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Regression of thrombus in response to treatment with direct oral anticoagulants (DOACs) in patients with extensive deep vein thrombosis (DVT) has not been fully evaluated. This study aimed to determine the therapeutic efficacy of rivaroxaban in the treatment of extensive DVT.We retrospectively evaluated 76 patients treated with rivaroxaban among 728 new DVT patients, at our hospital from January 2018 to March 2021. Extensive DVT was defined as thrombus connecting to 2 or more segments of the inferior vena cava (IVC), iliac vein, femoral vein, or popliteal vein. Localized DVT was defined as a thrombus confined to 1 segment of the inferior vena cava (IVC), iliac vein, femoral vein, or popliteal vein. We compared the changes in thrombus between the extensive DVT group (36 patients) and the localized DVT group (40 patients).In the localized DVT group, 14 (37%) had total recanalization within 3 weeks after DOAC initiation, and 30 (79%) had total recanalization within 3 months. In the extensive DVT group, only 3 (9%) had total recanalization within 3 weeks after starting DOAC, and even after 3 months, only 5 (15%) had total recanalization. Symptoms (P = 0.01) and extensive DVT (P 0.01) were significantly associated with the risk for failure of total recanalization.Rivaroxaban was highly effective for total recanalization of localized DVT but not for symptomatic or extensive DVT. In patients with symptomatic extensive DVT, catheter-based thrombolysis may be considered in selected cases.

OBJECTIVES We applied high-flow regional cerebral perfusion (HFRCP) for aortic arch reconstruction in neonates and infants by monitoring regional oxygen saturation of the thigh (rSO2T) using near-infrared spectroscopy to maintain peripheral perfusion. This study was designed to investigate the optimal perfusion flow of HFRCP for renal protection. METHODS From 2009 to 2021, 28 consecutive neonates and infants who underwent aortic arch reconstruction with HFRCP were enrolled. The median age of the patients was 27 days; the median body weight was 3.0 kg. In HFRCP, perfusion flow was targeted at approximately 80–100 mL/kg/min and then lowered corresponding to brain rSO2 levels and blood gas data. Isosorbide dinitrate and chlorpromazine were administered to enhance peripheral perfusion flow. Regional oxygen saturation of the forehead and thighs were monitored. The stage of acute kidney injury (AKI) was classified based on the Kidney Disease Improving Global Outcomes criteria. RESULTS No patients had neurological events and peritoneal dialysis after surgery. The incidence of AKI was 39.3% with only three patients having greater than stage 2 AKI. The maximum postoperative serum creatinine concentration was negatively associated with the lowest rSO2T during HFRCP. The rSO2T during HFRCP was a predictive factor for postoperative creatinine increase of ≧0.3 mg/dL. The area under receiver operating characteristic curve was 0.78 with the cutoff value of 48% for rSO2T. CONCLUSIONS The rSO2T during HFRCP is a potential predictor of postoperative renal function. To prevent AKI, the rSO2T should be preserved more than 48% by increasing HFRCP flow.

Cardiopulmonary bypass-associated acute kidney injury may appear postoperatively, but predictive factors are unclear. We investigated the potential of regional tissue oxygen saturation as a predictor of cardiopulmonary bypass-associated acute kidney injury. We analyzed the clinical data of 150 adult patients not on dialysis who underwent elective cardiac surgical procedures during January 2015-March 2017. Near-infrared spectroscopy was used to measure regional oxygen saturation. Sensors were placed on the patients' forehead, abdomen, and thigh. The incidence of acute kidney injury was 2% at the end of surgery, 13% at 24 h, and 9% at 48 h, with the highest at 24 h after surgery. The multiple regression analysis revealed that the thigh regional oximetry during cardiopulmonary bypass, oxygen delivery index, and neutrophil count at the end of cardiopulmonary bypass and surgery were independent risk factors for acute kidney injury. The receiver-operating characteristic curve analysis suggested that a cutoff of regional oxygen saturation at the thigh of ≤ 67% was predictive of acute kidney injury within 24 h after surgery. In conclusion, the regional oxygen saturation at the thigh during cardiopulmonary bypass is a crucial marker to predict postoperative acute kidney injury in adults undergoing cardiac surgery.

Calcitonin gene-related peptide (CGRP) regulates inflammation via signaling through receptor activity-modifying protein (RAMP) 1. Here, we investigated the role of RAMP1 signaling in growth of lymphatic vessels during inflammation. Lymphangiogenesis in the diaphragm of RAMP1-deficient (-/-) mice or their wild-type (WT) counterparts was induced by repeated intraperitoneal injection of lipopolysaccharide (LPS). Compared with WT mice, LPS-induced lymphangiogenesis in RAMP1-/- mice was suppressed. This was accompanied by the reduced expression of vascular endothelial growth factor (VEGF)-C and VEGF-D. The number of CD4+ cells in diaphragm tissue from WT mice was greater than RAMP1-/- mice. Removing CD4+ cells attenuated lymphangiogenesis and expression of VEGF-C and VEGF-D. CD4+ cells isolated from RAMP1-/- mice exhibited reduced expression of VEGF-C and VEGF-D. The number of CD11b+ cells from RAMP1-/- mice was higher than WT mice and was associated with the upregulated expression of genes related to pro-inflammatory macrophage phenotype and downregulation of reparative macrophage phenotype-related expression. When fluorescein isothiocyanate (FITC)-dextran was injected into the peritoneal cavity, the amount of residual FITC-dextran in WT mice was lower than that in RAMP1-/- mice. The present results suggest that RAMP1 signaling in immune cells plays a critical role in inflammation-related lymphangiogenesis; therefore, it represents a novel target for controlling lymphangiogenesis.

