SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.

SARS-CoV-2 mRNA vaccination in healthy individuals generates effective immune protection against COVID-19. Little is known, however, about the SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses in patients with multiple sclerosis on anti-CD20 (MS-aCD20) monotherapy following SARS-CoV-2 mRNA vaccination. Treatment with aCD20 significantly reduced Spike and RBD specific antibody and memory B cell responses in most patients, an effect that was ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. In contrast, all MS-aCD20 patients generated antigen-specific CD4 and CD8 T-cell responses following vaccination. However, treatment with aCD20 skewed these responses compromising circulating Tfh responses and augmenting CD8 T cell induction, while largely preserving Th1 priming. These data also revealed underlying features of coordinated immune responses following mRNA vaccination. Specifically, the MS-aCD20 patients who failed to generate anti-RBD IgG had the most severe defect in cTfh cell responses and more robust CD8 T cell responses compared to those who generated anti-RBD IgG, whose T cell responses were more similar to healthy controls. These data define the nature of SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients, and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making, patient education and public health policy for patients treated with aCD20 and other immunosuppressed patients.

Automatic camera systems produce very basic animations for virtual worlds. Users often view environments through two types of cameras: a camera that they control manually, or a very basic automatic camera that follows their character, minimizing occlusions. Real cinematography features much more variety producing more robust stories. Cameras shoot establishing shots, close-ups, tracking shots, and bird's eye views to enrich a narrative. Camera techniques such as zoom, focus, and depth of field contribute to framing a particular shot. We present an intelligent camera system that automatically positions, pans, tilts, zooms, and tracks events occurring in real-time while obeying traditional standards of cinematography. We design behavior trees that describe how a single intelligent camera might behave from low-level narrative elements assigned by "smart events". Camera actions are formed by hierarchically arranging behavior sub-trees encapsulating nodes that control specific camera semantics. This approach is more modular and particularly reusable for quickly creating complex camera styles and transitions rather then focusing only on visibility. Additionally, our user interface allows a director to provide further camera instructions, such as prioritizing one event over another, drawing a path for the camera to follow, and adjusting camera settings on the fly.We demonstrate our method by placing multiple intelligent cameras in a complicated world with several events and storylines, and illustrate how to produce a well-shot "documentary" of the events constructed in real-time. Disciplines

Background: Intraoperative imaging must supply data that can be used for accurate stereotactic navigation. This information should be at least as accurate as that acquired from diagnostic imagers. Objectives: The aim of this study was to compare the stereotactic accuracy of an updated compact intraoperative MRI (iMRI) device based on a 0.15-T magnet to standard surgical navigation on a 1.5-T diagnostic scan MRI and to navigation with an earlier model of the same system. Methods: The accuracy of each system was assessed using a water-filled phantom model of the brain. Data collected with the new system were compared to those obtained in a previous study assessing the older system. The accuracy of the new iMRI was measured against standard surgical navigation on a 1.5-T MRI using T1-weighted (W) images. Results: The mean error with the iMRI using T1W images was lower than that based on images from the 1.5-T scan (1.24 vs. 2.43 mm). T2W images from the newer iMRI yielded a lower navigation error than those acquired with the prior model (1.28 vs. 3.15 mm). Conclusions: Improvements in magnet design can yield progressive increases in accuracy, validating the concept of compact, low-field iMRI. Avoiding the need for registration between image and surgical space increases navigation accuracy.

OBJECTIVES/GOALS: The objective of this study was to use NIH RePORTER (Research Portfolio Online Reporting Tools) to analyze K99 funding trends and determine if R00 to R01 or R21 achievement time correlates with the future success of an early-stage NIH-funded investigator. METHODS/STUDY POPULATION: All award data were collected from NIH RePORTER. All K99 awards and funding data in this study were limited to All Clinical Departments (ACD). All researchers (n = 1,148) and awards (n = 2,022) were identified through a K99 search from FY 2007 to FY 2022 across ACD. Historic trends in K99 awards and funding from NIH Fiscal Year (FY) 2007 to FY 2022 were investigated. An R00 dataset was generated from NIH RePORTER. The K99 to R00 achievement statistics from FY 2007 to FY 2022 was investigated. NIH annual datafiles for FY 2007 to FY 2021 were aggregated to generate a master datafile of all R01 (n = 395,505) and R21 awards (n = 61,766). R01 and R21 award data were linked to the researcher previously identified through the K99 search. The connection between K99/R00 awardees and subsequent R01 or R21 awards was focused on. RESULTS/ANTICIPATED RESULTS: From FY 2008 to FY 2022, the number of K99 awards per year increased 123.4%, from 94 to 210. Over the same period, after correcting for inflation, the NIH K99 budget increased 127.0% while the NIH program level budget increased 17.3%. For researchers who achieved their first R01 or R21 0–3 years versus 3–6 years after the start of their R00, their average funding per year since the start of the R00 phase was $467,425 versus $290,604, respectively (p < 0.001). In summary, NIH investment in the K99 award pathway has substantially outpaced the NIH program level budget increase, and there is a strong relationship between average funding per year since the start of the R00 phase and time from R00 to R01 or R21. DISCUSSION/SIGNIFICANCE: Our study offers additional evidence of the Matthew effect in science, where previous success generates future success. This analysis may be useful to clinical departments as they evaluate selecting new and retaining current biomedical scientists for independent research positions.