334 research outputs found

    Comparison Between Diffusion-Weighted MRI and I-123-mIBG Uptake in Primary High-Risk Neuroblastoma

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    Background: High-risk neuroblastoma (HR-NB) has a variable response to preoperative chemotherapy. It is not possible to differentiate viable vs. nonviable residual tumor before surgery. Purpose: To explore the association between apparent diffusion coefficient (ADC) values from diffusion-weighted magnetic resonance imaging (DW-MRI), 123I-meta-iodobenzyl-guanidine (123I-mIBG) uptake, and histology before and after chemotherapy. Study Type: Retrospective. Subjects: Forty patients with HR-NB. Field Strength/Sequence: 1.5T axial DW-MRI (b = 0,1000 s/mm2 ) and T2-weighted sequences. 123I-mIBG scintigraphy planar imaging (all patients), with additional 123I-mIBG single-photon emission computed tomography / computerized tomography (SPECT/CT) imaging (15 patients). Assessment: ADC maps and 123I-mIBG SPECT/CT images were coregistered to the T2-weighted images. 123I-mIBG uptake was normalized with a tumor-to-liver count ratio (TLCR). Regions of interest (ROIs) for primary tumor volume and different intratumor subregions were drawn. The lower quartile ADC value (ADC25prc) was used over the entire tumor volume and the overall level of 123I-mIBG uptake was graded into avidity groups. Statistical Tests: Analysis of variance (ANOVA) and linear regression were used to compare ADC and MIBG values before and after treatment. Threshold values to classify tumors as viable/necrotic were obtained using ROC analysis of ADC and TLCR values. Results: No significant difference in whole-tumor ADC25prc values were found between different 123I-mIBG avidity groups pre- (P = 0.31) or postchemotherapy (P = 0.35). In the “intratumor” analysis, 5/15 patients (prechemotherapy) and 0/14 patients (postchemotherapy) showed a significant correlation between ADC and TLCR values (P < 0.05). Increased tumor shrinkage was associated with lower pretreatment tumor ADC25prc values (P < 0.001); no association was found with pretreatment 123I-mIBG avidity (P = 0.17). Completely nonviable tumors had significantly lower postchemotherapy ADC25prc values than tumors with >10% viable tumor (P < 0.05). Both pre- and posttreatment TLCR values were significantly higher in patients with >50% viable tumor than those with 10–50% viable tumor (P < 0.05). Data Conclusion: 123I-mIBG avidity and ADC values are complementary noninvasive biomarkers of therapeutic response in HR-NB. Level of Evidence: 4. Technical Efficacy Stage: 3

    Chiral symmetry breaking in dimensionally regularized nonperturbative quenched QED

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    In this paper we study dynamical chiral symmetry breaking in dimensionally regularized quenched QED within the context of Dyson-Schwinger equations. In D < 4 dimensions the theory has solutions which exhibit chiral symmetry breaking for all values of the coupling. To begin with, we study this phenomenon both numerically and, with some approximations, analytically within the rainbow approximation in the Landau gauge. In particular, we discuss how to extract the critical coupling alpha_c = pi/3 relevant in four dimensions from the D dimensional theory. We further present analytic results for the chirally symmetric solution obtained with the Curtis-Pennington vertex as well as numerical results for solutions exhibiting chiral symmetry breaking. For these we demonstrate that, using dimensional regularization, the extraction of the critical coupling relevant for this vertex is feasible. Initial results for this critical coupling are in agreement with cut-off based work within the currently achievable numerical precision.Comment: 24 pages, including 5 figures; submitted to Phys. Rev.

    Anti-tumor activity without on-target off-tumor toxicity of GD2-Chimeric Antigen Receptor T cells in patients with neuroblastoma

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    The reprogramming of a patient’s immune system through genetic modification of the T cell compartment with chimeric antigen receptors (CARs) has led to durable remissions in chemotherapy-refractory B cell cancers. Targeting of solid cancers by CAR-T cells is dependent on their infiltration and expansion within the tumor microenvironment, and thus far, fewer clinical responses have been reported. Here, we report a phase 1 study (NCT02761915) in which we treated 12 children with relapsed/refractory neuroblastoma with escalating doses of second-generation GD2-directed CAR-T cells and increasing intensity of preparative lymphodepletion. Overall, no patients had objective clinical response at the evaluation point +28 days after CAR-T cell infusion using standard radiological response criteria. However, of the six patients receiving ≥108/meter2 CAR-T cells after fludarabine/cyclophosphamide conditioning, two experienced grade 2 to 3 cytokine release syndrome, and three demonstrated regression of soft tissue and bone marrow disease. This clinical activity was achieved without on-target off-tumor toxicity. Targeting neuroblastoma with GD2 CAR-T cells appears to be a valid and safe strategy but requires further modification to promote CAR-T cell longevity

