Moored current meter, AVHRR, CTD, and drifter data from the Agulhas Current and Retroflexion region (1985-1987) Volume XLII

Stored in the Archives of the Woods Hole Oceanographic Institution is the floppy disk on which can be found the one-day average currents, the path of the Agulhas Current, CTD stations in "Live Atlas" format, SST frontal analyses (Chassignet and Olson, personal communcation) as well as programs written in QuickBASIC which allow one to access and display these observations. The programs are stored in ASCII and can be run under the Microsoft QuickBasic (Version 4.0 or higher). Instructions for running the programs can be found in a file entitled "read.me" on the disk.Data are presented from an experiment designed to explore the spatial and temporal structure of the Agulhas Current and Retroflexion by direct means. Included are the current meter results from 10 moorings in the Retroflexion region, CTD stations occupied on the deployment cruise in 1985, data from satellite tracked (ARGOS) freely during surface buoys and numerous images of the sea surface temperature.Funding was provided by the Office of Naval Research through Contract Nos. NOOO14-84C-O134, NOO014-85-C-0001, and NOOO14-87-K-0007

Satellite image processing for the Agulhas Retroflexion region

In order to analyze the Advanced Very High Resolution Radiometer satellite data from South Africa, a software package has been written. Methodology and algorithms are described which create geometrically corrected registered satellite images over the Agulhas Retroflexion region. Also discussed are programs to overlay latitude and longitude lines, ship tracks, and ancillary data. A method of masking the land and compositing images for cloud removal is also described.Funding was provided by the Office of Naval Research under contract Numbers N00014-82-C-0019, NR 083-004, N00014-85-C-001, NR 083-004, and N00014-87-K-0007, NR 083-004

Final Report for ''Client Server Software for the National Transport Code Collaboration''

OAK-B135 Tech-X Corporation designed and developed all the networking code tying together the NTCC data server with the data client and the physics server with the data server and physics client. We were also solely responsible for the data and physics clients and the vast majority of the work on the data server. We also performed a number of other tasks

Risk Informed Assessment of Regulatory and Design Requirements for Future Nuclear Power Plants (Cooperative Agreement DE-FC03-99SF21902, Am. M004) Final Technical Report

OAK-B135 Research under this project addresses the barriers to long term use of nuclear-generated electricity in the United States. It was agreed that a very basic and significant change to the current method of design and regulation was needed. That is, it was believed that the cost reduction goal could not be met by fixing the current system (i.e., an evolutionary approach) and a new, more advanced approach for this project would be needed. It is believed that a completely new design and regulatory process would have to be developed--a ''clean sheet of paper'' approach. This new approach would start with risk-based methods, would establish probabilistic design criteria, and would implement defense-in-depth only when necessary (1) to meet public policy issues (e.g., use of a containment building no matter how low the probability of a large release is) and (2) to address uncertainties in probabilistic methods and equipment performance. This new approach is significantly different from the Nuclear Regulatory Commission's (NRC) current risk-informed program for operating plants. For our new approach, risk-based methods are the primary means for assuring plant safety, whereas in the NRC's current approach, defense-in-depth remains the primary means of assuring safety. The primary accomplishments in the first year--Phase 1 were (1) the establishment of a new, highly risk-informed design and regulatory framework, (2) the establishment of the preliminary version of the new, highly risk-informed design process, (3) core damage frequency predictions showing that, based on new, lower pipe rupture probabilities, the design of the emergency core cooling system equipment can be simplified without reducing plant safety, and (4) the initial development of methods for including uncertainties in a new integrated structures-systems design model. Under the new regulatory framework, options for the use of ''design basis accidents'' were evaluated. It is expected that design basis accidents would be an inherent part of the Probabilistic Safety Assessment for the plant and their evaluation would be probabilistic. Other first year accomplishments include (1) the conversion of an NRC database for cross-referencing NRC criteria and industry codes and standards to Microsoft 2000 software, (2) an assessment of the NRC's hearing process which concluded that the normal cross-examination during public hearings is not actually required by the U.S. Administrative Procedures Act, (3) the identification and listing of reliability data sources, and (4) interfacing with other industry groups (e.g., NEI and IAEA) and NRC at workshops for risk-informing regulations. The major accomplishments during the second year consisted of (1) issuance of the final report for Subtask 1.1, ''Identify Current Applicable Regulatory Requirements [and Industry Standards],'' (2) issuance of the final report for Subtask 1.2,'' Identify Structures, Systems, and Components and Their Associate d Costs for a Typical Plant,'' (3) extension of the new, highly risk-informed design and regulatory framework to non-light-water-reactor technology, (4) completion of more detailed thermal-hydraulic and probabilistic analyses of advanced conceptual reactor system/component designs, (6) initial evaluation and recommendations for improvement of the NRC design review process, and (7) initial development of the software format, procedures and statistical routines needed to store, analyze and retrieve the available reliability data. Final reports for Subtasks 1.1 (regulatory and design criteria) and 1.2 (costs for structures, systems, and components) were prepared and issued. A final report for Subtask 1.3 (Regulatory Framework) was drafted with the aim to issue it in Phase 3 (Year 3). One technical report was produced for Subtask 1.4 (methods development) and two technical reports were produced for Subtask 1.6 (sample problem analysis). An interim report on the NRC design review process (Subtask 1.7) was prepared and issued. Finally, a report on Subtask 2.2 (database weaknesses) addressed the initial development of a new database to track reliability data. During the third and final year (Phase 3), work was completed on Subtasks 1.3 (regulatory framework), 1.6 (sample problem analysis), Subtask 1.7 (regulatory analysis), Subtask 1.8 (industry and NRC coordination), and Subtask 2.3 (reliability data improvements)

