THE INITIATION OF BINOCULAR RIVALRY

Binocular rivalry refers to the perceptual alternation that occurs while viewing incompatible images, in which one monocular image is dominant and the other is suppressed. Rivalry has been closely studied but the neural site at which it is initiated is still controversial. The central claim of this thesis is that primary visual cortex is responsible for its initiation. This claim is supported by evidence from four experimental studies. The first study (described in Chapter 4) introduces the methodology for measuring visual sensitivity during dominance and suppression and compares several methods to see which yields the greatest difference between these two sensitivities. Suppression depth was measured by comparing the discrimination thresholds to a brief test stimulus delivered during dominance and suppression phases. The deepest suppression was achieved after a learning period, with the test stimulus presented for 100 ms and with post-test masking. The second study (Chapter 5) compares two hypotheses for the mechanism of binocular rivalry. Under eye suppression, visibility decreases when the tested eye is being suppressed, regardless of the test stimulus’s features. Feature suppression, however, predicts that reduction of visibility is caused by suppression of a stimulus feature, no matter which eye is suppressed. Eye suppression claims that monocular channels in the visual system alternate between dominance and suppression, while Feature suppression assumes that the features of stimuli inhibit each other perceptually in the high-level cortex. The experiment used a test stimulus similar in features to one, but not the other, rivalry-inducing stimulus. Test sensitivity was found to be lowered when the test stimulus was presented to the eye whose rivalry-inducing stimulus was suppressed. Sensitivity was not lowered when the test stimulus was presented to the other eye, even when the test shared features with the suppressed stimulus. The conclusion is that feature suppression is weak or does not exist without eye suppression, and that rivalry therefore originates in the primary visual cortex. If binocular rivalry is initiated in the primary visual cortex, stimuli producing no coherent activity in that area should produce no rivalry. In the third study (Chapter 6) this idea was tested with rotating arrays of short-lifetime dots. The dots with the shortest lifetime produced an image with no rotation signal, and an infinite lifetime produced rigid rotation. Subjects could discriminate the rotation direction with high accuracy at all but the shortest lifetime. When the two eyes were presented with opposite directions of rotation, there was binocular rivalry only at the longest lifetimes. Stimuli with short lifetimes produce a coherent motion signal, since their direction can be discriminated, but do not produce rivalry. A simple interpretation of this observation is that binocular rivalry is initiated at a level in the visual hierarchy below that which supports the motion signal. The model supported by the results of previous chapters requires that binocular rivalry suppression be small in the primary visual cortex, and builds up as signals progress along the visual pathway. This model predicts that for judgements dependent on activity in high visual cortex: 1. Binocular rivalry suppression should be deep; 2. Responses should be contrast invariant. The fourth and last study (chapter 7) confirmed these predictions by measuring suppression depth in two ways. First, two similar forms were briefly presented to one eye: the difference in shapes required for their discrimination was substantially greater during suppression than during dominance. Second, the two forms were made sufficiently different in shape to allow easy discrimination at high contrast, and the contrast of these forms was lowered to find the discrimination threshold. The results in the second experiment showed that contrast sensitivity did not differ between the suppression and dominance states. This invariance in contrast sensitivity is interpreted in terms of steep contrast-response functions in cortex beyond the primary visual area. The work in this thesis supports the idea that binocular rivalry is a process distributed along the visual pathway. More importantly, the results provide several lines of evidence that binocular rivalry is initiated in primary visual cortex

A cost effeciency approach to universal access for public transport for disabled people

Purpose To determine the intervendor variability of Agatston scoring determined with state-of-the-art computed tomographic (CT) systems from the four major vendors in an ex vivo setup and to simulate the subsequent effects on cardiovascular risk reclassification in a large population-based cohort. Materials and Methods Research ethics board approval was not necessary because cadaveric hearts from individuals who donated their bodies to science were used. Agatston scores obtained with CT scanners from four different vendors were compared. Fifteen ex vivo human hearts were placed in a phantom resembling an average human adult. Hearts were scanned at equal radiation dose settings for the systems of all four vendors. Agatston scores were quantified semiautomatically with software used clinically. The ex vivo Agatston scores were used to simulate the effects of different CT scanners on reclassification of 432 individuals aged 55 years or older from a population-based study who were at intermediate cardiovascular risk based on Framingham risk scores. The Friedman test was used to evaluate overall differences, and post hoc analyses were performed by using the Wilcoxon signed-rank test with Bonferroni correction. Results Agatston scores differed substantially when CT scanners from different vendors were used, with median Agatston scores ranging from 332 (interquartile range, 114-1135) to 469 (interquartile range, 183-1381; P < .05). Simulation showed that these differences resulted in a change in cardiovascular risk classification in 0.5\%-6.5\% of individuals at intermediate risk when a CT scanner from a different vendor was used. Conclusion Among individuals at intermediate cardiovascular risk, state-of the-art CT scanners made by different vendors produced substantially different Agatston scores, which can result in reclassification of patients to the high- or low-risk categories in up to 6.5\% of cases. © RSNA, 2014

Imaging of pediatric great vessel stents: Computed tomography or magnetic resonance imaging?

