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Background In women with inflammatory bowel disease, at least 3 months of preconception corticosteroid-free remission (CFREM) is recommended by experts in current consensus statements. However, data are lacking on the appropriate preconception remission period. We investigated the appropriate preconception CFREM period in women with ulcerative colitis to reduce maternal disease activity and adverse pregnancy outcomes (ie, preterm birth, low birth weight, and small for gestational age). Methods We retrospectively examined 141 pregnancies in women with ulcerative colitis at 2 institutions. We categorized the patients into 3 subgroups by their preconception CFREM period (≥3 months, >0 to Results During pregnancy, the rate of active disease was significantly lower in the ≥3 months and >0 to 3 months CFREM group compared with those in the other groups, but this difference was not significant. Conclusions A preconception CFREM period of more than 3 months may be appropriate for better maternal and adverse pregnancy outcomes, as recommended in consensus statements.

A new electron accelerator has been designed and is now under construction at AIST, Tsukuba, Japan. The accelerator will be used to produce a pulsed neutron beam for materials analysis. The design maximizes the yield of slow neutrons with high pulse temporal resolution as described in a previous publication [K. Kino et al., Nuclear Inst. and Methods in Physics Research, A 927 (2019) 407–418]. The accelerator is composed of a thermal cathode type electron gun with S-Band buncher/accelerator cavity followed by three, 2.9 m long S-Band acceleration cavities. High power RF is supplied by three klystron units, with klystron No.1 supplying both the electron gun and the 1st cavity, and klystrons No.2 and No.3 connected to the 2nd and 3rd cavities respectively. The design parameters of the accelerator are; pulse rate: 100 Hz, pulse length: 10 μs, electron current: 250 mA, electron energy: 40 MeV. Operating at these parameters a maximum beam power of around 10 kW will be delivered to the water-cooled Ta target for neutron production. In this report we will describe the design and construction of the electron accelerator.

AJM300 is an oral, small-molecule α4-integrin antagonist. We assessed the efficacy and safety of AJM300 in patients with moderately active ulcerative colitis.This multicentre, randomised, double-blind, placebo-controlled, phase 3 study consisted of two phases: a treatment phase and an open-label re-treatment phase. The study was done at 82 hospitals and clinics in Japan. Patients with a Mayo Clinic score of 6-10, endoscopic subscore of 2 or more, rectal bleeding subscore of 1 or more, and an inadequate response or intolerance to mesalazine were enrolled. Patients were randomly allocated (1:1) via a website to either AJM300 (960 mg) or placebo by the minimisation method, which was adjusted centrally by dynamic assignment against the Mayo Clinic score (≥6 to ≤7, ≥8 to ≤10 points), any use of corticosteroid, anti-TNFα antibody, or immunosuppressants during the disease-active period (yes vs no), duration of induction therapy until randomisation (4 weeks vs ≥4 weeks) as the minimisation factors. Patients, investigators, site staff, assessors, and the sponsor were masked to treatment assignments. The study drug was administered orally, three times daily, for 8 weeks, and continued for up to 24 weeks if endoscopic remission was not achieved or rectal bleeding did not stop. The primary endpoint was the proportion of patients with a clinical response at week 8, and was analysed in the full analysis set. Clinical response was defined as a reduction in Mayo Clinic score of 30% or more and 3 or more, a reduction in rectal bleeding score of 1 or more or rectal bleeding subscore of 1 or less, and an endoscopic subscore of 1 or less at week 8. The study is registered with ClinicalTrials.gov, NCT03531892, and is closed to recruitment.Between June 6, 2018, and July 22, 2020, 203 patients were randomly assigned to AJM300 (n=102) or placebo (n=101). At week 8, 46 (45%) patients in the AJM300 group and 21 (21%) patients in the placebo group had a clinical response (odds ratio 3·30, 95% CI 1·73-6·29; p=0·00028). During the 8-week treatment and 16-week extension treatment periods, adverse events occurred in 39 (39%) of 101 patients in the placebo group and 39 (38%) of 102 patients in the AJM300 group. We found no difference in the incidence of adverse events between groups or after repeated administration of AJM300. The most common adverse event was nasopharyngitis (11 [11%] of 101 patients in the placebo group and ten [10%] of 102 patients in the AJM300 group). The most common treatment-related adverse event was also nasopharyngitis (four [4%] of 101 patients in the placebo group and three [3%] of 102 patients in the AJM300 group). Most adverse events were mild-to-moderate in severity. No deaths were reported. A serious adverse event was reported in the AJM300 group (one patient with anal abscess), but this was judged to be unrelated to study drug.AJM300 was well tolerated and induced a clinical response in patients with moderately active ulcerative colitis who had an inadequate response or intolerance to mesalazine. AJM300 could be a novel induction therapy for the treatment of patients with moderately active ulcerative colitis.EA Pharma and Kissei Pharmaceutical.For the Japanese translation of the abstract see Supplementary Materials section.

