189 results on '"Doggett J"'
Search Results
2. Don't Dream It, B It: DEI policies add up to belonging
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Doggett, J. Maija
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Workplace multiculturalism -- Management -- Forecasts and trends ,Company business management ,Market trend/market analysis ,Business ,Business, regional - Abstract
By now, you've seen the initialism DEI, and you know that the letter 'D' stands for diversity, the letter 'E' stands for equity, and the letter 'I' stands for inclusion. [...]
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- 2023
3. Utilizing sentiment analysis of X data to document the evolution of colorectal surgical innovations: The case of transanal total mesorectal excision.
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Weltermann, T., Eltyeb, H., Doggett, J., and Brady, R. R. W.
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Aim: The evolution of the utility of medical social media and its global reach has led to a much greater speed of dissemination of medical innovation, such as transanal total mesorectal excision (TaTME). The acceptability and discussions surrounding such innovations can be followed online. Here, we sought to determine if online discussions over time could match known models of innovation evolution using the example of TaTME since its initial description in 2010. Methods: Data on using the X hashtag #TaTME were analysed using the social media analytics tool Brandwatch. Trends in mentions, impressions and reach were highlighted over 13 years (1 May 2010 to 31 July 2023). Each mention's sentiment and emotional connotations were analysed using Brandwatch's natural language processing approach. Results: We identified 18 525 mentions of #TaTME by healthcare professionals, reaching over 30.6 million X users. A Gartner's hype‐cycle‐like pattern was identified for mention volume and emotional connotation over time. The majority of mentions had a neutral (84%; n = 15 341) or positive connotation (15%, n = 2675). A peak of negatively connotated mentions was identified surrounding the temporary suspension of TaTME in 2019. Conclusion: This study presents a novel method of monitoring online discussions surrounding new surgical innovations by healthcare professionals based on sentiment analysis of public social media data. Mention volume and emotional connotation were the most accurate parameters closely resembling Gartner's hype cycle. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Endochin-like quinolones (ELQs) and bumped kinase inhibitors (BKIs): Synergistic and additive effects of combined treatments against Neospora caninum infection in vitro and in vivo
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Anghel, Nicoleta, Imhof, Dennis, Winzer, Pablo, Balmer, Vreni, Ramseier, Jessica, Haenggeli, Kai, Choi, Ryan, Hulverson, Matthew A., Whitman, Grant R., Arnold, Samuel L.M., Ojo, Kayode K., Van Voorhis, Wesley C., Doggett, J. Stone, Ortega-Mora, Luis M., and Hemphill, Andrew
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- 2021
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5. Verifying Sincerity: A human resources perspective on vaccine mandates
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Doggett, J. Maija
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United States. Occupational Safety and Health Administration ,Vaccines ,Business ,Business, regional - Abstract
You can say I am a card-carrying, dyed-in-the-wool, devoted human resources professional. I got my bachelor's degree in business management, with an emphasis in human resource management, from UAA in [...]
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- 2022
6. In vitro activity, safety and in vivo efficacy of the novel bumped kinase inhibitor BKI-1748 in non-pregnant and pregnant mice experimentally infected with Neospora caninum tachyzoites and Toxoplasma gondii oocysts
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Imhof, Dennis, Anghel, Nicoleta, Winzer, Pablo, Balmer, Vreni, Ramseier, Jessica, Hänggeli, Kai, Choi, Ryan, Hulverson, Matthew A., Whitman, Grant R., Arnold, Samuel L.M., Ojo, Kayode K., Van Voorhis, Wesley C., Doggett, J. Stone, Ortega-Mora, Luis M., and Hemphill, Andrew
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- 2021
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7. Bumped Kinase Inhibitors as therapy for apicomplexan parasitic diseases: lessons learned
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Choi, Ryan, Hulverson, Matthew A., Huang, Wenlin, Vidadala, Rama S.R., Whitman, Grant R., Barrett, Lynn K., Schaefer, Deborah A., Betzer, Dana P., Riggs, Michael W., Doggett, J. Stone, Hemphill, Andrew, Ortega-Mora, Luis Miguel, McCloskey, Molly C., Arnold, Samuel L.M., Hackman, Robert C., Marsh, Kennan C., Lynch, James J., Freiberg, Gail M., Leroy, Bruce E., Kempf, Dale J., Choy, Robert K.M., de Hostos, Eugenio L., Maly, Dustin J., Fan, Erkang, Ojo, Kayode K., and Van Voorhis, Wesley C.
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- 2020
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8. Comparative efficacy of buparvaquone and imidocarb in inhibiting the in vitro growth of Babesia bovis.
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Cardillo, Natalia M., Lacy, Paul A., Villarino, Nicolas F., Doggett, J. Stone, Riscoe, Michael K., Bastos, Reginaldo G., Laughery, Jacob M., Ueti, Massaro W., and Suarez, Carlos E.
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BABESIA ,INHIBITORY Concentration 50 ,TICK-borne diseases ,PARASITEMIA - Abstract
Introduction: B. bovis is an apicomplexan parasite responsible for bovine babesiosis, a tick-borne disease with a worldwide impact. The disease remains inefficiently controlled, and few effective drugs, including imidocarb dipropionate (ID), are currently available in endemic areas. The objective of this study was to evaluate whether buparvaquone (BPQ), a drug currently used to treat cattle infected with the Babesia-related Theileria spp. parasites, could be active against Babesia parasites. Herein, we compared the effect of ID and BPQ on B. bovis growth in vitro erythrocyte culture. Methods: We compared the effect of ID and BPQ on the culture-adapted Texas T2Bo strain of B. bovis. In vitro cultured parasites were incubated with ID and BPQ at two starting parasitemia levels (PPE), 0.2% and 1%. In vitro cultured parasites were treated with ID or BPQ at concentrations ranging from 10 to 300 nM, during 4 consecutive days. Parasitemia levels were daily evaluated using microscopic examination. Data was compared using the independent Student's t-test. Results and Discussion: Both ID and BPQ significantly inhibited (p < 0.05) the growth of B. bovis, regardless of the initial parasitemia used. At 1% parasitemia, BPQ had lower calculated inhibitory concentration 50 (IC50: 50.01) values than ID (IC50: 117.3). No parasites were found in wells with 0.2% starting parasitemia, treated previously with 50 nM of BPQ or ID, after 2 days of culture without drugs. At 1% parasitemia, no parasite survival was detected at 150 nM of BPQ or 300 nM of ID, suggesting that both drugs acted as babesiacidals. Conclusion: Overall, the data suggests that BPQ is effective against B. bovis and shows a residual effect that seems superior to ID, which is currently the first-line drug for treating bovine babesiosis globally. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Synthesis of Deuterated Endochin-Like Quinolones.
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Pou, Sovitj, Winter, Rolf W., Liebman, Katherine M., Dodean, Rosie A., Nilsen, Aaron, DeBarber, Andrea, Doggett, J. Stone, and Riscoe, Michael K.
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QUINOLONE antibacterial agents ,VETERANS' health ,AWARDS ,MEDICAL research ,MASS spectrometry ,VETERINARY drugs - Abstract
Funding: This project was supported with funds from the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Program Award number i01 BX003312 (M.K.R.). M.K.R. is a recipient of a VA Research Career Scientist Award (14S-RCS001). Research reported in this publication was also supported by the US National Institutes of Health under award numbers R01AI100569 and R01AI141412 (M.K.R.) and by the US Department of Defense Peer Reviewed Medical Research Program (PR181134) (M.K.R.). This work was also funded by VA Merit Review Award BX004522 to JSD from the US Department of Veterans Affairs Biomedical Laboratory Research and Development. The National Science Foundation provided instrument funding for the BioAnalytical Mass Spectrometry Facility at Portland State University (NSF, MRI 1828573), which was used to generate HRMS analytical measurements. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Effectiveness of Two New Endochin-like Quinolones, ELQ-596 and ELQ-650, in Experimental Mouse Models of Human Babesiosis.
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Vydyam, Pratap, Chand, Meenal, Pou, Sovitj, Winter, Rolf W., Liebman, Katherine M., Nilsen, Aaron, Doggett, J. Stone, Riscoe, Michael K., and Ben Mamoun, Choukri
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- 2024
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11. Antimalarial proteasome inhibitor reveals collateral sensitivity from intersubunit interactions and fitness cost of resistance
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Kirkman, Laura A., Zhan, Wenhu, Visone, Joseph, Dziedziech, Alexis, Singh, Pradeep K., Fan, Hao, Tong, Xinran, Bruzual, Igor, Hara, Ryoma, Kawasaki, Masanori, Imaeda, Toshihiro, Okamoto, Rei, Sato, Kenjiro, Michino, Mayako, Alvaro, Elena Fernandez, Guiang, Liselle F., Sanz, Laura, Mota, Daniel J., Govindasamy, Kavitha, Wang, Rong, Ling, Yan, Tumwebaze, Patrick K., Sukenick, George, Shi, Lei, Vendome, Jeremie, Bhanot, Purnima, Rosenthal, Philip J., Aso, Kazuyoshi, Foley, Michael A., Cooper, Roland A., Kafsack, Bjorn, Doggett, J. Stone, Nathan, Carl F., and Lin, Gang
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- 2018
12. Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi
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Silva, Marta G., Bastos, Reginaldo G., Stone Doggett, J., Riscoe, Michael K., Pou, Sovitj, Winter, Rolf, Dodean, Rozalia A., Nilsen, Aaron, and Suarez, Carlos E.
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- 2020
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13. Genome Sequence of the Enterobacterial Phytopathogen Erwinia carotovora Subsp. atroseptica and Characterization of Virulence Factors
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Bell, K. S., Sebaihia, M., Pritchard, L., Holden, M. T. G., Hyman, L. J., Holeva, M. C., Thomson, N. R., Bentley, S. D., Churcher, L. J. C., Mungall, K., Atkin, R., Bason, N., Brooks, K., Chillingworth, T., Clark, K., Doggett, J., Fraser, A., Hance, Z., Hauser, H., Jagels, K., Moule, S., Norbertczak, H., Ormond, D., Price, C., Quail, M. A., Sanders, M., Walker, D., Whitehead, S., Salmond, G. P. C., Birch, P. R. J., Parkhill, J., Toth, I. K., and Haselkorn, Robert
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- 2004
14. Photoswitchable Inhibitors to Optically Control Specific Kinase Activity.
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Aguirre, Tim, Teichmann, Ellen, Römpp, Florian Q., Vivier, Ruthey, Bryant, Cole, Hulverson, Matthew A., Van Voorhis, Wesley C., Ojo, Kayode K., Doggett, J. Stone, Fiedler, Dorothea, and Hecht, Stefan
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- 2023
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15. Quinolone-3-amidoalkanol: A New Class of Potent and Broad-Spectrum Antimicrobial Agent.
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Dube, Phelelisiwe S., Angula, Klaudia T., Legoabe, Lesetja J., Jordaan, Audrey, Boitz Zarella, Jan M., Warner, Digby F., Doggett, J. Stone, and Beteck, Richard M.
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- 2023
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16. Endochin-like quinolones are highly efficacious against acute and latent experimental toxoplasmosis
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Doggett, J. Stone, Nilsen, Aaron, Forquer, Isaac, Wegmann, Keith W., Jones-Brando, Lorraine, Yolken, Robert H., Bordón, Claudia, Charman, Susan A., Katneni, Kasiram, Schultz, Tracey, Burrows, Jeremy N., Hinrichs, David J., Meunier, Brigitte, Carruthers, Vern B., and Riscoe, Michael K.
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- 2012
17. Transitions of Care in Nutrition: Implications of Creating a Care Pathway from Inpatient to Outpatient.
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Doggett, J., Fraser, A., and Roberts, T.
