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Accelerating innovation in the space of fluorescence imaging for surgical applications has increased interest in safely and expediently advancing these technologies to clinic through Food and Drug Administration-(FDA-) compliant trials. Conventional metrics for early phase trials include drug safety, tolerability, dosing, and pharmacokinetics. Most procedural imaging technologies rely on administration of an exogenous fluorophore and concurrent use of an imaging system; both of which must receive FDA approval to proceed to clinic. Because fluorophores are classified as medical imaging agents, criteria for establishing dose are different, and arguably more complicated, than therapeutic drugs. Since no therapeutic effect is desired, medical imaging agents are ideally administered at the lowest dose that achieves adequate target differentiation. Because procedural imaging modalities are intended to enhance and/or ease proceduralists’ identification or assessment of tissues, beneficial effects of these technologies may manifest in the form of qualitative endpoints such as: 1) confidence; 2) decision-making; and 3) satisfaction with the specified procedure. Due to the rapid expansion of medical imaging technologies, we believe that our field requires standardized criteria to evaluate existing and emerging technologies objectively so that both quantitative and qualitative aspects of their use may be measured and useful comparisons to assess their relative value may occur. Here, we present a 15-item consensus-based survey instrument to assess the utility of novel imaging technologies from the proceduralist’s standpoint.

Differentiation of true tumor progression (TP) from pseudoprogression (PsP) is a major unmet need in patients with glioblastoma. [18F]Fluciclovine is a synthetic amino acid PET radiotracer that is FDA-approved in biochemical recurrence in prostate cancer. The study aim was to assess the value of [18F]Fluciclovine PET in differentiation of histologically confirmed (“true”) TP and PsP in post-treatment of glioblastoma. METHODS: 23 patients with glioblastoma with new contrast-enhancing lesions or lesions showing increased enhancement ( > 25% increase) on standard MRI after completion of radiation underwent 60-minutes dynamic [18F]Fluciclovine PET imaging. Patients subsequently underwent resection of enhancing lesion and tumor percentage vs. treatment-related changes were quantified on histopathology. Patients were considered "true” TP if tumor represented ≥ 50% of the resected specimen, mixed TP-PsP if < 50% and > 10%, and PsP if tumor represented ≤ 10%. Summed 30- to 40-minute post-injection PET images were used to measure SUVpeak and SUVmax (g/mL units). RESULTS: 15 patients with “true” TP, 3 with mixed TP-PsP, and 5 with PsP were included. There was a positive correlation between SUVpeak by PET and tumor percentage by histology (Rho= 0.56, p= 0.006). Patients who demonstrated “true” TP had significantly higher SUVpeak compared to patients with histological PsP (4.8±1.6 vs 2.9± 1.0, p= 0.02, AUC= 0.91, n=20). SUVpeak cut-off of 3.3 provided 93% sensitivity, 80% specificity, and 90% accuracy for differentiation of “true” TP from PsP. Patients with “true” TP/mixed TP-PsP also had significantly higher SUVpeak than patients with PsP (4.6±1.5 vs 2.9± 1.0, p= 0.03, AUC= 0.88, n=23). SUVmax and partial volume-corrected SUVpeak and SUVmax exhibited similar performance. CONCLUSION: Our results indicated that [18F]Fluciclovine PET imaging can accurately differentiate “true” TP from PsP. Further studies are required to confirm these promising early results and determine optimal criteria for interpreting [18F]Fluciclovine PET to distinguish PsP from TP.

