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OBJECTIVE Gamma Knife radiosurgery (GKRS) is an established surgical option for the treatment of trigeminal neuralgia (TN), particularly for high-risk surgical candidates and those with recurrent pain. However, outcomes after three or more GKRS treatments have rarely been reported. Herein, the authors reviewed outcomes among patients who had undergone three or more GKRS procedures for recurrent TN. METHODS The authors conducted a multicenter retrospective analysis of patients who had undergone at least three GKRS treatments for TN between July 1997 and April 2019 at two different institutions. Clinical characteristics, radiosurgical dosimetry and technique, pain outcomes, and complications were reviewed. Pain outcomes were scored on the Barrow Neurological Institute (BNI) scale, including time to pain relief (BNI score ≤ III) and recurrence (BNI score > III). RESULTS A total of 30 patients were identified, including 16 women and 14 men. Median pain duration prior to the first GKRS treatment was 10 years. Three patients (10%) had multiple sclerosis. Time to pain relief was longer after the third treatment (p = 0.0003), whereas time to pain recurrence was similar across each of the successive treatments (p = 0.842). Complete or partial pain relief was achieved in 93.1% of patients after the third treatment. The maximum pain relief achieved after the third treatment was significantly better among patients with no prior percutaneous procedures (p = 0.0111) and patients with shorter durations of pain before initiation of GKRS therapy (p = 0.0449). New or progressive facial sensory dysfunction occurred in 29% of patients after the third GKRS treatment and was reported as bothersome in 14%. One patient developed facial twitching, while another experienced persistent lacrimation. No statistically significant predictors of adverse effects following the third treatment were found. Over a median of 39 months of follow-up, 77% of patients maintained complete or partial pain relief. Three patients underwent a fourth GKRS treatment, including one who ultimately received five treatments; all of them reported sustained pain relief at the extended follow-up. CONCLUSIONS The authors describe the largest series to date of patients undergoing three or more GKRS treatments for refractory TN. A third treatment may produce outcomes similar to those of the first two treatments in terms of long-term pain relief, recurrence, and adverse effects.

A 66 year-old man with a previous history of Sjögren's syndrome was admitted with anastomotic pseudoaneurysm and aortic dissection in the ascending aorta, which developed after Bentall's surgery, a procedure that has severe complications and high mortality. Using the reverse extra-anatomical aortic arch debranching technique, zone 0 thoracic endovascular aortic repair was performed emergently. The postoperative course was uneventful. Twenty months later, computed tomography showed remodeling of the dissection, resolution of the pseudoaneurysm, and patency of the reverse extra-anatomical aortic arch debranching graft.

Background/Introduction Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reported to have beneficial effects on heart failure in large clinical trials; however, the underlying mechanism is still unclear. Purpose The purpose of this study is to elucidate the mechanism of cardioprotective effect of empagliflozin in heart failure. Methods Eight-week-old mice deficient in cardiac and skeletal muscle-specific manganese superoxide dismutase, a mouse model of dilated cardiomyopathy (MnSOD-cKO mice), were given food mixed with or without 10 mg/kg empagliflozin for seven weeks and evaluated. Mitochondrial function in the cardiac muscle were measured by a high-resolution respirometer, Oxygraph-2K. Respiratory gas analysis were performed by indirect calorimetry (ARCO 2000) to estimate the energy consumption and energetic substrates. Results The survival rate (P=0.015) and cardiac fibrosis (P=0.036) were significantly improved in the empagliflozin group. The capacity of oxidative phosphorylation in cardiac mitochondria was significantly improved by empagliflozin. Blood lactate levels were decreased in the empagliflozin group, indicating that energy such as ATP could be produced without resorting to anaerobic metabolism. Respiratory gas analysis revealed significant improvement in energy expenditure along with increase in food intake. Respiratory quotient was not different between the two groups, showing the consumption of the carbohydrate to fat rate was not changed by empagliflozin in this study. Ketone levels in blood and HbA1c were neither significantly different between the two groups. Although a moderate amount glucose was excreted in urine in the empagliflozin group (128.3±20.4 mg/day, 0.51±0.08 kcal/day), the available energy substrates in the whole body nonetheless expanded because of the increased caloric intake (10.58±0.72 in control group vs. 13.55±0.08 kcal/day in empagliflozin group, P=0.018). Conclusion(s) We have shown that empagliflozin improved myocardial mitochondrial function and increased energy metabolism, which was accompanied by adequate energy intake and uptake, even in heart failure. Empagliflozin decreased myocardial fibrosis and improved prognosis in failing murine hearts through positive energetical properties including mitochondrial function. The finding that empagliflozin modulates cardiac metabolism in a positive way provides a novel mechanism for the cardioprotective effect of SGLT2 inhibitors in heart failure. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Boehringer Ingelheim Empa improved prognosis in HFEmpa improved mitochondrial function

Reflection type measurements were performed on narrow-gap semiconductors such as InSb and InAs bulk samples for harmonic generation using intense terahertz pulses from free electron laser. We successfully measured the characteristic azimuthal angle dependence of the third harmonic generation (THG). The results show cos3θ and cos6θ dependence at different polarization layouts for InAs(111).

