154 results on '"Hope, L."'
Search Results
2. Utilization of a cell‐penetrating peptide‐adaptor for delivery of human papillomavirus protein <scp>E2</scp> into cervical cancer cells to arrest cell growth and promote cell death
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Julia C. LeCher, Hope L. Didier, Robert L. Dickson, Lauren R. Slaughter, Juana C. Bejarano, Steven Ho, Scott J. Nowak, Carol A. Chrestensen, and Jonathan L. McMurry
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Cancer Research ,Oncology - Published
- 2023
3. Connecting Genetic Heterogeneity with Single-Cell Transcriptome Dysregulations in Pediatric Acute Myeloid Leukemia
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Upaasana Krishnan, Beena E Thomas, Swati S Bhasin, Hope L Mumme, and Manoj Bhasin
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
4. A Single Cell Atlas and Interactive Web-Resource of Pediatric Cancers and Healthy Bone Marrow
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Hope L Mumme, Swati S Bhasin, Mariam Nawaz, Beena E Thomas, Chenbin Huang, Deborah DeRyckere, Sharon M. Castellino, Daniel S. Wechsler, Sunil S. Raikar, Christopher C. Porter, Douglas K Graham, and Manoj Bhasin
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
5. Single-Cell Profiling of Acute Myeloid Leukemia Identified ARMH1, a Novel Protein Associated with Proliferation, Migration, and Drug Resistance
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Mojtaba Bakhtiarigheshlaghbakhtiar, Swati S Bhasin, Beena E Thomas, Hope L Mumme, and Manoj Bhasin
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
6. Clinical and Metabolic Characterization of Adults With Type 2 Diabetes by Age in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) Cohort
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Aroda, Vanita R., Krause-Steinrauf, Heidi, Kazemi, Erin J., Buse, John B., Gulanski, Barbara I., Florez, Hermes J., Ahmann, Andrew J., Loveland, Amy, Kuhn, Alexander, Lonier, Jacqueline Y., Wexler, Deborah J., Crandall, J.P., McKee, M.D., Behringer-Massera, S., Brown-Friday, J., Xhori, E., Ballentine-Cargill, K., Duran, S., Estrella, H., Gonzalez de la torre, S., Lukin, J., Phillips, L.S., Burgess, E., Olson, D., Rhee, M., Wilson, P., Raines, T.S., Boers, J., Costello, J., Maher-Albertelli, M., Mungara, R., Savoye, L., White, C.A., Gullett, C., Holloway, L., Morehead, F., Person, S., Sibymon, M., Tanukonda, S., Adams, C., Ross, A., Balasubramanyam, A., Gaba, R., Gonzalez Hattery, E., Ideozu, A., Jimenez, J., Montes, G., Wright, C., Hollander, P., Roe, E., Jackson, A., Smiley, A., Burt, P., Estrada, L., Chionh, K., Ismail-Beigi, F., Falck-Ytter, C., Sayyed Kassem, L., Sood, A., Tiktin, M., Kulow, T., Newman, C., Stancil, K.A., Cramer, B., Iacoboni, J., Kononets, M.V., Sanders, C., Tucker, L., Werner, A., Maxwell, A., McPhee, G., Patel, C., Colosimo, L., Krol, A., Goland, R., Pring, J., Alfano, L., Kringas, P., Hausheer, C., Tejada, J., Gumpel, K., Kirpitch, A., Schneier, H., Green, J.B., AbouAssi, H., Chatterjee, R., Feinglos, M.N., English Jones, J., Khan, S.A., Kimpel, J.B., Zimmer, R.P., Furst, M., Satterwhite, B.M., Thacker, C.R., Evans Kreider, K., Mariash, C.N., Mather, K.J., Ismail, H.M., Lteif, A., Mullen, M., Hamilton, T., Patel, N., Riera, G., Jackson, M., Pirics, V., Aguillar, D., Howard, D., Hurt, S., Bergenstal, R., Carlson, A., Martens, T., Johnson, M., Hill, R., Hyatt, J., Jensen, C., Madden, M., Martin, D., Willis, H., Konerza, W., Yang, S., Kleeberger, K., Passi, R., Fortmann, S., Herson, M., Mularski, K., Glauber, H., Prihoda, J., Ash, B., Carlson, C., Ramey, P.A., Schield, E., Torgrimson-Ojerio, B., Arnold, K., Kauffman, B., Panos, E., Sahnow, S., Bays, K., Berame, K., Cook, J., Ghioni, D., Gluth, J., Schell, K., Criscola, J., Friason, C., Jones, S., Nazarov, S., Barzilay, J., Rassouli, N., Puttnam, R., Ojoawo, B., Nelson, R., Curtis, M., Hollis, B., Sanders-Jones, C., Stokes, K., El-Haqq, Z., Kolli, A., Tran, T., Wexler, D., Larkin, M., Meigs, J., Chambers, B., Dushkin, A., Rocchio, G., Yepes, M., Steiner, B., Dulin, H., Cayford, M., Chu, K., DeManbey, A., Hillard, M., Martin, K., Thangthaeng, N., Gurry, L., Kochis, R., Raymond, E., Ripley, V., Stevens, C., Park, J., Aroda, V., Ghazi, A., Magee, M., Ressing, Ann, Loveland, A., Hamm, M., Hurtado, M., Kuhn, A., Leger, J., Manandhar, L., Sanchez, O., Young, T., Mofor, F., Garg, R., Lagari-Libhaber, V., Florez, H.J., Valencia, W.M., Marks, J., Casula, S., Oropesa-Gonzalez, L., Hue, L., Cuadot, A., Nieto-Martinez, R., Riccio Veliz, A.K., Gutt, M., Kendal, Y.J., Veciana, B., Ahmann, A., Aby-Daniel, D., Joarder, F., Morimoto, V., Sprague, C., Yamashita, D., Cady, N., Rivera-Eschright, N., Kirchhoff, P., Morales Gomez, B., Adducci, J., Goncharova, A., Hox, S.H., Petrovitch, H., Matwichyna, M., Jenkins, V., Broadwater, L., Ishii, R.R., Bermudez, N.O., Hsia, D.S., Cefalu, W.T., Greenway, F.L., Waguespack, C., King, E., Fry, G., Dragg, A., Gildersleeve, B., Arceneaux, J., Haynes, N., Thomassie, A., Pavlionis, M., Bourgeois, B., Hazlett, C., Mudaliar, S., Henry, R., Boeder, S., Pettus, J., Diaz, E., Garcia-Acosta, D., Maggs, S., DeLue, C., Stallings, A., Castro, E., Hernandez, S., Krakoff, J., Curtis, J.M., Killean, T., Khalid, M., Joshevama, E., Tsingine, K., Karshner, T., Albu, J., Pi-Sunyer, F.X., Frances, S., Maggio, C., Ellis, E., Bastawrose, J., Gong, X., Banerji, M.A., August, P., Lee, M., Lorber, D., Brown, N.M., Josephson, D.H., Thomas, L.L., Tsovian, M., Cherian, A., Jacobson, M.H., Mishko, M.M., Kirkman, M.S., Buse, J.B., Dostou, J., Machineni, S., Young, L., Bergamo, K., Goley, A., Kerr, J., Largay, J.F., Guarda, S., Cuffee, J., Culmer, D., Fraser, R., Almeida, H., Coffer, S., Debnam, E., Kiker, L., Morton, S., Josey, K., Fuller, G., Garvey, W.T., Cherrington, A.L., Dyer, D., Lawson, M.C.R., Griffith, O., Agne, A., McCullars, S., Cohen, R.M., Craig, J., Rogge, M.C., Burton, K., Kersey, K., Wilson, C., Lipp, S., Vonder Meulen, M.B., Adkins, C., Onadeko, T., Rasouli, N., Baker, C., Schroeder, E., Razzaghi, M., Lyon, C., Penaloza, R., Underkofler, C., Lorch, R., Douglass, S., Steiner, S., Sivitz, W.I., Cline, E., Knosp, L.K., McConnell, J., Lowe, T., Herman, W.H., Pop-Busui, R., Tan, M.H., Martin, C., Waltje, A., Katona, A., Goodhall, L., Eggleston, R., Kuo, S., Bojescu, S., Bule, S., Kessler, N., LaSalle, E., Whitley, K., Seaquist, E.R., Bantle, A., Harindhanavudhi, T., Kumar, A., Redmon, B., Bantle, J., Coe, M., Mech, M., Taddese, A., Lesne, L., Smith, S., Desouza, C., Kuechenmeister, L., Shivaswamy, V., Burbach, S., Rodriguez, M.G., Seipel, K., Alfred, A., Morales, A.L., Eggert, J., Lord, G., Taylor, W., Tillson, R., Schade, D.S., Adolphe, A., Burge, M., Duran-Valdez, E., Martinez, J., Bancroft, A., Kunkel, S., Ali Jamaleddin Ahmad, F., Hernandez McGinnis, D., Pucchetti, B., Scripsick, E., Zamorano, A., DeFronzo, R.A., Cersosimo, E., Abdul-Ghani, M., Triplitt, C., Juarez, D., Garza, R.I., Verastiqui, H., Wright, K., Puckett, C., Raskin, P., Rhee, C., Abraham, S., Jordan, L.F., Sao, S., Morton, L., Smith, O., Osornio Walker, L., Schnurr-Breen, L., Ayala, R., Kreymer, R.B., Sturgess, D., Utzschneider, K.M., Kahn, S.E., Alarcon-Casas, L., Wright, L., Boyko, E.J., Tsai, E.C., Trence, D.L., Trikudanathan, S., Fattaleh, B.N., Montgomery, B.K., Atkinson, K.M., Kozedub, A., Concepcion, T., Moak, C., Prikhodko, N., Rhothisen, S., Elasy, T.A., Martin, S., Shackelford, L., Goidel, R., Hinkle, N., Lovell, C., Myers, J., Lipps Hogan, J., McGill, J.B., Salam, M., Schweiger, T., Kissel, S., Recklein, C., Clifton, M.J., Tamborlane, W., Camp, A., Gulanski, B., Inzucchi, S.E., Pham, K., Alguard, M., Gatcomb, P., Lessard, K., Perez, M., Iannone, L., Magenheimer, E., Montosa, A., Burch, H.B., Bremer, A.A., Fradkin, J., Nathan, D.M., Lachin, J.M., Krause-Steinrauf, H., Younes, N., Backman, M., Bebu, I., Butera, N., Buys, C.J., Fagan Murphy, A., Gao, Y., Ghosh, A., Gramzinski, M.R., Kazemi, E., Hall, S.D., Legowski, E., Suratt, C., Tripputi, M., Arey, A., Bethepu, J., Lund, C., Mangat Dhaliwal, P., McGee, P., Mesimer, E., Ngo, L., Steffes, M., Seegmiller, J., Saenger, A., Arends, V., Gabrielson, D., Conner, T., Warren, S., Day, J., Huminik, J., Scrymgeour, A., Soliman, E.Z., Pokharel, Y., Zhang, Z.M., Campbell, C., Hu, J., Keasler, L., Hensley, S., Li, Y., Mihalcea, R., Min, D.J., Perez-Rosas, V., Prosser, L., Resnicow, K., Ye, W., Shao, H., Zhang, P., Luchsinger, J., Sanchez, D., Assuras, S., Groessl, E., Sakha, F., Chong, H., Hillery, N., Everett, B.M., Abdouch, I., Bahtiyar, G., Brantley, P., Broyles, F.E., Canaris, G., Copeland, P., Craine, J.J., Fein, W.L., Gliwa, A., Hope, L., Lee, M.S., Meiners, R., Meiners, V., O’Neal, H., Park, J.E., Sacerdote, A., Sledge, E., Soni, L., Steppel-Reznik, J., Turchin, A., Brooks-Worrell, B., Hampe, C.S., Newgard, C.B., Palmer, J.P., Shojaie, A., Higgins, J., Fischer, L., Golden, S., Gonzalez, J., Naik, A., Walker, E., Doner Lotenberg, L., Gallivan, J.M., Lim, J., and Tuncer, D.M.