An explicit martingale representation for random variables described as a functional of a Levy process will be given. The Clark-Ocone theorem shows that integrands appeared in a martingale representation are given by conditional expectations of Malliavin derivatives. Our goal is to extend it to random variables which are not Malliavin differentiable. To this end, we make use of Ito's formula, instead of Malliavin calculus. As an application to mathematical finance, we shall give an explicit representation of locally risk-minimizing strategy of digital options for exponential Levy models. Since the payoff of digital options is described by an indicator function, we also discuss the Malliavin differentiability of indicator functions with respect to Levy processes.

Background Little is known about the antineoplastic effect and the mechanism of Stearoyl-CoA desaturase (SCD) inhibitor which catalyzes the biosynthesis of monounsaturated fatty acids (MUFA). Mutant isocitrate dehydrogenase (IDH) catalyzes the NADPH-mediated reduction of α-ketoglutarate (αKG) to 2-hydroxyglutarate (2HG) and causes metabolic reprograming of lipid. In this study, to develop a feasible drug for IDH mutant glioma, we have investigated the changes of the lipid distribution and the mechanism of antineoplastic effect of SCD inhibition in IDH mutant glioma. Materials and Methods We prepared genetically engineered glioma cell lines (U251 wild type: U251WT and U251 IDH mutant: U251mut) and patient derived cell lines (TS603 and GSC923). Lipid metabolic analysis was conducted by using Raman imaging spectroscopy and LC-MS, and functional analysis for the role of SCD expression in IDH mutant glioma was investigated by RNA sequence and Western-blotting. Results: In LC-MS analysis of the extracted Endoplasmic Reticulum, MUFAs were distributed significantly higher in IDH mutant than wild type. SCD expression was increased in IDH mutant compared to wild type due to 2HG-mediated upregulation of SCD. Therefore, IDH mutant in which SCD expression level was high indicated high sensitivity to SCD inhibitor, and apoptosis was highly induced in IDH mutant compared to wild type. RNA sequencing was performed in U251mut treated with SCD inhibitor compared to U251mut treated with DMSO, and lipid droplet metabolism-associated RNA expression was significantly changed in U251mut treated with SCD inhibitor. We checked lipid droplet in U251mut with presence or absence of SCD inhibitor, and lipolysis was induced by SCD inhibitor treatment, suggesting that SCD inhibition is associated with the apoptosis in IDH mutant via enhanced lipolysis mechanism. Conclusions 2HG produced in IDH mutant glioma directly induces SCD expression and enhances sensitivity to SCD inhibitor, which suggests that SCD inhibitor is an IDH mutant glioma-specific treatment strategy.

