A mathematical model for describing the retinal nerve fiber bundle trajectories in the human eye:Average course, variability, and influence of refraction, optic disc size and optic disc position

Previously we developed a mathematical model for describing the retinal nerve fiber bundle trajectories in the superior-temporal and inferior-temporal regions of the human retina, based on traced trajectories extracted from fundus photographs. Aims of the current study were to (i) validate the existing model, (ii) expand the model to the entire retina and (iii) determine the influence of refraction, optic disc size and optic disc position on the trajectories. A new set of fundus photographs was collected comprising 28 eyes of 28 subjects. From these 28 photographs, 625 trajectories were extracted. Trajectories in the temporal region of the retina were compared to the existing model. In this region, 347 of 399 trajectories (87%) were within the 95% central range of the existing model. The model was extended to the nasal region. With this extension, the model can now be applied to the entire retina that corresponds to the visual field as tested with standard automated perimetry (up to approximately 30 eccentricity). There was an asymmetry between the superior and inferior hemifields and a considerable location-specific inter-subject variability. In the nasal region, we found two "singularities", located roughly at the one and five o'clock positions for the right optic disc. Here, trajectories from relatively widespread areas of the retina converge. Associations between individual deviations from the model and refraction, optic disc size and optic disc position were studied with multiple linear regression. Refraction (P = 0.021) and possibly optic disc inclination (P = 0.09) influenced the trajectories in the superior-temporal region. (C) 2012 Elsevier Ltd. All rights reserved

Influence of the Retinal Blood Vessel Topography on the Variability of the Retinal Nerve Fiber Bundle Trajectories in the Human Retina

PURPOSE. To determine the relationship between the retinal blood vessel topography and the retinal nerve fiber bundle (RNFB) trajectories in the human retina. METHODS. A previously collected dataset comprising 28 fundus photographs with traced RNFB trajectories was used. For all traced trajectories, the departure from our previously published RNFB trajectory model was calculated. Subsequently, we calculated, per subject, a "mean departure" for the superior-temporal and inferior-temporal region. We measured angles between a line connecting the optic nerve head (ONH) center and the fovea and lines connecting the ONH center and the crossings of the superior and inferior temporal arteries (arterial angles) and veins (venous angles) with circles around the ONH; circle radii were 25%, 50%, and 100% of the ONH center-to-fovea distance. We also defined two angles based on the location of the first arteriovenous crossing. Multiple linear regression analysis was performed with mean departure as dependent variable and refraction, ONH inclination, and vessel angles as independent variables. RESULTS. In the superior-temporal region, refraction (P = 0.017), ONH inclination (P = 0.021), and the arterial angle corresponding to the middle circle (P <0.001) were significant determinants of mean departure. Explained variance was 0.54. In the inferior-temporal region, the arterial angle corresponding to the largest circle (P = 0.002) was significant. Explained variance was 0.32. CONCLUSIONS. The retinal blood vessel topography explains a significant part of the RNFB trajectory variability but only if (1) the vessel topography is assessed at an appropriate distance from the ONH and (2) the superior and inferior hemifield are addressed independently

Influence of the Retinal Blood Vessel Topography on the Variability of the Retinal Nerve Fiber Bundle Trajectories in the Human Retina

Citation: Qiu K, Schiefer J, Nevalainen J, Schiefer U, Jansonius NM. Influence of the retinal blood vessel topography on the variability of the retinal nerve fiber bundle trajectories in the human retina. Invest Ophthalmol Vis Sci. 2015;56:6320-6325. DOI:10.1167/ iovs.15-17450 PURPOSE. To determine the relationship between the retinal blood vessel topography and the retinal nerve fiber bundle (RNFB) trajectories in the human retina. METHODS. A previously collected dataset comprising 28 fundus photographs with traced RNFB trajectories was used. For all traced trajectories, the departure from our previously published RNFB trajectory model was calculated. Subsequently, we calculated, per subject, a &apos;&apos;mean departure&apos;&apos; for the superior-temporal and inferior-temporal region. We measured angles between a line connecting the optic nerve head (ONH) center and the fovea and lines connecting the ONH center and the crossings of the superior and inferior temporal arteries (arterial angles) and veins (venous angles) with circles around the ONH; circle radii were 25%, 50%, and 100% of the ONH center-to-fovea distance. We also defined two angles based on the location of the first arteriovenous crossing. Multiple linear regression analysis was performed with mean departure as dependent variable and refraction, ONH inclination, and vessel angles as independent variables. RESULTS. In the superior-temporal region, refraction (P ¼ 0.017), ONH inclination (P ¼ 0.021), and the arterial angle corresponding to the middle circle (P &lt; 0.001) were significant determinants of mean departure. Explained variance was 0.54. In the inferior-temporal region, the arterial angle corresponding to the largest circle (P ¼ 0.002) was significant. Explained variance was 0.32. CONCLUSIONS. The retinal blood vessel topography explains a significant part of the RNFB trajectory variability but only if (1) the vessel topography is assessed at an appropriate distance from the ONH and (2) the superior and inferior hemifield are addressed independently. Keywords: retinal nerve fiber layer, retinal vessels, retinal vasculature G laucoma is one of the important causes of blindness, with irreversible damage to retinal ganglion cells, the retinal nerve fiber layer (RNFL), and the optic nerve as its pathological features. The detection of changes in these structures is part of the diagnostic armamentarium in glaucoma; a detailed anatomical knowledge of especially the retinal nerve fiber bundle (RNFB) trajectories is helpful to integrate information from each structure and to topographically correlate it with visual field data. In 2000, Garway-Heath et al. 1 reported nerve fiber bundle trajectories based on fundus photographs. Later, models based on axonal growth and maps based on the correspondence between optical coherence tomography thickness measurements and visual field data were published. It has been reported that the vascular and neuronal systems share many similarities. The blood vessels and nerves tend to develop in relative proximity, throughout the body of any species in general and in the primate retina in particular. 12 By using scanning laser polarimetry, Resch et al