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MEDICAL protocols , *OUTPATIENT services in hospitals , *CONFERENCES & conventions , *TRANSITIONAL care , *NUTRITION services - Published
- 2024
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18. A New Scalable Synthesis of ELQ-300, ELQ-316, and other Antiparasitic Quinolones
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Pou, Sovitj, Dodean, Rozalia A., Frueh, Lisa, Liebman, Katherine M., Gallagher, Rory T., Jin, Haihong, Jacobs, Robert T., Nilsen, Aaron, Stuart, David R., Doggett, J. Stone, Riscoe, Michael K., and Winter, Rolf W.
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Article - Abstract
The Endochin-Like Quinolone (ELQ) compound class may yield effective, safe treatments for a range of important human and animal afflictions. However, to access the public health potential of this compound series, a synthetic route needed to be devised that lowers costs and is amenable to large scale production. In the new synthetic route described here, a substituted β-keto ester, formed by an Ullmann reaction and subsequent acylation, is reacted with an aniline via a Conrad-Limpach reaction to produce 3-substituted 4(1H)-quinolones such as ELQ-300 and ELQ-316. This synthetic route, the first described to be truly amenable to industrial scale production, is relatively short (5 reaction steps), does not require palladium, chromatographic separation or protecting group chemistry, and may be performed without high vacuum distillation.
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- 2021
19. Babesia duncani as a Model Organism to Study the Development, Virulence, and Drug Susceptibility of Intraerythrocytic Parasites In Vitro and In Vivo.
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Pal, Anasuya C, Renard, Isaline, Singh, Pallavi, Vydyam, Pratap, Chiu, Joy E, Pou, Sovitj, Winter, Rolf W, Dodean, Rozalia, Frueh, Lisa, Nilsen, Aaron C, Riscoe, Michael K, Doggett, J Stone, Mamoun, Choukri Ben, and Ben Mamoun, Choukri
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PROTOZOA ,ATOVAQUONE ,PRODRUGS ,ANIMAL experimentation ,TICKS ,RESEARCH funding ,PARASITES ,QUINOLONE antibacterial agents ,MICROBIAL virulence ,MICE - Abstract
Human babesiosis is a malaria-like illness caused by tick-borne intraerythrocytic Babesia parasites of the Apicomplexa phylum. Whereas several species of Babesia can cause severe disease in humans, the ability to propagate Babesia duncani both in vitro in human erythrocytes and in mice makes it a unique pathogen to study Babesia biology and pathogenesis. Here we report an optimized B. duncani in culture-in mouse (ICIM) model that combines continuous in vitro culture of the parasite with a precise model of lethal infection in mice. We demonstrate that B. duncani-infected erythrocytes as well as free merozoites can cause lethal infection in C3H/HeJ mice. Highly reproducible parasitemia and survival outcomes could be established using specific parasite loads in different mouse genetic backgrounds. Using the ICIM model, we discovered 2 new endochin-like quinolone prodrugs (ELQ-331 and ELQ-468) that alone or in combination with atovaquone are highly efficacious against B. duncani and Babesia microti. [ABSTRACT FROM AUTHOR]
