787 to 39.8 ng/mL (median 5.87 ng/mL), 0 to 2.13 ng/mL (0.347 ng/mL), and 1.98 to 82.8 ng/mL (16.6 ng/mL), respectively. Such low concentrations of paracetamol were deemed irrelevant to therapeutic effect. Based on statistical analysis, the preliminary Japanese residue limits of unhydrolyzed and hydrolyzed paracetamol were determined to be 70.5 ng/mL and 112 ng/mL, respectively, in plasma, at a risk factor of 1 in 10,000. Furthermore, we detected paracetamol and orthocetamol in feed samples. A pharmacokinetics simulation showed that the presence of orthocetamol is most probably related to daily feed rations. As for paracetamol, feed can be one of the sources and other possible sources require further investigation. © 2020 John Wiley & Sons, Ltd.Clofarabine is active in refractory/relapsed acute myeloid leukemia (AML). In this phase 2 study, we treated 18- to 65-year-old AML patients refractory to first-line 3 + 7 daunorubicin/cytarabine induction or relapsing after 3 + 7 induction and high-dose cytarabine consolidation, with clofarabine (30 mg/m2 /d, Days 1-5), cytarabine (750 mg/m2 /d, Days 1-5), and mitoxantrone (12 mg/m2 /d, Days 3-5) (CLAM). Patients achieving remission received up to two consolidation cycles of 50% CLAM, with eligible cases bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT). The mutational profile of a 69-gene panel was evaluated. Twenty-six men and 26 women at a median age of 46 (22-65) years were treated. The overall response rate after the first cycle of CLAM was 90.4% (complete remission, CR 69.2%; CR with incomplete hematologic recovery, CRi 21.2%). Twenty-two CR/CRi patients underwent allo-HSCT. The 2-year overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were 65.8%, 45.7%, and 40.2%, respectively. Multivariate analyses showed that superior OS was associated with CR after CLAM (P = .005) and allo-HSCT (P = .005), and superior RFS and EFS were associated with allo-HSCT (P  less then  .001). Remarkably, CR after CLAM and allo-HSCT resulted in 2-year OS of 84.3% and 90%, respectively. Karyotypic aberrations and genetic mutations did not influence responses or survivals. Grade 3/4 neutropenia/thrombocytopenia and grade 3 febrile neutropenia occurred in all cases. Other nonhematologic toxicities were mild and uncommon. There was no treatment-related mortality and the performance of allo-HSCT was not compromised. Clofarabine, cytarabine, and mitoxantrone was highly effective and safe in refractory/relapsed AML. This study was registered at ClinicalTrials.gov (NCT02686593). © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.Suckling piglets play an important role at maintaining influenza A virus (IAV) infections in breeding herds and disseminating them to other farms at weaning. However, the role they play at weaning to support and promote genetic variability of IAV is not fully understood. The objective here was to evaluate the genetic diversity of IAV in pigs at weaning in farms located in the Midwestern USA. Nasal swabs (n = 9,090) collected from piglets in breed-to-wean farms (n = 52) over a six-month period across seasons were evaluated for the presence of IAV. Nasal swabs (n = 391) from 23 IAV-positive farms were whole-genome sequenced. Multiple lineages of HA (n = 7) and NA (n = 3) were identified in 96% (22/23) and 61% (237/391) of the investigated farms and individual piglets, respectively. Co-circulation of multiple types of functional HA and NA was identified in most (83%) farms. Whole IAV genomes were completed for 126 individual piglet samples and 25 distinct and 23 mixed genotypes were identified, highlighting significant genetic variability of IAV in piglets. Co-circulation of IAV in the farms and co-infection of individual piglets at weaning was observed at multiple time points over the investigation period and appears to be common in the investigated farms. Statistically significant genetic variability was estimated within and between farms by AMOVA, and varying levels of diversity between farms were detected using the Shannon-Weiner Index. Results reported here demonstrate previously unreported levels of molecular complexity and genetic variability among IAV at the farm and piglet levels at weaning. Movement of such piglets infected at weaning may result in emergence of new strains and maintenance of endemic IAV infection in the US swine herds. Results presented here highlight the need for developing and implementing novel, effective strategies to prevent or control the introduction and transmission of IAV within and between farms in the country. © 2020 Blackwell Verlag GmbH.OBJECTIVE The aim of this study was to explore the dose response of licogliflozin, a dual inhibitor of sodium/glucose cotransporter 1 (SGLT1) and 2 (SGLT2), by evaluating change in body weight in adults with overweight or obesity. METHODS This dose-response analysis evaluated change in body weight following 24 weeks with four once-daily and twice-daily licogliflozin doses (2.5-150 mg) versus placebo (primary end point). A further 24-week analysis evaluated the efficacy and safety of two once-daily licogliflozin doses in maintaining initial weight reduction. RESULTS Licogliflozin once daily or twice daily produced a significant dose-response signal for weight loss versus placebo (P  less then  0.0001). However, mean adjusted percent changes in body weight after 24 weeks were modest, ranging from -0.45% to -3.83% (in the 50 mg twice daily group [95% CI -5.26% to -2.48%]; n = 75).  https://www.selleckchem.com/products/resatorvid.html  Responder analysis of ≥ 5% weight loss at week 24 revealed significant differences versus placebo, which were most pronounced with highest doses of 50 mg twice daily (45.3%) and 150 mg once daily (42.9%) (both P  less then  0.01). While weight loss was greater at higher doses, gastrointestinal adverse events were also more frequent. The 50-mg once-daily dose had perhaps the best balance between efficacy and tolerability. CONCLUSIONS Licogliflozin produced significant reductions in body weight versus placebo. However, the magnitude of weight reduction was modest. © 2020 The Authors. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).