The purpose of this research is to collect fundamental data and to establish a performance-based design method for reinforced concrete beams under perpendicular impact load. Series of low speed ...impact experiments using reinforced concrete beams were performed varying span length, cross section and main reinforcement. The experimental results are evaluated focusing on the impact load characteristics and the impact behaviours of reinforced concrete beams. Various characteristic values and their relationships are investigated such as the collision energy, the impact force duration, the energy absorbed by the beams and the beam response values. Also the bending performance of the reinforced concrete beams against perpendicular impact is evaluated. An equation is proposed to estimate the maximum displacement of the beam based on the collision energy and the static ultimate bending strength. The validity of the proposed equation is confirmed by comparison with experimental results obtained by other researchers as well as numerical results obtained by FEM simulations. The proposed equation allows for a performance based design of the structure accounting for the actual deformation due to the expected impact action.
Background: Edoxaban (the free base of DU‐176b) is an oral, direct factor (F)Xa inhibitor in clinical development for the prevention and treatment of thromboembolic events. Objectives: The aim of the ...present study was to evaluate the efficacy and safety of edoxaban for the prevention of venous thromboembolism (VTE) in patients undergoing total knee arthroplasty (TKA). Patients/methods: This was a randomized, double‐blind, placebo‐controlled, multicenter study conducted in Japan. A total of 523 Japanese patients were assigned to receive edoxaban 5, 15, 30 or 60 mg once daily or placebo for 11–14 days. A placebo control was used as neither low‐molecular‐weight heparin (LMWH) nor fondaparinux had been approved for thromboprophylaxis at the time of the study in Japan. The primary efficacy outcome was the incidence of VTE (lower‐extremity deep vein thrombosis, symptomatic pulmonary embolism or symptomatic deep vein thrombosis). The primary safety outcome was the incidence of major and clinically relevant non‐major bleeding. Results: Edoxaban produced a significant dose‐related reduction in VTE: the incidence of VTE was 29.5%, 26.1%, 12.5% and 9.1% in the edoxaban 5‐, 15‐, 30‐ and 60‐mg treatment groups vs. 48.3% in the placebo group. The incidence of major and clinically relevant non‐major bleeding was similar across all groups without any significant differences among edoxaban doses or between edoxaban and placebo. Conclusions: Edoxaban demonstrated significant dose‐dependent reductions in VTE in patients undergoing TKA with a bleeding incidence similar to placebo. This trial is registered with JAPIC, JapicCTI‐060283 (ja).
Abstract Edoxaban, an oral direct factor Xa inhibitor, has proven antithrombotic efficacy. In a multicenter, phase II study, 264 total hip arthroplasty (THA) patients randomly received edoxaban 15 or ...30 mg once daily or enoxaparin 2000 IU (20-mg) twice daily for 11–14 days. Thromboembolic event incidences were 3.8% (3/78), 2.8% (2/72), and 4.1% (3/74) for edoxaban 15-mg, 30-mg, and enoxaparin, respectively ( P = 1.00). Edoxaban-induced prolongation of prothrombin time, international normalized ratio, and activated partial thromboplastin time were proportional to plasma edoxaban concentration. Major or clinically relevant non-major bleeding incidences were 2.2% (2/89), 1.2% (1/85), and 2.3% (2/87) for edoxaban 15-mg, 30-mg, and enoxaparin, respectively ( P = 1.00). Once-daily edoxaban showed similar efficacy and safety to enoxaparin for prevention of thromboembolic events in patients undergoing THA.
Spinal muscular atrophy is a rare, autosomal recessive, neuromuscular disease caused by biallelic loss of the survival motor neuron 1 (SMN1) gene, resulting in motor neuron dysfunction. In this ...STR1VE-EU study, we aimed to evaluate the safety and efficacy of onasemnogene abeparvovec gene replacement therapy in infants with spinal muscular atrophy type 1, using broader eligibility criteria than those used in STR1VE-US.
STR1VE-EU was a multicentre, single-arm, single-dose, open-label phase 3 trial done at nine sites (hospitals and universities) in Italy (n=4), the UK (n=2), Belgium (n=2), and France (n=1). We enrolled patients younger than 6 months (180 days) with spinal muscular atrophy type 1 and the common biallelic pathogenic SMN1 exon 7–8 deletion or point mutations, and one or two copies of SMN2. Patients received a one-time intravenous infusion of onasemnogene abeparvovec (1·1 × 1014 vector genomes vg/kg). The outpatient follow-up consisted of assessments once per week starting at day 7 post-infusion for 4 weeks and then once per month until the end of the study (at age 18 months or early termination). The primary outcome was independent sitting for at least 10 s, as defined by the WHO Multicentre Growth Reference Study, at any visit up to the 18 months of age study visit, measured in the intention-to-treat population. Efficacy was compared with the Pediatric Neuromuscular Clinical Research (PNCR) natural history cohort. This trial is registered with ClinicalTrials.gov, NCT03461289 (completed).
