Potential climate effects on Japanese rice productivity

Adaptation to climate change has become an important policy question in recent years. Agriculture is the economic activity most sensitive to climate change. We evaluate the dynamic effects of productivity change and individual efforts to adapt to climate change. Adaptation actions in agriculture are evaluated to determine how the climate affects production efficiency. In this paper, we use the bi-directional distance function method to measure Japanese rice production loss due to climate. We find that 1) accumulated precipitation has the greatest effect on rice production efficiency and 2) the climate effect on rice production efficiency decreases over time. Our results empirically support the benefit of an adaptation approach.Climate change, productivity analysis, agriculture

Impact of Hepatitis Virus on the Feasibility and Efficacy of Anticancer Agents in Patients With Hepatocellular Carcinoma in Phase I Clinical Trials

Chronic viral hepatitis is a risk factor for liver fibrosis and hepatocellular carcinoma (HCC). Patients with advanced HCC have limited effective therapeutic options and are considered potential candidates for early phase clinical trials of anti-cancer agents. The impact of chronic viral hepatitis on the efficacy of anticancer agents for patients with HCC in phase I trials (P-Is) still remains unclear and has not been reported. We retrospectively analyzed the outcomes of consecutive HCC patients in P-Is conducted in a single institute, focusing on chronic viral hepatitis. Of 85 patients enrolled in P-Is, 46 (54%) patients positive and 39 (46%) patients negative for chronic viral hepatitis showed no significant difference in clinical and laboratory variables and on the point of the best response based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria; moreover, the frequency of Grade ≥3 adverse events (AE) was not significantly different. The median time to treatment failure (TTF) and overall survival (OS) from the P-I enrolment were 2.0 and 13.7 months, respectively. No patient experienced reactivation of hepatitis B virus (HBV) or treatment-related death. Chronic viral hepatitis does not independently affect the outcomes of anticancer drugs. Advanced HCC patients with chronic viral hepatitis could be feasible for P-Is

First-In-Human Phase I Study of a Next-Generation, Oral, TGFβ Receptor 1 Inhibitor, LY3200882, in Patients with Advanced Cancer

Càncer avançat; Factor de creixement transformador betaAdvanced Cancer; Transforming Growth Factor betaCáncer avanzado; Factor de crecimiento transformador betaPurpose: A novel, selective, next-generation transforming growth factor beta (TGFβ) receptor type-1 small molecule inhibitor, LY3200882, demonstrated promising preclinical data. This first-in-human trial evaluated safety, tolerability, recommended phase II dose (RP2D), pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of LY3200882 as monotherapy or with other anticancer agents in patients with advanced cancer. Patients and Methods: This phase I multicenter study of oral LY3200882 (NCT02937272) comprised dose escalation, monotherapy expansion in grade 4 glioma, and combination therapy in solid tumors (LY3200882 and PD-L1 inhibitor LY3300054), pancreatic cancer (LY3200882, gemcitabine, and nab-paclitaxel), and head and neck squamous cell cancer (LY3200882, cisplatin, and radiation). Results: Overall, 139 patients with advanced cancer were treated. The majority (93.5%) of patients experienced ≥1 treatment-emergent adverse events (TEAE), with 39.6% LY3200882-related. Grade 3 LY3200882-related toxicities were only observed in combination therapy arms. One patient in the pancreatic cancer arm experienced cardiovascular toxicity. The LY3200882 monotherapy RP2Ds were established in two schedules: 50 mg twice a day 2-weeks-on/2-weeks-off and 35 mg twice a day 3-weeks-on/1-week-off. Four patients with grade 4 glioma had durable Revised Assessment in Neuro Oncology (RANO) partial responses (PR) with LY3200882 monotherapy (n = 3) or LY3200882-LY3300054 combination therapy (n = 1). In treatment-naïve patients with advanced pancreatic cancer, 6 of 12 patients achieved Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 PR and 3 of 12 patients demonstrated stable disease, for an overall 75% disease-control rate with the combination of LY3200882, gemcitabine, and nab-paclitaxel. Conclusions: LY3200882 as monotherapy and combination therapy was safe and well tolerated with preliminary antitumor activity observed in pancreatic cancer. Further studies to evaluate the efficacy of LY3200882 with gemcitabine and nab-paclitaxel in advanced pancreatic cancer are warranted

The critical role of Rap1-GAPs Rasa3 and Sipa1 in T cells for pulmonary transit and egress from the lymph nodes

Rap1-GTPase activates integrins and plays an indispensable role in lymphocyte trafficking, but the importance of Rap1 inactivation in this process remains unknown. Here we identified the Rap1-inactivating proteins Rasa3 and Sipa1 as critical regulators of lymphocyte trafficking. The loss of Rasa3 and Sipa1 in T cells induced spontaneous Rap1 activation and adhesion. As a consequence, T cells deficient in Rasa3 and Sipa1 were trapped in the lung due to firm attachment to capillary beds, while administration of LFA1 antibodies or loss of talin1 or Rap1 rescued lung sequestration. Unexpectedly, mutant T cells exhibited normal extravasation into lymph nodes, fast interstitial migration, even greater chemotactic responses to chemokines and sphingosine-1-phosphate, and entrance into lymphatic sinuses but severely delayed exit: mutant T cells retained high motility in lymphatic sinuses and frequently returned to the lymph node parenchyma, resulting in defective egress. These results reveal the critical trafficking processes that require Rap1 inactivation

