Upper-plate conduits linked to plate boundary that hosts slow earthquakes.

In shallow subduction zones, fluid behavior impacts various geodynamic processes capable of regulating slip behaviors and forming mud volcanoes. However, evidence of structures that control the fluid transfer within an overriding plate is limited and the physical properties at the source faults of slow earthquakes are poorly understood. Here we present high-resolution seismic velocity models and reflection images of the Hyuga-nada area, Japan, where the Kyushu-Palau ridge subducts. We image distinct kilometer-wide columns in the upper plate with reduced velocities that extend vertically from the seafloor down to 10-13 km depth. We interpret the low-velocity columns as damaged zones caused by seamount subduction and suggest that they serve as conduits, facilitating vertical fluid migration from the plate boundary. The lateral variation in upper-plate velocity and seismic reflectivity along the plate boundary correlates with the distribution of slow earthquakes, indicating that the upper-plate drainage system controls the complex pattern of seismic slip at subduction faults.

Subducting volcaniclastic-rich upper crust supplies fluids for shallow megathrust and slow slip.

Recurring slow slip along near-trench megathrust faults occurs at many subduction zones, but for unknown reasons, this process is not universal. Fluid overpressures are implicated in encouraging slow slip; however, links between slow slip, fluid content, and hydrogeology remain poorly known in natural systems. Three-dimensional seismic imaging and ocean drilling at the Hikurangi margin reveal a widespread and previously unknown fluid reservoir within the extensively hydrated (up to 47 vol % H2O) volcanic upper crust of the subducting Hikurangi Plateau large igneous province. This ~1.5 km thick volcaniclastic upper crust readily dewaters with subduction but retains half of its fluid content upon reaching regions with well-characterized slow slip. We suggest that volcaniclastic-rich upper crust at volcanic plateaus and seamounts is a major source of water that contributes to the fluid budget in subduction zones and may drive fluid overpressures along the megathrust that give rise to frequent shallow slow slip.

Detection of hydroacoustic signals on a fiber-optic submarine cable.

A ship-based seismic survey was conducted close to a fiber-optic submarine cable, and 50 km-long distributed acoustic sensing (DAS) recordings with air-gun shots were obtained for the first time. We examine the acquired DAS dataset together with the co-located hydrophones to investigate the detection capability of underwater acoustic (hydroacoustic) signals. Here, we show the hydroacoustic signals identified by the DAS measurement characterizing in frequency-time space. The DAS measurement can be sensitive for hydroacoustic signals in a frequency range from [Formula: see text] to a few tens of Hz which is similar to the hydrophones. The observed phases of hydroacoustic signals are coherent within a few kilometers along the submarine cable, suggesting the DAS is suitable for applying correlation analysis using hydroacoustic signals. Although our study suggests that virtual sensor's self-noise of the present DAS measurement is relatively high compared to the conventional in-situ hydroacoustic sensors above a few Hz, the DAS identifies the ocean microseismic background noise along the entire submarine cable except for some cable sections de-coupled from the seafloor.

Impact of Smoking History on Pulmonary Metastasis-free Survival in Patients With Soft-tissue Sarcoma.

Background/Aim: Although smoking history is predictive of poor pulmonary metastasis-free survival (PMFS) in patients with epithelial tumors, the impact of smoking history on PMFS in those with soft-tissue sarcoma (STS) is not known. Patients and Methods: Patients undergoing treatment for STS at our institutes between 2008 and 2017 were enrolled. Patients were excluded if they had metastatic lesion, or had a histopathological classification demonstrating small round-cell sarcoma. The impact of smoking history on PMFS and overall survival was examined with multivariate analysis using a Cox proportional hazards model. Results: A total of 250 patients were retrospectively reviewed. Patients with smoking history had worse PMFS on multivariate analysis (hazard ratio=2.00, 95% confidence interval=1.12-3.60). On the other hand, smoking history did not significantly affect overall survival (hazard ratio=1.26, 95% confidence interval=0.61-2.58). Conclusion: Patients with STS need to be followed-up by frequent clinical assessments if they have a smoking history.

