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Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer
Guiding the beta-emitting isotope lutetium-177 to prostate cancer lesions with the prostate-specific membrane antigen–targeted radioligand
177
Lu-PSMA-617 plus using standard care was compared with standard care in patients with metastatic castration-resistant prostate cancer. The radioligand therapy prolonged progression-free and overall survival. Adverse effects were more common, but quality of life was maintained.
Journal Article
Genomic Surveillance Reveals Diversity of Multidrug-Resistant Organism Colonization and Infection: A Prospective Cohort Study in Liver Transplant Recipients
In a prospective genomic surveillance study of liver transplant patients, we found that temporal dynamics differed between multidrug-resistant organisms with respect to onset of intestinal colonization, clearance, and infections. Whole-genome sequencing revealed an unexpected diversity of carbapenem-resistant Enterobacteriaceae.
Abstract
Background
Multidrug-resistant organisms (MDROs) are an important cause of morbidity and mortality after solid organ transplantation. We aimed to characterize MDRO colonization dynamics and infection in liver transplant (LT) recipients through innovative use of active surveillance and whole-genome sequencing (WGS).
Methods
We prospectively enrolled consecutive adult patients undergoing LT from March 2014 to March 2016. Fecal samples were collected at multiple timepoints from time of enrollment to 12 months posttransplant. Samples were screened for carbapenem-resistant Enterobacteriaceae (CRE), Enterobacteriaceae resistant to third-generation cephalosporins (Ceph-RE), and vancomycin-resistant enterococci. We performed WGS of CRE and selected Ceph-RE isolates. We also collected clinical data including demographics, transplant characteristics, and infection data.
Results
We collected 998 stool samples and 119 rectal swabs from 128 patients. MDRO colonization was detected in 86 (67%) patients at least once and was significantly associated with subsequent MDRO infection (0 vs 19.8%, P = .002). Child-Turcotte-Pugh score at LT and duration of post-LT hospitalization were independent predictors of both MDRO colonization and infection. Temporal dynamics differed between MDROs with respect to onset of colonization, clearance, and infections. We detected an unexpected diversity of CRE colonizing isolates and previously unrecognized transmission that spanned Ceph-RE and CRE phenotypes, as well as a cluster of mcr-1-producing isolates.
Conclusions
Active surveillance and WGS showed that MDRO colonization is a highly dynamic and complex process after LT. Understanding that complexity is crucial for informing decisions regarding MDRO infection control, use of therapeutic decolonization, and empiric treatment regimens.
Journal Article
Olaparib for Metastatic Castration-Resistant Prostate Cancer
Up to 30% of patients with metastatic castration-resistant prostate cancer have deleterious mutations in genes involved in homologous recombination repair of DNA damage. The use of the PARP inhibitor olaparib in such patients was associated with longer progression-free survival and a longer time to pain progression than control therapy.
Journal Article
Seismic analysis and design using the endurance time method
\"The endurance time method (ETM) is a seismic analysis procedure in which intensifying dynamic excitations are used as the loading function, and it provides many unique benefits in the design of structures. It can largely reduce the computational effort needed for the response history analysis of structures. This aids in the practical application of response history-based analysis in problems involving very large models and/or requiring numerous analyses to achieve optimal design goals. A single response history analysis through ETM provides an estimate of the system response at the entire range of seismic intensities of interest, thus making it ideal for applications such as seismic risk assessment, life-cycle cost analysis, and value-based seismic design. Conceptual simplicity also makes ETM a useful tool for preliminary response history analysis of structural systems. Features: Presents full coverage of the subject from basic concepts to advanced applied topics. Provides a coherent text on endurance time excitation functions that are essential in endurance time analysis. Seismic Analysis and Design using the Endurance Time Method serves as a comprehensive resource for students, researchers, and practicing structural engineers who want to familiarize themselves with the concepts and applications of the endurance time method (ETM) as a useful tool for dynamic structural analysis\"-- Provided by publisher.
Book
Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer
The PROfound trial showed that olaparib prolonged imaging-based progression-free survival among patients whose tumors contained defects in the homologous recombination repair genes
BRCA1
,
BRCA2
, or
ATM
. With longer follow-up, the trial now shows that olaparib prolonged overall survival in these patients. Toxic effects included anemia, nausea, and asthenia.
Journal Article
High-temperature mechanical hysteresis in ceramic-matrix composites
\"This book focuses on mechanical hysteresis behavior in different fiber-reinforced ceramic-matrix composites (CMCs), including 1D minicomposites, 1D unidirectional, 2D cross-ply, 2D plain-woven, 2.5D woven, and 3D needle-punched composites. Ceramic-matrix composites (CMCs) are considered to be the lightweight high-temperature materials for hot-section components in aeroengines with the most potential. To improve the reliability and safety of CMC components during operation, it is necessary to conduct damage and failure mechanism analysis, and to develop models to predict this damage as well as fracture over lifetime - mechanical hysteresis is a key damage behavior in fiber-reinforced CMCs. The appearance of hysteresis is due to a composite's internal damage mechanisms and modes, such as, matrix cracking, interface debonding, and fiber failure. Micromechanical damage models and constitutive models are developed to predict mechanical hysteresis in different CMCs. Effects of a composite's constituent properties, stress level, and the damage states of the mechanical hysteresis behavior of CMCs are also discussed. This book also covers damage mechanisms, damage models and micromechanical constitutive models for the mechanical hysteresis of CMCs. This book will be a great resource for students, scholars, material scientists and engineering designers who would like to understand and master the mechanical hysteresis behavior of fiber-reinforced CMCs\"-- Provided by publisher.
BOOK
Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer
In a trial, the median metastasis-free survival among men with nonmetastatic, castration-resistant prostate cancer and a short PSA doubling time was 36.6 months with enzalutamide and 14.7 months with placebo. Falls and heart problems were more common with enzalutamide.
Journal Article