Glossopharyngeal neuralgia (GN) is a nerve compression syndrome that presents with episodes of unilateral sharp, stabbing pain in the distribution of the ninth cranial nerve. This syndrome may present with cardiac and autonomic manifestations - a condition termed vagoglossopharyngeal neuralgia (VGPN). Most cases of VGPN arise from neurovascular insult at the cerebellopontine angle. Conservative treatment for VGPN includes antiepileptic medications. Surgical treatments include trigeminal tractotomy-nucleotomy, Gamma Knife® stereotactic radiosurgery, radiofrequency thermocoagulation, rhizotomy, and, as shown in this paper, endoscopic microvascular decompression (E-MVD). In this article, we present two cases. Case 1 demonstrates a 53-year-old male with right-sided GN symptoms that began to experience syncopal episodes 10-years after the initial presentation. Case 2 presents a 61-year-old female with a history of Ehlers-Danlos syndrome, and the malignant vasovagal syndrome that became associated with painful, shooting left anterior neck spasms consistent with GN. Both patients underwent E-MVD, leading to complete relief of neuralgia and cardiac symptoms. Our outcomes support previously published reports of successful treatment of VGPN using microvascular decompression (MVD) and describe a purely endoscopic surgical technique. MVD is the preferred treatment option for VGPN with evident neurovascular insult.

International audience; An internal consistency test of the calculation of coincidence-summing correction factors FC for volume sources is presented. The test is based on exact equations relating the values of FC calculated for three ideal measurement configurations. The test is applied to a number of 33 sets of FC values sent by 21 teams. Most sets passed the test, but not the results obtained using the quasi-point source approximation; in the latter case the test qualitatively indicated the magnitude of the bias of FC.

Tara Symonds,1 Jason A Randall,1 Deborah L Hoffman,2 Joanna M Zakrzewska,3 William Gehringer,4 John YK Lee5 1Clinical Outcomes Solutions, Clinical Outcome Assessments, Folkestone, UK; 2Biogen Inc., Cambridge, MA, USA; 3Eastman Dental Hospital – University College London Hospitals, Division of Diagnostic, Surgical and Medical Sciences, London, UK; 4Clinical Outcomes Solutions, Tucson, AZ, USA; 5University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA Background and objective: The Penn Facial Pain Scale (Penn-FPS) was originally developed as a supplemental module to the Brief Pain Inventory Pain Interference Index (BPI-PII) in order to fully assess the impact of trigeminal neuralgia (TN) pain on patients’ health-related quality of life (HRQoL). The current objective is to create and establish the content validity of a new stand-alone version of the measure, the Penn-FPS-Revised (Penn-FPS-R). Methods: Twenty participants (15 USA and 5 UK) with confirmed TN engaged in concept elicitation and cognitive debriefing interviews. These semi-structured interviews allowed participants to spontaneously describe the ways in which TN impacts on HRQoL and report on the extent to which the Penn-FPS and BPI-PII measure concepts are most relevant to them. Participants were also asked to report on the suitability of the instructions, recall period, and response options. Results: Concept elicitation revealed nine themes involving TN restrictions on daily activities and HRQoL, including: “talking,” “self-care,” “eating,” “eating hard foods/chewing foods,” “daily activities,” “activities with temperature change,” “touching,” “mood,” and “relationships.” Cognitive debriefing confirmed that all of the Penn-FPS concepts and some of the BPI-PII concepts (“mood,” “general activities,” and “relations with others”) were relevant, although some items required edits to better capture individuals’ experiences. The impact of temperature and/or weather on activities was also identified as an important concept that is not captured by the Penn-FPS or BPI-PII. Participants confirmed the acceptability of recall period, instructions, and response options. Results from the interviews were applied to create the Penn-FPS-R, a new brief outcome measure that assesses the impacts of TN most important to patients. Conclusion: The Penn-FPS-R is a new 12-item HRQoL outcome measure with content validity that can be used to assess and monitor the impact of TN treatment interventions in both clinical practice and research. Keywords: content validity, concept elicitation, cognitive debriefing, Penn Facial Pain Scale, trigeminal neuralgia, PRO development, patient reported outcome

A single pulse of 2.0 to 3.5 kJ of input energy from a 450 mF capacitor was applied to a commercially pure Ti rod in a N2atmosphere. The surface of the Ti rod transformed from TiO2into titanium nitride in times as short as 159 msec, providing a bimodal morphology of the cross-section. A much higher value of hardness that was observed at the edge of the cross-section was attributed to nitrogen-induced solid-solution hardening that occurred during the electrical discharge process. The activation energy (Ea) for the diffusion process was estimated to be approximately 86.9 kJ/mol. Results show that the electrical discharge process is a possible potential method for the nitriding of Ti; advantages include a short processing time and control of the nitrided layer without dimensional changes.