Introduction With wider use of stent grafts, treating nonagenarians with abdominal aortic aneurysm has become more common in Japan. This is the report of a 103 year old patient with a ruptured abdominal aortic aneurysm who successfully underwent emergency endovascular aortic repair. To the present authors’ knowledge, this report describes the oldest patient treated for a ruptured abdominal aortic aneurysm with a successful outcome. Report A 103 year old man with ruptured abdominal aortic aneurysm was successfully treated by endovascular aortic repair. The post-operative course was uneventful, and he was discharged from the hospital on post-operative day 11. Two months later, in the outpatient clinic, the patient was doing well. Conclusion It is important that decisions concerning the operative indications for a ruptured abdominal aortic aneurysm in elderly patients are based not only on age, but also on a comprehensive pre-operative assessment, including consideration of the patient's activity of daily life and personal wishes, as well as the desires of family members., Highlights • This is the case report of 103 year old man with RAAA treated by EVAR. • This is the oldest case of treated RAAA reported in the literature. • Two months after EVAR, the patient was doing well at the outpatient clinic.

Gallium nitride (GaN) single crystals with high carrier concentration up to 1020cm−3 order were evaluated by the terahertz time-domain spectroscopic ellipsometry. The electric properties such as carrier density are obtained by the fitting analysis based on Drude model. The terahertz ellipsometry is powerful non-contact and non-destructive evaluation method for semiconductors with high carrier concentration.

The temporal electric field distribution by the propagating picosecond electron bunches was measured by using electro-optic sampling in a ZnTe crystal with the near-infrared femtosecond laser pulses. The temporal profile of the electron bunches with a pulse width of 1.0 ps was measured. The signal with a reversed polarity to the peak by the electron bunch is observed and ascribed to the ionization and electron current which recovers the charge-up induced by the electron bunch excitation.

The left atrial appendage is thought to be responsible for the majority of embolic strokes, and has become an important target in the surgical management of atrial fibrillation. We present an original clip-and-loop technique using an AtriClip via a left minithoracotomy for post-stroke patients with atrial fibrillation. This procedure was performed in 43 cases between March 2018 and January 2020. No patient had a thrombus at the edge of the clip or communication into the left atrial appendage 3 months after surgery. Anticoagulant could be discontinued in all patients. Follow-up at 23 ± 10 months showed no recurrence of stroke.

Molecular testing for SARS-CoV-2 is the mainstay for accurate diagnosis of the infection, but the diagnostic performances of available assays have not been defined. We compared 12 molecular diagnostic assays, including 8 commercial kits using 155 respiratory samples (65 nasopharyngeal swabs, 45 oropharyngeal swabs, and 45 sputum) collected at 2 Japanese hospitals. Sixty-eight samples were positive for more than one assay and one genetic locus and were defined as true positive samples. All the assays showed a specificity of 100% (95% confidence interval, 95.8 to 100). The N2 assay kit of the US Centers for Disease Control and Prevention (CDC) and the N2 assay of the Japanese National Institute of Infectious Disease (NIID) were the most sensitive assays with 100% sensitivity (95% confidence interval, 94.7 to 100), followed by the CDC N1 kit, E assay by Corman, and NIID N2 assay multiplex with internal control reactions. These assays are reliable as first-line molecular assays in laboratories when combined with appropriate internal control reactions.

A novel BEOL compatible three-layered structure based on ferroelectric (FE) HfO 2 device is proposed for endurance improvement. This structure consists of an ultrathin Y 2 O 3 passivation layer, a FE Y-doped HfO 2 layer (YHO, deposited at room temperature (RT)) and a buffer CeOx layer. Y 2 O 3 is used for passivation of defects with the bottom electrode (NiSi 2 ) while CeOx is used to control oxygen vacancies in FE-YHO. Good FE hysteresis is observed in YHO (from 12.5 to 9.2 nm) while low temperature activation annealing (200°C-400°C after CeOx deposition), greatly enhances the FE-YHO properties. After annealing at 350□, this novel capacitor (YHO= 9.2nm) shows lower leakage current, initial remanent polarization of 25μC/cm2 (2Pr), excellent endurance up to 1e12 cycles at low power operation conditions and good data retention at RT.

