Notes

A two-frequency-two-coupling label of paired oscillators.
Strong resistance to phosphine (PH3) in the rusty grain beetle, Cryptolestes ferrugineus (Stephens) (Laemophloeidae Coleoptera) poses a serious risk to stored-grain biosecurity. Resistant populations hold risk of surviving in PH3 fumigation, particularly in storage structure that limits achieving very high concentrations of PH3, demanding the need for alternative fumigation strategies. Cofumigation with PH3 and carbon dioxide (CO2) is one alternative approach that has the potential to be used widely. CO2 fumigation of adults of strongly PH3-resistant reference strain of C. ferrugineus, for 48 h, showed that the effective concentration (LC50) of CO2 was 30.99%. This 30% level of CO2 in combination with PH3 decreased the LC50 of PH3 from 6.7 mg/liter to 0.84 mg/liter, an eightfold increase in PH3 efficacy relative to PH3 fumigation in normal air. The LC99.9 decreased from 16.2 mg/liter to 5.8 mg/liter, a 2.8-fold increase in PH3 efficacy. Comparison of mortality response data of PH3 alone and the PH3 + CO2 mixture confirmed that CO2 enhances the toxicity of PH3 synergistically in addition to exerting its own toxicity. These results were validated against three independently field-derived strains of strongly resistant C. ferrugineus that confirmed that observed enhancement in toxicity with the PH3 + CO2 mixture was consistent, irrespective of differences in resistance phenotypes and inherent tolerance levels. Results of the current study provide further opportunities to develop new commercially viable strategy to control strongly PH3-resistant C. Nintedanib in vitro ferrugineus. © The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail [email protected] Standard treatment for glioblastoma is radiation with concomitant and adjuvant temozolomide for six cycles, although the optimal number of cycles of adjuvant temozolomide has long been a subject of debate. We performed a phase II randomized, trial investigating whether extending adjuvant temozolomide for more than six cycles improved outcome. METHODS Glioblastoma patients treated at 20 Spanish hospitals who had not progressed after six cycles of adjuvant temozolomide were centrally randomized to stop (control arm) or continue (experimental arm) temozolomide up to a total of twelve cycles at the same doses they were receiving in cycle 6. Patients were stratified by MGMT methylation and measurable disease. The primary endpoint was differences in 6-month progression-free survival (PFS). Secondary endpoints were PFS, overall survival (OS) and safety. (Clinicaltrials.gov NCT02209948). RESULTS From August 2014 to November 2018, 166 patients were screened, seven of whom were ineligible. Seventy-nine patients were included in the stop arm and 80 in the experimental arm. All patients were included in the analyses of outcomes and of safety. There were no differences in 6-month PFS (control 55.7%; experimental 61.3%), PFS, or OS between arms. MGMT methylation and absence of measurable disease were independent factors of better outcome. Patients in the experimental arm had more lymphopenia (P less then 0.001), thrombocytopenia (P less then 0.001), and nausea and vomiting (P = 0.001). CONCLUSIONS Continuing temozolomide after six adjuvant cycles is associated with greater toxicity but confers no additional benefit in 6-month PFS. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail [email protected] This study was performed with the aim of investigating the temporal patterns and determinants associated with mortality from asbestosis among 21 cohorts of Asbestos-Cement (AC) workers who were heavily exposed to asbestos fibres. METHODS Mortality for asbestosis was analysed for a cohort of 13 076 Italian AC workers (18.1% women). Individual cumulative asbestos exposure index was calculated by factory and period of work weighting by the different composition of asbestos used (crocidolite, amosite, and chrysotile). Two different approaches to analysis, based on Standardized Mortality Ratios (SMRs) and Age-Period-Cohort (APC) models were applied. RESULTS Among the considered AC facilities, asbestos exposure was extremely high until the end of the 1970s and, due to the long latency, a peak of asbestosis mortality was observed after the 1990s. Mortality for asbestosis reached extremely high SMR values [SMR males 508, 95% confidence interval (CI) 446-563; females 1027, 95% CI 771-1336]. SMR increased steeply with the increasing values of cumulative asbestos exposure and with Time Since the First Exposure. APC analysis reported a clear age effect with a mortality peak at 75-80 years; the mortality for asbestosis increased in the last three quintiles of the cumulative exposure; calendar period did not have a significant temporal component while the cohort effect disappeared if we included in the model the cumulative exposure to asbestos. CONCLUSIONS Among heaviest exposed workers, mortality risk for asbestosis began to increase before 50 years of age. Mortality for asbestosis was mainly determined by cumulative exposure to asbestos. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.OBJECTIVES Tepotinib (MSC2156119J) is an oral, potent and highly selective small molecule mesenchymal-epithelial transition factor (MET) inhibitor for which the recommended Phase II dose of 500 mg once daily has been defined, based on the first-in-man trial conducted in the USA and Europe. We carried out a multicenter Phase I trial with a classic `3 + 3' design to determine the recommended Phase II dose in Japanese patients with solid tumors (NCT01832506). METHODS Patients aged ≥20 years with advanced solid tumors (refractory to standard therapy or for whom no effective standard therapy was available) received tepotinib at 215, 300 or 500 mg once daily in a 21-day cycle. Occurrence of dose-limiting toxicities during cycle 1 was used to determine the maximum tolerated dose. Efficacy, safety and pharmacokinetics were also evaluated to support the dose assessment. RESULTS Twelve patients were treated. Tepotinib was generally well tolerated with no observed dose-limiting toxicities; treatment-related adverse events were mainly grades 1-2.
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