Liquid metal magnetohydrodynamics (LMMHD) technology transfer feasibility study. Volume 2: Appendixes

For abstract, see N74-13466

Liquid metal magnetohydrodynamics (LMMHD) technology transfer feasibility study. Volume 1: Summary

The potential application of liquid metal magnetohydrodynamics (LMMHD) to central station utility power generation through the period to 1990 is examined. Included are: (1) a description of LMMHD and a review of its development status, (2) LMMHD preliminary design for application to central station utility power generation, (3) evaluation of LMMHD in comparison with conventional and other advanced power generation systems and (4) a technology development plan. One of the major conclusions found is that the most economic and technically feasible application of LMMHD is a topping cycle to a steam plant, taking advantage of high temperatures available but not usable by the steam cycle

Advanced Air Bag Technology Assessment

As a result of the concern for the growing number of air-bag-induced injuries and fatalities, the administrators of the National Highway Traffic Safety Administration (NHTSA) and the National Aeronautics and Space Administration (NASA) agreed to a cooperative effort that "leverages NHTSA's expertise in motor vehicle safety restraint systems and biomechanics with NASAs position as one of the leaders in advanced technology development... to enable the state of air bag safety technology to advance at a faster pace..." They signed a NASA/NHTSA memorandum of understanding for NASA to "evaluate air bag to assess advanced air bag performance, establish the technological potential for improved technology (smart) air bag systems, and identify key expertise and technology within the agency (i.e., NASA) that can potentially contribute significantly to the improved effectiveness of air bags." NASA is committed to contributing to NHTSAs effort to: (1) understand and define critical parameters affecting air bag performance; (2) systematically assess air bag technology state of the art and its future potential; and (3) identify new concepts for air bag systems. The Jet Propulsion Laboratory (JPL) was selected by NASA to respond to the memorandum of understanding by conducting an advanced air bag technology assessment. JPL analyzed the nature of the need for occupant restraint, how air bags operate alone and with safety belts to provide restraint, and the potential hazards introduced by the technology. This analysis yielded a set of critical parameters for restraint systems. The researchers examined data on the performance of current air bag technology, and searched for and assessed how new technologies could reduce the hazards introduced by air bags while providing the restraint protection that is their primary purpose. The critical parameters which were derived are: (1) the crash severity; (2) the use of seat belts; (3) the physical characteristics of the occupants; (4) the proximity of the occupants to the airbag module; (5) the deployment time, which includes the time to sense the need for deployment, the inflator response parameters, the air bag response, and the reliability of the air bag. The requirements for an advanced air bag technology is discussed. These requirements includes that the system use information related to: (1) the crash severity; (2) the status of belt usage; (3) the occupant category; and (4) the proximity to the air bag to adjust air bag deployment. The parameters for the response of the air bag are: (1) deployment time; (2) inflator parameters; and (3) air bag response and reliability. The state of occupant protection advanced technology is reviewed. This review includes: the current safety restraint systems, and advanced technology characteristics. These characteristics are summarized in a table, which has information regarding the technology item, the potential, and an date of expected utilization. The use of technology and expertise at NASA centers is discussed. NASA expertise relating to sensors, computing, simulation, propellants, propulsion, inflatable systems, systems analysis and engineering is considered most useful. Specific NASA technology developments, which were included in the study are: (1) a capacitive detector; (2) stereoscopic vision system; (3) improved crash sensors; (4) the use of the acoustic signature of the crash to determine crash severity; and (5) the use of radar antenna for pre-crash sensing. Information relating to injury risk assessment is included, as is a summary of the areas of the technology which requires further development

