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Background/Aims Leucine-rich α-2-glycoprotein (LRG) is a new serum biomarker reflecting the disease activity of ulcerative colitis (UC), but its change during the acute phase has not been enough investigated. Methods Patients with UC who initiated the induction therapy with steroid or advanced therapy (biologics or Janus kinase inhibitors) were prospectively enrolled. Associations of LRG, C-reactive protein (CRP) and fecal calprotectin (FC) at baseline, week 1, and week 8 with clinical remission at week 8 and subsequent endoscopic improvement within 1 year (Mayo endoscopic subscore of 0 or 1) were assessed. Results A total of 143 patients with UC were included. LRG and CRP at week 1 were significantly lower in the clinical remission group than in the non-remission group (LRG, 20.6 μg/mL vs. 28.4 μg/mL, P

Abstract The devastation caused by the January 2022 eruption of Hunga Tonga-Hunga Ha’apai volcano (HTHH) in the Tongan archipelago reminded us of the importance of monitoring shallow-sea volcanic activity. Seismic observations are essential for such monitoring, but there were no operational seismic stations in Tonga at the time of the eruption. There are only a few islands near Tongan volcanoes, and installation and maintenance of seismic stations on remote islands are expensive. Seismic observations based on distributed acoustic sensing (DAS) using a seafloor cable may provide a more practical and economical solution. To investigate the potential of this approach, we made preliminary DAS observations for 1 week using the seafloor domestic broadband telecommunications cable in Tonga. DAS equipment was installed at the landing station of the seafloor cable at Nuku’alofa on Tongatapu, the main island of Tonga. To provide reference data, we installed several seismometers on Tongatapu. The DAS data we obtained showed high noise levels in areas of shallow coral reef, but noise levels decreased greatly in deeper water areas, indicating that DAS is suitable for seismic observations of the deep seafloor. We detected many local and regional earthquakes during our week of observation and determined 17 earthquake hypocenters by picking P- and S-wave arrival times from the DAS and onshore seismic data. Although most of these were tectonic events related to the subduction of the Pacific plate along the Tonga trench, several events were detected around the volcanic chain of the Tongan archipelago including one event beneath the HTHH crater, implying that activity at HTHH has continued since the 2022 eruption. The much lower cost of installation of DAS equipment compared to that for pop-up type ocean-bottom seismometers and the ability of DAS systems to monitor seismic activity in real-time make it an attractive option for monitoring the activity of HTHH and other volcanoes near seafloor cables in the Tongan archipelago. Graphical Abstract

Abstract Detecting seismic events, discriminating between different event types, and picking P- and S-wave arrival times are fundamental but laborious tasks in seismology. In response to the ever-increasing volume of seismic observational data, machine learning (ML) methods have been applied to try to resolve these issues. Although it is straightforward to input standard (time-domain) seismic waveforms into ML models, many studies have used time–frequency-domain representations because the frequency components may be effective for discriminating events. However, detailed comparisons of the performances of these two methods are lacking. In this study, we compared the performances of 1D and 2D convolutional neural networks (CNNs) in discriminating events in datasets from two different tectonic settings: tectonic tremor and ordinary earthquakes observed at the Nankai trough, and eruption signals and other volcanic earthquakes at Sakurajima volcano. We found that the 1D and 2D CNNs performed similarly in these applications. Half of the misclassified events were misassigned the same labels in both CNNs, implying that the CNNs learned similar features inherent to the input signals and thus misclassified them similarly. Because the first convolutional layer of a 1D CNN applies a set of finite impulse response (FIR) filters to the input seismograms, these filters are thought to extract signals effective for discriminating events in the first step. Therefore, because our application was the discrimination of signals dominated by low- and high-frequency components, we tested which frequency components were effective for signal discriminations based on the filter responses alone. We found that the FIR filters comprised high-pass and low-pass filters with cut-off frequencies around 7–9 Hz, frequencies at which the magnitude relations of the input signal classes change. This difference in the power of high- and low-frequency components proved essential for correct signal classifications in our dataset. Graphical Abstract

Abstract Background and Aim Crohn's disease (CD) often causes intractable diarrhea after intestinal resection. Anion exchange resins have been reported to be effective in patients with bile acid diarrhea after distal ileectomy; furthermore, bile acid metabolism has been implicated in the pathogenesis of CD. Therefore, we aimed to examine the effectiveness of colestimide in the management of postoperative CD, and to compare its impact between patients with and those without ileocecal resection. Methods Postoperative CD patients prescribed colestimide for diarrhea between April 2017 and December 2020 were retrospectively evaluated for changes in the total Crohn's disease activity index (CDAI), each CDAI component including diarrhea frequency/week, albumin, and C‐reactive protein (CRP) was evaluated before and after the administration of colestimide. Furthermore, comprehensive patient and physician assessments were reviewed from medical records during the first outpatient visit as a global clinical judgment after the initiation of colestimide therapy. Results A total of 24 patients were included, of whom 17 had a previous history of ileocecal resection. Significant improvement was noted in CDAI and diarrhea frequency only in the ileocecal resection group (CDAI: 114.5 ± 52.7 and 95.4 ± 34.8, P

