96 results on '"S. Kedar"'
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2. Muon radiography for exploration of Mars geology
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S. Kedar, H. K. M. Tanaka, C. J. Naudet, C. E. Jones, J. P. Plaut, and F. H. Webb
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Geophysics. Cosmic physics ,QC801-809 - Abstract
Muon radiography is a technique that uses naturally occurring showers of muons (penetrating particles generated by cosmic rays) to image the interior of large-scale geological structures in much the same way as standard X-ray radiography is used to image the interior of smaller objects. Recent developments and application of the technique to terrestrial volcanoes have demonstrated that a low-power, passive muon detector can peer deep into geological structures up to several kilometers in size, and provide crisp density profile images of their interior at ten meter scale resolution. Preliminary estimates of muon production on Mars indicate that the near horizontal Martian muon flux, which could be used for muon radiography, is as strong or stronger than that on Earth, making the technique suitable for exploration of numerous high priority geological targets on Mars. The high spatial resolution of muon radiography also makes the technique particularly suited for the discovery and delineation of Martian caverns, the most likely planetary environment for biological activity. As a passive imaging technique, muon radiography uses the perpetually present background cosmic ray radiation as the energy source for probing the interior of structures from the surface of the planet. The passive nature of the measurements provides an opportunity for a low power and low data rate instrument for planetary exploration that could operate as a scientifically valuable primary or secondary instrument in a variety of settings, with minimal impact on the mission's other instruments and operation.
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- 2013
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3. Development of High-Resolution Melting Curve Analysis for rapid detection of SEC23B gene mutation causing Congenital Dyserythropoietic Anemia type II in Indian population
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Arati Nandan Saptarshi, Rashmi K. Dongerdiye, Tejashree Anil More, and Prabhakar S. Kedar
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Congenital dyserythropoietic anemia ,High-resolution melting curve ,Sanger sequencing ,Pediatrics ,RJ1-570 - Abstract
Abstract Background Congenital dyserythropoietic anemias (CDAs) are a very rare and heterogeneous group of disorders characterized by ineffective erythropoiesis. CDA II is caused by mutations in the SEC23B gene. The most common mutation reported in India is c.1385 A > G, p.Y462C. There is no simple and cost-effective confirmatory diagnostic test available for CDA, and therefore, many patients remain undiagnosed. High-resolution melting curve (HRM) analysis is a polymerase chain reaction (PCR) based technique applied to identify genetic differences and scan nucleic acid sequences. HRM can be used to rapidly screen the common mutation causing CDA II in the Indian population. Thus, we studied the use of High-Resolution Melting Curve Analysis to detect common mutation causing CDA II in the Indian population. Method 11 patients having SEC23B (Y462C) mutation causing CDA II are considered for this study. HRM was used to check the presence of Y462C mutation. To verify the accuracy of the HRM analysis, we compared HRM results with the results of Sanger sequencing. This helped us to confirm the diagnosis. Results We have described the clinical, hematological, and genetic data of eleven patients suffering from CDAII. According to HRM and Sanger sequencing, a homozygous SEC23B (Y462C) mutation was present in all patients, whereas a heterozygous Y462C mutation was present in their parents. Conclusion Our data showed that High-Resolution Melting (HRM) analysis could be used to rapidly screen common SEC23B mutation that causes CDA II in the Indian population.
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- 2023
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4. The InSight HP3 Penetrator (Mole) on Mars: Soil Properties Derived from the Penetration Attempts and Related Activities
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T. Spohn, T. L. Hudson, E. Marteau, M. Golombek, M. Grott, T. Wippermann, K. S. Ali, C. Schmelzbach, S. Kedar, K. Hurst, A. Trebi-Ollennu, V. Ansan, J. Garvin, J. Knollenberg, N. Müller, S. Piqueux, R. Lichtenheldt, C. Krause, C. Fantinati, N. Brinkman, D. Sollberger, P. Delage, C. Vrettos, S. Reershemius, L. Wisniewski, J. Grygorczuk, J. Robertsson, P. Edme, F. Andersson, O. Krömer, P. Lognonné, D. Giardini, S. E. Smrekar, and W. B. Banerdt
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- 2022
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5. SEIS: Insight’s Seismic Experiment for Internal Structure of Mars
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P. Lognonné, W. B. Banerdt, D. Giardini, W. T. Pike, U. Christensen, P. Laudet, S. de Raucourt, P. Zweifel, S. Calcutt, M. Bierwirth, K. J. Hurst, F. Ijpelaan, J. W. Umland, R. Llorca-Cejudo, S. A. Larson, R. F. Garcia, S. Kedar, B. Knapmeyer-Endrun, D. Mimoun, A. Mocquet, M. P. Panning, R. C. Weber, A. Sylvestre-Baron, G. Pont, N. Verdier, L. Kerjean, L. J. Facto, V. Gharakanian, J. E. Feldman, T. L. Hoffman, D. B. Klein, K. Klein, N. P. Onufer, J. Paredes-Garcia, M. P. Petkov, J. R. Willis, S. E. Smrekar, M. Drilleau, T. Gabsi, T. Nebut, O. Robert, S. Tillier, C. Moreau, M. Parise, G. Aveni, S. Ben Charef, Y. Bennour, T. Camus, P. A. Dandonneau, C. Desfoux, B. Lecomte, O. Pot, P. Revuz, D. Mance, J. tenPierick, N. E. Bowles, C. Charalambous, A. K. Delahunty, J. Hurley, R. Irshad, Huafeng Liu, A. G. Mukherjee, I. M. Standley, A. E. Stott, J. Temple, T. Warren, M. Eberhardt, A. Kramer, W. Kühne, E.-P. Miettinen, M. Monecke, C. Aicardi, M. André, J. Baroukh, A. Borrien, A. Bouisset, P. Boutte, K. Brethomé, C. Brysbaert, T. Carlier, M. Deleuze, J. M. Desmarres, D. Dilhan, C. Doucet, D. Faye, N. Faye-Refalo, R. Gonzalez, C. Imbert, C. Larigauderie, E. Locatelli, L. Luno, J.-R. Meyer, F. Mialhe, J. M. Mouret, M. Nonon, Y. Pahn, A. Paillet, P. Pasquier, G. Perez, R. Perez, L. Perrin, B. Pouilloux, A. Rosak, I. Savin de Larclause, J. Sicre, M. Sodki, N. Toulemont, B. Vella, C. Yana, F. Alibay, O. M. Avalos, M. A. Balzer, P. Bhandari, E. Blanco, B. D. Bone, J. C. Bousman, P. Bruneau, F. J. Calef, R. J. Calvet, S. A. D’Agostino, G. de los Santos, R. G. Deen, R. W. Denise, J. Ervin, N. W. Ferraro, H. E. Gengl, F. Grinblat, D. Hernandez, M. Hetzel, M. E. Johnson, L. Khachikyan, J. Y. Lin, S. M. Madzunkov, S. L. Marshall, I. G. Mikellides, E. A. Miller, W. Raff, J. E. Singer, C. M. Sunday, J. F. Villalvazo, M. C. Wallace, D. Banfield, J. A. Rodriguez-Manfredi, C. T. Russell, A. Trebi-Ollennu, J. N. Maki, E. Beucler, M. Böse, C. Bonjour, J. L. Berenguer, S. Ceylan, J. Clinton, V. Conejero, I. Daubar, V. Dehant, P. Delage, F. Euchner, I. Estève, L. Fayon, L. Ferraioli, C. L. Johnson, J. Gagnepain-Beyneix, M. Golombek, A. Khan, T. Kawamura, B. Kenda, P. Labrot, N. Murdoch, C. Pardo, C. Perrin, L. Pou, A. Sauron, D. Savoie, S. Stähler, E. Stutzmann, N. A. Teanby, J. Tromp, M. van Driel, M. Wieczorek, R. Widmer-Schnidrig, and J. Wookey
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- 2019
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6. Antibiotic prescription: An oral physician′s point of view
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Mahendra Patait, N Urvashi, M Rajderkar, S Kedar, Kinjal Shah, and Reeta Patait
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Antibiotics ,dental practice ,microbial disease recommended practice ,Pharmacy and materia medica ,RS1-441 ,Analytical chemistry ,QD71-142 - Abstract
Background: Antibiotics are important in the management and prophylaxis of infections in patients at a risk of experiencing microbial disease. Uses of systemic antibiotics in dentistry are limited since management of acute dental conditions is primarily based upon extraction of teeth or extirpation of the pulp. However, the literature provides evidence of inappropriate prescribing practices by practitioners, due to a number of factors from inadequate knowledge to social factors. Aim: The aim was to assess the therapeutic prescription of antibiotics in the dental office. Materials and Methods: In the current study, 42 faculty members of two dental colleges in the same vicinity were included. A questionnaire was drafted and sent to the dentists to collect data pertaining to the conditions in which antibiotics were prescribed and most commonly prescribed antibiotic. Results: During the study period, 42 faculty members from various departments in the institutes were surveyed, of which 41 questionnaires were completely filled. Amoxicillin was the most commonly prescribed antibiotic followed by other amoxicillin combinations; Metronidazole was most widely prescribed antibiotic for anaerobic infections. Conclusion: We have entered an era where cures may be few due to increasing microbial resistance. The biggest force for change will be if all practicing dentists looked at their prescribing and made it more rational.
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- 2015
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7. Interaction between DNA Polymerase β and BRCA1
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Aya Masaoka, Samuel H. Wilson, Kristine L. Witt, Natalie R. Gassman, Cheryl A. Hobbs, Kenjiro Asagoshi, Julie K. Horton, Padmini S. Kedar, Grace E. Kissling, and Keizo Tano
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DNA Repair ,endocrine system diseases ,DNA polymerase ,Immunofluorescence ,Fluorescent Antibody Technique ,lcsh:Medicine ,DNA polymerase beta ,Biochemistry ,Histones ,chemistry.chemical_compound ,0302 clinical medicine ,Molecular cell biology ,Breast Tumors ,Basic Cancer Research ,DNA Breaks, Double-Stranded ,RNA, Small Interfering ,skin and connective tissue diseases ,lcsh:Science ,Genetics ,0303 health sciences ,Multidisciplinary ,biology ,BRCA1 Protein ,Cancer Risk Factors ,Obstetrics and Gynecology ,Base excision repair ,Cell cycle ,3. Good health ,Nucleic acids ,Histone ,Oncology ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Medicine ,DNA modification ,Research Article ,Alkylating Agents ,DNA repair ,DNA damage ,Immunology ,03 medical and health sciences ,Cell Line, Tumor ,Breast Cancer ,Cancer Genetics ,Animals ,Humans ,Immunoprecipitation ,Protein Interactions ,Immunoassays ,Biology ,DNA Polymerase beta ,030304 developmental biology ,DNA synthesis ,lcsh:R ,Proteins ,Cancers and Neoplasms ,DNA ,Molecular biology ,chemistry ,Cell culture ,biology.protein ,Immunologic Techniques ,lcsh:Q ,Chickens - Abstract
The breast cancer 1 (BRCA1) protein is a tumor suppressor playing roles in DNA repair and cell cycle regulation. Studies of DNA repair functions of BRCA1 have focused on double-strand break (DSB) repair pathways and have recently included base excision repair (BER). However, the function of BRCA1 in BER is not well defined. Here, we examined a BRCA1 role in BER, first in relation to alkylating agent (MMS) treatment of cells and the BER enzyme DNA polymerase β (pol β). MMS treatment of BRCA1 negative human ovarian and chicken DT40 cells revealed hypersensitivity, and the combined gene deletion of BRCA1 and pol β in DT40 cells was consistent with these factors acting in the same repair pathway, possibly BER. Using cell extracts and purified proteins, BRCA1 and pol β were found to interact in immunoprecipitation assays, yet in vivo and in vitro assays for a BER role of BRCA1 were negative. An alternate approach with the human cells of immunofluorescence imaging and laser-induced DNA damage revealed negligible BRCA1 recruitment during the first 60 s after irradiation, the period typical of recruitment of pol β and other BER factors. Instead, 15 min after irradiation, BRCA1 recruitment was strong and there was γ-H2AX co-localization, consistent with DSBs and repair. The rapid recruitment of pol β was similar in BRCA1 positive and negative cells. However, a fraction of pol β initially recruited remained associated with damage sites much longer in BRCA1 positive than negative cells. Interestingly, pol β expression was required for BRCA1 recruitment, suggesting a partnership between these repair factors in DSB repair.
