1386pdimpower150 clinical safety tolerability and immune related adverse events in a phase iii study of atezolizumab atezo chemotherapy chemo bevacizumab bev vs chemo bev in 1l nonsquamous nsclc

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Teprasiran, a Small Interfering RNA, for the Prevention of Acute Kidney Injury in High-Risk Patients Undergoing Cardiac Surgery

Background: Acute kidney injury (AKI) affects up to 30% of patients undergoing cardiac surgery, leading to increased in-hospital and long-term morbidity and mortality. Teprasiran is a novel small interfering RNA that temporarily inhibits p53-mediated cell death that underlies AKI. Methods: This prospective, multicenter, double-blind, randomized, controlled phase 2 trial evaluated the efficacy and safety of a single 10 mg/kg dose of teprasiran versus placebo (1:1), in reducing the incidence, severity, and duration of AKI after cardiac surgery in high-risk patients. The primary end point was the proportion of patients who developed AKI determined by serum creatinine by postoperative day 5. Other end points included AKI severity and duration using various prespecified criteria. To inform future clinical development, a composite end point of major adverse kidney events at day 90, including death, renal replacement therapy, and ≥25% reduction of estimated glomerular filtration rate was assessed. Both serum creatinine and serum cystatin-C were used for estimated glomerular filtration rate assessments. Results: A total of 360 patients were randomly assigned in 41 centers; 341 dosed patients were 73±7.5 years of age (mean±SD), 72% were men, and median European System for Cardiac Operative Risk Evaluation score was 2.6%. Demographics and surgical parameters were similar between groups. AKI incidence was 37% for teprasiran- versus 50% for placebo-treated patients, a 12.8% absolute risk reduction, P=0.02; odds ratio, 0.58 (95% CI, 0.37-0.92). AKI severity and duration were also improved with teprasiran: 2.5% of teprasiran- versus 6.7% of placebo-treated patients had grade 3 AKI; 7% teprasiran- versus 13% placebo-treated patients had AKI lasting for 5 days. No significant difference was observed for the major adverse kidney events at day 90 composite in the overall population. No safety issues were identified with teprasiran treatment. Conclusions: The incidence, severity, and duration of early AKI in high-risk patients undergoing cardiac surgery were significantly reduced after teprasiran administration. A phase 3 study with a major adverse kidney event at day 90 primary outcome that has recently completed enrollment was designed on the basis of these findings (NCT03510897)

Thermodynamic study of interactions between ZnO and ZnO binding peptides using isothermal titration calorimetry

Whilst material specific peptide binding sequences have been identified using a combination of combinato-rial methods and computational modelling tools, a deep molecular level understanding of the fundamental principles through which these interactions occur and in some instances modify the morphology of inorganic materials is far from being fully realized. Understanding the thermodynamic changes that occur during peptide-inorganic interactions and correlating these to structural modifications of the inorganic materials could be the key to achieving and mastering con-trol over material formation processes. This study is a detailed investigation applying isothermal titration calorimetry (ITC) to directly probe thermodynamic changes that occur during interaction of ZnO binding peptides (ZnO-BPs) and ZnO. The ZnO-BPs used are reported sequences G-12 (GLHVMHKVAPPR), GT-16 (GLHVMHKVAPPR-GGGC) and alanine mutants of G-12 (G-12A6, G-12A11 and G-12A12) whose interaction with ZnO during solution synthesis studies have been extensively investigated. The interactions of the ZnO-BPs with ZnO yielded biphasic isotherms comprising both an endo-thermic and an exothermic event. Qualitative differences were observed in the isothermal profiles of the different pep-tides and ZnO particles studied. Measured ΔG values were between -6 and -8.5 kcal/mol and high adsorption affinity val-ues indicated the occurrence of favourable ZnO-BP-ZnO interactions. ITC has great potential in its use to understand peptide-inorganic interactions and with continued development, the knowledge gained may be instrumental for simplifi-cation of selection processes of organic molecules for the advancement of material synthesis and design

A conjugate complex facilitating the transport of a cargo through a medium

The present invention relates to conjugate complexes, comprising at least one biological entity, at least one cargo moiety, and at least one effector moiety that is capable of converting, degrading, and/or modifying a given medium, wherein the at least one cargo moiety and the at least one effector moiety are directly or indirectly coupled to the biological entity. The present invention further relates to uses thereof and methods for facilitating the transport of a cargo moiety through a given medium

A sequential attribute sampling inspection game for item facilities

The routine inspection of facilities storing large numbers of identical items is modeled as a two-person, sequential game. Timely detection of illegal activity is parameterized in terms of a critical time to detection, and equilibria are derived which provide inspection strategies. Necessary conditions for deterrence of illegal behavior are discussed. (C) 2001 John Wiley & Sons, Inc

Timely inspection and deterrence

Verification of compliance to formal agreements requires the performance of routine inspections for detection of illegal behavior. Deterrence of violations is generally taken to be the primary objective of any verification regime. If the inspections are carried out in such a way that the gain the inspectee may expect from illegal behavior is smaller than that for behaving legally, then the inspections may indeed be said to have deterred violation. In this paper inspection problems characterized additionally by a 'critical time' are considered for the first time in this context. The critical time is the maximum time interval within which illegal activity must be detected in order to meet the objectives of the agreement. Critically time-dependent inspection problems are modeled as two-person non-cooperative games between inspector and inspectee. They extend over a reference time interval in which the inspector performs by agreement precisely k inspections and in which the inspectee behaves illegally at most once. The inspections are assumed to incur statistical errors of the first and second kind, the former being detrimental to both protagonists. Variants for which the inspectee may or may not be in a position to take advantage of information gained during the reference time interval are considered. Equilibria are investigated and conditions for the existence of deterring inspection strategies are determined. (C) 2001 Elsevier Science B.V. All rights reserved