Abstract Background Productivities of bioactive compounds in high-value herbs and medicinal plants are often compromised by uncontrollable environmental parameters. Recent advances in the development of plant factories with artificial lighting (PFAL) have led to improved qualitative and/or quantitative production of bioactive compounds in several medicinal plants. However, information concerning the effect of light qualities on plant pharmaceutical properties is limited. The influence of three different light-emitting diode (LED) spectra on leaf fresh weight (FW), bioactive compound production and bioactivity of Artemisia annua L. against the malarial parasite Plasmodium falciparum NF54 was investigated. Correlation between the A. annua metabolites and antimalarial activity of light-treated plant extracts were also determined. Results Artemisia annua plants grown under white and blue spectra that intersected at 445 nm exhibited higher leaf FW and increased amounts of artemisinin and artemisinic acid, with enhanced production of several terpenoids displaying a variety of pharmacological activities. Conversely, the red spectrum led to diminished production of bioactive compounds and a distinct metabolite profile compared with other wavelengths. Crude extracts obtained from white and blue spectral treatments exhibited 2 times higher anti-Plasmodium falciparum activity than those subjected to the red treatment. Highest bioactivity was 4 times greater than those obtained from greenhouse-grown plants. Hierarchical cluster analysis (HCA) revealed a strong correlation between levels of several terpenoids and antimalarial activity, suggesting that these compounds might be involved in increasing antimalarial activity. Conclusions Results demonstrated a strategy to overcome the limitation of A. annua cultivation in Bangkok, Thailand. A specific LED spectrum that operated in a PFAL system promoted the accumulation of some useful phytochemicals in A. annua, leading to increased antimalarial activity. Therefore, the application of PFAL with appropriate light spectra showed promise as an alternative method for industrial production of A. annua or other useful medicinal plants with minimal environmental influence.

Abstract Recent studies have documented the occurrence of shallow very low frequency earthquakes (VLFE) in subduction zones. The heterogeneity of the materials or stresses that act on the plate interface results in the variable slip rate. Stress on the décollement can be controlled by the décollement geometry and the regional stress, which is also able to control the material properties. We determined the distribution of stress along the shallow portion of the décollement in the Nankai Trough using a three-dimensional (3D) seismic survey and regional stress analysis to construct maps of normalized slip tendency (T s ′) and dilation tendency (T d ). Alignments of VLFEs trend parallel to the trends of $${T}_{s}^{^{\prime}}$$ T s ′ and $${T}_{d}$$ T d . On the other hand, very low $${T}_{s}^{^{\prime}}$$ T s ′ and $${T}_{d}$$ T d areas probably act as barriers that limit the number of VLFEs that can migrate towards the trench. Because the $${T}_{s}^{^{\prime}}$$ T s ′ and $${T}_{d}$$ T d distributions are derived only from the décollement geometry and the regional stress without incorporating any data on sediment properties, the consistency between the trends suggests that the décollement geometry is the primary control on VLFE activity.

Artificial light has been used to control plant growth and secondary metabolite production. Artemisia annua L. plants were illuminated with three light-emitting diode (LED) spectra to investigate proteomic and biochemical responses. After 7 days, proteomic data revealed different protein numbers in leaves, stems, and roots under particular treatments. Results demonstrated increased accumulation of several proteins, including secondary metabolite-related proteins. The red light (R) (660 nm) highly induced terpenoid proteins. Similar biochemical profiles were observed in white light (W) (445, 544 nm) and blue light (B) (445 nm) conditions, while profiles from R treatment were different. Functional proteins of W and B treatments were involved in the MVA and MEP pathways and sesquiterpene biosynthesis. By contrast, unique proteins in R treatment were mainly expressed in sesquiterpene and tetraterpene biosynthesis. Specific relationships between biosynthetic proteins and sesquiterpenes were observed, suggesting the indispensable role of the light spectrum in regulating terpenoid biosynthesis.

