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The northwest European shelf (NWS) seas are environmentally and economically important, and an understanding of how their climate may change helps with their management. However, as the NWS seas are poorly represented in global climate models, a common approach is to dynamically downscale with an appropriate shelf sea model. We develop a set of physical marine climate projections for the NWS. We dynamically downscale 12 members of the HadGEM3-GC3.05 perturbed parameter ensemble (approximately 70 km horizontal resolution over Europe), developed for UKCP18, using the shelf sea model NEMO CO9 (7 km horizontal resolution). These are run under the RCP8.5 high-greenhouse-gas-emission scenario as continuous simulations over the period 1990–2098. We evaluate the simulations against observations in terms of tides, sea surface temperature (SST), surface and near-bed temperature and salinity, and sea surface height. These simulations represent the state of the art for NWS marine projections. We project an SST rise of 3.11 °C (± 2σ = 0.98 °C) and a sea surface salinity (SSS) freshening of −1.01 (± 2σ = 0.93; on the (unitless) practical salinity scale) for 2079–2098 relative to 2000–2019, averaged over the NWS (approximately bounded by the 200 m isobar and excluding the Norwegian Trench, the Skagerrak and Kattegat), a substantial seasonal stratification increase (23 d over the NWS seas), and a general weakening of the NWS residual circulation. While the patterns of NWS changes are similar to our previous projections, there is a greater warming and freshening that could reflect the change from the A1B emissions scenario to the RCP8.5 concentrations pathway or the higher climate sensitivity exhibited by HadGEM3-GC3.05. Off the shelf, south of Iceland, there is limited warming, consistent with a reduction in the Atlantic Meridional Overturning Circulation and associated northward heat transport. These projections have been publicly released, along with a consistent 200-year present-day control simulation, to provide an evidence base for climate change assessments and to facilitate climate impact studies. For example, we illustrate how the two products can be used to estimate climate trends, unforced variability and the time of emergence (ToE) of the climate signals. We calculate the average NWS SST ToE to be 2034 (with an 8-year range) and 2046 (with a 33-year range) for SSS. We also discuss how these projections can be used to describe NWS conditions under 2 and 4 °C global mean warming (compared with 1850–1900), as a policy-relevant exemplar use case.

Abstract While low‐resolution climate models at present struggle to appropriately simulate convectively coupled large‐scale atmospheric disturbances such as equatorial Kelvin waves (EKWs), superparameterization helps better reproduce such phenomena. To evaluate such model differences based on physical mechanisms, a linearized theoretical framework of convectively coupled EKWs was developed in a form readily applicable to model evaluation by allowing background stability and diabatic heating to have arbitrary vertical profiles rather than assuming simplified ones. A system of linearized equations of convection‐coupled gravity waves was derived as a two‐dimensional model of the convectively coupled EKWs. In this work, the basic states are taken from observations, CTL‐MIROC and SP‐MIROC experiments introduced in Part 1. The tendency of convectively coupled gravity waves to grow faster under top‐heavy heating is confirmed for realistic stratification profiles, as found in previous studies under constant stratifications. A comparison of linear unstable solutions with basic states taken from SP‐MIROC and CTL‐MIROC shows that the top‐heavy heating profile in SP‐MIROC largely contributes to the enhancement of the EKW‐like unstable modes, while subtle differences of stratification profiles considerably affect EKW behaviors. The bottom‐heavy heating bias in the CTL‐MIROC likely originates from insufficient modeling of subgrid stratiform precipitation in tropical organized systems. It is desirable to incorporate such stratiform components in cumulus parameterizations to achieve better EKW reproducibility.

Abstract The potential scope of superparameterization (SP) was extended to higher resolutions of the global climate model (GCM) component by devising a technique called blockwise coupling. In this method, a horizontal average of multiple GCM columns, instead of one, is coupled to a cloud‐resolving model (CRM) domain. This enables SP‐GCMs to reduce the computational cost drastically, enabling higher‐resolution GCMs to be superparameterized. A blockwise‐coupled SP‐GCM called SP‐MIROC was implemented by coupling the climate model MIROC6 to the CRM SCALE‐RM. The 4 × 4‐bundled SP‐MIROC successfully reproduced horizontal patterns and frequency distributions of precipitation and realistic amplitudes of equatorial Kelvin waves (EKWs), which were underestimated in the standard MIROC6. As discussed in Yamazaki and Miura (2024b, https://doi.org/10.1029/2023MS003837) of this study, the amplitude boost of EKWs was enabled by a top‐heavy heating in SP‐MIROC. Comparison of power spectra between the 4 × 4‐bundled SP‐MIROC and nonbundled SP‐MIROC indicated that the effective resolution of dynamic variables was not degraded by the blockwise technique. Rather, spectra in the 4 × 4‐bundled SP‐MIROC were more realistic than those in the nonbundled SP‐MIROC. Although the 4 × 4‐bundling limits convective coupling in the smallest GCM scale, it could offer the best match of resolutions between the GCM‐handled dynamics and SP‐derived physics because the effective resolution of the dynamics is lower than the nominal grid spacing.

Background: Neoadjuvant radiotherapy and chemotherapy, followed by surgical resection, are standard treatments for locally advanced rectal cancer (LARC). Emerging evidence has shown the efficacy of anti-programmed cell death protein 1 (anti-PD-1) therapy for patients with mismatch repair-deficient (dMMR) colorectal cancer, particularly in managing metastatic disease. Several ongoing clinical trials evaluating the efficacy of anti-PD-1 therapy in patients with dMMR LARC have reported outstanding responses. Patients and methods: Here, we present the VOLTAGE-2 study (EPOC 2201), a non-randomized, single-arm, phase II trial that aims to investigate the efficacy and safety of nivolumab monotherapy for 1 year in patients with dMMR-resectable LARC. Patients with clinical complete response (cCR) or near-complete response (nCR) will be observed with non-operative management (NOM) using the Memorial Sloan Kettering Regression Schema.The primary endpoint will be investigator-determined 2-year cCR rate for nivolumab monotherapy. We will investigate the surrogacy of circulating tumor DNA assay as a cCR using whole-genome sequencing (WGS)-based molecular residual disease (MRD) assay and will evaluate the biomarkers of the response to anti-PD-1 antibody using whole-exome sequencing (WES) plus whole-transcriptome sequencing (WTS)-based tumor genomics and immune microenvironment evaluations. We plan to carry out spatiotemporal trans-omics analyses using artificial intelligence and deep learning-driven genomics, transcriptomics, radiomics, pathomics, colonoscopic imaging, quality of life, and clinical features.

Background: In clinical oncology, it is widely recognized that data sharing and the integration of completed clinical trials can promote research and development (R&D). The Foundation Aide et Recherche en Cancérologie Digestive (ARCAD) database project was initiated in Europe and the United States in 2006. Approximately 40 000 individual patient data (IPD) for metastatic colorectal cancer were collected and constructed as an integrated database. Materials and methods: ARCAD-Asia was launched in 2021 and has been actively collecting Asian clinical trials. In addition, ARCAD-Asian data were periodically transferred to the Mayo Clinic, and IPD was integrated into the ARCAD database. Finally, all data were shared with three data centers, ARCAD-Asia and ARCAD, located in Europe, the United States, and Japan. We have developed a reproducible and reliable data conversion procedure based on the methodology established by ARCAD. Results: From September 2021 to April 2023, 2318 IPD from four first-line, two second-line, and three third-line trials for metastatic colorectal cancer were integrated and stored in ARCAD-Asia. By autumn 2023, three more trials (1565 IPD) will be included, resulting in 12 trials (3883 IPD) in the Asia database. These are transferred and shared with ARCAD. After integrating Asian data, the ARCAD database contained 70 trials with ∼50 000 IPD. Conclusions: Based on our active collaboration, ARCAD-Asia was established, and a global integrated database was constructed. As a next step, we will continue to collect Asian IPD and expand the cancer types, leading to a more comprehensive and available global database.

