Novel Animal Model of Spontaneous Cerebral Petechial Hemorrhage Using Focused Ultrasound in Rats.

Background and Objectives: Petechial cerebral hemorrhages can be caused by various factors, such as traumas, cerebral infarctions, and aging, and is related to the disruption of the blood-brain barrier or the cellular damage of blood vessels. However, there is no animal model that recapitulates cerebral petechial hemorrhages. Materials and Methods: Here, we implemented a petechial hemorrhage using a novel technology, i.e., microbubble-assisted focused ultrasound (MB + FUS). Results: This method increases the permeability of the blood-brain barrier by directly applying mechanical force to the vascular endothelial cells through cavitation of the microbubbles. Microbubble-enhanced cavitation has the advantage of controlling the degree and location of petechial hemorrhages. Conclusions: We thus generated a preclinical rat model using noninvasive focal MB + FUS. This method is histologically similar to actual petechial hemorrhages of the brain and allows the achievement of a physiologically resembling petechial hemorrhage. In the future, this method shall be considered as a useful animal model for studying the pathophysiology and treatment of petechial cerebral hemorrhages.

Clinical significance of vitamin D in idiopathic normal pressure hydrocephalus.

BACKGROUND: Although recent studies show vitamin D deficiency is associated with cognitive decline, urinary incontinence, and gait instability, there has been no study on the effect of vitamin D on idiopathic normal pressure hydrocephalus (iNPH) characterized by the classic symptom triad of cognitive decline, urinary incontinence, and gait instability. We investigated the clinical significance of vitamin D in patients with iNPH. METHODS: Between 2017 and 2020, 44 patients who underwent ventriculoperitoneal shunt surgery were divided into low (< 15 ng/mL) and high (≥ 15 ng/mL) vitamin D groups according to the concentration of 25(OH)D, an effective indicator of vitamin D status. They were respectively evaluated according to clinical and radiological findings. RESULTS: The low vitamin D group (n = 24) showed lower preoperative cognition compared to the high vitamin D group (n = 20) in terms of Korean-Mini Mental Status Examination (K-MMSE) and iNPH grading scale (iNPHGS) (K-MMSE: 20.5 ± 5.4 versus 24.0 ± 4.5, p = 0.041; iNPHGS cognitive score: 2 ± 0.9 versus 1 ± 0.6, p = 0.025). And the low vitamin D group showed pre- and postoperatively more severe urinary incontinence (preoperative iNPHGS urinary score: 1 ± 1.0 versus 0 ± 0.9, p = 0.012; postoperative iNPHGS urinary score:1 ± 1.0 versus 0 ± 0.9, p = 0.014). The score of narrow high-convexity sulci for the low vitamin D group was lower (low vitamin D group: 1 ± 0.7 versus high vitamin D group: 2 ± 0.4, p = 0.031). CONCLUSION: Lower concentration of vitamin D in iNPH may be related to lower preoperative cognition, pre- and postoperative urinary incontinence, and brain morphological change.

Stereotactic radiosurgery for intracranial dural arteriovenous fistulas: its clinical and angiographic perspectives.

BACKGROUND: To assess the efficacy of stereotactic radiosurgery (SRS) for intracranial dural arteriovenous fistulas (DAVFs), the authors retrospectively reviewed our 7-year experience. We evaluated the obliteration rate, improvement in clinical symptoms, and complications. METHODS: Thirty patients with DAVF underwent SRS using a Gamma Knife between 2009 and 2015. Twenty-three patients were treated with SRS alone, and seven patients underwent SRS for residual or recurrent DAVFs after embolization or surgery. Chemosis, diplopia, and pulsating tinnitus were the most common symptoms. Median target volume was 2.9 cm3 (range, 0.8-13.6 cm3), and median radiation dose to the target was 17 Gy (range, 12-20 Gy). Median follow-up period was 33 months (range, 6-82 months). RESULTS: At the last neuroimaging follow-up, DAVFs were totally obliterated in 23 patients (77%) and subtotally in 7 (23%). At the last clinical follow-up, 21 patients (70%) showed complete recovery, and 9 (30%) showed incomplete recovery in symptoms or signs. None experienced worsening symptoms or signs. Asymptomatic perilesional edema after SRS occurred in one patient (3%). Total obliteration rates after SRS were 43% at 1 year, 79% at 2 years, and 95% at 5 years. Improvement rates of neurological function after SRS were 12% at 1 month, 52% at 2 months, 72% at 3 months, and 96% at 6 months. A multivariate analysis revealed that Borden type 1 (p = 0.019, hazard ratio, 3.254, 95% confidence interval, 1.216-8.707) was significantly associated with symptom improvement. CONCLUSIONS: SRS for intracranial DAVFs provided a high obliteration rate and a relatively low risk of radiation-induced complications. In selected benign cases without cortical venous drainage, SRS is a safe and effective treatment for symptom relief and fistula obliteration, even though the time course of improvement is longer than those of embolization and surgery.

