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Outcomes of end-to-end nerve repairs are more successful compared with outcomes of repairs bridged by nerve grafts. However, end-to-end repairs are not always possible for large nerve gaps, as excessive tension may cause catastrophic failure. In this study, we built on previous nerve-lengthening studies to test the hypotheses that gradual lengthening of the proximal stump across a large nerve gap enables an end-to-end repair and such a repair results in more favourable regenerative outcomes than autografts, which represent the gold standard in bridging nerve gaps. To test these, we compared structural and functional outcomes in Lewis rats after repair of sciatic nerve gaps using either autografts or a novel compact internal fixator device, which was used to lengthen proximal nerve stumps towards the distal stump over 2 weeks, prior to end-to-end repair. Twelve weeks after the initial injury, outcomes following nerve lengthening/end-to-end repair were either comparable or superior in every measure compared with repair by autografting. The sciatic functional index was not significantly different between groups at 12 weeks. However, we observed a reduced rate of contracture and corresponding significant increase in paw length in the lengthening group. This functional improvement was consistent with structural regeneration; axonal growth distal to the injury was denser and more evenly distributed compared with the autograft group, suggesting substantial regeneration into both tibial and peroneal branches of the sciatic nerve. Our findings show that end-to-end repairs following nerve lengthening are possible for large gaps and that this strategy may be superior to graft-based repairs.

Intervertebral disc degeneration (IDD) is a major cause of chronic and debilitating back pain whose prevalence and severity make it a major health issue of substantial socioeconomic importance. The prevalence of chronic disabling back pain has tripled over the last 20 years [1] and the treatment of lower back pain in the United States is estimated to cost more than $100 billion per year. [2] Current treatment options are mostly palliative since disc tissue has little intrinsic repair capacity once a matrix synthesis/degradation imbalance occurs. Our bioengineered naturally secreted compositions have demonstrated the ability to decrease/remove protease and inflammatory cytokine activity and stimulate native cells to secrete new matrix production in vitro, and to maintain nucleus hydration and help to recover from the initial disc height loss in the semi-acute rabbit annular puncture model.

Fujikura Ltd., Chiba, Japan, has developed stable and high-throughput production techniques for REBCO coated conductors (CC) by using large-area ion-beam-assisted-deposition (IBAD), and hot-wall type pulsed-laser-deposition (PLD). Recently, we have been attempting to dope BaMO 3 (BMO, M: Zr or Hf) to REBCO layer in order to enhance in-field critical current density (J c ). In the course of optimizing deposition conditions of PLD for BaHfO 3 doped EuBCO films on IBAD templates, “high J c condition” and “high growth rate condition” were found. For samples prepared under these conditions, the magnetic field angle dependence of I c and REBCO thickness dependence were investigated. Finally, we succeeded in fabricating a 300-m-long CC with uniform I c distribution at the high-growth-rate condition. The longitudinal I c homogeneity (defined as standard deviation divided by average) at 77 K evaluated by magnetization method was 2.6%, which is comparable to nondoped conductors. Transport in-field I c for the both end points were 1756 and 1786 A/cm at 30 K, 2 T, respectively.

BaMO 3 (BMO, M: Zr or Hf)-doped REBCO-coated conductors were prepared by Hot-Wall PLD method on IBAD template. The highest J c was obtained for BaHfO 3 -doped EuBCO. Quite strong pinning force density (F p ) of 1.6 TN/m 3 was observed at 4.2 K, 15 T, for a sample deposited with growth rate of ~5 nm/s. It had strong c-axis correlated pinning at the temperature above 20 K with the matching field of ~5 T. A 45-m-long sample was formed by productive high growth rate over 20 nm/s, being consistent with commercial nondoped conductors. It had also large I c of 1687 A/cm and F p of 0.96 7 TN/m 3 was obtained at 4.2 K, 15 T. The end-to-end longitudinal Ic homogeneity (σ) at 77 K in low field was evaluated to be 2.2% by magnetization. Transport in-fields I c were also measured for the both end points at 30 K, 2 T, resulting in 1863 and 1883A/cm, respectively.