Type III endoleaks after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs) with the Endologix unibody endograft remain a major concern, despite fabric, system, and instructional updates. The purpose of this study was to examine real-world outcomes of repairing AAAs using the current version of the AFX2 main body in combination with an aortic cuff, specifically focusing on type III endoleaks and morphological changes of the endograft.We recruited facilities in Japan that used AFX2 combined with an aortic cuff for at least five cases between April 2017 and March 2018. A total of 175 cases in 24 facilities were analyzed. Patients' background information, including anatomic factors, operative findings, device component variations, and midterm outcomes at 3 years after the EVAR were collected. The data on computed tomography scans from cases registered as types I and III endoleaks and migration from each institute were sent to our department for verification.The mean patient age was 74.6 ± 8.1 years, and 48 cases (27%) were saccular aneurysms. The mean fusiform and saccular AAA diameters were 50.5 ± 5.8 mm and 43.5 ± 8.9 mm, respectively. No in-hospital deaths occurred. Data at 3 years, including computed tomography images, of 128 cases were analyzed. Overall survival, freedom from aneurysm-related mortality, and freedom from reintervention rates at 3 years were 85.8%, 99.3%, and 87.3%, respectively. There were three, one, and three cases of types I, IIIa, and IIIb endoleaks without sac dilatations, respectively. Among five migration cases, one case of aortic cuff migration presented as a type Ia endoleak, and four cases demonstrated sideways displacement, one of which presented as a type IIIa endoleak. The sac regression and enlargement rates at 3 years were 41.4% and 20.5% in the fusiform group and 44.2% and 16.7% in the saccular group, respectively. The proximal neck diameter slightly increased from 20.8 ± 2.7 mm before the EVAR to 22.2 ± 4.6 mm after the repair.Midterm outcomes of the AFX2 used in combination with an aortic cuff were acceptable, considering the rates of types I and III endoleaks. However, there were cases of sideways displacement that could cause future type IIIa endoleaks. When the AFX2 is used in combination with an aortic cuff, close surveillance for endograft deformations and subsequent adverse events, including type III endoleaks, is needed.

BACKGROUND When an internal iliac artery (IIA) has to be embolized during endovascular aneurysm repair (EVAR), buttock claudication sometimes poses problems. However, there is no established method to evaluate intraoperative blood flow to the gluteal muscles.Methods and Results:Gluteal regional oxygen saturation (rSO2) was monitored using near-infrared spectroscopy (NIRS) during surgery, and changes in rSO2were compared with treatment results. Twenty-seven patients who underwent EVAR and IIA embolization at our institution between April 2019 and May 2020 were included in this study. The association between intraoperative changes in rSO2and postoperative incidence of buttock claudication was analyzed. Furthermore, the presence or absence of communication between the superior and inferior gluteal arteries and the intraoperative changes in rSO2were compared to ascertain whether rSO2reflects blood flow change. Postoperative buttock claudication occurred in 4 of 19 patients (21%) with unilateral occlusion of IIA and in 4 of 8 patients (50%) with bilateral occlusion of IIAs. rSO2was found to decrease significantly further in patients with buttock claudication than in patients without buttock claudication (-15±12% vs. -4±16%, P

Background There is insufficient evidence regarding the optimal treatment method for distal deep vein thrombosis (DVT), including indications for anticoagulation therapy. Treatment results of patients with distal DVT were evaluated to clarify the risk factors that result in extension of distal DVT to the proximal vein and indications for anticoagulation therapy.Methods and Results:Among 430 patients with DVT between January 2018 and December 2019, 253 were diagnosed with distal DVT; 41 patients who had already started anticoagulation therapy were excluded, and the remaining 212 were included as study subjects. Anticoagulation therapy was not started immediately; conservative treatment with compression stockings was performed. Ultrasonography after 2 weeks revealed thrombus disappearance in 39 patients (21%), and thrombus reduction in 38 patients (20%). In contrast, extension of thrombus to the proximal vein was noted in 12 patients (6.3%) and anticoagulation therapy was commenced. After 3 months, the thrombus had disappeared in 75 patients (52%). No patient developed pulmonary thromboembolism during follow-up. With respect to the risk factors for extension to proximal vein during conservative treatment, active cancer (P=0.03), prolonged bed rest (P 8µg/mL (P=0.01) were identified. Conclusions It is reasonable to consider anticoagulation therapy in distal DVT patients with active cancer, prolonged bed rest or high D-dimer level.

Regional cerebral oximetry using near-infrared spectroscopy devices is commonly used for detecting cerebral ischemia during cardiopulmonary bypass, and aim to avoid poor cerebral perfusion which may result in perioperative neurological impairment. Today, several devices that can detect cerebral ischemia are commercially available. Although these devices operate on the same measurement principles, their algorithms for detecting and calculating cerebral ischemia are different and no criteria for directly comparing values measured by such different devices exist. From January 2017 to August 2017, 80 adult cardiovascular surgery patients were enrolled in the prospective study. In each patient, preoperative regional cerebral oxygen saturation values were measured by two different devices and their correlations with various preoperative factors were evaluated. Regional cerebral oxygen saturation levels were significantly higher for values of FORE-SIGHT ELITE (CAS Medical Systems, Branford, CT, USA) (F value) than those of the INVOS 5100C (Medtronic, Minneapolis, MN, USA) (I value). Scalp-cortex distance, hemoglobin concentration, and the presence or absence of hemodialysis showed significant correlations with ratios of measured values specific to each device (F/I). An appropriate device should be selected according to preoperative patient characteristics, and factors influencing regional cerebral oxygen saturation values should be considered to ensure the correct interpretation of measured values. This research was conducted with the approval of the ethics committee of our university (approval number: B16-96).