Abstract We estimate the hypocenter locations and the centroid moment tensor solutions of the shallow very-low-frequency earthquake (sVLFE) activity that occurred in the Kumano-nada region of the Nankai Trough megathrust zone in central Japan from December 2020 to January 2021. Using seafloor observation data, we examined the detailed spatio-temporal distribution of the sVLFE activity. During this episode, the activity area was within the vicinity in which the sVLFE activity has been observed in the past and can be divided into two major parts. The sVLFE activity started from the eastern side and remained there for the first 5 days and then migrated to the western side via secondary expansion. The eastern active area is located just below the outer ridge and coincides with the location where the paleo-Zenith Ridge subducted. The western activity area is centered between the outer wedge and the outer ridge with the primary active area being at the outer wedge. Comparing the activity in the eastern and western areas, the eastern side is more active, but the individual moment releases on this side are smaller than those on the western side. This may indicate a difference in the fluid pressure along the plate boundary between the eastern and western areas. After the second expansion of the active area, we observed several migration patterns within the expanded area with a faster velocity than those of the initial and second expansions. The direction of these migrations is opposite to that of the first and second expansions. This indicates that the fluid pressure and/or stress level in the sVLFE generation region changed with time within this episode. Furthermore, many waveforms with sVLFE characteristics were observed at only one or a few observation points near the trough axis in the middle to latter half of January 2021. This indicates the occurrence of small-scale sVLFEs in the vicinity of the trough axis at the end of this sVLFE episode. Graphical Abstract

Introduction: Bowel ultrasound is a noninvasive alternative to endoscopy for assessing the disease activity of ulcerative colitis; however, it is unclear whether bowel ultrasound can predict subsequent relapse from remission. Materials and Methods: A retrospective cohort study enrolled patients with ulcerative colitis who underwent bowel ultrasound between July 2018 and July 2021 during clinical remission (patient-reported outcome-2 ≤1 and no rectal bleeding) for at least 3 months and were followed up for 1 year. Ultrasonographic findings (bowel wall thickness, bowel wall flow, bowel wall stratification, and enlarged lymph nodes), Milan ultrasound criteria, Mayo endoscopic subscore, C-reactive protein, and fecal calprotectin levels and their association with subsequent clinical relapse were assessed. Relapse was defined as rectal bleeding score ≥1, stool frequency score ≥2, or treatment intensification for symptoms. Results: 31% of the patients (18/58) relapsed within 1 year. No single ultrasonographic finding predicted relapse, whereas Milan ultrasound criteria >6.2 (p = 0.019), Mayo endoscopic subscore ≥1 (p = 0.013), and fecal calprotectin ≥250 μg/g (p = 0.040) were associated with a shorter time to relapse in the log-rank test. Milan ultrasound criteria >6.2 (hazard ratio 3.22; 95% confidence interval 1.14–9.08, p = 0.027) and Mayo endoscopic subscore ≥1 (hazard ratio 8.70; 95% confidence interval 1.11–68.1, p = 0.039) showed a higher risk of relapse according to a Cox proportional hazards model. Conclusion: Bowel ultrasound can predict subsequent clinical relapse from remission in patients with ulcerative colitis using the Milan ultrasound criteria.

Introduction: A large proportion of small bowel lesions in Crohn’s disease (CD) may exist beyond the reach of ileocolonoscopy and there is no gold standard imaging modality to screen them, suggesting the need for optimal biomarkers. We aimed to compare the usefulness of C-reactive protein (CRP), faecal calprotectin (FC), and leucine-rich alpha-2 glycoprotein (LRG) in determining small bowel lesions of CD. Methods: This was a cross-sectional observational study. CRP, FC, and LRG were prospectively measured in patients with quiescent CD who underwent imaging examinations (capsule or balloon-assisted endoscopy, magnetic resonance enterography, or intestinal ultrasound) selected by the physician in clinical practice. Mucosal healing (MH) of the small bowel was defined as a lack of ulcers. Patients with a CD activity index >150 and active colonic lesions were excluded. Results: A total of 65 patients (27, MH; 38, small bowel inflammation) were analysed. The area under the curve (AUC) of CRP, FC, and LRG was 0.74 (95% confidence interval: 0.61–0.87), 0.69 (0.52–0.81), and 0.77 (0.59–0.85), respectively. The AUC of FC and LRG in a subgroup of 61 patients with CRP

