en with high-risk prostate cancer and minimal comorbidities should be encouraged to receive definitive local therapy regardless of other factors. These data suggest that significant barriers to life-extending treatment options for patients with prostate cancer remain.Importance There is currently no standard treatment strategy for patients with advanced non-small cell lung cancer (NSCLC) without driver gene variation after failure of 2 or more lines of chemotherapy. Objective To assess the efficacy and safety of apatinib combined with oral vinorelbine. Design, Setting, and Participants This phase 2 prospective nonrandomized clinical trial evaluating the efficacy and safety of apatinib plus vinorelbine recruited patients from Hunan Cancer Center, Hunan, China, from January 1, 2017, to November 30, 2018. Eligible patients were those with wild-type advanced NSCLC whose disease did not respond to at least 2 lines of chemotherapy. Patients were evaluated until December 31, 2019. Data were analyzed from July 2019 to December 2019. Intervention Apatinib at an initial dose of 500 mg once daily and oral vinorelbine 60 mg/m2 once weekly were administered until disease progression, patient withdrawal, or occurrence of unacceptable toxic effects. Main Outcomes and Measures The primarng grade 3 hand-foot syndrome observed in 5 patients (17%) and grade 4 hand-foot observed in 1 patient (3%). Grade 3 weakness was observed in 1 patient (3%). Conclusions and Relevance These findings suggest that apatinib combined with oral vinorelbine is a potentially effective regimen with an acceptable safety profile. This regimen may have potential as a treatment option for patients with wild-type advanced NSCLC whose disease failed at least 2 prior lines of chemotherapy. Trial Registration ClinicalTrials.gov Identifier NCT03652857.Importance The degree to which the presence of mental health disorders is associated with additional medical spending on non-mental health conditions is largely unknown. Objective To determine the proportion and degree of total spending directly associated with mental health conditions vs spending on other non-mental health conditions. Design, Setting, and Participants This retrospective cohort study of 4 358 975 fee-for-service Medicare beneficiaries in the US in 2015 compared spending and health care utilization among Medicare patients with serious mental illness (SMI; defined as bipolar disease, schizophrenia or related psychotic disorders, and major depressive disorder), patients with other common mental health disorders (defined as anxiety disorders, personality disorders, and posttraumatic stress disorder), and patients with no known mental health disorders. Data analysis was conducted from February to October 2019. Exposure Diagnosis of an SMI or other common mental health disorder. Main Outcomes and Mof a mental health disorder.Importance Poor health and unhealthy lifestyles are substantially more prevalent among individuals with low income than among individuals with high income, but the underlying mechanisms are not well understood. Objective To evaluate whether changes to unearned wealth from lotteries are associated with long-term health behaviors and overall health. Design, Setting, and Participants In this quasi-experimental cohort study, 4820 participants (aged 18-70 years at the time of winning) in 3 Swedish lotteries were surveyed from September 1, 2016, to November 11, 2016, between 5 and 22 years after a lottery event. Outcomes of participants in the same lottery who were randomly assigned prizes of different magnitudes by the lotteries but were ex ante identical in terms of their probability of winning different prizes were compared. Data were analyzed from December 22, 2016, to November 21, 2019. Exposures Lottery prizes ranged from $0 for nonwinning players to $1.6 million. Main Outcomes and Measures Four lifestyle facf Swedish lottery players, unearned wealth from random lottery prize winnings was not associated with subsequent healthy lifestyle factors or overall health. The findings suggest that large, random transfers of unearned wealth are unlikely to be associated with large, long-term changes in health habits or overall health.Glyphosate is a widely used herbicide worldwide. DNA Repair inhibitor In 2015, the International Agency for Research on Cancer (IARC) reviewed glyphosate cancer bioassays and human studies and declared that the evidence for carcinogenicity of glyphosate is sufficient in experimental animals. We analyzed ten glyphosate rodent bioassays, including those in which IARC found evidence of carcinogenicity, using a multi-response permutation procedure that adjusts for the large number of tumors eligible for statistical testing and provides valid false-positive probabilities. The test statistics for these permutation tests are functions of p-values from a standard test for dose-response trend applied to each specific type of tumor. We evaluated three permutation tests, using as test statistics the smallest p-value from a standard statistical test for dose-response trend and the number of such tests for which the p-value is less than or equal to 0.05 or 0.01. The false-positive probabilities obtained from two implementations of these three permutation tests are smallest p-value 0.26, 0.17, p-values ≤ 0.05 0.08, 0.12, p-values ≤ 0.01 0.06, 0.08. In addition, we found more evidence for negative dose-response trends than positive. Thus, we found no strong evidence that glyphosate is an animal carcinogen. The main cause for the discrepancy between IARC's finding and ours appears to be that IARC did not account for the large number of tumor responses analyzed and the increased likelihood that several of these would show statistical significance simply by chance. This work provides a more comprehensive analysis of the animal carcinogenicity data for this important herbicide than previously available. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email journals.permissions@oup.com.Being given a phylogenetic tree of both extant and extinct taxa in which the fossil ages are the only temporal information (namely, in which divergence times are considered unknown), we provide a method to compute the exact probability distribution of any divergence time of the tree with regard to any speciation (cladogenesis), extinction and fossilization rates under the Fossilized-Birth-Death model. We use this new method to obtain a probability distribution for the age of Amniota (the synapsid/sauropsid or bird/mammal divergence), one of the most-frequently used dating constraints. Our results suggest an older age (between about 322 and 340 Ma) than has been assumed by most studies that have used this constraint (which typically assumed a best estimate around 310-315 Ma) and provide, for the first time, a method to compute the shape of the probability density for this divergence time. © The Author(s) 2020. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved.