479 research outputs found

    Image-guided high-dose-rate brachytherapy: preliminary outcomes and toxicity of a joint interventional radiology and radiation oncology technique for achieving local control in challenging cases.

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    PurposeTo determine the ability of image-guided high-dose-rate brachytherapy (IG-HDR) to provide local control (LC) of lesions in non-traditional locations for patients with heavily pre-treated malignancies.Material and methodsThis retrospective series included 18 patients treated between 2012 and 2014 with IG-HDR, either in combination with external beam radiotherapy (EBRT; n = 9) or as monotherapy (n = 9). Lesions were located in the pelvis (n = 5), extremity (n = 2), abdomen/retroperitoneum (n = 9), and head/neck (n = 2). All cases were performed in conjunction between interventional radiology and radiation oncology. Toxicity was graded based on CTCAE v4.0 and local failure was determined by RECIST criteria. Kaplan-Meier analysis was performed for LC and overall survival.ResultsThe median follow-up was 11.9 months. Two patients had localized disease at presentation; the remainder had recurrent and/or metastatic disease. Seven patients had prior EBRT, with a median equivalent dose in 2 Gy fractions (EQD2) of 47.0 Gy. The median total EQD2s were 34 Gy and 60.9 Gy for patients treated with monotherapy or combination therapy, respectively. Image-guided high-dose rate brachytherapy was delivered in one to six fractions. Six patients had local failures at a median interval of 5.27 months with a one-year LC rate of 59.3% and a one-year overall survival of 40.7%. Six patients died from their disease at a median interval of 6.85 months from the end of treatment. There were no grade ≥ 3 acute toxicities but two patients had serious long term toxicities.ConclusionsWe demonstrate a good one year LC rate of nearly 60%, and a favorable toxicity profile when utilizing IG-HDR to deliver high doses of radiation with high precision into targets not readily accessible by other forms of local therapy. These preliminary results suggest that further studies utilizing this approach may be considered for patients with difficult to access lesions that require LC

    Itk Negatively Regulates Induction of  T Cell Proliferation by CD28 Costimulation

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    CD28 is a cell surface molecule that mediates a costimulatory signal crucial for T cell proliferation and lymphokine production. The signal transduction mechanisms of CD28 are not well understood. Itk, a nonreceptor protein tyrosine kinase specifically expressed in T cells and mast cells, has been implicated in the CD28 signaling pathway because of reports that it becomes phosphorylated on tyrosines and associates with CD28 upon cross-linking of the cell surface molecule. To determine whether Itk plays a functional role in CD28 signaling, we compared T cells from Itk-deficient mice and control mice for their responses to CD28 costimulation. T cells defective in Itk were found to be fully competent to respond to costimulation. Whereas the CD3-mediated proliferative response was severely compromised in the absence of Itk, the calcineurin-independent CD28-mediated response was significantly elevated when compared with cells from control animals. The augmented proliferation was not due to increased production of interleukin-2. The results suggest that Itk has distinct roles in the CD3 versus the CD28 signaling pathways. By negatively regulating the amplitude of signaling upon CD28 costimulation, Itk may provide a means for modulating the outcome of T cell activation during development and during antigen-driven immune responses

    Topological Regulation of Synaptic AMPA Receptor Expression by the RNA-Binding Protein CPEB3

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    SummarySynaptic receptors gate the neuronal response to incoming signals, but they are not homogeneously distributed on dendrites. A spatially defined receptor distribution can preferentially amplify certain synaptic inputs, resize receptive fields of neurons, and optimize information processing within a neuronal circuit. Thus, a longstanding question is how the spatial organization of synaptic receptors is achieved. Here, we find that action potentials provide local signals that influence the distribution of synaptic AMPA receptors along dendrites in mouse cerebellar stellate cells. Graded dendritic depolarizations elevate CPEB3 protein at proximal dendrites, where we suggest that CPEB3 binds to GluA2 mRNA, suppressing GluA2 protein synthesis leading to a distance-dependent increase in synaptic GluA2 AMPARs. The activity-induced expression of CPEB3 requires increased Ca2+ and PKC activation. Our results suggest a cell-autonomous mechanism where sustained postsynaptic firing drives graded local protein synthesis, thus directing the spatial organization of synaptic AMPARs

    Evaluating a Thrombosed Azygous Vein Aneurysm Combined with Pulmonary Arterial Thromboembolism by ECG-Gated Multidetector CT: a Case Report

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    Azygous vein aneurysm is a rare congenital lesion that needs to be differentiated from mediastinal mass lesions. Although almost of these anomalies are asymptomatic lesions, we experienced an interesting case in which a thrombus within an azygous vein aneurysm in a 75-year-old woman caused pulmonary thromboembolism. The patient was managed by medical treatment for one month and then the thrombus within both the azygous vein aneurysm and the pulmonary arteries completely resolved

    Avoided Quantum Criticality and Magnetoelastic Coupling in BaFe<sub>2-</sub>xNi<sub>x</sub>As<sub>2</sub>

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    We study the structural and magnetic orders in electron-doped BaFe2-xNixAs2 by high-resolution synchrotron X-ray and neutron scatterings. Upon Ni-doping x, the nearly simultaneous tetragonal-to-orthorhombic structural T_s and antiferromagnetic (T_N) phase transitions in BaFe2As2 are gradually suppressed and separated, resulting in T_s>T_N with increasing x as was previously observed. However, the temperature separation between T_s and T_N decreases with increasing x for x> 0.065,tendingtowardsaquantumbicriticalpointnearoptimalsuperconductivityatx=0.1.Thezerotemperaturetransitionispreemptedbytheformationofasecondaryincommensuratemagneticphaseintheregion0.088<x<0.104,resultinginafinitevalueofTNTc+10, tending towards a quantum bi-critical point near optimal superconductivity at x=0.1. The zero-temperature transition is preempted by the formation of a secondary incommensurate magnetic phase in the region 0.088< x < 0.104, resulting in a finite value of T_N \approx T_c+10 K above the superconducting dome around x0.1x\approx 0.1. Our results imply an avoided quantum critical point, which is expected to strongly influence the properties of both the normal and superconducting states.Comment: 7 pages; 5 figure
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