and 3929 (62.9%) White participants. Patients in lower nSES areas had higher rates of nonadherence, ranging from 51.7% in the lowest quartile (731 of 1086 participants) to 40.0% in the highest quartile (563 of 1086 participants) (P < .001). In adjusted analysis, patients living in the lower 2 nSES quartiles had significantly higher odds of nonadherence when compared with patients living in the highest nSES quartile (quartile 1: odds ratio [OR], 1.57 [95% CI, 1.35-1.83]; quartile 2: OR, 1.35 [95% CI, 1.16-1.56]). No mediation by access to transportation and pharmacy density was found, but a small amount of mediation by neighborhood walkability was observed. Conclusions and Relevance: In this retrospective cohort study of patients with HFrEF, living in a lower nSES area was associated with higher rates of GDMT nonadherence. These findings highlight the importance of considering neighborhood-level disparities when developing approaches to improve medication adherence.

Autonomic Neuropathy is Associated with More Densely Interconnected Cytokine Networks in People with HIV.

The autonomic nervous system (ANS) plays a complex role in the regulation of the immune system, with generally inhibitory effects via activation of ß-adrenergic receptors on immune cells. We hypothesized that HIV-associated autonomic neuropathy (HIV-AN) would result in immune hyperresponsiveness which could be depicted using network analyses. Forty-two adults with well-controlled HIV underwent autonomic testing to yield the Composite Autonomic Severity Score (CASS). The observed range of CASS was 2-5, consistent with normal to moderate HIV-AN. To construct the networks, participants were divided into 4 groups based on the CASS (i.e., 2, 3, 4 or 5). Forty-four blood-based immune markers were included as nodes in all networks and the connections (i.e., edges) between pairs of nodes were determined by their bivariate Spearman's Rank Correlation Coefficient. Four centrality measures (strength, closeness, betweenness and expected influence) were calculated for each node in each network. The median value of each centrality measure across all nodes in each network was calculated as a quantitative representation of network complexity. Graphical representation of the four networks revealed greater complexity with increasing HIV-AN severity. This was confirmed by significant differences in the median value of all four centrality measures across the networks (p ≤ 0.025 for each). Among people with HIV, HIV-AN is associated with stronger and more numerous positive correlations between blood-based immune markers. Findings from this secondary analysis can be used to generate hypotheses for future studies investigating HIV-AN as a mechanism contributing to the chronic immune activation observed in HIV.

Predicting severe disease in patients diagnosed with seasonal influenza in the emergency department.

Objectives: We sought to develop an evidence-based tool to risk stratify patients diagnosed with seasonal influenza in the emergency department (ED). Methods: We performed a single-center retrospective cohort study of all adult patients diagnosed with influenza in a large tertiary care ED between 2008 and 2018. We evaluated demographics, triage vital signs, chest x-ray and laboratory results obtained in the ED. We used univariate and multivariate statistics to examine the composite primary outcome of death or need for intubation. We validated our findings in patients diagnosed between 2018 and 2020. Results: We collected data from 3128 subjects; 2196 in the derivation cohort and 932 in the validation cohort. Medical comorbidities, multifocal opacities or pleural effusion on chest radiography, older age, elevated respiratory rate, hypoxia, elevated blood urea nitrogen, blood glucose, blood lactate, and red blood cell distribution width were factors associated with intubation or death. We developed the Predicting Intubation in seasonal Influenza Patients diagnosed in the ED (PIIPED) risk-stratification tool from these factors. The PIIPED tool predicted intubation or death with an area under the receiver operating characteristic curve (AUC) of 0.899 in the derivation cohort and 0.895 in the validation cohort. A version of the tool including only factors available at ED triage, before laboratory or radiographic evaluation, exhibited AUC of 0.852 in the derivation cohort and 0.823 in the validation cohort. Conclusion: Clinical findings during an ED visit predict severe outcomes in patients with seasonal influenza. The PIIPED risk stratification tool shows promise but requires prospective validation.

Autonomic Neuropathy as a Predictor of Morbidity and Mortality in People Living With HIV: A Retrospective, Longitudinal Cohort Study.