Characteristics of electro-discharge-sintering of the Ti-37.5at.% Si powder mixture was investigated as a function of the input energy, capacitance, and discharge time without applying any external pressure. A solid bulk of Ti5Si3was obtained only after in less than 129 μsec by the EDS process. During a discharge, the heat is generated to liquefy and alloy the particles, and which enhances the pinch pressure can condensate them without allowing a formation of pores. Three step processes for the self-consolidation mechanism during EDS are proposed; (a) a physical breakdown of oxide film on elemental as-received powder particles, (b) alloying and densifying the consolidation of powder particles by the pinch pressure, and (c) diffusion of impurities into the consolidated surface.

Electrical discharges using a capacitance of 450 μF at 0.5, 1.0, and 1.5 kJ input energies were applied in a N2atmosphere to obtain the mechanical alloyed Ti3Al powder without applying any external pressure. A solid bulk of nanostructured Ti3Al was obtained as short as 160 μsec by the Electrical discharge. At the same time, the surface has been modified into the form of Ti and Al nitrides due to the diffusion process of nitrogen to the surface. The input energy was found to be the most important parameter to affect the formation of a solid core and surface chemistry of the compact.

OBJECTIVEThe authors performed a study to evaluate the hemorrhagic rates of cerebral dural arteriovenous fistulas (dAVFs) and the risk factors of hemorrhage following Gamma Knife radiosurgery (GKRS).METHODSData from a cohort of patients undergoing GKRS for cerebral dAVFs were compiled from the International Radiosurgery Research Foundation. The annual posttreatment hemorrhage rate was calculated as the number of hemorrhages divided by the patient-years at risk. Risk factors for dAVF hemorrhage prior to GKRS and during the latency period after radiosurgery were evaluated in a multivariate analysis.RESULTSA total of 147 patients with dAVFs were treated with GKRS. Thirty-six patients (24.5%) presented with hemorrhage. dAVFs that had any cortical venous drainage (CVD) (OR = 3.8, p = 0.003) or convexity or torcula location (OR = 3.3, p = 0.017) were more likely to present with hemorrhage in multivariate analysis. Half of the patients had prior treatment (49.7%). Post-GRKS hemorrhage occurred in 4 patients, with an overall annual risk of 0.84% during the latency period. The annual risks of post-GKRS hemorrhage for Borden type 2–3 dAVFs and Borden type 2–3 hemorrhagic dAVFs were 1.45% and 0.93%, respectively. No hemorrhage occurred after radiological confirmation of obliteration. Independent predictors of hemorrhage following GKRS included nonhemorrhagic neural deficit presentation (HR = 21.6, p = 0.027) and increasing number of past endovascular treatments (HR = 1.81, p = 0.036).CONCLUSIONSPatients have similar rates of hemorrhage before and after radiosurgery until obliteration is achieved. dAVFs that have any CVD or are located in the convexity or torcula were more likely to present with hemorrhage. Patients presenting with nonhemorrhagic neural deficits and a history of endovascular treatments had higher risks of post-GKRS hemorrhage.