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- 2013
8. Hyperactivation of PARP triggers nonhomologous end-joining in repair-deficient mouse fibroblasts
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Samuel H. Wilson, Julie K. Horton, Natalie R. Gassman, Donna F. Stefanick, and Padmini S. Kedar
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Poly Adenosine Diphosphate Ribose ,DNA End-Joining Repair ,DNA Repair ,DNA polymerase ,DNA damage ,DNA repair ,Poly ADP ribose polymerase ,Poly (ADP-Ribose) Polymerase-1 ,lcsh:Medicine ,DNA-Activated Protein Kinase ,Biochemistry ,Stress Signaling Cascade ,Mice ,Necrosis ,03 medical and health sciences ,Molecular Cell Biology ,Animals ,Signaling in Cellular Processes ,lcsh:Science ,Ku Autoantigen ,Biology ,Cellular Stress Responses ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Cell Death ,DNA synthesis ,biology ,Lasers ,030302 biochemistry & molecular biology ,lcsh:R ,Nuclear Proteins ,Antigens, Nuclear ,DNA ,DNA Repair Pathway ,Base excision repair ,Methyl Methanesulfonate ,Molecular biology ,Signaling Cascades ,DNA-Binding Proteins ,Nucleic acids ,biology.protein ,lcsh:Q ,Poly(ADP-ribose) Polymerases ,DNA Damage ,Research Article ,Signal Transduction - Abstract
Regulation of poly(ADP-ribose) (PAR) synthesis and turnover is critical to determining cell fate after genotoxic stress. Hyperactivation of PAR synthesis by poly(ADP-ribose) polymerase-1 (PARP-1) occurs when cells deficient in DNA repair are exposed to genotoxic agents; however, the function of this hyperactivation has not been adequately explained. Here, we examine PAR synthesis in mouse fibroblasts deficient in the base excision repair enzyme DNA polymerase β (pol β). The extent and duration of PARP-1 activation was measured after exposure to either the DNA alkylating agent, methyl methanesulfonate (MMS), or to low energy laser-induced DNA damage. There was strong DNA damage-induced hyperactivation of PARP-1 in pol β nullcells, but not in wild-type cells. In the case of MMS treatment, PAR synthesis did not lead to cell death in the pol β null cells, but instead resulted in increased PARylation of the nonhomologous end-joining (NHEJ) protein Ku70 and increased association of Ku70 with PARP-1. Inhibition of the NHEJ factor DNA-PK, under conditions of MMS-induced PARP-1 hyperactivation, enhanced necrotic cell death. These data suggest that PARP-1 hyperactivation is a protective mechanism triggering the classical-NHEJ DNA repair pathway when the primary alkylated base damage repair pathway is compromised.
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- 2012
9. HMGB1 is a Co-factor in Mammalian Base Excision Repair
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Samuel H. Wilson, Shin Ichiro Kanno, Akira Yasui, Leesa J. Deterding, Kenjiro Asagoshi, Yuan Liu, Vladimir Poltoratsky, Kenneth B. Tomer, Esther W. Hou, Julie K. Horton, Rajendra Prasad, Padmini S. Kedar, Svetlana N. Khodyreva, and Olga I. Lavrik
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DNA Repair ,DNA repair ,DNA damage ,DNA polymerase ,Flap Endonucleases ,Green Fluorescent Proteins ,DNA polymerase beta ,chemical and pharmacologic phenomena ,Borohydrides ,Article ,Mass Spectrometry ,AP endonuclease ,chemistry.chemical_compound ,Mice ,Animals ,Humans ,Flap endonuclease ,HMGB1 Protein ,Molecular Biology ,DNA Polymerase beta ,biology ,Base excision repair ,Cell Biology ,Molecular biology ,Oxidative Stress ,Biochemistry ,Deoxyribose ,chemistry ,biology.protein ,Phosphorus-Oxygen Lyases ,DNA Damage ,HeLa Cells - Abstract
Summary Deoxyribose phosphate (dRP) removal by DNA polymerase β (Pol β) is a pivotal step in base excision repair (BER). To identify BER cofactors, especially those with dRP lyase activity, we used a Pol β null cell extract and BER intermediate as bait for sodium borohydride crosslinking. Mass spectrometry identified the high-mobility group box 1 protein (HMGB1) as specifically interacting with the BER intermediate. Purified HMGB1 was found to have weak dRP lyase activity and to stimulate AP endonuclease and FEN1 activities on BER substrates. Coimmunoprecipitation experiments revealed interactions of HMGB1 with known BER enzymes, and GFP-tagged HMGB1 was found to accumulate at sites of oxidative DNA damage in living cells. HMGB1 −/− mouse cells were slightly more resistant to MMS than wild-type cells, probably due to the production of fewer strand-break BER intermediates. The results suggest HMGB1 is a BER cofactor capable of modulating BER capacity in cells.
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- 2007
10. Congenital methemoglobinemia caused by Hb-MRatnagiri (-63CAT?TAT, His?Tyr) in an Indian family.
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Prabhakar S. Kedar, Anita H. Nadkarni, Supriya Phanasgoankar, Manisha Madkaikar, Kanjaksha Ghosh, Ajit C. Gorakshakar, Roshan B. Colah, and Dipika Mohanty
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- 2005
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11. Virtual personal assistance.
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K Aditya, G Biswadeep, S Kedar, and S Sundar
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- 2017
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12. Hyperactivation of PARP triggers nonhomologous end-joining in repair-deficient mouse fibroblasts.
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Natalie R Gassman, Donna F Stefanick, Padmini S Kedar, Julie K Horton, and Samuel H Wilson
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Medicine ,Science - Abstract
Regulation of poly(ADP-ribose) (PAR) synthesis and turnover is critical to determining cell fate after genotoxic stress. Hyperactivation of PAR synthesis by poly(ADP-ribose) polymerase-1 (PARP-1) occurs when cells deficient in DNA repair are exposed to genotoxic agents; however, the function of this hyperactivation has not been adequately explained. Here, we examine PAR synthesis in mouse fibroblasts deficient in the base excision repair enzyme DNA polymerase β (pol β). The extent and duration of PARP-1 activation was measured after exposure to either the DNA alkylating agent, methyl methanesulfonate (MMS), or to low energy laser-induced DNA damage. There was strong DNA damage-induced hyperactivation of PARP-1 in pol β nullcells, but not in wild-type cells. In the case of MMS treatment, PAR synthesis did not lead to cell death in the pol β null cells, but instead resulted in increased PARylation of the nonhomologous end-joining (NHEJ) protein Ku70 and increased association of Ku70 with PARP-1. Inhibition of the NHEJ factor DNA-PK, under conditions of MMS-induced PARP-1 hyperactivation, enhanced necrotic cell death. These data suggest that PARP-1 hyperactivation is a protective mechanism triggering the classical-NHEJ DNA repair pathway when the primary alkylated base damage repair pathway is compromised.
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- 2012
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13. DNA polymerases beta and lambda mediate overlapping and independent roles in base excision repair in mouse embryonic fibroblasts.
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Elena K Braithwaite, Padmini S Kedar, Deborah J Stumpo, Barbara Bertocci, Jonathan H Freedman, Leona D Samson, and Samuel H Wilson
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Medicine ,Science - Abstract
Base excision repair (BER) is a DNA repair pathway designed to correct small base lesions in genomic DNA. While DNA polymerase beta (pol beta) is known to be the main polymerase in the BER pathway, various studies have implicated other DNA polymerases in back-up roles. One such polymerase, DNA polymerase lambda (pol lambda), was shown to be important in BER of oxidative DNA damage. To further explore roles of the X-family DNA polymerases lambda and beta in BER, we prepared a mouse embryonic fibroblast cell line with deletions in the genes for both pol beta and pol lambda. Neutral red viability assays demonstrated that pol lambda and pol beta double null cells were hypersensitive to alkylating and oxidizing DNA damaging agents. In vitro BER assays revealed a modest contribution of pol lambda to single-nucleotide BER of base lesions. Additionally, using co-immunoprecipitation experiments with purified enzymes and whole cell extracts, we found that both pol lambda and pol beta interact with the upstream DNA glycosylases for repair of alkylated and oxidized DNA bases. Such interactions could be important in coordinating roles of these polymerases during BER.
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- 2010
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14. AI-based differential diagnosis of dementia etiologies on multimodal data.