Abstract Megathrust earthquakes that occur repeatedly along the plate interface of subduction zones can cause severe damage due to strong ground motion and the destructive tsunamis they can generate. We developed a set of scenario earthquakes to evaluate tsunami hazards and tsunami early warning systems for such devastating earthquakes. Although it is known that the slip distribution on a fault strongly affects the tsunami height distribution in near-field coastal areas, the slip distribution of future earthquakes cannot be exactly predicted. One way to resolve this difficulty is to create a set of scenario earthquakes in which a set of heterogeneous slip distributions on the source fault is stochastically generated based on a given slip probability density function (SPDF). The slip distributions generated in this manner differ from event to event, but their average over a large ensemble of models converges to a predefined SPDF resembling the long-term average of ruptures on the target fault zone. We created a set of SPDF-based scenario earthquakes for an expected future Mw 8.2 Tonankai earthquake in the eastern half of the Nankai trough, off southwest Japan, and computed the ensuing tsunamis. We found that the estimated peak coastal amplitudes among the ensemble of tsunamis along the near-field coast differed by factors of 3 to 9, and the earliest and latest arrivals at each observation site differed by 400 to 700 s. The variations in both peak tsunami amplitude and arrival time at each site were well approximated by a Gaussian distribution. For cases in which the slip distribution is unknown, the average and standard deviation of these scenario datasets can provide first approximations of forecast tsunami height and arrival time and their uncertainties, respectively. At most coastal observation sites, tsunamis modeled similarly but using a uniform slip distribution underpredicted tsunami amplitudes but gave earlier arrival times than those modeled with a heterogeneous slip distribution. Use of these earlier arrival times may be useful for providing conservative early warnings of tsunami arrivals. Therefore, tsunami computations for both heterogeneous and uniform slip distributions are important for tsunami disaster mitigation. Graphical abstract

Abstract To explore a local relationship between geological structures and the occurrence of very-low-frequency earthquakes (VLFEs), a particular class of slow earthquakes with characteristic periods of 10–100 s, we investigated three-dimensional (3D) structural features using reprocessed 3D seismic data from the Nankai Trough off Kumano, southwestern Japan. In this region, VLFEs have been observed along the subducting Philippine Sea Plate. Although the detailed source distribution of VLFEs was estimated by means of recent land-based and offshore seismic networks, the relation with geological features is not well understood. First, we reprocessed the 3D seismic data with advanced techniques and reinterpreted the fault distribution in the sediment layer of the accretionary prism and tracked two key horizons: a décollement and the oceanic crust surface. In the accretionary prism sediments, multiple continuous reflectors of basal detachments in the underthrust sequence and conjugate faults cutting the shallow imbricated thrust sequence were identified. In contrast to the gentle variation in the décollement surface, the topographic relief of the oceanic crust was prominent, with ridges and surface displacement due to faults in the oceanic crust. Then, we compared the structural features with the VLFE source locations. Most VLFEs were located deep in the underthrust sediments where the sediments may consist of underconsolidated muds. Furthermore, a high spatial correlation was observed between the VLFE distribution and the oceanic crust topographic relief. The maximum stress direction, which was inferred from the conjugate faults in the imbricated thrust zone, was consistent with the spatial relation between the VLFE localization and the oceanic crust central ridge. Oceanic crust ridges may cause strain accumulation in the underthrust sediments on the landward sides of the ridges, and low-angle slow thrust movements might be caused using weak slip planes in the underthrust muddy sediments. That is, the topographic relief of the oceanic crust may control the occurrence of shallow VLFEs in the Nankai Trough.

Background/Aims The pharmacokinetics of tacrolimus (TAC) is known to be largely influenced by single-nucleotide polymorphisms (SNPs) in CYP3A5. Patients starting TAC require careful dose adjustment, owing to the wide range of optimal dosages, depending on their CYP3A5 expression status. Here, we evaluated whether individualization of TAC dosages based on CYP3A5 SNPs would improve its therapeutic efficacy in ulcerative colitis. Methods Twenty-one patients were prospectively treated, with their initial dosage adjusted according to their CYP3A5 status (0.1, 0.15, and 0.2 mg/kg/day for CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1, respectively). Their clinical outcomes were compared with those of patients treated with a fixed dose (0.1 mg/kg/day). Results The first blood trough level of CYP3A5 expressors, CYP3A5*1/*3 or CYP3A5*1/*1, and the overall rate in achieving the target blood trough level within a week in the individualized-dose group were significantly higher than those in the fixed-dose group (5.15±2.33 ng/mL vs. 9.63±0.79 ng/mL, P=0.035 and 12.5% vs. 66.7%, P=0.01). The remission rate at 2 weeks in the expressors was as high as that in the nonexpressors, CYP3A5*3/*3, in the individualized-dose group. Conclusions Individualized TAC treatment is effective against ulcerative colitis regardless of the CYP3A5 genotype.