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Clinical Care/Education/Nutrition/Psychosocial Research - Abstract
OBJECTIVE: Differences in type 2 diabetes phenotype by age are described, but it is not known whether these differences are seen in a more uniformly defined adult population at a common early stage of care. We sought to characterize age-related clinical and metabolic characteristics of adults with type 2 diabetes on metformin monotherapy, prior to treatment intensification. RESEARCH DESIGN AND METHODS: In the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), participants were enrolled who had type 2 diabetes duration
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- 2022
7. Inequality in Immunization: Holding on to Equity as We ‘Catch Up’
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Devaki Nambiar, Ahmad Reza Hosseinpoor, Nicole Bergen, M. Carolina Danovaro-Holliday, Aaron Wallace, and Hope L. Johnson
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Pharmacology ,Infectious Diseases ,Drug Discovery ,Immunology ,Pharmacology (medical) - Abstract
Immunization, hailed as one of the most successful public health interventions in the world, has contributed to major advancements in health as well as social and economic development [...]
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- 2023
8. Diagnostics to make immunisation programmes more efficient, equitable, and effective
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Lee M Hampton, Hope L Johnson, and Seth F Berkley
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Microbiology (medical) ,Infectious Diseases ,Immunization Programs ,Virology ,Vaccination ,Immunization ,Microbiology - Published
- 2022
9. Gavi Support for Typhoid Conjugate Vaccines: Moving From Global Investments to Country Introduction
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Lee M. Hampton, Stephen Sosler, Hope L. Johnson, Adam Soble, and Zeenat Patel
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Microbiology (medical) ,Economic growth ,enteric fever ,global health ,Supplement Articles ,Typhoid Conjugate Vaccine and the Future of Enteric Fever Control and Prevention ,Typhoid fever ,Global policy ,medicine ,Global health ,Humans ,Typhoid Fever ,Vaccines ,Vaccines, Conjugate ,business.industry ,Immunization Programs ,Typhoid-Paratyphoid Vaccines ,medicine.disease ,Investment (macroeconomics) ,immunizations ,Infectious Diseases ,Investment decisions ,AcademicSubjects/MED00290 ,New product development ,typhoid conjugate vaccine ,business ,Enteric fever - Abstract
Nine years elapsed between Gavi’s investment decision to support typhoid conjugate vaccines (TCVs) in 2008 and Gavi support becoming available for countries to introduce TCV. The protracted path toward Gavi support for TCV highlights the challenges of vaccine development for lower-income countries and the importance of Gavi engagement as early as possible in product development processes to support the alignment of manufacturing, global policy, and program implementation. Early engagement would provide inputs to inform strategic vaccine investment decisions that transition more efficiently toward country implementation. Several countries have been approved for Gavi support to introduce TCV in 2019–2020. The paucity of generalizable typhoid epidemiological data in early introducing countries has reinforced the need for continued evidence generation regarding typhoid epidemiology and TCV impact. This has led to the development of guidance and tools to support country decision making for TCV introduction based on enhanced understanding of local typhoid burden and risk.
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- 2020
10. Humoral and Mucosal Immune Responses to Human Norovirus in the Elderly
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Emilio DeBess, Emilie M. Cooper, Hope L. Hardaker, Jan Vinjé, Aron J. Hall, Veronica Costantini, Paul R Cieslak, and Lore E. Lee
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Male ,0301 basic medicine ,Immunoglobulin A ,Saliva ,Population ,medicine.disease_cause ,Asymptomatic ,Article ,Immunoglobulin G ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,Seroconversion ,education ,Aged ,Caliciviridae Infections ,education.field_of_study ,biology ,business.industry ,Norovirus ,Middle Aged ,Virus Shedding ,030104 developmental biology ,Infectious Diseases ,Case-Control Studies ,Immunology ,biology.protein ,Female ,medicine.symptom ,Antibody ,business - Abstract
Background Most information on mucosal and systemic immune response to norovirus infection is derived from human challenge studies, birth cohort studies, or vaccine trials in healthy adults. However, few data are available on immune responses to norovirus in the elderly. Methods To study the mucosal and systemic immune response against norovirus, 43 long-term care facilities were enrolled prospectively in 2010–2014. Baseline saliva samples from 17 facilities, cases and controls up to day 84 from 10 outbreaks, as well as acute and convalescent sera were collected. Results Norovirus-specific immunoglobulin A (IgA) levels in baseline saliva samples were low and increased in both symptomatic patients and asymptomatic shedders at day 5 after onset during outbreaks. Receiver operating characteristics analysis correctly assigned prior norovirus infection in 23 (92%) of 25 participants. Cases and asymptomatic shedders showed seroconversion for IgG (80%), IgA (78%), and blockade antibodies (87%). Salivary IgA levels strongly correlated with increased convalescent serum IgA titers and blockade antibodies. Conclusions Salivary IgA levels strongly correlated with serum IgA titers and blockade antibodies and remained elevated 3 months after a norovirus outbreak. A single salivary sample collected on day 14 could be used to identify recent infection in a suspected outbreak or to monitor population salivary IgA.
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- 2020
11. Single cell transcriptomic landscape of diabetic foot ulcers
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Georgios Theocharidis, Beena E. Thomas, Debasree Sarkar, Hope L. Mumme, William J. R. Pilcher, Bhakti Dwivedi, Teresa Sandoval-Schaefer, Ruxandra F. Sîrbulescu, Antonios Kafanas, Ikram Mezghani, Peng Wang, Antonio Lobao, Ioannis S. Vlachos, Biraja Dash, Henry C. Hsia, Valerie Horsley, Swati S. Bhasin, Aristidis Veves, and Manoj Bhasin
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Keratinocytes ,Bioinformatics ,Science ,General Physics and Astronomy ,Article ,General Biochemistry, Genetics and Molecular Biology ,Diabetes complications ,Matrix Metalloproteinase 11 ,Exome Sequencing ,Diabetes Mellitus ,Leukocytes ,Humans ,Chitinase-3-Like Protein 1 ,Transcriptomics ,Skin ,Wound Healing ,Multidisciplinary ,Macrophages ,Endothelial Cells ,High-Throughput Nucleotide Sequencing ,General Chemistry ,Fibroblasts ,Hypoxia-Inducible Factor 1, alpha Subunit ,Diabetic Foot ,Gene Expression Regulation ,Matrix Metalloproteinase 3 ,Matrix Metalloproteinase 1 ,Single-Cell Analysis ,Transcriptome ,Cell Adhesion Molecules ,Biomarkers - Abstract
Diabetic foot ulceration (DFU) is a devastating complication of diabetes whose pathogenesis remains incompletely understood. Here, we profile 174,962 single cells from the foot, forearm, and peripheral blood mononuclear cells using single-cell RNA sequencing. Our analysis shows enrichment of a unique population of fibroblasts overexpressing MMP1, MMP3, MMP11, HIF1A, CHI3L1, and TNFAIP6 and increased M1 macrophage polarization in the DFU patients with healing wounds. Further, analysis of spatially separated samples from the same patient and spatial transcriptomics reveal preferential localization of these healing associated fibroblasts toward the wound bed as compared to the wound edge or unwounded skin. Spatial transcriptomics also validates our findings of higher abundance of M1 macrophages in healers and M2 macrophages in non-healers. Our analysis provides deep insights into the wound healing microenvironment, identifying cell types that could be critical in promoting DFU healing, and may inform novel therapeutic approaches for DFU treatment., Diabetic foot ulcers (DFUs) remain a complication of diabetes that are difficult to heal and lead to disability. Here the authors use single-cell RNA-sequencing and spatial transcriptomics to characterize the DFU cellular landscape and identify a population of fibroblasts that is associated with successful wound closure.
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- 2022
12. A Tesla Turbine & Prony Brake Dynamometer Kit for Remote Benchtop Gas Turbine Educational Experimentation
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Ava C. Nemanic, Sarah Garcia, Hope L. Weiss, and Matthew J. Traum
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- 2022
13. Knowledge Engineering Tools for Probability Elicitation
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Hope, L R, Nicholson, A E, and Korb, K B
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Other information and computing sciences not elsewhere classified - Abstract
Unwieldy probability entry interfaces are the norm for Bayesian Network knowledge engineers. This requires domain experts to provide unreasonably accurate probability estimates. To solve these problems, we have developed two applications: CPTable improves direct probability entry, and provides node customisation and sliding scale binary elicitation;Verbal Elicitor allows entry of probability values in ordinary English. The domain expert selects a verbal cue such as “unlikely” or “almost certain.” The probabilities are then set manually or optimised to minimise probabilistic incoherency.
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- 2022
- Full Text
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14. A Bayesian Metric for Evaluating Machine Learning Algorithms
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Hope, L R and Korb, K B
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Other information and computing sciences not elsewhere classified - Abstract
How to assess the performance of machine learning algorithms is a problem of increasing interest and urgency as the data mining application of myriad algorithms grows. The standard approach of employing predictive accuracy has rightly been losing favor in the AI community. The alternative of cost-sensitive metrics provides a far better approach, given the availability of useful cost functions. For situations where no useful cost function can be found we need other alternatives to predictive accuracy. We propose that information-theoretic reward functions be applied. The first such proposal for assessing specifically machine learning algorithms was made by Kononenko and Bratko [1]. Here we improve upon our alternative Bayesian metric [2], which provides a fair betting assessment of any machine learner. We include an empirical analysis of various Bayesian classification learners, ranging from Naïve Bayes learners to causal discovery algorithms.
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- 2022
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15. An Information-theoretic Approach to Causal Power
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Hope, L R and Korb, K B
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Other information and computing sciences not elsewhere classified - Abstract
The measurement of causal power has been of long-standing interest in philosophy and psychology. With the development of Bayesian network technology, the interest has spread to artificial intelligence. We introduce a metric which applies information theory to Bayesian networks. We show that it generalizes prior metrics restricted to linear and noisy-or models, while providing a metric appropriate to the full representational power of Bayesian nets.
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- 2022
- Full Text
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16. PedSCAtlas: An Interactive Online Resource of Integrated Pediatric Cancers and Healthy Samples Single-Cell Data
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Hope L. Mumme, Mariam Nawaz, Beena E. Thomas, Chenbin Huang, Kathleen Imbach, Deborah DeRyckere, Greg Gibson, Sharon M. Castellino, Daniel S. Wechsler, Sunil S. Raikar, Christopher C. Porter, Douglas K. Graham, Swati S. Bhasin, and Manoj Bhasin
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
17. TakeHeart II: A tool to support clinical cardiovascular risk assessment
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Hope, L R, Nicholson, A E, and Korb, K B
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Other information and computing sciences not elsewhere classified - Abstract
Bayesian networks are powerful reasoning engines for decision support systems, due to their accomodation for a wide range of queries, and clear presentation of independence assumptions. However, their practical use hinges on an accessible presentation of the knowledge they represent: a user should be exposed to only the functionality they need to get their job done. We desired to build a software tool which generates easy to use domain-specific graphical user interfaces based on pre-existing Bayesian networks. We demonstrate the tool with TakeHeart II, a decision support system for assessing heart attack risk.