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- 2022
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20. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
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Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ, Novo S, Krum H, Varigos J, Siostrzonek P, Sinnaeve P, Gotcheva N, Yong H, Urina-Triana M, Milicic D, Vettus R, Manolis AJ, Wyss F, Sigurdsson A, Fucili A, Veze I, Petrauskiene B, Salvador L, Klemsdal TO, Medina F, Budaj A, Otasevic P, Lainscak M, Seung KB, Commerford P, Donath M, Hwang JJ, Kultursay H, Bilazarian S, East C, Forgosh L, Harris B, Ligueros M, Bohula E, Charmarthi B, Cheng S, Chou S, Danik J, McMahon G, Maron B, Ning M, Olenchock B, Pande R, Perlstein T, Pradhan A, Rost N, Singhal A, Taqueti V, Wei N, Burris H, Cioffi A, Dalseg AM, Ghosh N, Gralow J, Mayer T, Rugo H, Fowler V, Limaye AP, Cosgrove S, Levine D, Lopes R, Scott J, Hilkert R, Tamesby G, Mickel C, Manning B, Woelcke J, Tan M, Manfreda S, Ponce T, Kam J, Saini R, Banker K, Salko T, Nandy P, Tawfik R, O’Neil G, Manne S, Jirvankar P, Lal S, Nema D, Jose J, Collins R, Bailey K, Blumenthal R, Colhoun H, Gersh B, Abreu M, Actis MV, Aiub J, Aiub F, Albisu J, Alvarisqueta A, Avalos V, Barreto M, Berli MA, Blumberg C, Bocanera M, Botta C, Bowen L, Budassi N, Buhlman S, Westberg JC, Carabajal T, Caruso G, Casala J, Cendali G, Coloma G, Berra FC, Cuneo C, Degennaro N, Dellasa M, Diaz M, Dos Santos P, Espinosa V, Facello A, Facello M, Farias E, Fernandez AA, Ferrari V, Pacora FF, Flores GS, Franco M, Gabito A, Viola HG, Garcia F, Garcia Duran R, Garcia Pinna J, Glenny J, Godoy Sanchez M, Grosse A, Guzman P, Hasbani E, Hominal M, Ibañez J, Jure H, Jure D, Vico ML, Liniado G, Luciardi H, Luquez H, Maehara G, Maffei L, Majul C, Mallagray M, Marinaro S, Martinez J, Massaccesi R, De Los Milagros Had M, Azize GM, Montana O, Montenegro E, Morell Y, Muntaner J, Navarrete S, Olmedo M, Paganini M, Paz S, Perez Manghi F, Piskorz D, Polato C, Recoaro R, Romano A, Salinger M, Sanchez A, Saravia MA, Sarjanovich R, Scaro G, Schiavi LB, Soler J, Tinnirello V, Tomassi A, Valle M, Vallejo MA, Venturini C, Marcela Wenetz LM, Yossen M, Zaidman C, Zalazar L, Zangroniz P, Amerena J, Brady L, Colquhoun D, Eccleston D, Ferreira-Jardim A, French J, Jayasinghe R, Mcintosh C, Ord M, Plotz M, Purnell P, Roberts-Thomson P, Schultz C, Shanahan T, Tan R, Taverner P, Turner F, Vibert J, Vorster M, William M, Youssef G, Bergler-Klein J, Brath H, Brodmann M, Fliesser-Goerzer E, Haider K, Heeren G, Hiden C, Mandic L, Paulweber B, Ploechl A, Prenner A, Steringer-Mascherbauer R, Strohner-Kaestenbauer H, Barbato E, Bouvy C, Briké C, Charlier F, Cools F, De Knijf K, De Wolf L, Delforge M, Deweerdt N, Gits F, Goffinet C, Hermans K, Hollanders G, Mestdagh I, Pirenne B, Servaes V, Simons N, Tahon S, Theunissen E, Van Genechten G, Vervoort G, Vissers C, Vranckx P, Vrolix M, Abib E Jr, Abrantes J, Araujo Fonseca M, Barbosa E, Barroso W, Barroso A, Bodanese L, Botelho R, Costa Amorim R, Da Costa F, Da Silva A, Da Silva O Jr, Da Silva D Jr, Ferreira Dos Santos T, Dos Santos F, Dos Santos A, Duda N, Feitosa G, Felario Junior GA, Ferraz R, Filho P, Fonseca A, Wanderley FF, Freitas E, Fucci F, Marengo Garcia De Carvalho L, Hernandez M, Hettwer Magedanz E, Julião K, Kormann A, Lameira A, Lima F, Lino E, Maia L, Manenti E, Marchi AL, Fischer SM, Michalaros Y, Moraes J Jr, Moreira L, Pagnan M, Pesce F, Pinheiro L, Rassi S, Reis G, Reis H, Resende I, Roel A, Ruschel K, Saporito W, Saraiva JF, Seroqui M, Silva R, Unterkircher B, Vicente C, Vieira N, Xavier JP, Zucchetti C, Angelova I, Dimitrov G, Genova D, Gospodinov K, Goudev A, Grigorova V, Hristova K, Makedonska JJ, Katova T, Kostov K, Lazov P, Manov E, Manukov I, Manukov D, Milanova M, Kabakchieva VM, Petrov D, Petrusheva T, Pramatarova I, Raev D, Runev N, Sirakova-Taseva A, Tisheva-Gospodinova S, Todorova A, Tzekova M, Yakovova S, Yanev T, Abulencia K, Arora S, Baker A, Bata IR, Beaudry M, Belle Isle J, Bilodeau N, Boivin MC, Bolduc H, Bourgeois S, Brons S, Cantor W, Chaussé I, Chhabra A, Chouinard G, Cleveland T, Dattani D, Deslongchamps F, Diodati J, Drouin K, Duchesne L, Fontaine S, d'Amours DG, Gervais B, Gosselin G, Graham J, Grover A, Gupta A, Haldane H, Hartleib M, Hickey L, Huynh T, Johnston J, Julien VE, Lachance P, Lake J, Lamontagne C, Lauzon C, Lepage S, Maheux K, Manyari D, Martin E, McPherson C, Mehta S, Michaud N, Kouz SM, Murphy G, OKeefe D, Otis R, Ouimet F, Pandey S, Peck C, Perkins L, Richert L, Robbins K, Robinson S, Cabau JR, Ross B, Roy C, Roy M, Roy A, Rupka D, Affaki GS, Saunders K, Savard D, Soucy D, St Amour E, Thiessen S, Vertes G, Vezina M, Vincelli G, Weisnagel SJ, Zadra R, Chen J, Chen Y, Dong X, Feng Y, Feng Z, Fu G, Han B, Hao Y, He Y, He Z, Hong T, Jia Z, Jiang T, Jiang J, Jiang X, Ke Y, Li Y, Li Z, Li W, Li X, Liu P, Liu Y, Liu B, Liu S, Liu L, Lu Z, Lv Y, Ma C, Ma G, Peng L, Qing L, Ren L, Sang X, Song M, Sun Z, Wang J, Wang Y, Wei J, Wu W, Wu J, Xu H, Yan J, Yang P, Yang K, Yao Z, Yaoqing H, Yuan Z, Zhai Z, Zhang J, Zhang Y, Zhao R, Zhou H, Accini Mendoza JL, Aparicio CV, Castillo T, Chaverra I, Conrado Y, Coronel J, Cotes C, Cuentas I, Cuervo A, Dussan MA, Echeverria L, Hernandez E, Ibarra J, Isaza D, Jimenez D, Lopez P, Manzur F, Mejia I, Mendoza Y, Molina DI, Patino JM, Rodriguez D, Rodriguez LM, Rodriguez SM, Sanchez Vallejo G, Luz Serrano H, Sotomayor A, Urina M, Vesga B, Yupanqui H, Akrap B, Busic N, Ciglenecki N, Cmrecnjak J, Fucak E, Gabor M, Jeric