Robust humoral and cellular recall responses to AZD1222 attenuate breakthrough SARS-CoV-2 infection compared to unvaccinated

Background: Breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in coronavirus disease 2019 (COVID-19) vaccinees typically produces milder disease than infection in unvaccinated individuals. Methods: To explore disease attenuation, we examined COVID-19 symptom burden and immuno-virologic responses to symptomatic SARS-CoV-2 infection in participants (AZD1222: n=177/17,617; placebo: n=203/8,528) from a 2:1 randomized, placebo-controlled, phase 3 study of two-dose primary series AZD1222 (ChAdOx1 nCoV-19) vaccination (NCT04516746). Results: We observed that AZD1222 vaccinees had an overall lower incidence and shorter duration of COVID-19 symptoms compared with placebo recipients, as well as lower SARS-CoV-2 viral loads and a shorter median duration of viral shedding in saliva. Vaccinees demonstrated a robust antibody recall response versus placebo recipients with low-to-moderate inverse correlations with virologic endpoints. Vaccinees also demonstrated an enriched polyfunctional spike-specific Th-1-biased CD4+ and CD8+ T-cell response that was associated with strong inverse correlations with virologic endpoints. Conclusion: Robust immune responses following AZD1222 vaccination attenuate COVID-19 disease severity and restrict SARS-CoV-2 transmission potential by reducing viral loads and the duration of viral shedding in saliva. Collectively, these analyses underscore the essential role of vaccination in mitigating the COVID-19 pandemic

Phase I Safety, Pharmacokinetics, and Pharmacogenetics Study of the Antituberculosis Drug PA-824 with Concomitant Lopinavir-Ritonavir, Efavirenz, or Rifampin

There is an urgent need for new antituberculosis (anti-TB) drugs, including agents that are safe and effective with concomitant antiretrovirals (ARV) and first-line TB drugs. PA-824 is a novel antituberculosis nitroimidazole in late-phase clinical development. Cytochrome P450 (CYP) 3A, which can be induced or inhibited by ARV and antituberculosis drugs, is a minor (∼20%) metabolic pathway for PA-824. In a phase I clinical trial, we characterized interactions between PA-824 and efavirenz (arm 1), lopinavir/ritonavir (arm 2), and rifampin (arm 3) in healthy, HIV-uninfected volunteers without TB disease. Participants in arms 1 and 2 were randomized to receive drugs via sequence 1 (PA-824 alone, washout, ARV, and ARV plus PA-824) or sequence 2 (ARV, ARV with PA-824, washout, and PA-824 alone). In arm 3, participants received PA-824 and then rifampin and then both. Pharmacokinetic sampling occurred at the end of each dosing period. Fifty-two individuals participated. Compared to PA-824 alone, plasma PA-824 values (based on geometric mean ratios) for maximum concentration (C(max)), area under the concentration-time curve from 0 to 24 h (AUC(0–24)), and trough concentration (C(min)) were reduced 28%, 35%, and 46% with efavirenz, 13%, 17%, and 21% with lopinavir-ritonavir (lopinavir/r) and 53%, 66%, and 85% with rifampin, respectively. Medications were well tolerated. In conclusion, lopinavir/r had minimal effect on PA-824 exposures, supporting PA-824 use with lopinavir/r without dose adjustment. PA-824 exposures, though, were reduced more than expected when given with efavirenz or rifampin. The clinical implications of these reductions will depend upon data from current clinical trials defining PA-824 concentration-effect relationships. (This study has been registered at ClinicalTrials.gov under registration no. NCT01571414.