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- 2022
- Full Text
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18. Single cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia
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Ryan J. Summers, Bhakti Dwivedi, Christopher C. Porter, Sharon M. Castellino, Douglas K. Graham, Sunil S. Raikar, Beena E. Thomas, Melinda Pauly, Himalee S. Sabnis, Debasree Sarkar, Hope L Mumme, Daniel S. Wechsler, Deborah DeRyckere, Swati S. Bhasin, Pruthvi Perumalla, Sunita I. Park, Manoj Bhasin, and Gulay B. Ulukaya
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Tumor microenvironment ,Single-cell analysis ,business.industry ,hemic and lymphatic diseases ,Pediatric acute myeloid leukemia ,Cancer research ,Medicine ,business - Abstract
Relapse- and continuous complete remission (CCR)-associated pediatric acute myeloid leukemia (AML) patient bone marrows collected at the time of diagnosis (Dx), end of induction (EOI) and relapse were analyzed by single cell RNA sequencing. A novel AML blasts-associated 7-genes signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH) displayed a strong correlation with blast percentages and overall survival in the TARGET AML dataset (HR = 2.3; P-value = .007). Distinct clusters of AML-blasts at Dx were observed for relapse- and CCR-associated samples with differential expression of genes associated with survival. Relapse-associated samples demonstrated enrichment of exhausted T cells and M2 macrophages as opposed to inflammatory M1 macrophages in CCR-associated samples at Dx. EOI treatment resistant blast cells overexpressed fatty acid oxidation, tumor growth and stemness genes. Also, a relapse-associated EOI samples T cells subset showed downregulation of MHC Class I and regulatory genes. Altogether, this study deeply characterizes pediatric AML relapse-/CCR-associated tumor microenvironment transcriptome landscape.
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- 2021
19. Decision-maker led implementation research on immunization: learning from low- and middle-income countries
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Arielle Mancuso, Abdul Ghaffar, Hope L Johnson, Alyssa Sharkey, Zubin Cyrus Shroff, Asm Shahabuddin, and Binay Kumar
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Introduction ,Economic growth ,medicine.medical_specialty ,Health Policy ,Public health ,Decision Making ,Vaccination ,Health services research ,Immunization (finance) ,Decision maker ,Health administration ,Low and middle income countries ,Income ,medicine ,Humans ,Immunization ,Business ,Implementation research ,Public aspects of medicine ,RA1-1270 ,Developing Countries ,Health policy - Published
- 2021
20. Gas Turbine Dynamic Dynamometry: A New Energy Engineering Laboratory Module
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Zhiyuan Yang, Hope L. Weiss, and Matthew J. Traum
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- 2021
21. How Did that Happen? Teachers’ Explanations for Low Test Scores
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Thomas A. Schwandt, Rebecca M. Teasdale, Margaret Evans, Hope L. Crenshaw, Nora Gannon-Slater, Jennifer C. Greene, and Priya Goel La Londe
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Publishing ,business.industry ,Value judgment ,ComputingMilieux_COMPUTERSANDEDUCATION ,Mathematics education ,Psychology ,business ,Attribution ,Publication ,Education ,Test (assessment) - Abstract
Context Educators often engage with student performance data to make important instructional decisions, yet limited research has analyzed how educators make sense of student performance data. In addition, scholars suggest that teachers recognize a relationship between their instruction and student performance data, but this is a relatively untested assumption. Focus of Study We investigated if and how teachers referenced instruction as a contributing factor for why students performed in particular ways on assessments. We also studied other explanations that teachers offered for student performance data. Research Design Our research team conducted a qualitative case study of six grade-level teams of teachers who met biweekly to make meaning of student performance data. Using data collected from 44 hours of observation of teacher team meetings, 16 individual interviews, and six group interviews with participating teachers, we analyzed the ways in which and the extent to which teachers referenced instruction as a contributing factor to student performance data. Findings: Teachers connected student performance data to their instruction approximately 15% of the time. Teachers more frequently connected student performance data to student characteristics. Notably, student behavior accounted for 32% of all teacher explanations for student performance. We offer five distinct categories of teachers’ explanations of student performance and the extent to which teachers invoked each category. Conclusions The findings in this study build on research on teachers’ attributions for assessment data. In contrast to other studies, our findings suggest that teachers invoked student characteristics in distinct ways when explaining student performance. At times, teachers were knowledgeable about student characteristics, which offered verifiable insights into the “problem” of low achievement. At other times, teachers voiced negative viewpoints of students that served to blame students for their poor performance. We suggest that the practice of data-driven decision making offers an opportunity to bolster educators’ informed judgment and undermine negative, unverifiable claims about children.
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- 2019
22. Amino acid enantiomers in old and young dissolved organic matter: Implications for a microbial nitrogen pump
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Matthew D. McCarthy, Thomas P. Guilderson, Taylor A. B. Broek, A. L. Bour, and Hope L. Ianiri
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chemistry.chemical_classification ,010504 meteorology & atmospheric sciences ,food and beverages ,chemistry.chemical_element ,010502 geochemistry & geophysics ,01 natural sciences ,Deep sea ,Nitrogen ,Amino acid ,Water column ,chemistry ,Geochemistry and Petrology ,Environmental chemistry ,Dissolved organic carbon ,Composition (visual arts) ,Carbon ,Refractory (planetary science) ,0105 earth and related environmental sciences - Abstract
Dissolved organic nitrogen (DON) represents the largest reservoir of fixed N in the surface ocean and a significant portion accumulates in the deep sea, where it can persist for millennial time scales. However, like the dissolved organic carbon (DOC) pool, the origin and composition of long-lived, refractory DON remains largely unknown. In recent years, the “microbial carbon pump” hypothesis has emerged from abundant evidence showing that microbial processes are primarily responsible for refractory DOC accumulation. However, a similar mechanism for DON has rarely been investigated. In the study of DON, spectroscopic evidence has indicated a primarily amide composition, implying a dominant contribution from peptides. Therefore, if an analogous “microbial nitrogen pump” controls refractory DON accumulation, the amino acid component should bear increasing signatures of microbial origin with increasing age. Here we investigate the microbial sequestration of N via the production of refractory DON, for the first time considering together DOM Δ14C with amino acid (AA) molar abundance (Mol%) and D/L ratio (as a tracer for prokaryotic input). Measurements were made on a unique set of high and low molecular weight (HMW, LMW) DOM isolates with 14C ages and chemical compositions generally consistent with semi-labile and refractory DOM respectively. The samples were collected in the North Pacific Subtropical Gyre where deep waters contain some of the oldest DOC in the world ocean. We observe higher D/L ratios in older, LMW DOM isolates for almost all analyzed AAs. Using mass spectral data, we also quantify three D-AAs in all samples (D-valine, D-phenylalanine, and D-leucine), which have not previously been confirmed in ocean DOM. These newly identified D-AAs are concentrated in the LMW refractory DOM fraction and have oceanographically consistent depth profiles. Our results suggest that several novel D-AA subgroupings may be unique tracers for different prokaryotic source processes. D-alanine appears to have largely independent cycling from the other D-AAs with a connection to the production of HMW DON, which we hypothesize is linked to water column peptidoglycan. In contrast, D-leucine, D-valine, and D-phenylalanine appear to be most strongly related to the production of LMW DON. Trends in both the HMW and LMW fractions suggest a linkage to sinking particles and local microbial transformations, implying that LMW DON has a direct biological source rather than originating from successive microbial reprocessing of HMW DON. Taken together, our observations are consistent with the dominant production of refractory LMW DON by prokaryotic organisms and suggests that different AA sub-groupings that can be used to track different processes within the DON pool.
- Published
- 2019
23. Predictors of Short‐Term Prognosis While in Pediatric Headache Care: An Observational Study
- Author
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Joanne Kacperski, Jessica Weberding, Scott W. Powers, Marielle A. Kabbouche, Serena L. Orr, Shannon White, Abigail Turner, Mimi N. Miller, Paul S. Horn, Hope L. O’Brien, Susan L. LeCates, and Andrew D. Hershey
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Outpatient Clinics, Hospital ,Adolescent ,Migraine Disorders ,Population ,Severity of Illness Index ,Article ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Chronic Migraine ,medicine ,Humans ,030212 general & internal medicine ,Young adult ,Child ,education ,Retrospective Studies ,education.field_of_study ,business.industry ,Age Factors ,Retrospective cohort study ,Hospitals, Pediatric ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Outcome and Process Assessment, Health Care ,Neurology ,Migraine ,Chronic Disease ,Disease Progression ,Anxiety ,Female ,Observational study ,Neurology (clinical) ,Headaches ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
OBJECTIVES: To characterize the short-term prognosis of a clinical population of pediatric and young adult patients with migraine and explore predictors of clinical worsening while in care. METHODS: This was a retrospective study of all migraine patients seen at the Cincinnati Children’s Hospital Headache Center from 09/01/2006 to 12/31/2017, who had at least one follow-up visit within 1–3 months of the index visit analyzed. Included data were: age, sex, race, primary ICHD diagnosis, chronic migraine, medication overuse, history of status migrainosus, BMI percentile, headache frequency, headache severity, PedMIDAS score, allodynia, preventive treatment type, lifestyle habits, disease duration, depressive and anxiety symptoms. Clinical worsening was defined as an increase of 4 or more headache days per month between the index visit and the follow-up visit. RESULTS: Data for 13,160 visit pairs (index and follow-up), from 5,316 patients were analyzed. Clinical worsening occurred in only 14.5% (1,908/13,160), whereas a reduction in headache frequency was observed in 56.8% of visit intervals (7,475/13,160), with 34.8% of the intervals (4,580/13,160) showing a reduction of 50% or greater. The change in headache frequency was minimal (increase in 0–3 headaches/month) in 28.7% of intervals (3,737/13,160). In the multivariable model, the odds of worsening were significantly higher with increasing age, female sex, chronic migraine, status migrainosus, depressive symptoms, higher PedMIDAS scores, and use of nutraceuticals, whereas the odds of worsening were lower for summer visits, caffeine drinkers, higher headache frequencies and use of pharmaceuticals. CONCLUSIONS: The majority of pediatric patients who receive multimodal interdisciplinary care for migraine improve over time. Our findings highlight a set of clinical features that may help in identifying specific factors that may contribute to an unfavorable short-term prognosis.
- Published
- 2019
24. Photopolymerized microdomains in both lipid leaflets establish diffusive transport pathways across biomimetic membranes
- Author
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Hope L. Mumme, Eric C. Freeman, Michelle M. Makhoul-Mansour, and Joyce El-Beyrouthy
- Subjects
Biomimetic membranes ,Lipid composition ,Lipid Bilayers ,Transport pathways ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Permeability ,Polymerization ,Diffusion ,Structure-Activity Relationship ,Dissolution ,Phospholipids ,Aqueous solution ,Chemistry ,Bilayer ,fungi ,Aqueous two-phase system ,Water ,Electrochemical Techniques ,General Chemistry ,Photochemical Processes ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,0104 chemical sciences ,Cross-Linking Reagents ,Membrane ,Chemical engineering ,0210 nano-technology ,Porosity - Abstract
Controlled transport within a network of aqueous subcompartments provides a foundation for the construction of biologically-inspired materials. These materials are commonly assembled using the droplet interface bilayer (DIB) technique, adhering droplets together into a network of lipid membranes. DIB structures may be functionalized to generate conductive pathways by enhancing the permeability of pre-selected membranes, a strategy inspired by nature. Traditionally these pathways are generated by dissolving pore-forming toxins (PFTs) in the aqueous phase. A downside of this approach when working with larger DIB networks is that transport is enabled in all membranes bordering the droplets containing the PFT, instead of occurring exclusively between selected droplets. To rectify this limitation, photopolymerizable phospholipids (23:2 DiynePC) are incorporated within the aqueous phase of the DIB platform, forming conductive pathways in the lipid membranes post-exposure to UV-C light. Notably these pathways are only formed in the membrane if both adhered droplets contain the photo-responsive lipids. Patterned DIB networks can then be generated by controlling the lipid composition within select droplets which creates conductive routes one droplet thick. We propose that the incorporation of photo-polymerizable phospholipids within the aqueous phase of DIB networks will improve the resolution of the patterned conductive pathways and reduce diffusive loss within the synthetic biological network.