Metastases of soft tissue sarcoma to the liver: A Historical Cohort Study from a Hospital-based Cancer Registry.

BACKGROUND: Hepatic metastasis of soft tissue sarcoma is rare compared to lung metastasis, and the literature is scarce. We examined the risk of hepatic metastasis according to the site of occurrence and histological type. METHODS: From a Hospital-based Cancer Registry, 658 patients registered between 2007 and 2017 with soft tissue sarcomas were evaluated. The exclusion criteria were gastrointestinal stromal tumors, tumors of unknown origin, and follow-up periods of less than 1 month. SPSS 25 was used for statistical analysis. RESULTS: The risk of hepatic metastasis was significantly higher in the retroperitoneum (HR, 5.981; 95% CI, 2.793-12.808) and leiomyosarcoma (HR, 4.303; 95% CI, 1.782-10.390). Multivariate analysis showed that the risk of hepatic metastasis as first distant metastasis was high in leiomyosarcoma (HR, 4.546; 95% CI, 2.275-9.086) and retroperitoneal onset (HR, 4.588; 95% CI, 2.280-9.231). The 2-year survival rate after hepatic metastasis was 21.7%. CONCLUSIONS: The onset of hepatic metastasis indicates a poor prognosis. However, hepatic metastasis from retroperitoneal sarcoma and leiomyosarcoma may be the first distant metastasis in some cases. For retroperitoneal sarcoma and leiomyosarcoma, additional screening for hepatic metastasis such as contrast CT should be considered during staging and follow-up after treatment.

Breast cancer cells expressing cancer-associated sialyl-Tn antigen have less capacity to develop osteolytic lesions in a mouse model of skeletal colonization.

Breast cancer is one of the most prevalent malignancies in women, and approximately 75-80% of patients with advanced breast cancer develop bone metastasis. Expression of the cancer-associated carbohydrate antigen sialyl-Tn (STn) in breast cancer is associated with a poor prognosis; however, involvement of STn in the development of metastatic bone lesions remains unclear. We investigated whether STn expression on breast cancer cells influences intraosseous tumor growth and bone response in mice models of skeletal colonization. STn-positive (STn+) breast cancer cells were generated by stable transfection of an expression vector encoding ST6GaLNAc I into the breast cancer cell line MDA-MB-231. Parental MDA-MB-231 cells not expressing STn antigen were used as STn-negative (STn-) breast cancer cells. Contrary to expectations, STn expression attenuated the development of destructive bone lesions in the in vivo mice models. An in vitro study demonstrated that STn expression impaired adhesion of MDA-MB-231cells to bone marrow stromal cells. This finding in vitro was also confirmed by another breast cancer cell line MCF-7. Cell adhesion to fibronectin and type I collagen was also impaired in STn+ MDA-MB-231 cells compared to that in STn- MDA-MB-231 cells, suggesting integrin dysfunction. Given that the integrin ß1 subunit is the main carrier of the STn epitope, it is likely that changes in glycan structure impaired the adhesive capacity of ß1 integrin in the bone environment, leading to attenuation of tumor cell engraftment. In conclusion, breast cancer cells expressing STn antigen had less capacity for skeletal colonization, possibly due to impaired adhesive capability.

Effects of femoral bone defect morphology on initial polished tapered stem stability in massive defect model: a biomechanical study.