Patient: Male, 77 Final Diagnosis: Cerebral amyloid angiopathy Symptoms: Aphasia • hemiparesis Medication: — Clinical Procedure: Hematoma evacuation Specialty: Neurosurgery Objective: Unusual clinical course Background: Cerebral amyloid angiopathy (CAA) results from progressive deposition of amyloid-β in the walls of cortical and leptomeningeal vessels, leading to CAA-associated intracerebral hemorrhage (ICH). Hematoma expansion is a common early complication of spontaneous ICH, and is a strong independent predictor of poor outcome. However, there are limited reports of hematoma expansion related to CAA-associated ICH. Herein, we describe a novel case of hematoma expansion with a fluid-blood level in the cystic cavity of CAA-associated ICH. Case report: A 76-year-old male was initially diagnosed with probable CAA according to the modified Boston criteria, and presented with lobar ICH in the left frontal lobe 4 months later. Admission computed tomography scans showed an ICH including a high-density hematoma within a cystic cavity, revealing a clearly lower-density fluid component. Serial computed tomography scans showed no evidence of an expansion of the high-density clot, but obvious expansion of the fluid component containing a fluid-blood level. We recognized a bleeding site with no enhancement on preoperative magnetic resonance imaging. Left frontal craniotomy revealed a liquefied hematoma, which was removed by suction. We subsequently evacuated the blood clot extending into the left frontal sulcus, and confirmed and cauterized the bleeding site, leading to successful hemostasis. Conclusions: We report a CAA-associated ICH case showing hematoma expansion with a fluid-blood level. Intraparenchymal fluid-blood level suggests extravasation of blood into pre-existing cystic cavities because of hematoma lique-faction. Thus, fluid-blood levels are an important finding of hematoma expansion in acute CAA-associated ICH, and early treatment should be considered.

We have designed and been constructing a compact accelerator-driven neutron facility for Bragg edge transmission imaging of structural materials to obtain position dependent crystallographic information. In order to combine a high neutron wavelength resolution, which is especially required for strain measurements, and an intense neutron beam flux at the sample position, which is required for obtaining high quality statistics within practical measurement times, the components of the neutron facility are optimized. To achieve a high wavelength resolution while maintaining an intense neutron beam flux at the sample position, a solid methane decoupled cold moderator at about 20 K coupled with neutron guide tubes is employed. The target–moderator system, especially the moderator thickness was optimized using the Monte-Carlo simulation code PHITS. Neutrons will be produced using a 35-MeV electron accelerator which is currently under construction. The accelerator has a design maximum beam power of 10 kW, a maximum repetition rate of 100 Hz and a maximum pulse width of 10 μ s . The combination of the flight path length of about 8 m and the repetition rate is suitable for efficient Bragg edge measurements. The pulse width of the electron beam is suitable to achieve a high wavelength resolution with the solid methane decoupled moderator. The estimated flux of the neutron beam at the sample position is 1.2 × 104 ∼ 4 . 5 × 104 /cm2/s depending on the usage of super mirror guide tubes. The wavelength resolution at the sample is 0.5 ∼ 0.7% in the wavelength region from 0.3 to 0.4 nm.

This study aimed to reveal the influence of sound absorption in general dwellings on the subjective evaluation of acoustics. First, a subjective experiment was conducted using a full-scale room model. The results indicate that the feelings of silence and serenity can be experienced at absorption coefficients above 0.17, particularly above 0.25. Additionally, we used the recorded binaural sounds for a subjective test instead of using a full-scale room model. This trial showed that the reverberance, feeling of silence, and feeling of serenity can also be evaluated using a headphone listening test. We also measured the reverberation times and recorded the sound environments in three bedrooms, three living and dining (LD) rooms, and three child rooms in modern Japanese dwellings. The average absorption coefficients of the LD and child rooms were lower than 0.17, in the range of 500 Hz to 4 kHz. Therefore, we analyzed the subjective effect of absorption through a psychological test using binaural recorded sounds. The bedrooms with absorption coefficients of 0.18–0.23 were significantly less reverberant, quieter, and more serene than the other rooms.

We have constructed a compact accelerator-based neutron facility at the National Institute of Advanced Industrial Science and Technology (AIST) in Japan aiming at development of structural materials of transportation vehicles for weight reduction. The facility consists of electron linear accelerator, neutron source, and a neutron beamline with a measurement hutch. Currently we are commissioning the accelerator and expecting a first neutron beam in 2019.

