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Aim: Global warming and deforestation are pushing species closer to their physiological limit, especially for species with habitat‐restricted life stages because sunlit areas have higher maximum temperatures. Here, we examined the critical thermal maximum (CTmax), and maximum environmental water temperature (Tmax) of larvae from 29 anuran species across a latitudinal gradient (22–43° N) to test how latitude and habitat type (open or closed‐forest ponds) affected warming tolerance, an index of vulnerability to climate change. Location: Taiwan, Korea, Japan. Time period: Present. Major taxa studied: Anurans. Results: We showed that open ponds lowered warming tolerance, regardless of latitude and phylogenetic clustering, contrasting the established literature that warming tolerance is lower at tropical latitudes, which only applied to species in forest ponds in this study. Importantly, biophysical models at the local scale suggest that increasing deforestation will exacerbate the effects of climate warming on warming tolerance. Main conclusions: Local effects of accelerated warming and habitat modification mean that species with range‐restricted life stages will become more vulnerable to anthropogenic change. [ABSTRACT FROM AUTHOR]

Introduction: This final analysis of a long-term extension (LTE) study assessed the safety, tolerability, and effectiveness of peficitinib (ASP015K), a pan-Janus kinase inhibitor, in Asian patients with rheumatoid arthritis (RA). Methods: Patients had previously completed the 12-week phase 2b (RAJ1), or 52-week phase 3 (RAJ3 and RAJ4) peficitinib studies in Japan, Korea, and Taiwan, and received oral peficitinib 50 or 100 mg/day. Dose increase to 150 mg/day or reduction to 50 mg/day was permitted. Efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates, 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP), and ACR components. Safety endpoints included treatment-emergent adverse events (TEAEs), and incidence rates (IRs) of adverse events of special interest per 100 patient-years (PY). Results: Overall, 843 patients received peficitinib for a mean 32.0 months (maximum 85.2 months), and most (64.4%) received peficitinib 100 mg/day as a maximum dose. Respective ACR20/50/70 response rates were maintained from baseline (week 0 of LTE; 71.6, 52.1, and 34.7%) to end of treatment (78.7, 63.3, and 44.1%); continuous improvements in ACR components and DAS28-CRP were observed from the baselines of preceding studies and throughout the LTE. Overall, 796/843 (94.4%) patients experienced TEAEs; most were severity grade 1/2. Most common TEAEs were nasopharyngitis (47.0%) and herpes zoster (17.3%). Drug-related TEAEs leading to permanent discontinuation occurred in 140 (16.6%) patients, and IRs (95% confidence interval) per 100 PY of serious infections, herpes zoster-related disease, and malignancies were 2.7 (2.1, 3.4), 7.3 (6.2, 8.6), and 1.2 (0.9, 1.8), respectively. Two deaths occurred during the study; one each from diffuse large B cell lymphoma and pneumonia, which were, respectively considered probably and possibly related to study drug. Conclusions: Improvements in effectiveness variables were maintained during this long-term study of peficitinib in Asian patients with RA; peficitinib was generally well tolerated over a mean 32 months' duration. Trial Registration: ClinicalTrials.gov. NCT01638013, retrospectively registered on 11 July 2012 https://clinicaltrials.gov/ct2/show/NCT01638013. [ABSTRACT FROM AUTHOR]