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prospective trials of dose-escalated RT (median EQD2 Gy using the LQ model: 70 Gy, a/b Z 10). Cardiac dose was calculated using modern algorithms (AAA, Varian Medical Systems) and all doses have been biologically corrected to EQD2 Gy (a/b Z 2.5). Grade 3+ CEs were defined per CTCAE4.03. In patients without baseline CAD, Hard-Coronary-Heart-Disease 10-year Framingham risk scores (FRS) were calculated based on age, cholesterol, blood pressure, hypertension (HTN), and smoking status. Diabetes and chemotherapy were also evaluated. Fine and Gray multivariable analyses (MVA) were utilized to develop models of Grade 3+ CEs; a predicted rate of ! 5% within 2 years was considered elevated. Results: Median follow-up was 51 months for surviving patients. The median age was 66 years, 76% were male, 94% were current/former smokers, and 84% received concurrent chemotherapy. Median mean heart dose (MHD) was 11 Gy (IQR Z 7-19). Of those with available cardiac data 71/105 (68%) did not have baseline CAD and of those, 48/71 (68%) had a FRS !10. In MVA, MHD (HR Z 1.10, 95% CI Z 1.02-1.18, P Z 0.01) was significantly associated with increased hazard of Grade 3+ CEs. Similar findings were noted with V5 or V30. In addition, FRS was marginally associated with CEs (HR Z 1.09, 95% CI Z 0.99-1.21, P Z 0.08). At a MHD ! 20 Gy, patients with a FRS ! 10 had a predicted Grade 3+ CE rate ! 5% within 2 years. High-risk individuals included male smokers ! 50 years old, males ! 60 years old with HTN, or female smokers ! 70 years old with HTN. Conclusion: In a cohort of prospectively treated patients, cardiac dose was independently associated with an increased rate of Grade 3+ CEs in those without baseline CAD. Patients with FRS ! 10 who require a MHD exceeding 20 Gy for adequate tumor coverage may be at elevated risk of Grade 3+ CEs. If validated in additional studies, such patients may be appropriate for primary cardioprotective medication investigation.

Photovoltaic polarity is studied on obliquely deposited CdTe films. The sign of the photopotential that appears on the electrode on the far side of an evaporator is always negative in the case of front illumination. The polarity reverses from positive to negative with an increase of the wavelength of light in the case of illumination through a glass substrate. The critical wavelength of inversion shifts towards longer wavelengths with a decrease of the substrate temperature and an increase of the film thickness.

Objective: The morphology of the primary particles in the active pharmaceutical ingredient (API) is one of the most important determinants for formulation function. However, it has not been possible to visualize primary particles in a tablet using various imaging methods, including spectroscopic mappings, because these particles usually exist as aggregated clusters in tablets. We revealed that the Raman spectrum of crystalline particles is determined depending upon the angle between the crystallographic axis and the polarization direction of the excitation laser. In this paper, we report a method to visualize primary particles within the aggregated cluster based on the Raman spectral change on the boundary of primary particles. Method: Metformin hydrochloride was chosen as a model API for this study. The crystal structure of metformin hydrochloride was solved using X-ray crystal structure analysis. The Raman spectra of metformin hydrochloride crystal along the xyz axes were recorded and resolved into components along the abc axes. Using the abc components, Raman mapping of metformin hydrochloride in tablets was performed to visualize the crystal orientation at each data point. Results: Metformin hydrochloride crystals recrystallized from water/ethanol formed a primitive monoclinic cell. Datasets of five distinct peak areas from the metformin hydrochloride Raman spectrum were used for analyses. Raman crystal orientation mapping (RCOM) from the tablet cross-section provided an image of primary particles within the aggregation cluster of metformin hydrochloride in the tablet. Conclusion: Based on the RCOM, we developed a visualization method for primary API particles in tablets. Because the morphology of primary particles is the key factor of formulation function, this method would contribute to better formulation development and quality control.