Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Rapidly tuned buncher structure for the Los Alamos Proton Storage Ring (PSR)

In the PSR's short-bunch operating mode, accumulated beam currents are intense and change rapidly. The resonant frequency of the 503.125-MHz buncher used in this mode must be rapidly adjusted through a 100-kHz range to maintain the correct 90/sup 0/ phase relation between cavity voltage and beam current. Modulation rates are up to 3 kHz/..mu..s. Each structure consists of two side-coupled buncher cavities, resonantly coupled to a ferrite-loaded tuner cavity. The needed frequency change ..delta..f in the buncher cells is produced by a 50 x ..delta..f change in the tuner, accomplished by varying a magnetic field applied to the ferrite perpendicular to the rf magnetic field. Fast modulation of this bias is provided by a low-inductance ferrite-core magnet excited by a special function generator. The resonantly coupled multicavity structure configuration allows buncher and tuner cells to be independently optimized for their specific functions. This paper describes the buncher design, ferrite selection, and test results from a prototype ferrite-loaded tuner cavity. The tests have demonstrated the tuning scheme's feasibility, showing that the necessary 5-MHz range can be attained with only 12% of the tuner cell filled with ferrite, and that losses in the ferrite are small throughout this frequency interval

Fabrication and cold test of photonic band gap resonators and accelerator structures

We present the detailed description of the successful design and cold test of photonic band gap (PBG) resonators and traveling-wave accelerator structures. Those tests provided the essential basis for later hot test demonstration of the first PBG accelerator structure at 17.140 GHz [E. I. Smirnova, A. S. Kesar, I. Mastovsky, M. A. Shapiro, and R. J. Temkin, Phys. Rev. Lett., 95, 074801 (2005).PRLTAO0031-900710.1103/PhysRevLett.95.074801]. The advantage of PBG resonators is that they were built to support only the main, TM_{01}-like, accelerator mode while not confining the higher-order modes (HOM) or wakefields. The design of the PBG resonators was based on a triangular lattice of rods, with a missing rod at the center. Following theoretical analysis, the rod radius divided by the rod spacing was held to a value of about 0.15 to avoid supporting HOM. For a single-cell test the PBG structure was fabricated in X-band (11 GHz) and brazed. The mode spectrum and Q factor (Q=5 000) agreed well with theory. Excellent HOM suppression was evident from the cold test. A six-cell copper PBG accelerator traveling-wave structure with reduced long-range wakefields was designed and was built by electroforming at Ku-band (17.140 GHz). The structure was tuned by etching the rods. Cold test of the structure yielded excellent agreement with the theoretical design. Successful results of the hot test of the structure demonstrating the acceleration of the electron beam were published in E. I. Smirnova, A. S. Kesar, I. Mastovsky, M. A. Shapiro, and R. J. Temkin, Phys. Rev. Lett., 95, 074801 (2005).PRLTAO0031-900710.1103/PhysRevLett.95.07480

High-heat flux testing of an interceptive device for an intense proton beam

An interceptive device referred to here as a scraper has been designed and tested for use in a diagnostic device [1]. The scraper will be used to probe a proton beam in order to detect the formation of beam halo [2]. Probing the proton beam exposes the scraper to high heat fluxes on the order of 610 kW/cm{sup 2}. The high-heat flux exposure is cyclic since the beam is probed while in pulsed mode. In order to test the design repetitive high-heat flux testing has been performed on a prototype design of the scraper. This paper describes the design, analysis, and testing of the scraper

Defective Associations between Blood Vessels and Brain Parenchyma Lead to Cerebral Hemorrhage in Mice Lacking αv Integrins

Mouse embryos genetically null for the αv integrin subunit develop intracerebral hemorrhages at midgestation and die shortly after birth. A key question is whether the hemorrhage arises from primary defects in vascular endothelial cells or pericytes or from other causes. We have previously reported normal initiation of cerebral vessels comprising branched tubes of endothelial cells. Here we show that the onset of hemorrhage is not due to defects in pericyte recruitment. Additionally, most αv-null vessels display ultrastructurally normal endothelium-pericyte associations and normal interendothelial cell junctions. Thus, endothelial cells and pericytes appear to establish their normal relationships in cerebral microvessels. However, by both light and electron microscopy, we detected defective associations between cerebral microvessels and the surrounding brain parenchyma, composed of neuroepithelial cells, glia, and neuronal precursors. These data suggest a novel role for αv integrins in the association between cerebral microvessels and central nervous system parenchymal cells