Aortoenteric fistula (AEF) after endovascular aortic repair (EVAR) is a rare complication, with only 32 cases reported previously. A 71-year-old man who presented with severe duodenal bleeding due to primary AEF (PAEF) underwent successful EVAR. Four years later, the AEF recurred because of dilatation of the aneurysm sac. He underwent emergent surgery, removal of the stent graft, and replacement of an artificial bifurcated graft with placement of a greater omental flap. EVAR for PAEF was an effective option for acute treatment, but it caused refistulization in the long term. EVAR should be considered as a bridge therapy to definitive surgery.

Background We performed a clinical and pathological analysis of cases of acute vascular rejection (AVR), characterized by intimal arteritis and transmural arteritis (Banff v score) after kidney transplantation, in an attempt to clarify the mechanisms underlying the development and prognostic significance of AVR. Methods AVR (Banff score: v >0) was diagnosed in 31 renal allograft biopsy specimens (BS) obtained from 31 renal transplant patients receiving follow-up care at the Department of Urology, Tokyo Women's Medical University, between January 2010 and April 2016. Results AVR was diagnosed at a median of 124.6 days after transplantation. Among the 31 BS showing evidence of AVR, AVR was mild (v1 in Banff's classification) in 25 cases, moderate (v2) in 6, and severe (v3) in none. We classified the 31 BS with evidence of AVR by their overall histopathological features as follows: isolated v lesions were observed in 6 BS, acute antibody-mediated rejection (AAMR) in 7, acute T-cell–mediated rejection (ATCMR) in 12, and both ATCR and AAMR in 6. Loss of the renal allograft occurred during the observation period in 3 patients, and, of the remaining cases with functioning grafts, deterioration of renal allograft function after biopsy occurred in only 2 patients. Conclusions The results of our study suggest that ATCMR contributes to AVR in 40% to 60% of cases, AAMR in 20% to 40% of cases, and isolated v lesions in 20% of cases. The prognosis of the patient with the graft that had AVR was relatively good under the present immunosuppression protocol and current anti-rejection therapies.

Bisphosphonates (BPs) and teriparatide (TPTD) are both effective treatments for osteoporosis, but BP treatment prior to daily TPTD treatment has been shown to impair the effect of TPTD in some clinical studies. In contrast, the loss of bone mineral density (BMD) that occurs after withdrawal of TPTD can be prevented by BP treatment. Although various studies have investigated the combination and/or sequential use of BP and TPTD, there have been no clinical studies investigating sequential treatment with zoledronic acid (ZOL) and TPTD (or vice versa). In this study, we evaluated the effects of sequential treatment with TPTD followed by ZOL, and ZOL followed by TPTD, using ovariectomized (OVX) rats. Two months after OVX, osteopenic rats were treated with ZOL, TPTD, or vehicle for a period of 4 months (first treatment period), and then the treatments were switched and administered for another 4 months (second treatment period). The group treated with ZOL followed by TPTD showed an immediate increase in BMD of the proximal tibia and greater BMD and bone strength of the lumbar vertebral body, femoral diaphysis, and proximal femur than the group treated with ZOL followed by vehicle. Serum osteocalcin, a marker of bone formation, increased rapidly after switching to TPTD from ZOL. The group treated with TPTD followed by ZOL did not lose BMD in the proximal tibia after TPTD was stopped, while the group treated with TPTD followed by vehicle did lose BMD. The BMD and bone strength of the lumbar vertebral body, femoral diaphysis, and proximal femur were greater in the group treated with TPTD followed by ZOL than in the group treated with TPTD followed by vehicle. The increase in serum osteocalcin and urinary CTX after withdrawal of TPTD was prevented by the switch from TPTD to ZOL. In conclusion, our results demonstrate that switching from ZOL to TPTD resulted in a non-attenuated anabolic response in the lumbar spine and femur of OVX rats. In addition, switching from TPTD to ZOL caused BMD to be maintained or further increased. If these results can be reproduced in a clinical setting, the sequential use of ZOL followed by TPTD or vice versa in the treatment of osteoporosis patients would contribute to increases in BMD that, hopefully, would translate into a corresponding decrease in the incidence of vertebral and non-vertebral fractures., Highlights • Sequential treatment of zoledronic acid followed by teriparatide immediately increased bone mineral density. • Sequential treatment of zoledronic acid followed by teriparatide immediately increased bone formation. • Sequential treatment of teriparatide followed by zoledronic acid prevented the decrease of bone mineral density. • Sequential treatment of teriparatide followed by zoledronic acid prevented the increase of bone resorption.