Summary Background Mizagliflozin is a novel oral sodium-glucose cotransporter 1 (SGLT1) inhibitor that increases luminal glucose and water. This study assessed the efficacy and safety of mizagliflozin in patients with functional constipation. Methods In this multicentre, randomised, double-blind phase 2 trial at 32 hospitals and community outpatient clinics in Japan, we enrolled patients with functional constipation or constipation-predominant irritable bowel syndrome, aged 20 years or older. Patients were randomly assigned (1:1:1), by use of an independent centralised registration system and dynamic allocation method, to receive mizagliflozin 5 mg, mizagliflozin 10 mg, or placebo, orally once daily for 4 weeks. Patients, investigators, staff, and the sponsor were blinded to the group assignments. The primary outcome was the change from baseline in the number of spontaneous bowel movements per week after 1 week. Efficacy analysis was done in all patients except those who deviated from good clinical practice, did not receive at least one dose of the study drug, withdrew before starting treatment, were ineligible, or for whom the primary outcome could not be assessed, and safety was assessed in all patients except those who deviated from good clinical practice, who did not receive the study drug, or who withdrew before receiving treatment. This trial is registered with ClinicalTrials.gov , number NCT02281630 , and is completed. Findings Between Oct 15, 2014, and March 7, 2015, 258 patients with functional constipation were randomly assigned: 86 patients per group. Two patients from the placebo group and three from the 10 mg mizagliflozin group were excluded because the primary outcome could not be assessed, and one patient from the 5 mg mizagliflozin group was excluded for not receiving the study drug; therefore 84 patients in the placebo group, 85 in the 5 mg mizagliflozin group, and 83 in the 10 mg mizagliflozin group were included in the full analysis population. Mean change from baseline in the number of spontaneous bowel movements per week after 1 week with mizagliflozin 5 mg (3·85 [SD 3·96]) and mizagliflozin 10 mg (5·85 [6·01]) was significantly greater than those in the placebo group (1·80 [1·80]; p Interpretation The SGLT1 inhibitor mizagliflozin showed favourable efficacy and tolerability at 5 mg and 10 mg doses in patients with functional constipation, providing a potential alternative therapy to available drugs. Funding Kissei Pharmaceutical.

The purpose of this research is to develop a useful training device for people with gait disorders. The proposed device was evaluated by some experiments such as the timed up and go test (TUG) and measuring of step length in Parkinson's disease. The training effect with this device appeared to improve gait freezing and step length. The proposed device can be expected to be easy to use for training at home.

In this paper, we consider Malliavin differentiability of indicator functions on canonical Levy spaces. We give necessary and sufficient conditions for it. This is a Levy space version of a result of Sekiguchi and Shiota (1985).

To comprehensively investigate the correlation between free volume properties (size and distribution) in the interior of polyamide (PA) active layer and mass transport mechanism, six polyamide thin film composite (TFC) membranes were characterized using positron annihilation lifetime spectroscopy (PALS). In case of pressurized filtration conditions, the rejection rate of boron across all PA membranes was found to be inversely proportional to the free volume size. The more boron transport occurred at the membrane containing larger free volume. In addition, the transition of the neutral boron transport mechanism from convection to diffusion was found to occur at a membrane free volume radius around 0.275 nm within the applied pressure range (2 and 10 bar), as verified by PALS and the dimensionless Peclet number. We believe that mass transport mechanism transition from convection to diffusion is caused by the compression of polyamide active layer due to applied hydraulic pressure (10 bar), resulting in lowering the convective mass transport pathway inside polyamide active layer. These membrane free volume size criteria and experimental filtration results may subsequently be used as new design guidelines for the development of high boron rejection polyamide TFC membranes having a low energy consumption.