- Published
- 2019
25. Migraine in children
- Author
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Scott W. Powers, Shalonda K. Slater, and Hope L. O’Brien
- Subjects
Pediatric migraine ,medicine.medical_specialty ,Adolescent ,Vomiting ,Migraine Disorders ,medicine.medical_treatment ,Treatment outcome ,MEDLINE ,Pediatrics ,Disability Evaluation ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,030212 general & internal medicine ,Child ,Psychiatry ,Evidence-Based Medicine ,Cognitive Behavioral Therapy ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Evidence-based medicine ,Analgesics, Non-Narcotic ,Serotonin 5-HT1 Receptor Agonists ,medicine.disease ,Response to treatment ,3. Good health ,Cognitive behavioral therapy ,Treatment Outcome ,Migraine ,Chronic Disease ,Pediatrics, Perinatology and Child Health ,Presentation (obstetrics) ,business ,030217 neurology & neurosurgery - Abstract
The current review presents findings from investigations of migraine in children. The presentation of pediatric migraine, related consequences, and medication treatments are reviewed.A number of advancements have been made in the study of the presentation, disability, and treatments for migraine in children. However, recent research suggests that not all approaches are equally effective in the treatment of migraine in children. Specifically, a recent study comparing pharmacological interventions found that preventive medications were not statistically more effective than placebo in children. Consistent findings showing clinically meaningful placebo response rates, shorter duration of headaches and other characteristic features (e.g. frontal, bilateral location) have been barriers to the design of randomized clinical trials in children and adolescents with migraine. Better understanding of treatment mechanisms for medication interventions is needed.Several migraine treatments have determined to be effective for use in children but few controlled studies have evaluated the effectiveness of medication treatments. Recent research suggests that preventive medications may not be more effective than placebo. Additional research is needed to evaluate the effectiveness of medication treatment in migraine headache care.
- Published
- 2018
26. Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: a modelling study
- Author
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Li, Xiang, Mukandavire, Christinah, Cucunubá, Zulma M, Echeverria Londono, Susy, Abbas, Kaja, Clapham, Hannah E, Jit, Mark, Johnson, Hope L, Papadopoulos, Timos, Vynnycky, Emilia, Brisson, Marc, Carter, Emily D, Clark, Andrew, de Villiers, Margaret J, Eilertson, Kirsten, Ferrari, Matthew J, Gamkrelidze, Ivane, Gaythorpe, Katy AM, Grassly, Nicholas C, Hallett, Timothy B, Hinsley, Wes, Jackson, Michael L, Jean, Kévin, Karachaliou, Andromachi, Klepac, Petra, Lessler, Justin, Li, Xi, Moore, Sean M, Nayagam, Shevanthi, Nguyen, Duy Manh, Razavi, Homie, Razavi-Shearer, Devin, Resch, Stephen, Sanderson, Colin, Sweet, Steven, Sy, Stephen, Tam, Yvonne, Tanvir, Hira, Tran, Quan Minh, Trotter, Caroline L, Truelove, Shaun, van Zandvoort, Kevin, Verguet, Stéphane, Walker, Neff, Winter, Amy, Woodruff, Kim, Ferguson, Neil M, Garske, Tini, Vaccine Impact Modelling Consortium, Trotter, Caroline [0000-0003-4000-2708], and Apollo - University of Cambridge Repository
- Subjects
Male ,Immunization Programs ,Cost-Benefit Analysis ,Vaccination ,Models, Theoretical ,Global Health ,Communicable Diseases ,Child, Preschool ,Communicable Disease Control ,Humans ,Female ,Quality-Adjusted Life Years ,Mortality ,Developing Countries - Abstract
BACKGROUND: The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. METHODS: 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. FINDINGS: We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52-88) deaths between 2000 and 2030, of which 37 million (30-48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36-58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52-66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93-150) deaths will be averted by vaccination, of which 58 million (39-76) are due to measles vaccination and 38 million (25-52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59-81) reduction in lifetime mortality in the 2019 birth cohort. INTERPRETATION: Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. FUNDING: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.
- Published
- 2021
27. Breaking down barriers to care: Understanding migraine knowledge gaps among women's healthcare providers
- Author
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Hope L. O'Brien and Rashmi B. Halker Singh
- Subjects
medicine.medical_specialty ,business.industry ,Health Personnel ,Migraine Disorders ,MEDLINE ,medicine.disease ,Health Services Accessibility ,Article ,Neurology ,Migraine ,Family medicine ,Medicine ,Humans ,Female ,Neurology (clinical) ,business ,Healthcare providers ,Needs Assessment ,Qualitative Research - Abstract
BACKGROUND: Studies suggest that migraine is often underdiagnosed and inadequately treated in the primary care setting, despite many patients relying on their primary care provider (PCP) to manage their migraine. Many women consider their women’s healthcare provider to be their PCP, yet very little is known about migraine knowledge and practice patterns in the women’s healthcare setting. OBJECTIVE: The objective of this study was to assess women’s healthcare providers’ knowledge and needs regarding migraine diagnosis and treatment. METHODS: The comprehensive survey assessing migraine knowledge originally developed for PCPs was used in this study, with the addition of a section regarding the use of hormonal medications in patients impacted by migraine. Surveys were distributed online, and primarily descriptive analyses were performed. RESULTS: The online survey was completed by 115 women’s healthcare providers (response rate 28.6%; 115/402), who estimated that they serve as PCPs for approximately one-third of their patients. Results suggest that women’s healthcare providers generally recognize the prevalence of migraine, but experience some knowledge gaps regarding migraine management. Despite 82.6% (95/115) of survey respondents feeling very comfortable or somewhat comfortable with diagnosing migraine, only 57.9% (66/114) reported routinely asking patients about headaches during annual visits. Very few were familiar with the American Academy of Neurology guidelines on preventative treatment (6.3%; 7/111) and the Choosing Wisely Campaign recommendations on migraine treatment (17.3%; 19/110), and many prescribed medications known to contribute to medication overuse headache. In addition, only 24.3% (28/115) would order imaging for a new type of headache, 35.7% (41/115) for worsening headache, and 47.8% (55/115) for headache with neurologic symptoms; respondents cited greater tendency with sending patients to an emergency department for the same symptoms. Respondents had limited knowledge of evidence-based, non-pharmacological treatments for migraine (i.e., biofeedback or cognitive behavioral therapy), with nearly none placing referrals for these services. Most providers were comfortable prescribing hormonal contraception (mainly progesterone only) to women with migraine without aura (80.9%; 89/110) and with aura (72.5%; 79/109), and followed American College of Obstetricians and Gynecologists (ACOG) guidelines to limit combination hormonal contraception for patients with aura. When queried, 6.3% or less (5/79) of providers would prescribe estrogen-containing contraception for women with migraine with aura. Only 37.3% (41/110) of respondents reported having headache/migraine education. Providers indicated interest in education pertaining to migraine prevention and treatment (96.3%; 105/109), migraine-associated disability (74.3%; 81/109), and diagnostic testing (59.6%; 65/109). CONCLUSION: Women’s healthcare providers appear to have several knowledge gaps regarding the management of migraine in their patients. These providers would likely benefit from access to a headache-specific educational curriculum to improve provider performance and patient outcomes.
- Published
- 2020
28. Bacterial sources and cycling dynamics of amino acids in high and low molecular weight dissolved organic nitrogen in the ocean
- Author
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Hope L. Ianiri, Yuan Shen, Taylor A.B. Broek, and Matthew D. McCarthy
- Subjects
Environmental Chemistry ,General Chemistry ,Oceanography ,Water Science and Technology - Published
- 2022
29. Realizing the potential of embedded implementation research: Lessons from Pakistan
- Author
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Abdul Ghaffar, Hope L Johnson, Stefan Peterson, Kumanan Rasanathan, Assad Hafeez, and Nhan Tran
- Subjects
Engineering management ,Health Policy ,Political science ,Editorials ,Public Health, Environmental and Occupational Health ,MEDLINE ,Humans ,Pakistan ,Implementation research ,Research Personnel ,Implementation Science - Published
- 2020
30. The Development of the Medical Transfer Packet for Transition of Care of the Pediatric Patient with Headache
- Author
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Thilinie Rajapakse, Serena L. Orr, Andrew D. Hershey, Klaus Werner, Cheryl Lavell, Anna Marissa Lagman‐Bartolome, Christina L. Szperka, Hope L. O'Brien, Amy A. Gelfand, Jennifer Hranilovich, Juliana H. VanderPluym, Marielle A. Kabbouche, Rashmi Rao, Marcy Yonker, and Samantha L. Irwin
- Subjects
Patient Transfer ,Adult ,Transition to Adult Care ,Consensus ,Adolescent ,business.industry ,Network packet ,Headache Disorders ,Headache ,MEDLINE ,medicine.disease ,Pediatrics ,Article ,Pediatric patient ,Young Adult ,Neurology ,Practice Guidelines as Topic ,Medicine ,Humans ,Neurology (clinical) ,Medical emergency ,Child ,business ,Societies, Medical - Published
- 2020
31. Endothelial Reprogramming by Disturbed Flow Revealed by Single-Cell RNA and Chromatin Accessibility Study
- Author
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Hope L. Mumme, Julian I. Perez, Hanjoong Jo, Nicolas Villa-Roel, Sandeep Kumar, Juyoung Kim, Dong Won Kang, and Aitor Andueza
- Subjects
0301 basic medicine ,endothelium ,Endothelium ,single-cell RNA sequencing ,General Biochemistry, Genetics and Molecular Biology ,Article ,single-cell ATAC sequencing ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,blood flow ,Animals ,Humans ,Progenitor cell ,lcsh:QH301-705.5 ,Chemistry ,reprogramming ,Endothelial Cells ,Cellular Reprogramming ,Chromatin ,endothelial-to-mesenchymal transition ,Cell biology ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,KLF4 ,KLF2 ,RNA ,Stem cell ,Reprogramming ,030217 neurology & neurosurgery - Abstract
SUMMARY Disturbed flow (d-flow) induces atherosclerosis by regulating gene expression in endothelial cells (ECs). For further mechanistic understanding, we carried out a single-cell RNA sequencing (scRNA-seq) and scATAC-seq study using endothelial-enriched single cells from the left- and right carotid artery exposed to d-flow (LCA) and stable-flow (s-flow in RCA) using the mouse partial carotid ligation (PCL) model. We find eight EC clusters along with immune cells, fibroblasts, and smooth muscle cells. Analyses of marker genes, pathways, and pseudotime reveal that ECs are highly heterogeneous and plastic. D-flow induces a dramatic transition of ECs from atheroprotective phenotypes to pro-inflammatory cells, mesenchymal (EndMT) cells, hematopoietic stem cells, endothelial stem/progenitor cells, and an unexpected immune cell-like (EndICLT) phenotypes. While confirming KLF4/KLF2 as an s-flow-sensitive transcription factor binding site, we also find those sensitive to d-flow (RELA, AP1, STAT1, and TEAD1). D-flow reprograms ECs from atheroprotective to proatherogenic phenotypes, including EndMT and potentially EndICLT., Graphical Abstract, In Brief To determine the effect of proatherogenic disturbed flow on transcriptomic and epigenomic chromatin accessibility profiles in endothelial cells at single-cell resolution, Andueza et al. perform scRNA-seq and scATAC-seq analyses using mouse carotid arteries following the partial carotid ligation. Disturbed flow reprograms endothelial cells to proatherogenic phenotypes, including EndMT and endothelial-to-immune cell-like transition.