Potential climate effects on Japanese rice productivity

Adaptation to climate change has become an important policy question in recent years. Agriculture is the economic activity most sensitive to climate change. We evaluate the dynamic effects of productivity change and individual efforts to adapt to climate change. Adaptation actions in agriculture are evaluated to determine how the climate affects production efficiency. In this paper, we use the bi-directional distance function method to measure Japanese rice production loss due to climate. We find that 1) accumulated precipitation has the greatest effect on rice production efficiency and 2) the climate effect on rice production efficiency decreases over time. Our results empirically support the benefit of an adaptation approach

Potential climate effects on Japanese rice productivity

Adaptation to climate change has become an important policy question in recent years. Agriculture is the economic activity most sensitive to climate change. We evaluate the dynamic effects of productivity change and individual efforts to adapt to climate change. Adaptation actions in agriculture are evaluated to determine how the climate affects production efficiency. In this paper, we use the bi-directional distance function method to measure Japanese rice production loss due to climate. We find that 1) accumulated precipitation has the greatest effect on rice production efficiency and 2) the climate effect on rice production efficiency decreases over time. Our results empirically support the benefit of an adaptation approach

Vedolizumab for pediatric IBD

Pediatric ulcerative colitis is likely to be more severe than adult ulcerative colitis. Failure to thrive should be considered during therapy. A 10-year-old boy was diagnosed with ulcerative colitis based on his clinical presentation and colonoscopy and biopsy results. The administration of 5-aminosalicylic acid and prednisolone resulted in remission ; however, the symptoms reappeared after the discontinuation of prednisolone. Then, infliximab was administered ; however, the patient was resistant to it and appeared to be dependent on prednisolone. Vedolizumab, a monoclonal antibody against α4β7 integrin, was administered, which resulted in rapid remission. A steady decrease in prednisolone followed, and remission was maintained even after prednisolone discontinuation. Vedolizumab may be effective in pediatric patients with moderate-to-severe refractory ulcerative colitis. Vedolizumab prevents lymphocytes from binding to MAdCAM-1, which is selectively expressed in the gastrointestinal submucosa, leading to the mitigation of the systemic side effects of immunosuppression, such as infections. In Japan, vedolizumab use is not yet approved for use in children, but its effectiveness and safety in children is expected to be investigated in the future

Osteoarticular infections in childhood

Objectives : Osteomyelitis (OM) and septic arthritis (SA) in childhood might cause complications, sequelae, or even death if diagnosis and treatment are delayed. Here, we examined the outcomes of OM / SA at a pediatric emergency core hospital in Japan. Methods : This was a single-center, retrospective, observational cohort study at a pediatric emergency core hospital in Japan. Pediatric outpatients who underwent magnetic resonance imaging at the hospital in the period 2012–2020 were recruited. Primary outcomes were sequelae, recurrent symptoms, chronicity, and death. Results : Fifteen OM / SA patients (9 OM, 4 SA, 2 OM+SA) were recruited. The identified major pathogens included methicillin-susceptible Staphylococcus aureus (40.0 %, n = 6) and methicillin-resistant S. aureus (13.3 %, n = 2). Mean time from onset to first hospital visit, hospitalization, and initiation of effective antibiotics was 2 days, 3.9 ± 1.8 days, and 4.9 ± 2.2 days, respectively. All OM / SA patients recovered without complications or sequelae. Conclusions : In this study, all patients with OM / SA showed a good prognosis. Despite the small sample size, this pilot study suggests that the pediatric emergency core system in Japan provides early treatment and a good prognosis for patients diagnosed with OM / SA

Three-dimensional electronic structure in ferromagnetic Fe3Sn2\textrm{Fe}_3\textrm{Sn}_2 with breathing kagome bilayers

A large anomalous Hall effect (AHE) has been observed in ferromagnetic $\textrm{Fe}_3\textrm{Sn}_2$ with breathing kagome bilayers. To understand the underlying mechanism for this, we investigate the electronic structure of $\textrm{Fe}_3\textrm{Sn}_2$ by angle-resolved photoemission spectroscopy (ARPES). In particular, we use both vacuum ultraviolet light (VUV) and soft x ray (SX), which allow surface-sensitive and relatively bulk-sensitive measurements, respectively, and distinguish bulk states from surface states, which should be unlikely related to the AHE. While VUV-ARPES observes two-dimensional bands mostly due to surface states, SX-ARPES reveals three-dimensional band dispersions with a periodicity of the rhombohedral unit cell in the bulk. Our data show a good consistency with a theoretical calculation based on density functional theory, suggesting a possibility that $\textrm{Fe}_3\textrm{Sn}_2$ is a magnetic Weyl semimetal.Comment: 6 pages, 4 figure