Numerical Modeling of Mixing of Chemically Reacting, Non-Newtonian Slurry for Tank Waste Retrieval

Many highly radioactive wastes will be retrieved by installing mixer pumps that inject high-speed jets to stir up the sludge, saltcake, and supernatant liquid in the tank, blending them into a slurry. This slurry will then be pumped out of the tank into a waste treatment facility. Our objectives are to investigate interactions-chemical reactions, waste rheology, and slurry mixing-occurring during the retrieval operation and to provide a scientific basis for the waste retrieval decision-making process. Specific objectives are to: (1) Evaluate numerical modeling of chemically active, non-Newtonian tank waste mixing, coupled with chemical reactions and realistic rheology; (2) Conduct numerical modeling analysis of local and global mixing of non-Newtonian and Newtonian slurries; and (3) Provide the bases to develop a scientifically justifiable, decision-making support tool for the tank waste retrieval operation

Immune-based classification of HPV-associated oropharyngeal cancer with implications for biomarker-driven treatment de-intensification

Background There is significant interest in treatment de-escalation for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) patients given the generally favourable prognosis. However, 15-30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to risk stratify HPV+ OPSCC patients. Methods We created an immune score (UWO3) associated with survival outcomes in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes. Findings A three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival compared to the immune desert (HR = 9.0, 95% CI: 3.2-25.5, P = 3.6 x 10-5) and mixed (HR = 6.4, 95% CI: 2.2-18.7, P = 0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two small treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation. Interpretation With additional prospective validation, the UWO3 score could enable biomarker-driven clinical decision-making for patients with HPV+ OPSCC based on robust outcome prediction across six independent cohorts. Prospective de-escalation and intensification clinical trials are currently being planned. Copyright (C) 2022 The Author(s). Published by Elsevier B.V