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Xue C, Kowshik SS, Lteif D, Puducheri S, Jasodanand VH, Zhou OT, Walia AS, Guney OB, Zhang JD, Pham ST, Kaliaev A, Andreu-Arasa VC, Dwyer BC, Farris CW, Hao H, Kedar S, Mian AZ, Murman DL, O'Shea SA, Paul AB, Rohatgi S, Saint-Hilaire MH, Sartor EA, Setty BN, Small JE, Swaminathan A, Taraschenko O, Yuan J, Zhou Y, Zhu S, Karjadi C, Alvin Ang TF, Bargal SA, Plummer BA, Poston KL, Ahangaran M, Au R, and Kolachalama VB
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- Humans, Diagnosis, Differential, Female, Male, Aged, Cognitive Dysfunction diagnosis, Cognitive Dysfunction diagnostic imaging, Neuroimaging, Aged, 80 and over, ROC Curve, Neuropsychological Tests, Middle Aged, Dementia diagnosis, Dementia etiology, Artificial Intelligence
- Abstract
Differential diagnosis of dementia remains a challenge in neurology due to symptom overlap across etiologies, yet it is crucial for formulating early, personalized management strategies. Here, we present an artificial intelligence (AI) model that harnesses a broad array of data, including demographics, individual and family medical history, medication use, neuropsychological assessments, functional evaluations and multimodal neuroimaging, to identify the etiologies contributing to dementia in individuals. The study, drawing on 51,269 participants across 9 independent, geographically diverse datasets, facilitated the identification of 10 distinct dementia etiologies. It aligns diagnoses with similar management strategies, ensuring robust predictions even with incomplete data. Our model achieved a microaveraged area under the receiver operating characteristic curve (AUROC) of 0.94 in classifying individuals with normal cognition, mild cognitive impairment and dementia. Also, the microaveraged AUROC was 0.96 in differentiating the dementia etiologies. Our model demonstrated proficiency in addressing mixed dementia cases, with a mean AUROC of 0.78 for two co-occurring pathologies. In a randomly selected subset of 100 cases, the AUROC of neurologist assessments augmented by our AI model exceeded neurologist-only evaluations by 26.25%. Furthermore, our model predictions aligned with biomarker evidence and its associations with different proteinopathies were substantiated through postmortem findings. Our framework has the potential to be integrated as a screening tool for dementia in clinical settings and drug trials. Further prospective studies are needed to confirm its ability to improve patient care., (© 2024. The Author(s).)
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- 2024
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15. The Increasing Burden of Emergency Department and Inpatient Consultations for "Papilledema".
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Ray HJ, Okrent Smolar AL, Dattilo M, Bouthour W, Berman G, Peragallo JH, Kedar S, Pendley AM, Greene JG, Keadey MT, Wright DW, Bruce BB, Newman NJ, and Biousse V
- Abstract
Background: Increasing incidence of idiopathic intracranial hypertension (IIH), overreported radiologic signs of intracranial hypertension, difficult access to outpatient neuro-ophthalmology services, poor insurance coverage, and medicolegal concerns have lowered the threshold for emergency department (ED) visits for "papilledema." Our objective was to examine referral patterns and outcomes of neuro-ophthalmology ED and inpatient consultations for concern for papilledema., Methods: At one university-based quaternary care center, all adults referred for "papilledema" over one year underwent a standardized ED "papilledema protocol." We collected patient demographics, final diagnoses, and referral patterns., Results: Over 1 year, 153 consecutive patients were referred for concern for papilledema. After papilledema protocol, 89 of 153 patients (58%) had bilateral optic disc edema, among whom 89% (79/89) had papilledema (intracranial hypertension). Of the 38 of 153 (25%) consultations for suspected disorder of intracranial pressure without previous fundus examination (Group 1), 74% (28/38) did not have optic disc edema, 21% (8/38) had papilledema, and 5% (2/38) had other causes of bilateral disc edema. Of the 89 of 153 (58%) consultations for presumed papilledema seen on fundus examination (Group 2), 58% (66/89) had confirmed papilledema, 17% (15/89) had pseudopapilledema, and 9% (8/89) had other causes of bilateral optic disc edema. Of the 26 of 153 (17%) patients with known IIH (Group 3), 5 had papilledema and 4 required urgent intervention. The most common diagnosis was IIH (58/79). Compared with IIH, patients with secondary causes of intracranial hypertension were older (P = 0.002), men (P < 0.001), not obese (P < 0.001), and more likely to have neurologic symptoms (P = 0.002)., Conclusion: Inpatient and ED consultations for "papilledema" are increasing. Of the 153 ED and inpatient neuro-ophthalmology consultations seen for "papilledema" over 1 year, one-third of patients with optic disc edema of unknown cause before presentation to our ED had new vision- or life-threatening disease, supporting the need for prompt identification and evaluation of optic disc edema in the ED. In the face of limited access to neuro-ophthalmologists, this study supports the need for emergency department access to expert eye-care evaluation or ocular fundus camera for prompt identification of optic disc edema and standardized evaluation for neurologic emergencies., Competing Interests: V. Biousse is a consultant for GenSight Biologics and Neurophoenix and receives research support from GenSight Biologics. N. J. Newman is a consultant for GenSight Biologics, Chiesi, Stoke, Neurophth, Avidity and Neurophoenix; receives research support from GenSight Biologics and Santhera/Chiesi; is a participant in educational webinars sponsored by WebMD-Global Medscape and First Class. The remaining authors report no conflicts of interest., (Copyright © 2024 North American Neuro-Ophthalmology Society.)
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- 2024
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16. Interpretation of the Visual Field in Neuro-ophthalmic Disorders.
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Banc A and Kedar S
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- Humans, Artificial Intelligence, Activities of Daily Living, Quality of Life, Visual Field Tests methods, Visual Fields, Optic Nerve Diseases diagnosis
- Abstract
Purpose of Review: In this review, we will describe current methods for visual field testing in neuro-ophthalmic clinical practice and research, develop terminology that accurately describes patterns of field deficits, and discuss recent advances such as augmented or virtual reality-based perimetry and the use of artificial intelligence in visual field interpretation., Recent Findings: New testing strategies that reduce testing times, improve patient comfort, and increase sensitivity for detecting small central or paracentral scotomas have been developed for static automated perimetry. Various forms of machine learning-based tools such as archetypal analysis are being tested to quantitatively depict and monitor visual field abnormalities in optic neuropathies. Studies show that the combined use of optical coherence tomography and standard automated perimetry to determine the structure-function relationship improves clinical care in neuro-ophthalmic disorders. Visual field assessment must be performed in all patients with neuro-ophthalmic disorders affecting the afferent visual pathway. Quantitative visual field analysis using standard automated perimetry is critical in initial diagnosis, monitoring disease progression, and guidance of therapeutic plans. Visual field defects can adversely impact activities of daily living such as reading, navigation, and driving and thus impact quality of life. Visual field testing can direct appropriate occupational low vision rehabilitation in affected individuals., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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17. A multi-centre case series of patients with coexistent intracranial hypertension and malignant arterial hypertension.
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Sattarova V, Flowers A, Gospe SM 3rd, Chen JJ, Stunkel L, Bhatti MT, Dattilo M, Kedar S, Biousse V, McClelland CM, and Lee MS
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- Humans, Female, Adult, Male, Retrospective Studies, Vision Disorders diagnosis, Vision Disorders etiology, Intracranial Pressure physiology, Papilledema diagnosis, Papilledema etiology, Intracranial Hypertension complications, Intracranial Hypertension diagnosis, Hypertension complications, Hypertension, Malignant complications, Hypertension, Malignant diagnosis, Pseudotumor Cerebri complications
- Abstract
Objective: To describe the clinical characteristics, outcomes, and management of a large cohort of patients with concomitant malignant arterial hypertension and intracranial hypertension., Methods: Design: Retrospective case series., Subjects: Patients aged ≥ 18 years with bilateral optic disc oedema (ODE), malignant arterial hypertension and intracranial hypertension at five academic institutions. Patient demographics, clinical characteristics, diagnostic studies, and management were collected., Results: Nineteen patients (58% female, 63% Black) were included. Median age was 35 years; body mass index (BMI) was 30 kg/m
2 . Fourteen (74%) patients had pre-existing hypertension. The most common presenting symptom was blurred vision (89%). Median blood pressure (BP) was 220 mmHg systolic (IQR 199-231.5 mmHg) and 130 mmHg diastolic (IQR 116-136 mmHg) mmHg), and median lumbar puncture opening pressure was 36.5 cmH2 O. All patients received treatment for arterial hypertension. Seventeen (89%) patients received medical treatment for raised intracranial pressure, while six (30%) patients underwent a surgical intervention. There was significant improvement in ODE, peripapillary retinal nerve fibre layer thickness, and visual field in the worst eye (p < 0.05). Considering the worst eye, 9 (47%) presented with acuity ≥ 20/25, while 5 (26%) presented with ≤ 20/200. Overall, 7 patients maintained ≥ 20/25 acuity or better, 6 demonstrated improvement, and 5 demonstrated worsening., Conclusions: Papilloedema and malignant arterial hypertension can occur simultaneously with potentially greater risk for severe visual loss. Clinicians should consider a workup for papilloedema among patients with significantly elevated blood pressure and bilateral optic disc oedema., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)- Published
- 2024
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18. Neuro-ophthalmology Emergency Department and Inpatient Consultations at a Large Academic Referral Center.
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Okrent Smolar AL, Ray HJ, Dattilo M, Bouthour W, Berman G, Peragallo JH, Kedar S, Pendley AM, Greene JG, Keadey MT, Wright DW, Bruce BB, Newman NJ, and Biousse V
- Subjects
- Adult, Humans, Inpatients, Emergency Service, Hospital, Referral and Consultation, Ophthalmology, Neurology
- Abstract
Purpose: Prompt neuro-ophthalmology consultation prevents diagnostic errors and improves patient outcomes. The scarcity of neuro-ophthalmologists means that the increasing outpatient demand cannot be met, prompting many emergency department (ED) referrals by non-neuro-ophthalmologists. We describe our quaternary care institution's ED and inpatient neuro-ophthalmology consultation patterns and patient outcomes., Design: Prospective observational study., Participants: Consecutive neuro-ophthalmology ED and inpatient consultation requests over 1 year., Methods: We collected patient demographics, distance traveled, insurance status, referring provider details, consultation question, final diagnosis, complexity of consultation, time of consultation, and need for outpatient follow-up., Main Outcome Measures: Consultation patterns and diagnoses, complexity, and follow-up., Results: Of 494 consecutive adult ED and inpatient neuro-ophthalmology consultations requested over 1 year, 241 of 494 consultations (49%) occurred at night or during weekends. Of ED consultations (322 of 494 [65%]), 127 of 322 consultations (39%) occurred during weekdays, 126 of 322 consultations (39%) occurred on weeknights, and 69 of 322 consultations (22%) occurred on weekends or holidays. Of 322 ED consultations, 225 of 322 consultations (70%) were patients who initially sought treatment in the ED with a neuro-ophthalmic chief symptom. Of the 196 patients sent to the ED by a health care professional, 148 patients (148/196 [76%]) were referred by eye care specialists (74 optometrists and 74 ophthalmologists). The most common ED referral questions were for papilledema (75 of 322 [23%]) and vision loss (72 of 322 [22%]). A total of 219 of 322 patients (68%) received a final active neuro-ophthalmic diagnosis, 222 of 322 patients (69%) were cases of high or very high complexity, and 143 of 322 patients (44%) required admission. Inpatient consultations (n = 172) were requested most frequently by hospitalists, including neurologists (71 of 172 [41%]) and oncologists (20 of 172 [12%]) for vision loss (43 of 172 [25%]) and eye movement disorders (36 of 172 [21%]) and by neurosurgeons (58 of 172 [33%]) for examination for mass or a preoperative evaluation (19 of 172 [11%]). An active neuro-ophthalmic diagnosis was confirmed in 67% of patients (116 of 172). Outpatient neuro-ophthalmology follow-up was required for 291 of 494 patients (59%)., Conclusions: Neuro-ophthalmology consultations are critical to the diagnosis and management in the hospital setting. In the face of a critical shortage of neuro-ophthalmologists, this study highlights the need for technological and diagnostic aids for greater outpatient access., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
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- 2023
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19. Analysis of Retinal Structure and Electrophysiological Function in Visual Snow Syndrome: An Exploratory Case Series.
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Zaroban NJ, Kedar S, Anderson D, and Vuppala AD
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- Humans, Adult, Young Adult, Retrospective Studies, Visual Acuity, Vision Disorders diagnosis, Electroretinography methods, Tomography, Optical Coherence, Evoked Potentials, Visual, Retina pathology
- Abstract
Background: Visual snow (VS) is a rare but distressing phenomenon of persistent granular or pixelated visual distortions that may occur in isolation or as a component of visual snow syndrome (VSS). The current understanding of VS pathogenesis, including the role of retinal involvement structurally and functionally, is limited. The objective of this study is to investigate retinal structural and electrophysiological abnormalities in VS., Methods: This retrospective case series included 8 subjects (7 with VSS and 1 with isolated VS). Patients with other ocular and neurologic diseases were excluded. Data were assessed from automated perimetry, optical coherence tomography (OCT), visual evoked potential (VEP), and full-field electroretinography (ffERG) testing. The VEP and ffERG data of visual snow subjects were compared with age- and sex-matched control subjects for statistical significance., Results: The mean age of the cohort was 29.4 years (SD = ±5.3) with 50% gender split. The mean age of VS onset was 24.2 years (SD = ±3.8). All subjects had normal visual acuity, color vision, brain MRI, automated perimetry, OCT parameters (peripapillary retinal nerve fiber layer and macular ganglion cell layer thickness), and P100 and N135 wave pattern on VEP. Compared with controls, VS subjects had a greater mean b-wave amplitude in response to light-adapted 3.0 stimuli ( t test; P = 0.035 right eye and P = 0.072 left eye), greater mean light-adapted 3.0 flicker amplitude ( t test; P = 0.028 right eye P = 0.166 left eye) and greater b-wave amplitude in response to dark-adapted 10.0 stimuli ( t test; P = 0.102 right eye; P = 0.017 left eye) on ERG., Conclusions: Patients with VS and VSS have normal retinal structure, but abnormal electrophysiology compared with control subjects. The increased b-wave and flicker amplitudes observed with ffERG suggest increased responsiveness of the rod and cone photoreceptors and may contribute to VS pathophysiology., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by North American Neuro-Ophthalmology Society.)
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- 2023
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20. NANOS Illustrated Curriculum for Neuro-Ophthalmology.
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Lombardo NT, Seay MD, Hull BE, Digre KB, and Kedar S
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- Humans, Curriculum, Ophthalmology education, Neurology education
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- 2023
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21. Presumptive Idiopathic Intracranial Hypertension Based on Neuroimaging Findings: A Referral Pattern Study.
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Aung AB, Chen BS, Wicks J, Bruce BB, Meyer BI, Dattilo M, Kedar S, Saindane A, Newman NJ, and Biousse V
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- Humans, Lipopolysaccharides, Obesity complications, Neuroimaging, Cerebrospinal Fluid Leak diagnosis, Retrospective Studies, Pseudotumor Cerebri complications, Pseudotumor Cerebri diagnosis, Pseudotumor Cerebri epidemiology, Intracranial Hypertension diagnosis, Papilledema diagnosis, Papilledema epidemiology, Papilledema etiology
- Abstract
Background: Radiologic findings of intracranial hypertension (RAD-IH) are common in idiopathic intracranial hypertension (IIH) patients. Paralleling the increasing rates of obesity, the burden of IIH is growing. Urgent neuro-ophthalmology consultations for possible IIH in patients with incidentally detected RAD-IH are increasing, with many patients receiving unnecessary lumbar punctures (LPs) and treatments. This retrospective observational study aimed to determine the prevalence of neuro-ophthalmology consultations for RAD-IH, rate of funduscopic examination by referring providers, prevalence of papilledema, outcomes after neuro-ophthalmic evaluation, and rates of misdiagnosis., Methods: Records of 1,262 consecutive new patients seen in one neuro-ophthalmology clinic from January 2019 to January 2020 were reviewed. We identified patients who were: 1) referred with concern for IIH because of findings of RAD-IH; 2) referred for "papilledema"; 3) referred with a diagnosis of IIH; and 4) referred for spontaneous cranial cerebrospinal fluid (CSF) leaks. In addition to basic demographic profiles for all groups, detailed information was collected for patients referred solely for RAD-IH, including referral patterns, prior history of IIH, previous LPs, prior medical or surgical treatment(s), risk factors for increased intracranial pressure (ICP), presenting symptoms, radiologic features observed on neuroimaging, and final disposition. When available, the neuroimaging was reviewed by an expert neuroradiologist., Results: Of 1,262 consecutive new patients, 66 (5%) were referred specifically for RAD-IH; most referrals came from neurologists (58%); 8/66 (12%) patients had papilledema; 16/66 (24%) patients had prior LP and 13/66 (20%) were already treated based on MRI findings; and 22/66 (33%) patients had ≤2 RAD-IH. Only 34/66 (52%) of patients referred for RAD-IH had prior funduscopic examinations. We confirmed papilledema in 26/82 (32%) patients referred for "papilledema." Only 29/83 (35%) patients referred with a diagnosis of IIH had active papilledema, and 3/16 (19%) patients with spontaneous CSF leaks had papilledema. In total, 247/1,262 (20%) new patients were referred to our clinic over 1 year with concern for IIH, among whom only 66 (27%) were confirmed to have active IIH with papilledema., Conclusions: One in 5 new patient referrals seen in our neuro-ophthalmology clinic were referred because of concern for increased ICP, but only 1/4 had active papilledema. Most patients referred for isolated RAD-IH do not have papilledema, many having undergone unnecessary LPs and treatments. The burden of these "rule-out IIH" consultations is overwhelming and will only continue to increase with the concurrent rise of obesity and IIH, straining the already limited neuro-ophthalmologic resources available in the US., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by North American Neuro-Ophthalmology Society.)
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- 2023
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22. Neurology education in the era of artificial intelligence.
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Kedar S and Khazanchi D
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- Humans, Machine Learning, Artificial Intelligence, Neurology
- Abstract
Purpose of Review: The practice of neurology is undergoing a paradigm shift because of advances in the field of data science, artificial intelligence, and machine learning. To ensure a smooth transition, physicians must have the knowledge and competence to apply these technologies in clinical practice. In this review, we describe physician perception and preparedness, as well as current state for clinical applications of artificial intelligence and machine learning in neurology., Recent Findings: Digital health including artificial intelligence-based/machine learning-based technology has made significant inroads into various aspects of healthcare including neurological care. Surveys of physicians and healthcare stakeholders suggests an overall positive perception about the benefits of artificial intelligence/machine learning in clinical practice. This positive perception is tempered by concerns for lack of knowledge and limited opportunities to build competence in artificial intelligence/machine learning technology. Literature about neurologist's perception and preparedness towards artificial intelligence/machine learning-based technology is scant. There are very few opportunities for physicians particularly neurologists to learn about artificial intelligence/machine learning-based technology., Summary: Neurologists have not been surveyed about their perception and preparedness to adopt artificial intelligence/machine learning-based technology in clinical practice. We propose development of a practical artificial intelligence/machine learning curriculum to enhance neurologists' competence in these newer technologies., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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23. Authors' reply, re: A response to Zhou et al. regarding thiamine supplementation in altered mental status.
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Zhou DJ and Kedar S
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- Humans, Dietary Supplements, Thiamine therapeutic use, Mental Disorders
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- 2023
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24. Ocular Optical Coherence Tomography in the Evaluation of Sellar and Parasellar Masses: A Review.
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Banc A, Biousse V, Newman NJ, and Kedar S
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- Humans, Retinal Ganglion Cells, Optic Chiasm diagnostic imaging, Optic Nerve, Vision Disorders, Tomography, Optical Coherence methods, Optic Nerve Diseases diagnostic imaging
- Abstract
Compression of the anterior visual pathways by sellar and parasellar masses can produce irreversible and devastating visual loss. Optical coherence tomography (OCT) is a noninvasive high-resolution ocular imaging modality routinely used in ophthalmology clinics for qualitative and quantitative analysis of optic nerve and retinal structures, including the retinal ganglion cells. By demonstrating structural loss of the retinal ganglion cells whose axons form the optic nerve before decussating in the optic chiasm, OCT imaging of the optic nerve and retina provides an excellent tool for detection and monitoring of compressive optic neuropathies and chiasmopathies due to sellar and parasellar masses. Recent studies have highlighted the role of OCT imaging in the diagnosis, follow-up, and prognostication of the visual outcomes in patients with chiasmal compression. OCT parameters of optic nerve and macular scans such as peripapillary retinal nerve fiber layer thickness and macular ganglion cell thickness are correlated with the degree of visual loss; additionally, OCT can detect clinically significant optic nerve and chiasmal compression before visual field loss is revealed on automated perimetry. Preoperative values of OCT optic nerve and macular parameters represent a prognostic tool for postoperative visual outcome. This review provides a qualitative analysis of the current applications of OCT imaging of the retina and optic nerve in patients with anterior visual pathway compression from sellar and parasellar masses. We also review the role of new technologies such as OCT-angiography, which could improve the prognostic ability of OCT to predict postoperative visual function., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)
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- 2023
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25. In Situ Regolith Seismic Velocity Measurement at the InSight Landing Site on Mars.
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Brinkman N, Schmelzbach C, Sollberger D, Pierick JT, Edme P, Haag T, Kedar S, Hudson T, Andersson F, van Driel M, Stähler S, Nicollier T, Robertsson J, Giardini D, Spohn T, Krause C, Grott M, Knollenberg J, Hurst K, Rochas L, Vallade J, Blandin S, Lognonné P, Pike WT, and Banerdt WB
- Abstract
Interior exploration using Seismic Investigations, Geodesy and Heat Transport's (InSight) seismometer package Seismic Experiment for Interior Structure (SEIS) was placed on the surface of Mars at about 1.2 m distance from the thermal properties instrument Heat flow and Physical Properties Package (HP
3 ) that includes a self-hammering probe. Recording the hammering noise with SEIS provided a unique opportunity to estimate the seismic wave velocities of the shallow regolith at the landing site. However, the value of studying the seismic signals of the hammering was only realized after critical hardware decisions were already taken. Furthermore, the design and nominal operation of both SEIS and HP3 are nonideal for such high-resolution seismic measurements. Therefore, a series of adaptations had to be implemented to operate the self-hammering probe as a controlled seismic source and SEIS as a high-frequency seismic receiver including the design of a high-precision timing and an innovative high-frequency sampling workflow. By interpreting the first-arriving seismic waves as a P-wave and identifying first-arriving S-waves by polarization analysis, we determined effective P- and S-wave velocities of v P = 11 9 - 21 + 45 m/s and v S = 6 3 - 7 + 11 m/s, respectively, from around 2,000 hammer stroke recordings. These velocities likely represent bulk estimates for the uppermost several 10s of cm of regolith. An analysis of the P-wave incidence angles provided an independent vP / vS ratio estimate of 1.8 4 - 0.35 + 0.89 that compares well with the traveltime based estimate of 1.8 6 - 0.25 + 0.42 . The low seismic velocities are consistent with those observed for low-density unconsolidated sands and are in agreement with estimates obtained by other methods., (© 2022. The Authors.)- Published
- 2022
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26. Multimodal deep learning for Alzheimer's disease dementia assessment.