The clinical significance of fascin expression in a newly diagnosed primary glioblastoma.

The actin-binding protein fascin has been associated with clinically aggressive tumors and poor prognosis. The purpose of this study was to investigate possibility of fascin expression as a prognostic factor in a newly diagnosed primary glioblastoma (GBM). Between July 2007 and December 2013, 37 out of 126 patients diagnosed with GBM satisfied the following inclusion criteria: (1) the presence of immunohistochemically-available tissue, (2) a new primary GBM, (3) gross-total resection, and (4) standardized adjuvant treatment, known as the Stupp regimen. The median follow-up period was 18 months (range 5-95). According to the staining intensity of fascin, progression-free survival (PFS) in the low-intensity fascin group (median PFS 9.0 months; 95 % CI 6.0-12.0) was longer than PFS in the high-intensity fascin group (median PFS 7.0 months; 95 % CI 5.6-10.4; p = 0.024). Overall survival (OS) in the low-intensity fascin group (median OS 20.0 months; 95 % CI 17.7-22.4) was longer than OS in the high-intensity fascin group (median OS 13.0 months; 95 % CI 8.2-17.8; p = 0.031). And, the staining intensity of fascin was a statistically significant factor in PFS and OS according to univariate and multivariate analyses (univariate analysis p = 0.043 and p = 0.043; multivariate analysis p = 0.041 and p = 0.044). Our clinical study showed that fascin expression intensity may be correlated with clinical outcomes of a newly diagnosed primary GBM, especially with regard to PFS and OS.

Surface Functionalized Graphene Biosensor on Sapphire for Cancer Cell Detection.

Graphene has several unique physical, optical and electrical properties such as a two-dimensional (2D) planar structure, high optical transparency and high carrier mobility at room temperature. These make graphene interesting for electrical biosensing. Using a catalyst-free chemical vapor deposition (CVD) method, graphene film is grown on a sapphire substrate. There is a single or a few sheets as confirmed by Raman spectroscopy and atomic force microscopy (AFM). Electrical graphene biosensors are fabricated to detect large-sized biological analytes such as cancer cells. Human colorectal carcinoma cells are sensed by the resistance change of an active bio-functionalized graphene device as the cells are captured by the immobilized antibody surface. The functionalized sensors show an increase in resistance as large as ~20% of the baseline with a small number of adhered cells. This study suggests that the bio-functionalized electrical graphene sensors on sapphire, which is a highly transparent material, can potentially detect circulating tumor cells (CTCs) and monitor cellular electrical behavior while being compatible with fluorescence-based optical-detection bioassays.

Electrical characteristics of multilayer MoS2 FET's with MoS2/graphene heterojunction contacts.

The electrical properties of multilayer MoS2/graphene heterojunction transistors are investigated. Temperature-dependent I-V measurements indicate the concentration of unintentional donors in exfoliated MoS2 to be 3.57 × 10(11) cm(-2), while the ionized donor concentration is determined as 3.61 × 10(10) cm(-2). The temperature-dependent measurements also reveal two dominant donor levels, one at 0.27 eV below the conduction band and another located at 0.05 eV below the conduction band. The I-V characteristics are asymmetric with drain bias voltage and dependent on the junction used for the source or drain contact. I-V characteristics of the device are consistent with a long channel one-dimensional field-effect transistor model with Schottky contact. Utilizing devices, which have both graphene/MoS2 and Ti/MoS2 contacts, the Schottky barrier heights of both interfaces are measured. The charge transport mechanism in both junctions was determined to be either thermionic-field emission or field emission depending on bias voltage and temperature. On the basis of a thermionic field emission model, the barrier height at the graphene/MoS2 interface was determined to be 0.23 eV, while the barrier height at the Ti/MoS2 interface was 0.40 eV. The value of Ti/MoS2 barrier is higher than previously reported values, which did not include the effects of thermionic field emission.

