The Onion Sign in Neovascular Age-Related Macular Degeneration Represents Cholesterol Crystals

PURPOSE: To investigate the frequency, natural evolution, and histologic correlates of layered, hyperreflective, subretinal pigment epithelium (sub-RPE) lines, known as the onion sign, in neovascular age-related macular degeneration (AMD). DESIGN: Retrospective observational cohort study and experimental laboratory study. PARTICIPANTS: Two hundred thirty eyes of 150 consecutive patients with neovascular AMD and 40 human donor eyes with histopathologic diagnosis of neovascular AMD. METHODS: Spectral-domain optical coherence tomography (SD OCT), near-infrared reflectance (NIR), color fundus images, and medical charts were reviewed. Donor eyes underwent multimodal ex vivo imaging, including SD OCT, before processing for high-resolution histologic analysis. MAIN OUTCOME MEASURES: Presence of layered, hyperreflective sub-RPE lines, qualitative analysis of their change in appearance over time with SD OCT, histologic correlates of these lines, and associated findings within surrounding tissues. RESULTS: Sixteen of 230 eyes of patients (7.0%) and 2 of 40 donor eyes (5.0%) with neovascular AMD had layered, hyperreflective sub-RPE lines on SD OCT imaging. These appeared as refractile, yellow-gray exudates on color imaging and as hyperreflective lesions on NIR. In all 16 patient eyes, the onion sign persisted in follow-up for up to 5 years, with fluctuations in the abundance of lines and association with intraretinal hyperreflective foci. Patients with the onion sign disproportionately were taking cholesterol-lowering medications (P=0.025). Histologic analysis of 2 donor eyes revealed that the hyperreflective lines correlated with clefts created by extraction of cholesterol crystals during tissue processing. The fluid surrounding the crystals contained lipid, yet was distinct from oily drusen. Intraretinal hyperreflective foci correlated with intraretinal RPE and lipid-filled cells of probable monocytic origin. CONCLUSIONS: Persistent and dynamic, the onion sign represents sub-RPE cholesterol crystal precipitation in an aqueous environment. The frequency of the onion sign in neovascular AMD in a referral practice and a pathology archive is 5% to 7%. Associations include use of cholesterol-lowering medication and intraretinal hyperreflective foci attributable to RPE cells and lipid-filled cells of monocyte origin

Matched Filter Stochastic Background Characterization for Hyperspectral Target Detection

Algorithms exploiting hyperspectral imagery for target detection have continually evolved to provide improved detection results. Adaptive matched filters can be used to locate spectral targets by modeling scene background as either structured (geometric) with a set of endmembers (basis vectors) or as unstructured (stochastic) with a covariance or correlation matrix. These matrices are often calculated using all available pixels in a data set. In unstructured background research, various techniques for improving upon scene-wide methods have been developed, each involving either the removal of target signatures from the background model or the segmentation of image data into spatial or spectral subsets. Each of these methods increase the detection signal-to-background ratio (SBR) and the multivariate normality (MVN) of the data from which background statistics are calculated, thus increasing separation between target and non-target species in the detection statistic and ultimately improving thresholded target detection results. Such techniques for improved background characterization are widely practiced but not well documented or compared. This paper provides a review and comparison of methods in target exclusion, spatial subsetting and spectral pre-clustering, and introduces a new technique which combines these methods. The analysis provides insight into the merit of employing unstructured background characterization techniques, as well as limitations for their practical application

Study of fuel cells using storable rocket propellants Final report, 18 Aug. 1965 - 23 Jun. 1969

Operating fuel cells on gaseous nitrogen tetroxide and aerozine 5

Prospects for multiwavelength polarization observations of GRB afterglows and the case GRB 030329

We explore the prospects for simultaneous, broad-band, multiwavelength polarimetric observations of GRB afterglows. We focus on the role of cosmic dust in GRB host galaxies on the observed percentage polarization of afterglows in the optical/near-infrared bands as a function of redshift. Our driving point is the afterglow of GRB 030329, for which we obtained polarimetric data in the R band and K band simultaneously about 1.5 days after the burst. We argue that polarimetric observations can be very sensitive to dust in a GRB host, because dust can render the polarization of an afterglow wavelength-dependent. We discuss the consequences for the interpretation of observational data and emphasize the important role of very early polarimetric follow-up observations in all bands, when afterglows are still bright, to study the physical properties of dust and magnetic fields in high-z galaxies.Comment: accepted for publication in Astronomy & Astrophysic

Darwin's Duchenne: Eye constriction during infant joy and distress

Darwin proposed that smiles with eye constriction (Duchenne smiles) index strong positive emotion in infants, while cry-faces with eye constriction index strong negative emotion. Research has supported Darwin's proposal with respect to smiling, but there has been little parallel research on cry-faces (open-mouth expressions with lateral lip stretching). To investigate the possibility that eye constriction indexes the affective intensity of positive and negative emotions, we first conducted the Face-to-Face/Still-Face (FFSF) procedure at 6 months. In the FFSF, three minutes of naturalistic infant-parent play interaction (which elicits more smiles than cry-faces) are followed by two minutes in which the parent holds an unresponsive still-face (which elicits more cry-faces than smiles). Consistent with Darwin's proposal, eye constriction was associated with stronger smiling and with stronger cry-faces. In addition, the proportion of smiles with eye constriction was higher during the positive-emotion eliciting play episode than during the still-face. In parallel, the proportion of cry-faces with eye constriction was higher during the negative-emotion eliciting still-face than during play. These results are consonant with the hypothesis that eye constriction indexes the affective intensity of both positive and negative facial configurations. A preponderance of eye constriction during cry-faces was observed in a second elicitor of intense negative emotion, vaccination injections, at both 6 and 12 months of age. The results support the existence of a Duchenne distress expression that parallels the more well-known Duchenne smile. This suggests that eye constriction-the Duchenne marker-has a systematic association with early facial expressions of intense negative and positive emotion. © 2013 Mattson et al