BACKGROUND: Good outcomes have been reported in revision total hip replacement with massive segmental defects using impaction bone grafting with circumferential metal meshes. However, the morphology of defects that require a mesh is poorly defined. The purpose of this study was to evaluate the effects of a variety of segmental defects on load transmission to the proximal femur under both axial and rotational loads. METHODS: Initial stability of the Exeter stem was investigated in a composite bone model using three medial bone defect morphologies: Long (length 5 cm × width 2 cm), Short (2.5 cm × 2 cm), Square (3.2 cm × 3.2 cm), Square with mesh (3.2 cm × 3.2 cm defect covered with metal mesh), and with no defect as control. Specimens (5 per group) were axially loaded and internally rotated up to 20° or to failure. Strain distributions of the femora were measured using a strain gauge. RESULTS: All Square group specimens failed while rotation was increasing. In the other four groups, failure was not observed in any specimens. Mean torsional stiffness in the Long (4.4 ± 0.3 Nm/deg.) and Square groups (4.3 ± 0.3 Nm/deg.) was significantly smaller than in the Control group (4.8 ± 0.3 Nm/deg.). In the medio-cranial region, the magnitude of the maximum principal strain in the Square group (1176.4 ± 100.9) was significantly the largest (Control, 373.2 ± 129.5, p < 0.001; Long, 883.7 ± 153.3, p = 0.027; Short, 434.5 ± 196.8, p < 0.001; Square with mesh, 256.9 ± 100.8, p < 0.001). Torsional stiffness, and both maximum and minimum principal strains in the Short group showed no difference compared to the Control group in any region. CONCLUSIONS: Bone defect morphology greatly affected initial stem stability and load transmission. If defect morphology is not wide and the distal end is above the lower end of the lesser trochanter, it may be acceptable to fill the bone defect region with bone cement. However, this procedure is not acceptable for defects extending distally below the lower end of the lesser trochanter or defects 3 cm or more in width.

Corticosteroid dose increase is a risk factor for nonalcoholic fatty liver disease and contralateral osteonecrosis of the femoral head: a case report.

BACKGROUND: The incidence of bilateral corticosteroid-induced osteonecrosis of the femoral head (ONFH) is high. Although the precise mechanism of corticosteroid-induced ONFH development is unclear, hepatic enzyme abnormalities such as low activity of hepatic cytochrome P450 3A could be one cause. Herein, we report the case of a patient who developed ONFH in the contralateral hip after the dose of corticosteroids for idiopathic thrombocytopenic purpura was increased. Liver biopsy was done to rule out autoimmune hepatitis. CASE PRESENTATION: A 32-year-old woman had been treated with continuous corticosteroids of up to 10 mg/day for Sjögren's syndrome for 25 years and corticosteroid-induced ONFH in the left side. At age 33, idiopathic thrombocytopenia developed, which was treated by increasing the corticosteroid dose (40 mg/day). Two months later, liver enzyme level began to increase slightly and continued to increase. A year after corticosteroid dose increase, contralateral ONFH developed, and a liver biopsy demonstrated nonalcoholic fatty liver disease (NAFLD). CONCLUSIONS: The current case indicates that corticosteroid dose increase is a potential risk factor for NAFLD and contralateral ONFH. Therefore, it would be useful and important for to screen and monitor patients with hepatic enzyme abnormality for ONFH occurrence.

A mathematical model for predicting postoperative leg shortening after curved intertrochanteric varus osteotomy for osteonecrosis of the femoral head.

Despite good clinical outcomes associated with curved intertrochanteric varus osteotomy for the treatment of osteonecrosis of the femoral head, post-operative leg-length discrepancy is frequently reported and might reduce patient satisfaction. Although previous report showed that varus angulation affected post-operative leg-length discrepancy, sufficient varus angulation is the most important factor for obtaining a lateral intact portion. Therefore, to ensure better postoperative outcomes, detection of other parameters associated with leg shortening may prove useful. This study aimed to detect other factors influencing post-operative leg-length discrepancy and to develop a theory for pre-operative planning. The study included 42 hips of 36 patients with osteonecrosis of the femoral head [25 men and 11 women; mean age at the time of surgery, 33.8 years (range, 17 to 53 years)]. Patients were assessed their clinical and radiological results bofore and after surgery. Additionally, a mathematical model was developed to predict leg shortening after curved intertrochanteric varus osteotomy based on the degree of varus angulation and the distance between the femoral head and osteotomy arc centers. Predicted and actual leg shortening in patients were compared to verify the accuracy of our model. Post-operatively, mean varus angle was 21.7° (range, 15 to 38°) and mean leg shortening was 1.7 mm (range, -5.1 to 11.4 mm). Univariate analysis showed that varus angulation and lateral shift of the osteotomy arc might influence the degree of leg shortening. Furthermore, mathematically predicted leg shortening significantly correlated with actual leg shortening (r = 0.905, p < 0.001), suggesting the usefulness of our model for predicting complications of curved intertrochanteric varus osteotomy. This study indicates the importance of not positioning the center of the osteotomy arc lateral from the center of the femoral head to minimize leg shortening after curved intertrochanteric osteotomy.