The primary treatment for brain tumors often involves surgical resection for diagnosis, relief of mass effect, and prolonged survival. In neurosurgery, it is of utmost importance to achieve maximal safe resection while minimizing iatrogenic neurologic deficit. Thus, neurosurgeons often rely on extra tools in the operating room, such as neuronavigation, intraoperative magnetic resonance imaging, and/or intraoperative rapid pathology. However, these tools can be expensive, not readily available, time-consuming, and/or inaccurate. Recently, fluorescence-guided surgery has emerged as a cost-effective method to accurately visualize neoplastic areas in real-time to guide resection. Currently, 5-aminolevulinic-acid (5-ALA) remains the only fluorophore that has been approved specifically for fluorescence-guided tumor resection. Its use has demonstrated improved resection rates and prolonged progression-free survival. However, protoporphyrin-IX, the metabolic product of 5-ALA that accumulates in neoplastic cells, fluoresces in the visible-light range, which suffers from limited tissue penetration and significant auto-fluorescence. Near-infrared fluorescence, on the other hand, overcomes these problems with ease. Since 2012, researchers at our institution have developed a novel technique using indocyanine-green, which is a well-known near-infrared fluorophore used traditionally for angiography. This Second-Window-ICG (SWIG) technique takes advantage of the increased endothelial permeability in peritumoral tissue, which allows indocyanine-green to accumulate in these areas for intraoperative visualization of the tumor. SWIG has demonstrated utility in gliomas, meningiomas, metastases, pituitary adenomas, chordomas, and craniopharyngiomas. The main benefits of SWIG stem from its highly sensitive detection of neoplastic tissue in a wide variety of intracranial pathologies in real-time, which can help neurosurgeons both during surgical resections and in stereotactic biopsies. In this review of this novel technique, we summarize the development and mechanism of action of SWIG, provide evidence for its benefits, and discuss its limitations. Finally, for those interested in near-infrared fluorescence-guided surgery, we provide suggestions for maximizing the benefits while minimizing the limitations of SWIG based on our own experience thus far.

Background Near-infrared (NIR) tumor contrast is achieved through the "second-window ICG" technique, which relies on passive accumulation of high doses of indocyanine green (ICG) in neoplasms via the enhanced permeability and retention effect. Objective To report early results and potential challenges associated with the application of second-window ICG technique in endonasal endoscopic, ventral skull-base surgery, and to determine potential predictors of NIR signal-to-background ratio (SBR) using endoscopic techniques. Methods Pituitary adenoma (n = 8), craniopharyngioma (n = 3), and chordoma (n = 4) patients received systemic infusions of ICG (5 mg/kg) approximately 24 h before surgery. Dual-channel endoscopy with visible light and NIR overlay were photodocumented and analyzed post hoc. Results All tumors (adenoma, craniopharyngioma, chordoma) demonstrated NIR positivity and fluoresced with an average SBR of 3.9 ± 0.8, 4.1 ± 1.7, and 2.1 ± 0.6, respectively. Contrast-enhanced T1 signal intensity proved to be the single best predictor of observed SBR (P = .0003). For pituitary adenomas, the sensitivity, specificity, positive predictive value, and negative predictive value of NIR-guided identification of tumor was 100%, 20%, 71%, and 100%, respectively. Conclusion In this preliminary study of a small set of patients, we demonstrate that second-window ICG can provide NIR optical tumor contrast in 3 types of ventral skull-base tumors. Chordomas demonstrated the weakest NIR signal, suggesting limited utility in those patients. Both nonfunctional and functional pituitary adenomas appear to accumulate ICG, but utility for margin detection for the adenomas is limited by low specificity. Craniopharyngiomas with third ventricular extension appear to be a particularly promising target given the clean brain parenchyma background and strong SBR.

Background Meningiomas are well-encapsulated benign brain tumors and surgical resection is often curative. Nevertheless, this is not always possible due to the difficulty of identifying residual disease intraoperatively. We hypothesized that meningiomas overexpress folate receptor alpha (FRα), allowing intraoperative molecular imaging by targeting FRα with a near-infrared (NIR) dye. Objective To determine FRα expression in both human and canine meningioma cohorts to prepare for future clinical studies. Present a case study of a meningioma resection with intraoperative NIR fluorescence imaging. Methods Tissue samples of 27 human meningioma specimens and 7 canine meningioma specimens were immunohistochemically stained for FRα along with normal dura, skeletal muscle, and kidney tissue. We then enrolled a patient with a pituitary adenoma and tuberculum sella meningioma in a clinical trial in which the patient received an infusion of folate-linked, NIR fluorescent dye prior to surgery. Results In the cohort of human meningiomas, 9 WHO grade I, 12 grade II, and 6 grade III tumors were identified. Eighty-nine percent of WHO grade I, 67% of grade II, and 50% of grade III tumors overexpressed FRα. In the 7 canine meningioma samples, 100% stained positively for FRα. Both human and canine normal dura from autopsy samples demonstrated no evidence of FRα overexpression. In the case study, the meningioma demonstrated a high NIR signal-to-background-ratio of 4.0 and demonstrated strong FRα immunohistochemistry staining. Conclusion This study directly demonstrates FRα overexpression in both human and canine meningiomas. We also demonstrate superb intraoperative imaging of a meningioma using a FRα-targeting dye.