M, Jutrisa N, Kordic K, Planinc I, Popovic Z, Radeljic V, Sesto I, Sutalo K, Tusek S, Belohlavek J, Budkova J, Busak L, Capova L, Cech V, Cermak O, Coufalova Z, Cyprian R, Dedek V, Dedkova S, Ferkl R, Hanak P, Hanustiakova A, Homza M, Horackova K, Houra M, Iveta H, Kaiserova L, Kala P, Karel I, Kellnerova I, Koleckar P, Kreckova M, Krupicka J, Lorenc Z, Machova V, Malik J, Masarikova L, Matyasek I, Mikus M, Mikusova T, Ondrasik J, Otava M, Palubova L, Pavlickova L, Peterka M, Petrova I, Pokorna B, Povolny P, Radvan M, Reznakova S, Rickova Z, Roszkowska P, Rotreklova M, Samkova D, Skalicka H, Slechticka A, Sternthal P, Telekes P, Tesak M, Vesely P, Vesely J, Vins P, Vitovec M, Vodnansky P, Zidova M, Keba E, Laane E, Pool T, Randvee L, Ratnik E, Reimand M, Reinmets S, Rivis L, Siemann M, Stern M, Toom M, Vahula V, Apel T, Axthelm C, Ayasse D, Ayasse M, Baar M, Baeumer A, Bagi ES, Becker B, Binder A, Blankenberg S, Braun P, Johansen BB, Contzen C, Delfonso F, Denecke C, Dengler T, Donaubauer T, Eichinger G, Englmann E, Erhard M, Faghih M, Foerster A, Frankenstein L, Fuchs R, Furch G, Gaeb-Strasas B, Germann H, Giese C, Goette A, Gravenhorst-Muenter U, Haege R, Haenel T, Hagemann D, Hagenow A, Hanefeld M, Heider J, Heisters J, Hennig D, Hielscher S, Himpel-Boenninghoff A, Holscher A, Hornig M, Jeserich M, Kaczmarek N, Kanitz S, Kara YD, Khariouzov A, Kiefer R, Kiroglu K, Klamm M, Klein C, Korth-Wiemann B, Krapivsky A, Kuenzler J, Kuntzsch A, Landers B, Lappo M, Laube S, Leggewie S, Lehmann D, Lepp H, Lierse T, Lindner C, Luecke-Uzar M, Luedemann J, Marschke T, Maruzzo S, Mauersberger K, Maus O, Meinrich M, Meissner A, Moehring B, Muehlhaus J, Mueller S, Muenter KC, Muenzel T, Naumann R, Nebel J, Neumann J, Nuding S, Overhoff U, Papke B, Pencz I, Peter Y, Peukert AM, Radde I, Rau T, Regner S, Reichenbach D, Reimer D, Rinke A, Roettges R, Romanski A, Rummel R, Samer H, Sanuri M, Sarnighausen HE, Schäfer B, Scheibner T, Schermaul KH, Schindler A, Schlundt C, Schmidt E, Schmidt K, Schnabel A, Schoen N, Schorn K, Schroeder T, Schulenburg D, Schulz M, Schulze U, Schulze J, Schumacher M, Schwerin G, Schwerin M, Stadelmeier S, Stahl HD, Stahl A, Stockhausen J, Stockhausen G, Stoessel J, Stolze K, Stratmann M, Szymanowski N, Teschner AB, Teske A, Uecker C, Veit S, Voeller H, Walter I, Walter J, Walther I, Weber HG, Weimer J, Wichterich K, Wiebusch A, Willmerdinger M, Willner C, Winkelmann B, Winkler J, Wistuba T, Woehrle J, Wohnlich T, Wolf S, Woyczak D, Wrage P, Zirlik A, Anadiotis A, Chachalis G, Dermitzakis A, Kafarakis P, Kaldara E, Kolokathis F, Kostakou P, Lekakis J, Manolis A, Mantas I, Megalou A, Milkas A, Nanas J, Olympios CD, Patsilinakos S, Perperis A, Poulimenos L, Saloustros I, Tsioufis K, Tsorbatzoglou K, Vardas P, Zarifis I, Aguilar M, Arango JL, Borrayo NA, Corona V, Guerrero A, Guzman I, Haase F, De Krumbach L, Montenegro P, Munoz R, Munoz N, Paniagua A, Solares A, Vogel