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Qiu S, Miller MI, Joshi PS, Lee JC, Xue C, Ni Y, Wang Y, De Anda-Duran I, Hwang PH, Cramer JA, Dwyer BC, Hao H, Kaku MC, Kedar S, Lee PH, Mian AZ, Murman DL, O'Shea S, Paul AB, Saint-Hilaire MH, Alton Sartor E, Saxena AR, Shih LC, Small JE, Smith MJ, Swaminathan A, Takahashi CE, Taraschenko O, You H, Yuan J, Zhou Y, Zhu S, Alosco ML, Mez J, Stein TD, Poston KL, Au R, and Kolachalama VB
- Subjects
- Disease Progression, Humans, Neuroimaging methods, Alzheimer Disease diagnostic imaging, Alzheimer Disease psychology, Cognitive Dysfunction diagnosis, Cognitive Dysfunction pathology, Deep Learning
- Abstract
Worldwide, there are nearly 10 million new cases of dementia annually, of which Alzheimer's disease (AD) is the most common. New measures are needed to improve the diagnosis of individuals with cognitive impairment due to various etiologies. Here, we report a deep learning framework that accomplishes multiple diagnostic steps in successive fashion to identify persons with normal cognition (NC), mild cognitive impairment (MCI), AD, and non-AD dementias (nADD). We demonstrate a range of models capable of accepting flexible combinations of routinely collected clinical information, including demographics, medical history, neuropsychological testing, neuroimaging, and functional assessments. We then show that these frameworks compare favorably with the diagnostic accuracy of practicing neurologists and neuroradiologists. Lastly, we apply interpretability methods in computer vision to show that disease-specific patterns detected by our models track distinct patterns of degenerative changes throughout the brain and correspond closely with the presence of neuropathological lesions on autopsy. Our work demonstrates methodologies for validating computational predictions with established standards of medical diagnosis., (© 2022. The Author(s).)
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- 2022
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27. What do patients with glaucoma see: a novel iPad app to improve glaucoma patient awareness of visual field loss.
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Gagrani M, Ndulue J, Anderson D, Kedar S, Gulati V, Shepherd J, High R, Smith L, Fowler Z, Khazanchi D, Nawrot M, and Ghate D
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- Aged, Humans, Middle Aged, Retina, Vision Disorders diagnosis, Visual Field Tests methods, Visual Fields, Glaucoma diagnosis, Mobile Applications
- Abstract
Purpose: Glaucoma patients with peripheral vision loss have in the past subjectively described their field loss as 'blurred' or 'no vision compromise'. We developed an iPad app for patients to self-characterise perception within areas of glaucomatous visual field loss., Methods: Twelve glaucoma patients with visual acuity ≥20/40 in each eye, stable and reliable Humphrey Visual Field (HVF) over 2 years were enrolled. An iPad app (held at 33 cm) allowed subjects to modify 'blur' or 'dimness' to match their perception of a 2×2 m wall-mounted poster at 1 m distance. Subjects fixated at the centre of the poster (spanning 45° of field from centre). The output was degree of blur/dim: normal, mild and severe noted on the iPad image at the 54 retinal loci tested by the HVF 24-2 and was compared to threshold sensitivity values at these loci. Monocular (Right eye (OD), left eye (OS)) HVF responses were used to calculate an integrated binocular (OU) visual field index (VFI). All three data sets were analysed separately., Results: 36 HVF and iPad responses from 12 subjects (mean age 71±8.2y) were analysed. The mean VFI was 77% OD, 76% OS, 83% OU. The most common iPad response reported was normal followed by blur. No subject reported dim response. The mean HVF sensitivity threshold was significantly associated with the iPad response at the corresponding retinal loci (For OD, OS and OU, respectively (dB): normal: 23, 25, 27; mild blur: 18, 16, 22; severe blur: 9, 9, 11). On receiver operative characteristic (ROC) curve analysis, the HVF retinal sensitivity cut-off at which subjects reported blur was 23.4 OD, 23 OS and 23.3 OU (dB)., Conclusions: Glaucoma subjects self-pictorialised their field defects as blur; never dim or black. Our innovation allows translation of HVF data to quantitatively characterise visual perception in patients with glaucomatous field defects., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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28. Thiamine supplementation in hospitalized patients with altered mental status: does it help?
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Zhou DJ, Samson KK, Joseph N, Fahad I, Purbaugh MV, Villafuerte-Trisolini BJ, Kodali N, Guda P, Grogan W, Mukherjee U, and Kedar S
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- Adult, Dietary Supplements, Humans, Length of Stay, Retrospective Studies, Hospitalization, Thiamine therapeutic use
- Abstract
Objective: To describe thiamine-prescribing patterns and to study the association of thiamine supplementation with clinical outcomes in hospitalized patients with altered mental status (AMS)., Methods: We conducted a retrospective cohort study of all adult hospitalized patients with AMS with index admission in calendar year 2017. We studied the association of a) supplemental thiamine and b) timing of thiamine relative to glucose, with hospital outcomes - length of stay (LOS), 90-day readmission rates, and mortality rates - using linear, logistic, and extended Cox models, respectively. We also modeled association of supplemental thiamine on time to resolution of AMS using extended Cox models in patients admitted with AMS., Results: Of 985 patients, 178 (18%) received thiamine, including 123 (12.5%) who received thiamine before, with, or without glucose (thiamine first). We identified 365 (37%) patients who received intravenous glucose before or without thiamine (glucose first). We found that patients who received glucose first had longer LOS and higher rate of in-hospital deaths compared to those who did not. Patients who received thiamine supplementation had longer LOS compared to those who did not. There were no significant differences in other hospital outcomes or AMS resolution by discharge compared to their respective reference groups., Conclusion: Although thiamine supplementation was not associated with better hospital or cognitive outcomes, we do not have enough evidence to suggest a change in current practice. Thiamine must be administered prior to glucose in hospitalized patients with AMS.
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- 2022
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29. Effects of Acute Intracranial Pressure Changes on Optic Nerve Head Morphology in Humans and Pig Model.
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Kedar S, Tong J, Bader J, Havens S, Fan S, Thorell W, Nelson C, Gu L, High R, Gulati V, and Ghate D
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- Animals, Humans, Intracranial Pressure physiology, Intraocular Pressure, Swine, Tomography, Optical Coherence, Tonometry, Ocular, Optic Disk
- Abstract
Purpose: The lamina cribrosa (LC) is a layer of fenestrated connective tissue tethered to the posterior sclera across the scleral canal in the optic nerve head (ONH). It is located at the interface of intracranial and intraocular compartments and is exposed to intraocular pressure (IOP) anteriorly and intracranial pressure (ICP) or Cerebrospinal fluid (CSF) pressure (CSFP) posteriorly. We hypothesize that the pressure difference across LC will determine LC position and meridional diameter of scleral canal (also called Bruch's membrane opening diameter; BMOD)., Methods: We enrolled 19 human subjects undergoing a medically necessary lumbar puncture (LP) to lower CSFP and 6 anesthetized pigs, whose ICP was increased in 5 mm Hg increments using a lumbar catheter. We imaged ONH using optical coherence tomography and measured IOP and CSFP/ICP at baseline and after each intervention. Radial tomographic ONH scans were analyzed by two independent graders using ImageJ, an open-source software. The following ONH morphological parameters were obtained: BMOD, anterior LC depth and retinal thickness. We modeled effects of acute CSFP/ICP changes on ONH morphological parameters using ANOVA (human study) and generalized linear model (pig study)., Results: For 19 human subjects, CSFP ranged from 5 to 42 mm Hg before LP and 2 to 19.4 mm Hg after LP. For the six pigs, baseline ICP ranged from 1.5 to 9 mm Hg and maximum stable ICP ranged from 18 to 40 mm Hg. Our models showed that acute CSFP/ICP changes had no significant effect on ONH morphological parameters in both humans and pigs., Conclusion: We conclude that ONH does not show measurable morphological changes in response to acute changes of CSFP/ICP. Proposed mechanisms include compensatory and opposing changes in IOP and CSFP/ICP and nonlinear or nonmonotonic effects of IOP and CSFP/ICP across LC.
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- 2022
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30. Limited-Montage EEG as a Tool for the Detection of Nonconvulsive Seizures.
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Swingle N, Vuppala A, Datta P, Pedavally S, Swaminathan A, Kedar S, Samson KK, Wichman CS, Myers J, and Taraschenko O
- Subjects
- Electrodes, Humans, Infant, Newborn, Electroencephalography, Seizures diagnosis
- Abstract
Purpose: Prefabricated arrays with a limited number of electrodes offer an opportunity to hasten the diagnosis of seizures; however, their accuracy to detect seizures is unknown. We examined the utility of two limited-montage EEG setups for the detection of nonconvulsive seizures., Methods: Thirty previously interpreted EEG segments with nonconvulsive seizures from 30 patients and 60 segments with background slowing or normal EEG from 60 patients were rendered in a bipolar "double banana" montage, a double distance "neonatal" montage, and a circumferential "hatband" montage. Experts reviewed 60 to 180 seconds long segments to determine whether seizures were present and if the EEG data provided were sufficient to make a decision on escalation of clinical care by ordering an additional EEG or prescribing anticonvulsants. The periodic patterns on the ictal-interictal continuum were specifically excluded for this analysis to keep the focus on definite electrographic seizures., Results: The sensitivities for seizure of the neonatal and hatband montages were 0.96 and 0.84, respectively, when compared with full montage EEG, whereas the specificities were 0.94 and 0.98, respectively. Appropriate escalation of care was suggested for 96% and 92% of occurrences of seizure patterns in neonatal and hatband montages, respectively. When compared with clinical EEG, the sensitivities of the neonatal and hatband montages for seizure diagnosis were 0.85 and 0.69, respectively., Conclusions: Nonconvulsive seizures were detected with high accuracy using the limited electrode array configuration in the neonatal and hatband montages. The sensitivity of the neonatal montage EEG in detecting seizures was superior to that of a hatband montage. These findings suggest that in some patients with nonconvulsive seizures, limited-montage EEG may allow to differentiate ictal and slow patterns., Competing Interests: S. Kedar has a licensed technology through EON Reality Inc. for the Advanced Pupil Simulator. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2020 by the American Clinical Neurophysiology Society.)
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- 2022
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31. The InSight HP 3 Penetrator (Mole) on Mars: Soil Properties Derived from the Penetration Attempts and Related Activities.
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Spohn T, Hudson TL, Marteau E, Golombek M, Grott M, Wippermann T, Ali KS, Schmelzbach C, Kedar S, Hurst K, Trebi-Ollennu A, Ansan V, Garvin J, Knollenberg J, Müller N, Piqueux S, Lichtenheldt R, Krause C, Fantinati C, Brinkman N, Sollberger D, Delage P, Vrettos C, Reershemius S, Wisniewski L, Grygorczuk J, Robertsson J, Edme P, Andersson F, Krömer O, Lognonné P, Giardini D, Smrekar SE, and Banerdt WB
- Abstract
The NASA InSight Lander on Mars includes the Heat Flow and Physical Properties Package HP
3 to measure the surface heat flow of the planet. The package uses temperature sensors that would have been brought to the target depth of 3-5 m by a small penetrator, nicknamed the mole. The mole requiring friction on its hull to balance remaining recoil from its hammer mechanism did not penetrate to the targeted depth. Instead, by precessing about a point midway along its hull, it carved a 7 cm deep and 5-6 cm wide pit and reached a depth of initially 31 cm. The root cause of the failure - as was determined through an extensive, almost two years long campaign - was a lack of friction in an unexpectedly thick cohesive duricrust. During the campaign - described in detail in this paper - the mole penetrated further aided by friction applied using the scoop at the end of the robotic Instrument Deployment Arm and by direct support by the latter. The mole tip finally reached a depth of about 37 cm, bringing the mole back-end 1-2 cm below the surface. It reversed its downward motion twice during attempts to provide friction through pressure on the regolith instead of directly with the scoop to the mole hull. The penetration record of the mole was used to infer mechanical soil parameters such as the penetration resistance of the duricrust of 0.3-0.7 MPa and a penetration resistance of a deeper layer ( > 30 cm depth) of 4.9 ± 0.4 MPa . Using the mole's thermal sensors, thermal conductivity and diffusivity were measured. Applying cone penetration theory, the resistance of the duricrust was used to estimate a cohesion of the latter of 2-15 kPa depending on the internal friction angle of the duricrust. Pushing the scoop with its blade into the surface and chopping off a piece of duricrust provided another estimate of the cohesion of 5.8 kPa. The hammerings of the mole were recorded by the seismometer SEIS and the signals were used to derive P-wave and S-wave velocities representative of the topmost tens of cm of the regolith. Together with the density provided by a thermal conductivity and diffusivity measurement using the mole's thermal sensors, the elastic moduli were calculated from the seismic velocities. Using empirical correlations from terrestrial soil studies between the shear modulus and cohesion, the previous cohesion estimates were found to be consistent with the elastic moduli. The combined data were used to derive a model of the regolith that has an about 20 cm thick duricrust underneath a 1 cm thick unconsolidated layer of sand mixed with dust and above another 10 cm of unconsolidated sand. Underneath the latter, a layer more resistant to penetration and possibly containing debris from a small impact crater is inferred. The thermal conductivity increases from 14 mW/m K to 34 mW/m K through the 1 cm sand/dust layer, keeps the latter value in the duricrust and the sand layer underneath and then increases to 64 mW/m K in the sand/gravel layer below., Supplementary Information: The online version contains supplementary material available at 10.1007/s11214-022-00941-z., Competing Interests: Competing InterestsThe authors declare that they have no conflict of interest., (© The Author(s) 2022.)- Published
- 2022
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32. The shallow structure of Mars at the InSight landing site from inversion of ambient vibrations.
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Hobiger M, Hallo M, Schmelzbach C, Stähler SC, Fäh D, Giardini D, Golombek M, Clinton J, Dahmen N, Zenhäusern G, Knapmeyer-Endrun B, Carrasco S, Charalambous C, Hurst K, Kedar S, and Banerdt WB
- Abstract
Orbital and surface observations can shed light on the internal structure of Mars. NASA's InSight mission allows mapping the shallow subsurface of Elysium Planitia using seismic data. In this work, we apply a classical seismological technique of inverting Rayleigh wave ellipticity curves extracted from ambient seismic vibrations to resolve, for the first time on Mars, the shallow subsurface to around 200 m depth. While our seismic velocity model is largely consistent with the expected layered subsurface consisting of a thin regolith layer above stacks of lava flows, we find a seismic low-velocity zone at about 30 to 75 m depth that we interpret as a sedimentary layer sandwiched somewhere within the underlying Hesperian and Amazonian aged basalt layers. A prominent amplitude peak observed in the seismic data at 2.4 Hz is interpreted as an Airy phase related to surface wave energy trapped in this local low-velocity channel., (© 2021. The Author(s).)
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- 2021
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33. Approach to optic neuritis: An update.
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Phuljhele S, Kedar S, and Saxena R
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- Antibodies, Monoclonal, Humans, Neuroimaging, Prognosis, Recurrence, Optic Neuritis diagnosis, Optic Neuritis drug therapy
- Abstract
Over the past few years, there has been remarkable development in the area of optic neuritis. The discovery of new antibodies has improved our understanding of the pathology of the disease. Antiaquaporin4 antibodies and antimyelin oligodendrocytes antibodies are now considered as distinct entities of optic neuritis with their specific clinical presentation, neuroimaging characteristics, treatment options, and course of the disease. Similarly, there has been a substantial change in the treatment of optic neuritis which was earlier limited to steroids and interferons. The development of new immunosuppressant drugs and monoclonal antibodies has reduced the relapses and improved the prognosis of optic neuritis as well as an associated systemic disease. This review article tends to provide an update on the approach and management of optic neuritis., Competing Interests: None
- Published
- 2021
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34. A Reconstruction Algorithm for Temporally Aliased Seismic Signals Recorded by the InSight Mars Lander.
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Sollberger D, Schmelzbach C, Andersson F, Robertsson JOA, Brinkman N, Kedar S, Banerdt WB, Clinton J, van Driel M, Garcia R, Giardini D, Grott M, Haag T, Hudson TL, Lognonné P, Pierick JT, Pike W, Spohn T, Stähler SC, and Zweifel P
- Abstract
In December 2018, the NASA InSight lander successfully placed a seismometer on the surface of Mars. Alongside, a hammering device was deployed at the landing site that penetrated into the ground to attempt the first measurements of the planetary heat flow of Mars. The hammering of the heat probe generated repeated seismic signals that were registered by the seismometer and can potentially be used to image the shallow subsurface just below the lander. However, the broad frequency content of the seismic signals generated by the hammering extends beyond the Nyquist frequency governed by the seismometer's sampling rate of 100 samples per second. Here, we propose an algorithm to reconstruct the seismic signals beyond the classical sampling limits. We exploit the structure in the data due to thousands of repeated, only gradually varying hammering signals as the heat probe slowly penetrates into the ground. In addition, we make use of the fact that repeated hammering signals are sub-sampled differently due to the unsynchronized timing between the hammer strikes and the seismometer recordings. This allows us to reconstruct signals beyond the classical Nyquist frequency limit by enforcing a sparsity constraint on the signal in a modified Radon transform domain. In addition, the proposed method reduces uncorrelated noise in the recorded data. Using both synthetic data and actual data recorded on Mars, we show how the proposed algorithm can be used to reconstruct the high-frequency hammering signal at very high resolution., (© 2021. The Authors. Earth and Space Science published by Wiley Periodicals LLC on behalf of American Geophysical Union.)
- Published
- 2021
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35. Radiation-Induced Bilateral Oculomotor Nerve Palsy 20 Years After Radiation Treatment.
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Grassmeyer JJ, Fernandes JA, Helvey JT, and Kedar S
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- Encephalomalacia diagnostic imaging, Female, Frontal Lobe diagnostic imaging, Humans, Magnetic Resonance Imaging, Middle Aged, Neurosurgical Procedures, Oculomotor Nerve Diseases diagnostic imaging, Oculomotor Nerve Diseases etiology, Radiation Injuries diagnostic imaging, Radiation Injuries etiology, Radiotherapy adverse effects, Time Factors, Astrocytoma therapy, Brain Neoplasms therapy, Oculomotor Nerve Diseases diagnosis, Radiation Injuries diagnosis
- Published
- 2021
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36. The Effects of Acute Intracranial Pressure Changes on the Episcleral Venous Pressure, Retinal Vein Diameter and Intraocular Pressure in a Pig Model.
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Ghate D, Kedar S, Havens S, Fan S, Thorell W, Nelson C, Gu L, Tong J, and Gulati V
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- Acute Disease, Animals, Biomarkers, Disease Models, Animal, Female, Retinal Vein diagnostic imaging, Sus scrofa, Tomography, Optical Coherence, Tonometry, Ocular, Intracranial Hypertension physiopathology, Intracranial Pressure physiology, Intraocular Pressure physiology, Retinal Vein pathology, Sclera blood supply, Venous Pressure physiology
- Abstract
Purpose: Orbital veins such as the retinal veins and episcleral veins drain into the cavernous sinus, an intracranial venous structure. We studied the effects of acute intracranial pressure (ICP) elevation on episcleral venous pressure, intraocular pressure and retinal vein diameter in an established non-survival pig model., Methods: In six adult female domestic pigs, we increased ICP in 5 mm Hg increments using saline infusion through a lumbar drain. We measured ICP (using parenchymal pressure monitor), intraocular pressure (using pneumatonometer), episcleral venous pressure (using venomanometer), retinal vein diameter (using OCT images) and arterial blood pressure at each stable ICP increment. The average baseline ICP was 5.4 mm Hg (range 1.5-9 mm Hg) and the maximum stable ICP ranged from 18 to 40 mm Hg. Linear mixed models with random intercepts were used to evaluate the effect of acute ICP increase on outcome variables., Results: With acute ICP elevation, we found loss of retinal venous pulsation and increased episcleral venous pressure, intraocular pressure and retinal vein pressure in all animals. Specifically, acute ICP increase was significantly associated with episcleral venous pressure (β = 0.31; 95% CI 0.14-0.48, p < .001), intraocular pressure (β = 0.37, 95%CI 0.24-0.50; p < .001) and retinal vein diameter (β = 11.29, 95%CI 1.57-21.00; p = .03) after controlling for the effects of arterial blood pressure., Conclusion: We believe that the ophthalmic effects of acute ICP elevation are mediated by increased intracranial venous pressure producing upstream pressure changes within the orbital and retinal veins. These results offer exciting possibilities for the development of non-invasive ophthalmic biomarkers to estimate acute ICP elevations following significant neuro-trauma.
- Published
- 2021
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37. Glaucomatous visual fields and neurocognitive function are independently associated with poor lane maintenance during driving simulation.
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Anderson DE, Bader JP, Boes EA, Gagrani M, Smith LM, Ndulue JK, Kedar S, Gulati V, Ghate DA, and Rizzo M
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- Humans, Quality of Life, Reproducibility of Results, Surveys and Questionnaires, Vision Disorders, Visual Field Tests, Visual Fields, Automobile Driving, Glaucoma
- Abstract
Background: Driving simulators are a safe alternative to on-road vehicles for studying driving behavior in glaucoma drivers. Visual field (VF) loss severity is associated with higher driving simulator crash risk, though mechanisms explaining this relationship remain unknown. Furthermore, associations between driving behavior and neurocognitive performance in glaucoma are unexplored. Here, we evaluated the hypothesis that VF loss severity and neurocognitive performance interact to influence simulated vehicle control in glaucoma drivers., Methods: Glaucoma patients (n = 25) and suspects (n = 18) were recruited into the study. All had > 20/40 corrected visual acuity in each eye and were experienced field takers with at least three stable (reliability > 20%) fields over the last 2 years. Diagnosis of neurological disorder or cognitive impairment were exclusion criteria. Binocular VFs were derived from monocular Humphrey VFs to estimate a binocular VF index (OU-VFI). Montreal Cognitive Assessment (MoCA) was administered to assess global and sub-domain neurocognitive performance. National Eye Institute Visual Function Questionnaire (NEI-VFQ) was administered to assess peripheral vision and driving difficulties sub-scores. Driving performance was evaluated using a driving simulator with a 290° panoramic field of view constructed around a full-sized automotive cab. Vehicle control metrics, such as lateral acceleration variability and steering wheel variability, were calculated from vehicle sensor data while patients drove on a straight two-lane rural road. Linear mixed models were constructed to evaluate associations between driving performance and clinical characteristics., Results: Patients were 9.5 years older than suspects (p = 0.015). OU-VFI in the glaucoma group ranged from 24 to 98% (85.6 ± 18.3; M ± SD). OU-VFI (p = .0066) was associated with MoCA total (p = .0066) and visuo-spatial and executive function sub-domain scores (p = .012). During driving simulation, patients showed greater steering wheel variability (p = 0.0001) and lateral acceleration variability (p < .0001) relative to suspects. Greater steering wheel variability was independently associated with OU-VFI (p = .0069), MoCA total scores (p = 0.028), and VFQ driving sub-scores (p = 0.0087), but not age (p = 0.61)., Conclusions: Poor vehicle control was independently associated with greater VF loss and worse neurocognitive performance, suggesting both factors contribute to information processing models of driving performance in glaucoma. Future research must demonstrate the external validity of current findings to on-road performance in glaucoma.
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- 2020
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38. The 2020 Update to North American Neuro-Ophthalmology Society's (NANOS) Neuro-Ophthalmology Curriculum.
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Kedar S, Digre KB, and Biousse V
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- Humans, United States, Curriculum, Neurology, Ophthalmology, Societies, Medical
- Published
- 2020
- Full Text
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39. Development and validation of an interpretable deep learning framework for Alzheimer's disease classification.
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Qiu S, Joshi PS, Miller MI, Xue C, Zhou X, Karjadi C, Chang GH, Joshi AS, Dwyer B, Zhu S, Kaku M, Zhou Y, Alderazi YJ, Swaminathan A, Kedar S, Saint-Hilaire MH, Auerbach SH, Yuan J, Sartor EA, Au R, and Kolachalama VB
- Subjects
- Aged, Aged, 80 and over, Algorithms, Alzheimer Disease pathology, Australia, Biomarkers, Brain pathology, Cognitive Dysfunction physiopathology, Deep Learning, Disease Progression, Female, Humans, Magnetic Resonance Imaging methods, Male, Models, Statistical, Neuroimaging methods, Neuropsychological Tests, Alzheimer Disease classification, Alzheimer Disease diagnosis
- Abstract
Alzheimer's disease is the primary cause of dementia worldwide, with an increasing morbidity burden that may outstrip diagnosis and management capacity as the population ages. Current methods integrate patient history, neuropsychological testing and MRI to identify likely cases, yet effective practices remain variably applied and lacking in sensitivity and specificity. Here we report an interpretable deep learning strategy that delineates unique Alzheimer's disease signatures from multimodal inputs of MRI, age, gender, and Mini-Mental State Examination score. Our framework linked a fully convolutional network, which constructs high resolution maps of disease probability from local brain structure to a multilayer perceptron and generates precise, intuitive visualization of individual Alzheimer's disease risk en route to accurate diagnosis. The model was trained using clinically diagnosed Alzheimer's disease and cognitively normal subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset (n = 417) and validated on three independent cohorts: the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) (n = 382), the Framingham Heart Study (n = 102), and the National Alzheimer's Coordinating Center (NACC) (n = 582). Performance of the model that used the multimodal inputs was consistent across datasets, with mean area under curve values of 0.996, 0.974, 0.876 and 0.954 for the ADNI study, AIBL, Framingham Heart Study and NACC datasets, respectively. Moreover, our approach exceeded the diagnostic performance of a multi-institutional team of practicing neurologists (n = 11), and high-risk cerebral regions predicted by the model closely tracked post-mortem histopathological findings. This framework provides a clinically adaptable strategy for using routinely available imaging techniques such as MRI to generate nuanced neuroimaging signatures for Alzheimer's disease diagnosis, as well as a generalizable approach for linking deep learning to pathophysiological processes in human disease., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2020
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40. Uveomeningeal syndrome in a healthy, young male: an unusual presentation of West Nile virus.
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Rearigh L, Kedar S, and Bares SH
- Subjects
- Adult, Chorioretinitis pathology, Humans, Male, Syndrome, Chorioretinitis virology, West Nile Fever complications
- Abstract
West Nile virus (WNV) is an RNA flavivirus transmitted through a mosquito vector. In 2018 Nebraska reported 242 cases, the highest incidence of WNV since 2003. This included 119 neuroinvasive cases (49%) and 11 deaths (4.5%) (DHHS 2018). Clinical presentation ranges from uncomplicated symptoms including fever, headache, and myalgias to neuroinvasive disease characterized by meningoencephalitis, flaccid paralysis, and other neurologic manifestations. Neuroinvasive WNV usually occurs in elderly and immunocompromised individuals, and ocular involvement is often not detected until later in the disease course. We describe a case of neuroinvasive WNV presenting with uveomeningitis in a young and otherwise healthy patient.
- Published
- 2020
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41. Neurophysiologic and ophthalmic markers of chemotherapy-related cognitive impairment in patients diagnosed with hematologic cancer: A feasibility study.
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Anderson DE, Kedar S, Bhatt VR, Schmid K, Holstein SA, and Rizzo M
- Subjects
- Feasibility Studies, Humans, Neuropsychological Tests, Tomography, Optical Coherence, Chemotherapy-Related Cognitive Impairment, Hematologic Neoplasms complications, Hematologic Neoplasms drug therapy
- Abstract
Background: Biomarkers of chemotherapy-related cognitive impairment (CRCI) in hematologic cancer are understudied and underdeveloped. We evaluated the feasibility of using ophthalmic and neurophysiologic markers to assess CRCI in hematologic cancer., Methods: Hematologic cancer patients either receiving (Ctx+) or not receiving (Ctx-) chemotherapy were recruited from a tertiary medical center. Demographically-matched healthy controls (HC) were also recruited. Ctx+ participants completed the following study visits: (1) after diagnosis but prior to chemotherapy (baseline); (2) after one treatment cycle (one-month post-baseline); and (3) after three treatment cycles (three-months post-baseline). Comparison subjects completed assessments at similar intervals. Participants completed: (1) neuropsychological assessments of attention and executive function; (2) neurophysiologic assessments of control over spatial attention and working memory; and (3) ophthalmic assessments of contrast sensitivity and optical coherence tomography (OCT)., Results: We enrolled 45 participants (15 per group), and 30 participants (Ctx+ = 8; Ctx- = 10; HC = 12) completed all study visits. Ctx+ participants performed worse than HC participants on neuropsychological measures of attention and executive function. Both Ctx+ and Ctx- participants showed changes in neurophysiologic measures of control over spatial attention that differed from HC participants. Ctx+ participants showed chemotherapy-related declines in contrast sensitivity that were predicted by OCT retinal nerve fiber layer thickness (RNFL) changes. Changes in neurophysiologic measures of control over spatial attention were also predicted by OCT RNFL changes., Conclusion: We demonstrated the feasibility of using ophthalmic and neurophysiologic markers as rapid and non-invasive measures that may be useful for tracking CRCI in hematologic cancer., Competing Interests: Declaration of Competing Interest Sachin Kedar has a licensed technology for Advanced Pupil Simulator with EON Reality Inc. All other authors declare there is no conflict of interest regarding the publication of this work., (Published by Elsevier B.V.)
- Published
- 2020
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42. Visual Pathway Degeneration in Chemotherapy-Related Neurotoxicity: A Review and Directions for Future Research.
- Author
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Anderson DE, Holstein SA, and Kedar S
- Abstract
Chemotherapy-related neurotoxicity (CRNT) is an emerging public health concern. Visual pathway degeneration may be a symptom of CRNT. We surveyed the current literature for evidence of visual pathway degeneration in cancer patients receiving chemotherapy. A systematic review was conducted in PubMed. Six published articles met our inclusion criteria. The studies showed reduced retinal thickness, primarily in the retinal nerve fibre layer, and impaired inner retinal function in patients receiving chemotherapy. In summary, the current literature suggests chemotherapy may induce visual pathway degeneration. Future research may benefit from improving study design, exploring mechanisms of chemotherapy-related visual pathway degeneration, and incorporating these findings into biomarker development., (© 2019 Taylor & Francis Group, LLC.)
- Published
- 2020
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43. Indirect Traumatic Optic Neuropathy Induced by Primary Blast: A Fluid-Structure Interaction Study.
- Author
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Tong J, Kedar S, Ghate D, and Gu L
- Abstract
Current knowledge of traumatic ocular injury is still limited as most studies have focused on the ocular injuries that happened at the anterior part of the eye, whereas the damage to the optic nerve known as traumatic optic neuropathy (TON) is poorly understood. The goal of this study is to understand the mechanism of the TON following the primary blast through a fluid-structure interaction model. An axisymmetric three-dimensional (3D) eye model with detailed orbital components was developed to capture the dynamics of the eye under the blast wave. Our numerical results demonstrated a transient pressure elevation in both vitreous and cerebrospinal fluid (CSF). A high strain rate over 100 s-1 was observed throughout the optic nerve during the blast with the most vulnerable part located at the intracanalicular region. The optic nerve deforming at such a high strain rate may account for the axonal damage and vision loss in patients subjected to the primary blast. The results from this work would enhance the understanding of indirect TON and provide guidance in the design of protective eyewear against such injury., (Copyright © 2019 by ASME.)
- Published
- 2019
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44. Neurological and Ophthalmological Manifestations of Varicella Zoster Virus.
- Author
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Kedar S, Jayagopal LN, and Berger JR
- Subjects
- Antiviral Agents therapeutic use, Herpes Zoster Ophthalmicus drug therapy, Humans, Immunocompromised Host, Nervous System Diseases drug therapy, Polymerase Chain Reaction, Quality of Life, Serologic Tests, Herpes Zoster Ophthalmicus diagnosis, Nervous System Diseases diagnosis
- Abstract
Background: Approximately 1 million new cases of herpes zoster (HZ) occur in the United States annually, including 10%-20% with herpes zoster ophthalmicus (HZO). Postherpetic neuralgia, a debilitating pain syndrome occurs in 30% HZ, whereas 50% HZO develop ophthalmic complications. Diplopia from cranial nerve palsy occurs in less than 30% HZO, whereas optic neuropathy is seen in less than 1% HZO. We reviewed recent developments in the diagnosis, treatment, and prevention of HZ as well as neurological and ophthalmological complications of relevance to the neuro-ophthalmologist., Evidence Acquisition: We searched the English language literature on Pubmed and Google scholar for articles relevant to the various sections of this review., Results: Antiviral treatment should be initiated within 48-72 hours of onset of HZ and HZO to decrease pain and reduce complications. We recommend neuroimaging in all patients with neuro-ophthalmic manifestations such as diplopia and acute vision loss. Diagnostic confirmation using polymerase chain reaction and serology on paired serum and cerebrospinal fluid samples should be obtained in those with neurological signs and symptoms or abnormal imaging. Patients with neurological and/or retinal varicella zoster virus (VZV) infection should be treated promptly with intravenous acyclovir. Patients with isolated optic neuropathy or cranial nerve palsy can be managed with oral antivirals. The prognosis for visual recovery is good for patients with isolated optic neuropathy and excellent for patients with isolated ocular motor cranial nerve palsy., Conclusions: HZ produces a spectrum of potentially blinding and life-threatening complications that adversely affect quality of life and increase health care costs. Individuals at risk for HZ, such as the elderly and immunocompromised, should be encouraged to receive the highly effective VZV vaccine to prevent HZ and its complications.
- Published
- 2019
- Full Text
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45. Relative Contributions of Intracranial Pressure and Intraocular Pressure on Lamina Cribrosa Behavior.
- Author
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Tong J, Ghate D, Kedar S, and Gu L
- Abstract
Purpose: To characterize the relative contributions of intraocular pressure (IOP) and intracranial pressure (ICP) on lamina cribrosa (LC) behavior, specifically LC depth (LCD) and LC peak strain., Methods: An axially symmetric finite element model of the posterior eye was constructed with an elongated optic nerve and retro-orbital subarachnoid space ensheathed by pia and dura mater. The mechanical environment in LC was evaluated with ICP ranging from 5 to 15 mmHg and IOP from 10 to 45 mmHg. LCD and LC peak strains at various ICP and IOP levels were estimated using full factorial experiments. Multiple linear regression analyses were then applied to estimate LCD and LC peak strain using ICP and IOP as independent variables., Results: Both increased ICP and decreased IOP led to a smaller LCD and LC peak strain. The regression correlation coefficient for LCD was -1.047 for ICP and 1.049 for IOP, and the ratio of the two regression coefficients was -1.0. The regression correlation coefficient for LC peak strain was -0.025 for ICP and 0.106 for IOP, and the ratio of the two regression coefficients was -0.24. A stiffer sclera increased LCD but decreased LC peak strain; besides, it increased the relative contribution of ICP on the LCD but decreased that on the LC peak strain., Conclusions: ICP and IOP have opposing effects on LCD and LC peak strain. While their effects on LCD are equivalent, the effect of IOP on LC peak strain is 3 times larger than that of ICP. The influences of these pressure are dependent on sclera material properties, which might explain the pathogenesis of ocular hypertension and normal-tension glaucoma.
- Published
- 2019
- Full Text
- View/download PDF
46. Neuro-Ophthalmology Virtual Education Library (NOVEL) 2019 Update: North American Neuro-Ophthalmology Society's Neuro-Ophthalmology Examination Techniques (NExT) and Illustrated Curriculum are Online.
- Author
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Lombardo N, Kedar S, and Digre K
- Subjects
- Curriculum, Humans, Libraries, Medical, North America, Diagnostic Techniques, Neurological, Diagnostic Techniques, Ophthalmological, Eye Diseases diagnosis, Neurology education, Ophthalmology education, Societies, Medical, Virtual Reality
- Published
- 2019
- Full Text
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47. Should Antiviral/Anti-Varicella Zoster Virus Treatment Be Used in Patients With Giant Cell Arteritis?
- Author
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Liao YJ and Kedar S
- Subjects
- Humans, Temporal Arteries pathology, Antigens, Viral analysis, Antiviral Agents therapeutic use, Giant Cell Arteritis drug therapy, Herpesvirus 3, Human immunology, Temporal Arteries immunology
- Published
- 2019
- Full Text
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48. A Tough NUT to Crack: A 47-Year-Old With Diplopia From a Rare Malignancy.
- Author
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Maloley L, Helvey J, Bridge J, DiMaio D, Ghate D, and Kedar S
- Subjects
- Biopsy, Diagnosis, Differential, Diplopia physiopathology, Fatal Outcome, Female, Head and Neck Neoplasms diagnosis, Head and Neck Neoplasms metabolism, Humans, Magnetic Resonance Imaging, Middle Aged, Neoplasm Proteins metabolism, Nuclear Proteins metabolism, Positron-Emission Tomography, Rare Diseases, Tomography, X-Ray Computed, Diplopia etiology, Head and Neck Neoplasms complications, Vision, Binocular physiology
- Published
- 2019
- Full Text
- View/download PDF
49. SEIS: Insight's Seismic Experiment for Internal Structure of Mars.
- Author
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Lognonné P, Banerdt WB, Giardini D, Pike WT, Christensen U, Laudet P, de Raucourt S, Zweifel P, Calcutt S, Bierwirth M, Hurst KJ, Ijpelaan F, Umland JW, Llorca-Cejudo R, Larson SA, Garcia RF, Kedar S, Knapmeyer-Endrun B, Mimoun D, Mocquet A, Panning MP, Weber RC, Sylvestre-Baron A, Pont G, Verdier N, Kerjean L, Facto LJ, Gharakanian V, Feldman JE, Hoffman TL, Klein DB, Klein K, Onufer NP, Paredes-Garcia J, Petkov MP, Willis JR, Smrekar SE, Drilleau M, Gabsi T, Nebut T, Robert O, Tillier S, Moreau C, Parise M, Aveni G, Ben Charef S, Bennour Y, Camus T, Dandonneau PA, Desfoux C, Lecomte B, Pot O, Revuz P, Mance D, tenPierick J, Bowles NE, Charalambous C, Delahunty AK, Hurley J, Irshad R, Liu H, Mukherjee AG, Standley IM, Stott AE, Temple J, Warren T, Eberhardt M, Kramer A, Kühne W, Miettinen EP, Monecke M, Aicardi C, André M, Baroukh J, Borrien A, Bouisset A, Boutte P, Brethomé K, Brysbaert C, Carlier T, Deleuze M, Desmarres JM, Dilhan D, Doucet C, Faye D, Faye-Refalo N, Gonzalez R, Imbert C, Larigauderie C, Locatelli E, Luno L, Meyer JR, Mialhe F, Mouret JM, Nonon M, Pahn Y, Paillet A, Pasquier P, Perez G, Perez R, Perrin L, Pouilloux B, Rosak A, Savin de Larclause I, Sicre J, Sodki M, Toulemont N, Vella B, Yana C, Alibay F, Avalos OM, Balzer MA, Bhandari P, Blanco E, Bone BD, Bousman JC, Bruneau P, Calef FJ, Calvet RJ, D'Agostino SA, de Los Santos G, Deen RG, Denise RW, Ervin J, Ferraro NW, Gengl HE, Grinblat F, Hernandez D, Hetzel M, Johnson ME, Khachikyan L, Lin JY, Madzunkov SM, Marshall SL, Mikellides IG, Miller EA, Raff W, Singer JE, Sunday CM, Villalvazo JF, Wallace MC, Banfield D, Rodriguez-Manfredi JA, Russell CT, Trebi-Ollennu A, Maki JN, Beucler E, Böse M, Bonjour C, Berenguer JL, Ceylan S, Clinton J, Conejero V, Daubar I, Dehant V, Delage P, Euchner F, Estève I, Fayon L, Ferraioli L, Johnson CL, Gagnepain-Beyneix J, Golombek M, Khan A, Kawamura T, Kenda B, Labrot P, Murdoch N, Pardo C, Perrin C, Pou L, Sauron A, Savoie D, Stähler S, Stutzmann E, Teanby NA, Tromp J, van Driel M, Wieczorek M, Widmer-Schnidrig R, and Wookey J
- Abstract
By the end of 2018, 42 years after the landing of the two Viking seismometers on Mars, InSight will deploy onto Mars' surface the SEIS ( S eismic E xperiment for I nternal S tructure) instrument; a six-axes seismometer equipped with both a long-period three-axes Very Broad Band (VBB) instrument and a three-axes short-period (SP) instrument. These six sensors will cover a broad range of the seismic bandwidth, from 0.01 Hz to 50 Hz, with possible extension to longer periods. Data will be transmitted in the form of three continuous VBB components at 2 sample per second (sps), an estimation of the short period energy content from the SP at 1 sps and a continuous compound VBB/SP vertical axis at 10 sps. The continuous streams will be augmented by requested event data with sample rates from 20 to 100 sps. SEIS will improve upon the existing resolution of Viking's Mars seismic monitoring by a factor of ∼ 2500 at 1 Hz and ∼ 200 000 at 0.1 Hz. An additional major improvement is that, contrary to Viking, the seismometers will be deployed via a robotic arm directly onto Mars' surface and will be protected against temperature and wind by highly efficient thermal and wind shielding. Based on existing knowledge of Mars, it is reasonable to infer a moment magnitude detection threshold of M w ∼ 3 at 40 ∘ epicentral distance and a potential to detect several tens of quakes and about five impacts per year. In this paper, we first describe the science goals of the experiment and the rationale used to define its requirements. We then provide a detailed description of the hardware, from the sensors to the deployment system and associated performance, including transfer functions of the seismic sensors and temperature sensors. We conclude by describing the experiment ground segment, including data processing services, outreach and education networks and provide a description of the format to be used for future data distribution., Electronic Supplementary Material: The online version of this article (10.1007/s11214-018-0574-6) contains supplementary material, which is available to authorized users.
- Published
- 2019
- Full Text
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50. Teaching NeuroImages: Presentation of diffuse large B-cell lymphoma with bilateral sequential oculomotor neuropathy.
- Author
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Galla KM, Cameron-Smith E, Bares SH, Braun A, Punsoni M, Foster K, Helvey J, and Kedar S
- Subjects
- Anti-Retroviral Agents therapeutic use, CD79 Antigens metabolism, HIV Infections complications, HIV Infections diagnostic imaging, HIV Infections drug therapy, Humans, Male, Middle Aged, Lymphoma, B-Cell complications, Lymphoma, B-Cell diagnosis, Oculomotor Nerve Diseases complications, Oculomotor Nerve Diseases diagnosis
- Published
- 2018
- Full Text
- View/download PDF
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