Background For recanalization of coronary chronic total occlusion (CTO) lesions, subintimal guidewire tracking in both antegrade and retrograde approaches are commonly used. Purpose This study aimed to assess the impact of subintimal tracking on long-term clinical outcomes after recanalization of CTO lesions. Methods Between January 2009 and December 2016, 474 CTO lesions (434patients) were successfully recanalized in our center. After guidewire crossing in a CTO lesion, those lesions were divided into intimal tracking group (84.6%, n=401) and subintimal tracking group (15.4%, n=73) according to intravascular ultrasound (IVUS) findings. Long-term clinical outcomes including death, target lesion revascularization (TLR), target vessel revascularization (TVR) were compared between the two groups. In addition, the rate of re-occlusion after successful revascularization was also evaluated. Results The median follow-up period was 4.7 years (interquartile range, 2.8–6.1). There was no significant difference of the rate of cardiac death between the two groups (intimal tracking vs. subintimal tracking: 7.0% vs. 4.1%; hazard ratio, 0.61; 95% confidence interval [CI], 0.19 to 2.00; p=0.41), TLR (14.3% vs. 16.2%; hazard ratio, 1.34; 95% CI, 0.71 to 2.53; p=0.37), and TVR (17.5% vs. 20.3%; hazard ratio, 1.27; 95% CI, 0.72 to 2.23; p=0.42). However, the rate of re-occlusion was significantly higher in the subintimal tracking group than intimal tracking group at 3-years re-occlusion (4.2% vs. 14.5%; log-rank test, p=0.002, Figure). In the multivariate COX regression, subintimal guidewire tracking was an independent predictor of re-occlusion after CTO recanalization (HR: 5.40; 95% CI: 2.11–13.80; p Figure 1 Conclusions Subintimal guidewire tracking for recanalization of coronary CTO was associated with significantly higher incidence of target lesion re-occlusion during long-term follow-up period.

We propose a novel adsorption pad for wall climbing robot and irregular surface object using capillary force and water sealing. We call this adsorption pad as Super Wet Adsorption pad. The SWA pad has a porous part and a capillary part. The porous part is made by salt reaching method. When the SWA pad adsorbs to the wall which some sand and dust are attached, water comes from the porous part to avoid vacuum breaking. The capillary part is connected to the porous part to supply and stock the water. In this paper, we show the design of the porous part and the capillary part, fabrication process of each parts, and perform the evaluation experiment of the capillary force and adsorption of uneven surfaces, demonstration of wall climbing robot and adsorption of irregular surface foods.

Background: Drug interaction is an important and effective phenomenon in the area of anesthesiology because of drugs combinations potentially possessing novel properties. The characteristics of anesthesia with co-administration of JM-1232(-), benzodiazepine receptor agonist, and propofol, the most popular anesthetics, was studied using mice. Methods: Male adult mice were each administered JM-1232(-), propofol and various combinations of the two drugs intravenously. Loss of the righting reflex was evaluated as achieving hypnosis and the time until recovery of the reflex was measured as hypnosis time. After determining the ED50, double and triple the ED50 dose of propofol with JM-1232(-) were injected to compare hypnosis time. The injections were repeated 4 times and each hypnosis time was compared. Separately, flumazenil was administered immediately after the last dose was injected. Results: The ED50s ([95% confidence interval]) for hypnosis were 3.76 [3.36 - 4.10] for JM-1232(-) and 9.88 [8.03 - 11.58] mg kg-1 for propofol. Co-administration of 0.05- and 0.1-mg kg-1 of JM-1232(-) reduced the ED50 of propofol to 1.76 [1.21 - 2.51] and 1.00 [0.46 - 1.86] mg kg-1. The interaction of the drug combinations for hypnosis was supra-additive. Hypnosis time was significantly shorter in the groups given the mixtures as compared to each hypnotic administered alone. After repeated injections, hypnosis time with the mixtures showed smaller prolongation than that with sole hypnotics. Flumazenil antagonized the supra-additive effects of the mixtures. Conclusions: The combination of JM-1232(-) and propofol shows supra-additive interaction and the reduced hypnotic dose translates to faster recovery even after multiple injections. Keywords: JM-1232(-), Propofol, Supra-additive interaction, Flumazenil.

The authors investigated Daikyo CZ cyclic olefin polymer for storing a labile protein-ADAMTS13 and culturing adherent mammalian cells. ADAMTS13 was stored in different containers for one and four months. Protein recovery assays suggest that ADAMTS13 remained enzymatically active. ADAMTS13 recovered from CZ containers is comparable to that of polypropylene vials, and is 10% greater than glass vials. LN229 and HUVEC cells were cultured in CZ containers. Cell proliferation, viability, and migration were studied. LN229 cells cultured in CZ containers exhibited 36% higher proliferation rate and an increase in cell migration, as compared to the polystyrene containers. HUVEC proliferated slower in CZ containers.

