Low-Intrusion Techniques and Sensitive Information Management for Warhead Counting and Verification: FY2012 Annual Report

Progress in the second year of this project is described by the series of technical reports and manuscripts that make up the content of this report. These documents summarize successes in our goals to develop our robust image-hash templating and material-discrimination techniques and apply them to test image data

Imaging for dismantlement verification: information management and analysis algorithms

The level of detail discernible in imaging techniques has generally excluded them from consideration as verification tools in inspection regimes. An image will almost certainly contain highly sensitive information, and storing a comparison image will almost certainly violate a cardinal principle of information barriers: that no sensitive information be stored in the system. To overcome this problem, some features of the image might be reduced to a few parameters suitable for definition as an attribute. However, this process must be performed with care. Computing the perimeter, area, and intensity of an object, for example, might reveal sensitive information relating to shape, size, and material composition. This paper presents three analysis algorithms that reduce full image information to non-sensitive feature information. Ultimately, the algorithms are intended to provide only a yes/no response verifying the presence of features in the image. We evaluate the algorithms on both their technical performance in image analysis, and their application with and without an explicitly constructed information barrier. The underlying images can be highly detailed, since they are dynamically generated behind the information barrier. We consider the use of active (conventional) radiography alone and in tandem with passive (auto) radiography

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Low-Intrusion Techniques and Sensitive Information Management for Warhead Counting and Verification: FY2012 Annual Report

Progress in the second year of this project is described by the series of technical reports and manuscripts that make up the content of this report. These documents summarize successes in our goals to develop our robust image-hash templating and material-discrimination techniques and apply them to test image data

Imaging for dismantlement verification: information management and analysis algorithms

The level of detail discernible in imaging techniques has generally excluded them from consideration as verification tools in inspection regimes. An image will almost certainly contain highly sensitive information, and storing a comparison image will almost certainly violate a cardinal principle of information barriers: that no sensitive information be stored in the system. To overcome this problem, some features of the image might be reduced to a few parameters suitable for definition as an attribute. However, this process must be performed with care. Computing the perimeter, area, and intensity of an object, for example, might reveal sensitive information relating to shape, size, and material composition. This paper presents three analysis algorithms that reduce full image information to non-sensitive feature information. Ultimately, the algorithms are intended to provide only a yes/no response verifying the presence of features in the image. We evaluate the algorithms on both their technical performance in image analysis, and their application with and without an explicitly constructed information barrier. The underlying images can be highly detailed, since they are dynamically generated behind the information barrier. We consider the use of active (conventional) radiography alone and in tandem with passive (auto) radiography

Spreader-Bar Radiation Detection System Enhancements: A Modeling and Simulation Study

This report provides the modeling and simulation results of the investigation of enhanced spreader bar radiation detection systems