Background Stereotactic radiosurgery (SRS) is a treatment option for persistent or recurrent acromegaly secondary to a growth hormone secreting pituitary adenoma, but its efficacy is inadequately defined. Objective To assess, in a multicenter, retrospective cohort study, the outcomes of SRS for acromegaly and determine predictors. Methods We pooled and analyzed data from 10 participating institutions of the International Gamma Knife Research Foundation for patients with acromegaly who underwent SRS with endocrine follow-up of ≥6 mo. Results The study cohort comprised 371 patients with a mean endocrine follow-up of 79 mo. IGF-1 lowering medications were held in 56% of patients who were on pre-SRS medical therapy. The mean SRS treatment volume and margin dose were 3.0 cm3 and 24.2 Gy, respectively. The actuarial rates of initial and durable endocrine remission at 10 yr were 69% and 59%, respectively. The mean time to durable remission after SRS was 38 mo. Biochemical relapse after initial remission occurred in 9%, with a mean time to recurrence of 17 mo. Cessation of IGF-1 lowering medication prior to SRS was the only independent predictor of durable remission (P = .01). Adverse radiation effects included the development of ≥1 new endocrinopathy in 26% and ≥1 cranial neuropathy in 4%. Conclusion SRS is a definitive treatment option for patients with persistent or recurrent acromegaly after surgical resection. There appears to be a statistical association between the cessation of IGF-1 lowering medications prior to SRS and durable remission.

Statistical methods often distinguish between in-sample and out-of-sample approaches. In particular this is the case when time is involved. Then often time series methods are proposed that extrapolate past patterns into the future via complicated recursion formulas. Standard statistical inference is on the other hand concerned with estimating parameters within the given sample. This review paper is about a statistical methodology, where all parameters are estimated in-sample while producing a forecast out-of-sample without recursion or extrapolation. A new super-simulation algorithm ensures a faster implementation of the simplest and perhaps most important version of in-sample forecasting.

A variety of lesions may arise within the cerebellopontine angle (CPA). Schwannomas and meningiomas are most commonly found in this location. Imaging characteristics of meningiomas include hyperdensity on head computed tomography (CT) and avid contrast enhancement on T1-weighted postcontrast magnetic resonance imaging (MRI). Here, we present the case of a 49-year-old woman with enlarging right CPA meningioma. The patient reported mild hearing loss on the right but her neurological exam was otherwise benign. Since the lesion was enlarging and symptomatic, the patient was offered resection of the mass for diagnosis and treatment via an endoscopic retrosigmoid approach. We provide a video that illustrates the steps taken to resect this mass endoscopically. After cerebrospinal fluid (CSF) was drained to achieve brain relaxation, the tumor was visualized. The tumor had a rich vascular supply and had the appearance of a typical meningioma. The bipolar was used to cauterize the tumor's vascular supply. The tumor capsule was then opened with the microscissors. The round knife, suction, and ultrasonic tissue debrider were used to debulk the tumor. After internal debulking of the tumor, the capsule was dissected off the cerebellum and mobilized. A combination of blunt and sharp dissection was done to free the tumor capsule from the adjacent structures. Inferiorly, the lower cranial nerves were visualized. Tissue pathology confirmed a diagnosis of grade I meningioma. A gross total resection was achieved and the patient remained neurologically stable, postoperatively. Furthermore, T1-weighted postcontrast brain MRI, 1 year after surgery, showed no residual.The link to the video can be found at: https://youtu.be/X9c_inLp-So.