Designing freshwater protected areas (FPAs) for indiscriminate fisheries

Freshwater protected areas (FPAs) are increasingly important for biodiversity conservation, given the intensive use of these systems for water, energy and food production. However, the fisheries benefits of FPAs are not well understood, particularly for indiscriminate fisheries typical of tropical systems. Here we report the results of a model that tests the fisheries effects of no-take protected areas in conditions unique to indiscriminate riverine/floodplain systems. The model has a generalized form applicable to a wide range of systems. We report the results of the general model, as well as those from a specialized form parameterized for the Tonle Sap lake, Cambodia. Both the general and Tonle Sap versions of the model show that FPAs can pay important fisheries benefits, especially where it is difficult to control fishing mortality through gear restrictions or other means. The harvest and profit benefit response curves have similar shapes, with additional FPAs paying high dividends at less than approximately 50% FPA coverage, and then truncating and declining thereafter. In the specific setting of the Tonle Sap of Cambodia, FPAs would pay a large increase in harvest because current FPA coverage is low. It may be counterintuitive to community fisheries managers in Cambodia that the best way to increase harvest is to restrict fishing, but at very high levels of fishing effort, reducing effort or area fished will improve both harvest and profit. In Cambodia, it may make sense to maximize harvest rather than profit because fishers living in poverty need to maximize protein offtake, but the benefits of FPAs remain. Similar considerations may apply in many freshwater and indiscriminate fisheries

Designing freshwater protected areas (FPAs) for indiscriminate fisheries

Freshwater protected areas (FPAs) are increasingly important for biodiversity conservation, given the intensive use of these systems for water, energy and food production. However, the fisheries benefits of FPAs are not well understood, particularly for indiscriminate fisheries typical of tropical systems. Here we report the results of a model that tests the fisheries effects of no-take protected areas in conditions unique to indiscriminate riverine/floodplain systems. The model has a generalized form applicable to a wide range of systems. We report the results of the general model, as well as those from a specialized form parameterized for the Tonle Sap lake, Cambodia. Both the general and Tonle Sap versions of the model show that FPAs can pay important fisheries benefits, especially where it is difficult to control fishing mortality through gear restrictions or other means. The harvest and profit benefit response curves have similar shapes, with additional FPAs paying high dividends at less than approximately 50% FPA coverage, and then truncating and declining thereafter. In the specific setting of the Tonle Sap of Cambodia, FPAs would pay a large increase in harvest because current FPA coverage is low. It may be counterintuitive to community fisheries managers in Cambodia that the best way to increase harvest is to restrict fishing, but at very high levels of fishing effort, reducing effort or area fished will improve both harvest and profit. In Cambodia, it may make sense to maximize harvest rather than profit because fishers living in poverty need to maximize protein offtake, but the benefits of FPAs remain. Similar considerations may apply in many freshwater and indiscriminate fisheries

Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Prognostic Biomarkers in Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab

Systemic inflammation is a key risk factor for hepatocellular carcinoma (HCC) progression and poor outcomes. Inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) may have prognostic value in HCC treated with standard of care atezolizumab plus bevacizumab (Atezo-Bev). We conducted a multicenter, international retrospective cohort study of patients with unresectable HCC treated with Atezo-Bev to assess the association of NLR and PLR with overall survival (OS), progression-free survival (PFS), and objective response rates. Patients with NLR ≥ 5 had a significantly shorter OS (9.38 vs. 16.79 months, p < 0.001) and PFS (4.90 vs. 7.58 months, p = 0.03) compared to patients with NLR < 5. NLR ≥ 5 was an independent prognosticator of worse OS (HR 2.01, 95% CI 1.22–3.56, p = 0.007) but not PFS. PLR ≥ 300 was also significantly associated with decreased OS (9.38 vs. 15.72 months, p = 0.007) and PFS (3.45 vs. 7.11 months, p = 0.04) compared to PLR < 300, but it was not an independent prognosticator of OS or PFS. NLR and PLR were not associated with objective response or disease control rates. NLR ≥ 5 independently prognosticated worse survival outcomes and is worthy of further study and validation

Reproducible safety and efficacy of atezolizumab plus bevacizumab for HCC in clinical practice: Results of the AB-real study