Background/Introduction Left atrial appendage (LAA) occlusion is an effective strategy for thromboembolism prevention in patients with atrial fibrillation (AF), and the novel methods of occlusion is various. The acute thrombosis after percutaneous LAA occlusion devices has been recently reported, but thrombus formation after surgical LAA occlusion is still unclear. Purpose This study aimed to analyse the incidence and prognosis of thrombus formation on closure stump line in patients with AF who underwent surgical LAA occlusion. Methods This study retrospectively analised the data from patients treated with two methods of surgical LAA closure, resection or clipping, from January 2014 to November 2018. Results A total of 187 consecutive patients with AF underwent surgical LAA closure (31 clipping and 156 stapler resection). 170 patients (91%) underwent cardiac CT for LAA imaging on postoperative day 2. The incidence of acute procedure-related thrombus formation in full cohort was 19% (35 cases). The incidence of acute thrombus in patients with clipping and resection was 19% and 16%, respectively (Fisher's exact test, p=0.8). All of 35 patients who had thrombus on LAA closure stump line underwent cardiac CT again 3 months after the primary CT. In all patients with secondary cardiac CT, thrombus on LAA closure stump line disappeared. No symptomatic thromboembolism occurred during the follow-up from operation to secondary CT scan. Conclusion(s) Thrombus formation on stump after surgical LAA closure may often occur on acute phase. The optimal LAA imaging and anti-coagulation therapy after surgical LAA occlusion will prevent patients with acute thrombus from thromboembolism.

The Ultra Fine Sun Sensor (UFSS) on board the HINODE solar observing satellite is one of the most successful sun sensors. It is the linear CCD sun sensor with a special detection method using multiple slits, called the periodic reticle. The angular resolution of 0.14 arcsec in the noise equivalent angle (NEA) and 1 arcsec stability were achieved by the sensor head, of 1.2 kg weight. The concept of the detection method and processing algorithm of the Sun’s direction is described. The system is modeled and the dynamic response of the system is characterized by the first-order lag system. By utilizing this characteristic, a resolution improvement three times higher can be expected by adjusting the parameters with a small modification to the HINODE UFSS processing algorithm. The design for a new UFSS for the next generation solar observation satellite, SOLAR-C, shall include these modifications. The thermomechanical design is also reviewed to improve stability and a design policy is obtained.

A six-pole Q-band waveguide filter with a notch frequency above the Q-band has been developed for plasma diagnostics. The previous paper [Nishiura et al., J. Instrum. 10, C12014 (2015)] reported that the notch frequency exists within the standard band. In this study, the newly required notch filter extends the function, which prevents a thorny wave from being mixed into an instrument beyond the standard bandwidth of the waveguide. The mode control technique for cavities realizes a deep and sharp filter shape for Q-band notch filters with 56 and 77 GHz notches, respectively. The former filter has an attenuation more than 50 dB at 56.05 GHz and a bandwidth of 1.1 GHz at -3 dB. The latter filter has an attenuation more than 55 dB at 76.95 GHz and a bandwidth of 1.6 GHz at -3 dB. The electron cyclotron emission imaging and the electron cyclotron emission (ECE) diagnostics for the Q-band implemented a pair of the fabricated filters and demonstrated the ECE measurement successfully in the intense stray radiation from a 56 GHz gyrotron.

Earthquakes can result in disasters affecting infrastructure and assets that are exposed and vulnerable and thus prone to damage. Considering earthquake cascades, we can reveal the immediate and intermediate effects of earthquakes causing infrastructure damage. In this study, we propose a network analytical modeling approach to analyze earthquake cascades. The analytical framework integrates incident causation modeling and probabilistic network analysis. The linear effects from earthquakes are delineated in incident chains to represent the consequences of earthquakes to infrastructure; the incident chains are then remodeled topologically by the network theory to reveal the nonlinear cascading effects of earthquakes to infrastructure. The network of earthquakes’ effects and intermediate effects is then structurally analyzed by probabilistic network analysis that uncovers the unifying principles and statistical topology of earthquake cascades to infrastructure. The results show that earthquakes can directly cause significant damage to infrastructure and indirectly cascade the effects to infrastructure damage via intermediate effects; each effect or intermediate effects in earthquake cascades have their own role in leading to infrastructure damage. The critical infrastructure damage due to earthquakes and critical intermediate effects in propagating earthquake cascades are revealed in this study by the network analysis of network density, degree centrality, closeness centrality, betweenness centrality, and cascade quantification. To reduce infrastructure damage due to earthquake cascades, we suggest tackling the directed interdependent intermediate effects to minimize the risks associated with earthquakes to infrastructure damage. The network analytical framework in this study can be used to understand the propagation damage of earthquakes on infrastructure; thus, our work can provide valuable insight into earthquake preparedness and emergency management.