Background Secondary lymphedema commonly arises as a complication of cancer surgery and radiation treatment; however, the underlying mechanisms are poorly understood. Receptor activity-modifying protein 1 (RAMP1) forms a complex with calcitonin receptor–like receptor to generate the receptor for calcitonin gene–related peptide. The present study examined whether RAMP1 plays a role in increased lymphangiogenesis during secondary lymphedema. Methods A model of lymphedema was generated by surgical removal of pre-existing lymphatic vessels from the subcutaneous tissue on the tails of RAMP1-deficient (RAMP1−/−) mice and their wild-type (WT) counterparts. The maximum diameter of the tail, lymphangiogenesis, and macrophage recruitment were then examined. Results Compared with that in WT mice, lymphedema in the tails in RAMP1−/− mice was sustained, with suppressed lymphangiogenesis and reduced expression of vascular endothelial growth factor-C and vascular endothelial growth factor receptor 3 at the distal edge of the lesions. The newly formed lymphatic vessels in RAMP1−/− mice were dilated, with impaired lymphatic flow. RAMP1 was expressed by macrophages recruited into edematous tail tissues distal to the wound. The number of macrophages in RAMP1−/− mice was higher than that in WT mice. Expression of messenger RNA encoding M1 macrophage-related genes, including tumor necrosis factor-α and interleukin-1, was higher in RAMP1−/− mice than in WT mice, whereas expression of messenger RNA encoding M2 macrophage genes, including interleukin-10, was lower. Conclusions RAMP1 signaling improves lymphedema and accelerates lymphangiogenesis associated with reduced recruitment of pro-inflammatory macrophages.

A 38-year-old man underwent surgical repair of a type A aortic dissection. After aortic surgery, his left ventricular ejection fraction was progressively reduced from 65% to 15%, causing a refractory low cardiac output depending on the intravenous inotropes. There was a luminal stenosis of the descending aorta due to enlarged pseudolumen. The peak-to-peak pressure gradient at the stenosis was 25 mmHg, which was thought to contribute to the systolic dysfunction. He underwent thoracic endovascular aortic repair (TEVAR) with the use of a bare self-expanding stent. After TEVAR, the peak-to-peak pressure gradient was decreased to 9 mmHg, resulting in hemodynamic improvement.

OBJECTIVES In this study, we investigated the early and midterm outcomes of initial watch-and-wait strategy for Stanford type A intramural haematoma and acute aortic dissection with thrombosed false lumen of the ascending aorta in patients with a maximum aortic diameter of ≤50 mm, pain score of ≤3/10 and no ulcer-like projection in the ascending aorta. METHODS Inpatient and outpatient records were retrospectively reviewed. RESULTS Of the 81 patients with type A intramural haematoma and acute aortic dissection with the thrombosed false lumen of the ascending aorta between April 2011 and April 2019, a watch-and-wait strategy was selected in 46 patients. The mean age of the patients was 68 years, and 22 (48%) patients were female. Ten patients underwent emergency pericardial drainage for cardiac tamponade at the time of presentation and 8 patients underwent aortic repair during hospitalization for new ulcer-like projection, re-dissection or rupture. In-hospital mortality occurred in 2 (4%) patients. During follow-up, survival at 1 and 2 years was 95% and 92%, respectively. There was no significant difference in survival or aortic events between patients in whom the watch-and-wait strategy and emergency surgical treatment were indicated. CONCLUSIONS The early and midterm outcomes of the initial watch-and-wait strategy were favourable for type A intramural haematoma and acute aortic dissection with the thrombosed false lumen of the ascending aorta in Japanese patients with a maximum aortic diameter of ≤50 mm, pain score of ≤3/10 and no ulcer-like projection. Further study is required to show the safety of this strategy.

Regional cerebral oximetry using near-infrared spectroscopy device, an INVOS 5100 C (Medtronic, Minneapolis, MN, USA), during cardiac surgery aims to avoid perioperative neurological impairment, especially during cardiopulmonary bypass. However, it is not uncommon to encounter critically low initial cerebral regional oxygen saturation or a low value unresponsive to intervention. Therefore, it is important to identify factors associated with low saturation value other than true cerebral hypoxia. We investigated the relationship between preoperative regional cerebral oxygen saturation and clinical variables during cardiac surgery. From January 2013 to May 2016, 462 patients underwent elective cardiac surgery. Patient's ≤12 years of age, with acute cerebral infarction, with previous intracranial hemorrhage or neurosurgery, with concomitant aortic surgery, and having off-pump coronary artery bypass surgery were excluded. The remaining 223 patients were monitored by intraoperative regional cerebral oximetry. Univariate analysis found that scalp-cortex distance, cerebrospinal fluid thickness, left ventricular ejection fraction, hemoglobin concentration, estimated glomerular filtration rate, and hemodialysis were significantly correlated with the initial regional oxygen saturation value. Multiple regression analysis revealed that scalp-cortex distance, left ventricular ejection fraction, hemoglobin, and hemodialysis remained as significant variables. A receiver operating characteristic analysis found that for a low initial regional oxygen saturation value of 40%, the thresholds of scalp-cortex distance, left ventricular ejection fraction, and hemoglobin concentration were 17.6 mm, 45.2%, and 7.5 g/dl, respectively. In conclusion, brain atrophy, poor left ventricular function, anemia, and hemodialysis were associated with low initial cerebral regional oxygen saturation values in adult cardiac surgery patients.

In the original publication, the length unit of the SCD in Table 1 and Fig. 2 has been incorrectly published as cm. The correct length unit is mm.

Patients with mechanical aortic valves are generally contraindicated for left ventricular assist device (LVAD) insertion because the prosthetic valve often becomes fixed in closed position. A 41-year-old woman with mechanical aortic valve prosthesis experienced sudden chest pain and developed cardiogenic shock. A paracorporeal pulsatile LVAD and a monopivot centrifugal pump as a right VAD (RVAD) were implanted. The mechanical aortic valve was intentionally left in place. Soon after the operation, LVAD support was discontinued daily for few seconds to allow the mechanical aortic valve to open and to avoid thrombus formation. The patient was successfully weaned off RVAD and received anticoagulation therapy with warfarin. On postoperative day 141, she was transferred to a university hospital where a HeartMate II LVAD was implanted, and the aortic valve was successfully replaced with a bioprosthetic valve. The patient is currently awaiting heart transplantation.