Background/Aims Oral mesalazine is an important treatment for ulcerative colitis (UC), and non-adherence to mesalazine increases the risk of relapse. Controlled-release (CR) mesalazine has 2 formulations: tablets and granules. The relative acceptabilities of these formulations may influence patient adherence; however, they have not been compared to date. This study aimed to evaluate the acceptabilities of the 2 formulations of CR mesalazine in relation to patient adherence using a crossover questionnaire survey. Methods UC patients were randomly assigned to 2 groups in a 1:1 ratio. Patients in each group took either 4 g of CR mesalazine tablets or granules for 6 to 9 weeks, and then switched to 4 g of the other formulation for a further 6 to 9 weeks. The acceptability and efficacy were evaluated by questionnaires, and adherence was assessed using a visual analog scale. The difference in acceptabilities between the 2 formulations and its impact on adherence were assessed. Results A total of 49 patients were prospectively enrolled and 33 patients were included in the analysis. Significantly more patients found the tablets to be less acceptable than the granules (76% vs. 33%, P=0.0005). The granules were preferable to the tablets when the 2 formulations were compared directly (73% vs. 21%, P=0.004), for their portability, size, and numbers of pills. The adherence rate was slightly better among patients taking the granules (94% vs. 91%) during the observation period, but the difference was not significant (P=0.139). Conclusions CR mesalazine granules are more acceptable than tablets, and may therefore be a better option for long-term medication.

We have detected an event of pore pressure change (hereafter, we refer it to “pore pressure event”) from borehole stations in real time in March 2020, owing to the network developed by connecting three borehole stations to the Dense Oceanfloor Network System for Earthquakes and Tsunamis (DONET) observatories near the Nankai Trough. During the pore pressure event, shallow very low-frequency events (sVLFEs) were also detected from the broadband seismometers of DONET, which suggests that the sVLFE migrated toward updip region along the subduction plate boundary. Since one of the pore pressure sensors have been suffered from unrecognized noise after the replacement of sensors due to the connecting operation, we assume four cases for crustal deformation component of the pore pressure change. Comparing the four possible cases for crustal deformation component of the volumetric strain change at C0010 with the observed sVLFE migration and the characteristic of previous SSEs, we conclude that the pore pressure event can be explained from SSE migration toward the updip region which triggered sVLFE in the passage. This feature is similar to the previous SSE in 2015 and could be distinguished from the unrecognized noise on the basis of t-test. Our new finding is that the SSE in 2020 did not reach very shallow part of the plate interface because the pore pressure changes at a borehole station installed in 2018 close to the trough axis was not significant. In the present study, we estimated the amount, onset and termination time of the pore pressure change for the SSE in 2020 by fitting regression lines for the time history. Since the change amount and duration time were smaller and shorter than the SSE in 2015, respectively, we also conclude that the SSE in 2020 had smaller magnitude that the SSE in 2015. These results would give us a clue to monitor crustal deformation along the Nankai Trough directly from other seafloor observations.

Some monocotyledonous plants, including liliaceous, amaryllidaceous and iridaceous ones, produce flowers with petaloid tepals in whorls 1 and 2 organs. For explaining the molecular mechanism of two-layered petaloid tepal development, the modified ABC model has been proposed, in which B class genes are expressed in whorl 1 organs as well as in whorls 2 and 3 organs. We have previously obtained results strongly support the modified ABC model by chimeric repressor gene-silencing technology (CRES-T)-mediated suppression of B function in the liliaceous plant Tricyrtis sp. In the present study, we introduced a CRES-T construct derived from the B class gene of Tricyrtis sp. (TrihDEFa-SRDX) into Lilium sp. in order to examine the effect of suppressing B function on the floral organ identity. Flowers of transgenic plants did not open fully and had pale pink-colored tepals with decreased numbers of papillae on the adaxial side in whorls 1 and 2 compared with those of non-transgenic plants. No apparent morphological alterations were observed in whorls 3 and 4 organs. Both the amount of total anthocyanins and the expression levels of endogenous flavonoid biosynthesis-related genes (LhMYB12, LhbHLH2, LhCHS, LhF3H, LhF3'H, LhDFR and LhANS) decreased in whorls 1 and 2 organs of transgenic plants compared with non-transgenic plants. In addition, the expression levels of endogenous B class genes (LFDEF, LFGLOA and LFGLOB) decreased in transgenic plants and the level was negatively correlated with the degree of morphological alteration. Thus suppression of B function may reduce the identity of petaloid tepals in whorls 1 and 2 of transgenic Lilium sp.