Abstract In this paper, we present the first high‐speed video observation of a cloud‐to‐ground lightning flash and its associated downward‐directed Terrestrial Gamma‐ray Flash (TGF). The optical emission of the event was observed by a high‐speed video camera running at 40,000 frames per second in conjunction with the Telescope Array Surface Detector, Lightning Mapping Array, interferometer, electric‐field fast antenna, and the National Lightning Detection Network. The cloud‐to‐ground flash associated with the observed TGF was formed by a fast downward leader followed by a very intense return stroke peak current of −154 kA. The TGF occurred while the downward leader was below cloud base, and even when it was halfway in its propagation to ground. The suite of gamma‐ray and lightning instruments, timing resolution, and source proximity offer us detailed information and therefore a unique look at the TGF phenomena.

GRAPES-3 is a mid-altitude (2200 m) and near-equatorial (11.°4N) air shower array, overlapping in its field of view for cosmic-ray observations with experiments that are located in the Northern and Southern Hemispheres. We analyze a sample of 3.7 × 10 ^9 cosmic-ray events collected by the GRAPES-3 experiment between 2013 January 1 and 2016 December 31 with a median energy of ∼16 TeV for study of small-scale (

Superconducting (SC) tokamak JT-60SA plays an essential role in fusion research and development by supporting and complementing the ITER project, providing directions to the DEMO design activity and fostering next generation scientists and engineers. Since the short circuit incident at the terminal joints of equilibrium field coil #1 during the integrated commissioning (IC) in March 2021, both EU and JA implementing agencies (IAs) have examined how to ensure safe operation of JT-60SA by mitigating the risk of possible discharge occurrence inside the cryostat. Based on the experience of the global Paschen tests, the IAs have established a strategy of risk mitigation measures, which is a combination of (i) reinforcement of insulation, (ii) avoiding unnecessary voltage application to the coil systems and (iii) immediate de-energization of the coils when deteriorated vacuum conditions are detected. Thanks to the considerable efforts of the Integrated Project Team members, the IC restarted in May 2023. After confirmation of the SC state of the coil systems (TF, EF and CS), the coil energization test and the plasma operation phase 1 (OP-1) started. The first plasma was successfully achieved on 23 October 2023 with a limited value of voltage and current applied to the coils. The plasma configuration control was also confirmed with low plasma current and low auxiliary heating power conditions. Based on the IO–F4E–QST collaboration, activities of JT-60SA have been shared with the IO and provided an important lesson for ITER assembly and commissioning, and will provide an outstanding contribution to fusion research at large. After OP-1, maintenance & enhancement phase 1 (M/E-1) starts from January 2024, in which in-vessel components are installed, and heating and diagnostic systems are extensively upgraded to allow a high power heating experiment planned in OP-2. In order to make the best use of JT-60SA, a newly organized JT-60SA experiment team will refine the research plan for the future high heating power operation phase.

The quasi-biennial oscillation (QBO) is quasi-periodic oscillation of the tropical zonal wind in the stratosphere. When the tropical lower stratospheric wind is easterly (westerly), the winter Northern Hemisphere (NH) stratospheric polar vortex tends to be weak (strong). This relation is known as the Holton–Tan relationship. Several mechanisms for this relationship have been proposed, especially linking the tropics with high latitudes through stratospheric pathway. Although QBO impacts on the troposphere have been extensively discussed, a tropospheric pathway of the Holton–Tan relationship has not been explored previously. Here, we propose a tropospheric pathway of the QBO impact, which may partly account for the Holton–Tan relationship in early winter, especially in the November–December period. The study is based on analyses of observational data and results from a simple linear model and atmospheric general circulation model (AGCM) simulations. The mechanism is summarized as follows: the easterly phase of the QBO is accompanied with colder temperature in the tropical tropopause layer, which enhances convective activity over the tropical western Pacific and suppresses it over the Indian Ocean, thus enhancing the Walker circulation. This convection anomaly generates a Rossby wave train, propagating into the midlatitude troposphere, which constructively interferences with the climatological stationary waves, especially in wavenumber 1, resulting in enhanced upward propagation of the planetary wave and a weakened polar vortex.

The polar night jet (PNJ) is a strong stratospheric westerly circumpolar wind at around 65° N in winter, and the strength of the climatological PNJ is widely recognized to increase from October through late December. Remarkably, the climatological PNJ temporarily stops increasing during late November. We examined this short break in terms of the atmospheric dynamical balance and the climatological seasonal march. We found that it results from an increase in the upward propagation of climatological planetary waves from the troposphere to the stratosphere in late November, which coincides with a maximum of the climatological Eliassen–Palm (EP) flux convergence in the lower stratosphere. The upward propagation of planetary waves at 100 hPa, which is strongest over Siberia, is related to the climatological strengthening of the tropospheric trough over Siberia. We suggest that longitudinally asymmetric forcing by land–sea heating contrasts caused by their different heat capacities can account for the strengthening of the trough.

Optimisation methods were successfully used to calibrate parameters in an atmospheric component of a climate model using two variants of the Gauss–Newton line-search algorithm: (1) a standard Gauss–Newton algorithm in which, in each iteration, all parameters were perturbed and (2) a randomised block-coordinate variant in which, in each iteration, a random sub-set of parameters was perturbed. The cost function to be minimised used multiple large-scale multi-annual average observations and was constrained to produce net radiative fluxes close to those observed. These algorithms were used to calibrate the HadAM3 (third Hadley Centre Atmospheric Model) model at N48 resolution and the HadAM3P model at N96 resolution.For the HadAM3 model, cases with 7 and 14 parameters were tried. All ten 7-parameter cases using HadAM3 converged to cost function values similar to that of the standard configuration. For the 14-parameter cases several failed to converge, with the random variant in which 6 parameters were perturbed being most successful. Multiple sets of parameter values were found that produced multiple models very similar to the standard configuration. HadAM3 cases that converged were coupled to an ocean model and run for 20 years starting from a pre-industrial HadCM3 (3rd Hadley Centre Coupled model) state resulting in several models whose global-average temperatures were consistent with pre-industrial estimates. For the 7-parameter cases the Gauss–Newton algorithm converged in about 70 evaluations. For the 14-parameter algorithm, with 6 parameters being randomly perturbed, about 80 evaluations were needed for convergence. However, when 8 parameters were randomly perturbed, algorithm performance was poor. Our results suggest the computational cost for the Gauss–Newton algorithm scales between P and P2, where P is the number of parameters being calibrated.For the HadAM3P model three algorithms were tested. Algorithms in which seven parameters were perturbed and three out of seven parameters randomly perturbed produced final configurations comparable to the standard hand-tuned configuration. An algorithm in which 6 out of 13 parameters were randomly perturbed failed to converge.These results suggest that automatic parameter calibration using atmospheric models is feasible and that the resulting coupled models are stable. Thus, automatic calibration could replace human-driven trial and error. However, convergence and costs are likely sensitive to details of the algorithm.

The objective of this study was to investigate the alterations in renal morphology and function in an animal model of obesity, and to determine the possible effect of fish oil (FO) supplementation on these alterations. Six-week-old male mice were fed during eight weeks with regular rodent chow (R) or a high-fat diet (HFD), 53.09% fat. After this, they were supplemented orally for 30 days with FO. The weight gain of HFD group was almost three times higher than R. Albuminuria induced by HFD was significantly reduced by FO. The reduction in fractional sodium excretion (FENa+) observed in HFD group was reversed by FO. The HFD was able to increase in almost 100% the concentration of TNF-α in renal tissue, an effect reversed by FO. Intrarenal expression of vimentin was significantly higher in tubulointerstitial cells of HFD group, an effect reversed by FO. In summary, FO partially reverses renal alterations induced by an HFD.

Background: In many countries, gastric cancer is not diagnosed until an advanced stage. An Internet-based e-learning system to improve the ability of endoscopists to diagnose gastric cancer at an early stage was developed and was evaluated for its effectiveness. Methods: The study was designed as a randomized controlled trial. After receiving a pre-test, participants were randomly allocated to either an e-learning or non-e-learning group. Only those in the e-learning group gained access to the e-learning system. Two months after the pre-test, both groups received a post-test. The primary endpoint was the difference between the two groups regarding the rate of improvement of their test results. Findings: 515 endoscopists from 35 countries were assessed for eligibility, and 332 were enrolled in the study, with 166 allocated to each group. Of these, 151 participants in the e-learning group and 144 in the non-e-learning group were included in the analysis. The mean improvement rate (standard deviation) in the e-learning and non-e-learning groups was 1·24 (0·26) and 1·00 (0·16), respectively (P