- Published
- 2020
32. Competitive Growth Assay of Mutagenized Chlamydomonas reinhardtii Compatible With the International Space Station Veggie Plant Growth Chamber
- Author
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Marcio F. R. Resende, A. Mark Settles, Fang Bai, Ying Hu, Kevin N. Tyre, Jian Zhang, Hope L. Hersh, Bárbara S. F. Müller, and Bala Rathinasabapathi
- Subjects
0301 basic medicine ,Mutant ,Mutagenesis (molecular biology technique) ,Photobioreactor ,Chlamydomonas reinhardtii ,Plant Science ,lcsh:Plant culture ,Photosynthesis ,genetic fitness ,03 medical and health sciences ,0302 clinical medicine ,Ultraviolet light ,lcsh:SB1-1110 ,Gene ,Life support system ,Original Research ,algae ,biology ,Chemistry ,population genetics ,biology.organism_classification ,space environment ,030104 developmental biology ,Biochemistry ,030220 oncology & carcinogenesis - Abstract
A biological life support system for spaceflight would capture carbon dioxide waste produced by living and working in space to generate useful organic compounds. Photosynthesis is the primary mechanism to fix carbon into organic molecules. Microalgae are highly efficient at converting light, water, and carbon dioxide into biomass, particularly under limiting, artificial light conditions that are a necessity in space photosynthetic production. Although there is great promise in developing algae for chemical or food production in space, most spaceflight algae growth studies have been conducted on solid agar-media to avoid handling liquids in microgravity. Here we report that breathable plastic tissue culture bags can support robust growth of Chlamydomonas reinhardtii in the Veggie plant growth chamber, which is used on the International Space Station (ISS) to grow terrestrial plants. Live cultures can be stored for at least 1 month in the bags at room temperature. The gene set required for growth in these photobioreactors was tested using a competitive growth assay with mutations induced by short-wave ultraviolet light (UVC) mutagenesis in either wild-type (CC-5082) or cw15 mutant (CC-1883) strains at the start of the assay. Genome sequencing identified UVC-induced mutations, which were enriched for transversions and non-synonymous mutations relative to natural variants among laboratory strains. Genes with mutations indicating positive selection were enriched for information processing genes related to DNA repair, RNA processing, translation, cytoskeletal motors, kinases, and ABC transporters. These data suggest that modification of DNA repair, signal transduction, and metabolite transport may be needed to improve growth rates in this spaceflight production system.
- Published
- 2020
33. L’analyse de la communication non verbale: Les dangers de la pseudoscience en contextes de sécurité et de justice
- Author
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Denault, V., Plusquellec, P., Jupe, L. M., St-Yves, M., Dunbar, N. E., Hartwig, M., Sporer, S. L., Rioux-Turcotte, J., Jarry, J., Walsh, D., Otgaar, H., Viziteu, A., Talwar, V., Keatley, D. A., Blandón-Gitlin, I., Townson, C., Deslauriers-Varin, N., Lilienfeld, S. O., Patterson, M. L., Areh, I., Allan, A., Cameron, H. E., Boivin, R., Ten Brinke, L., Masip, J., Bull, R., Cyr, M., Hope, L., Strömwall, L. A., Bennett, S. J., Menaiya, F. A., Leo, R. A., Vredeveldt, A., Laforest, M., Honts, C. R., Manzanero, A. L., Mann, S., Granhag, P. -A, Ask, K., Fiona Gabbert, Guay, J. -P, Coutant, A., Hancock, J., Manusov, V., Burgoon, J. K., Kleinman, S. M., Wright, G., Landström, S., Freckelton, I., Vernham, Z., Koppen, P. J., RS: FPN CPS IV, Section Forensic Psychology, RS: FdR Institute MICS, Criminal Law and Criminology, Criminology, A-LAB, and Empirical and Normative Studies
- Subjects
Synergology ,SPOT ,SDG 16 - Peace, Justice and Strong Institutions ,Behavior Analysis Interview ,Pseudoscience ,Nonverbal Communication - Abstract
For security and justice professionals, the thousands of peer-reviewed articles on nonverbal communication represent important sources of knowledge. However, despite the scope of the scientific work carried out on this subject, professionals can turn to programs, methods and approaches that fail to reflect the state of science. The objective of this article is to examine (i) concepts of nonverbal communication conveyed by these programs, methods and approaches, but also (ii) the consequences of their use. To achieve this objective, we describe the scope of scientific research on nonverbal communication. A program (SPOT; “Screening of Passengers by Observation Techniques”), a method (the BAI; “Behavior Analysis Interview”) and an approach (synergology) that each run counter to the state of science are examined. Finally, we outline five hypotheses to explain why some organizations in the fields of security and justice are turning to pseudoscience and pseudoscientific techniques.
- Published
- 2020
34. Utilization of a cell-penetrating peptide-adaptor for delivery of HPV protein E2 into cervical cancer cells to arrest cell growth and promote cell death
- Author
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Jonathan L. McMurry, Hope L. Didier, Scott J. Nowak, Juana C. Bejarano, Lauren R. Slaughter, Robert L. Dickson, Steven Ho, Carol A. Chrestensen, and Julia C. LeCher
- Subjects
Cervical cancer ,Programmed cell death ,Cell growth ,Endosome ,medicine ,Cell-penetrating peptide ,Cancer research ,Cancer ,Transfection ,Biology ,Carcinogenesis ,medicine.disease_cause ,medicine.disease - Abstract
Cervical cancer is the second leading cause of cancer deaths in women worldwide. Human papillomavirus (HPV) is the causative agent of nearly all forms of cervical cancer, which arises upon viral integration into the host genome and concurrent loss of regulatory gene E2. E2 protein regulates the expression and activity of viral oncoproteins E6 and E7. Loss of E2 upon viral integration results in overexpression of E6 and E7 Loss of E2 upon viral integration results in overexpression of E6 and E7which in turn promotes carcinogenesis. Previous studies using gene-based delivery show that reintroduction of E2 into cervical cancer cell lines can reduce proliferative capacity and promote apoptosis. However, owing in part to limitations on transfection in vivo , E2 reintroduction has yet to achieve therapeutic usefulness. A promising new approach is protein-based delivery systems utilizing cell-penetrating peptides (CPPs). CPPs readily traverse the cell9s plasma membrane and are able to carry with them biomolecular ‘cargos’ to which they are attached. Though more than two decades of research have been dedicated to their development for delivery of biomolecular therapeutics, the full potential of CPPs has yet to be realized as the field is hindered by the tendency of CPP-linked cargos to be trapped in endosomes as well as significant off-target potential in vivo. Using a CPP-adaptor system that reversibly binds cargo thereby overcoming the endosomal entrapment that hampers of CPP methods, bioactive E2 protein was delivered via CPP-adaptors into living cervical cancer cells, resulting in inhibition of cellular proliferation and promotion of cell death in a time- and dose-dependent manner. The results suggest that this nucleic acid- and virus-free delivery method could be harnessed to develop novel, effective protein therapeutics for treatment of cervical cancer.
- Published
- 2020
35. Endothelial Reprogramming by Disturbed Flow Revealed by Single-Cell RNA and Chromatin Accessibility Study
- Author
-
Aitor Andueza, Sandeep Kumar, Dong Won Kang, Hanjoong Jo, Hope L. Mumme, Julian I. Perez, and Juyoung Kim
- Subjects
Haematopoiesis ,medicine.anatomical_structure ,Endothelium ,KLF4 ,Chemistry ,Mesenchymal stem cell ,KLF2 ,medicine ,Progenitor cell ,Stem cell ,Reprogramming ,Cell biology ,Chromatin - Abstract
SUMMARYDisturbed flow (d-flow) induces atherosclerosis by regulating gene expression in endothelial cells (ECs). For further mechanistic understanding, we carried out a single-cell RNA sequencing (scRNAseq) and scATACseq study using endothelial-enriched single-cells from the left- and right carotid artery exposed to d-flow (LCA) and stable-flow (s-flow in RCA) using the mouse partial carotid ligation (PCL) model. We found 8 EC clusters along with immune cells, fibroblasts, and smooth muscle cells. Analyses of marker genes, pathways, and pseudo-time revealed that ECs are highly heterogeneous and plastic. D-flow induced a dramatic transition of ECs from atheroprotective phenotypes to pro-inflammatory, mesenchymal (EndMT), hematopoietic stem cells, endothelial stem/progenitor cells, and an unexpected immune cell-like (EndICLT) phenotypes. While confirming KLF4/KLF2 as s-flow-sensitive transcription factor binding site, we also found those sensitive to d-flow (RELA, AP1, STAT1, and TEAD1). D-flow reprograms ECs from atheroprotective to pro-atherogenic phenotypes including EndMT and potentially EndICLT.
- Published
- 2020
36. Evaluation of a Low Cost Prosthetic Hand Controlled by Surface EMG Sensors and Vibrotactile Feedback
- Author
-
Cameron J Spitzfaden, Hope L Ayers, Victor Argueta-Diaz, and Durham Basso
- Subjects
Prosthetic hand ,medicine.medical_specialty ,Physical medicine and rehabilitation ,Training set ,Control algorithm ,genetic structures ,Subjective data ,medicine.diagnostic_test ,Computer science ,medicine ,Visual feedback ,Electromyography ,Signal - Abstract
This study proposes a prosthetic hand with a simple control algorithm and off-the-shelf electronics. We designed this hand to be used and repaired in underdeveloped regions. A differential sEMG signal is obtained from the flexor digitorum superficialis and extensor digitorum muscles to control the position of the hand’s grasp. Three different hand control schemes (visual, vibrotactile and visual plus vibrotactile) were compared and tested in ten able-bodied individuals. We observed a better performance of the visual and vibrotactile control overall, but the vibrotactile feedback increased performance after several interactions. In subjective data evaluations vibrotactile and visual feedback had the highest scores in light and medium pressures, while visual-only feedback type had the highest average score for hard pressure.
- Published
- 2018
37. Investigating the Kinetics of Montmorillonite Clay-Catalyzed Conversion of Anthracene to 9,10-Anthraquinone in the Context of Prebiotic Chemistry
- Author
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Hope L. Juntunen, Michael O. Gaylor, Bethany Theiling, Lucas J. Leinen, Laura M. Barge, Patrick Videau, Samantha M. O’Hanlon, and Briann K. Pitts
- Subjects
010504 meteorology & atmospheric sciences ,Origin of Life ,Kinetics ,Anthraquinones ,Context (language use) ,01 natural sciences ,Anthraquinone ,Redox ,Catalysis ,chemistry.chemical_compound ,0103 physical sciences ,Organic chemistry ,Polycyclic Aromatic Hydrocarbons ,010303 astronomy & astrophysics ,Ecology, Evolution, Behavior and Systematics ,0105 earth and related environmental sciences ,Anthracenes ,Anthracene ,Temperature ,General Medicine ,Chemistry, Inorganic ,Montmorillonite ,chemistry ,Space and Planetary Science ,Bentonite ,Clay ,Clay minerals - Abstract
Carbonaceous meteorites contributed polycyclic aromatic hydrocarbons (PAHs) to the organic inventory of the primordial Earth where they may have reacted on catalytic clay mineral surfaces to produce quinones capable of functioning as redox species in emergent biomolecular systems. To address the feasibility of this hypothesis, we assessed the kinetics of anthracene (1) conversion to 9,10-anthraquinone (2) in the presence of montmorillonite clay (MONT) over the temperature range 25 to 250 °C. Apparent rates of conversion were concentration independent and displayed a sigmoidal relationship with temperature, and conversion efficiencies ranged from 0.027 to 0.066%. Conversion was not detectable in the absence of MONT or a sufficiently high oxidation potential (in this case, molecular oxygen (O2)). These results suggest a scenario in which meteoritic 1 and MONT interactions could yield biologically important quinones in prebiotic planetary environments.
- Published
- 2018
38. The Profile and Prognosis of Youth With Status Migrainosus: Results From an Observational Study
- Author
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Andrew D. Hershey, Shannon White, Abigail Turner, Paul S. Horn, Mimi N. Miller, Scott W. Powers, Hope L. O’Brien, Joanne Kacperski, Jessica Weberding, Susan L. LeCates, Serena L. Orr, and Marielle A. Kabbouche
- Subjects
Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Migraine Disorders ,Population ,Odds ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Chronic Migraine ,Medicine ,Humans ,030212 general & internal medicine ,Young adult ,education ,Child ,Ohio ,Retrospective Studies ,education.field_of_study ,business.industry ,Age Factors ,medicine.disease ,Prognosis ,Neurology ,Migraine ,Disease Progression ,Anxiety ,Observational study ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Body mass index ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
To characterize the clinical features of a large sample of children, adolescents, and young adults with a history of status migrainosus (SM) and to describe their short-term prognosis.Data on the clinical characteristics of children and adolescents with SM are sparse and little is known about the prognosis of this population.This was a retrospective clinical cohort study that included patients from the Cincinnati Children's Headache Center if they had a diagnosis of migraine and data available for a 1-3 months follow-up interval. Data extracted from the initial interval visit (visit A) included: age, sex, race, migraine diagnosis, SM history, chronic migraine, medication overuse headache (MOH), body mass index (BMI), headache frequency, headache severity, disability, allodynia and lifestyle habits: caffeine intake, meal skipping, sleep duration, exercise frequency, and fluid intake. Data extracted from the initial consultation visit included: months with headache at initial consultation visit, patient endorsing "feeling depressed" and anxiety symptoms. Headache frequency and visit type were also measured at the second visit (visit B) in the follow-up interval. A multivariate logistic regression model with a backward elimination procedure was created to model the odds of having a diagnosis of SM using the cross-sectional predictor variables above. Second, chi-square tests were used to compare the proportion of patients with SM to the proportion of patients without SM who had each of the following outcomes in the short-term follow-up window: treatment response (50% or greater reduction in headache frequency), overall reduction in headache frequency (reduction of 1 or more headache days/month), minimal change in headache frequency (increase in 0-3 headache days/month), and clinical worsening (increase in 4 or more headache days/month).A total of 5316 youth with migraine were included and 559 (10.5%) had a history of SM. In the multivariate logistic regression model, predictors significantly associated with SM were: older age (OR = 1.13, 95% CI = 1.09-1.17, P .0001), migraine with aura (MWA) (OR = 1.30, 95% CI = 1.03-1.65, P = .03), MOH (OR = 1.72, 95% CI = 1.30-2.28, P = .0001), headache frequency (OR = 0.99, 95% CI = 0.97-0.99, P = .030), higher headache severity (OR = 1.08, 95% CI = 1.02-1.15, P = .009), months with headache at initial consultation (OR = 1.00, 95% CI = 1.00-1.01, P = .042), and admission to infusion center at visit B (OR = 2.27, 95% CI = 1.38-3.72, P = .001). Patients with a history of SM were more likely to experience an increase in 4 or more headache days per month at follow-up: 15.2% as compared to 11.1% of those without SM, χYouth with SM represent a distinct subgroup of the migraine population and have an unfavorable short-term prognosis.
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- 2019
39. Predictors of First-Line Treatment Success in Children and Adolescents Visiting an Infusion Center for Acute Migraine
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Hope L. O'Brien, Mimi N. Miller, Serena L. Orr, Shannon White, Susan L. LeCates, Jessica Weberding, Andrew D. Hershey, Marielle A. Kabbouche, Paul S. Horn, Joanne Kacperski, and Scott W. Powers
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,Metoclopramide ,Migraine Disorders ,Population ,Comorbidity ,Logistic regression ,Odds ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Chronic Migraine ,030225 pediatrics ,Internal medicine ,Headache Disorders, Secondary ,Humans ,Medicine ,Child ,Infusions, Intravenous ,education ,Retrospective Studies ,Analgesics ,education.field_of_study ,business.industry ,Prochlorperazine ,medicine.disease ,Treatment Outcome ,Neurology ,Migraine ,Female ,Observational study ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
OBJECTIVES To characterize a population of pediatric patients visiting an infusion center for acute migraine and determine predictors of first-line treatment success in this population. BACKGROUND Though migraine is common in the pediatric emergency department and specialized infusion centers, little is known about this patient population and whether or not clinical data can be used to predict treatment response. METHODS This was an observational study involving a retrospective analysis of data from visits to the Cincinnati Children's Hospital infusion center for treatment of an acute migraine. Data were extracted from a database and chart reviews were completed for missing or outlying data. Descriptive statistics were used to outline patient: sex, age, race, primary ICHD-III diagnosis, chronic migraine, medication overuse headache (MOH), headache frequency, month of treatment, headache severity, headache duration, use of acute medication at home in the past 24 hours and treatment received (metoclopramide vs prochlorperazine and dexamethasone vs no dexamethasone). The odds of success of first-line intervention were modeled using simple logistic regression with the above characteristics used as predictors. Predictors with a P value
- Published
- 2018
40. Assessment of Multiple Solvents for Extraction and Direct GC–MS Determination of the Phytochemical Inventory of Sansevieria Extrafoliar Nectar Droplets
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Patrick Videau, Donna Hazelwood, Hope L. Juntunen, and Michael O. Gaylor
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0106 biological sciences ,Plant Nectar ,Phytochemicals ,Sansevieria ,Ethyl acetate ,010603 evolutionary biology ,01 natural sciences ,Organic compound ,Gas Chromatography-Mass Spectrometry ,Analytical Chemistry ,chemistry.chemical_compound ,Hexanes ,Dichloromethane ,chemistry.chemical_classification ,Methylene Chloride ,Chromatography ,Extraction (chemistry) ,food and beverages ,General Medicine ,Toluene ,Hexane ,Solvent ,chemistry ,Solvents ,Gas chromatography–mass spectrometry ,010606 plant biology & botany - Abstract
Considerable effort has been devoted to analytical determinations of sugar and amino acid constituents of plant nectars, with the primary aim of understanding their ecological roles, yet few studies have reported more exhaustive organic compound inventories of plant nectars or extrafoliar nectars. This work evaluated the efficacy of four solvents (ethyl acetate, dichloromethane, toluene and hexane) to extract the greatest number of organic compound classes and unique compounds from extrafoliar nectar drops produced by Sansevieria spp. Aggregation of the results from each solvent revealed that 240 unique compounds were extracted in total, with 42.5% of those detected in multiple extracts. Aliphatic hydrocarbons dominated in all but the ethyl acetate extracts, with 44 unique aliphatic hydrocarbons detected in dichloromethane (DCM) extracts, followed by 41, 19 and 8 in hexane, toluene and ethyl acetate extracts, respectively. Hexane extracted the most unique compounds (79), followed by DCM (73), ethyl acetate (56) and toluene (32). Integrated total ion chromatographic peak areas of extracted compound classes were positively correlated with numbers of unique compounds detected within those classes. In addition to demonstrating that multi-solvent extraction with direct GC-MS detection is a suitable analytical approach for determining secondary nectar constituents, to the best of our knowledge, this study also represents: (i) the first attempt to inventory the secondary phytochemical constituents of Sansevieria spp. extrafoliar nectar secretions and (ii) the largest organic solvent extractable compound inventory reported for any plant matrix to date.
- Published
- 2018
41. Reading Balzac's Eugénie Grandet (1833) in Julien Green's Adrienne Mesurat (1927)
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Hope L. Christiansen
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Reading (process) ,media_common.quotation_subject ,General Engineering ,Art history ,Art ,media_common - Published
- 2018
42. Analysis of Single Cell Transcriptomics in Paired Pediatric T-ALL Samples Collected at Diagnosis and Following End of Induction Therapy Reveals an MRD-Associated Stem Cell Signature
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Sharon M. Castellino, Debasree Sarkar, Swati S Bhasin, Douglas K. Graham, Manoj Bhasin, Beena E Thomas, Hope L Mumme, Mohammed Emam Mansour, Deborah DeRyckere, Sunita I. Park, William Pilcher, and Ryan J. Summers
- Subjects
hemic and lymphatic diseases ,Single cell transcriptomics ,Immunology ,End of induction ,Cell Biology ,Hematology ,Biology ,Stem cell ,Signature (topology) ,Biochemistry ,Molecular biology - Abstract
Introduction Despite recent improvement in outcomes for de novo disease, pediatric T-cell acute lymphoblastic leukemia (T-ALL) remains challenging to treat at relapse. Investigation into genomic markers of treatment response and therapy resistance offers an opportunity to further enhance outcomes for these patients. We previously identified a T-ALL blast-associated gene signature at diagnosis (Dx) and characterized the immune microenvironment in Dx T-ALL marrow samples using single cell transcriptome analysis (Bhasin et al. Blood 2020(ASH)). This approach allowed us to generate a granular expression map of both the T-ALL landscape and the Dx bone marrow (BM) immune microenvironment. Here we expand this work by evaluating samples collected from the same patients Dx and End of Induction (EOI) BM samples from pediatric T-ALL patients. The use of paired samples provides insight into treatment-induced changes in the microenvironment. Further, the inclusion of both minimal residual disease (MRD) positive and MRD negative samples allowed us to compare differences between these groups. Methods Using the 10X genomics platform, we profiled the single cell transcriptome of ~18,000 BM and immune microenvironment cells from viably frozen samples collected from T-ALL patients at Dx or EOI. Five paired Dx and EOI samples and one EOI sample from a patient with relapsed T-ALL were evaluated, for a total of 11 samples. Three paired samples were MRD positive at EOI and two were MRD negative; the relapsed sample was MRD negative. Cell clustering was performed using the Seurat package and differential expression analysis was performed using R/Bioconductor packages (Hao et al. Cell 2021). Cell communication analysis was conducted using the CellChat R tool (v 1.0.0) to infer cell-cell communication within the EOI MRD positive and MRD negative subsets and compare their communication networks (Jin et al. Nature Comm 2021). Results Using our previously described blast-associated gene signature (Bhasin et al. ASH 2020) we were able to identify residual blast populations at EOI in MRD-positive samples. Comparative analysis of gene profiles at Dx and EOI showed significant changes in the microenvironment cell populations with highest increase in erythroid cell populations after induction therapy. The gene expression profiles were significantly different for immune cells at Dx and EOI and the relapsed sample had greater similarity to the Dx samples indicating a persistent immunosuppressive environment. Clustering analysis of the EOI samples (3 MRD positive and 2 MRD negative) demonstrated the presence of patient specific blast cells in MRD positive samples that retained patient-specific transcriptomeheterogeneity at EOI (Fig.1A). Analysis of communication networks between different cell types based on receptor and ligand expression levels between different cell types identified a CD34 + cluster of stem cells that had different interactions with other immune populations in the MRD positive and negative subsets. Differential expression analysis between the MRD positive and MRD negative cells in this CD34 + stem cell cluster identified higher expression of myeloid associated genes such as CEBPB, CEBPD, AZU1 in the MRD negative group relative to the MRD positive cells, which showed higher expression of B-cell related genes such as IGHM, VPREB1, CD79A/ B along with upregulation of P13K signaling in B-lymphocytes, B-cell receptor signaling and autophagy pathways. Analysis of upstream regulators based on the differential gene signature between the MRD positive and MRD negative group demonstrated upregulation of MYC and TCF3 activity and inhibition of TGFB1, CSF3 and CEBPA in MRD positive compared to MRD negative samples (Fig.1B). Conclusions: Leukemic blasts exhibit patient-specific gene expression signatures that are present at EOI in MRD positive samples. Exploration of the impact of minimal residual disease at EOI revealed differential gene expression patterns in stem cells from MRD positive samples, characterized by activation of B cell related signaling pathways and regulators such as MYC and TCF3. In contrast, a more myeloid-like expression signature was observed in stem cells from MRD negative samples. These findings open the avenues for exploration of therapeutic targets of T-ALL progression. Figure 1 Figure 1. Disclosures DeRyckere: Meryx: Other: Equity ownership. Graham: Meryx: Membership on an entity's Board of Directors or advisory committees, Other: Equity ownership.
- Published
- 2021
43. Single Cell RNA Sequencing Driven Characterization of Rare B/Myeloid and T/Myeloid Mixed Phenotype Acute Leukemia
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Douglas K. Graham, Sunil S. Raikar, Swati S Bhasin, Manoj Bhasin, Sharon M. Castellino, Beena E Thomas, Hope L Mumme, and Deborah DeRyckere
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medicine.anatomical_structure ,Mixed phenotype acute leukemia ,Myeloid ,Immunology ,Cell ,medicine ,RNA ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Molecular biology - Abstract
Introduction: Pediatric mixed phenotype acute leukemia (MPAL), a rare subgroup of leukemia, contains features of both myeloid and lymphoid lineage blasts, which makes the disease more difficult to diagnose/treat. More information is needed to understand the origins of the major pediatric MPAL subtypes, B/Myeloid (B-MPAL) and T/Myeloid (T-MPAL), and how they relate to other leukemias. Single-cell RNA sequencing (scRNA-seq) analysis of bone marrow (BM) can provide in-depth information about the leukemia microenvironment and reveal differences/similarities between MPAL subtypes and other types of leukemia that could be exploited to develop novel diagnostics/therapies. Methods: We analyzed ~16,000 cells from five pediatric MPAL BM samples to generate a transcriptomic landscape of B-MPAL and T-MPAL blasts and associated microenvironment cells. Samples collected at the time of diagnosis (Dx) were used to generate scRNA-Seq data using a droplet-based barcoding technique (Panigrahy et al. JCI 2019, Tellechea et al. JID, 2020). After data normalization, cell clusters were identified using principal component analysis (PCA) and Uniform Manifold Approximation and Projection (UMAP) approach (Becht et al. Nat. Biotech 2018). Meta-analysis was performed using single cell samples from ongoing studies in the Bhasin lab (Bhasin, et al. Blood 2020 (ASH), Thomas et al. Blood 2020 (ASH)) and publicly available single cell data from GEO biorepository. Unsupervised analysis using UMAP and PCA was performed to determine the overall relationship among B-MPAL, T-MPAL and other leukemias (acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL), T-cell ALL (T-ALL)). Supervised differentially expressed gene (DEG) analysis was performed to identify B- and T- MPAL blast cell signatures (P value < 0.001 and log2 FC > 0.5). Transcriptomic profiles in MPAL samples and normal BM stem and immune cells were compared using data from the Human Cell Atlas Data Portal (humancellatlas.org). Gene set enrichment analysis (GSEA) was performed, and significantly enriched pathways were compared in MPAL subtypes (P value < 0.001). Results: PCA analysis showed transcriptome similarity between B-MPAL and both B-ALL and AML, while T-MPAL transcriptome correlated with T-ALL and AML (Fig. 1A). B- and T-MPAL subtype blasts clustered separately from each other in UMAP analyses, with T-MPAL blasts clustering with T-ALL blasts, and B-MPAL somewhat overlapping with B-ALL blasts. Subtype DEG analysis of leukemia blasts and healthy BM revealed distinct significantly upregulated gene signatures in B-MPAL (YBX3, SOCS2, BCL11A, and HIST1H1C) and T-MPAL (ITM2A, HPGD, PDLIM1, and TRDC) blasts (Fig. 1B). Pathway analysis showed upregulated gene activity related to TNFA signaling via NFKB, B-cell survival, and the AP1, FRA, and NGF transcription factors in B-MPAL blasts. In contrast, IL-17 and IL-12, T-cell apoptosis, and Stathmin pathways were upregulated in T-MPAL blasts (Fig. 1C). T-MPAL T-cells also expressed higher levels of T-cell exhaustion markers compared to T-cells in B-MPAL samples and healthy bone marrow. After filtering out genes that are significantly expressed in immune cells, we identified genes that are differentially expressed at diagnosis in MPAL blasts from patients that relapsed after treatment (Dx1) versus patients that achieved remission (Dx2). These genes are potential prognostic markers for B-MPAL and T-MPAL relapse/remission. These include MDM2 and NEIL1 from Dx1 and FOSL2 and CDKN1A in Dx2 B-MPAL blasts. In T-MPAL, expression of HES4 and SPINK2 is associated with Dx1 blasts and GNAQ and ITGA4 with Dx2 blasts. Pathway enrichment analysis on B-MPAL blasts revealed upregulation of interferon gamma and PD-1 signaling in Dx1 samples and increased HSP27 and Cell Cycle pathways in the Dx2 subset. T-MPAL Dx1 associated pathways included prostaglandin synthesis and IL-17, while cell-cell junction and extracellular matrix interactions were increased in T-MPAL Dx2 samples (Fig. 1D). Conclusion: Single-cell profiling was used to characterize the molecular landscapes of MPAL blasts and the bone marrow microenvironment and identified gene signatures and pathways that are specifically enriched in B- and T-MPAL subtypes. Figure 1 Figure 1. Disclosures DeRyckere: Meryx: Other: Equity ownership. Graham: Meryx: Membership on an entity's Board of Directors or advisory committees, Other: Equity ownership.
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- 2021
44. Implementation and outcomes of an evidence-based precepting program for burn nurses
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Hope L. Greeley, Krystal K. Valdez-Delgado, Colleen Mitchell, Johnnie Robbins, Linda H. Yoder, Elizabeth J. Hayes, Nicole W. Caldwell, Elizabeth A. Mann-Salinas, and Michaèl G. Barba
- Subjects
Evidence-based practice ,medicine.medical_treatment ,Burn Units ,Specialty ,Personnel Turnover ,Critical Care and Intensive Care Medicine ,Coaching ,Job Satisfaction ,03 medical and health sciences ,0302 clinical medicine ,Nursing ,medicine ,Humans ,Outpatient clinic ,030212 general & internal medicine ,Nurse education ,Education, Nursing ,Medical education ,Rehabilitation ,030504 nursing ,business.industry ,Burn center ,Preceptor ,General Medicine ,Evidence-Based Practice ,Preceptorship ,Emergency Medicine ,Surgery ,Clinical Competence ,Burns ,0305 other medical science ,business - Abstract
Introduction There is significant nationwide interest in transitioning new and new-to-specialty nurses into practice, especially in burn care. Lack of a structured transition program in our Burn Center was recognized as a contributing factor for nursing dissatisfaction and increased turnover compared to other hospital units. Employee evaluations exposed a need for more didactic instruction, hands-on learning, and preceptor support. The goal of this project was to implement an evidence-based transition to practice program specific to the burn specialty. Material and methods The Iowa Model of Evidence-based Practice served as the model for this project. A working group was formed consisting of nurse scientists, clinical nurse leaders, clinical nurse specialists, lead preceptors, staff nurse preceptors and wound care coordinators. A systematic review of the literature was conducted focusing on nurse transition; preceptor development and transitioning nurse training programs with competency assessment, ongoing multifaceted evaluation and retention strategies were created. The evidence-based Vermont Nurses in Partnership (VNIP) Clinical Transition Framework was selected and subsequent education was provided to all Burn Center leaders and staff. Benchmarks for basic knowledge assessment (BKAT) and burn wound care were established among current staff by work site and education level to help evaluate transitioning nurses. Policies were modified to count each preceptor/transitioning nurse dyad as half an employee on the schedule. Multiple high-fidelity simulation scenarios were created to expand hands-on opportunities. Results From September 2012–December 2013, 110 (57% acute care nursing) Burn Center staff attended the VNIP Clinical Coaching Course, to include 34 interdisciplinary staff (rehabilitation, education, respiratory therapy, and outpatient clinic staff) and 100% of identified preceptors (n = 33). A total of 30 new nurses participated in the transition program: 26 (87%) completed, 3 (10%) did not complete, and 1 (3%) received exception (no patient care). Transitioning nurses achieved passing BKAT scores (n = 22; 76%) and WC scores (n = 24; 93%); individual remediation was provided for those failing to achieve unit benchmarks and transition training was modified to improve areas of weakness. Transitioning nurses’ weekly competency progression average initial ratings on a 10 point scale (10 most competent) were 5 ± 2; final ratings averaged 9 ± 1 (n = 25) (p Conclusions An evidence-based team practice approach toward preceptorship created a standardized, comprehensive and flexible precepting program to assist and support transition to specialty burn practice for experienced nurses. Use of objective metrics enabled ongoing assessment and made training adaptable, individualized, and cost effective. Application of this standardized approach across our organization may improve consistency for all transitions in practice specialty.
- Published
- 2017
45. Deep Immune Profiling of an Arginine-Enriched Nutritional Intervention in Patients Undergoing Surgery
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Cindy Kin, Martha Tingle, Andrew A. Shelton, Garry P. Nolan, Dyani Gaudilliere, Hope L. Lancero, Kent P. Jensen, Martin S. Angst, Nima Aghaeepour, Robin Okada, Leslie McNeil, Benjamin Choisy, Edward A. Ganio, Amy S. Tsai, and Brice Gaudilliere
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,medicine.medical_specialty ,Arginine ,business.industry ,Immunology ,Surgery ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,Immune system ,Intervention (counseling) ,medicine ,Immunology and Allergy ,Mass cytometry ,Elective surgery ,business ,Adverse effect - Abstract
Application of high-content immune profiling technologies has enormous potential to advance medicine. Whether these technologies reveal pertinent biology when implemented in interventional clinical trials is an important question. The beneficial effects of preoperative arginine-enriched dietary supplements (AES) are highly context specific, as they reduce infection rates in elective surgery, but possibly increase morbidity in critically ill patients. This study combined single-cell mass cytometry with the multiplex analysis of relevant plasma cytokines to comprehensively profile the immune-modifying effects of this much-debated intervention in patients undergoing surgery. An elastic net algorithm applied to the high-dimensional mass cytometry dataset identified a cross-validated model consisting of 20 interrelated immune features that separated patients assigned to AES from controls. The model revealed wide-ranging effects of AES on innate and adaptive immune compartments. Notably, AES increased STAT1 and STAT3 signaling responses in lymphoid cell subsets after surgery, consistent with enhanced adaptive mechanisms that may protect against postsurgical infection. Unexpectedly, AES also increased ERK and P38 MAPK signaling responses in monocytic myeloid-derived suppressor cells, which was paired with their pronounced expansion. These results provide novel mechanistic arguments as to why AES may exert context-specific beneficial or adverse effects in patients with critical illness. This study lays out an analytical framework to distill high-dimensional datasets gathered in an interventional clinical trial into a fairly simple model that converges with known biology and provides insight into novel and clinically relevant cellular mechanisms.
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- 2017
46. Advancing equity in accountability and organizational cultures of data use
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Jennifer C. Greene, Hope L. Crenshaw, Thomas A. Schwandt, Nora Gannon-Slater, Margaret Evans, and Priya Goel La Londe
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Equity (economics) ,Public Administration ,business.industry ,Discourse analysis ,05 social sciences ,Primary education ,050401 social sciences methods ,050301 education ,Organizational culture ,Public relations ,Education ,0504 sociology ,Interim ,Professional learning community ,Pedagogy ,Accountability ,Organizational learning ,Sociology ,business ,0503 education - Abstract
PurposeData use cultures in schools determine data use practices. Such cultures can be muted by powerful macro accountability and organizational learning cultures. Further, strong equity-oriented data use cultures are challenging to establish. The purpose of this paper is to engage these cultural tensions.Design/methodology/approachThe data discourse and decisions of four grade-level teams in two elementary schools in one district were studied through observation of 62 grade-level meetings over the course of a year. The observations focused on “data talk,” defined as the structure and content of team conversations about interim student performance data.FindingsDistinct macro cultures of accountability and organizational learning existed in the two schools. The teams’ own data use cultures partly explained the absence of a focus on equity, and none of the teams used student performance data to make instructional decisions in support of the district’s equity aims. Leadership missed opportunities to cultivate an equity-focused data use culture.Practical implicationsSchool leaders who advocate that equity importantly guides data use routines, and can anticipate how cultures of accountability or organizational learning “show up” in data use conversations, will be better prepared to redirect teachers’ interpretations of data and clarify expectations of equity reform initiatives.Originality/valueThis study is novel in its concept of “data talk,” which provided a holistic but nuanced account of data use practices in grade-level meetings.
- Published
- 2017
47. Trajectory of Improvement in Children and Adolescents With Chronic Migraine: Results From the Cognitive-Behavioral Therapy and Amitriptyline Trial
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Marium Zafar, Susmita Kashikar-Zuck, James Peugh, Susan L. LeCates, Hope L. O’Brien, Janelle R. Allen, Chad E. Shenk, Ashley M. Kroon Van Diest, Andrew D. Hershey, Scott W. Powers, Marielle A. Kabbouche, John Kroner, and Shalonda K. Slater
- Subjects
Male ,Treatment response ,medicine.medical_specialty ,Adolescent ,Amitriptyline ,Migraine Disorders ,medicine.medical_treatment ,Medical Records ,Article ,03 medical and health sciences ,0302 clinical medicine ,Chronic Migraine ,Daily headache ,Humans ,Medicine ,Longitudinal Studies ,030212 general & internal medicine ,Child ,Cognitive Behavioral Therapy ,business.industry ,Medical record ,Analgesics, Non-Narcotic ,Clinical trial ,Cognitive behavioral therapy ,Treatment Outcome ,Anesthesiology and Pain Medicine ,Neurology ,Chronic Disease ,Time course ,Linear Models ,Physical therapy ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Follow-Up Studies ,medicine.drug - Abstract
We compared headache frequency trajectories between clinical trial participants who received cognitive-behavioral therapy (CBT) and amitriptyline (CBT+A) or headache education (HE) and amitriptyline (HE+A) to determine if there was a differential time course of treatment response between the groups. One hundred thirty-five patients (age 10–17 years) diagnosed with chronic migraine participated, attending 8 one-hour one-on-one CBT or HE sessions with a trained psychologist for 8 weekly sessions, 2 sessions at weeks 12 and 16, and a post-treatment visit at week 20. Participants kept daily headache diaries and completed take-home assignments between visits. Data from daily headache diaries are presented for each day and according to 28-day periods. Trajectories of improvement indicate initial decrease in headache days began during the first month of treatment, for both groups, and continued to decrease throughout treatment. The CBT+A group had greater daily improvement than the HE+A group. A significantly greater proportion of the CBT+A group had a ≥50% reduction in headache days each month, and a significantly greater proportion of the CBT+A group had ≤4 headache days per month in months 3 through 5. Results indicate the trajectory of decrease in headache days is significantly better for patients receiving CBT+A versus HE+A. Perspective This article presents daily information about headache frequency over a 20-week clinical trial. Youth with chronic migraine who received CBT+A improved faster than those in the control group. Findings provide clinicians with evidence-based expectations for treatment response over time and ways of monitoring treatment success. Trial registration clinicaltrials.gov identifier NCT00389038 .
- Published
- 2017
48. Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: a modelling study
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Hira Tanvir, T. Papadopoulos, Yvonne Tam, Petra Klepac, Emilia Vynnycky, Kaja Abbas, Michael L. Jackson, Mark Jit, Katy A. M. Gaythorpe, Andrew Clark, Amy Winter, Nicholas C. Grassly, Quan Minh Tran, Colin Sanderson, Homie Razavi, Xiang Li, Caroline Trotter, Andromachi Karachaliou, Sean M. Moore, Matthew J. Ferrari, Stephen Sy, Duy M. H. Nguyen, Steven Sweet, Kirsten Eilertson, Justin Lessler, Christinah Mukandavire, Devin Razavi-Shearer, Stephen C Resch, Emily D Carter, Wes Hinsley, Ivane Gamkrelidze, Tini Garske, Shaun A. Truelove, Susy Echeverria Londono, Shevanthi Nayagam, Neil M. Ferguson, Kévin Jean, Hannah E. Clapham, Kevin van Zandvoort, Timothy B. Hallett, Hope L. Johnson, Margaret J. de Villiers, Zulma M. Cucunubá, Kim Woodruff, Stéphane Verguet, Xi Li, Neff Walker, Marc Brisson, Imperial College London, London School of Hygiene and Tropical Medicine (LSHTM), National University of Singapore (NUS), Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), University of Oxford, The University of Hong Kong (HKU), Public Health England [London], Gavi Alliance, University of Southampton, Université Laval [Québec] (ULaval), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Colorado State University [Fort Collins] (CSU), Pennsylvania State University (Penn State), Penn State System, Center for Disease Analysis Foundation [Lafayette, CO, États-Unis], Kaiser Permanente Washington Health Research Institute [Seattle] (KPWHRI), Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité), University of Cambridge [UK] (CAM), University of Notre Dame [Indiana] (UND), Dublin City University [Dublin] (DCU), Harvard T.H. Chan School of Public Health, Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation., Bill & Melinda Gates Foundation, World Health Organization, and Medical Research Council (MRC)
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Male ,Cost-Benefit Analysis ,CHILDREN ,030204 cardiovascular system & hematology ,Global Health ,DISEASE ,0302 clinical medicine ,Global health ,030212 general & internal medicine ,11 Medical and Health Sciences ,Vaccines ,Vaccination ,General Medicine ,Articles ,IMMUNIZATION ,Child, Preschool ,Income ,Female ,Quality-Adjusted Life Years ,BURDEN ,Life Sciences & Biomedicine ,Vaccine Impact Modelling Consortium ,medicine.medical_specialty ,Rubella ,Measles ,Communicable Diseases ,03 medical and health sciences ,Medicine, General & Internal ,Environmental health ,General & Internal Medicine ,BENEFITS ,medicine ,Humans ,Mortality ,Poverty ,Developing Countries ,Disease burden ,Science & Technology ,business.industry ,Immunization Programs ,Public health ,GAVI ,Models, Theoretical ,medicine.disease ,TRENDS ,Quality-adjusted life year ,Immunization ,Communicable Disease Control ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology ,business - Abstract
Summary Background The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. Methods 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. Findings We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52–88) deaths between 2000 and 2030, of which 37 million (30–48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36–58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52–66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93–150) deaths will be averted by vaccination, of which 58 million (39–76) are due to measles vaccination and 38 million (25–52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59–81) reduction in lifetime mortality in the 2019 birth cohort. Interpretation Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. Funding Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.
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- 2019
49. Estimating the health impact of vaccination against 10 pathogens in 98 low and middle income countries from 2000 to 2030
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Li, Xiang, Mukandavire, Christinah, Cucunubá, Zulma M, Abbas, Kaja, Clapham, Hannah E, Jit, Mark, Johnson, Hope L, Papadopoulos, Timos, Vynnycky, Emilia, Brisson, Marc, Carter, Emily D, Clark, Andrew, de Villiers, Margaret J, Eilertson, Kirsten, Ferrari, Matthew J, Gamkrelidze, Ivane, Gaythorpe, Katy, Grassly, Nicholas C, Hallett, Timothy B, Jackson, Michael L, Jean, Kévin, Karachaliou, Andromachi, Klepac, Petra, Lessler, Justin, Li, Xi, Moore, Sean M, Nayagam, Shevanthi, Nguyen, Duy Manh, Razavi, Homie, Razavi-Shearer, Devin, Resch, Stephen, Sanderson, Colin, Sweet, Steven, Sy, Stephen, Tam, Yvonne, Tanvir, Hira, Tran, Quan Minh, Trotter, Caroline L, Truelove, Shaun, van Zandvoort, Kevin, Verguet, Stéphane, Walker, Neff, Winter, Amy, Ferguson, Neil M, and Garske, Tini
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medicine.medical_specialty ,business.industry ,Public health ,Hepatitis B ,medicine.disease ,medicine.disease_cause ,Rubella ,Measles ,Vaccination ,Immunization ,Rotavirus ,medicine ,business ,Disease burden ,Demography - Abstract
BackgroundThe last two decades have seen substantial expansion of childhood vaccination programmes in low and middle income countries (LMICs). Here we quantify the health impact of these programmes by estimating the deaths and disability-adjusted life years (DALYs) averted by vaccination with ten antigens in 98 LMICs between 2000 and 2030.MethodsIndependent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B (HepB), Haemophilus influenzae type b (Hib), human papillomavirus (HPV), Japanese encephalitis (JE), measles, Neisseria meningitidis serogroup A (MenA), Streptococcus pneumoniae, rotavirus, rubella, yellow fever. Using standardized demographic data and vaccine coverage estimates for routine and supplementary immunization activities, the impact of vaccination programmes on deaths and DALYs was determined by comparing model estimates from the no vaccination counterfactual scenario with those from a default coverage scenario. We present results in two forms: deaths/DALYs averted in a particular calendar year, and in a particular annual birth cohort.FindingsWe estimate that vaccination will have averted 69 (2.5-97.5% quantile range 52-88) million deaths between 2000 and 2030 across the 98 countries and ten pathogens considered, 35 (29-45) million of these between 2000-2018. From 2000-2018, this represents a 44% (36-57%) reduction in deaths due to the ten pathogens relative to the no vaccination counterfactual. Most (96% (93-97%)) of this impact is in under-five age mortality, notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 122 (96-147) million deaths will be averted by vaccination, of which 58 (39-75) and 38 (26-52) million are due to measles and Hepatitis B vaccination, respectively. We estimate that recent increases in vaccine coverage and introductions of additional vaccines will result in a 72% (61-79%) reduction in lifetime mortality caused by these 10 pathogens in the 2018 birth cohort.InterpretationIncreases in vaccine coverage and the introduction of new vaccines into LMICs over the last two decades have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained.
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- 2019
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50. On the Relationship between the Vortices from an Underbody Diffuser in Ground-Effect and the Resulting Downforce
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Hope L. Weiss, Ramitha Edirisinghe, and Salvador Mayoral
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Physics ,Ground effect (aerodynamics) ,Diffuser (automotive) ,Mechanics ,Downforce ,Vortex - Published
- 2019
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