Mass Cytometry Defines Virus-Specific CD4 + T Cells in Influenza Vaccination

The antiviral response to influenza virus is complex and multifaceted, involving many immune cell subsets. There is an urgent need to understand the role of CD4+ T cells, which orchestrate an effective antiviral response, to improve vaccine design strategies. In this study, we analyzed PBMCs from human participants immunized with influenza vaccine, using high-dimensional single-cell proteomic immune profiling by mass cytometry. Data were analyzed using a novel clustering algorithm, denoised ragged pruning, to define possible influenza virus-specific clusters of CD4+ T cells. Denoised ragged pruning identified six clusters of cells. Among these, one cluster (Cluster 3) was found to increase in abundance following stimulation with influenza virus peptide ex vivo. A separate cluster (Cluster 4) was found to expand in abundance between days 0 and 7 postvaccination, indicating that it is vaccine responsive. We examined the expression profiles of all six clusters to characterize their lineage, functionality, and possible role in the response to influenza vaccine. Clusters 3 and 4 consisted of effector memory cells, with high CD154 expression. Cluster 3 expressed cytokines like IL-2, IFN-γ, and TNF-α, whereas Cluster 4 expressed IL-17. Interestingly, some participants had low abundance of Clusters 3 and 4, whereas others had higher abundance of one of these clusters compared with the other. Taken together, we present an approach for identifying novel influenza virus-reactive CD4+ T cell subsets, a method that could help advance understanding of the immune response to influenza, predict responsiveness to vaccines, and aid in better vaccine design

A general look at the history of geography education in the United States

This paper presents an overview of the history of geography education in the United States as well as attempts to uncover the vague history of its progress. In this article, therefore, the reform movements of geography as a school subject were thoroughly examined. In this study, especially upon the recognition of geography as one of the core subjects in the school curricula in Goals 2000 in addition to the development of National Geography Standards, the true renaissance of geography education in the United States was brought up and due to these reform movements how geography as a school subject experienced a shift in its pedagogy from the “old” to the “new” geography was investigated

437. Asymptomatic Healthcare Worker COVID-19 Testing Program

Abstract Background The SARS-CoV-2 pandemic remains a major threat worldwide. Healthcare workers (HCWs) are particularly impacted by the COVID-19 pandemic with high infection rates reported from HCWs in hard-hit regions2,3, raising concerns about nosocomial infections and the effectiveness of personal protective equipment in protecting HCWs. Asymptomatic infection is estimated 17.9% to 33.3%4 and is a common source of transmission5. We designed a HCW testing program to address patient and employee concerns about exposures in the healthcare setting at our 808-bed health system. During the time of employee testing, the mean (range) number of inpatients with a diagnosis of COVID was 30 (22–38) of a mean (range) daily census of 560 (492–602) (approximately 5.4%). Methods This opt-in program offered SARS-CoV-2 testing of asymptomatic HCWs with paired nasopharyngeal or mid-turbinate swab for PCR (Roche) and serum IgG antibody testing (Diazyme). While initially designed as a pilot project in the Emergency Departments and COVID-19 units, it was quickly expanded to a health system-wide initiative. Results From April 22 to June 2, PCR testing was performed on 5826 asymptomatic HCWs with four PCR tests resulting positive (0.09%). Of 5589 serologic tests (anti-SARS-CoV-2 IgG) performed, 57 tested positive (1.02 %). All HCW with a positive IgG had a concurrent negative PCR. Conclusion In this cross-sectional evaluation, the point prevalence of SARS-CoV-2 IgG in asymptomatic HCWs at UC San Diego was less than 1%, supporting modeling estimations at the San Diego County level of very low levels of community exposure at the time of this testing. Further analyses of incidence rates and potential risk factors such as employee roles within the healthcare system, community and healthcare exposures, and home zip code are underway. Asymptomatic HCW testing is a strategy that can provide the perception of additional safety to both the workforce and patients as the health system reopens, while potentially reduce transmission from asymptomatic persons through active case finding and isolation. Disclosures Randy Taplitz, MD, Merck (Advisor or Review Panel member

The integration of real and virtual magnetic resonance imaging experiments in a single instrument

We present the design of an integrated system for performing both real and virtual (simulated) magnetic resonance imaging (MRI) experiments. We emphasize the approaches used to maximize the level of integration and also the benefits that tight real-virtual integration brings for a scientific instrument. The system has been implemented for both low field (0.2 T) and high field (9.4 T) imaging systems. The simulations can run for any MRI experiment and we demonstrate the operation of the system for T1, T2, T2 17, and diffusion contrasts.Peer reviewed: YesNRC publication: Ye

Association of time to craniectomy with survival in patients with severe combat-related brain injury