This study reports the results of large eddy simulations with the standard Smagorinsky model of the velocity fields within a cross-ventilation model sheltered by block arrays. A very fine resolution of 1/100 of the building height was adopted. The objectives are to understand the sheltering effect of the surrounding building array and quantify the ventilation rate in the cross-ventilation model. Two types of block arrays and opening positions were simulated. Comparisons of the numerical and experimental results justify that the present simulations reproduced the characteristics of the mean as well as turbulent flows introduced in the ventilation model. In addition, the simultaneous observations of the outdoor and indoor velocities enabled us to conclude that the change in the outdoor flow patterns caused a dramatic change in the indoor velocity distributions, although the opening position was identical in all such cases. Using these detailed flow fields, we compared three types of ventilation rates: the net, gross, and instantaneous ventilation rates. Moreover, we estimated the instantaneous ventilation rate using a random variable following the Gaussian distribution. The ventilation due to the turbulent inflow was crucial in the model with its opening on the lateral side of the block, whereas the mean flow primarily determined the ventilation rate for the block with its opening on the streamwise walls. In both cases, the estimation model could predict the instantaneous ventilation rate well with a maximum overestimation of only 3%. This means that the model was justified for all the present array and opening conditions.

Background Immune checkpoint inhibitors (ICI) have been established as a novel strategy for non-small cell lung cancer (NSCLC). However, definitive biomarkers that can predict response to ICI therapy remains established. Some prostate factors are suggested, Neutrophile-lymphocyte ratio (NLR), advanced lung cancer inflammation index (ALI), Lung Immune Prognostic Index (LIPI), then we investigate their efficiency. Methods The medical records of consecutive 296 patients with NSCLC who were treated with nivolumab at Kinki-chuo Chest Medical Center between December 17, 2015 and December 31, 2018 were collected. Nivolumab was the only ICI validated for advanced NSCLC in a second-line treatment setting. We investigated the relationship between median progression free survival (PFS) and already known prognostic factors (NLR, ALI, LIPI and so on). Results The median age was 70 (range, 40-90) years. 206 patients were male, and 224 patients were good PS group (PS 0-1). The median PFS was 3.0 months in all patients. The median PFS was 4.7 (NLR Conclusion NLR, ALI and LIPI score have the potential to be predictive factors of ICI response in NSCLC patients. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure A. Tamiya: Research grant / Funding (self): Taiho; Research grant / Funding (self): pfizer; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Ono pharmaceutical; Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Chugai pharmaceutical; Research grant / Funding (self): Eli Lilly; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): MSD; Research grant / Funding (self): Kissei. S. Atagi: Research grant / Funding (self): Ono pharamaceutical; Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Taiho; Research grant / Funding (self): Chugai pharmaceutical; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Eli Lilly; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Yakult pharmaceutical; Research grant / Funding (self): MSD. All other authors have declared no conflicts of interest.

Background Nivolumab is one of immune checkpoint inhibitors, which is reported to have efficacy in previously treated patients with advanced non-small cell lung cancer (NSCLC) in checkmate 017 / 057 / 078. It is suggested nivolumab treatment beyond progression disease (PD) may be associated with improved survival in patients with melanoma and renal cell carcinoma. However, the efficacy of beyond PD in patients with NSCLC is still unclear. Methods To evaluate the efficacy of beyond PD about nivolumab, we retrospectively reviewed the continuous patients with advanced NSCLC, who received nivolumab as 2nd line treatment in our institution between February 2016 and February 2019. The patients were eligible if they had been diagnosed PD using RECIST v1.1 by 28 February 2019. Baseline characteristics, overall response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), the period between RECIST v1.1 PD and clinical PD, post-PD OS, and safety were evaluated on 26 July 2019. Results Of the 144 advancer NSCLC patients treated with 2nd line nivolumab, 95 patients were eligible. Post-PD OS was 12.2 months (95% confidence interval [CI]: 5.8–26.6) in 28 patients continuing nivolumab beyond PD, 9.3 months (95% CI: 6.4–13.8) in 46 patients switching to other anti-cancer therapy, and 0.7 months (95% CI: 0.4–1.7) in 21 patients receiving no further therapy. The median period between RECIST v1.1 PD and clinical PD was 3.8 months (95% CI: 2.8–6.6) in 28 patients continuing nivolumab beyond PD. During nivolumab beyond PD, one patient died due to acute liver involvement and interstitial lung disease, one patient stopped to receive nivolumab due to grade 3 diarrhea, and one patient stopped to receive nivolumab due to grade 2 interstitial lung disease. Conclusion Post-PD OS trended to be longer in patients continuing nivolumab beyond PD than in patients switching to other anti-cancer therapy. Within the limitations of this retrospective analysis, this study suggests nivolumab treatment beyond PD may have efficacy and safety in patients with advanced NSCLC. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Author(s): Sung, Jaemyoung | Advisor(s): Shah, Sameer B; Bloodgood, Brenda L | Abstract: Peripheral nerves span one or more articulating joints, and must accommodate mechanical loads during day-to-day activities. Axons are protected in part by their undulation within the nerve, implied by the Bands of Fontana. In addition, previous studies have identified regions of increased epineurial strain and compliance, particularly near joints. Most of these studies have focused on regional differences in epineurial strain; however, how internal nerve compartments, including the axons, perceive this increased deformation is less understood. Using transgenic mice expressing a fluorescent reporter within their neurons, we tested 1) whether mesoneurial tissue contributes to regional variability in epineurial strain, and 2) whether nerves increase their local axonal undulation in regions of high epineurial strain, as a strategy to protect nerve fibers from strain-induced damage.In our results, we observed a decoupling between regions of high epineurial strain and high axonal tortuosity. Consistent with previous studies, decompression resulted in significant differences in regional strain, confirming strong mesoneurial influences on epineurial strain. However, regional differences in axonal tortuosity were largely unchanged by decompression or excision, signaling that epineurial measurements may not fully represent the response of the inner nerve. Based on our findings and previous literatures, we propose a neuromechanical model that permits axons to unravel along their length due to looser coupling between the peri/endoneurium. This capability may result in enhanced axonal protection to injury than suspected. These findings have implications for our understanding of nerve biomechanics as well as the progression of nerve dysfunction due to injury, disease, or surgery.

