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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. FPH1 mw © 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. The tolerability profile of tepotinib was similar to that observed in non-Japanese populations. Pharmacokinetics in Japanese and Western patients was comparable. One patient with gastric cancer and one patient with urachal cancer had stable disease of ≥12 weeks in duration. The observed safety profile and pharmacokinetics are comparable with those in patients from the USA and Europe, and the recommended Phase II dose of tepotinib in Japanese patients was confirmed as 500 mg once daily. CONCLUSIONS These results, including initial signals of antitumor activity, support further development of tepotinib in Japanese patients with cancer. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND General practitioner (GP) consultation has long been considered an important component of general practice, but few studies have focused on its characteristics in China. OBJECTIVE This study aimed to explore the content and elucidate the characteristics of GP consultations in general practice in China. METHODS A multimethod investigation of GP consultations in eight community health centres in Guangzhou and Shenzhen, China was conducted between July 2018 and January 2019. Data from 445 GP consultations were collected by direct observation and audio tape and analysed by a modified Davis Observation Code with indicators for frequencies and detailed time durations. GP and patient characteristics were collected by post-visit surveys. RESULTS The mean visit duration was approximately 5.4 minutes. GPs spent the most time on treatment planning, history taking, negotiating, notetaking and physical examination and less time on health promotion, family information collecting, discussing substance use, procedures and counselling. The time spent on procedures ranked first (66 seconds), followed by history taking (65 seconds) and treatment planning (63 seconds). Besides, patients were very active in the consultation, specifically for topics related to medicine ordering and drug costs. CONCLUSIONS This study described the profile of GP consultations and illustrated the complexity of care provided by GPs in China. As patient activation in GP consultations becomes increasingly important, future studies need to explore how to promote the engagement of patients in the whole consultation process other than just requesting for medicine. © The Author(s) 2020. Published by Oxford University Press. All rights reserved.For permissions, please e-mail journals.permissions@oup.com.The phenotypes conferred by recombinant plasmids upon host cells often exhibit variability between replicate populations. This statistical noise is mostly a consequence of adaptive evolution in response to fitness burdens imposed by the plasmids themselves. We developed a novel strategy, 'ribosome pegging', to exclude common unwanted mutations that benefit host cells at the expense of heterologous gene expression. Plasmids that constitutively co-expressed the fluorescent reporter tagRFP and ribosomal protein L23 (rplW) were used to transform Escherichia coli cells that lacked the essential chromosomal rplW gene. Cells within the population that expressed too little L23, or too much, were evidently inviable. Ribosome pegging obviates the need for antibiotics, thus facilitating the deployment of recombinant bacteria in uncontrolled environments. We show that ribosome-pegged E. coli carrying a plasmid that constitutively expresses L23 and an artificially evolved enzyme protects fruit flies from otherwise toxic doses of the insecticide malathion. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND Alcohol and cannabis are frequently co-used, as 20-50% of those who drink alcohol report co-using cannabis. This study is based on the argument that alcohol researchers should enroll cannabis users in human laboratory studies of alcohol use disorder (AUD) to strengthen generalizability. This study examines how heavy drinking cannabis users differ from non-cannabis using heavy drinkers. METHODS In a community sample of non-treatment-seeking heavy drinkers (n = 551, 35% female), cannabis users were identified through (a) self-reported cannabis use in the past 6 months and (b) positive urine toxicology test for tetrahydrocannabinol (THC). Cannabis users, identified as described previously, were compared with non-cannabis users on demographic and clinical characteristics. RESULTS Those who endorsed cannabis use in the past 6 months reported more binge drinking days. Participants who tested positive for THC had higher Alcohol Use Disorder Identification Test scores and more binge drinking days. Younger ness and likely increase clinical severity. © The Author(s) 2020. Medical Council on Alcohol and Oxford University Press. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Lutzomyia longipalpis sand flies are the major natural vector of Leishmania infantum parasites, responsible for the transmission of visceral leishmaniasis in the New World. Several experimental studies highlight its permissive nature, translated to the ability to sustain the development of different Leishmania species. Still, no study deeply explored the potential vector competence of Lu. longipalpis sand flies to Leishmania species other than L. infantum. Here, we show that Lu. longipalpis is a competent vector of L. major parasites, being able to acquire parasites from cutaneous leishmaniasis active lesions, sustain mature infections, and transmit them to naïve hosts, causing disease. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.Glioblastomas are the most common form of malignant primary brain tumor and an important cause of morbidity and mortality. In recent years there have been important advances in understanding the molecular pathogenesis and biology of these tumors, but this has not translated into significantly improved outcomes for patients. In this consensus review from the Society For Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of isocitrate dehydrogenase-wildtype (IDHwt) glioblastomas will be discussed. In addition, novel therapies such as targeted molecular therapies, agents targeting DNA damage response and metabolism, immunotherapies and viral therapies will be reviewed, as well as the current challenges and future directions for research. © 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 journals.permissions@oup.com.BACKGROUND Lower-grade gliomas (LGG) with isocitrate dehydrogenase (IDH1/2) mutations have long survival times making evaluation of treatment efficacy difficult. We investigated the volumetric growth rate of IDH mutant gliomas before and after treatment with established glioma therapies to determine whether a significant change in growth rate could be documented and perhaps be used in the future to evaluate treatment response to investigational agents in LGG trials. METHODS In this multicenter retrospective study, 230 adult patients with IDH1/2 mutated lower-grade gliomas (WHO grade II or III) undergoing surgery, radiation or chemotherapy for progressive non-enhancing tumor were identified.  Subjects were required to have 3 MRI scans containing T2/FLAIR imaging spanning a minimum of 6 months prior to treatment. A mixed-effect model was used to estimate tumor growth prior to treatment. A subset of 95 patients who received chemotherapy, radiotherapy, or chemoradiotherapy and had 2 post-treatment imaging time poUniversity Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.INTRODUCTION Malnutrition, suboptimal hydration, and inadequate body composition can have negative consequences on soldiers' performance and health. A recent consensus statement concerning "soldiers' physical performance" points to the scarcity of data in specific military populations. Therefore, the aim of the present study was to assess and compare dietary intake, hydration status, and body composition of three military groups during their specific military training. MATERIALS AND METHODS Eighty-five soldiers (ie, 21 in a qualification course to join the Special Forces [SF], 22 Infantrymen [Chasseurs Ardennais, CA], and 42 Recruits [REs]) participated in this 3- to 4-day study. Body mass was assessed before and after each study period. All soldiers self-reported their dietary intakes, from which energy and macronutrient intakes were calculated. In addition, their morning urine samples were collected daily to assess urine specific gravity (USG) as a measure of hydration status. Fat mass was estimated at the ditions. © Association of Military Surgeons of the United States 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.The aquatic carnivorous plant Aldrovanda vesiculosa L. is critically endangered worldwide; its peculiar lifestyle raises many questions and poses problems both intriguing on their own and relevant to conservation. While establishing a culture system for its propagation and restoring its natural habitat in Hozoji pond in Saitama, Japan, we conducted ultrastructural observations to examine various aspects of Aldrovanda's way of life. Electron microscopic observation in combination with cryo-techniques produced novel information which could not be obtained by other methods. Some of the results are phosphorous is stored in petiole cells of turions during winter; mucilaginous guides are provided for pollen tubes in parietal placental ovaries; storage of potassium in the vicinity of the midrib of carnivorous leaves may contribute to the rapid closing of the carnivorous leaves; dynamic sequential changes of the ultrastructure of digestive glands is involved in synthesis and secretion of digestive enzymes including protease and acid phosphatase.

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