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Aim: Osimertinib is a third-generation, irreversible, oral EGFR tyrosine kinase inhibitor. We report real-world effectiveness and safety data. Patients & methods: EGFR T790M positive advanced non-small-cell lung cancer adults, who received ≥1 prior EGFR tyrosine kinase inhibitor, received osimertinib 80 mg daily. Primary effectiveness outcome: overall survival. Secondary effectiveness outcomes included: investigator-assessed clinical response, progression-free survival, time-to-treatment discontinuation. Results: At data cutoff, 3015 patients had enrolled: 57.1% had investigator-assessed response (95% CI: 55.2–58.9). Median progression-free survival: 11.1 months (95% CI: 11.0–12.0) and median time-to-treatment discontinuation: 13.5 months (95% CI: 12.6–13.9). Interstitial lung disease/pneumonitis-like events reported in 28 (1%) patients. Conclusion: Osimertinib demonstrated clinical effectiveness similar to efficacy observed in the clinical trial program with no new safety signals.

This study compared vaginal temperature, physiologic, and productive parameters in lactating dairy cows supplemented or not with Omnigen-AF (Phibro Animal Health, Teaneck, NJ) during the summer months in a tropical environment. Thirty-two lactating, primiparous (n = 16) and multiparous (n = 16) pregnant Holstein × Gir cows were ranked by parity, days in milk, body weight, and body condition score (BCS), and assigned to receive (SUPP; n = 16) or not (CON; n = 16) Omnigen-AF (Phibro Animal Health, Teaneck, NJ) at 56 g/cow daily (as-fed basis). During the experimental period (d -6 to 56), cows were maintained in a single drylot pen with ad libitum access to water and a total mixed ration, and milked twice daily. Cows received Omnigen-AF mixed with 200 g of corn (as-fed basis) after the daily morning milking through self-locking head gates, whereas CON cows concurrently received 56 g of kaolin mixed with 200 g of corn. For feed intake evaluation, cows from both treatments were randomly divided in 4 groups of 8 cows each, and allocated to 8 individual feeding stations for 3 d. Intake was evaluated 4 times per group from d 1 to 56. From d -6 to 0, d 15 to 28, and d 43 to 56, cow vaginal temperature was recorded hourly. Environmental temperature-humidity index (THI) was also recorded hourly from d 15 to 28 and d 43 to 56. Cows were evaluated for body weight and BCS on d -6 and 56, individual milk production was recorded daily from d -6 to 56, and milk samples were collected on d -6, 0, 7, 14, 21, 28, 35, 42, 49, and 56 for analyses of somatic cell count and milk components. Blood samples were collected on d -6, -3, 0, 9, 15, 18, 21, 24, 27, 36, 45, 48, 51, 54, and 56. Results from samples or observations collected from d -6 to 0 were included as an independent covariate in each respective analysis. Environmental THI was 74.2 ± 0.5 and cows were exposed to THI >68 for 633 h within a total of 672 h of evaluation. Cows assigned to CON had greater vaginal temperature on d 28, 43, 45, and from d 48 to 55 (by 0.38 to 0.52%), as well as greater mean somatic cell count (by 97%) and serum haptoglobin concentrations (by 89%) compared with SUPP cows. Cows assigned to SUPP had greater mean dry matter intake (by 7%), BCS on d 56 (by 11%), and mean serum insulin concentrations (by 35%) compared with CON cows. Hence, SUPP ameliorated hyperthermia, improved nutritional status, and modulated systemic and mammary gland immune parameters in lactating dairy cows exposed to heat stress conditions.

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The standard (p° = 0.1MPa) molar enthalpies of formation for 1,2-, 1,3-, and 1,4-dimethoxybenzene and 1,2,3- and 1,3,5-trimethoxybenzene in the gaseous phase were derived from the standard molar enthalpies of combustion, in oxygen, at T = 298.15 K, measured by static bomb combustion calorimetry and the standard molar enthalpies of evaporation at T = 298.15 K, measured by Calvet microcalorimetry:  1,2-dimethoxybenzene, −(202.4 ± 3.4) kJ·mol-1; 1,3-dimethoxybenzene, −(221.8 ± 2.4) kJ·mol-1; 1,4-dimethoxybenzene, −(211.5 ± 3.0) kJ·mol-1; 1,2,3-trimethoxybenzene, −(339.0 ± 2.2) kJ·mol-1; 1,3,5-trimethoxybenzene, −(371.4 ± 3.0) kJ·mol-1. Ab initio geometry optimizations for the three dimethoxybenzene and the three trimethoxybenzene isomers were performed using the 3-21G* and the 6-31G* basis sets. Single-point MP2/6-31G* and DFT energy calculations allowed the estimation of the enthalpies of formation of all methoxy-substituted benzenes.