__Background:__ Complications might occur after great vessel stent implantation in children. Therefore follow- up using imaging is warranted. __Purpose:__ To determine the optimal imaging modality for the assessment of stents used to treat great vessel obstructions in children. __Material and methods:__ Five different large vessel stents were evaluated in an in-vitro setting. All stents were expanded to the maximal vendor recommended diameter (20mm; n = 4 or 10mm; n = 1), placed in an anthropomorphic chest phantom and imaged with a 256-slice CT-scanner. MRI images were acquired at 1.5T using a multi-slice T2-weighted turbo spin echo, an RFspoiled three-dimensional T1-weighted Fast Field Echo and a balanced turbo field echo 3D seq

Development and validation of an efficient and highly sensitive enzyme-linked immunosorbent assay for alemtuzumab quantification in human serum and plasma

Background:Alemtuzumab is a humanized monoclonal antibody that targets the CD52 glycoprotein expressed on most lymphocytes, subsequently inducing complement-mediated and antibody-mediated cytotoxicity. Owing to its ability to induce profound immune depletion, alemtuzumab is frequently used in patients before allogeneic hematopoietic stem cell transplantation to prevent graft rejection and acute graft-versus-host disease. In this clinical context, a stable immunoassay with high sensitivity and specificity to determine alemtuzumab levels is essential for performing pharmacokinetic and pharmacodynamic analyses; however, the available methods have several limitations. Here, we report the successful development and validation of an efficient and highly sensitive enzyme-linked immunosorbent assay technique based on commercially available reagents to quantify alemtuzumab in human serum or plasma.Methods:This enzyme-linked immunosorbent assay technique was developed and validated in accordance with the European Medicines Agency guidelines on bioanalytical method validation.Results:The assay sensitivity (lower limit of quantification) is 0.5 ng center dot mL(-1), and the dynamic range is 0.78-25 ng center dot mL(-1). To accommodate quantification of peak concentration and concentrations below the lympholytic level (<0.1 mcg center dot mL(-1)), patients' serum samples were prediluted 20-400 times according to the expected alemtuzumab concentration. The overall within-run accuracy was between 96% and 105%, whereas overall within-run precision (coefficient of variation) was between 3% and 9%. The between-run assessment provided an overall accuracy between 86% and 95% and an overall coefficient of variation between 5% and 14%.Conclusions:The developed assay provides accurate insight into alemtuzumab exposure and its effects on the clinical response to treatment, which is key to optimizing treatment strategies.Personalised Therapeutic

Exposure-response analysis of alemtuzumab in pediatric allogeneic HSCT for nonmalignant diseases: the ARTIC study

Alemtuzumab (anti-CD52 antibody) is frequently prescribed to children with nonmalignant diseases undergoing allogeneic hematopoietic stem cell transplantation (HSCT) to prevent graft failure (GF) and acute graft-versus-host disease (aGVHD). The aim of this multicenter study was the characterization of alemtuzumab population pharmacokinetics to perform a novel modelbased exposure-response analysis in 53 children with nonmalignant immunological or hematological disease and a median age of 4.4 years (interquartile range [IQR], 0.8-8.7). The median cumulative alemtuzumab dose was 0.6 mg/kg (IQR, 0.6-1) administered over 2 to 7 days. A 2-compartment population pharmacokinetics model with parallel linear and nonlinear elimination including allometrically scaled bodyweight (median, 17.50 kg; IQR, 8.76-33.00) and lymphocyte count at baseline (mean, 2.24 x 10(9)/L; standard deviation +/- 1.87) as significant pharmacokinetic predictors was developed using nonlinear mixed effects modeling. Based on the model-estimated median concentration at day of HSCT (0.77 mu g/mL; IQR, 0.33-1.82), patients were grouped into a low- (0.77 mu g/mL) exposure groups. High alemtuzumab exposure at day of HSCT correlated with delayed CD4(+) and CD8(+) T-cell reconstitution (P value = 2, mortality, chimerism at 1 year, viral reactivations, and autoimmunity at a median follow-up of 3.3 years (IQR, 2.5-8.0). In conclusion, this novel population pharmacokinetics model is suitable for individualized intravenous precision dosing to predict alemtuzumab exposure in pediatric allogeneic HSCT for nonmalignant diseases, aiming at the achievement of early T-cell reconstitution and prevention of GF in future prospective studies.Transplantation and immunomodulatio