From Aug 16, 2018, to Sept 11, 2020, 41 patients with spinal muscular atrophy were assessed for eligibility. The median age at onasemnogene abeparvovec dosing was 4·1 months (IQR 3·0–5·2). 32 (97%) of 33 patients completed the study and were included in the ITT population (one patient was excluded despite completing the study because of dosing at 181 days). 14 (44%, 97·5% CI 26–100) of 32 patients achieved the primary endpoint of functional independent sitting for at least 10 s at any visit up to the 18 months of age study visit (vs 0 of 23 untreated patients in the PNCR cohort; p<0·0001). 31 (97%, 95% CI 91–100) of 32 patients in the ITT population survived free from permanent ventilatory support at 14 months compared with six (26%, 8–44) of 23 patients in the PNCR natural history cohort (p<0·0001). 32 (97%) of 33 patients had at least one adverse event and six (18%) had adverse events that were considered serious and related to onasemnogene abeparvovec. The most common adverse events were pyrexia (22 67% of 33), upper respiratory infection (11 33%), and increased alanine aminotransferase (nine 27%). One death, unrelated to the study drug, occurred from hypoxic-ischaemic brain damage because of a respiratory tract infection during the study.
STR1VE-EU showed efficacy of onasemnogene abeparvovec in infants with symptomatic spinal muscular atrophy type 1. No new safety signals were identified, but further studies are needed to show long-term safety. The benefit–risk profile of onasemnogene abeparvovec seems favourable for this patient population, including those with severe disease at baseline.
Novartis Gene Therapies.
A membrane reformer is composed of a steam reformer equipped with palladium-based alloy membrane modules and can perform steam reforming reaction of natural gas and hydrogen separation processes ...simultaneously, without shift converters and purification systems. We have developed a membrane reformer system with nominal hydrogen production capacity of 40Nm3/h. The system has demonstrated the potential advantages of the membrane reformer: simple system configuration as benefited by single-step production of high-purity hydrogen (99.999% level), compactness, and high-energy efficiency of 70–76%. We are promoting development towards commercialization of the membrane reformer technology, focusing on further improvement of energy efficiency, proof of long-term durability and reliability, and establishment of system engineering technologies. The target of our current project is to develop a membrane reformer system that can produce 99.99% or higher-purity hydrogen from natural gas at a rate of 40Nm3/h with hydrogen production energy efficiency of over 80%.
Micrometeorites (MMs) recovered from surface snow near the Dome Fuji Station, Antarctica are almost free from terrestrial weathering and contain very primitive materials, and are suitable for ...investigation of the evolution and interaction of inorganic and organic materials in the early solar system. We carried out a comprehensive study on seven porous and fluffy MMs four Chondritic porous (CP) MMs and three fluffy fine-grained (Fluffy Fg) MMs and one fine-grained type 1 (Fg C1) MM for comparison with scanning electron microscope, transmission electron microscope, X-ray absorption near-edge structure analysis, and secondary ion mass spectrometer.
They show a variety of early aqueous activities. Four out of the seven CP MMs contain glass with embedded metal and sulfide (GEMS) and enstatite whiskers/platelets and do not have hydrated minerals. Despite the same mineralogy, organic chemistry of the CP MMs shows diversity. Two of them contain considerable amounts of organic materials with high carboxyl functionality, and one of them contains nitrile (CN) and/or nitrogen heterocyclic groups with D and 15N enrichments, suggesting formation in the molecular cloud or a very low temperature region of the outer solar system. Another two CP MMs are poorer in organic materials than the above-mentioned MMs. Organic material in one of them is richer in aromatic C than the CP MMs mentioned above, being indistinguishable from those of hydrated carbonaceous chondrites. In addition, bulk chemical compositions of GEMS in the latter organic poor CP MMs are more homogeneous and have higher Fe/(Si+Mg+Fe) ratios than those of GEMS in the former organic-rich CP MMs. Functional group of the organic materials and amorphous silicate in GEMS in the organic-poor CP MMs may have transformed in the earliest stage of aqueous alteration, which did not form hydrated minerals.
Three Fluffy Fg MMs contain abundant phyllosilicates, showing a clear evidence of aqueous alteration. Phyllosilicates in thee MMs are richer in Fe than those in hydrated IDPs, typical fine-grained hydrated (Fg C1) MMs, and hydrated carbonaceous chondrites. One of the Fluffy Fg MMs contains amorphous silicate, which is richer in Fe than GEMS and contains little or no nanophase Fe metal but contains Fe sulfide. Because the chemical compositions of the amorphous silicate are within the compositional field of GEMS in CP IDPs, the amorphous silicate may be alteration products of GEMS. The entire compositional field of GEMS in the CP MMs and the amorphous silicate in the Fluffy Fg MM matches that of the previously reported total compositional range of GEMS in IDPs.
One Fluffy Fg MM contains Mg-rich phyllosilicate along with Fe-rich phyllosilicate and Mg-Fe carbonate. Mg-rich phyllosilicate and Mg-Fe carbonate may have been formed through the reaction of Fe-rich phyllosilicate, Mg-rich olivine and pyroxene, and water with C-bearing chemical species.
These data indicate that CP MMs and Fluffy Fg MMs recovered from Antarctic surface snow contain materials that throw a light on the earliest stages of aqueous alteration on very primitive solar system bodies. Because mineralogy and isotopic and structural features of organic materials in D10IB009 are comparable with isotopically primitive IDPs, its parent body could be comets or icy asteroids showing mass ejection (active asteroids). By contrast, organic-poor CP MMs may have experienced the earliest stage of aqueous alteration and Fluffy Fg MMs experienced weak aqueous alteration. The precursor materials of the parent bodies of Fluffy Fg MMs probably contained abundant GEMS or GEMS-like materials like CP IDPs, which is common to fine-grained matrices of very primitive carbonaceous chondrites such as CR3s. However, highly porous nature of organic-poor CP MMs and Fluffy Fg MMs suggests that parent bodies of these MMs must have been much more porous than the parent bodies of primitive carbonaceous chondrites. Given no phyllosilicate among the returned samples of 81P/Wild 2 comet, the MMs may have been derived from porous icy asteroids such as active asteroids as well as P- and D-type asteroids rather than comets.
Hayabusa2 is an asteroid exploration mission to return surface samples of a near-Earth C-type asteroid (162173) 1999 JU3. Because asteroids are the evolved remnants of planetesimals that were the ...building blocks of planets, detailed observation by a spacecraft and analysis of the returned samples will provide direct evidence regarding planet formation and the dynamic evolution of the solar system. Moreover, C-type asteroids are expected to preserve the most pristine materials in the solar system, a mixture of minerals, ice, and organic matter that interact with each other. Space missions are the only way to obtain such pristine materials with geologic context and without terrestrial contamination. Hayabusa2 will launch off in 2014, arrive at 1999 JU3 in mid-2018, and fully investigate and sample the asteroid at three different locations during its 18-month stay. The concept and design of the Hayabusa2 sampler are basically the same as that on-board Hayabusa, and impact sampling with a 5-g Ta bullet will be made at three locations of the asteroid. The sample container has three separate chambers inside to store samples obtained at different locations separately. The spacecraft will return to Earth with samples in December 2020. Returned samples will be investigated by state-of-the-art analytical techniques in 2020 to understand the evolutionary history of the solar system from 4.56 Gyr ago to the present by combining results from laboratory examinations of the returned samples with remote-sensing datasets and comparing all results of observations of meteorites, interplanetary dust particles, and future returned samples.
•This study aims to constrain the composition of the lunar magma ocean.•We focus on the geophysical and geochemical conditions for lunar crust formation.•An incremental polybaric fractionation model ...is developed for lunar differentiation.•FeO must be ∼1.3–1.8times the Earth unless Al2O3 is extremely higher than the Earth.•Oxidized lunar formation disk or oxidized impactor of the giant impact is suggested.
The present study aims to constrain the composition of the initial lunar magma ocean (LMO) with fluid dynamic and thermodynamic consideration. A plausible range of the initial LMO composition is investigated by developing an incremental polybaric fractional crystallization model with variable fractionation efficiency to satisfy three conditions for the anorthosite crust formation: (1) the amount of anorthite crystallized from the LMO is abundant enough to form the crust with the observed thickness, (2) the Mg# (=Mg/(Mg+Fe)) of orthopyroxene crystallized with anorthite in the cooling LMO is consistent with that observed in the lunar highland rocks, ferroan anorthosite, and (3) crystallized anorthite separated to float in the turbulent LMO. A plausible range of FeO and Al2O3 contents of the bulk LMO is successfully constrained as a crescent region tight for FeO and loose for Al2O3. The FeO content must be higher than 1.3 times the bulk silicate Earth (BSE) and lower than 1.8×BSE unless the Al2O3 content of the Moon is extremely higher than the Earth. These upper and lower limits for FeO are positively correlated with the initial Al2O3 content and fractionation efficiency. The FeO–rich LMO composition may suggest that the circum-Earth disk just after the giant impact of the Earth–Moon system formation was more oxidizing or the impactor was richer in FeO than the Earth’s mantle.
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