The Integrated Ocean Drilling Program (IODP) Expedition 343, Japan Trench Fast Drilling Project (JFAST) drilled and cored across the plate-boundary decollement at Site C0019 near the Japan Trench, where large slip occurred during the 2011 Tohoku-Oki earthquake ( M w 9.0). Anisotropy of magnetic susceptibility (AMS) data obtained from core samples show a striking change in magnetic fabric across the decollement. In the frontal prism above the decollement, the maximum AMS axes display a strong preferred orientation in the northeast–southwest direction, with the intermediate and minimum AMS axes distributed in the vertical plane. In the underthrust sediments below the decollement, the maximum and intermediate AMS axes are subhorizontal but variable in direction, and the minimum AMS axes display an approximately vertical preferred orientation. The AMS ellipsoids for all samples have an oblate component, but the AMS ellipsoids of the underthrust sediments are generally less oblate than those of the frontal prism. The magnetic fabric of the sediments in the prism are consistent with horizontal tectonic shortening nearly parallel to the plate convergence direction in the Japan Trench, while that in the underthrust sediments represents a vertical, uniaxial strain. The magnetic fabrics of the frontal prism and underthrust sediments indicate an abrupt change in strain across the decollement at shallow depths, and imply that large co-seismic slip occurred along a weak plate-boundary decollement that is mainly decoupled over the long-term.

Recruited macrophages play a critical role in liver repair after acute liver injury. Leukotriene B4 (LTB4) is a potent chemoattractant for macrophages. In this study, we investigated the role of LTB4 receptor type 1 (BLT1) in liver repair during hepatic ischemia/reperfusion (I/R) injury. BLT1-knockout mice (BLT1(-/-)) or their wild-type counterparts (WT) were subjected to partial hepatic I/R. Compared with WT, BLT1(-/-) exhibited delayed liver repair and hepatocyte proliferation accompanied by a 70% reduction in the recruitment of macrophages and a 70-80% attenuation in hepatic expression of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and VEGF receptor 1 (VEGFR1). Disruption of BLT1 signaling also reduced the expression of EGF by 67% on recruited macrophages expressing VEGFR1 in the injured liver. Treatment of WT mice with an EGF-neutralizing antibody delayed liver repair and reduced macrophage recruitment, compared with control immunoglobulin G (IgG). BLT1 signaling enhanced the expression of VEGF, VEGFR1, and EGF in isolated peritoneal macrophages in vitro. These results indicate that BLT1 signaling plays a role in liver repair after hepatic I/R through enhanced expression of EGF in recruited macrophages and that the development of a specific agonist for BLT1 could be useful for liver recovery from acute liver injury.

Annual geomagnetic variations with a maximum amplitude of 5 nT, and in phase with ground temperature variations at a depth of 1–2 m, were observed in the baseline values of fluxgate magnetometers installed at three JMA magnetic observatories. A possible origin of the annual variations is a change in magnetization of the soil due to changes in ground temperature. In order to examine the effect of temperature changes on soil magnetization, we measured the magnetic properties of soil samples collected at the JMA observatories. Magnetization of soil samples in a magnetic field of 0.05 mT ranged within 0.05 × 10−3−1.6 × 10−3 A m2/kg and the temperature dependence of magnetization ranged within 0.3 × 10−6−14 × 10−6 A m2/kg °C, except for a sample having an extraordinarily strong magnetization. Based on the measured magnetization, and their temperature dependence, of samples from Memambetsu, which shows the largest values among the samples from the three observatories, we determined the distribution of the geomagnetic field and its annual variation produced by soil magnetization. The maximum amplitude of annual variation in the geomagnetic field is 7 nT, which is consistent with the observed annual variation of the baseline value of the magnetometers.

It is known that the neural system plays a fundamental role in neovascularization. A neuropeptide, calcitonin gene-related peptide (CGRP), is widely distributed in the central and peripheral neuronal systems. However, it remains to be elucidated the role of CGRP in angiogenesis during ischemia. The present study examined whether endogenous CGRP released from neuronal systems facilitates revascularization in response to ischemia using CGRP knockout mice (CGRP−/−). CGRP−/− or their wild-type littermates (CGRP+/+) were subjected to unilateral hindlimb ischemia. CGRP−/− exhibited impaired blood flow recovery from ischemia and decreased capillary density expressed in terms of the number of CD-31-positive cells in the ischemic tissues compared with CGRP+/+. In vivo microscopic studies showed that the functional capillary density in CGRP−/− was reduced. Hindlimb ischemia increased the expression of pro-CGRP mRNA and of CGRP protein in the lumbar dorsal root ganglia. Lack of CGRP decreased mRNA expression of growth factors, including CD31, vascular endothelial growth factor-A, basic fibroblast growth factor, and transforming growth factor-β, in the ischemic limb tissue. The application of CGRP enhanced the mRNA expression of CD31 and VEGF-A in human umbilical vein endothelial cells (HUVECs) and fibroblasts. Subcutaneous infusion of CGRP8–37, a CGRP antagonist, using miniosmotic pumps delayed angiogenesis and reduced the expression of proangiogenic growth factors during hindlimb ischemia. These results indicate that endogenous CGRP facilitates angiogenesis in response to ischemia. Targeting CGRP may provide a promising approach for controlling angiogenesis related to pathophysiological conditions.

Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide produced by tissue-specific alternative splicing of the primary transcript of the calcitonin/CGRP gene. CGRP is widely distributed in the central and peripheral neuronal systems and exhibits numerous biological activities in mammals. Recently, it was clarified that endogenous CGRP released from primary afferent neurons facilitates the neovascularization indispensable to tumor growth. Angiogenesis in surgical sponge models that mimics tumor stromal reaction was inhibited by a CGRP antagonist, CGRP8-37. The unilateral sciatic nerves (L1-5) of mice were cut, and Lewis lung carcinoma (LLC) cells were implanted into the subcutaneous tissues of the legs. Tumor growth was significantly reduced in the sites of denervation of these mice, compared with the sham-operated mice. In CGRP knockout mice, the tumor growth and tumor-associated angiogenesis of implanted LLC cells were significantly reduced compared with those in wild-type mice. In LLC-bearing wild-type mice, CGRP precursor mRNA levels in the dorsal root ganglion were increased compared with those in non-LLC bearing mice. This increase was abolished by denervation. In a co-culture system using human umbilical vein endothelial cells (HUVEC) and fibroblasts, CGRP increased tube formation by endothelial cells. VEGF expression was up-regulated in the tumor implantation models in a CGRP-dependent manner. These recent results suggest that sensory nerves facilitate tumor-associated angiogenesis and tumor growth during tumor development via a release of CGRP. The same was true in the processes of wound healing and gastric ulcer healing. Further, CGRP was also reported to enhance the angiogenesis in hind-limb ischemia model. These recent results indicate CGRP may become a novel therapeutic target for controlling angiogenesis.

A megasplay fault branching from the subduction boundary megathrust in the Nankai Trough is thought to have caused large tsunamis associated with past Tonankai earthquakes. Because the temperature recorded in the fault can constrain parameters of seismic slip, we evaluated several temperature proxies (fluid-mobile trace element concentrations, Sr isotopes, magnetic minerals, inorganic carbon content, and Raman spectra of carbonaceous material) in material from a localized slip zone, sampled at Site C0004 by Integrated Ocean Drilling Program Expedition 316. Our results showed that the shallow part of the megasplay fault has not experienced temperatures above 300 °C. We also found that in addition to shear stress and slip distance, slip rate and porosity are effective parameters for frictional heat, as demonstrated by numerical analysis incorporating thermal diffusion. The slip rate estimated through these proxies may indicate that the fault did not slip with high velocity near the seafloor.

Actin cytoskeletal remodeling is essential for neurite outgrowth. LIM kinase 1 (LIMK1) regulates actin cytoskeletal remodeling by phosphorylating and inactivating cofilin, an actin filament-disassembling factor. In this study, we investigated the role of LIMK1 in calcium signal-induced neurite outgrowth. The calcium ionophore ionomycin induced LIMK1 activation and cofilin phosphorylation in Neuro-2a neuroblastoma cells. Knockdown of LIMK1 or expression of a kinase-dead mutant of LIMK1 suppressed ionomycin-induced cofilin phosphorylation and neurite outgrowth in Neuro-2a cells. Ionomycin-induced cofilin phosphorylation and neurite outgrowth were also blocked by KN-93, an inhibitor of Ca(2+)/calmodulin-dependent protein kinases (CaMKs), and STO-609, an inhibitor of CaMK kinase. An active form of CaMKIV but not CaMKI enhanced Thr-508 phosphorylation of LIMK1 and increased the kinase activity of LIMK1. Moreover, the active form of CaMKIV induced cofilin phosphorylation and neurite outgrowth, and a dominant negative form of CaMKIV suppressed ionomycin-induced neurite outgrowth. Taken together, our results suggest that LIMK1-mediated cofilin phosphorylation is critical for ionomycin-induced neurite outgrowth and that CaMKIV mediates ionomycin-induced LIMK1 activation.

1999年に起きた台湾集集（Chi-Chi）地震（Mw7.6）を引き起こしたチェルンプ断層は，その南部と北部では，地震時に生じた断層の挙動に明瞭な違いが認められた．この挙動の違いは，地震時の断層の強度を減少させる“場”の違いや，強度低下を引き起こす機構の違いに起因すると考えられ，これらを明らかにする目的で，2003年に地震断層を貫く台湾チェルンプ断層掘削計画（TCDP）が開始された．その結果，Hole A（掘削深度2000 m）およびHole B（同1350 m）より，孔内検層と併せ地震断層を貫くコア試料が採取され，これまでに種々の面から分析が行なわれた．本総説では，この断層の動的強度低下機構と地震直後の断層のヒーリング過程を知る上で重要な断層帯内部の物理・化学的環境変化についてのコア試料の物性計測や化学分析等の研究成果についてレビューし，その結果を踏まえ現段階で考えられる作業仮説について論述した．

Chemical and isotopic variations in crushed material along the Chelungpu fault in Taiwan are suggestive of interactions at high temperatures with coseismically generated aqueous fluids. High fluid pressures along the fault zone during the magnitude 7.6 Chi-Chi earthquake in 1999 could have reduced friction and fault strength. Aqueous fluids are thought to have an essential role in faulting and the dynamic propagation of earthquake rupture. Fluid overpressure can affect earthquake nucleation1,2 and in a process termed thermal pressurization, pore fluid pressure produced by frictional heating can reduce the effective normal stress acting on the fault surface3,4,5. This may lead to a marked reduction in fault strength during slip. However, the coseismic presence of fluids within slip zones and the role of fluids in dynamic fault weakening is still a matter of debate. Here we present compositions of major and trace elements as well as isotope ratios of core samples representing relatively undamaged as well as very fine-grained deformed material from three active zones of the Chelungpu fault, Taiwan. Depth profiles across the most intensely sheared bands that range in thickness from 2–15 cm exhibit sharp compositional peaks of fluid-mobile elements and of strontium isotopes. We suggest that high-temperature fluids (>350 ∘C) derived from heating of sediment pore fluids during the earthquake interacted with material within the fault zone and mobilized the elements. The coseismic presence of high-temperature fluids under conditions of low hydraulic diffusivity6 within the fault zone is favourable for thermal pressurization. This effect may have caused a dynamic decrease of friction along the Chelungpu fault during the 1999 magnitude 7.6 Chi-Chi earthquake.

We carried out thermomagnetic susceptibility analyses of fault rocks from core samples from Hole B of the Taiwan Chelungpu Fault Drilling Project (TCDP) to investigate the cause of high magnetic susceptibilities in the fault core. Test samples were thermally and mechanically treated by heating to different maximum temperatures of up to 900 °C and by high-velocity frictional tests before magnetic analyses. Thermomagnetic susceptibility analyses of natural fault rocks revealed that magnetization increased at maximum heating temperatures above 400 °C in the heating cycle, and showed three step increases, at 600 to 550 °C and at 300 °C during the cooling cycle. These behaviors are consistent with the presence of pyrite, siderite and chlorite, suggesting that TCDP gouge originally included these minerals, which contributed to the generation the magnetic susceptibility by thermomechanical reactions. The change in magnetic susceptibility due to heating of siderite was 20 times that obtained by heating pyrite and chlorite, so that only a small fraction of siderite decomposition is enough to cause the slight increase of the susceptibility observed in the fault core. Color measurement results indicate that thermal decomposition by frictional heating took place under low-oxygen conditions at depth, which prevented the minerals from oxidizing to reddish hematite. This finding supports the inference that a mechanically driven chemical reaction partly accounts for the high magnetic susceptibility. A kinetic model analysis confirmed that frictional heating can cause thermal decomposition of siderite and pyrite. Our results show that decomposition of pyrite to pyrrhotite, siderite and, to some extent, chlorite to magnetite is the probable mechanism explaining the magnetic anomaly within the Chelungpu fault zone.

大阪湾の海水組成と海底堆積物の磁気特性の分析を行い，初期続成による酸化鉄鉱物の溶解と硫化鉄鉱物の形成に，海水環境が及ぼす影響を考察した．大阪湾の海水構造は，夏場に湾奥部で密度成層が強くなり，海底に貧酸素水塊が形成されていたが，湾奥部だけではなく，海底が溶存酸素に富む湾中央部でも，表層堆積物はフランボイダルパイライトとグレイガイトが形成される還元的な環境であった．これは，湾に多量に供給される有機物を分解するために，溶存酸素が堆積物のごく表層で消費されるためと考えられる．一方，海底の溶存酸素とヘマタイトの含有率との間に，明瞭な対応関係が見られた．これは，溶存酸素に富み，酸化鉄の溶解があまり進んでいない湾中央部では，ヘマタイトが選択的に溶け残っていることを反映していると考えられる．ヘマタイトの含有率の磁気的指標であるS比が，大阪湾では海水環境の指標となる可能性がある．

We presented the total and inorganic carbon contents of core samples recovered from the Taiwan Chelungpu fault system, which slipped at the 1999 Chi-Chi earthquake, and reported lower contents of inorganic carbon within the black gouge zone in FZB1136 (fault zone at depth 1136 m in Hole B) and in the black-material disks in FZB1194 and FZB1243.

Vascular endothelial growth factor-A (VEGF-A) induces actin reorganization and migration of endothelial cells through a p38 mitogen-activated protein kinase (MAPK) pathway. LIM-kinase 1 (LIMK1) induces actin remodeling by phosphorylating and inactivating cofilin, an actin-depolymerizing factor. In this study, we demonstrate that activation of LIMK1 by MAPKAPK-2 (MK2; a downstream kinase of p38 MAPK) represents a novel signaling pathway in VEGF-A-induced cell migration. VEGF-A induced LIMK1 activation and cofilin phosphorylation, and this was inhibited by the p38 MAPK inhibitor SB203580. Although p38 phosphorylated LIMK1 at Ser-310, it failed to activate LIMK1 directly; however, MK2 activated LIMK1 by phosphorylation at Ser-323. Expression of a Ser-323-non-phosphorylatable mutant of LIMK1 suppressed VEGF-A-induced stress fiber formation and cell migration; however, expression of a Ser-323-phosphorylation-mimic mutant enhanced these processes. Knockdown of MK2 by siRNA suppressed VEGF-A-induced LIMK1 activation, stress fiber formation, and cell migration. Expression of kinase-dead LIMK1 suppressed VEGF-A-induced tubule formation. These findings suggest that MK2-mediated LIMK1 phosphorylation/activation plays an essential role in VEGF-A-induced actin reorganization, migration, and tubule formation of endothelial cells.

14C ages of benthic foraminifera and planktonic foraminifera in sediment core PC4 (41°07.10′N, 142°24.17′E) collected from the northwestern Pacific were measured by accelerator mass spectrometry. The purpose of this study was to investigate the changes in intermediate water ventilation in the northwestern Pacific during the last glacial period. We used age differences between benthic foraminifera and planktonic foraminifera from the same sediment horizons to estimate the ventilation time of intermediate water. Planktonic 14C ages show that the core recorded paleoenvironmental changes during the last 35 kyr. Glacial benthic–planktonic age differences were smaller in the early deglacial period (15 000–17 000 cal yr BP) than in the period (19 000–30 000 cal yr BP) before and during the last glacial maximum. The results at intermediate depths are consistent with those from a Pacific deep-water site.

Four distinct components of natural remanent magnetization were isolated from a single site in welded tuffs in the Upper Cretaceous Kisin Group of the Sikhote Alin mountain range, Russia. In order to contribute toward a basis for an interpretation of multicomponent magnetization, rock magnetic experiments were performed on the welded tuffs. All four magnetization components essentially reside in magnetite. The lowest-temperature component up to 300 °C (component A: D =349.3°, I =60.9°, α 95 =7.3°, N =7) is a present day viscous magnetization. The third-removed component (component C: D =41.4°, I =51.8°, α 95 =3.5°, N =8), isolated over the temperature range of 450–560 °C, is a primary remanence. The second- and fourth-demagnetized components (component B: D =174.7°, I =−53.1°, α 95 =21.2°, N =3 and component D: D =188.1°, I =−64.5°, α 95 =4.0°, N =8, respectively) are secondary magnetizations related to a thermal event in Sikhote Alin between 66 and 51 Ma. Components B and D were acquired through different remagnetization processes. Component B is ascribed to a thermoviscous remanent magnetization carried by single-domain magnetite, and component D is a chemical remanent magnetization.

SUMMARY We conducted a mineral magnetic study on sand samples from the Taklimakan desert, Tarim Basin in western China. Modern sands were collected at 19 sites in the central and western parts of the Taklimakan desert. We carried out low-field susceptibility measurements, ARM and IRM acquisitions, high- and low-temperature measurements and hysteresis measurements on these samples. Nearly stoichiometric magnetite is the dominant magnetic mineral of these samples. The presence of titanomagnetite is unlikely, and contributions from a high-coercivity mineral(s) are minor. Magnetic grain size is estimated to be that of larger pseudo-single domain or even greater. We compared the hysteresis data against loess samples from both pristine and weathered loess sections from the Chinese Loess Plateau. We found an apparent decreasing grain size trend from the Taklimakan to the central Loess Plateau through the western Loess Plateau. These lines of evidence favour the idea that the Taklimakan desert is one of the potential dust source areas, even though it is located more than 2000 km west of the central Loess Plateau.

SUMMARY Rock magnetic measurements of Chinese loess–palaeosol samples from the Beiyuan section in Linxia City suggest the presence of two magnetic components: a background component and an enhanced component. The magnetic properties of the enhanced component suggest strong grain-size control, which is in contrast with variable grain-size distribution in loess–palaeosol from the central Loess Plateau. Chemically formed magnetic grains do not fulfil the requirements in the case of the western Loess Plateau because they may show shifts in the grain-size distribution. The difference in climate between the western and central Loess Plateau may lead to different origins and different preservation conditions of the pedogenic magnetite.

Magnetic carriers in remagnetized Cretaceous granitic rocks of northeast Japan were studied using paleomagnetism, rock magnetism, optical microscopy and scanning electron microscopy (SEM) by comparison with unremagnetized granitic rocks. The natural remanent magnetization (NRM) of the remagnetized rocks is strong (0.3–1.7 A/m) and shows a northwesterly direction with moderate inclination (NW remanence), whereas the unremagnetized rocks preserve weak NRM (

The 28 m high-resolution Shajinping loess section in Lanzhou on the western Chinese Loess Plateau records a 60 ka, millennial summer monsoon variation. The record shows that Asian summer monsoons have rapid episodic pulse enhancements spanning only ca. 1–2 ka in high-frequency domain and having sub-Milankovitch cycles of progressive weakening in low frequency domain in the last glaciation. Soil formation seems to occur with a surprisingly fast response to these summer monsoon enhancements, resulting in weakly or moderately developed paleosol sequences. Both the pattern and timing of the summer monsoon enhancements show that they can be correlated to most major warm (Dansgaard–Oeschger) episodes and long-term cooling (Bond) cycles of the North Atlantic climatic records, indicating a possible teleconnection between tropic oceanic air masses and the North Atlantic climatic system. But differences exist for the transition of MIS 2/3 and the Holocene, where extraordinarily heavy dust-input events and fairly variable climatic fluctuations occur for the former and latter, respectively. A westerlies-swing model is proposed to interpret this link.

A 72-year-old male was admitted to the hospital because of chest oppression. The patient was operated on under a diagnosis of mediastinum tumor. The tumor invaded the great arteries, pericardium, left lung and bilateral phrenic nerves. The pathological diagnosis was carcinoid tumor of the thymus. Serum neuron specific enolase (NSE) levels decreased after the surgery. NSE may be a useful marker for the diagnosis and follow-up of thymic cartinoids.

Stressed Out Large seismic events such as the 2011 magnitude 9.0 Tohoku-Oki earthquake can have profound effects not just on the severity of ground motion and tsunami generation, but also on the overall state of the crust in the surrounding regions. Lin et al. (p. 687 ) analyzed the stress 1 year after the Tohoku-Oki earthquake and compared it with the estimated stress state before the earthquake. In situ resistivity images were analyzed from three boreholes drilled into the crust across the plate interface where the earthquake occurred. Stress values indicate a nearly complete drop in stress following the earthquake such that the type of faulting above the plate boundary has changed substantially. These findings are consistent with observations that the sea floor moved nearly 50 meters during the earthquake.

In a 65-year-old man who had been diagnosed as having lung cancer, invasive thymoma was pointed out on chest computed tomography. First, he underwent a right upper lobectomy. The pathological diagnosis was squamous cell carcinoma of the lung. After a month of the first operation, he underwent a thymothymectomy including left diaphragmatic nerve resection. Nearly 3 years after the second operation, he was urgently admitted to our hospital because of respiratory failure. A diagnosis of respiratory muscle failure due to diaphragmatic paralysis was made. He received mechanical ventilation followed by daily training for respiration. Mechanical ventilation was needed only at night. Thus, we decided that home mechanical ventilation (HMV) was possible. His present condition has been steady using HMV at home. HMV is effective for achieving a better quality of life.

A 37-year-old female with complaints of lower abdominal pain and nausea was admitted to our hospital. An emergency operation was performed after a diagnosis of acute appendicitis was made. At laparotomy, a whitish, appendiceal tumor was found invading the cecum, and ileocecal resection was performed. The microscopic diagnosis of the tumor was mucinous cystadenocarcinoma of the appendix infiltrating the cecum. At a second look operation three days after the first operation, peritoneal calcinosis was found in the Douglas cavity but no regional lymph node metastasis was detected. Right hemicolectomy with lymph node dissection was then performed.Preoperative diagnosis of primary carcinoma of the appendix is difficult. Thus, intraoperative rapid histological diagnosis by frozen block is necessary, in addition to preoperative examinations, including echography and CT scans.

The main science goal of the Japan Trench Fast Drilling Project (JFAST) is to understand the physical mechanisms and dynamics of large slip earthquakes, which is fundamental to understanding the huge tsunami that caused extensive damage during the 2011 Tohoku earthquake. Specifically, the level of frictional stress during the earthquake rupture and the physical characteristics of the fault zone are investigated through drilling. The objectives of JFAST include locating the fault that ruptured during the Tohoku event using logging while drilling (LWD); characterizing the composition, architecture, and fundamental mechanisms of dynamic frictional slip and healing processes along the fault by taking core samples; and estimating the frictional heat and stress within and around the fault zone by placing a temperature measurement observatory across the fault. During the main JFAST expedition (Integrated Ocean Drilling Program [IODP] Expedition 343 in April and May 2012), LWD was completed in a borehole drilled to 850.5 meters below seafloor (mbsf) (total depth [TD] = 7740 meters below sea level [mbsl]), and a coring hole was drilled to 844.5 mbsf (TD = 7734 mbsl) to acquire 21 cores that spanned the two main fault targets. Because of delays associated with severe weather and technical challenges of operating in great water depths, installation of the observatories for temperature and pressure measurements was not completed during the main expedition; however, temperature sensors were successfully deployed during a short technical extension of JFAST, IODP Expedition 343T (JFAST II), in July 2012. Principal results of Expedition 343/343T include the following: 1. The overall structure at the drill site consists of a prism of faulted and folded clayey to silty mudstones above, and in fault contact (at ~820 mbsf) with, a largely undeformed, relatively thin sequence of hemipelagic and pelagic sediments that were deposited on top of the incoming Pacific plate. The primary constituents of the mudstones that make up the prism are terrigenous silt and clay, vitric ash, and biogenic silica. The fault contact, interpreted as the plate boundary decollement, is defined by a subhorizontal