Pituitary carcinoma with fourth ventricle metastasis: treatment by excision and Gamma-knife radiosurgery.

Pituitary carcinomas, which are rare, generally present with craniospinal and systemic metastases. Although several treatments exist, the prognoses of patients with pituitary carcinomas are extremely poor to date. In this report, the authors describe the case of a 23-year-old male who had undergone trans-sphenoidal surgery and radiotherapy for an invasive prolactinoma. Seven years later, he presented with a new 4th ventricle metastasis from the pituitary lesion, and it was diagnosed with a pituitary carcinoma. He underwent resection and Gamma-knife radiosurgery (GKRS). The tumor has been well controlled for over 3 years. To our knowledge, there have been no reports of the effects of GKRS in patients with pituitary carcinomas. GKRS might have considerable effects in the treatment of pituitary carcinomas.

Metal free growth of graphene on quartz substrate using chemical vapor deposition (CVD).

Graphene was grown on (0001) quartz substrate (z-cut) using catalyst free Chemical Vapor Deposition (CVD). Methane was used as a carbon source and hydrogen was introduced independently to optimize the growth. The effect of growth temperature was investigated while varying the temperature between 1000 and 1300 degrees C. With an optimized condition, a thin (< or = 2 mono-layer) continuous graphene film was grown as confirmed by Raman spectroscopy, optical transmission, and electrical measurements. The best quality film showed the Raman D-peak to G-peak intensity ratio of approximately 0.8 with the 2D-peak width of approximately 60 cm(-1). High resolution X-ray Photoelectron Spectroscopy (XPS) revealed that the grown graphene is slightly oxidized but there is no detectable Si--C chemical bond in the graphene/quartz system. Hall effect measurements exhibited a carrier mobility of approximately 400 cm2/V x s with a sheet carrier density of approximately 5 x 10(12) cm(-2).

Border Zone Maybe Correlated with Radiation Necrosis After Radiosurgery in Metastatic Brain Tumor.

BACKGROUND: Radiation necrosis (RN) after stereotactic radiosurgery (SRS) in brain metastases has been extensively evaluated, and RN is correlated with various risk factors. However, no study comprehensively analyzed the correlation between RN and the border zones of the brain that are vulnerable to ischemia. We hypothesized that patients with tumors in the border zone are at high risk of RN. Hence, the current study aimed to assess the correlation between border zone lesions and RN, with consideration of other predetermined factors. METHODS: This retrospective study included 117 patients with 290 lesions who underwent Gamma Knife SRS. Radiological and clinical analyses were performed to identify factors possibly correlated with RN. Notably, the lesion location was classified into 2 groups (border zone and nonborder zone) based on the blood supply. RESULTS: In total, 22 (18.8%) patients with 22 (7.5%) lesions developed RN. Univariate analysis revealed a significant correlation between RN and external border zone lesions, second course of SRS administered at the same site of the previous SRS, prescribed dose, and tumor volume. Multivariate analysis showed that border zone lesions, second course of SRS at the same site of the previous SRS, and tumor volume were significantly correlated with RN. CONCLUSIONS: Patients with tumors in the border zone are at high risk of RN. The potential risks of RN can be attributed hypothetically to hypoperfusion. Hence, the association between RN and border zone lesions seems reasonable.

Switching strategy for mechanical thrombectomy of acute large vessel occlusion in the anterior circulation.

BACKGROUND AND PURPOSE: We introduce the concept of a switching strategy for mechanical thrombectomy with period-to-period analysis. In period 1, forced arterial suction thrombectomy with a Penumbra reperfusion catheter was performed, even in difficult cases; in period 2, forced arterial suction thrombectomy was initially performed, with switching to Solitaire in difficult cases. METHODS: We analyzed 135 consecutive patients treated with mechanical thrombectomy with acute large vessel occlusion in the anterior circulation, 61 from period 1 and 74 from period 2. We defined difficult case for both periods as ≥3 failed attempts at recanalization. RESULTS: Period 2 showed a trend for better angiographic outcome of Thrombolysis in Cerebral Infarction 2b-3 (73.8%, period 1 versus 85.1%, period 2; P=0.10). In interperiod subgroup analysis of difficult cases, switching significantly outperformed nonswitching in Thrombolysis in Cerebral Infarction 2b-3 recanalization (52.7% versus 82.9%; P=0.030). Differences in puncture-to-recanalization time, symptomatic intracranial hemorrhage incidence, and procedure-related complications were not statistically significant. CONCLUSIONS: A switching strategy using 2 mechanical thrombectomy techniques (forced arterial suction thrombectomy to Solitaire) may harbor better angiographic outcomes than a 1 technique only strategy (forced arterial suction thrombectomy).

Rescue strategy for acute carotid stent thrombosis during carotid stenting with distal filter protection using forced arterial suction thrombectomy with a reperfusion catheter of the Penumbra System: a technical note.

BACKGROUND: Among the procedural complications related to carotid artery stenting (CAS), internal carotid artery (ICA) flow arrest is one of the most drastic complications, as it can cause major ischemic stroke. Acute carotid stent thrombosis (ACST) is a rare etiology of ICA flow arrest during carotid artery stenting with distal filter protection, but the most devastating. Moreover, no definitive management strategy has been established so far for treating ACST. METHODS: We introduce a rescue management strategy for differential diagnosis of ICA flow arrest and for recanalization of ACST with a simple endovascular mechanical thrombectomy technique. RESULTS: In three cases of ICA flow arrest caused by ACST, selective angiography with a 1.7 F microcatheter provided confirmative diagnosis. Recanalization was then achieved with a Penumbra System (PS) reperfusion catheter using the forced arterial suction thrombectomy (FAST) technique. Successful recanalization with a Thrombolysis In Cerebral Infarction score of 3 was achieved for all three patients. Recanalization was confirmed with follow-up angiography at least 24 h after the procedure. No complications associated with this technique occurred. CONCLUSIONS: Based on our preliminary experiences, selective microangiography can be helpful for rapid diagnosis of ACST, and the present mechanical thrombectomy technique, using a modification of the PS, can play a role in adjuvant management or as a last resort for the treatment of ACST during CAS.

Intramedullary spinal cord metastasis in renal cell carcinoma: a case report of the surgical experience.

Intramedullary spinal cord metastasis (ISCM) from renal cell carcinoma (RCC) is rare manifestation and most of them are treated by adjuvant treatment modalities like radiotherapy. Despite the radio-resistance of RCC itself, focal radiotherapy has been preferred as the first-line treatment modality of ISCM from RCC and only a few cases underwent surgical treatment. We describe a case of ISCM from RCC, which underwent surgical excision and pathologically confirmed. A 44-yr-old man was presented with rapid deterioration of motor weakness during focal radiotherapy for ISCM from RCC. After the surgery for removal of the tumor mass and spinal cord decompression, his motor power was dramatically improved to ambulate by himself. We report the first published Korean case of ISCM from RCC confirmed pathologically and describe our surgical experience and his clinical characteristics.

Venous ectasia preceding intra-tumoral hemorrhage in a case of gliosarcoma with transverse sinus involvement.

Although intratumoral hemorrhage is common in patients with malignant brain tumors, reports on its clinical course are scarce. This report presents a rare case of a patient with intratumoral hemorrhage with gliosarcoma invading the venus sinus. This invasion and a small draining vein were observed at diagnosis. Magnetic resonance imaging performed 1 week later showed new-onset venous ectasia, which caused intratumoral hemorrhage. This case provides insight into the mechanisms underlying intratumoral hemorrhage and highlights the emergence of new intratumoral vasculature as a potential warning sign for hemorrhage.

Improvement of carrier mobility of top-gated SiC epitaxial graphene transistors using a PVA dielectric buffer layer.

The effects of treatment with polyvinyl alcohol (PVA) and a dielectric film of HfO(2) on the properties of SiC based epitaxial graphene have been explored and analyzed. We have characterized the carrier mobility of graphene on Si-face and C-face SiC with a layer of HfO(2), with or without an initial PVA treatment on the device active layer. Epitaxial graphene grown on the C-face displays a higher mobility than a film grown on the silicon face. Also, the mobility in the presence of the PVA treatment with HfO(2) dielectric layer has been improved, compared with the mobility after deposition of only gate dielectric: ∼20% in C-face graphene and ∼90% in Si-face graphene. This is a major improvement over the degradation normally observed with dielectric/graphene systems.