Radiation dose reduction for CT assessment of urolithiasis using iterative reconstruction: A prospective intra-individual study

Objective: To assess the performance of hybrid (HIR) and model-based iterative reconstruction (MIR) in patients with urolithiasis at reduced-dose computed tomography (CT). Methods: Twenty patients scheduled for unenhanced abdominal CT for follow-up of urolithiasis were prospectively included. Routine dose acquisition was followed by three low-dose acquisitions at 40%, 60% and 80% reduced doses. All images were reconstructed with filtered back projection (FBP), HIR and MIR. Urolithiasis detection rates, gall bladder, appendix and rectosigmoid evaluation and overall subjective image quality were evaluated by two observers. Results: 74 stones were present in 17 patients. Half the stones were not detected on FBP at the lowest dose level, but this improved with MIR to a sensitivity of 100%. HIR resulted in a slight decrease in sensitivity at the lowest dose to 72%, but outperformed FBP. Evaluation of other structures with HIR at 40% and with MIR at 60% dose reductions was comparable to FBP at routine dose, but 80% dose reduction resulted in non-evaluable images. Conclusions: CT radiation dose for urolithiasis detection can be safely reduced by 40 (HIR)–60 (MIR) % without affecting assessment of urolithiasis, possible extra-urinary tract pathology or overall image quality. Key Points: • Iterative reconstruction can be used to substantially lower the radiation dose. • This allows for radiation reduction without affecting sensitivity of stone detection. • Possible extra-urinary tract pathology evaluation is feasible at 40–60% reduced dose

Increased PD-L1 and T-cell infiltration in the presence of HLA class I expression in metastatic high-grade osteosarcoma: a rationale for T-cell-based immunotherapy

Transplantation and immunomodulatio

A large-scale evaluation of automatic pulmonary nodule detection in chest CT using local image features and k-nearest-neighbour classification.

Contains fulltext : 81262.pdf (publisher's version ) (Closed access)A scheme for the automatic detection of nodules in thoracic computed tomography scans is presented and extensively evaluated. The algorithm uses the local image features of shape index and curvedness in order to detect candidate structures in the lung volume and applies two successive k-nearest-neighbour classifiers in the reduction of false-positives. The nodule detection system is trained and tested on three databases extracted from a large-scale experimental screening study. The databases are constructed in order to evaluate the algorithm on both randomly chosen screening data as well as data containing higher proportions of nodules requiring follow-up. The system results are extensively evaluated including performance measurements on specific nodule types and sizes within the databases and on lesions which later proved to be malignant. In a random selection of 813 scans from the screening study a sensitivity of 80% with an average 4.2 false-positives per scan is achieved. The detection results presented are a realistic measure of a CAD system performance in a low-dose screening study which includes a diverse array of nodules of many varying sizes, types and textures

"Reply to Hochheggar et al."

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DNAM-1 mediates epithelial cell-specific cytotoxicity of aberrant intraepithelial lymphocyte lines from refractory celiac disease type II patients

In refractory celiac disease (RCD), intestinal epithelial damage persists despite a gluten-free diet. Characteristic for RCD type II (RCD II) is the presence of aberrant surface TCR-CD3(-) intraepithelial lymphocytes (IELs) that can progressively replace normal IELs and eventually give rise to overt lymphoma. Therefore, RCD II is considered a malignant condition that forms an intermediate stage between celiac disease (CD) and overt lymphoma. We demonstrate in this study that surface TCR-CD3(-) IEL lines isolated from three RCD II patients preferentially lyse epithelial cell lines. FACS analysis revealed that DNAM-1 was strongly expressed on the three RCD cell lines, whereas other activating NK cell receptors were not expressed on all three RCD cell lines. Consistent with this finding, cytotoxicity of the RCD cell lines was mediated mainly by DNAM-1 with only a minor role for other activating NK cell receptors. Furthermore, enterocytes isolated from duodenal biopsies expressed DNAM-1 ligands and were lysed by the RCD cell lines ex vivo. Although DNAM-1 on CD8(+) T cells and NK cells is known to mediate lysis of tumor cells, this study provides, to our knowledge, the first evidence that (pre)malignant cells themselves can acquire the ability to lyse epithelial cells via DNAM-1. This study confirms previous work on epithelial lysis by RCD cell lines and identifies a novel mechanism that potentially contributes to the gluten-independent tissue damage in RCD II and RCD-associated lymphoma.Transplantation and autoimmunit