Is There an Association Between Borderline-to-mild Dysplasia and Hip Osteoarthritis? Analysis of CT Osteoabsorptiometry.

BACKGROUND: The definitive treatment of borderline-to-mild dysplasia remains controversial. A more comprehensive understanding of the etiology of osteoarthritis (OA) and clarification of any possible association between borderline-to-mild dysplasia and the pathogenesis of OA are essential. QUESTIONS/PURPOSES: (1) Does the distribution of acetabular subchondral bone density increase according to dysplasia severity? (2) Is there an association between borderline-to-mild dysplasia and OA pathogenesis? METHODS: We evaluated bilateral hips of patients with developmental dysplasia of the hip who underwent eccentric rotational acetabular osteotomy (ERAO) for inclusion in the dysplasia group and contralateral hips of patients with unilateral idiopathic osteonecrosis of the femoral head (ONFH) who underwent curved intertrochanteric varus osteotomy (CVO) for the control group. ERAO was performed in 46 patients and CVO was performed in 32 patients between January 2013 and August 2016 at our institution. All patients underwent bilateral hip CT. The study included 55 hips categorized according to dysplasia severity: (1) borderline-mild, 19 hips (15° ≤ lateral center-edge angle [LCEA] < 25°); (2) moderate, 20 hips (5° ≤ LCEA < 15°); (3) severe, 16 hips (LCEA < 5°); and (4) control, 15 hips. Thirty-seven dysplastic hips (age < 15 or > 50 years old, prior hip surgery, subluxation, aspherical femoral head, cam deformity, and radiographic OA) and 17 control hips (age < 15 or > 50 years old, bilateral ONFH, LCEA < 25° or ≥ 35°, cam deformity, and radiographic OA) were excluded. CT-osteoabsorptiometry (OAM) predicts physiologic biomechanical conditions in joints by evaluating subchondral bone density. We evaluated the distribution of subchondral bone densities in the acetabulum with CT-OAM, dividing the stress distribution map into six segments: anteromedial, anterolateral, centromedial, centrolateral, posteromedial, and posterolateral. We calculated the percentage of high-density area, which was defined as the upper 30% of Hounsfield units values in each region and compared least square means difference estimated by the random intercept model among the four groups. RESULTS: In all regions, the percentage of high-density area did not differ between the borderline-mild group and the control (eg, anterolateral, 16.2 ± 5.6 [95% CI, 13.4 to 18.9] versus 15.5 ± 5.7 [95% CI, 12.4 to 18.5, p = 0.984]; centrolateral, 39.1 ± 5.7 [95% CI, 36.4 to 41.8] versus 39.5 ± 4.7 [95% CI, 36.6 to 42.5, p = 0.995]; posterolateral, 10.9 ± 5.2 [95% CI, 8.0 to 13.8] versus 15.1 ± 6.8 [95% CI, 11.7 to 18.5, p = 0.389]). In the anterolateral region, a smaller percentage of high-density area was observed in the borderline-mild group than in both the moderate group (16.2 ± 5.6 [95% CI, 13.4-18.9] versus 28.2 ± 5.1 [95% CI, 25.5-30.9], p < 0.001) and the severe group (16.2 ± 5.6 [95% CI, 13.4-18.9] versus 22.2 ± 6.8 [95% CI, 19.2-25.2, p = 0.026). CONCLUSIONS: Our results suggest that the cumulative hip stress distribution in borderline-to-mild dysplasia was not concentrated on the lateral side of the acetabulum, unlike severe dysplasia. CLINICAL RELEVANCE: Based on the stress distribution pattern, our results may suggest that there is no association between borderline-to-mild dysplasia and the pathogenesis of OA. Further studies are needed to evaluate the association between borderline-to-mild dysplasia and instability of the hip.

Transcriptional profile of human macrophages stimulated by ultra-high molecular weight polyethylene particulate debris of orthopedic implants uncovers a common gene expression signature of rheumatoid arthritis.

Osteolysis is a serious postoperative complication of total joint arthroplasty that leads to aseptic loosening and surgical revision. Osteolysis is a chronic destructive process that occurs when host macrophages recognize implant particles and release inflammatory mediators that increase bone-resorbing osteoclastic activity and attenuate bone-formation osteoblastic activity. Although much progress has been made in understanding the molecular responses of macrophages to implant particles, the pathways/signals that initiate osteolysis remain poorly characterized. Transcriptomics and gene-expression profiling of these macrophages may unravel key mechanisms in the pathogenesis of osteolysis and aid the identification of molecular candidates for therapeutic intervention. To this end, we analyzed the transcriptional profiling of macrophages exposed to ultra-high molecular weight polyethylene (UHMWPE) particles, the most common components used in bearing materials of orthopedic implants. Regulated genes in stimulated macrophages were involved in cytokine, chemokine, growth factor and receptor activities. Gene enrichment analysis suggested that stimulated macrophages elicited common gene expression signatures for inflammation and rheumatoid arthritis. Among the regulated genes, tumor necrosis factor superfamily member 15 (TNFSF15) and chemokine ligand 20 (CCL20) were further characterized as molecular targets involved in the pathogenesis of osteolysis. Treatment of monocyte cultures with TNFSF15 and CCL20 resulted in an increase in osteoclastogenesis and bone-resorbing osteoclastic activity, suggesting their potential contribution to loosening between implants and bone tissues. STATEMENT OF SIGNIFICANCE: Implant loosening due to osteolysis is the most common mode of arthroplasty failure and represents a great challenge to orthopedic surgeons and a significant economic burden for patients and healthcare services worldwide. Bone loss secondary to a local inflammatory response initiated by particulate debris from implants is considered the principal feature of the pathogenesis of osteolysis. In the present study, we analyzed the transcriptional profiling of human macrophages exposed to UHMWPE particles and identified a large number of inflammatory genes that were not identified previously in macrophage responses to wear particles. Our data provide a new insight into the molecular pathogenesis of osteolysis and highlights a number of molecular targets with prognostic and therapeutic implications.

Evidence for frozen melts in the mid-lithosphere detected from active-source seismic data.

The interactions of the lithospheric plates that form the Earth's outer shell provide much of the evidentiary basis for modern plate tectonic theory. Seismic discontinuities in the lithosphere arising from mantle convection and plate motion provide constraints on the physical and chemical properties of the mantle that contribute to the processes of formation and evolution of tectonic plates. Seismological studies during the past two decades have detected seismic discontinuities within the oceanic lithosphere in addition to that at the lithosphere-asthenosphere boundary (LAB). However, the depth, distribution, and physical properties of these discontinuities are not well constrained, which makes it difficult to use seismological data to examine their origin. Here we present new active-source seismic data acquired along a 1,130 km profile across an old Pacific plate (148-128 Ma) that show oceanic mid-lithosphere discontinuities (oceanic MLDs) distributed 37-59 km below the seafloor. The presence of the oceanic MLDs suggests that frozen melts that accumulated at past LABs have been preserved as low-velocity layers within the current mature lithosphere. These observations show that long-offset, high-frequency, active-source seismic data can be used to image mid-lithospheric structure, which is fundamental to understanding the formation and evolution of tectonic plates.

A rare case of multiple phosphaturic mesenchymal tumors along a tendon sheath inducing osteomalacia.

BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia, reduction of 1,25-dihydroxyl vitamin D, and bone calcification disorders. Tumors associated with TIO are typically phosphaturic mesenchymal tumors that are bone and soft tissue origin and often present as a solitary tumor. The high production of fibroblast growth factor 23 (FGF23) by the tumor is believed to be the causative factor responsible for the impaired renal tubular phosphate reabsorption, hypophosphatemia and osteomalacia. Complete removal of the tumors by surgery is the most effective procedure for treatment. Identification of the tumors by advanced imaging techniques is difficult because TIO is small and exist within bone and soft tissue. However, systemic venous sampling has been frequently reported to be useful for diagnosing TIO patients. CASE PRESENTATION: We experienced a case of 39-year-old male with diffuse bone pain and multiple fragility fractures caused by multiple FGF23-secreting tumors found in the hallux. Laboratory testing showed hypophosphatemia due to renal phosphate wasting and high levels of serum FGF23. Contrast-enhanced MRI showed three soft tissue tumors and an intraosseous tumor located in the right hallux. Systemic venous sampling of FGF23 revealed an elevation in the right common iliac vein and external iliac vein, which suggested that the tumors in the right hallux were responsible for overproduction of FGF23. Thereafter, these tumors were surgically removed and subjected to histopathological examinations. The three soft tissue tumors were diagnosed as phosphaturic mesenchymal tumors, which are known to be responsible for TIO. The fourth tumor had no tumor structure and was consisting of hyaline cartilage and bone tissue. Immediately after surgery, we noted a sharply decrease in serum level of FGF23, associated with an improved hypophosphatemia and a gradual relief of systematic pain that disappeared within two months of surgery. CONCLUSION: The authors reported an unusual case of osteomalacia induced by multiple phosphaturic mesenchymal tumors located in the hallux. Definition of tumors localization by systemic venous sampling led to successful treatment and cure this patient. The presence of osteochondral tissues in the intraosseous tumor might be developed from undifferentiated mesenchymal cells due to high level of FGF23 produced by phosphaturic mesenchymal tumors.

Efficacy of teriparatide in the treatment of nontraumatic osteonecrosis of the femoral head: a retrospective comparative study with alendronate.

BACKGROUND: Collapse of the femoral head associated with nontraumatic osteonecrosis (NOFH) is one of the most common causes of disability in young adult patients. Excessive bone resorption by osteoclast coincident with the suppression of osteogenesis are believed to be responsible for collapse progression. Alendronate that inhibits bone resorption by inducing osteoclast apoptosis has been traditionally used for treating NOFH; however, several reports documented serious complications by the use of this drug. On the other hand, teriparatide activates osteoblasts leading to an overall increase in bone volume, and is expected to reduce the progression of femoral head collapse in NOFH. Therefore, the present study was undertaken to examine pharmacological effects of teriparatide on collapse progression of NOFH and to compare these effects with alendronate. METHODS: We conducted a retrospective study in our facility for comparing the pharmacological effects of teriparatide and alendronate on 32 NOFH patients diagnosed with osteoporosis. Between 2007 and 2013, patients were treated with daily administration of 20 µg teriparatide (15 patients: 18 hips), or with 35 mg of alendronate once a week (17 patients: 22 hips). The mean period of follow-up was 18.7 months. The progression of collapse was evaluated prior to the administration and later every three months by anteroposterior radiographs. Collapse progression with > 1 mm was defined as advanced collapse, while with < 1 mm was defined as stable radiologic disease. Student's t-test and the chi-square test was used to do compare the pharmacological effects of the two groups. RESULTS: Treatment with terparatide had a tendency to reduce the rate of advanced collapse as compared to that with alendronate (p = 0.105). Kaplan-Meier curves related to stable radiologic disease showed that teriparatide-treated patients had better stable states than these treated with alendronate (p = 0.08, log-rank test). Moreover, treatment with teriparatide resulted in a significant reduction in collapse progression as compared to that with alendronate, noted at the end of follow-up period (p = 0.049). CONCLUSION: The present study suggests that teriparatide has greater pharmacological effects than alendronate for treating NOFH and preventing the collapse of femoral head. TRIAL REGISTRATION: The registration number in UMIN Clinical Trial Registry is UMIN000017582 . The date of registration is May 5, 2015.

Comparison of femoral head translation following eccentric rotational acetabular osteotomy and rotational acetabular osteotomy.

PURPOSE: Eccentric rotational acetabular osteotomy (ERAO) is a modification of rotational acetabular osteotomy (RAO); it has been reported that ERAO allows the femoral head to translate medially and distally. However, no study has compared femoral head translation following RAO or ERAO. The purpose of this study was to compare immediate postoperative translation of the femoral head after RAO and ERAO in comparison with the preoperative position by radiological methods. METHODS: Patients treated by RAO or ERAO between 2006 and 2014 were retrospectively evaluated. 19 hips (17 patients) were treated with RAO, and 25 hips (22 patients) were treated with ERAO. The acetabular roof angle and the location of the femoral head were measured on anteroposterior pelvic radiographs. RESULTS: The mean preoperative acetabular roof angle was 20.9° in the RAO group and 22.0° in the ERAO group, showing no significant difference. The mean acetabular roof angle immediately postoperatively was -0.5° in the RAO group and -0.4° in the ERAO group, again showing no significant difference. The mean femoral head translation immediately postoperatively was 3.1 mm (95% confidence interval (CI), 1.5-4.7 mm) laterally and 3.0 mm (95% CI, 1.3-4.7 mm) proximally in the RAO group and 0.8 mm (95% CI, -0.7-2.3 mm) medially and 2.8 mm (95% CI, 1.5-4.1 mm) distally in the ERAO group; this difference was very highly significant (p<0.001). CONCLUSIONS: In contrast with RAO, ERAO resulted in significant femoral head translation both medially and distally immediately postoperatively.

Structure of the tsunamigenic plate boundary and low-frequency earthquakes in the southern Ryukyu Trench.

It has been recognized that even weakly coupled subduction zones may cause large interplate earthquakes leading to destructive tsunamis. The Ryukyu Trench is one of the best fields to study this phenomenon, since various slow earthquakes and tsunamis have occurred; yet the fault structure and seismic activity there are poorly constrained. Here we present seismological evidence from marine observation for megathrust faults and low-frequency earthquakes (LFEs). On the basis of passive observation we find LFEs occur at 15-18 km depths along the plate interface and their distribution seems to bridge the gap between the shallow tsunamigenic zone and the deep slow slip region. This suggests that the southern Ryukyu Trench is dominated by slow earthquakes at any depths and lacks a typical locked zone. The plate interface is overlaid by a low-velocity wedge and is accompanied by polarity reversals of seismic reflections, indicating fluids exist at various depths along the plate interface.

Simultaneous inhibition of Src and Aurora kinases by SU6656 induces therapeutic synergy in human synovial sarcoma growth, invasion and angiogenesis in vivo.

Synovial sarcoma is an obstinate, high-grade malignancy because of its modest responses to radiotherapy and chemotherapy; the identification of effective therapeutics for this sarcoma is therefore necessary. Inhibition of Src family kinases (SFKs) suppresses the proliferation of synovial sarcoma cells in vitro, as we have previously reported. In this study, to validate the efficacy of Src inhibition in vivo, we employed SU6656, which was originally identified as a specific SFK inhibitor. SU6656 treatment significantly impaired the growth of established, existing tumours formed by synovial sarcoma cells in mice. Tumour cell invasion into the surrounding tissues was also abolished by SU6656. It is noteworthy that SU6656 but not PP2 induced a defect in cleavage furrow formation during cytokinesis, resulting in G2/M accumulation and subsequent apoptosis. Intriguingly, SU6656 abrogated the catalytic activities of Aurora kinases and led to the down-regulation of phosphorylated histone H3 coincidently with p53 accumulation, as did the Aurora kinase inhibitor VX-680. Structural comparison indicated an extensive similarity between the catalytic domains of SFKs and Aurora kinases. The structural analysis also revealed the potential binding mode of SU6656 to the ATP-binding cleft of Aurora B via four hydrogen bonds. SU6656 prevented angiogenesis within the tumours by attenuating vascular endothelial growth factor (VEGF) production by tumour cells and the subsequent chemotaxis of endothelial cells; these effects were the result of the inhibition of SFKs but not Aurora kinases. Based on these results, we hereby report a novel property of SU6656 as a dual inhibitor of SFKs and Aurora kinases, the suppression of both of which effectively abrogates tumour development and the progression of synovial sarcoma in vivo.