    The Reader, the text, the Context: An Exploration of a Choreographed Response to Literature

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    Much current theory about response to literature stresses the reader's active role in constructing meaning, with reader, text, and context affecting the responses of individual readers (Beach, 1993). Response to literature, like most classroom interaction, tends to take a linguistic form. In a supportive classroom environment, however, a range of response media can potentially mediate students' transactions with literature. The present exploratory study used stimulated recall to elicit a retrospective account from two alternative school students who choreographed a dance to depict their understanding of the relationship between the two central characters in a short story. In their account they indicate that in composing their text they (a) initiated their interpretation by empathizing with the characters, (b) represented the characters' relationship through spatial images and configurations, and (c) used the psychological tool of dance to both represent and develop their thinking about the story. Their thought and activity were further mediated by the social context of learning, including the communication genres of the classroom, their own interaction, their teacher's intervention, and the stimulated recall interview itself. Their account illustrates the way in which reader, text, and context participate in a complex transaction when readers construct meaning for literature. Their experience also illustrates the ways in which the values of an instructional setting influence the extent to which learners may take advantage of the psychological tools available to them for growth.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

    The Depth and Dynamics of Context: Tracing the Sources and Channels of Engagement and Disengagement in Students' Response to Literature

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    In this article, we analyze one coauthor's 12th-grade English class, focusing on a small group of students who interpreted the character of Gertrude in Hamlet through a body biography, a life-sized human outline that students filled with words and images that represented their understanding of the character. We analyze the body biography production as a function of the social context of activity and then analyze the processes of composition involved in their production. Analysis of the data reveals that (a) the students exhibited different degrees of commitment to and involvement in the group task, (b) the degree of equity in productivity and social relations varied within the group in accordance with these different degrees of engagement, and (c) the inequity in social relations and contributions to the group product belied the degree to which the final interpretive product met the teacher's assessment criteria. We conclude with a reconsideration of the notion of engagement that includes attention to both the immediate social relations within the classroom and the histories of engagement that students bring to class.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

    The economic case for prioritizing governance over financial incentives in REDD+

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    This article contributes to the ongoing debate on the role of public policies and financial incentives in Reducing Emissions from Deforestation and forest Degradation (REDD+). It argues that the subordination of policies to results-based payments for emission reductions causes severe economic inefficiencies affecting the opportunity cost, transaction cost and economic rent of the programme. Such problems can be addressed by establishing sound procedural, land and financial governance at the national level, before REDD+ economic incentives are delivered at scale. Consideration is given to each governance dimension, the entry points for policy intervention and the impact on costs. International support must consider the financial and political cost of governance reforms, and use a pay-for-results ethos based on output and outcome indicators. This can be done in the readiness process but only if the latter’s legal force, scope, magnitude and time horizon are adequately reconsidered. In sum, the paper provides ammunition for the institutionalist argument that UNFCCC Parties must prioritise governance reform between now and the entry into force of the new climate agreement in 2020, and specific recommendations about how this can be done: only by doing so will they create the basis for the programme’s financial sustainability

    The impact of rheumatoid foot on disability in Colombian patients with rheumatoid arthritis

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    <p>Abstract</p> <p>Background</p> <p>Alterations in the feet of patients with rheumatoid arthritis (RA) are a cause of disability in this population. The purpose of this research was to evaluate the impact that foot impairment has on the patients' global quality of life (QOL) based on validated scales and its relationship to disease activity.</p> <p>Methods</p> <p>This was a cross-sectional study in which 95 patients with RA were enrolled. A complete physical examination, including a full foot assessment, was done. The Spanish versions of the Health Assessment Questionnaire (HAQ) Disability Index and of the Disease Activity Score (DAS 28) were administered. A logistic regression model was used to analyze data and obtain adjusted odds ratios (AORs).</p> <p>Results</p> <p>Foot deformities were observed in 78 (82%) of the patients; hallux valgus (65%), medial longitudinal arch flattening (42%), claw toe (lesser toes) (39%), dorsiflexion restriction (tibiotalar) (34%), cock-up toe (lesser toes) (25%), and transverse arch flattening (25%) were the most frequent. In the logistic regression analysis (adjusted for age, gender and duration of disease), forefoot movement pain, subtalar movement pain, tibiotalar movement pain and plantarflexion restriction (tibiotalar) were strongly associated with disease activity and disability. The positive squeeze test was significantly associated with disability risk (AOR = 6,3; 95% CI, 1.28–30.96; P = 0,02); hallux valgus, and dorsiflexion restriction (tibiotalar) were associated with disease activity.</p> <p>Conclusion</p> <p>Foot abnormalities are associated with active joint disease and disability in RA. Foot examinations provide complementary information related to the disability as an indirect measurement of quality of life and activity of disease in daily practice.</p
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