Eliciting imitation in early infancy

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Midgut epithelial endocrine cells are a rich source of the neuropeptides APSGFLGMRamide (Cancer borealis tachykinin-related peptide Ia) and GYRKPPFNGSIFamide (Gly\u3csup\u3e1\u3c/sup\u3e-SIFamide) in the crabs Cancer borealis, Cancer magister and Cancer productus

Over a quarter of a century ago, Mykles described the presence of putative endocrine cells in the midgut epithelium of the crab Cancer magister (Mykles, 1979). In the years that have followed, these cells have been largely ignored and nothing is known about their hormone content or the functions they play in this species. Here, we used a combination of immunohistochemistry and mass spectrometric techniques to investigate these questions. Using immunohistochemistry, we identified both SIFamide-and tachykinin-related peptide (TRP)-like immunopositive cells in the midgut epithelium of C. magister, as well as in that of Cancer borealis and Cancer productus. In each species, the SIFamide-like labeling was restricted to the anterior portion of the midgut, including the paired anterior midgut caeca, whereas the TRP-like immunoreactivity predominated in the posterior midgut and the posterior midgut caecum. Regardless of location, label or species, the morphology of the immunopositive cells matched that of the putative endocrine cells characterized ultrastructurally by Mykles (Mykles, 1979). Matrix-assisted laser desorption/ ionization-Fourier transform mass spectrometry identified the peptides responsible for the immunoreactivities as GYRKPPFNGSIFamide (Gly 1-SIFamide) and APSGFLGMRamide [Cancer boreatis tachykinin-related peptide Ia (CabTRP Ia)], respectively, both of which are known neuropeptides of Cancer species. Although the function of these midgut-derived peptides remains unknown, we found that both Gly1-SIFamide and CabTRP Ia were released when the midgut was exposed to high-potassium saline. In addition, CabTRP Ia was detectable in the hemolymph of crabs that had been held without food for several days, but not in that of fed animals, paralleling results that were attributed to TRP release from midgut endocrine cells in insects. Thus, one function that midgut-derived CabTRP Ia may play in Cancer species is paracrine/hormonal control of feeding-related behavior, as has been postulated for TRPs released from homologous cells in insects

Species Used for Drug Testing Reveal Different Inhibition Susceptibility for 17beta-Hydroxysteroid Dehydrogenase Type 1

Steroid-related cancers can be treated by inhibitors of steroid metabolism. In searching for new inhibitors of human 17beta-hydroxysteroid dehydrogenase type 1 (17β-HSD 1) for the treatment of breast cancer or endometriosis, novel substances based on 15-substituted estrone were validated. We checked the specificity for different 17β-HSD types and species. Compounds were tested for specificity in vitro not only towards recombinant human 17β-HSD types 1, 2, 4, 5 and 7 but also against 17β-HSD 1 of several other species including marmoset, pig, mouse, and rat. The latter are used in the processes of pharmacophore screening. We present the quantification of inhibitor preferences between human and animal models. Profound differences in the susceptibility to inhibition of steroid conversion among all 17β-HSDs analyzed were observed. Especially, the rodent 17β-HSDs 1 were significantly less sensitive to inhibition compared to the human ortholog, while the most similar inhibition pattern to the human 17β-HSD 1 was obtained with the marmoset enzyme. Molecular docking experiments predicted estrone as the most potent inhibitor. The best performing compound in enzymatic assays was also highly ranked by docking scoring for the human enzyme. However, species-specific prediction of inhibitor performance by molecular docking was not possible. We show that experiments with good candidate compounds would out-select them in the rodent model during preclinical optimization steps. Potentially active human-relevant drugs, therefore, would no longer be further developed. Activity and efficacy screens in heterologous species systems must be evaluated with caution

Testing the “Learning Journey” of MSW Students in a Rural Program

Using a quasi-experimental one-group, pretest–posttest design with non-random convenience sampling, the researchers assessed 61 advanced standing MSW students who matriculated at a rural intermountain Northwest school of social work. Changes in students\u27 knowledge and attitudes toward lesbian, gay, and bisexual (LGB) people were measured using subscales of the LGB-KASH scale and include knowledge of LGB history, religious conflict, internalized affirmation of LGB people and issues, hatred and violence toward LGB people, and knowledge and attitudes toward extension and exclusion of civil rights for LGB people. Completion of required, highly experiential bridge course content regarding LGB history and experience appears to be significant in reducing religious conflict, increasing knowledge of LGB issues, and enhancing internalized affirmation of LGB individuals