Spindle cell oncocytoma of the sella turcica with anaplastic features and rapid progression in short-term follow-up: a case report with proposal of distinctive radiologic features.

We present a rare case of spindle cell oncocytoma (SCO) of the sella turcica with malignant histologic features and rapid progression. A 42-year-old woman experienced bilateral blurred vision and was preoperatively misdiagnosed as having a pituitary macroadenoma on magnetic resonance imaging. After surgery, SCO was diagnosed by the histopathologic features of interlacing fascicles of spindle tumor cells with finely granular, eosinophilic cytoplasm. Focal anaplastic changes and necrosis were present. Immunohistochemically, the tumor cells were positive for vimentin, epithelial membrane antigen, S-100, galectin-3, and thyroid transcription factor 1. Four months later, the tumor had progressed, and second surgery with adjuvant radiotherapy was performed; the patients remains under observation. In this report, we proposed distinctive radiologic features for differential diagnosis between SCO and other pituitary tumors.

Effect of Cadherin-11 Expression on the Prognosis of a Newly Diagnosed Primary Glioblastoma.

BACKGROUND: Cadherin-11, a cell-to-cell adhesion molecule, is associated with higher tumor grade and decreased patient survival. The purpose of this study was to investigate the clinical significance of cadherin-11 expression in the progression and prognosis of a newly diagnosed primary glioblastoma (GBL). METHODS: Between 2007 and 2016, 52 out of 178 patients diagnosed with a GBL and satisfied the following criteria: 1) a new primary GBL, 2) gross-total resection, 3) immunohistochemically-available tissue, and 4) standardized adjuvant treatment. RESULTS: In terms of staining intensity, the low-intensity cadherin-11 group showed longer progression-free survival (PFS) than the high-intensity cadherin-11 group (median PFS, 12.0 months [95% CI, 11.1-12.9] vs. median PFS, 6.0 months [95% CI, 3.7-8.3]; p<0.001). The low-intensity cadherin-11 group revealed longer overall survival (OS) than the high-intensity cadherin-11 group (median OS, 20.0 months [95% CI, 11.8-16.6] vs. median OS, 15.0 months [95% CI, 11.8-18.2]; p=0.003). The staining intensity of cadherin-11 was a statistically significant factor in PFS and OS in terms of univariate and multivariate analyses (univariate analysis: p<0.001 and p=0.005; multivariate analysis: p<0.001 and p=0.005). CONCLUSION: Our clinical study demonstrates high cadherin-11 expression may be associated with poor PFS and OS for a newly diagnosed primary GBL.

The retrogasserian zone versus dorsal root entry zone: comparison of two targeting techniques of gamma knife radiosurgery for trigeminal neuralgia.

BACKGROUND: We performed a comparative study of the retrogasserian zone (RGZ) with the dorsal root entry zone (DREZ) target to determine effective gamma knife radiosurgery (GKRS) technique in patients with medically refractory trigeminal neuralgia (TN). METHODS: We retrospectively reviewed the records of 39 patients with refractory TN undergoing GKRS between April 2005 and October 2008. Until October 2007, DREZ was used as the primary target point. Since November 2007, RGZ has been targeted, located anterior to DREZ. The pain outcome of patient, pain recurrence, and treatment-related complications were evaluated. FINDINGS: Using the Barrow Neurologic Index (BNI) pain score, 15 (93.8%) RGZ and 20 (87.0%) DREZ cases achieved treatment success (BNI pain score I-IIIb) (p = 0.631). Seven (43.8%) RGZ and four (17.4%) DREZ patients reported complete pain relief without medications (BNI pain score I). The time to a response after the GKRS was significantly shorter in the RGZ group (mean 4.1 weeks) than in the DREZ group (mean 6.4 weeks) (p = 0.044). The total complication rate (25.0%) in the RGZ group was similar to the DREZ group (26.1%); however, frequency of bothersome facial numbness and dry eye syndrome was lower in the RGZ group (0%, 0%) compared to the DREZ group (13.1%, 8.7%) (p = 0.255 and 0.503). CONCLUSIONS: The RGZ targeting technique in the GKRS for TN had a better treatment success, with fewer bothersome complications compared to the DREZ target.

Epitaxial growth of graphitic carbon on C-face SiC and Sapphire by chemical vapor deposition (CVD).

Epitaxial, graphitic carbon thin films were directly grown on C-face/ (0001̄) SiC and (0001) sapphire by chemical vapor deposition (CVD), using propane as a carbon source and without any catalytic metal on the substrate surface. Raman spectroscopy shows the signature of multilayer graphene/graphite growth on both the SiC and sapphire. Raman 2D-peaks have Lorentzian lineshapes with FWHM of ~60 cm(-1) and the ratio of the D-peak to G-peak intensity (I(D)/I(G)) linearly decreases (down to 0.06) as growth temperature is increased. The epitaxial relationship between film and substrates were determined by x-ray diffraction. On both substrates, graphitic layers are oriented parallel to the substrate, but exhibit significant rotational disorder about the surface normal, and predominantly rhombohedral stacking. Film thicknesses were determined to be a function of growth time, growth temperature, and propane flow rate.

Gamma Knife Radiosurgery Using Co-Registration with PET-CT and MRI for Recurrent Nasopharyngeal Carcinoma with Previous Radiotherapy : A Single Center 14-Year Experience.

OBJECTIVE: We retrospectively evaluated the efficacy of Gamma Knife radiosurgery (GKS) for recurrent nasopharyngeal carcinoma (NPC) in patients who previously underwent radiotherapy, and analyzed the treatment outcomes over 14 years. METHODS: Ten patients with recurrent NPC who had previously received radiotherapy underwent stereotactic radiosurgery using a Gamma Knife® (Elekta Inc, Atlanta, GA, USA) between 2005 and 2018. The median target volume was 8.2 cm3 (range, 1.7-17.8), and the median radiation dose to the target was 18 Gy (range, 12-30). The median follow-up period was 18 months (range, 6-76 months). Overall and local failure-free survival rates were determined using the Kaplan-Meier method. RESULTS: The NPCs recurred at the primary cancer site in seven patients (70%), as distant brain metastasis in two (20%), and as an extension into brain in one (10%). The recurrent tumors in seven of the 10 patients (70%) were found on the routine follow-up imaging studies. Two patients presented with headache and one with facial pain. Local failure after GKS occurred in five patients (50%) : two of whom died eight and 6 months after GKS, respectively. No adverse radiation effects were noted after GKS. The 1- and 3-year overall survival rates after GKS were 90% and 77%, respectively. The local failure-free survival rates at 6 months, 1 year, and 3 years after GKS were 80%, 48%, and 32%, respectively. The median interval from GKS to local failure was 8 months (range, 6-12). Univariate analysis revealed that using co-registration with positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) was associated with a lower local failure rate of recurrent NPC (p=0.027). CONCLUSION: GKS is an acceptable salvage treatment option for patients with recurrent NPC who previously received radiation therapy. PET-CT and MRI co-registration for dose planning can help achieve local control of recurrent NPC.

Chronic Hyperglycemia before Spinal Cord Injury Increases Inflammatory Reaction and Astrogliosis after Injury: Human and Rat Studies.

Traumatic spinal cord injury (SCI) can cause permanent disabilities that seriously reduce quality of life. We evaluated the effects of chronic hyperglycemia before SCI on inflammatory markers and functional recovery after SCI in human patients and a rat model. In the human study, multivariate logistical regression analysis revealed that hemoglobin A1c (HbA1c) values, reflecting average plasma glucose concentration over a 3 month period, at admission were a significant risk factor for poor functional recovery. Moreover, patients with chronic hyperglycemia (HbA1c ≥ 6.5%) had high concentrations of inflammatory biomarkers (interleukin [IL]-6 and IL-8) of cerebrospinal fluid after SCI. Consistent with patient findings, chronic hyperglycemia before SCI in rats was associated with increased inflammatory responses and oxygen-free radicals in the spinal cord and blood, thus resulting in poor functional recovery and histological outcomes. Tight glucose control before SCI decreased the harmful effects of hyperglycemia after SCI in both human and rat studies. Our findings suggest that chronic hyperglycemia before SCI may be a significant prognostic factor with a negative impact on functional and histological outcomes, highlighting the importance of tight glucose control before SCI.