This study was carried out to investigate the physicochemical and sensory properties of milk with added powdered peanut sprout extract microcapsules (PPSEM) during the storage at 4°C for 16 d. The size of PPSEM varies from 3 to 10 μm as observed by the scanning electron microscopy (SEM). The pH values of all samples ranged from 6.8 to 6.6 during the storage. Release of resveratrol for 0.5 and 1% PPSEM addition was about 0.89 μl/ml and TBARS value found to lower during storage of 16 d. The a* and b* color values of high concentrations (1.5, 2.0, 2.5 and 3.0%) of PPSEM-added milk samples were significantly increased during the storage (p

Introduction We sought to identify factors associated with increased length of stay (LOS) and morbidity in patients undergoing resection of pituitary macroadenomas. Methods We reviewed records of 203 consecutive patients who underwent endoscopic endonasal resection of a pituitary macroadenoma (mean age = 55.7 [16-88]) years, volume = 11.3 (1.0-134.3) cm3. Complete resection was possible in 60/29.6% patients. Mean follow-up was 575 days. Multivariate logistic regression was performed using MATLAB. Results Mean LOS was 4.67 (1-66) days and was associated with CSF leak (p = 0.025), lumbar drain placement (p = 0.041; n = 8/3.9% intraoperative, n = 20/9.9% postoperative), and any infection (p = 0.066). Age, diabetes insipidus (n = 17/8.37%), and syndrome of inappropriate antidiuretic hormone secretion (n = 12/5.9%) were not associated with increased LOS (p > 0.2). Postoperative CSF leak in the hospital (n = 21/10.3%) was associated with intraoperative CSF leak (p = 0.002; n = 82/40.4%) and complete resection (p = 0.012). There was no significant association (p > 0.1) between postoperative CSF leak in the hospital following surgery and the use of a fat graft (n = 61/30.1%), nasoseptal flap (155/76.4%), or perioperative lumbar drain placement (n = 8/3.94%). Conclusion Complete resection is associated with increased risk of CSF leak and LOS. Operative strategies including placement of fat graft, nasoseptal flap, or intraoperative lumbar drain placement may have limited value in reducing the risk of postoperative CSF leak.

Background Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense. Objective To propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease. Methods Fifteen patients were identified and administered a Food and Drug Administration-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) before surgical resection. An NIR camera was utilized to localize the tumor before resection and to visualize surgical margins following resection. Neuropathology and magnetic resonance imaging data were used to assess the accuracy and precision of NIR fluorescence in identifying tumor tissue. Results NIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low-grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12 of 15 tumors were visualized with the NIR camera. The mean signal-to-background ratio was 9.5 ± 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with signal-to-background ratio (P = .03). Nonenhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71). Conclusion With the use of Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity. Abbreviations 5-ALA, 5-aminolevulinic acidEPR, enhanced permeability and retentionFDA, Food and Drug AdministrationGBM, glioblastomaICG, indocyanine greenNIR, near-infraredNPV, negative predictive valuePPV, positive predictive valueROC, receiver operating characteristicROI, region of interestSBR, signal-to-background ratioWHO, World Health Organization.

Background Mutations in the isocitrate dehydrogenase enzyme are present in a majority of lower-grade gliomas and secondary glioblastomas. This mis-sense mutation results in the neomorphic reduction of isocitrate dehydrogenase resulting in an accumulation of the “oncometabolite” 2-hydroxyglutarate (2HG). Detection of 2HG can thus serve as a surrogate biomarker for these mutations, with significant translational implications including improved prognostication. Two dimensional localized correlated spectroscopy (2D L-COSY) at 7T is a highly-sensitive non-invasive technique for assessing brain metabolism. This study aims to assess tumor metabolism using 2D L-COSY at 7T for the detection of 2HG in IDH-mutant gliomas. Methods Nine treatment-naïve patients with suspected intracranial neoplasms were scanned at 7T MRI/MRS scanner using the 2D L-COSY technique. 2D-spectral processing and analyses were performed using a MATLAB-based reconstruction algorithm. Cross and diagonal peak volumes were quantified in the 2D L-COSY spectra and normalized with respect to the creatine peak at 3.0 ppm and quantified data were compared with previously-published data from six normal subjects. Detection of 2HG was validated using findings from immunohistochemical (IHC) staining in patients who subsequently underwent surgical resection. Results 2HG was detected in both of the IDH-mutated gliomas (grade III Anaplastic Astrocytoma and grade II Diffuse Astrocytoma) and was absent in IDH wild-type gliomas and in a patient with breast cancer metastases. 2D L-COSY was also able to resolve complex and overlapping resonances including phosphocholine (PC) from glycerophosphocholine (GPC), lactate (Lac) from lipids and glutamate (Glu) from glutamine (Gln). Conclusions This study demonstrates the ability of 2D L-COSY to unambiguously detect 2HG in addition to other neuro metabolites. These findings may aid in establishing 2HG as a biomarker of malignant progression as well as for disease monitoring in IDH-mutated gliomas.

