Staying Engaged in Your Career Without Burning Out: A Call for Action to Build Resilience

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Essential (and Largely Untaught) Skills for Clinical Pharmacology in Oncology Drug Development

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Phase 1 study of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in East Asian cancer patients: pharmacokinetics and recommended phase 2 dose

Purpose This phase 1 study assessed the pharmacokinetics (PK), maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), safety, and preliminary efficacy of the investigational Aurora A kinase inhibitor, alisertib, in East Asian patients with advanced solid tumors or lymphomas. Patients and Methods Patients received alisertib twice-daily (BID) for 7 days in 21-day cycles. Doses were escalated (3 + 3) from 30 mg BID based on cycle 1 dose-limiting toxicities (DLTs) until the MTD, followed by expansion for PK/safety characterization. Results Thirty-six patients (61 % Chinese, 36 % Korean, 3 % Malay) received alisertib (30 mg BID, n = 30; 40 mg BID, n = 6; median, 2.5 cycles). Alisertib exposures increased approximately dose proportionally, and mean half-life was 16 h. Geometric mean apparent oral clearance (2.65 L/h) was 40 % lower than previous estimates in Western patients, resulting in approximately 70 % higher mean dose-normalized, steady-state exposures (735 nM*h/mg) in East Asian patients. Two patients experienced DLTs at 40 mg BID (grade 3 stomatitis; grade 4 neutropenia); the MTD/RP2D was 30 mg BID. Common toxicities (grade a parts per thousand yen3 at RP2D) were neutropenia (50 %), diarrhea (13 %), and stomatitis (10 %). One patient with extranodal T-/NK-cell lymphoma (nasal type) achieved a partial response and 18 (51 %) had stable disease. Conclusion The MTD/RP2D of alisertib in East Asian patients (30 mg BID) was lower than in Western patients (50 mg BID), consistent with higher systemic exposures in the East Asian population. Alisertib was generally well tolerated and showed signs of antitumor activity in East Asian cancer patients

Microbiological corrosion of ASTM SA105 carbon steel pipe for industrial fire water usage

The large number of metallic systems developed for last few decades against both general uniform corrosion and localized corrosion. Among all microbiological induced corrosion (MIC) is attractive, multidisciplinary and complex in nature. Many chemical processing industries utilizes fresh water for fire service to nullify major/minor fire. One such fire water service line pipe attacked by micro-organisms leads to leakage which is industrially important from safety point of view. Also large numbers of leakage reported in similar fire water service of nearby food processing plant, paper & pulp plant, steel plant, electricity board etc...In present investigation one such industrial fire water service line failure analysis of carbon steel line pipe was analyzed to determine the cause of failure. The water sample subjected to various chemical and bacterial analyses. Turbidity, pH, calcium hardness, free chlorine, oxidation reduction potential, fungi, yeasts, sulphide reducing bacteria (SRB) and total bacteria (TB) were measured on water sample analysis. The corrosion rate was measured on steel samples and corrosion coupon measurements were installed in fire water for validating non flow assisted localized corrosion. The sulphide reducing bacteria (SRB) presents in fire water causes a localized micro biological corrosion attack of line pipe