Cerium oxide nanoparticles are potent antioxidants, based on their ability to either donate or receive electrons as they alternate between the +3 and +4 valence states. The dual oxidation state of ceria has made it an ideal catalyst in industrial applications, and more recently, nanoceria's efficacy in neutralizing biologically generated free radicals has been explored in biological applications. Here, we report the in vivo characteristics of custom-synthesized cerium oxide nanoparticles (CeNPs) in an animal model of immunological and free-radical mediated oxidative injury leading to neurodegenerative disease. The CeNPs are 2.9 nm in diameter, monodispersed and have a -23.5 mV zeta potential when stabilized with citrate/EDTA. This stabilizer coating resists being 'washed' off in physiological salt solutions, and the CeNPs remain monodispersed for long durations in high ionic strength saline. The plasma half-life of the CeNPs is ∼4.0 h, far longer than previously described, stabilized ceria nanoparticles. When administered intravenously to mice, the CeNPs were well tolerated and taken up by the liver and spleen much less than previous nanoceria formulations. The CeNPs were also able to penetrate the brain, reduce reactive oxygen species levels, and alleviate clinical symptoms and motor deficits in mice with a murine model of multiple sclerosis. Thus, CeNPs may be useful in mitigating tissue damage arising from free radical accumulation in biological systems.

The current study evaluated the relationship between various operationalizations of the Advanced PlacementÒ (AP) exam and course information with first-year grade point average (FYGPA) in college to better understand the role of AP in college admission decisions. In particular, the incremental validity of the different AP variables, above relevant demographic and academic variables, in predicting FYGPA was explored using hierarchical linear modeling. The AP variables of interest included the following: the number of AP exams the student took, the number of AP exams the student took and received a score of 3 or higher, the proportion of the number AP exams the student took out of the number AP courses offered at his or her high school, and his or her average AP score, highest AP score, and lowest AP score. Results showed that the AP predictor that most improved model fit was the average AP exam score. The final model that included multiple AP variables and most improved model fit included the average AP score, the number of AP exams the student took and received a score of 3 or higher, and the AP exam proportion (which had a negative relationship with FYGPA). These results are particularly relevant and timely for college admission and measurement professionals as AP course-taking information as opposed to AP exam score information tends to be more regularly factored into admission decisions if and when AP information is considered at all.

Throughout the college retention literature, there is a recurring theme that students leave college for a variety of reasons making retention a difficult phenomenon to model. In the current study, cluster analysis techniques were employed to investigate whether multiple empirically based profiles of nonreturning students existed to more fully understand the types of students with particular characteristics that are related to leaving college. Based on over 18,000 students who left their initial institution after the first year, analyses supported three clusters, which were labeled as Affordability Issues, Unexpected Underperformers, and Underprepared and Facing Hurdles. Follow-up analyses were then conducted to determine whether students from each cluster had different higher education trajectories. Students in the Underprepared and Facing Hurdles cluster were most likely to drop out of higher education completely or transfer to a 2-year institution. Those students in the Affordability Issues cluster were most likely to transfer to a less expensive 4-year institution. Finally, the Unexpected Underperformers behaved somewhere in between the other two clusters with regard to dropout and transfer behavior. The implications of these findings in terms of developing more thoughtful and targeted retention interventions for these different types of students are discussed.

BackgroundFluoropyrimidines (fluorouracil [5-FU], capecitabine) and irinotecan are commonly prescribed chemotherapy agents for gastrointestinal (GI) malignancies. Pharmacogenetic (PGx) testing for germline DPYD and UGT1A1 variants associated with reduced enzyme activity holds the potential to identify patients at high risk for severe chemotherapy-induced toxicity. Slow adoption of PGx testing in routine clinical care is due to implementation barriers, including long test turnaround times, lack of integration in the electronic health record (EHR), and ambiguity in test cost coverage. We sought to establish PGx testing in our health system following the Exploration, Preparation, Implementation, Sustainment (EPIS) framework as a guide. Our implementation study aims to address barriers to PGx testing.MethodsThe Implementing Pharmacogenetic Testing in Gastrointestinal Cancers (IMPACT-GI) study is a non-randomized, pragmatic, open-label implementation study at three sites within a major academic health system. Eligible patients with a GI malignancy indicated for treatment with 5-FU, capecitabine, or irinotecan will undergo PGx testing prior to chemotherapy initiation. Specimens will be sent to an academic clinical laboratory followed by return of results in the EHR with appropriate clinical decision support for the care team. We hypothesize that the availability of a rapid turnaround PGx test with specific dosing recommendations will increase PGx test utilization to guide pharmacotherapy decisions and improve patient safety outcomes. Primary implementation endpoints are feasibility, fidelity, and penetrance. Exploratory analyses for clinical effectiveness of genotyping will include assessing grade ≥3 treatment-related toxicity using available clinical data, patient-reported outcomes, and quality of life measures.ConclusionWe describe the formative work conducted to prepare our health system for DPYD and UGT1A1 testing. Our prospective implementation study will evaluate the clinical implementation of this testing program and create the infrastructure necessary to ensure sustainability of PGx testing in our health system. The results of this study may help other institutions interested in implementing PGx testing in oncology care.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT04736472, identifier [NCT04736472].

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