Background: Symptomatic cavernous malformations involving the brainstem are frequently difficult to access via traditional methods. Conventional skull-base approaches require significant brain retraction or bone removal to provide an adequate operative corridor. While there has been a trend toward limited employment of the most invasive surgical approaches, recent advances in endoscopic technology may complement existing methods to access these difficult to reach areas. Case Descriptions: Four consecutive patients were treated for symptomatic, hemorrhagic brainstem cavernous malformations via fully endoscopic approaches (endonasal, transclival; retrosigmoid; lateral supracerebellar, infratentorial; endonasal, transclival). Together, these lesions encompassed all three segments of the brainstem. Three of the patients had complete resection of the cavernous malformation, while one patient had stable residual at long-term follow up. Associated developmental venous anomalies were preserved in the two patients where one was identified preoperatively. Three of the four patients maintained stable or improved neurological examinations following surgery, while one patient experienced ipsilateral palsies of cranial nerves VII and VIII. The first transclival approach resulted in a symptomatic cerebrospinal fluid leak requiring re-operation, but the second did not. Although there are challenges associated with endoscopic approaches, relative to our prior microsurgical experience with similar cases, visualization and illumination of the surgical corridors were superior without significant limitations on operative mobility. Conclusion: The endoscope is a promising adjunct to the neurosurgeon's ability to approach difficult to access brainstem cavernous malformations. It allows the surgeon to achieve well-illuminated, panoramic views, and by combining approaches, can provide minimally invasive access to most regions of the brainstem.

We perform full 3D topology optimization (in which “every voxel” of the unit cell is a degree of freedom) of photonic-crystal structures in order to find optimal omnidirectional band gaps for various symmetry groups, including fcc (including diamond), bcc, and simple-cubic lattices. Even without imposing the constraints of any fabrication process, the resulting optimal gaps are only slightly larger than previous hand designs, suggesting that current photonic crystals are nearly optimal in this respect. However, optimization can discover new structures, e.g. a new fcc structure with the same symmetry but slightly larger gap than the well known inverse opal, which may offer new degrees of freedom to future fabrication technologies. Furthermore, our band-gap optimization is an illustration of a computational approach to 3D dispersion engineering which is applicable to many other problems in optics, based on a novel semidefinite-program formulation for nonconvex eigenvalue optimization combined with other techniques such as a simple approach to impose symmetry constraints. We also demonstrate a technique for robust topology optimization, in which some uncertainty is included in each voxel and we optimize the worst-case gap, and we show that the resulting band gaps have increased robustness to systematic fabrication errors., United States. Air Force Office of Scientific Research (Grant FA9550-11-1-0141), MIT-Chile Program (Seed Fund), United States. Air Force Office of Scientific Research. Multidisciplinary University Research Initiative (Complex and Robust On-chip Nanophotonics Grant FA9550-09-1-0704), Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Contract W911NF-07-D0004)

