Visual function assessment in medical imaging research

Background: Medical image perception research relies on visual data to study the diagnostic relationship between observers and medical images. A consistent method to assess visual function for participants in medical imaging research has not been developed and represents a significant gap in existing research. Methods: Three visual assessment factors appropriate to observer studies were identified: visual acuity, contrast sensitivity, and stereopsis. A test was designed for each, and 30 radiography observers (mean age 31.6 years) participated in each test. Results: Mean binocular visual acuity for distance was 20/14 for all observers. The difference between observers who did and did not use corrective lenses was not statistically significant (P ! .12). All subjects had a normal value for near visual acuity and stereoacuity. Contrast sensitivity was better than population norms. Conclusion: All observers had normal visual function and could participate in medical imaging visual analysis studies. Protocols of evaluation and populations norms are provided. Further studies are necessary to understand fully the relationship between visual performance on tests and diagnostic accuracy in practice

Electrical ageing studies of polymeric insulation for power cables (estudo do envelhecimento eléctrico do isolante polimérico de cabos eléctricos

Dissertação apresentada para obtenção do Grau de Doutor em Engenharia Física - Física Aplicada pela Universidade Nova de Lisboa, Faculdade de Ciências e TecnologiaPolymers have been widely used as electrical insulators in power cables. Polyethylene, initially low density and more recently crosslinked, are one of the more commonly used insulators in medium and high voltage power cables. They suffer electrical ageing in different forms, such as water treeing, electrical treeing and finally dielectric breakdown. The last one leading to costly cable failure. Many research works have been developed on this subject despite of the progress made up to now, results are still sometimes contradictory and difficult to reproduce. Any new insight into this problem is a step further in preventing failure of the cables and increasing their useful lifetime. The aim of this thesis was to relate ageing in two different aspects of electrical ageing: localised damage and changes in bulk properties of the polyethylene. For this different experimental techniques were used. Localised damage was water treeing and breakdown channels since no electrical trees were observed. The methods used for this study were FTIR,estimation of fractal dimension of water trees and statistics of dielectric breakdown. The changes of electric and dielectric bulk properties were accessed using mostly DRS, FTSDC and PEA. From the FTIR results it was possible to find oxidation products (mainly ketones and carboxylate ions) and chain scission. The values estimated for fractal dimension point to the same underlying microscopic mechanism for water treeing (at least for samples aged at different frequency and temperature). Breakdown statistics point to the important role of manufacture and processing of the insulator, since early breakdown is mostly dependent on defects resulting from these processes. A correlation between DRS, FTSDC and PEA shows the role played by space charge and trapping on ageing for longer times. The two different aspects (localised and bulk) are difficult to correlate because the first one has a stochastic behaviour. However the presence of space charge found in bulk studies can be regard as one of the initiator factors for localised damage.Fundação Calouste Gulbenkia

Keep an eye on your hands: on the role of visual mechanisms in processing of haptic space

The present paper reviews research on a haptic orientation processing. Central is a task in which a test bar has to be set parallel to a reference bar at another location. Introducing a delay between inspecting the reference bar and setting the test bar leads to a surprising improvement. Moreover, offering visual background information also elevates performance. Interestingly, (congenitally) blind individuals do not or to a weaker extent show the improvement with time, while in parallel to this, they appear to benefit less from spatial imagery processing. Together this strongly points to an important role for visual processing mechanisms in the perception of haptic inputs

Analytical techniques for multiplex analysis of protein biomarkers

Introduction: The importance of biomarkers for pharmaceutical drug development and clinical diagnostics is more significant than ever in the current shift toward personalized medicine. Biomarkers have taken a central position either as companion markers to support drug development and patient selection, or as indicators aiming to detect the earliest perturbations indicative of disease, minimizing therapeutic intervention or even enabling disease reversal. Protein biomarkers are of particular interest given their central role in biochemical pathways. Hence, capabilities to analyze multiple protein biomarkers in one assay are highly interesting for biomedical research. Areas covered: We here review multiple methods that are suitable for robust, high throughput, standardized, and affordable analysis of protein biomarkers in a multiplex format. We describe innovative developments in immunoassays, the vanguard of methods in clinical laboratories, and mass spectrometry, increasingly implemented for protein biomarker analysis. Moreover, emerging techniques are discussed with potentially improved protein capture, separation, and detection that will further boost multiplex analyses. Expert commentary: The development of clinically applied multiplex protein biomarker assays is essential as multi-protein signatures provide more comprehensive information about biological systems than single biomarkers, leading to improved insights in mechanisms of disease, diagnostics, and the effect of personalized medicine

Thermal- and Oxidative Stress Causes Enhanced Release of NKG2D Ligand-Bearing Immunosuppressive Exosomes in Leukemia/Lymphoma T and B Cells

Immune evasion from NK surveillance related to inadequate NK-cell function has been suggested as an explanation of the high incidence of relapse and fatal outcome of many blood malignancies. In this report we have used Jurkat and Raji cell lines as a model for studies of the NKG2D receptor-ligand system in T-and B cell leukemia/lymphoma. Using real-time quantitative RT-PCR and immunoflow cytometry we show that Jurkat and Raji cells constitutively express mRNA and protein for the stress-inducible NKG2D ligands MICA/B and ULBP1 and 2, and up-regulate the expression in a cell-line specific and stress-specific manner. Furthermore, we revealed by electron microscopy, immunoflow cytometry and western blot that these ligands were expressed and secreted on exosomes, nanometer-sized microvesicles of endosomal origin. Acting as a decoy, the NKG2D ligand-bearing exosomes downregulate the in vitro NKG2D receptor-mediated cytotoxicity and thus impair NK-cell function. Interestingly, thermal and oxidative stress enhanced the exosome secretion generating more soluble NKG2D ligands that aggravated the impairment of the cytotoxic response. Taken together, our results might partly explain the clinically observed NK-cell dysfunction in patients suffering from leukemia/lymphoma. The adverse effect of thermal and oxidative stress, enhancing the release of immunosuppressive exosomes, should be considered when cytostatic and hyperthermal anti-cancer therapies are designed

Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes.

BACKGROUND: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. RESULTS: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. CONCLUSION: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.</p