The time accuracy of geomagnetic data is an important specification for one-second data distributions. We tested a procedure to verify the time accuracy of a fluxgate magnetometer by using a GPS pulse generator. The magnetometer was equipped with a high time resolution (100 Hz) output, so the data delay could be checked directly. The delay detected from one-second data by a statistical method was larger than those from 0.1-s- and 0.01-s-resolution data. The test of the time accuracy revealed the larger delay and was useful for verifying the quality of the data.

Tumor cells can migrate in 3D matrices in either a mesenchymal-like or amoeboid mode. HT1080 fibrosarcoma cells cultured in 3D collagen gels change their morphology from mesenchymal-like (elongated) to amoeboid (round) following protease inhibitor (PI) treatment or active Rho or ROCK expression. In this study, we examined the role of LIM-kinase 1 (LIMK1) in the PI- or Rho/ROCK-induced cell morphological change. We showed that LIMK1 was activated after PI treatment of HT1080 cells in 3D collagen gels and this activation was blocked by a ROCK inhibitor. While overexpression of LIMK1 induced cell rounding, knockdown of LIMK1 or the expression of kinase-inactive LIMK1 suppressed PI- or Rho/ROCK-induced cell rounding. These results suggest that LIMK1 plays an essential role in the PI- or Rho/ROCK-induced mesenchymal-to-amoeboid cell morphological transition of HT1080 cells cultured in 3D collagen gels. Furthermore, LIMK1 knockdown suppressed the invasive activity of HT1080 cells in collagen gels with or without PIs, indicating that LIMK1 mediates both the mesenchymal and amoeboid modes of invasion of HT1080 cells.

[1] To understand the chemical reactions of clay minerals in a fault zone during an earthquake, we analyzed the clay minerals in the Chelungpu fault, which slipped during the 1999 Chi-Chi earthquake. X-ray diffraction spectroscopy showed that kaolinite and smectite contents were lower in the black gouge zone than in the surrounding gray gouge, breccia, or fracture-damaged zones. We applied a chemical kinetics approach to examine whether dehydroxylation of kaolinite and dehydration of interlayer water, dehydroxylation, and illitization of smectite occurred during coseismic frictional heating, and found that the first two reactions could complete under the temperature-time profile of the Chi-Chi earthquake, reconstructed by a previous study. Because dehydration of smectite interlayer water and dehydroxylation of kaolinite would have completed 3.6 and 8.2 s after the beginning of slip, the resulting release of water might have affected the frictional mechanism during the earthquake.

[1] A duplicate high-resolution magnetic record was obtained from two parallel loess sections separated by about 300 m near Baoji city, southern Chinese Loess Plateau. This reveals at least eight short-lived reversed polarity episodes in the uppermost part of the Olduvai normal polarity subchronozone. Rock magnetic experiments and anisotropy of low-field magnetic susceptibility confirm that the multiple occurrence of short-lived reversals is not due to rock-magnetic and/or sedimentary causes. Assuming a constant accumulation rate within the Olduvai subchron, the short episode zone was estimated to span about 24–30 ka and 24–31 ka for the two sections, respectively. The duration of each short episode ranges from about 0.3 ka to 2.1 ka. The present results together with previous worldwide observations show that the occurrence of numerous short reversals is peculiar to the latest Olduvai subchron. The geodynamo may have been in an anomalous state at that time.

[1] In the paper ‘‘A chemical kinetic approach to estimate dynamic shear stress during the 1999 Taiwan Chi-Chi earthquake’’ by T. Hirono et al. (Geophysical Research Letters, 34, L19308, doi:10.1029/2007GL030743), the equation for estimation of dynamic shear stress, the calculations provided for stresses normal to the fault, and the resultant shear stresses and frictional coefficients were incorrect. [2] The fourth sentence of paragraph 1 should read as follows. [3] The dynamic shear stress during the Chi-Chi earthquake was deduced to be 1.37 MPa, and the frictional coefficient to be 0.03–0.08. [4] The second sentence of paragraph 11 including equation (9) should read as follows. [5] From equations (2), (4), (8), and f(a) = (1 a), a in the center of the fault zone (x = 0) is expressed as

To characterize the fault-related rocks within the Chelungpu fault, we performed X-ray computed tomography (CT) image analyses and microstructural observations of Hole B core samples from the Taiwan Chelungpu-fault Drilling Project. We identified the slip zone associated with the 1999 Chi-Chi earthquake, within the black gouge zone in the shallowest major fault zone, by comparison with previous reports. The slip zone was characterized by low CT number, cataclastic (or ultracataclastic) texture, and high possibility to have experienced a mechanically fluidized state. Taking these characteristics and previous reports of frictional heating in the slip zone into consideration, we suggested that thermal pressurization was the most likely dynamic weakening mechanism during the earthquake.

International audience; Estimation of the dynamic shear stress on a fault during an earthquake is important for understanding the earthquake itself. Using a chemical kinetic approach, we examined the thermal decomposition of carbonate minerals to estimate the shear stress on the Taiwan Chelungpu fault, which slipped during the 1999 Chi-Chi earthquake. The reaction rate of the decomposition was related to temperature by using the Arrhenius equation, and the chemical kinetics, taking into account the temperature change over time caused by frictional heating and heat conduction, was solved by the finite difference method. The dynamic shear stress during the Chi-Chi earthquake was deduced to be 1.31 MPa, and the frictional coefficient to be 0.04– 0.05. This estimated value agrees with the hypothesis that friction along the Chelungpu fault was low.