Risk Assessment Model for Breast Cancer in Women Using MERIT Cohort Study

https://openworks.mdanderson.org/sumexp22/1121/thumbnail.jp

Investigating the Photoyield of Spacecraft Materials

Understanding the photon-induced charging of spacecraft materials is necessary in modeling the overall charging of a spacecraft. Measuring the photoyields of insulators requires sophistication, since insulators\u27 electrons must overcome a greater potential energy barrier, than electrons in a metal, to move within a solid. In order to determine the photoyields of insulating and semiconducting materials for NASA\u27s Solar Probe Mission (PBN, Alumina) and James Webb Space Telescope project (SixPI-ExVDA), a chopper and lock-in amplifier were added to a photoyield measurement system. A standard (Au) photoemission spectrum was compared with Au spectrum taken before addition of the lock-in to verify the validity of the modified system. Two insulators (polyboron nitride and Alumina) under investigation for the NASA/APL Solar Probe Mission and materials for the JWST project (vapor deposited aluminum and silicon on substrate Kapton E) were then studied using the modified photoemission measurement system. The resulting spectra were used to calculate the solar photoelectron yield and work function of each of the materials

Vincristine Metabolism and the Role of CYP3A5

Indiana University-Purdue University Indianapolis (IUPUI)Vincristine is metabolized by the cytochrome P450 3A subfamily of enzymes possibly including CYP3A5, a genetically polymorphic enzyme. The contribution of CYP3A5 to the metabolism of vincristine was quantified by various in vitro models: cDNA-expressed enzymes, human liver microsomes, and human hepatocytes. With these models, the major CYP metabolite of vincristine, M1, was identified and extensively characterized. The rates of M1 formation in the cDNA-expressed enzyme models were at least 7-fold higher with CYP3A5 than CYP3A4; approximately 90% of the hepatic metabolism was predicted to be CYP3A5-mediated. For human liver microsomes with high CYP3A5 expression, the CYP3A5 contribution was substantial, approximately 80%. Human hepatocytes with at least one CYP3A5*1 allele also metabolized vincristine, albeit at a slower rate (10-fold) than human liver microsomes. The CYP3A5 low-expressing hepatocytes did not metabolize vincristine. We conclude that for high CYP3A5 expressers, the majority of the CYP metabolism is mediated by CYP3A5. By in vitro/in vivo scaling with microsomes, the hepatic clearances of high CYP3A5 expressers are predicted to have a 5-fold higher hepatic clearance than low expressers. However, the role of metabolism in the systemic clearance of vincristine is unknown. To study the disposition of vincristine in vivo, a sensitive and selective LC/MS/MS assay was validated for the quantification of vincristine and M1 quantification in human plasma. Vincristine and M1 were identified and quantified in select pediatric plasma and urine samples. For future large-scale clinical studies, the vincristine and M1 concentrations in plasma will be quantified to understand the role of CYP3A5 genotype in vincristine pharmacokinetics. For patients that are CYP3A5 high expressers, the systemic clearance of vincristine may be higher than that of low CYP3A5 expressers. Thus, CYP3A5 genotype may be an important determinant of inter-individual variability in clinical outcomes

Electron-Induced Electron Yields of Uncharged Insulating Materials

This study presents electron-induced electron yield measurements from high-resistivity, high-yield materials to validate a model for the yield of uncharged insulators. These measurements are accomplished by using a low-fluence, pulsed incident electron beam and charge neutralization to minimize charge accumulation. Our measurements show large changes in total yield curves and yield decay curves, even for incident electron fluences of/mm2. We model the evolution of the yield as charge accumulates in the material in terms of electron re-capture based on the extended Chung-Everhart model of the electron emission spectrum. This model is used to explain anomalies measured in high yield ceramics, and to provide a method for determining the uncharged yield in highly insulating, high yield materials. Relevance of these results to spacecraft charging will also be discussed

Low-fluence Electron Yields of Highly Insulating Materials

Electron-induced electron yields of high-resistivity high-yield materials - ceramic polycrystalline aluminum oxide and polymer polyimide (Kapton HN) - were made by using a low-fluence pulsed incident electron beam and charge neutralization electron source to minimize charge accumulation. Large changes in the energy-dependent total yield curves and yield decay curves were observed, even for incident electron fluences of \u3c 3 fC/mm2. The evolution of the electron yield as charge accumulates in the material is modeled in terms of electron recapture based on an extended Chung-Everhart model of the electron emission spectrum. This model is used to explain the anomalies measured in highly insulating high-yield materials and to provide a method for determining the limiting yield spectra of uncharged dielectrics. The relevance of these results to spacecraft charging is also discussed

Insights from wildfire science: A resource for fire policy discussions

Record blazes swept across parts of the US in 2015, burning more than 10 million acres. The four biggest fire seasons since 1960 have all occurred in the last 10 years, leading to fears of a ‘new normal’ for wildfire. Fire fighters and forest managers are overwhelmed, and it is clear that the policy and management approaches of the past will not suffice under this new era of western wildfires. In recent decades, state and federal policymakers, tribes, and others are confronting longer fire seasons (Jolly et al. 2015), more large fires (Dennison et al. 2014), a tripling of homes burned, and a doubling of firefighter deaths (Rasker 2015). Federal agencies now spend $2 to$3 billion annually fighting fires (and in the case of the US Forest Service, over 50% of their budget), and the total cost to society may be up to 30 times more than the direct cost of firefighting. If we want to contain these costs and reduce risks to communities, economies, and natural systems, we can draw on the best available science when designing fire management strategies, as called for in the recent federal report on Wildland Fire Science and Technology. Here, we highlight key science insights that can contribute to the public discourse on wildfire policy and associated management of forests, woodlands, and shrublands. This information is fundamental to decisions that will promote resilient communities and landscapes facing more fire in the future

Validation of a Blood-Based Protein Biomarker Panel for a Risk Assessment of Lethal Lung Cancer in the Physicians\u27 Health Study

This study aimed to assess a four-marker protein panel (4MP)\u27s performance, including the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19, for predicting lung cancer in a cohort enriched with never- and ever-smokers. Blinded pre-diagnostic plasma samples collected within 2 years prior to a lung cancer diagnosis from 25 cases and 100 sex-, age-, and smoking-matched controls were obtained from the Physicians\u27 Health Study (PHS). The 4MP yielded AUC performance estimates of 0.76 (95% CI: 0.61-0.92) and 0.69 (95% CI: 0.56-0.82) for predicting lung cancer within one year and within two years of diagnosis, respectively. When stratifying into ever-smokers and never-smokers, the 4MP had respective AUCs of 0.77 (95% CI: 0.63-0.92) and 0.72 (95% CI: 0.17-1.00) for a 1-year risk of lung cancer. The AUCs of the 4MP for predicting metastatic lung cancer within one year and two years of the blood draw were 0.95 (95% CI: 0.87-1.00) and 0.78 (95% CI: 0.62-0.94), respectively. Our findings indicate that a blood-based biomarker panel may be useful in identifying ever- and never-smokers at high risk of a diagnosis of lung cancer within one-to-two years

High Intratumoral Stromal Content Defines Reactive Breast Cancer as a Low-risk Breast Cancer Subtype

The current study evaluated associative effects of breast cancer cells with the tumor microenvironment and its influence on tumor behavior