Search

Introduction: Arguments over the appropriate Crisis Standards of Care (CSC) for public health emergencies often assume that there is a tradeoff between saving the most lives, saving the most life-years, and preventing racial disparities. However, these assumptions have rarely been explored empirically. To quantitatively characterize possible ethical tradeoffs, we aimed to simulate the implementation of five proposed CSC protocols for rationing ventilators in the context of the COVID-19 pandemic. Methods: A Monte Carlo simulation was used to estimate the number of lives saved and life-years saved by implementing clinical acuity-, comorbidity- and age-based CSC protocols under different shortage conditions. This model was populated with patient data from 3707 adult admissions requiring ventilator support in a New York hospital system between April 2020 and May 2021. To estimate lives and life-years saved by each protocol, we determined survival to discharge and estimated remaining life expectancy for each admission. Results: The simulation demonstrated stronger performance for age-sensitive protocols. For a capacity of 1 bed per 2 patients, ranking by age bands saves approximately 29 lives and 3400 life-years per thousand patients. Proposed protocols from New York and Maryland which allocated without considering age saved the fewest lives (~13.2 and 8.5 lives) and life-years (~416 and 420 years). Unlike other protocols, the New York and Maryland algorithms did not generate significant disparities in lives saved and life-years saved between White non-Hispanic, Black non-Hispanic, and Hispanic sub-populations. For all protocols, we observed a positive correlation between lives saved and life-years saved, but also between lives saved overall and inequality in the number of lives saved in different race and ethnicity sub-populations. Conclusion: While there is significant variance in the number of lives saved and life-years saved, we did not find a tradeoff between saving the most lives and saving the most life-years. Moreover, concerns about racial discrimination in triage protocols require thinking carefully about the tradeoff between enforcing equality of survival rates and maximizing the lives saved in each sub-population. [ABSTRACT FROM AUTHOR]

While animal model studies have extensively defined the mechanisms controlling cell diversity in the developing mammalian lung, there exists a significant knowledge gap with regards to late-stage human lung development. The NHLBI Molecular Atlas of Lung Development Program (LungMAP) seeks to fill this gap by creating a structural, cellular and molecular atlas of the human and mouse lung. Transcriptomic profiling at the single-cell level created a cellular atlas of newborn human lungs. Frozen single-cell isolates obtained from two newborn human lungs from the LungMAP Human Tissue Core Biorepository, were captured, and library preparation was completed on the Chromium 10X system. Data was analyzed in Seurat, and cellular annotation was performed using the ToppGene functional analysis tool. Transcriptional interrogation of 5500 newborn human lung cells identified distinct clusters representing multiple populations of epithelial, endothelial, fibroblasts, pericytes, smooth muscle, immune cells and their gene signatures. Computational integration of data from newborn human cells and with 32,000 cells from postnatal days 1 through 10 mouse lungs generated by the LungMAP Cincinnati Research Center facilitated the identification of distinct cellular lineages among all the major cell types. Integration of the newborn human and mouse cellular transcriptomes also demonstrated cell type-specific differences in maturation states of newborn human lung cells. Specifically, newborn human lung matrix fibroblasts could be separated into those representative of younger cells (n = 393), or older cells (n = 158). Cells with each molecular profile were spatially resolved within newborn human lung tissue. This is the first comprehensive molecular map of the cellular landscape of neonatal human lung, including biomarkers for cells at distinct states of maturity. [ABSTRACT FROM AUTHOR]

The dose-related safety, immunogenicity, and protective efficacy of an experimental trivalent influenza virus hemagglutinin (rHAO) vaccine produced in insect cells were determined using recombinant baculoviruses. The findings suggested that it is possible to generate a substantial amount of protection in an immunologically primed population against influenza with a pure hemagglutinin vaccine, even in the presence of significant antigenic drift.

Introduction: In clinical and translational research, data science is often and fortuitously integrated with data collection. This contrasts to the typical position of data scientists in other settings, where they are isolated from data collectors. Because of this, effective use of data science techniques to resolve translational questions requires innovation in the organization and management of these data. Methods: We propose an operational framework that respects this important difference in how research teams are organized. To maximize the accuracy and speed of the clinical and translational data science enterprise under this framework, we define a set of eight best practices for data management. Results: In our own work at the University of Rochester, we have strived to utilize these practices in a customized version of the open source LabKey platform for integrated data management and collaboration. We have applied this platform to cohorts that longitudinally track multidomain data from over 3000 subjects. Conclusions: We argue that this has made analytical datasets more readily available and lowered the bar to interdisciplinary collaboration, enabling a team-based data science that is unique to the clinical and translational setting. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is a leading cause of infant respiratory disease. Infant airway microbiota has been associated with respiratory disease risk and severity. The extent to which interactions between RSV and microbiota occur in the airway, and their impact on respiratory disease susceptibility and severity, are unknown.Methods: We carried out 16S rRNA microbiota profiling of infants in the first year of life from (1) a cross-sectional cohort of 89 RSV-infected infants sampled during illness and 102 matched healthy controls, and (2) a matched longitudinal cohort of 12 infants who developed RSV infection and 12 who did not, sampled before, during, and after infection.Results: We identified 12 taxa significantly associated with RSV infection. All 12 taxa were differentially abundant during infection, with 8 associated with disease severity. Nasal microbiota composition was more discriminative of healthy vs infected than of disease severity.Conclusions: Our findings elucidate the chronology of nasal microbiota dysbiosis and suggest an altered developmental trajectory associated with RSV infection. Microbial temporal dynamics reveal indicators of disease risk, correlates of illness and severity, and impact of RSV infection on microbiota composition. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants. The causes and correlates of severe illness in the majority of infants are poorly defined.Methods: We recruited a cohort of RSV-infected infants and simultaneously assayed the molecular status of their airways and the presence of airway microbiota. We used rigorous statistical approaches to identify gene expression patterns associated with disease severity and microbiota composition, separately and in combination.Results: We measured comprehensive airway gene expression patterns in 106 infants with primary RSV infection. We identified an airway gene expression signature of severe illness dominated by excessive chemokine expression. We also found an association between Haemophilus influenzae, disease severity, and airway lymphocyte accumulation. Exploring the time of onset of clinical symptoms revealed acute activation of interferon signaling following RSV infection in infants with mild or moderate illness, which was absent in subjects with severe illness.Conclusions: Our data reveal that airway gene expression patterns distinguish mild/moderate from severe illness. Furthermore, our data identify biomarkers that may be therapeutic targets or useful for measuring efficacy of intervention responses. [ABSTRACT FROM AUTHOR]