We systematically investigate the pore structure of cellulose triacetate (CTA) and polyamide (PA) forward osmosis (FO) membranes with positron annihilation lifetime spectroscopy (PALS) and fractional rejection (FR) method to better understand the relationship between membrane pores (atomic-scale free volume) and separation performance. The results reported in this study suggest a range of membrane pore sizes and inner structures appropriate for the osmotic membrane process regardless of membrane materials. The PALS data suggest that the active layer of both FO membranes is mainly composed of generally uniform pores of larger size (0.29−0.30 nm) compared to seawater reverse osmosis (SWRO) (0.20−0.24 nm) membranes. The membrane pore size distribution (PSD) deduced by the FR method suggest that the PSD of both FO membranes are significantly shifted to smaller sizes under pressurized conditions, possibly due to the overall compression of the FO membranes. The effects of applied pressure on the structure and performance of active layer should be further investigated along with other properties such as thickness, swelling and sorption properties.

Native defects and ion-implantation induced defects in GaN were studied by means of positron annihilation. Measurements of Doppler broadening spectra of the annihilation radiation for GaN layers grown on Si substrates showed that optically active vacancy-type defects were formed in the layers. Charge transition of the defects due to electron capture occurred when the layers were irradiated by photons with energy above 2.7 eV. It was found that Ti deposition and subsequent annealing introduced vacancy clusters. We also characterized vacancy-type defects in Mg-implanted GaN. The major defect species of vacancies introduced by Mg-implantation was a complex between Ga-vacancy (VGa) and nitrogen vacancies (VNs). After annealing above 1000C, these defects started to agglomerate, and the major defect species became (VGa)2 coupled with VNs. Through this work, we have demonstrated that positron annihilation spectroscopy is a powerful tool for characterizing vacancy-type defects in GaN for power devices applications.

In this article, we describe the discovery of an aryl ether series of potent and selective Nav1.3 inhibitors. Based on structural analogy to a similar series of compounds we have previously shown bind to the domain IV voltage sensor region of Nav channels, we propose this series binds in the same location. We describe the development of this series from a published starting point, highlighting key selectivity and potency data, and several studies designed to validate Nav1.3 as a target for pain.

This paper investigates passivity-based control for a 3DOF manipulator with antagonistic bi-articular muscles towards robotic rehabilitation. The dynamics of a 3DOF manipulator with antagonistic bi-articular muscles is obtained from the 3DOF standard robot dynamics and the visco-elastic muscle model. In our approach, we design a input torque for the 3DOF bi-articular manipulator to preserve the passivity property. Stability analysis for the closed-loop system of the constructed error system and the proposed control law is discussed through Lyapunov stability theorem.

Dihydroxybenzoic acid (DHB) crystal layers were formed via mist deposition. Crystal layers exhibiting whiskers measuring a few hundred micrometers were formed at a nozzle temperature of 200 °C. DHB crystal layers exhibited strong absorbance in the ultra-violet wavelength regions, and Raman spectroscopy confirmed their vibrational property. The lipid component was analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging using a DHB crystal layer as the mass ionization assist agent. Cholesterols, diacylglycerides, and triglycerides were detected as sodium adducts. By preventing heterogeneous co-crystallization with analytes, mass images were clearer than when using the conventional aerosol spray method.

A new X-ray tube using a ring-shaped emitter as a field emission electron source has been developed. By using a ring shaped cathode, X-rays can be extracted along the axial direction through the central hole. This cylindrically symmetrical design allows for the tube to be arranged in the axial direction with the high voltage target at one end and the X-ray beam at the other. The newly developed X-ray tube can operate at a tube voltage of more than 100 kV and at a tube current of more than 4 mA, and can be used for irradiation experiments with an irradiation dose range from mGy up to kGy. The X-ray tube can be used immediately after turning on (i.e. there is no stand-by time). In the experimental model, we demonstrated stable electron emission at a tube voltage of 100 kV and at a tube current of 4 mA during a 560 h continuous test.

In this note, we correct mistakes concerning Theorem 3.1, Propositions 3.3 and 3.4 in Suzuki (2018).