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Item Automated Microaneurysms Detection in Retinal Images Using Radon Transform and Supervised Learning: Application to Mass Screening of Diabetic Retinopathy(IEEE, 2021) Tavakoli, Meysam; Mehdizadeh, Alireza; Aghayan, Afshin; Shahri, Reza Pourreza; Ellis, Tim; Dehmeshki, Jamshid; Physics, School of ScienceDetection of red lesions in color retinal images is a critical step to prevent the development of vision loss and blindness associated with diabetic retinopathy (DR). Microaneurysms (MAs) are the most frequently observed and are usually the first lesions to appear as a consequence of DR. Therefore, their detection is necessary for mass screening of DR. However, detecting these lesions is a challenging task because of the low image contrast, and the wide variation of imaging conditions. Recently, the emergence of computer-aided diagnosis systems offers promising approaches to detect these lesions for diagnostic purposes. In this paper we focus on developing unsupervised and supervised techniques to cope intelligently with the MAs detection problem. In the first step, the retinal images are preprocessed to remove background variation in order to achieve a high level of accuracy in the detection. In the main processing step, important landmarks such as the optic nerve head and retinal vessels are detected and masked using the Radon transform (RT) and multi-overlapping windows. Finally, the MAs are detected and numbered by using a combination of RT and a supervised support vector machine classifier. The method was tested on three publicly available datasets and a local database comprising a total of 749 images. Detection performance was evaluated using sensitivity, specificity, and FROC analysis. From the image analysis viewpoint, DR was detected with a sensitivity of 100% and a specificity of 93% on average across all of these databases. Moreover, from lesion-based analysis the proposed approach detected the MAs with sensitivity of 95.7% with an average of 7 false positives per image. These results compare favourably with the best of the published results to date.Item Drosophila homer is required in a small set of neurons including the ellipsoid body for normal ethanol sensitivity and tolerance(Society for Neuroscience, 2007-04-25) Urizar, Nancy L.; Yang, Zhiyong; Edenberg, Howard J.; Davis, Ronald L.; Biochemistry and Molecular Biology, School of MedicineThe molecular mechanisms occurring in the nervous system that underlie behavioral responses to ethanol remain poorly understood. Here, we report that molecular requirements for two of these responses, initial sensitivity and the development of rapid tolerance, comap to the same small set of neurons. We show that null homer mutant flies exhibit both increased sensitivity to the sedative effects of ethanol and failure to develop normal levels of rapid tolerance. Both the sensitivity and rapid tolerance phenotypes of the homer mutants are rescued by the expression of wild-type homer in a subset of neurons that include the ellipsoid body. Thus, some of the molecular- and systems-level requirements for these two behavioral responses to ethanol are identical.Item Offspring of parents with an alcohol use disorder prefer higher levels of brain alcohol exposure in laboratory experiments involving computer-assisted self-infusion of ethanol (CASE)(SpringerLink, 2009-03) Zimmermann, Ulrich S.; Mick, Inge; Laucht, Manfred; Vitvitskiy, Victor; Plawecki, Martin H.; Mann, Karl F.; O’Connor, Sean; Psychiatry, School of MedicineRationale: Acute alcohol effects may differ in social drinkers with a positive family history of alcohol use disorders (FHP) compared to FH negative (FHN) controls. Objectives: To investigate whether FHP subjects prefer higher levels of brain alcohol exposure than do FHN controls. Materials and methods: Twenty-two young healthy nondependent social drinkers participated in two identical sessions of computer-assisted self-infusion of ethanol (CASE); the first for practicing the procedures, the second to test hypotheses. All 12 FHP (four women) and ten FHN (three women) participants received a priming exposure, increasing arterial blood alcohol concentration (aBAC) to 30 mg% at 10 min and decreasing it to 15 mg% at 25 min. A 2-h self-administration period followed, during which only the subjects could increase their aBAC by pressing a button connected to a computer controlling the infusion pump. Infusion rate profiles were calculated instantaneously to increase aBAC by precisely 7.5 mg% within 2.5 min after each button press, followed by a steady descent. Subjects were instructed to produce the same alcohol effects as they would do at a weekend party. Results: The mean and maximum aBAC during the self-administration period and the number of alcohol requests (NOAR) were significantly higher in the FHP vs. FHN participants. Conclusions: This is the first laboratory experiment demonstrating higher alcohol self-administration in FHP compared to FHN subjects. A practice session increases the sensitivity of CASE experiments for detection of subtle differences in human alcohol self-administration.Item Plasma Total-Tau and Neurofilament Light Chain as Diagnostic Biomarkers of Alzheimer's Disease Dementia and Mild Cognitive Impairment in Adults with Down Syndrome(IOS Press, 2021) Petersen, Melissa E.; Rafii, Michael S.; Zhang, Fan; Hall, James; Julovich, David; Ances, Beau M.; Schupf, Nicole; Krinsky-McHale, Sharon J.; Mapstone, Mark; Silverman, Wayne; Lott, Ira; Klunk, William; Head, Elizabeth; Christian, Brad; Foroud, Tatiana; Lai, Florence; Rosas, H. Diana; Zaman, Shahid; Wang, Mei-Cheng; Tycko, Benjamin; Lee, Joseph H.; Handen, Benjamin; Hartley, Sigan; Fortea, Juan; O’Bryant, Sid; Alzheimer’s Biomarker Consortium – Down Syndrome (ABC-DS); Medical and Molecular Genetics, School of MedicineBackground: The need for diagnostic biomarkers of cognitive decline is particularly important among aging adults with Down syndrome (DS). Growing empirical support has identified the utility of plasma derived biomarkers among neurotypical adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD); however, the application of such biomarkers has been limited among the DS population. Objective: This study aimed to investigate the cross-sectional diagnostic performance of plasma neurofilament light chain (Nf-L) and total-tau, individually and in combination among a cohort of DS adults. Methods: Plasma samples were analyzed from n = 305 (n = 225 cognitively stable (CS); n = 44 MCI-DS; n = 36 DS-AD) participants enrolled in the Alzheimer's Biomarker Consortium -Down Syndrome. Results: In distinguishing DS-AD participants from CS, Nf-L alone produced an AUC of 90%, total-tau alone reached 74%, and combined reached an AUC of 86%. When age and gender were included, AUC increased to 93%. Higher values of Nf-L, total-tau, and age were all shown to be associated with increased risk for DS-AD. When distinguishing MCI-DS participants from CS, Nf-L alone produced an AUC of 65%, while total-tau alone reached 56%. A combined model with Nf-L, total-tau, age, and gender produced an AUC of 87%. Both higher values in age and total-tau were found to increase risk for MCI-DS; Nf-L levels were not associated with increased risk for MCI-DS. Conclusion: Advanced assay techniques make total-tau and particularly Nf-L useful biomarkers of both AD pathology and clinical status in DS and have the potential to serve as outcome measures in clinical trials for future disease-modifying drugs.