Background and Objectives: HIV-associated autonomic neuropathy (HIV-AN) is common; however, its clinical effect is unclear. Previously, it was shown that the composite autonomic severity score is associated with markers of morbidity such as the Veterans Affair Cohort Study index. In addition, it is known that cardiovascular autonomic neuropathy due to diabetes is associated with poor cardiovascular outcomes. This study aimed to evaluate whether HIV-AN is predictive of important adverse clinical outcomes. Method: The electronic medical records of HIV-infected participants who underwent autonomic function tests at the Mount Sinai Hospital between April 2011 and August 2012 were reviewed. The cohort was stratified into those who had no or mild autonomic neuropathy (HIV-AN [-], CASS ≤3) and those with moderate or severe autonomic neuropathy (HIV-AN [+], CASS >3). The primary outcome was a composite of the incidence of death from any cause, new major cardiovascular or cerebrovascular event, or development of severe renal or hepatic disease. Time-to-event analysis was performed using Kaplan-Meier analysis and multivariate Cox proportional hazards regression models. Results: One hundred eleven of 114 participants had follow-up data (median follow-up for HIV-AN (-) was 94.00 months, and HIV-AN (+) was 81.29 months) and were included in the analysis. Participants were followed until March 1, 2020. The HIV-AN (+) group (N = 42) was significantly associated with the presence of hypertension, higher HIV-1 viral load, and more abnormal liver function. Seventeen (40.48%) events occurred in the HIV-AN (+) group, and 11 (15.94%) occurred in the HIV-AN (-) group. Six (14.29%) cardiac events occurred in the HIV-AN (+) group, whereas 1 (1.45%) occurred in the HIV-AN (-) group. The other subgroups of the composite outcome had a similar trend. The adjusted Cox proportional hazards model showed that the presence of HIV-AN predicted our composite outcome (HR 3.85, CI 1.61-9.20). Discussion: These findings suggest that HIV-AN is associated with the development of severe morbidity and mortality in people living with HIV. People living with HIV with autonomic neuropathy may benefit from closer cardiac, renal, and hepatic surveillance.

Understanding and Addressing Bias in Grading: Progress at Washington University School of Medicine.

In 2020, the authors published work examining disparities in clerkship grading and found students who identify as White were more likely to receive honors grades compared with students from races/ethnicities traditionally underrepresented in medicine. Through a quality improvement approach, the authors identified the following 6 areas where improvements could mitigate grading disparities and, therefore, put processes in place to: ensure equitable access to examination preparation resources, change student assessment, develop medical student curriculum interventions, improve the learning environment, change house staff and faculty recruitment and retention practices, and provide ongoing program evaluation and continuous quality improvement processes to monitor for success. While the authors cannot yet be sure that they have achieved their goal of promoting equity in grading, they believe this evidence-based, multipronged intervention is a clear step in the right direction and encourage other schools to consider a similar approach to tackling this critically important problem at their own institutions.

Autonomic Neuropathy is Associated with More Densely Interconnected Cytokine Networks in People with HIV.

Introduction: The autonomic nervous system (ANS) plays a complex role in the regulation of the immune system, with generally inhibitory effects via activation of ß-adrenergic receptors on immune cells. We hypothesized that HIV-associated autonomic neuropathy (HIV-AN) would result in immune hyperresponsiveness which could be depicted using network analyses. Methods: Forty-two adults with well-controlled HIV underwent autonomic testing to yield the Composite Autonomic Severity Score (CASS). The observed range of CASS was 2-5, consistent with normal to moderate HIV-AN. To construct the networks, participants were divided into 4 groups based on the CASS (i.e., 2, 3, 4 or 5). Forty-four blood-based immune markers were included as nodes in all networks and the connections (i.e., edges) between pairs of nodes were determined by their bivariate Spearman's Rank Correlation Coefficient. Four centrality measures (strength, closeness, betweenness and expected influence) were calculated for each node in each network. The median value of each centrality measure across all nodes in each network was calculated as a quantitative representation of network complexity. Results: Graphical representation of the four networks revealed greater complexity with increasing HIV-AN severity. This was confirmed by significant differences in the median value of all four centrality measures across the networks (p≤0.025 for each). Conclusion: Among people with HIV, HIV-AN is associated with stronger and more numerous positive correlations between blood-based immune markers. Findings from this secondary analysis can be used to generate hypotheses for future studies investigating HIV-AN as a mechanism contributing to the chronic immune activation observed in HIV.

Undue burden: Black faculty, COVID-19, and the racial justice movement.

A crucial reckoning was initiated when the COVID-19 pandemic began to expose and intensify long-standing racial/ethnic health inequities, all while various sectors of society pursued racial justice reform. As a result, there has been a contextual shift towards broader recognition of systemic racism, and not race, as the shared foundational driver of both societal maladies. This confluence of issues is of particular relevance to Black populations disproportionately affected by the pandemic and racial injustice. In response, institutions have initiated diversity, equity, and inclusion (DEI) efforts as a way forward. This article considers how the dual pandemic climate of COVID-19-related health inequities and the racial justice movement could exacerbate the "time and effort tax" on Black faculty to engage in DEI efforts in academia and biomedicine. We discuss the impact of this "tax" on career advancement and well-being, and introduce an operational framework for considering the interconnected influence of systemic racism, the dual pandemics, and DEI work on the experience of Black faculty. If not meaningfully addressed, the "time and effort tax" could contribute to Black and other underrepresented minority faculty leaving academia and biomedicine - consequently, the very diversity, equity, and inclusion work meant to increase representation could decrease it.

Phenotyping autonomic neuropathy using principal component analysis.

To identify autonomic neuropathy (AN) phenotypes, we used principal component analysis on data from participants (N = 209) who underwent standardized autonomic testing including quantitative sudomotor axon reflex testing, and heart rate and blood pressure at rest and during tilt, Valsalva, and standardized deep breathing. The analysis identified seven clusters: 1) normal, 2) hyperadrenergic features without AN, 3) mild AN with hyperadrenergic features, 4) moderate AN, 5) mild AN with hypoadrenergic features, 6) borderline AN with hypoadrenergic features, 7) mild balanced deficits across parasympathetic, sympathetic and sudomotor domains. These findings demonstrate a complex relationship between adrenergic and other aspects of autonomic function.

Climate Change and the Epidemiology of Infectious Diseases in the United States.

The earth is rapidly warming, driven by increasing atmospheric carbon dioxide and other gases that result primarily from fossil fuel combustion. In addition to causing arctic ice melting and extreme weather events, climatologic factors are linked strongly to the transmission of many infectious diseases. Changes in the prevalence of infectious diseases not only reflect the impacts of temperature, humidity, and other weather-related phenomena on pathogens, vectors, and animal hosts but are also part of a complex of social and environmental factors that will be affected by climate change, including land use, migration, and vector control. Vector- and waterborne diseases and coccidioidomycosis are all likely to be affected by a warming planet; there is also potential for climate-driven impacts on emerging infectious diseases and antimicrobial resistance. Additional resources for surveillance and public health activities are urgently needed, as well as systematic education of clinicians on the health impacts of climate change.

A flexible approach for variable selection in large-scale healthcare database studies with missing covariate and outcome data.

BACKGROUND: Prior work has shown that combining bootstrap imputation with tree-based machine learning variable selection methods can provide good performances achievable on fully observed data when covariate and outcome data are missing at random (MAR). This approach however is computationally expensive, especially on large-scale datasets. METHODS: We propose an inference-based method, called RR-BART, which leverages the likelihood-based Bayesian machine learning technique, Bayesian additive regression trees, and uses Rubin's rule to combine the estimates and variances of the variable importance measures on multiply imputed datasets for variable selection in the presence of MAR data. We conduct a representative simulation study to investigate the practical operating characteristics of RR-BART, and compare it with the bootstrap imputation based methods. We further demonstrate the methods via a case study of risk factors for 3-year incidence of metabolic syndrome among middle-aged women using data from the Study of Women's Health Across the Nation (SWAN). RESULTS: The simulation study suggests that even in complex conditions of nonlinearity and nonadditivity with a large percentage of missingness, RR-BART can reasonably recover both prediction and variable selection performances, achievable on the fully observed data. RR-BART provides the best performance that the bootstrap imputation based methods can achieve with the optimal selection threshold value. In addition, RR-BART demonstrates a substantially stronger ability of detecting discrete predictors. Furthermore, RR-BART offers substantial computational savings. When implemented on the SWAN data, RR-BART adds to the literature by selecting a set of predictors that had been less commonly identified as risk factors but had substantial biological justifications. CONCLUSION: The proposed variable selection method for MAR data, RR-BART, offers both computational efficiency and good operating characteristics and is utilitarian in large-scale healthcare database studies.

Interpreting resting heart rate variability in complex populations: the role of autonomic reflexes and comorbidities.

