192 research outputs found

    Yield Curve Shapes and the Asymptotic Short Rate Distribution in Affine One-Factor Models

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    We consider a model for interest rates, where the short rate is given by a time-homogenous, one-dimensional affine process in the sense of Duffie, Filipovic and Schachermayer. We show that in such a model yield curves can only be normal, inverse or humped (i.e. endowed with a single local maximum). Each case can be characterized by simple conditions on the present short rate. We give conditions under which the short rate process will converge to a limit distribution and describe the limit distribution in terms of its cumulant generating function. We apply our results to the Vasicek model, the CIR model, a CIR model with added jumps and a model of Ornstein-Uhlenbeck type

    Polymer-coated superparamagnetic iron oxide nanoparticles as T-2 contrast agent for MRI and their uptake in liver

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    Aim: To study the efficiency of multifunctional polymer-based superparamagnetic iron oxide nanoparticles (bioferrofluids) as a T-2 magnetic resonance contrast agent and their uptake and toxicity in liver. Materials & methods: Mice were intravenously injected with bioferrofluids and Endorem (R). The magnetic resonance efficiency, uptake and in vivo toxicity were investigated by means of magnetic resonance imaging (MRI) and histological techniques. Results: Bioferrofluids are a good T-2 contrast agent with a higher r(2)/r(1) ratio than Endorem. Bioferrofluids have a shorter blood circulation time and persist in liver for longer time period compared with Endorem. Both bioferrofluids and Endorem do not generate any noticeable histological lesions in liver over a period of 60 days post-injection. Conclusion: Our bioferrofluids are powerful diagnostic tool without any observed toxicity over a period of 60 days post-injection. Lay abstract: Several superparamagnetic iron oxide nanoparticles (SPIONs) preparations have been approved by US FDA for clinical use as MRI contrast agents. In recent years, we have been developing a synthetic multifunctional platform for SPIONs based on the use of polymers. In this report, we explored the diagnostic potential of these nanoparticles (herein called bioferrofluids) as an MRI contrast agent and their uptake in liver, without neglecting their toxicological effects. Results show that our bioferrofluids are a good T-2 contrast agent without any observed toxicity in liver

    Bioluminescence imaging in brain tumor: a powerful tool

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    Glioblastoma represents the most malignant and lethal among brain tumours because of its highly infiltration capacity and invasion into the normal brain that account for its resistance to treatments (chemotherapy and radiotherapy). Recent advance and development of technologies to non-invasively image brain tumour growth in living animals can open an opportunity to monitor directly the efficacy of the treatment on tumour development. In vivo bioluminescence imaging is based on light-emitting enzymes, luciferases, which require specific substrates for light production. When linked to a specific biological process/pathway in an animal model of human disease, the enzyme-substrate interactions become biological indicators that can be studied. In order to explore and compare different imaging modalities (MRI and bioluminescence imaging) we have validated the use of bioluminescence imaging to monitor glioblastoma progression in vivo. The human glioma cell line (DBTRG-05MG) derived from an adult patient with glioblastoma multiforme who had been treated with local brain irradiation and multidrug chemotherapy has been used for the experiment. The DBTRG-05MG cell line was stably transfected with TCF-luciferase and orthotopic implantated onto immunodeficient mice. Bioluminescence technology was used to follow tumour growth in parallel with classical MRI on the same animals

    Inhibition of tyrosine kinase receptors by SU6668 promotes abnormal stromal development at the periphery of carcinomas

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    Dynamic contrast-enhanced (albumin-Gd-DTPA) magnetic resonance imaging, performed during 2 weeks of daily administration of an inhibitor of tyrosine kinase receptors (SU6668) in an HT-29 colon carcinoma model, revealed the onset of a hyper-enhancing rim, not observed in untreated tumours. To account for tissue heterogeneity in the quantitative analysis, we segmented tumours into three subunits automatically identified by cluster analysis of the enhancement curves using a k-means algorithm. Transendothelial permeability (Kps) and fractional plasma volume (fPV) were calculated in each subunit. An avascular and necrotic region, an intermediate zone and a well-vascularised periphery were reliably identified. During untreated tumour growth, the identified sub-regions did not substantially change their enhancement pattern. Treatment with SU6668 induced major changes at tumour periphery where a significant increase of Kps and fPV was observed with respect to control tumours. Histology revealed a sub-capsular layer composed of hyper-dense viable tumour cells in the periphery of untreated tumours. The rim of viable neoplastic cells was reduced in treated tumours, and replaced by loose connective tissue characterised by numerous vessels, which explains the observed hyper-enhancement. The present data show a peripheral abnormal development of cancer-associated stroma, indicative of an adaptive response to anti-angiogenic treatment

    Initial clinical experience with frameless optically guided stereotactic radiosurgery/radiotherapy in pediatric patients

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    The objective of this study is to report our initial experience treating pediatric patients with central nervous system tumors using a frameless, optically guided linear accelerator. Pediatric patients were selected for treatment after evaluation by a multidisciplinary neuro-oncology team including neurosurgery, neurology, pathology, oncology, and radiation oncology. Prior to treatment, all patients underwent treatment planning using magnetic resonance imaging (MRI) and treatment simulation on a standard computed tomography scanner (CT). For CT simulation, patients were fitted with a customized plastic face mask with a bite block attached to an optical array with four reflective markers. After ensuring adequate reproducibility, these markers were tracked during treatment by an infra-red camera. All treatments were delivered on a Varian Trilogy linear accelerator. The follow-up period ranges from 1–18 months, with a median follow-up of 6 months. Nine patients, ages ranging from 12 to 19 years old (median age 15 years old), with a variety of tumors have been treated. Patients were treated for juvenile pilocytic astrocytoma (JPA; n = 2), pontine low-grade astrocytoma (n = 1), pituitary adenoma (n = 3), metastatic medulloblastoma (n = 1), acoustic neuroma (n = 1), and pineocytoma (n = 1). We followed patients for a median of 12 months (range 3–18 months) with no in-field failures and were able to obtain encouraging toxicity profiles. Frameless stereotactic optically guided radiosurgery and radiotherapy provides a feasible and accurate tool to treat a number of benign and malignant tumors in children with minimal treatment-related morbidity

    Pilocarpine-Induced Status Epilepticus in Rats Involves Ischemic and Excitotoxic Mechanisms

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    The neuron loss characteristic of hippocampal sclerosis in temporal lobe epilepsy patients is thought to be the result of excitotoxic, rather than ischemic, injury. In this study, we assessed changes in vascular structure, gene expression, and the time course of neuronal degeneration in the cerebral cortex during the acute period after onset of pilocarpine-induced status epilepticus (SE). Immediately after 2 hr SE, the subgranular layers of somatosensory cortex exhibited a reduced vascular perfusion indicative of ischemia, whereas the immediately adjacent supragranular layers exhibited increased perfusion. Subgranular layers exhibited necrotic pathology, whereas the supergranular layers were characterized by a delayed (24 h after SE) degeneration apparently via programmed cell death. These results indicate that both excitotoxic and ischemic injuries occur during pilocarpine-induced SE. Both of these degenerative pathways, as well as the widespread and severe brain damage observed, should be considered when animal model-based data are compared to human pathology
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