Background: IMbrave150 has established the superiority of atezolizumab plus bevacizumab over sorafenib in patients with unresectable hepatocellular carcinoma (HCC). Methods: We generated a prospectively maintained database including patients treated with atezolizumab plus bevacizumab for unresectable HCC across Europe, Asia and USA. Clinico-pathologic characteristics were assessed for their prognostic influence on overall survival (OS) and progression-free survival (PFS) in univariable and multivariate analyses. Overall response rate by RECIST v1.1 and treatment-related adverse events (TRAEs) per CTCAE v.5.0 were reported. Results: Out of 433 patients, 296 Child-Pugh A and ECOG performance status01 patients received atezolizumab plus bevacizumab in first line and were included. Patients were mostly male (82.7%), cirrhotic (75%) with history of viral hepatitis (65.9%). Overall, 68.9% had Barcelona Clinic Liver Cancer C-stage HCC with portal vein tumour thrombosis (PVTT, 35%) and extrahepatic spread (EHS, 51.7%). After a median follow-up of 10.0 months (95% confidence interval (CI): 9.4–10.4), median OS and PFS were 15.7 (95% CI: 14.5-NE) and 6.9 months (95% CI: 6.1–8.3), respectively. In the response-evaluable patients (n = 273), overall response rate was 30.8%. Overall, 221 patients (74.6%) developed TRAEs, with 70 (23.6%) reporting grade 3 or higher TRAEs; 25 (8.4%) patients had bleeding events. OS was independently associated with baseline Albumin-bilirubin (ALBI) grade and PVTT. Shorter PFS was associated with AFP≥ 400 ng/ml, worse ALBI and presence of EHS. Conclusion: This global observational study confirms the reproducible safety and efficacy of atezolizumab plus bevacizumab in routine clinical practice. Within Child-Pugh-A criteria, the presence of PVTT and higher ALBI grade identify patients with poorer survival

A meta-analysis and real-world cohort study on the sex-related differences in efficacy and safety of immunotherapy for hepatocellular carcinoma

Background & Aims: Sex-related differences in the immune pathogenesis of hepatocellular carcinoma (HCC), particularly related to oestrogen-dependent secretion of pro-tumourigenic cytokines, are well-known. Whether sex influences the efficacy and safety of immunotherapy is not known. Methods: We performed a restricted maximum likelihood random effects meta-analysis of five phase III trials that evaluated immune checkpoint inhibitors (ICIs) in advanced HCC and reported overall survival (OS) hazard ratios (HRs) stratified by sex to evaluate sex-related differences in OS. In a real-world cohort of 840 patients with HCC from 22 centres included between 2018 and 2023, we directly compared the efficacy and safety of atezolizumab + bevacizumab (A+B) between sexes. Radiological response was reported according to RECIST v1.1. Uni- and multivariable Cox regression analyses were performed for OS and progression-free survival (PFS). Results: In the meta-analysis, immunotherapy was associated with a significant OS benefit only in male (pooled HR 0.79; 95% CI 0.73–0.86) but not in female (pooled HR 0.85; 95% CI 0.70–1.03) patients with HCC. When directly comparing model estimates, no differences in the treatment effect between sexes were observed. Among 840 patients, 677 (81%) were male (mean age 66 ± 11 years), and 163 (19%) were female (mean age 67 ± 12 years). Type and severity of adverse events were similar between the two groups. OS and PFS were comparable between males and females upon uni- and multivariable analyses (aHR for OS and PFS: 0.79, 95% CI 0.59–1.04; 1.02, 95% CI 0.80–1.30, respectively). Objective response rates (24%/22%) and disease control rates (59%/59%) were also similar between sexes. Conclusion: Female phase III trial participants experienced smaller OS benefit following ICI therapy for advanced HCC, while outcomes following A+B treatment were comparable between sexes in a large real-world database. Based on the ambiguous sex-related differences in survival observed here, further investigation of sex-specific clinical and biologic determinants of responsiveness and survival following ICIs are warranted. Impact and implications: While immune checkpoint inhibitors have emerged as standard of care for the treatment of hepatocellular carcinoma, there are conflicting reports on whether the efficacy of cancer immunotherapy differs between females and males. Our study suggests ambiguous sex-related differences in outcomes from immunotherapy in hepatocellular carcinoma. Further investigation of sex-specific clustering in clinicopathologic and immunologic determinants of responsiveness to immune checkpoint inhibitor therapy should be prioritised. Systematic review registration: PROSPERO CRD42023429625