PURPOSE: Resting heart rate variability (HRV) is an important biomarker linking mental health to cardiovascular outcomes. However, resting HRV is also impaired in autonomic neuropathy, a common and underdiagnosed complication of common medical conditions which is detected by testing autonomic reflexes. We sought to describe the relationship between autonomic reflex abnormalities and resting HRV, taking into consideration medical comorbidities and demographic variables. METHODS: Participants (n = 209) underwent a standardized autonomic reflex screen which was summarized as the Composite Autonomic Severity Score (CASS) and included measures of reflexive HRV, e.g., heart rate with deep breathing (HRDB). Resting HRV measures were: pNN50 (percentage of NN intervals that differ by > 50 ms) and cvRMSSD (adjusted root mean square of successive differences). RESULTS: In univariate analyses, lower resting HRV was associated with: older age, higher CASS, neuropathy on examination, hypertension, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, and psychiatric disease. Adaptive regression spline analysis revealed that HRDB explained 27% of the variability in resting HRV for participants with values of HRDB in the normal range. Outside this range, there was no linear relationship because: (1) when HRDB was low (indicating autonomic neuropathy), resting HRV was also low with low variance; and (2) when HRDB was high, the variance in resting HRV was high. In multivariate models, only HRDB was significantly independently associated with cvRMSSD and pNN50. CONCLUSION: Subclinical autonomic neuropathy, as evidenced by low HRDB and other autonomic reflexes, should be considered as a potential confounder of resting HRV in research involving medically and demographically diverse populations.

Disparities in telehealth utilization in patients with pain during COVID-19.

Introduction: The shift from in-person visits to telehealth visits during the COVID-19 pandemic presented unique challenges for patients with pain. Disparities in health care access already existed, and the impact of telehealth on these inequities has not been studied. Objectives: To identify sociodemographic characteristics of patients with pain obtaining care through video, telephone, and in-person visits as social distancing restrictions evolved during the COVID-19 pandemic. Methods: Using our institutional clinical data warehouse, we identified 3314 patients with pain receiving care at a large academic institution in New York City during a baseline period (September 23, 2019-March 22, 2020) and counted telephone, video, and in-person visits during the following conditions: a shutdown period (March 23, 2020-May 23, 2020), when nonessential in-person visits were strictly limited, and a reopening period (May 23, 2020-September 23, 2020), when restrictions were relaxed and in-person visits were available. Patients were categorized into 4 groups based on the technology used to complete a visit: (1) video, (2) telephone, (3) in-person, and (4) no visit. Results: Patients who were older, publicly insured, and identified as Black or Hispanic were overrepresented in the telephone visit group during shutdown and the in-person group during reopening. A video visit during shutdown increased the likelihood of continued video visit use during reopening despite the return of in-person visits. Conclusions: Results show differences in how patients with pain accessed clinical care in a socially distanced world and that flexibility in method of health care delivery may reduce barriers to access. Future research will identify factors (eg, Internet access, digital literacy, provider-patient relationships) driving heterogeneity in telehealth use in patients with pain.

A Systematic Review of the Biological Effects of Cordycepin.

We conducted a systematic review of the literature on the effects of cordycepin on cell survival and proliferation, inflammation, signal transduction and animal models. A total of 1204 publications on cordycepin were found by the cut-off date of 1 February 2021. After application of the exclusion criteria, 791 papers remained. These were read and data on the chosen subjects were extracted. We found 192 papers on the effects of cordycepin on cell survival and proliferation and calculated a median inhibitory concentration (IC50) of 135 µM. Cordycepin consistently repressed cell migration (26 papers) and cellular inflammation (53 papers). Evaluation of 76 papers on signal transduction indicated consistently reduced PI3K/mTOR/AKT and ERK signalling and activation of AMPK. In contrast, the effects of cordycepin on the p38 and Jun kinases were variable, as were the effects on cell cycle arrest (53 papers), suggesting these are cell-specific responses. The examination of 150 animal studies indicated that purified cordycepin has many potential therapeutic effects, including the reduction of tumour growth (37 papers), repression of pain and inflammation (9 papers), protecting brain function (11 papers), improvement of respiratory and cardiac conditions (8 and 19 papers) and amelioration of metabolic disorders (8 papers). Nearly all these data are consistent with cordycepin mediating its therapeutic effects through activating AMPK, inhibiting PI3K/mTOR/AKT and repressing the inflammatory response. We conclude that cordycepin has excellent potential as a lead for drug development, especially for age-related diseases. In addition, we discuss the remaining issues around the mechanism of action, toxicity and biodistribution of cordycepin.

Student Response Initiatives: A Case Study of COVID-19 at Washington University.

The COVID-19 pandemic disrupted medical education worldwide, leading medical students to organize response initiatives. This paper summarizes the Washington University Medical Student COVID-19 Response (WUMS-CR) and shares lessons to guide future initiatives. We used a three-principle framework of community needs assessment, faculty mentorship, and partnership with pre-existing organizations to address needs in St. Louis, including contact tracing and childcare. In total, over 12,000 h were volunteered across 15+ projects. Overall, student response initiatives should use appropriate frameworks to guide projects and should capitalize on volunteer participation, speed and flexibility, and the diversity of student interests and skills for maximal impact.

DAS181 Treatment of Severe Lower Respiratory Tract Parainfluenza Virus Infection in Immunocompromised Patients: A Phase 2 Randomized, Placebo-Controlled Study.

BACKGROUND: There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV. METHODS: Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment. RESULTS: A total of 111 patients were randomized to DAS181 (n = 74) or placebo (n = 37). CSS was achieved by 45.0% DAS181-treated patients in the SO stratum compared with 31.0% for placebo (P = .15), whereas patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with placebo (34.5%) at day 28 (P = .17). In a post hoc analysis of solid organ transplant, hematopoietic cell transplantation within 1 year, or chemotherapy within 1 year, more SO stratum patients achieved RTRA on DAS181 (51.8%) compared with placebo (15.8%) by day 28 (P = .012). CONCLUSIONS: The primary endpoint was not met, but post hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation. Clinical Trials Registration. NCT01644877.

Broad Antibody and Cellular Immune Response From a Phase 2 Clinical Trial With a Novel Multivalent Poxvirus-Based Respiratory Syncytial Virus Vaccine.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in young children and the elderly. Protective immunity is not generated after repeated infections, but vaccination may hopefully prove effective. METHODS: This phase 2 clinical study investigated a multivalent RSV vaccine (MVA-BN-RSV) designed to induce broad antibody and cellular immune responses by encoding RSV surface proteins F, G (for both A and B subtypes), and internal antigens (M2, N). This study evaluated the immune response in adults aged ≥55 years to identify the optimal MVA-BN-RSV dose and vaccination schedule. RESULTS: A single dose increased the levels of neutralizing (plaque reduction neutralization test to RSV A and B) and total (IgG and IgA ELISA) antibodies (1.6 to 3.4-fold increase from baseline) and induced a broad Th1-biased cellular immune response (interferon-γ ELISPOT) to all 5 vaccine inserts (5.4 to 9.7-fold increases). Antibody responses remained above baseline for 6 months. A 12-month booster dose elicited a booster effect in antibody and T-cell responses (up to 2.8-fold from preboost levels). No drug-related serious adverse events were reported. CONCLUSIONS: MVA-BN-RSV induces a broad immune response that persists at least 6 months and can be boosted at 12 months, without significant safety findings. CLINICAL TRIALS REGISTRATION: NCT02873286.

Washington University School of Medicine in St. Louis Case Study: A Process for Understanding and Addressing Bias in Clerkship Grading.

In 2018, in response to a news story featuring the Icahn School of Medicine's decision to eliminate its chapter of Alpha Omega Alpha (AOA) due to perceived racial inequities, students at Washington University School of Medicine in St. Louis (WUSM) brought similar concerns to leadership. WUSM leadership evaluated whether students' race, ethnicity, and gender were associated with their receipt of honors in the 6 core clerkships, key determinants of AOA selection. In preliminary analysis of the school's data, statistically significant racial and ethnic disparities were associated with receipt of honors in each clerkship. Leaders shared these findings with the WUSM community along with a clear message that such discrepancies are unacceptable to the school. An effort to further analyze what lay behind the findings as well as to identify steps to resolve the problem was launched. Using a quality improvement framework, data from focus groups and student surveys were analyzed and 2 overarching themes emerged. Students perceived that both assessment and the learning environment impacted racial/ethnic disparities in clerkship grades. In multivariable logistic regression models, shelf exam scores (a part of student assessment) were found to be associated with receipt of honors in each clerkship; in some (but not all) clerkships, shelf exam scores attenuated the effect of race/ethnicity on receipt of honors, so that when the shelf scores were added to the model, the race/ethnicity effect was no longer significant. This case study describes WUSM's process to understand and address bias in clerkship grading and AOA nomination so that other medical schools might benefit from what has been learned.