Comparative analytical performance of multiple plasma Aβ42 and Aβ40 assays and their ability to predict positron emission tomography amyloid positivity

INTRODUCTION: This report details the approach taken to providing a dataset allowing for analyses on the performance of recently developed assays of amyloid beta (Aβ) peptides in plasma and the extent to which they improve the prediction of amyloid positivity. METHODS: Alzheimer's Disease Neuroimaging Initiative plasma samples with corresponding amyloid positron emission tomography (PET) data were run on six plasma Aβ assays. Statistical tests were performed to determine whether the plasma Aβ measures significantly improved the area under the receiver operating characteristic curve for predicting amyloid PET status compared to age and apolipoprotein E (APOE) genotype. RESULTS: The age and APOE genotype model predicted amyloid status with an area under the curve (AUC) of 0.75. Three assays improved AUCs to 0.81, 0.81, and 0.84 (P < .05, uncorrected for multiple comparisons). DISCUSSION: Measurement of Aβ in plasma contributes to addressing the amyloid component of the ATN (amyloid/tau/neurodegeneration) framework and could be a first step before or in place of a PET or cerebrospinal fluid screening study. HIGHLIGHTS: The Foundation of the National Institutes of Health Biomarkers Consortium evaluated six plasma amyloid beta (Aβ) assays using Alzheimer's Disease Neuroimaging Initiative samples. Three assays improved prediction of amyloid status over age and apolipoprotein E (APOE) genotype. Plasma Aβ42/40 predicted amyloid positron emission tomography status better than Aβ42 or Aβ40 alone

Workshopping the revolution? On the phenomenon of joker training in the Theatre of the Oppressed

The article brings together observations and insights on the emerging phenomenon of training the trainers, also known as joker training in the Theatre of the Oppressed (TO). The concerns raised in this article are twofold: first, how does the modularised, workshop format of joker training affect the core principles of TO? Second, what are the implications of professionalising the work of the joker? These questions relate to the critique of ‘creative industries’ and debates around precarisation that profoundly impact arts and humanities education in contemporary Europe. They also serve as a call to interrogate concepts central to TO, such as participation, empowerment and community, in terms of how these concepts are appropriated and made docile in the increasingly neoliberal environment of European cultural and educational policies. The article proposes that a training in TO must view the dissemination of techniques and methods of joker practice as inseparable from a deep commitment to a ‘conscientised’ understanding of the complex social problems that the theatre seeks to address. The focus on a technical training alone bears the danger of reinforcing Freire's ‘banking method’ of pedagogy, which is counterproductive to the political objectives of TO. The article observes that professional jokers work in precarious conditions far removed from the promises of the economic rewards of creative enterprise. The proliferation of project-based freelance work creates a situation where jokers tend to become de-territorialised and alienated from actual problems, thus propagating biographic and short-term approaches to systemic contradictions. The study aims to problematise these issues and contribute to a debate that might lead to politically and professionally viable paths for the future of TO

A multivariate method for ultrasound tissue segmentation for biomarker analysis of tumor growth

The traditional means of analysis of tumor growth and morphology is to excise the tumor and study thin, histopathology slices under the microscope. This method requires a different subject for each time Estpoint and runs the real risk of missing some aspect of the tumor not collected in the slice. Ultrasound provide a means to study the tumor in vivo but the images can be hard to interpret. In this research, pixel intensity and contrast and entropy measurements of texture, derived from a cooccurrence function of the image, are used in a robust multivariate image segmentation algorithm to classify the tumor into viable and necrotic cells, reducing misclassification of tissue in the absence of reliable a priori information while allowing for a variable cost function for the type of misclassification. A nude mouse with an Hras tumor was used to establish the model and four nude mice with B16-F10 tumors were used to study the tumor growth over 14 days post cell injection. Histopathology images, one for the Hras tumor and one from mouse 3 of the B16-F10 tumors, were used to validate the segmented image. The multivariate method identified 73% of the necrosis using the mean pixel intensity and texture information while the intensity-alone method identified only 39% of the necrotic-associated pixels.

Whole body PD-L1 PET in patients with NSCLC and melanoma.

Background: PD-(L)1 immunotherapy is effective in multiple tumors, including NSCLC and melanoma, but tumor PD-L1 IHC correlates only moderately with treatment outcome. This study aims to assess 1) safety of 18F-BMS-986192 (18F-PD-L1) in human, 2) PD-L1 quantification in tumors using 18F-PD-L1 PET, 3) PD-L1 PET correlation with IHC and treatment outcome, and 4) intra and inter subject tracer uptake variability. Methods: Pts with NSCLC (N = 10) and melanoma (N = 3) were included. At baseline, pts received a static or multiphase dynamic whole body PET scan after injecting 200 MBq 18F-BMS-986192. For NSCLC pts, (1) SUV(max, peak and mean) were measured for each delineable tumor (N = 32, 1-7 tumors/pt), (2) PD-L1 IHC (28.8 assay) was performed on the biopsy, and (3) response to Nivolumab therapy assessed by RECIST 1.1. Intra and inter subject variability and intraclass correlation were calculated using SUVs of all assessed tumors. Equal variance for PD-L1 status was evaluated by a Levene’s test. Four (3 female) pts underwent dosimetry study (ICRP 60). Results: No AEs related to radiotracer was observed. Dosimetry study demonstrated whole body exposure of 30 mGy at dose > 1400 MBq. Biodistribution among pts is comparable. PD-L1 IHC from 13 biopsied lesions were evaluated, 5 <1%, 4 ≥1%, and 4 ≥50%. Tumor tracer uptake was measured in NSCLC pts and categorized by PDL-1 IHC as ≥50% or <50%. Clinical trial information: 2015-004760-11. Tumor SUVs did not correlate with RECIST 1.1 assessment. Lesion heterogeneity was reflected in both inter and intra pt variability (CVinter = 41%, CVintra = 53%, ICC = 0.41 for SUVpeak). Levene’s test showed no significance in variability between the two PD-L1 categories. Conclusions: PET-imaging with 18F-BMS-986192 is safe and feasible in pts with NSCLC and melanoma. Pts with higher PD-L1 PET SUV have higher PD-L1 by IHC. Intra pt variability is similar to inter pt variability. With limited number of pts, no clear correlation of PET PD-L1 and tumor response is observed. A prospective study with this tracer is underway to further investigate 18F-BMS-986192 in understanding of PD-L1 expression