Abstract Megathrust earthquakes have occurred repeatedly at intervals of 100 to 150 years along the Nankai Trough, situated in the southwest of Japan. Given that it has been 70 years since the last event, the occurrence of the next devastating earthquake is anticipated in the near future. On April 1, 2016, a moderate earthquake (Mw 5.9, MJMA 6.5) occurred off the southeastern coast of Mie Prefecture in the source region of the 1944 Tonankai earthquake (Mw 8.2). In this study, we investigated the influence of the 2016 earthquake on future megathrust earthquakes. We first determined the hypocenter distributions using a precise velocity structure obtained from seismic surveys in the source region. Using data obtained from the DONET ocean-bottom observation network, we found that this earthquake occurred along the plate boundary fault, which is also believed to have slipped during past megathrust earthquakes. We then performed a preliminary numerical simulation to reproduce the occurrence of a moderate earthquake in the middle of a megathrust earthquake cycle. We used a hierarchical asperity model, in which smaller asperities causing moderate earthquakes are embedded in a hyper-asperity that serves as the source region of megathrust earthquakes. The simulation shows that moderate earthquakes, caused by ruptures of a smaller asperity, occur as a result of shrinkage of strongly coupled areas in the hyper-asperity. This result is consistent with the observation that the hypocenter of the 2016 earthquake was located at the edge of a strongly coupled region along the plate boundary. The simulation also reproduced postseismic slip (afterslip/slow slip) along the plate boundary updip of the hyper-asperity, which is consistent with the observations of slow slip events and very-low-frequency earthquakes after the 2016 earthquake. Thus, the occurrence of the moderate earthquake offshore southeastern Mie Prefecture in the middle of the megathrust earthquake cycle implies that the shrinkage of the strongly coupled area along the plate boundary is occurring as a preparatory process for the next megathrust earthquake in the region.

Slow earthquakes are now increasingly recognised to occur at plate boundaries globally. Here, the authors examine seafloor observational data from the Nankai trough and find that very-low-frequency events and slow-slip events frequently occur together and share the same common source fault.

In the Nankai subduction zone a low-velocity zone (LVZ) has been detected. Here, the authors present shear wave velocity profiles to show that low frequency earthquakes correlate with the distribution of the LVZ in the Nankai subduction zone.

Extracolonic involvement of the gastrointestinal tract is extremely uncommon in ulcerative colitis (UC) and rarely found in the upper gastrointestinal tract or in postoperative cases since it typically responds to steroids. Here we report a case of UC complicated by extensive ileal inflammation that was refractory to steroids. A 20-year-old man was diagnosed with UC of typical pancolitis without ileal involvement and started treatment with pH-dependent mesalazine and oral prednisolone. Although his symptoms transiently resolved, the condition flared when the steroid dose was tapered down. Computed tomography revealed marked thickening of the ileal wall, and capsule endoscopy and balloon-assisted enteroscopy found diffuse mucosal inflammation with ulcers in the ileum. On the contrary, the inflammation in the colon and rectum was improving. Since the response to the second steroid course was inadequate, treatment with adalimumab and 6-mercaptopurine was initiated and finally achieved clinical and endoscopic remission. The investigation of small intestinal lesions is necessary in patients with UC whose clinical deterioration cannot be explained by colonic lesions.

Abstract We determined the three-dimensional structure of the crust and upper mantle off the Boso Peninsula, Japan, by analyzing seismograms recorded by ocean-bottom seismometers and land stations between 2011 and 2013. We employed seismic tomography to determine the P- and S-wave velocity structures and earthquake locations simultaneously. The tomographic image shows that the mantle parts of the Pacific and the Philippine Sea plates have high-velocity anomalies. The upper boundary of the Philippine Sea plate is delineated as approximately 2–6 km shallower than that previously estimated from land-based data for the area 140.5°E–141.5°E and 35°N–35.5°N. A pronounced low-velocity anomaly in P- and S-waves with low-V p/V s ratio (1.5–1.6) was observed at depths shallower than 20 km in the overriding North American plate. This anomaly may be caused by the presence of rocks with a low-V p/V s ratio, such as quartzite, and the water expelled from the subducted Pacific and Philippine Sea plates. Graphical Abstract .

This research discusses how system dynamics is used to develop an educational game, called CANDY OG, to learn how to improve supply chain performance under conflict of key performance indicators (KPIs). Its objective is to explore applicability of system dynamics to design a business game for fostering interpersonal skills. A causal loop diagram is used to confirm the game design so that the participants can learn by playing about importance of understanding other stakeholder’s mental model to improve supply chain performance. The game was played for experiments to evaluate effectiveness of the game design by surveys and other qualitative methods such as samples’ memos during the game, follow-up interviews and participatory observations. Our experimental results suggest a possibility that the game provides experiential learning to develop interpersonal skills at managing conflicts of KPIs, and thus indicate that the use of system dynamics helps to ensure appropriate designing of the game. The originality is a use of system dynamics for designing an educational game, leveraging its capability to analyze mental models of stakeholders in a system.