Recent development of production technique for RE123 coated conductors was reviewed, using Hot-wall PLD/ IBAD process. Lot-to-lot distributions for both average value and longitudinal uniformity of Ic at 77 K, 0 T were summarized for 127 run of 300-500-m-long 10-mm-wide CC. By optimizing hotwall PLD process parameters we found a reproducible high Jc production condition (20% enhancement in field at 20 K), less angular dependent to applied magnetic field. Furthermore, new hermetic type Cu stabilization foil configuration was developed and general mechanical properties against tensile strain, etc. were surveyed.

A B S T R A C T Improving early seedling growth is crucial for direct-seeding rice cultivation. In this study, field and laboratory experiments were conducted to determine the effects of Plant Growth Regulators (PGRs) such as gibberellic acid (GA3) and ethephon (ET) on the early growth of direct-seeded rice. Seeds were treated with the PGRs and pre-germinated at 30°C in the dark. For the field experiment, two Flooding Depth (FD) regimes were established during the growth period: 0 cm (drained condition) and 2 cm (flooded condition). Treatment of seeds with ET or GA3 alone promoted the growth of seedling organs compared to that of the control at both the FDs in some cases. However, combined application of ET and GA3 (ET+GA3) synergistically improved the growth of different seedling organs at both the FDs in most cases with slight exception: the coleoptile and mesocotyl plus coleoptile (mesocotyl+coleoptile) length were not different across the PGR treatments under drained condition. Further, the growth of the second node tiller was stimulated by the application of ET alone under drained conditions. The laboratory experiment revealed that ET+GA3 increased the growth rate of mesocotyl+coleoptile and that of the first leaf. These results suggest that the combined application of ET and GA3 might be useful for improving the growth performance of rice seedlings in the direct seeding method.

Purpose: Gafchromic film for quantitative analysis was renewed from EBT2 to EBT3 film in November 2011. The purpose of this study is to investigate the relevant characteristics of EBT3 film for its application in dosimetric verification for IMRT/VMAT or proton therapy.Method:We investigated the characteristics of EBT3 film with comparison of previous EBT2 film. The experiments in this study composed two categories. At first, the photo spectroscopy for the irradiated film was compared between EBT2 and EBT3. The film 1 day after the irradiation was analyzed by a photo spectrometer (SR520: JASCO Corporation, Japan). Secondly, we investigated several calibration curves which obtained by same batch. The films were calibrated by irradiation the films to 13 dose steps. The irradiated films were scanned by a flatbed scanner (ES‐10000XL, Epson‐Seiko Corporation, Japan). The difference on scan orientation was evaluated alternate portrait and landscape directions. The photon and proton beams were delivered from Clinac 21EX (Varian) and Mitsubishi machine, respectively. Results: The peak absorption wavelength of EBT3 film and its response at all active range were basically same with that of EBT2 film. The peak wavelength of photo absorption in EBT3 was observed at 585 and 634 nm. The fog optical density was increased due to the hazy matte polyester for active layer. However, there is no change the tendency of the calibration curve responding to megavoltage photon and proton beams. The scan orientation dependency of EBT3 film was observed with similar to EBT2 film. The optical density of portrait orientation was 10% higher than that of landscape orientation. Conclusion: The dosimetric characteristics of EBT3 film were basically same with EBT2 film. With regard to the matte polyester, the creation of Newton's rings during scanning procedure was reduced. However, the suitable scan protocol should be used for accurate film dosimetry.