OBJECTIVE In combat and austere environments, evacuation to a location with neurosurgery capability is challenging. A planning target in terms of time to neurosurgery is paramount to inform prepositioning of neurosurgical and transport resources to support a population at risk. This study sought to examine the association of wait time to craniectomy with mortality in patients with severe combat-related brain injury who received decompressive craniectomy. METHODS Patients with combat-related brain injury sustained between 2005 and 2015 who underwent craniectomy at deployed surgical facilities were identified from the Department of Defense Trauma Registry and Joint Trauma System Role 2 Registry. Eligible patients survived transport to a hospital capable of diagnosing the need for craniectomy and performing surgery. Statistical analyses included unadjusted comparisons of postoperative mortality by elapsed time from injury to start of craniectomy, and Cox proportional hazards modeling adjusting for potential confounders. Time from injury to craniectomy was divided into quintiles, and explored in Cox models as a binary variable comparing early versus delayed craniectomy with cutoffs determined by the maximum value of each quintile (quintile 1 vs 2-5, quintiles 1-2 vs 3-5, etc.). Covariates included location of the facility at which the craniectomy was performed (limited-resource role 2 facility vs neurosurgically capable role 3 facility), use of head CT scan, US military status, age, head Abbreviated Injury Scale score, Injury Severity Score, and injury year. To reduce immortal time bias, time from injury to hospital arrival was included as a covariate, entry into the survival analysis cohort was defined as hospital arrival time, and early versus delayed craniectomy was modeled as a time-dependent covariate. Follow-up for survival ended at death, hospital discharge, or hospital day 16, whichever occurred first. RESULTS Of 486 patients identified as having undergone craniectomy, 213 (44%) had complete date/time values. Unadjusted postoperative mortality was 23% for quintile 1 (n = 43, time from injury to start of craniectomy 30-152 minutes); 7% for quintile 2 (n = 42, 154-210 minutes); 7% for quintile 3 (n = 43, 212-320 minutes); 19% for quintile 4 (n = 42, 325-639 minutes); and 14% for quintile 5 (n = 43, 665-3885 minutes). In Cox models adjusted for potential confounders and immortal time bias, postoperative mortality was significantly lower when time to craniectomy was within 5.33 hours of injury (quintiles 1-3) relative to longer delays (quintiles 4-5), with an adjusted hazard ratio of 0.28, 95% CI 0.10-0.76 (p = 0.012). CONCLUSIONS Postoperative mortality was significantly lower when craniectomy was initiated within 5.33 hours of injury. Further research to optimize craniectomy timing and mitigate delays is needed. Functional outcomes should also be evaluated

<em>In Vivo</em> Open-Bore MRI Reveals Region- and Sub-Arc-Specific Lengthening of the Unloaded Human Posterior Cruciate Ligament

<div><p>Open-bore MRI scanners allow joint soft tissue to be imaged over a large, uninterrupted range of flexion. Using an open-bore scanner, 3D para-sagittal images of the posterior cruciate ligament (PCL) were collected from seven healthy subjects in unloaded, recumbent knee extension and flexion. PCL length was measured from one 2D MRI slice partition per flexion angle, per subject. The anterior surface of the PCL lengthened significantly between extension and flexion (<em>p</em><0.001). Conversely, the posterior surface did not. Changes were not due to the PCL moving relative to the 2D slice partition; measurements made from 3D reconstructions, which compensated for PCL movement, did not differ significantly from measurements made from 2D slice partitions. In a second experiment, videos of knee flexion were made by imaging two subjects at several flexion angles. Videos allowed soft tissue tracking; examples are included. In a third experiment, unloaded knees of seven healthy, recumbent subjects were imaged at extension and at 40°, 70°, 90°, 100°, 110° and 120° flexion. The distance between PCL attachments increased between extension and 100°, and then decreased (<em>p</em><0.001). The anterior surface of the PCL lengthened over the flexion angles measured (<em>p</em><0.01). The posterior surface of the PCL lengthened between extension and 40° and then shortened (<em>p</em><0.001). Both attachment separation and anterior surface length increased dramatically between extension and 40°, but varied less afterwards. Results indicate that PCL dynamics differ between terminal extension and active function sub-arcs. Also, attachment separation cannot predict the lengthening of all parts of the PCL, nor can lengthening of one part of the PCL predict the lengthening of another part. A potential connection between lengthening and loading is discussed. We conclude that low-field MRI can assess ligament lengthening during flexion, and that the dynamics of the PCL for any given region and sub-arc should be measured directly.</p> </div

Diagnosis of pseudoprogression using MRI perfusion in patients with glioblastoma multiforme may predict improved survival

AIMS: This retrospective study determined the survival of glioblastoma patients with or without pseudoprogression. METHODS: A total of 68 patients were included. Overall survival was compared between patients showing pseudoprogression (in most cases diagnosed using perfusion MRI with ferumoxytol) and in patients without pseudoprogession. MGMT methylation status was also analyzed in the pseudoprogression cases. RESULTS: Median survival in 24 (35.3%) patients with pseudoprogression was 34.7 months (95% CI: 20.3–54.1), and 13.4 months (95% CI: 11.1–19.5) in 44 (64.7%) patients without pseudoprogression (p < 0.0001). The longest survival was a median of 54.1 months in patients with combination of pseudoprogression and (MGMT) promoter methylation. CONCLUSION: Pseudoprogression is associated with better outcome, especially if concurring with MGMT promoter methylation. Patients never diagnosed with pseudoprogression had poor survival. This study emphasizes the importance of differentiating tumor progression and pseudoprogression using perfusion MRI

The length of the PCL measured from 2D slice partitions and 3D reconstructions.

*<p><i>p</i><0.001 compared to “Anterior surface – Extended” of same measurement technique.</p>+<p>Not significantly different from “Posterior surface – Extended” of same measurement technique (<i>p</i> = 0.28 for 2D slice partition comparison; <i>p</i> = 0.19 for 3D reconstruction comparison).</p