The Banff Working Group on Liver Allograft Pathology reviewed and discussed literature evidence regarding antibody-mediated liver allograft rejection at the 11th (Paris, France, June 5-10, 2011), 12th (Comandatuba, Brazil, August 19-23, 2013), and 13th (Vancouver, British Columbia, Canada, October 5-10, 2015) meetings of the Banff Conference on Allograft Pathology. Discussion continued online. The primary goal was to introduce guidelines and consensus criteria for the diagnosis of liver allograft antibody-mediated rejection and provide a comprehensive update of all Banff Schema recommendations. Included are new recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization. In an effort to create a single reference document, previous unchanged criteria are also included.

III International Symposium on Citrus Biotechnology

Typical inertial confinement fusion (ICF) plasmas have ultra-high energy density state (UHEDs) with an energy density exceeding 1 × 108 Jcm−3, which corresponds to a pressure of beyond 1 Gbar. In previous investigation, it is suggested that such an UHEDs condition could be generated with a tabletop ultrahigh intensity laser, by irradiating onto a nanowire array. In this research, we have developed to observe the laser energy absorption and transport mechanism in nanowire array samples with x-ray free electron laser facility SACLA. We obtained time-resolved snapshots of x-ray shadowgraph image with very high temporal resolution. From the measured images, however, the UHEDs might be generated only on very thin portion of the target surface because the mean density of the nanowire array was large. On the other hand, we observed significant rear surface expansion in late timing, suggesting that large laser energy deposition was achieved for the nanowire array samples.

The purpose of the present study is to assess the perioperative changes in the cognitive function of patients after cardiovascular surgery (CVS) and to find out risk factors for early postoperative cognitive decline. From December 2013 to March 2017, 291 patients underwent elective or urgent CVS with cardiopulmonary bypass in our institution. One hundred and fifteen patients, who agreed to an evaluation of their cognitive function, were included in this study. The cognitive function was evaluated by the HDS-R and MMSE at three time points: before surgery, in the early postoperative period and at discharge. The patients’ characteristics, perioperative data, HDS-R and MMSE scores were obtained by reviewing their medical records retrospectively. The patients were stratified into three age groups. In all of the age groups, the early postoperative cognitive functional scores were severely decreased in comparison to the preoperative values. However, by the time of discharge, the function had improved to the same level as before surgery in each of the groups. In addition, the similar tendency was observed in patients with preoperative cognitive dysfunction. Moreover, multiple regression analysis demonstrated that preoperative cognitive function and age were significant risk factors for early cognitive impairment. Although preoperative cognitive decline and patients’ age were the risk factors for early postoperative cognitive impairment after CVS, a significant recovery can be expected even in elderly patients or patients with low preoperative cognitive function by the time of discharge.

We report a case of living related renal transplantation that used the recipient's saphenous vein as a graft to extend the length of the right donor renal vein. A 41-year-old woman underwent ABO-incompatible living related renal transplantation from her 74-year-old mother in November 2014. A retroperitoneal laparoscopic right donor nephrectomy was performed, because the right kidney showed a cyst on preoperative computed tomography. As the right kidney after donor nephrectomy had a short renal vein and the kidney was large at 280 g, anastomosis with the external iliac vein was difficult. Therefore, we obtained the recipient's 15-cm-long right saphenous vein and created a 1 cm saphenous vein graft. We anastomosed 1 side of the saphenous vein graft to the allograft renal vein in bench surgery and performed end-to-side anastomosis of the other end to the recipient's external iliac vein. The allograft renal artery was used to perform end-to-end anastomosis to the recipient's internal iliac artery. Allograft kidney function was good after transplantation. When the longer axis of the renal graft vein is short, as in the right kidney, a saphenous vein graft may be useful.