Epistemic Beliefs in Science—A Systematic Integration of Evidence From Multiple Studies

Recent research has integrated developmental and dimensional perspectives on epistemic beliefs by implementing an approach in which profiles of learners’ epistemic beliefs are modeled across multiple dimensions. Variability in study characteristics has impeded the comparison of profiles of epistemic beliefs and their relations with external variables across studies. We examined this comparability by integrating data on epistemic beliefs about the source, certainty, development, and justification of knowledge in science from six studies comprising N = 10,932 German students from elementary to upper secondary school. Applying latent profile analyses to these data, we found that profiles of epistemic beliefs that were previously conceptualized were robust across multiple samples. We found indications that profiles of epistemic beliefs homogenize over the course of students’ education, are related to school tracking, and demonstrate robust relations with students’ personal characteristics and socioeconomic background. We discuss implications for the theory, assessment, and education of epistemic beliefs. © 2022, The Author(s)

Science and Heritage Language Integrated Learning (SHLIL) : Evidence for the effectiveness of an innovative science outreach program for migrant students

Migrant students tend to underperform in Science, Technology, Engineering, and Mathematics (STEM) subjects and are less likely to pursue higher education in STEM when compared with their nonmigrant peers. Given the substantial increase in migration, this disparity has been a central concern in science education in many European countries. The purpose of this study was to investigate the effectiveness of an innovative science outreach program that brings together migrant students and STEM professionals with the same linguistic and cultural backgrounds. The program consists of one‐off workshops that follow an inquiry‐based approach and include hands‐on activities and science communication in the students' heritage language. Using surveys with adapted scales and open‐ended questions, we applied a randomized block design with waitlist control groups and repeated measures. Eighty‐three Portuguese‐speaking migrant students aged 6–17 years participated in the workshops in Germany and the United Kingdom. Results indicate that both the students and STEM professionals evaluated the program positively and that students who participated in the workshops tended to demonstrate an increase in their attainment value for science and an increase in their self‐concept of ability for the heritage language 4 weeks after the intervention when compared with students in the control condition. These effects were particularly pronounced for students with low prior motivation to study science or speak the heritage language. Our results thus show that it is possible to foster migrant students' attainment value for science and increase their self‐concept of ability regarding the heritage language through a brief science outreach intervention

Insights into the Pathogenesis of Anaplastic Large-Cell Lymphoma through Genome-wide DNA Methylation Profiling.

Aberrant DNA methylation patterns in malignant cells allow insight into tumor evolution and development and can be used for disease classification. Here, we describe the genome-wide DNA methylation signatures of NPM-ALK-positive (ALK+) and NPM-ALK-negative (ALK-) anaplastic large-cell lymphoma (ALCL). We find that ALK+ and ALK- ALCL share common DNA methylation changes for genes involved in T cell differentiation and immune response, including TCR and CTLA-4, without an ALK-specific impact on tumor DNA methylation in gene promoters. Furthermore, we uncover a close relationship between global ALCL DNA methylation patterns and those in distinct thymic developmental stages and observe tumor-specific DNA hypomethylation in regulatory regions that are enriched for conserved transcription factor binding motifs such as AP1. Our results indicate similarity between ALCL tumor cells and thymic T cell subsets and a direct relationship between ALCL oncogenic signaling and DNA methylation through transcription factor induction and occupancy.G.E. was funded by the Austrian Science Foundation (FWF) (P 27616 and V 102). M.R.H. was supported by a L’Oréal for Women in Science grant. S.D.T. receives funding from Bloodwise (formerly Leukaemia and Lymphoma Research). L.K. has been funded by the FWF (P 26011 and P 29251), as well as the MSCA-ITN-2015-ETN ALKATRAS (No. 675712). D.J.W. is a paid consultant for Zymo Research Corporation.This is the final version of the article. It first appeared from Elsevier (Cell Press) via http://dx.doi.org/10.1016/j.celrep.2016.09.01

The glaciers climate change initiative: Methods for creating glacier area, elevation change and velocity products

Glaciers and their changes through time are increasingly obtained from a wide range of satellite sensors. Due to the often remote location of glaciers in inaccessible and high-mountain terrain, satellite observations frequently provide the only available measurements. Furthermore, satellite data provide observations of glacier character- istics that are difficult to monitor using ground-based measurements, thus complementing the latter. In the Glaciers_cci project of the European Space Agency (ESA), three of these characteristics are investigated in detail: glacier area, elevation change and surface velocity. We use (a) data from optical sensors to derive glacier outlines, (b) digital elevation models from at least two points in time, (c) repeat altimetry for determining elevation changes, and (d) data from repeat optical and microwave sensors for calculating surface velocity. For the latter, the two sensor types provide complementary information in terms of spatio-temporal coverage. While (c) and (d) can be generated mostly automatically, (a) and (b) require the intervention of an analyst. Largely based on the results of various round robin experiments (multi-analyst benchmark studies) for each of the products, we suggest and describe the most suitable algorithms for product creation and provide recommendations concerning their practical implementation and the required post-processing. For some of the products (area, velocity) post-processing can influence product quality more than the main-processing algorithm

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation