24 results on '"Douglas, Morgan"'
Search Results
2. Multi-omic evaluation of metabolic alterations in multiple sclerosis identifies shifts in aromatic amino acid metabolism
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Fitzgerald, Kathryn C., Smith, Matthew D., Kim, Sol, Sotirchos, Elias S., Kornberg, Michael D., Douglas, Morgan, Nourbakhsh, Bardia, Graves, Jennifer, Rattan, Ramandeep, Poisson, Laila, Cerghet, Mirela, Mowry, Ellen M., Waubant, Emmanuelle, Giri, Shailendra, Calabresi, Peter A., and Bhargava, Pavan
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- 2021
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3. Transparência e accountability de algoritmos governamentais: o caso do sistema eletrônico de votação brasileiro
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DOUGLAS MORGAN FULLIN SALDANHA and MARCELA BARBOSA DA SILVA
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Governo eletrônico ,Governança digital ,Urna eletrônica ,Boas práticas ,Princípios ,Business ,HF5001-6182 - Abstract
Resumo Nos últimos anos, uma série de movimentos de dados abertos tem surgido ao redor do mundo, assegurando aos cidadãos mais oportunidades para acessar informações, sendo a transparência um fator associado à confiança nas organizações públicas e no governo. A transparência em algoritmos traduz-se no conhecimento dos passos realizados e critérios adotados para a obtenção de determinado resultado. O objetivo deste estudo consiste em identificar as características de transparência e accountability do sistema eletrônico de votação brasileiro. Por meio do estudo de caso, foram confrontadas recomendações e boas práticas de transparência - que propiciam controle e fiscalização por parte da sociedade em algoritmos - com as particularidades do sistema de votação eletrônico brasileiro. Este estudo avança na discussão da influência das novas tecnologias na democracia, situando o sistema eletrônico de votação brasileiro nos limites da transparência e accountability de algoritmos e do governo em geral.
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- 2020
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4. Transparency and accountability of government algorithms: the case of the Brazilian electronic voting system/Transparencia e accountability de algoritmos governamentais: o caso do sistema eletronico de votacao brasileiro/Transparencia y accountability de algoritmos gubernamentales: el caso del sistema electoral electronic brasileno
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Saldanha, Douglas Morgan Fullin and Da Silva, Marcela Barbosa
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- 2020
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5. Effects of nonnutritive sugar inclusion in laboratory diets and attracticidal spheres on survivorship and mobility of 2 Dipteran species, Rhagoletis pomonella (Diptera: Tephritidae) and Drosophila suzukii (Diptera: Drosophilidae).
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Nixon, Laura J, Douglas, Morgan, Ibrahim, Aya, Jones, Sharon, Piñero, Jaime C, and Leskey, Tracy C
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DROSOPHILA suzukii ,DROSOPHILIDAE ,DIPTERA ,TEPHRITIDAE ,INSECTICIDE application ,SPECIES ,SWEETENERS - Abstract
Native apple maggot fly, Rhagoletis pomonella , and invasive spotted-wing drosophila, Drosophila suzukii , are key pests of apple and small fruit, respectively, in the United States. Both species are typically managed with standard insecticide applications. However, interest in alternative strategies that result in insecticide reductions has led to evaluations of nonnutritive sugars as toxicants for Drosophila species and development of attracticidal spheres for both species. Here, we evaluated the survivorship of R. pomonella and D. suzukii when provided with standard diets that substituted saccharin, sucralose, aspartame, erythritol, dextrose, or mannitol for the sucrose component and compared them with standard diets and water-only controls for up to 15 days. Presence of erythritol and mannitol significantly decreased survivorship of R. pomonella and erythritol significantly decreased the survivorship of D. suzukii. However, mobility trials following a 2 h exposure to aqueous solutions of each sugar treatment resulted in no strong impact on either species. Survivorship after 30 min exposure to erythritol or mannitol alone, or in combination with varying concentrations of sucrose (serving as a phagostimulant) at 30 min and 24 h were evaluated for both species. Only D. suzukii survivorship was affected with decreased survivorship on erythritol:sucrose solutions of 20:0% and 15:5% for 24 h. Based on all results, erythritol appeared most promising, and was integrated into attracticidal spheres as a toxicant but even at the highest concentration, survivorship remained unaffected for either species, thus making this nonnutritive sugar impractical and ineffective as a toxicant substitute in attracticidal spheres. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Cryopreservation of Anopheles stephensi (MOSQUITO) EGGS: EFFECTS ON GENOTYPIC AND PHENOTYPIC CHARACTERISTICS
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Douglas, Morgan, Inbar, Ehud, Sharakov, Igor, El-Sayed, Najib M., Belew, Ashton T., Overby, James, Matheny, Steve, Addisu, Fantahun, Abebe, Yonas, Koutzoumis, Dimitri, Springer, Kerri, Eappen, Abraham, Billingsley, Peter F., and James, Eric R.
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- 2023
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7. HIV related hypochlorhydria does not appear to respond to anti-retroviral therapy in Zambian adults: a case control study
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Violet Kayamba, Aaron Shibemba, Kanekwa Zyambo, Douglas Corbett Heimburger, Douglas Morgan, and Paul Kelly
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hiv ,intestinal metaplasia ,hypochlorhydria ,gastric atrophy ,pepsinogen ,Medicine - Abstract
INTRODUCTION: Human Immunodeficiency Virus (HIV) infection is associated with hypochlorhydria but the mechanism is unknown. The objective of this study was to determine effects of anti-retroviral therapy (ART) on gastric physiology as measured by validated markers. METHODS: we studied HIV infected individuals who were either ART-naïve or on treatment with undetectable viral loads. We measured H.pylori IgG antibodies, pepsinogen (PG) 1 and 2 levels and fasting gastrin-17 using Biohit GastroPanel. Gastric antral biopsies and juice were obtained for histology and pH respectively. Also included were historical data from HIV negative participants (n = 72) in a previous study, for reference. RESULTS: we enrolled 84 HIV positive individuals with a median age 42 years (IQR 37-40 years). 55(66%) were female, 32(38%) were ART naïve, and 52(62%) were on ART. Hypochlorhydria (pH4) was present in 48(57%) of the HIV positive and 18(25%) of the HIV negative individuals (OR 4: 95% CI 1.9-8.5, p=0.001) with no significant effect of ART (OR 0.9: 95% CI 0.3-2.3, P = 0.82). Hypochlorhydria was not associated with the serological detection of corpus atrophy using low PG 1:2 ratio (OR 2.1: 95% CI 0.5-10.2, P = 0.37) or GastroPanel algorithm, (OR 0.7: 95% CI 0.01-60.1, P = 1.0). ART reduced the frequency of low PG 1:2 ratio (P = 0.001), but not the histological detection in the antrum of atrophy or non-atrophic gastritis. CONCLUSION: ART use is associated with reduced serological evidence of corpus atrophy but has no effect on fasting pH, supporting earlier data that suggest that the mechanism of HIV-associated hypochlorhydria is multifactorial.
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- 2018
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8. Effects of Myopia on Rates of Change in Optical Coherence Tomography Measured Retinal Layer Thicknesses in People with Multiple Sclerosis and Healthy Controls.
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Kalaitzidis, Grigorios, Pellegrini, Nicole, Nagy, Natalia, Vasileiou, Eleni, Ehrhardt, Henrik, Reppen, Abbey, Murphy, Olwen C., Moussa, Hussein, Filippatou, Angeliki, Lambe, Jeffrey, DuVal, Anna, Fioravante, Nicholas, Kwakyi, Ohemaa, Nguyen, James, Davis, Simidele, Douglas, Morgan, Ramirez, Alexandra, Ecoff, Katie, Valenzuela, Alyssandra, and Reyes-Mantilla, Maria
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OPTICAL coherence tomography ,MYOPIA ,MULTIPLE sclerosis ,REFRACTIVE errors ,RETINAL artery ,NERVE fibers ,CHOROID - Abstract
To quantify the associations of myopia with longitudinal changes in retinal layer thicknesses in people with multiple sclerosis (PwMS) and healthy controls (HC). A cohort of PwMS and HC with recorded refractive error (RE) prospectively scanned on Cirrus HD-OCT at the Johns Hopkins MS Center was assessed for inclusion. Exclusion criteria included OCT follow-up < 6 months, ocular comorbidities, incidental OCT pathologies, and inadequate scan quality. Eyes were classified as having high myopia (HM) (RE≤ −6 diopters), low myopia (LM) (RE> −6 and ≤ −3 diopters), or no myopia (NM) (RE> −3 and ≤ +2.75). Linear mixed-effects regression models were used in analyses. A total of 213 PwMS (eyes: 67 HM, 98 LM, 207 NM) and 80 HC (eyes: 26 HM, 37 LM, 93 NM) were included. Baseline average ganglion cell/inner plexiform (GCIPL) and peri-papillary retinal nerve fiber layer (pRNFL) thicknesses were lower in MS HM compared with MS NM (diff: −3.2 µm, 95% CI: −5.5 to −0.8, p = 0.008 and −5.3 µm, 95% CI: −9.0 to −1.7, p = 0.004, respectively), and similarly in HC HM, as compared with HC NM. Baseline superior, inferior, and nasal pRNFL thicknesses were lower in HM compared with NM, while temporal pRNFL thickness was higher, both in MS and HC (MS: 7.1 µm, 95% CI: 2.7–11.6, p = 0.002; HC: 4.7 µm, 95% CI: −0.3 to 9.7, p = 0.07). No longitudinal differences in rates of GCIPL change were noted between HM and LM vs. NM, either in MS or HC. Cross-sectional differences in average GCIPL and pRNFL thicknesses are commonly seen in people with HM as compared to reference normative values from people with NM and can lead to false attribution of pathology if RE is not taken into account. However, our study suggests that longitudinal changes in average GCIPL thickness in PwMS with myopia are similar in magnitude to PwMS with NM, and therefore are appropriate for monitoring disease-related pathology. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Molecular Imaging of Gastric Neoplasia with Near-Infrared Fluorescent Activatable Probes
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Shengli Ding, Randall Eric Blue, Yijing Chen, Brooks Scull, Pauline Kay Lund, and Douglas Morgan
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Biology (General) ,QH301-705.5 ,Medical technology ,R855-855.5 - Abstract
Gastric cancer is the second leading cause of cancer mortality worldwide and is projected to rise to tenth in all-cause mortality in the near term. Early detection requires improved sensitivity and specificity of endoscopic imaging with novel methods. The objective of this study was to evaluate the utility of activatable molecular probes for the detection of gastric cancer both in vivo and ex vivo in a preclinical model. Smad4 +/− mice, which develop spontaneous gastric neoplasia, were compared to normal wild-type controls. Cathepsin-activatable and matrix metalloproteinase (MMP)-activatable molecular probes were injected 24 hours and 6 hours before imaging, respectively. In vivo imaging was performed using quantitative tomographic near-infrared fluorescence (NIRF) imaging. For validation, ex vivo imaging and histologic examination were performed. Molecular imaging in vivo of Smad4 +/− gastric cancer murine models revealed intense activation of both cathepsin B and MMP probes. Ex vivo imaging and histology confirmed that the detected neoplasms were adenocarcinomas and hyperplastic lesions. This study provides proof of principle that the cathepsin- and MMP-activatable molecular probes are activated in the Smad4 +/− murine model of spontaneous gastric adenocarcinoma and can be imaged by both in vivo and ex vivo NIRF methods. The cathepsin probe also detects hyperplastic lesions.
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- 2012
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10. The Epidemiology of Functional Gastrointestinal Disorders in Mexico: A Population-Based Study
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Aurelio López-Colombo, Douglas Morgan, Dalia Bravo-González, Alvaro Montiel-Jarquín, Socorro Méndez-Martínez, and Max Schmulson
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Aims. The frequency of functional gastrointestinal disorders (FGIDs) in the general population of Mexico is unknown. Methods. To determine the prevalence of FGIDs, associated depression, and health care utilization, a population-based sampling strategy was used to select 500 households in the State of Tlaxcala, in central Mexico. Household interviews were conducted by two trained physicians using the Rome II Modular Questionnaire, a health-care and medication used questionnaire and the CES-D depression scale. Results. The most common FGIDs were IBS: 16.0% (95% CI: 12.9–19.5); functional bloating: 10.8% (8.2–13.9); unspecified functional bowel disorder: 10.6% (8.0–13.6); and functional constipation (FC): 7.4% (5.3–10.1). Uninvestigated heartburn was common: 19.6% (16.2–23.4). All FGIDs were equally prevalent among both genders, except for IBS (P=0.001), IBS-C (P
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- 2012
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11. Risk Factors for Infection and Health Impacts of the Coronavirus Disease 2019 (COVID-19) Pandemic in People With Autoimmune Diseases.
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Fitzgerald, Kathryn C, Mecoli, Christopher A, Douglas, Morgan, Harris, Samantha, Aravidis, Berna, Albayda, Jemima, Sotirchos, Elias S, Hoke, Ahmet, Orbai, Ana-Maria, Petri, Michelle, Christopher-Stine, Lisa, Baer, Alan N, Paik, Julie J, Adler, Brittany L, Tiniakou, Eleni, Timlin, Homa, Bhargava, Pavan, Newsome, Scott D, Venkatesan, Arun, and Chaudhry, Vinay
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GLUCOCORTICOIDS ,COVID-19 ,ACQUISITION of data methodology ,CONFIDENCE intervals ,INFLAMMATION ,AUTOIMMUNE diseases ,MENTAL health ,RISK assessment ,SOCIOECONOMIC factors ,MEDICAL records ,QUESTIONNAIRES ,IMMUNOLOGICAL adjuvants ,DESCRIPTIVE statistics ,HEALTH behavior ,HEALTH impact assessment ,IMMUNOSUPPRESSIVE agents ,ODDS ratio ,SOCIAL distancing ,COVID-19 pandemic ,LONGITUDINAL method ,COMORBIDITY ,DISEASE complications - Abstract
Background People with autoimmune or inflammatory conditions taking immunomodulatory/suppressive medications may have higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences. Methods We included participants with autoimmune or inflammatory conditions followed by specialists at Johns Hopkins. Participants completed periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. We assessed whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterized pandemic-associated changes to care and mental health. Results In total, 265 (5.6%) developed COVID-19 over 9 months of follow-up (April–December 2020). Patient characteristics (age, race, comorbidity, medications) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in models incorporating behavior and other potential confounders (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95% CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95% CI: 1.24, 2.28), and kidney disease (OR: 1.76; 95% CI: 1.04, 2.97) were associated with higher odds of COVID-19. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions therein, which disproportionately affected individuals experiencing changes to employment or income. Conclusions Glucocorticoid exposure may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions. [ABSTRACT FROM AUTHOR]
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- 2022
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12. A Case for Incorporating Aboriginal\n Perspectives in Education
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Douglas Morgan and Malcolm Slade
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Special aspects of education ,LC8-6691 - Published
- 1998
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13. Species identity influences belowground arthropod assemblages via functional traits.
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Gorman, Courtney E., Read, Quentin D., Van Nuland, Michael E., Bryant, Jessica A. M., Welch, Jessica N., Altobelli, Joseph T., Douglas, Morgan J., Genung, Mark A., Haag, Elliot N., Jones, Devin N., Long, Hannah E., Wilburn, Adam D., Schweitzer, Jennifer A., and Bailey, Joseph K.
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- 2013
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14. Gastroesophageal Reflux Disease as an Etiology of Sleep Disturbance in Subjects with Insomnia and Minimal Reflux Symptoms: A Pilot Study of Prevalence and Response to Therapy.
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Nicholas Shaheen, Ryan Madanick, Maha Alattar, Douglas Morgan, Paris Davis, Joseph Galanko, Melissa Spacek, and Bradley Vaughn
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GASTROESOPHAGEAL reflux ,ESOPHAGUS diseases ,SLEEP disorders ,INSOMNIA - Abstract
Abstract Background Gastroesophageal reflux disease (GERD) is a well-recognized cause of impaired sleep in patients with frequent GERD symptoms, as well as those with sleep apnea. GERD’s role in sleep disturbance of minimally symptomatic patients with poor sleep quality is less clear. Aim We aimed to define the prevalence of GERD-related sleep disturbance in minimally-symptomatic subjects with demonstrated insomnia, and to assess the changes in sleep efficiency in these subjects after vigorous acid suppression. Methods We recruited subjects aged 18–75 years reporting at least 6 months of insomnia, and sleep difficulty at least three nights per week. Subjects with a BMI > 30, a history of snoring or ongoing use of proton pump inhibitor or H2 receptor antagonist were excluded. Subjects underwent concurrent sleep study with dual channel 24-h pH study. Sleep efficiency, defined as the percentage of time after sleep initiation that the subject actually slept, and spontaneous arousal index, defined as the number of arousals per hour, were calculated. Those with a sleep study demonstrating poor sleep quality (sleep efficiency of 10 arousals/h for those aged 15 for those who were 45 or older) and no obstructive sleep apnea were treated with rabeprazole 20 mg PO BID × 14 days. After 14 days, the subjects underwent repeat sleep study with pH monitoring. The GERD Symptom Assessment Scale (GSAS), the Epworth Sleepiness Scale (ESS) and the Functional Outcomes of Sleep Questionnaire (FOSQ) were administered to subjects at study inception and after 2 weeks of therapy. Results Twenty-four subjects reporting insomnia were enrolled, and 20 met criteria for disordered sleep and no OSA. Seventeen completed both the first and second studies, and 16 were adequate for analysis. Baseline GSAS demonstrated trivial or no reflux symptoms in the cohort (no subject scored >8 out of 45 on GSAS, corresponding to a median rating of reflux symptoms of “not at all”). Four of 16 subjects (25%) demonstrated abnormal pH studies at baseline. All four had normalization of acid exposures on PPI. After 2 weeks of treatment, three of these four subjects had normalization of sleep efficiency, compared to 4 of 12 of the subjects with normal Johnson-DeMeester scores. Repeated measures analysis showed significant improvement in spontaneous arousal index between the first and second study for the whole group (P Conclusions Despite the lack of GERD symptoms, a significant minority of subjects with sleep disturbance have abnormal acid exposures. These preliminary data suggest that aggressive treatment of GERD in such patients may result in improvement in sleep efficiency. [ABSTRACT FROM AUTHOR]
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- 2008
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15. Chandra Early-type Galaxy Atlas.
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Dong-Woo Kim, Craig Anderson, Douglas Burke, Raffaele D’Abrusco, Giuseppina Fabbiano, Antonella Fruscione, Jennifer Lauer, Michael McCollough, Douglas Morgan, Amy Mossman, Ewan O’Sullivan, Alessandro Paggi, Saeqa Vrtilek, and Ginevra Trinchieri
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- 2019
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16. BINARY PROPERTIES FROM CEPHEID RADIAL VELOCITIES (CRaV).
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Nancy Remage Evans, Leonid Berdnikov, Jennifer Lauer, Douglas Morgan, Joy Nichols, H. Moritz Günther, Natalya Gorynya, Alexey Rastorguev, and Pawel Moskalik
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- 2015
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17. Fire Promotes Pollinator Visitation: Implications for Ameliorating Declines of Pollination Services.
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Van Nuland, Michael E., Haag, Elliot N., Bryant, Jessica A. M., Read, Quentin D., Klein, Robert N., Douglas, Morgan J., Gorman, Courtney E., Greenwell, Trey D., Busby, Mark W., Collins, Jonathan, LeRoy, Joseph T., Schuchmann, George, Schweitzer, Jennifer A., and Bailey, Joseph K.
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POLLINATORS ,ECOSYSTEMS ,AGRICULTURE ,INFORMATION theory ,COMPARATIVE studies ,PLANT spacing - Abstract
Pollinators serve critical roles for the functioning of terrestrial ecosystems, and have an estimated annual value of over $150 billion for global agriculture. Mounting evidence from agricultural systems reveals that pollinators are declining in many regions of the world, and with a lack of information on whether pollinator communities in natural systems are following similar trends, identifying factors which support pollinator visitation and services are important for ameliorating the effects of the current global pollinator crisis. We investigated how fire affects resource structure and how that variation influences floral pollinator communities by comparing burn versus control treatments in a southeastern USA old-field system. We hypothesized and found a positive relationship between fire and plant density of a native forb, Verbesina alternifolia, as well as a significant difference in floral visitation of V. alternifolia between burn and control treatments. V. alternifolia density was 44% greater and floral visitation was 54% greater in burned treatments relative to control sites. When the density of V. alternifolia was experimentally reduced in the burn sites to equivalent densities observed in control sites, floral visitation in burned sites declined to rates found in control sites. Our results indicate that plant density is a proximal mechanism by which an imposed fire regime can indirectly impact floral visitation, suggesting its usefulness as a tool for management of pollination services. Although concerns surround the negative impacts of management, indirect positive effects may provide an important direction to explore for managing future ecological and conservation issues. Studies examining the interaction among resource concentration, plant apparency, and how fire affects the evolutionary consequences of altered patterns of floral visitation are overdue. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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18. Reassessment of the Cross-Florida Barge Canal: A probability approach
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Mercer, Lloyd J and Douglas Morgan, W
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- 1976
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19. Alternative interpretations of market saturation: Evaluation for the automobile market in the late twenties
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Mercer, Lloyd J and Douglas Morgan, W
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- 1971
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20. Effects of Ibudilast on Retinal Atrophy in Progressive Multiple Sclerosis Subtypes: Post Hoc Analyses of the SPRINT-MS Trial.
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Ehrhardt H, Lambe J, Moussa H, Vasileiou ES, Kalaitzidis G, Murphy OC, Filippatou AG, Pellegrini N, Douglas M, Davis S, Nagy N, Quiroga A, Hu C, Zambriczki Lee A, Duval A, Fitzgerald KC, Prince JL, Calabresi PA, Sotirchos ES, Bermel R, and Saidha S
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- Humans, Retina pathology, Pyridines therapeutic use, Tomography, Optical Coherence methods, Atrophy drug therapy, Atrophy pathology, Multiple Sclerosis complications, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis drug therapy, Multiple Sclerosis, Chronic Progressive diagnostic imaging, Multiple Sclerosis, Chronic Progressive drug therapy, Multiple Sclerosis, Chronic Progressive pathology, Retinal Degeneration diagnostic imaging, Retinal Degeneration drug therapy, Retinal Degeneration pathology
- Abstract
Background and Objectives: Ganglion cell + inner plexiform layer (GCIPL) thinning, measured by optical coherence tomography (OCT), reflects global neurodegeneration in multiple sclerosis (MS). Atrophy of the inner (INL) and outer nuclear layer (ONL) may also be prominent in progressive MS (PMS). The phase 2, SPRINT-MS trial found reduced brain atrophy with ibudilast therapy in PMS. In this post hoc analysis of the SPRINT-MS trial, we investigate (1) retinal atrophy (2) differences in response by subtype and (3) associations between OCT and MRI measures of neurodegeneration., Methods: In the multicenter, double-blind SPRINT-MS trial, participants with secondary progressive MS (SPMS) or primary progressive MS (PPMS) were randomized to ibudilast or placebo. OCT and MRI data were collected every 24 weeks for 96 weeks. Extensive OCT quality control and algorithmic segmentation produced consistent results across Cirrus HD-OCT and Spectralis devices. Primary endpoints were GCIPL, INL, and ONL atrophy, assessed by linear mixed-effects regression. Secondary endpoints were associations of OCT measures, brain parenchymal fraction, and cortical thickness, assessed by partial Pearson correlations., Results: One hundred thirty-four PPMS and 121 SPMS participants were included. GCIPL atrophy was 79% slower in the ibudilast (-0.07 ± 0.23 µm/y) vs placebo group (-0.32 ± 0.20 µm/y, p = 0.003). This effect predominated in the PPMS cohort (ibudilast: -0.08 ± 0.29 µm/y vs placebo: -0.60 ± 0.29 µm/y, a decrease of 87%, p < 0.001) and was not detected in the SPMS cohort (ibudilast: -0.21 ± 0.28 µm/y vs placebo: -0.14 ± 0.27 µm/y, p = 0.55). GCIPL, INL, and ONL atrophy rates correlated with whole brain atrophy rates across the cohort ( r = 0.27, r = 0.26, and r = 0.20, respectively; p < 0.001). Power calculations from these data show future trials of similar size and design have ≥80% power to detect GCIPL atrophy effect sizes of approximately 40%., Discussion: Ibudilast treatment decreased GCIPL atrophy in PMS, driven by the PPMS cohort, with no effect seen in SPMS. Modulated atrophy of retinal layers may be detectable in sample sizes smaller than the SPRINT-MS trial and correlate with whole brain atrophy in PMS, further highlighting their utility as outcomes in PMS., Classification of Evidence: This study provides Class II evidence that ibudilast reduces composite ganglion cell + inner plexiform layer atrophy, without reduction of inner or outer nuclear layer atrophy, in patients with primary progressive MS but not those with secondary progressive MS., (© 2023 American Academy of Neurology.)
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- 2023
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21. Discordant humoral and T cell immune responses to SARS-CoV-2 vaccination in people with multiple sclerosis on anti-CD20 therapy.