We demonstrate that a calibrated amount of a biomolecule can be microdeposited using a commercially available quartz crystal microbalance (QCM) and a piezoelectric inkjet head with a flattened surface surrounding the ejection hole. Covering the QCM with a stainless-steel cover perforated with a precisely-machined hole both significantly decreased background noise due to external sources such as air flow and temperature fluctuations and allowed accurate droplet ejection at a constant temperature. Anti-c reactive protein antibody solution (anti-CRP; 1.0 mg/ml) was continuously ejected onto a microchannel target using a piezoelectric injector; its microdeposition was monitored shot-by-shot using a 30 MHz QCM. The dispersion of the QCM frequency change per shot decreased from 7.87 to 1.01 Hz when a perforated stainless-steel cover was installed. The primary antibody was precisely deposited on the target with high reproducibility. The variation in luminescence measured by enzyme-linked immunosorbant assay (ELISA) decreased from 9.67% to 1.16% when calibrating the amount of primary antibody deposition with this developed technique.

In sputtering deposition process of TiO2, metal Ti or sintered TiO2 target is used as deposition source. In this study, we have compared the characteristic of target materials. When TiO2 target was used, stoichiometric TiO2 films was deposited under the Ar atmosphere containing 1.0% of oxygen. The highest sputtering rate under this atmosphere was 3.9nm/min at 3.4W/cm2. But, sintered TiO2 target is fragile and cannot endure higher density of input power than 3.4W/cm2. On the other hand, Ti target needs higher oxygen concentration (8%) in sputtering gas atmosphere for obtaining rutile/anatase. Even though Ti target can be input twice power density of 7.9W/cm2, the highest deposition rate for Ti target was 1.4/nm, which was ~35% of the highest rate for TiO2 target. Then we have study out the composite target consisting of Ti plate and TiO2 chips. Using the composite target, stoichiometric TiO2 films were prepared in the rate of 9.6nm/min at 6.8 W/cm2 under the atmosphere of Ar/2.5%O2. Furthermore, we have found that the TiO2 films obtained from the composite target consisted of about 100% anatase, whereas TiO2 films obtained from other target have rutile dominant structure. The optical band gap energy of the film is determined by using the Tauc plot. The calculated band gap energies for the films deposited by Ti target and composite target were 2.95 and 3.24eV, which are equivalent to that of rutile and anatase structure, respectively.

The absolute detection efficiencies of a microchannel plate detector (MCP) were determined experimentally for neutral hydrogen, carbon, and tungsten atoms with impact energies of 0.5–4.5 keV. We measured detection efficiencies using our recently developed method, which uses coincidence counting between neutralized incident ions and ionized target atoms in single-electron capture collisions. The obtained detection efficiencies showed similar impact-energy and mass dependence to those of rare gas atoms (Ne, Ar, Kr, and Xe), measured previously using our method. The detection efficiencies increased with increasing impact energy and converged to the open area ratio (∼50%) of the MCP used. The efficiencies at fixed energies decreased as the mass of the incident atom increased. The absolute detection efficiencies obtained for H, C, W, Ne, Ar, Kr, and Xe atoms could be scaled according to the average electron emission yield estimated using the formulas for electronic and nuclear stopping powers.

The lengthening of ferrite plates in a high-strength low carbon low alloy steel, which contained 1.62 mass% Mn and small amounts of Si, Mo, Ni, Cr, and Nb, was observed in situ under high-temperature confocal laser scanning microscopy. Applying the analysis by Speich and Cohen to the growth of a lath-type plate, it was found that the measured lengthening rates are likely to fall between those calculated assuming para- and NPLE modes from the semiempirical equation proposed by Hillert, while they scattered widely presumably because the plate morphology was not a lenticular disk. In the temperature range of measurement, solute drag due to alloying element segregation at the boundary between plate tip and the matrix may not operate to an appreciable extent. The retardation of lengthening from that calculated under paraequilibrium could occur by intrinsic friction of α/γ boundary.