Background/aimsThe small bowel is affected in more than half of patients with Crohn's disease (CD) at the time of diagnosis, and small bowel involvement has a negative impact on the long-term outcome. Many patients reportedly have active lesions in the small intestine even in patients in clinical remission. This study was performed to compare findings of magnetic resonance enterography (MRE) and ileocolonoscopy.MethodsA single-center retrospective study was conducted in 50 patients (60 imaging series) with CD, for whom MRE was additionally performed during the bowel preparation for subsequent ileocolonoscopy. Endoscopic remission was defined as a Simple Endoscopic Score for CD (SES-CD) of ResultsImportantly, 7 of 29 patients (24.1%) with endoscopic remission had a MaRIA score of ≥50. Both SES-CD and MaRIA correlated with the need for treatment escalation (P = 0.025, P = 0.009, respectively). MRE predicted the need for treatment escalation even in patients with endoscopic remission. Although no correlation was present between SES-CD and MaRIA score in patients with structuring/penetrating disease, or insufficient ileal insertion (ConclusionsThe MaRIA score predicts the need for treatment escalation even in patients with endoscopic remission, indicating that addition of MRE to conventional ileocolonoscopy alone can be a useful, noninvasive tool for monitoring CD especially in stricturing or penetrating disease.

This study systematically analyzed life cycle CO2 (LCCO2) emissions of a comprehensive set of mass-produced 2,000 cc class sedan-type vehicles, using a hybrid life cycle inventory approach. Gasoline and diesel internal combustion engine vehicles (ICEVs), hybrid electric vehicle (HEV) as well as battery electric vehicle (BEV) and fuel cell vehicle (FCV) were investigated, considering (i) the current BEV market trends, (ii) Japan's energy mix (the average for 2012–2014), and (iii) the use of the HVAC system. The results show that the annual average increment of CO2 emissions in use phase by HVAC system in Japan (assumed annual mean temperature of 15°C) was presumed to be evenly 9% regardless of vehicle types, although further detail analysis is required. The CO2 emissions in use phase of BEV were higher than those of HEV and FCV (applied hydrogen produced by steam reforming of LPG (on-site)) due to thermal power dominant electricity generation mix in Japan in recent years. As a consequence of high CO2 emissions from power supply and battery production, the LCCO2 emissions of BEV equipped with 75 kWh battery were higher than those of HEV, FCV (on-site), and conventional ICEV (diesel). By reducing the battery capacity to 40 kWh or less, the LCCO2 emissions of BEV become lower than those of ICEVs and FCV (on-site), making BEV a competitive alternative. However, it is difficult that BEV mitigates both LCCO2 emissions and driver's range anxiety. In conclusion, HEV shows the competitive performance in terms of LCCO2 emissions with long driving range in Japan.

Fecal calprotectin (FC) is well accepted as a non-invasive biomarker which objectively reflects colonic inflammation in ulcerative colitis (UC). However, its value as a marker of response during the early phase of remission induction treatment has not been well studied. The aim of this study is to evaluate the significance of FC for predicting the short-term outcomes of remission induction treatment in patients with UC.A prospective observational study was conducted among 31 patients with active UC. FC was monitored with two-item patient-reported outcome (PRO2), partial Mayo score (PMS), and Lichtiger clinical activity index (CAI) during the first 4 weeks of remission induction treatment. Clinical response was defined as a decrease in CAI of 3 or more points below baseline. Mucosal healing (MH) was defined as Mayo endoscopic subscore 0 or 1. Within-day and within-stool variability of FC were assessed during the first week of treatment.In week 4-clinical responders, PRO2, PMS, and CAI significantly decreased from day 3, however, FC did not show significant reduction until week 2. Among all markers, the decrease in PRO2 at week 4 most accurately predicted MH at week 12. Within-day variability of FC was remarkably wide even at the first week in clinical responders. Within-stool variability was extremely small.PRO2 predicted the short-term outcomes of remission induction treatment earlier than FC possibly because of the wide within-day variability of FC in active UC.

Energy security is a difficult issue to evaluate due to its polysemic and multifaceted nature. Recent studies have evaluated energy security by considering a multitude of dimensions (i.e., availability, affordability, etc.). However, these works lack coherence, as performance in one dimension is not necessarily relevant to performance in others. Due to this consideration, an ex-ante evaluation (i.e., policy analysis) of energy security cannot be reliably performed. This paper proposes an integrated simulation approach to address this apparent shortcoming. We consider energy security performance as a feature that emerges from interactions between the components of energy security dimensions. Integration is completed by identifying and establishing relationships between these components. A model is developed for the simulation that uses system dynamics as a modeling tool. The evaluation of Indonesia’s energy security is presented as an example. It is found that the policies intended to improve Indonesia’s energy security may conflict with each other. Increasing energy production will maintain the performance of the availability dimension at a high level in the short term, but this benefit is outweighed by the resulting degradation to the performance of the acceptability dimension. Subsidy elimination will increase the availability of energy due to lower energy consumption at the expense of maintaining energy affordability for the public. This study shows that the interrelationships between the dimensions of energy security is an important aspect to consider in energy security evaluations, as they can reveal tradeoffs between policies and improve the reliability of analyses.