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Gadani SP, Reyes-Mantilla M, Jank L, Harris S, Douglas M, Smith MD, Calabresi PA, Mowry EM, Fitzgerald KC, and Bhargava P
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- Adult, Aged, Antibodies, Monoclonal, Humanized therapeutic use, COVID-19 prevention & control, COVID-19 virology, COVID-19 Vaccines immunology, Female, Humans, Immunologic Factors therapeutic use, Leukocytes, Mononuclear cytology, Leukocytes, Mononuclear metabolism, Male, Middle Aged, Multiple Sclerosis drug therapy, SARS-CoV-2 immunology, SARS-CoV-2 isolation & purification, Vaccination, COVID-19 immunology, COVID-19 Vaccines administration & dosage, Immunity, Cellular, Immunity, Humoral, Multiple Sclerosis pathology
- Abstract
Background: Sphingosine-1-phosphate receptor (S1P) modulators and anti-CD20 therapies impair humoral responses to SARS-CoV-2 mRNA vaccines. Relatively few studies have assessed the impact of an array of disease modifying therapies (DMTs) for multiple sclerosis (MS) on T cell immune responses to SARS-CoV-2 vaccination., Methods: In 101 people with MS, we measured humoral responses via an immunoassay to measure IgG against the COVID-19 spike S1 glycoprotein in serum. We also measured T cell responses using FluoroSpot assay for interferon gamma (IFN-γ) (Mabtech, Sweden) using cryopreserved rested PBMCs and then incubated in cRPMI with 1µg/ml of pooled peptides spanning the entire spike glycoprotein (Genscript, 2 pools; 158 peptides each). Plates were read on an AID iSpot Spectrum to determine the number of spot forming cells (SFC)/10
6 PBMCs. We tested for differences in immune responses across DMTs using linear models., Findings: Humoral responses were detected in 22/39 (56.4%) participants on anti-CD20 and in 59/63 (93.6%) participants on no or other DMTs. In a subset (n=88; 87%), T cell responses were detected in 76/88 (86%), including 32/33 (96.9%) participants on anti-CD20 therapies. Anti-CD20 therapies were associated with an increase in IFN-γ SFC counts relative to those on no DMT or other DMTs (for anti-CD20 vs. no DMT: 425.9% higher [95%CI: 109.6%, 1206.6%] higher; p<0.001; for anti-CD20 vs. other DMTs: 289.6% [95%CI: 85.9%, 716.6%] higher; p<0.001)., Interpretation: We identified a robust T cell response in individuals on anti-CD20 therapies despite a reduced humoral response to SARS-CoV-2 vaccination. Follow up studies are needed to determine if this translates to protection against COVID-19 infection., Funding: This study was funded partially by 1K01MH121582-01 from NIH/NIMH and TA-1805-31136 from the National MS Society (NMSS) to KCF and TA-1503-03465 and JF-2007-37655 from the NMSS to PB. This study was also supported through the generosity of the collective community of donors to the Johns Hopkins University School of Medicine for COVID research., Competing Interests: Declaration of Competing Interest SPG has nothing to disclose. MRM has nothing to disclose. LJ has nothing to disclose. SH has nothing to disclose. MD has nothing to disclose. MDS has nothing to disclose. PAC has received consulting fees from Disarm and Biogen and is PI on grants to JHU from Genentech, Principia, and Annexon. EMM reports receiving research funding as site PI or for investigator-initiated studies from Biogen, Genentech, and Teva. She receives royalties for editorial duties from UpToDate. KCF has nothing to disclose. PB reports receiving research funding from Genentech, Amylyx pharmaceuticals and EMD Serono and has received honoraria from EMD-Serono and Sanofi-Genzyme., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)- Published
- 2021
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22. RISK FACTORS FOR INFECTION AND HEALTH IMPACTS OF THE COVID-19 PANDEMIC IN PEOPLE WITH AUTOIMMUNE DISEASES.
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Fitzgerald KC, Mecoli CA, Douglas M, Harris S, Aravidis B, Albayda J, Sotirchos ES, Hoke A, Orbai AM, Petri M, Christopher-Stine L, Baer AN, Paik JJ, Adler BL, Tiniakou E, Timlin H, Bhargava P, Newsome SD, Venkatesan A, Chaudhry V, Lloyd TE, Pardo CA, Stern BJ, Lazarev M, Truta B, Saidha S, Chen ES, Sharp M, Gilotra N, Kasper EK, Gelber AC, Bingham CO 3rd, Shah AA, and Mowry EM
- Abstract
Background: People with autoimmune or inflammatory conditions who take immunomodulatory/suppressive medications may have a higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences., Objective: Assess whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterize pandemic-associated changes to care., Design: Longitudinal registry study., Participants: 4666 individuals with autoimmune or inflammatory conditions followed by specialists in neurology, rheumatology, cardiology, pulmonology or gastroenterology at Johns Hopkins., Measurements: Periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare., Results: A total of 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medication exposure) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in multivariable models incorporating behavior and other potential confounders (OR: 1.43; 95%CI: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95%CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95%CI: 1.24, 2.28), and chronic kidney disease (OR: 1.76; 95%CI: 1.04, 2.97) were each associated with higher odds of COVID-19. Pandemic-related disruption to care was common. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions. Individuals experiencing changes to employment or income were at highest odds of care disruption., Limitations: Results may not be generalizable to all patients with autoimmune or inflammatory conditions. Information was self-reported., Conclusions: Exposure to glucocorticoids may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.
- Published
- 2021
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23. Multiple sclerosis management during the COVID-19 pandemic.
- Author
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Moss BP, Mahajan KR, Bermel RA, Hellisz K, Hua LH, Hudec T, Husak S, McGinley MP, Ontaneda D, Wang Z, Weber M, Tagliani P, Cárdenas-Robledo S, Zabalza A, Arrambide G, Carbonell-Mirabent P, Rodríguez-Barranco M, Sastre-Garriga J, Tintore M, Montalban X, Douglas M, Ogbuokiri E, Aravidis B, Cohen JA, Mowry EM, and Fitzgerald KC
- Subjects
- Adult, Age Factors, Betacoronavirus, COVID-19, Comorbidity, Coronavirus Infections prevention & control, Delivery of Health Care, Disease Management, Disease Susceptibility, Educational Status, Female, Health Behavior, Health Services Accessibility, Home Infusion Therapy, Humans, Hypertension epidemiology, Male, Middle Aged, Multivariate Analysis, Obesity epidemiology, Pandemics prevention & control, Pneumonia, Viral prevention & control, Risk Factors, SARS-CoV-2, Spain epidemiology, United States epidemiology, Coronavirus Infections epidemiology, Employment, Immunologic Factors therapeutic use, Multiple Sclerosis therapy, Occupational Therapy, Physical Therapy Modalities, Pneumonia, Viral epidemiology, Social Class
- Abstract
Background: People with multiple sclerosis (MS) may be at higher risk for complications from the 2019 coronavirus (COVID-19) pandemic due to use of immunomodulatory disease modifying therapies (DMTs) and greater need for medical services., Objectives: To evaluate risk factors for COVID-19 susceptibility and describe the pandemic's impact on healthcare delivery., Methods: Surveys sent to MS patients at Cleveland Clinic, Johns Hopkins, and Vall d'Hebron-Centre d'Esclerosi Múltiple de Catalunya in April and May 2020 collected information about comorbidities, DMTs, exposures, COVID-19 testing/outcomes, health behaviors, and disruptions to MS care., Results: There were 3028/10,816 responders. Suspected or confirmed COVID-19 cases were more likely to have a known COVID-19 contact (odds ratio (OR): 4.38; 95% confidence interval (CI): 1.04, 18.54). In multivariable-adjusted models, people who were younger, had to work on site, had a lower education level, and resided in socioeconomically disadvantaged areas were less likely to follow social distancing guidelines. 4.4% reported changes to therapy plans, primarily delays in infusions, and 15.5% a disruption to rehabilitative services., Conclusion: Younger people with lower socioeconomic status required to work on site may be at higher exposure risk and are potential targets for educational intervention and work restrictions to limit exposure. Providers should be mindful of potential infusion delays and MS care disruption.
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- 2020
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24. Pelagic larval duration predicts extinction risk in a freshwater fish clade.
- Author
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Douglas M, Keck BP, Ruble C, Petty M, Shute JR, Rakes P, and Hulsey CD
- Subjects
- Animals, Biological Evolution, Fishes, Fossils, Fresh Water, Models, Biological, Phylogeny, Risk, Species Specificity, Time Factors, Extinction, Biological, Larva physiology, Perciformes physiology
- Abstract
Pelagic larval duration (PLD) can influence evolutionary processes ranging from dispersal to extinction in aquatic organisms. Using estimates of PLD obtained from species of North American darters (Percidae: Etheostomatinae), we demonstrate that this freshwater fish clade exhibits surprising variation in PLD. Comparative analyses provide some evidence that higher stream gradients favour the evolution of shorter PLD. Additionally, similar to patterns in the marine fossil record in which lower PLD is associated with greater extinction probability, we found a reduced PLD in darter lineages was evolutionarily associated with extinction risk. Understanding the causes and consequences of PLD length could lead to better management and conservation of organisms in our increasingly imperiled aquatic environments.
- Published
- 2013
- Full Text
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