著者人数: 153名（所属. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS): 堂谷, 忠靖; 羽澄, 昌史; 今田, 大皓; 満田, 和久; 坂井, 真一郎; Tomida, T.; 辻本, 匡弘; Yamamoto, R.; 山崎, 典子）, Accepted: 2018-04-30, 資料番号: SA1180210000

Background VEGF and Ang2 signaling have key functions in tumor angiogenesis and have an immunosuppressive effect in the tumor microenvironment. Preclinical data show that combined inhibition of VEGF/Ang2 and PD-1 enhances the tumor microenvironment to support T-cell mediated destruction of tumor cells. BI 836880 is a humanized bispecific nanobody that targets VEGF and Ang2, and BI 754091 is an anti-PD-1 antibody. Each have shown safety and preliminary activity as monotherapy in phase I (recommended phase 2 dose [RP2D] 720 mg intravenous [iv] every 3 weeks [q3w] for BI 836880 [Caucasian pts] and 240 mg iv q3w for BI 754091 [Caucasian and Japanese pts]). An ongoing phase Ib study (NCT03468426) will determine the RP2D, safety and preliminary activity of BI 836880 + BI 754091 in Caucasian pts. The current phase I study will determine the maximum tolerated dose (MTD)/RP2D of BI 836880 alone or in combination with BI 754091 in Japanese pts with advanced solid tumors. Trial design This open-label, multi-center, dose-escalation trial will enroll pts with a confirmed diagnosis of advanced, unresectable and/or metastatic solid tumors (any type) whose disease is not amenable to standard therapies or where there is no therapy of proven efficacy. Pts are required to have an ECOG PS ≤ 1 and adequate organ function. The study has 2 parts: Part 1 will assess BI 836880 monotherapy and Part 2 will assess BI 836880 + BI 754091. Pts will receive BI 836880 at a starting dose of 360 mg iv q3w in Part 1 and of 120 mg iv q3w in Part 2 (in combination with BI 754091 240 mg iv q3w). Administration will continue until progressive disease, unacceptable toxicity or other withdrawal criteria. Dose escalation will be guided by Bayesian logistic regression models with overdose control in both Parts, with oversight from a safety monitoring committee. Primary endpoint is MTD/RP2D of BI 836880 alone (Part 1) and in combination with BI 754091 (Part 2). Secondary/further endpoints will document the safety, pharmacokinetics, anti-tumor activity and immunogenic response of BI 836880 alone and in combination with BI 754091. It is planned to enroll 24 pts. Clinical trial identification NCT03972150. Legal entity responsible for the study Boehringer Ingelheim. Funding Boehringer Ingelheim. Disclosure K. Yamazaki: Speaker Bureau / Expert testimony: Chugai; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho; Speaker Bureau / Expert testimony: Yakult; Speaker Bureau / Expert testimony: Ono; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Lily; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Merck-Serono; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Bristol-Myers Squibb. T. Shimizu: Honoraria (self): Clinical Research Joint Scientific Committee Review Member for Phase 1 trials in Hong Kong; Honoraria (self): HKSAR China; Advisory / Consultancy, Research grant / Funding (institution): Takeda Oncology; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Daiichi-Sankyo; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Chordia Therapeutics; Research grant / Funding (institution): 3D-Medicine; Research grant / Funding (institution): Symbio Pharmaceuticals; Research grant / Funding (institution): PharmaMar; Research grant / Funding (institution): Five Prime; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): AbbVie. T. Takahashi: Honoraria (self), Research grant / Funding (institution): AstraZeneca KK; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan K.K.; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical Co., Ltd.; Honoraria (self), Research grant / Funding (institution): MSD K.K.; Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim Japan, INC; Honoraria (self): Roche Diagnostics K.K.; Research grant / Funding (institution): Pfizer Japan Inc. Y. Tanaka: Full / Part-time employment: Boehringer Ingelheim. H. Myobudani: Full / Part-time employment: Boehringer Ingelheim. N. Yamamoto: Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy: Otsuka; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy: Cimic; Advisory / Consultancy, Research grant / Funding (institution): Chugai; Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Ono; Speaker Bureau / Expert testimony: Sysmex; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Daiichi-Sankyo; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Kyowa-Hakko Kirin; Research grant / Funding (institution): Janssen Pharma; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Merck. All other authors have declared no conflicts of interest.

Purpose Klinefelter syndrome (KS) (47, XXY) is the most common sex chromosome abnormality in humans. KS is characterized by gynecomastia, tall stature, small testes, low testosterone levels, learning disabilities, and behavioral problems. KS is also associated with infertility due to non‐obstructive azoospermia (NOA). The mechanism underlying NOA is still poorly understood, and although there is no current treatment, the use of microdissection testicular sperm extraction (micro‐TESE) followed by in vitro fertilization can result in successful conception. The generation of induced pluripotent stem (iPS) cells derived from KS patients may be useful for studying the disease mechanism and identifying novel therapies. Methods Cells from a KS patient were transduced with Sendai viral vectors encoding four transcription factors, OCT4, SOX2, KLF4, and C‐MYC, and the transduced cells were analyzed for in vitro and in vivo pluripotency. Results KS patient‐derived iPS cells were successfully generated and shown to produce teratomas in the testes of SCID mice. In vitro differentiation of the iPS cells into cardiomyocyte‐like cells was confirmed by the presence of clusters of beating cells. Conclusions KS patient‐derived iPS cells that could differentiate into cardiomyocyte‐like cells were established.

High integration of photonics circuits and electronic circuits is expected in Si photonics technology. The small size of integrated photonics circuits is expected to lead to low costs and high-density optical interconnection. On the other hand, reduction in packaging costs will become vital toward lowering costs because of the demand for highly accurate assembly processes in optical coupling. Harmony between integrated devices and packaging design should be consider to realize miniature size and low cost transceiver. We propose advanced devices and Packaging of an Si-photonics-based optical transceiver for optical interconnection.

The next Japanese solar mission, SOLAR-C, which has been envisaged after successful science operation of Hinode (SOLAR-B) mission, is perusing two plans: plan-A and plan-B, and under extensive study from science objectives as well as engineering point of view. The plan-A aims at performing out-of-ecliptic observations for investigating, with helioseismic approach, internal structure and dynamo mechanisms of the Sun. It also explores polar regions where fast solar wind is believed to originate. A baseline orbit for plan-A is a circular orbit of 1 AU distance from the Sun with its inclination at around or greater than 40 degrees. The plan-B aims to study small-scale plasma processes and structures in the solar atmosphere which attract researchers’ growing interest, followed by many Hinode discoveries [1], for understanding fully dynamism and magnetic nature of the atmosphere. With plan-B, high-angular-resolution investigation of the entire solar atmosphere (from the photosphere to the corona, including their interface layers, i.e., chromosphere and transition region) is to be performed with enhanced spectroscopic and spectro-polarimetric capability as compared with Hinode, together with enhanced sensitivity towards ultra-violet wavelengths. The orbit of plan-B is either a solar synchronous polar orbit of altitude around 600 km or a geosynchronous orbit to ensure continuous solar observations. After the decision of any one of the two plans, the SOLAR-C will be proposed for launch in mid-2010s. In this paper, we will present a basic design of one of major planned instrumental payload for the plan-B: the Solar Ultra-violet Visible and near IR observing Telescope (hereafter referred to as SUVIT). The basic concept in designing the SUVIT is to utilize as much as possible a heritage of successful telescope of the Solar Optical Telescope (SOT) aboard Hinode [2]. Major differences of SUVIT from SOT are the three times larger aperture of 1.5 m, which enables to collect one order of magnitude more photons than SOT, relatively shorter telescope length of 2.8 m to accommodate a launcher’s nosecone size for possible dual-satellite-launch configuration, and much wider observing wavelength from UV (down to 250 nm) through near IR (up to 1100 nm). The large aperture is essentially important to attain scientific goals of the plan-B, especially for accurate diagnostics of the dynamic solar chromosphere as revealed by Hinode, although this make it difficult to design the telescope because of ten times more solar heat load introduced into the telescope. The SUVIT consists of two optically separable components; the telescope assembly (TA) and an accompanying focal plane package equipped with filtergraphs and spectrographs. Opto-mechanical and -thermal performance of the TA is crucial to attain high-quality solar observations and here we present a status of feasible study in its optical and thermal designing for diffraction-limited performance at visible wavelength in a reasonably wide field of view.

Summary Background Despite the introduction of plasmapheresis and immunoglobulin therapy, many patients with Guillain-Barre syndrome still have an incomplete recovery. Evidence from pathogenesis studies suggests the involvement of complement-mediated peripheral nerve damage. We aimed to investigate the safety and efficacy of eculizumab, a humanised monoclonal antibody against the complement protein C5, in patients with severe Guillain-Barre syndrome. Methods This study was a 24 week, multicentre, double-blind, placebo-controlled, randomised phase 2 trial done at 13 hospitals in Japan. Eligible patients with Guillain-Barre syndrome were aged 18 years or older and could not walk independently (Guillain-Barre syndrome functional grade 3–5). Patients were randomly assigned (2:1) to receive 4 weeks of intravenous immunoglobulin plus either eculizumab (900 mg) or placebo; randomisation was done via a computer-generated process and web response system with minimisation for functional grade and age. The study had a parallel non-comparative single-arm outcome measure. The primary outcomes were efficacy (the proportion of patients with restored ability to walk independently [functional grade ≤2] at week 4) in the eculizumab group and safety in the full analysis set. For the efficacy endpoint, we predefined a response rate threshold of the lower 90% CI boundary exceeding 50%. This trial is registered with ClinicalTrials.gov, number, NCT02493725. Findings Between Aug 10, 2015, and April 21, 2016, 34 patients were assigned to receive either eculizumab (n=23) or placebo (n=11). At week 4, the proportion of the patients able to walk independently (functional grade ≤2) was 61% (90% CI 42–78; n=14) in the eculizumab group, and 45% (20–73; n=5) in the placebo group. Adverse events occurred in all 34 patients. Three patients had serious adverse events: two in the eculizumab group (anaphylaxis in one patient and intracranial haemorrhage and abscess in another patient) and one in the placebo group (depression). The possibility that anaphylaxis and intracranial abscess were related to eculizumab could not be excluded. No deaths or meningococcal infections occurred. Interpretation The primary outcome measure did not reach the predefined response rate. However, because this is a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials. Funding The Japan Agency for Medical Research and Development, Ministry of Health, Labor and Welfare, and Alexion Pharmaceuticals.