Within ASEAN, Malaysia is a major oil-exporting country; however, it is expected to become a net oil-importing country in the near future. This issue brings concerns over Malaysia’s energy security, particularly on the aspect of oil import dependency. This is because its transportation and industrial sectors are still heavily dependent on oil products. By simulating dynamic interplays between developments in Malaysia’s oil sector and its economy sectors, this study explores the possible years of the transformation and the extent to which it will be dependent on oil import. Four scenarios related to enhanced oil recovery, exploration and production investment, subsidy elimination and technology advances are considered for the simulation. In isolation, the subsidy elimination scenario provides the best result. However, if all scenarios are considered simultaneously, an undesired effect emerges. The earliest that Malaysia is expected to become a net oil-importing country is 2012 and the latest is 2021. Malaysia’s dependence on oil imports is expected to continue increasing. In all scenarios, the shares of oil import in the total supply rise to above 90% in 2030, with the highest share at 97%.

This study is focused on the reduction of CO2 emissions and costs associated with ultra-low viscosity (ULV) engine oils for passenger vehicles. Specifically, the reduction in life cycle CO2 (LCCO2) emissions from lower-viscosity engine oil and the oil drain interval (ODI) extension were estimated taking into account both mineral engine oil and synthetic engine oil. Furthermore, the cost-effectiveness of ULV engine oils were investigated by performing base-stock cost analysis. When the volatility limit of the Noack test (American Society for testing and materials (ASTM) D5800) was set to 15 wt %, the results indicated that the lower limit of kinematic viscosity at 100 °C (KV100) for mineral engine oil (with Group-III base-stock) and synthetic engine oil (with polyalphaolefin (PAO) base-stock) were approximately 5.3 and 4.5 mm2/s, respectively. Compared to conventional 0W-16 mineral engine oil (KV100 6.2 mm2/s), the effect of reducing LCCO2 emissions on ULV mineral engine oil (ULV-Mineral, KV100 5.3 mm2/s) was estimated at 0.6%, considering 1.5⁻1.8 L gasoline engines in New European Driving Cycles (NEDC) mode. ULV-Mineral, which continues to use a mineral base-stock, is considered highly cost-effective since its cost is similar to the conventional 0W-16 mineral engine oil. On the other hand, compared with ULV-Mineral, the vehicle fuel efficiency improvement from the use of ULV synthetic engine oil (ULV-PAO, KV100 4.5 mm2/s) was estimated to be 0.5%. However, considering CO2 emissions during engine oil production, the reduction of LCCO2 emission from ULV-PAO compared with ULV-Mineral was estimated to be only 0.1% or less using 2030 standards (assuming a vehicle fuel efficiency of 66.5 g-CO2/km) when ODI is set equivalent (7500 km) to mineral engine oil. As a result, ULV-PAO’s cost-effectiveness, considering the cost increase of PAO base-stock, was found to be nominal. Contrariwise, when the characteristics of PAO base-stock with higher oxidation stability are used comparatively with the mineral base-stock while extending the ODI to 15,000 km, the effect of reducing LCCO2 emissions of ULV-PAO was estimated to be 0.7% in 2030, making ULV-PAO a competitive and cost-effective alternative. In other words, the popularization of synthetic engine oil toward 2030 will require the consideration of both viscosity reduction and ODI extension.

Popularity of clean energy vehicles (CEVs) are expected in order to reduce CO2 emissions to mitigate the global warming. However, the popularity provides not only environmental but also economic impacts. An EV requires a battery, but does not require the engine parts any more, which will bring a structural change of the auto parts industry. It is necessary to understand the characteristics of parts used in each CEV type and analyze the economic effects before considering the portfolio for introducing CEVs. In this study, CEV types which have a battery or a fuel cell based powertrain system are considered as well as gasoline, diesel or natural gas engines. This paper proposes an economic ripple effect model using the Input-Output Table. Simulation results show economic impacts in Japan in 2020 and 2030 for the target sales of CEVs assumed by the Ministry of the Environment in 2010. For example, simulation results indicates that production amount in Japan in 2030 is expected to decrease about 1.5 trillion yen compared to 2010.