International audience; The Sodium-cooled fast neutron reactor ASTRID is currently under design and development in France. Traditional ECCO/ERANOS fast reactor code system used for ASTRID core design calculations relies on multi-group JEFF-3.1.1 data library. To gauge the use of ENDF/B-VII.0 and JEFF-3.1.1 nuclear data libraries in the fast reactor applications, two recent OECD/NEA computational benchmarks specified by Argonne National Laboratory were calculated. Using the continuous-energy TRIPOLI-4 Monte Carlo transport code, both ABR-1000 MWth MOX core and metallic (U-Pu) core were investigated. Under two different fast neutron spectra and two data libraries, ENDF/B-VII.0 and JEFF-3.1.1, reactivity impact studies were performed. Using JEFF-3.1.1 library under the BOEC (Beginning of equilibrium cycle) condition, high reactivity effects of 808 ± 17 pcm and 1208 ± 17 pcm were observed for ABR-1000 MOX core and metallic core respectively. To analyze the causes of these differences in reactivity, several TRIPOLI-4 runs using mixed data libraries feature allow us to identify the nuclides and the nuclear data accounting for the major part of the observed reactivity discrepancies.

Legal coercion seems morally problematic because it is susceptible to the Hegelian objection that it fails to respect individuals in a way that is 'due to them as men'. But in what sense does legal coercion fail to do so? And what are the grounds for this requirement to respect? This paper is an attempt to answer these questions. It argues that (a) legal coercion fails to respect individuals as reason-responsive agents; and (b) individuals ought to be respected as such in virtue of the fact that they are human beings. Thus it is in this sense that legal coercion fails to treat individuals with the kind of respect 'due to them as men'. © 2013 Springer Science+Business Media Dordrecht.

With the humongous amount and variety of ethical cosmopolitan positions in the contemporary literature, Stan van Hooft’s Cosmopolitanism is a great introduction to those who would like to be acquainted with the position, as it argues for 21 essential features in ethical cosmopolitanism ((19-20); I shall not list them out here due to limited space). The area that is covered by this list is extremely extensive: partiality, universal human rights, what we owe to distant others, the self-determination of peoples and nation-states, just war theory, international relations, global governance, toleration etc.

DNA was successfully isolated from numerous Aspergillus spp. by use of a commercial kit. DNA that was easily digested and yielded PCR products up to 8.5 kb in size was recovered from broth or agar cultures. The ease and speed of this protocol provide an alternative to physical methods of DNA isolation.

The BRAHMS experiment at RHIC has measured pions, kaons and protons and their antiparticles over a wide range of rapidity and transverse momenta. Au+Au collisions, d+Au and p+p interactions have been studied. From the net-proton rapidity distribution a stopping power of 73% can be deduced for central Au+Au collisions. The rapidity distributions of produced particles exhibit Gaussian shapes. At midrapidity the nuclear modification factor for central Au+Au collisions shows a strong pion suppression at intermediate transverse momenta; a suppression which is even stronger at forward rapidities. The nuclear modification factor for d+Au changes from a Cronin-like enhancement of charged hadrons at midrapidity to a suppression at forward rapidities.

We present transverse momentum spectra of unidentified charged hadrons at two pseudo-rapidities (η = 0, 2.2) as well as the first results on identified negatively charged pions at rapidity 2.2 from Au+Au collisions at $\sqrt{s_{NN}} = 200$ GeV. The high p T yields of charged hadrons in the most central collisions show a strong suppression when compared to expected binary-scaled yields from nucleon-nucleon collisions or semi-peripheral collisions. The π– spectra at forward rapidity (y = 2.2) also indicate a clear suppression of high p T π– yields in central collisions. PACS: 25.75.Dw Particle and resonance production

An enhanced version of indirect advancing front technique is proposed for the construction of full quadrilateral anisotropic meshes on 3D surfaces. The final quadrilateral mesh is constructed from a background triangular mesh and the merging procedure is carried out in the parametric space. The proposed method employed the systemic merging technique for the formation of quadrilaterals and the metric specifications for controlling the anisotropic characteristics of the elements. In order to generate well-graded anisotropic quadrilaterals, the selection criteria of base segment for merging are carefully defined. Furthermore, in order to improve the shape quality of the final mesh, a set of new local smoothing algorithms for anisotropic quadrilateral mesh quality enhancement has been proposed and tested in this study. Numerical examples obtained indicate that the proposed enhanced local smoothing schemes can effectively improve the quality of the quadrilateral meshes produced and increase the robustness of the mesh generation scheme. Copyright © 2003 John Wiley & Sons, Ltd.