Background Adult-onset Still9s disease (AOSD) is a systemic inflammatory disease of unknown etiology. Overproduction of multiple inflammatory cytokines and subsequent hyperactivation of monocytes/macrophages are prominent characteristics of AOSD. However, there are no convenient and precise methods for evaluating monocyte/macrophage activation in AOSD. We previously reported that monocyte CD64 (mCD64) expression could be quantitatively measured by flow cytometry and its expression was tightly correlated with the activity of systemic lupus erythematosus. Objectives We examined the association between mCD64 expression and AOSD disease activity. Methods This was a prospective, single-center, observational study conducted between January 2013 and December 2016. Eleven active AOSD patients who fulfilled the Yamaguchi9s criteria for AOSD and had the modified Pouchot score of ≥2 were enrolled. The mCD64 expression levels were quantitatively measured by flow cytometry and individually assessed both before (Pouchot score ≥2) and after treatment (score 0). Other disease-related laboratory data, such as C-reactive protein, ferritin, and white blood cell count, were simultaneously measured. As a control, 16 active systemic lupus erythematosus (SLE) patients (SLE disease activity index ≥6), 22 active rheumatoid arthritis (RA) patients (disease activity score with 28-joint counts >3.2), and 20 healthy controls (HC) (female, 55%; mean age, 38.7±9.1 years) were enrolled. Statistical analysis was performed by the Mann-Whitney and Wilcoxon-paired tests. Results The median mCD64 expression levels were 73,339 [interquartile range (IQR), 45,861–88,181] and 16,443 (IQR, 45,891–88,181) molecules/cell before and after treatment, respectively. Thus, mCD64 expression levels were significantly decreased during the inactive phase compared with those in the active phase in AOSD (p=0.0001). The mCD64 expression levels were significantly higher in patients with active AOSD than in those with active SLE [34,648 (IQR, 44,204–24,657) molecules/cell, p=0.001], active RA [25,167 (IQR, 35,778–22,301) molecules/cell, p Conclusions These results suggest that mCD64 expression levels are highly upregulated in AOSD and tightly correlated with disease activity. The mCD64 expression level may be a useful biomarker for assessing the disease activity of AOSD. References Rau M, et al. J Rheumatol. 2010 Nov;37(11):2369–76. Kikuchi-Taura A, et al. Lupus. 2015 Sep;24(10):1076–80. Pouchot J, et al. Medicine. 1991;70:118–36. Disclosure of Interest None declared

Background and aims Lupus nephritis (LN) is one of the most serious clinical manifestations of systemic lupus erythematosus (SLE). Recently, we have reported that the expression levels of CD64 on monocyte (mCD64), a high-affinity receptor for IgG (FcgRI), correlate with the disease activity of SLE (Lupus 2015;24:1076–80). However, the relation between lupus nephritis (LN) and mCD64 expression is yet to be elucidated. The aim of this study is to investigate whether or not mCD64 expression level correlates with the activity of LN. Methods We quantitatively measured the mCD64 expression levels by flow cytometry in eight SLE patients with biopsy proven LN before and after treatment. All patients fulfilled the 1997 American College of Rheumatology classification criteria for SLE. The mCD64 expression levels of the individual patients were measured both at active (presence of proteinuria >0.5 g/day and/or active urinary sediment) and inactive phase (absence of proteinuria and active urinary sediment). The changes were analysed statistically (Wilcoxon signed-rank test). Results The mean±SD of mCD64 expression levels before and after treatment were 42 463±15 466 and 19 190±1696 molecules/cell, respectively (p Conclusions The mCD64 expression level correlates with the activity of LN, although a larger scale study is needed to confirm the results.