M, Anita S, Blazsek Z, Decsi K, Fulop T, Hangyal T, Hegedus V, Kalina A, Karakai H, Katona A, Kiss RG, Kovacs A, Laszlo Z, Lupkovics G, Medvegy M, Merkely B, Mihaly N, Nagy AC, Dékány JN, Nikoletta P, Noori E, Penzes J, Poor F, Sarszegi Z, Simay A, Simon J, Szakal I, Szatmarine V, Szocs A, Zilahi Z, Karsai XZ, Andersen K, Sigurdadottir E, Skuladottir F, Abdullakutty J, Abhaichand R, Abhyankar A, Agarwal DK, Aggarwal RK, Ahire N, Awasthi AK, Babu R, Bai A, Bali HK, Banker D, 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Ellis M, Erickson B, Ervin W, Eskridge L, Fail P, Falcon D, Fang C, Fattal P, Fawson A, Felix L, Ferdinand K, Fien E, Fintel D, Firek C, Fitz-Patrick D, Flores E, Flores E, Flores H, Floro T, Forker A, Foster M, Foucauld J, Lehman KF, Fox B, Francoeur L, Frandsen B, Frandsen B, Frivold G, Fruchter G, Fullerton D, Gabriel J, Gacioch G, Garas S, Garcia N, Garcia Rinaldi R, Garcia-Fragoso V, Garcia-Portela M, Gelb R, George F, Ghali J, Gilbert J, Gilley J, Glancy R, Goff R, Goldberg N, Gonzales D, Gonzales V, Gonzalez E, Gorges R, Gould R, Grabeau R, Grable M, Graham JA, Graif J, Green E, Greener R, Greenway F, Grieshaber V, Griffin S, Gros C, Gudipati RVC, Guillinta P, Gupta V, Gutmann J, Gwyn M, El Hachem M, Hage F, Hageman T, Haidar A, Hakas J, Haldis T, Hall L, Hall C, Hall S, Halpern S, Hamud-Socoro A, Hardee L, Harrell W, Harrington A, Hartwell J, Hasan F, Hattler B, Haught H, Haynes E, Haywood A, Heaney L, Hecht J, Hernandez I, Herzog W, Hess E, Hill H, Hilton T, Hinderaker P, Hodnett P, Hoffman M, Hogan C, Holmes Z, Rees DH, Hotchkiss D, Huang P, Humbert J, Hutchens E, Iachini K, Ibarra M, Igbokidi O, Ilahi T, Imbrognio M, Ipp E, Iteld B, Jacques G, Jafri A, Jafry B, Jardula M, Jefferson D, Jenkins R, Johnson E, Johnson J, Jones S, Kawahara M, Kelehan S, Kelly R, Kendall T, Kereiakes D, Khan M, Khan S, Kick J, Kimmel M, King T, King A, Kirkland S, Kissel S, Kitchens D, Klein P, Klugherz B, Korban E, Koren M, Korte M, Kostis J, Kotek L, Kozak M, Kreutter F, Kusnick B, Labovitz R, Lail J, Lamance J, Lamas G, Lambert J, Lambert C, Landzberg J, Langdon J, Lavoie W, Ledger G, Lee T, Lee K, Lehman R, Leimbach W, Lennard M, Lepor N, Lester F, Levin P, Levinson L, Lewis D, Lillo J, Link L, Long C, Longaker R, Lorch G, Lucksinger G, Lynd S, Rhudy JM, Madder R, Magness K, Maheshwari A, Alan A, Malek M, Maletz L, Malhotra V, Malhotra S, Mandviwala M, Mani CK, Manuel J, Marchelletta N, Marshall L, Marsters M, Martin L, Martinez E, Mavromatis K, Maynard R, Mays M, Mays B, Mbulaiteye A, Mcalister R, Mccoy C, Mccrary D Jr, Mccullough-O'Brien H, Mcdonald M, Mcgill J, Mcgrew F, Mckenzie C, Mclaurin B, Mclellan BA, Mcneil D, Mcneill R, Mehrle A, Melbie K, Melliza T, Messina T, Meyer R, Michel K, Mikdadi G, Miller C, Miller R, Miller A, Miller G, Miller W, Mitchell J, Moats DJR, Mody F, Moffat J, Molk B, Molter D, Monroe T, Montero H, Montgomery R, Mookherjee D, Moran J, Moriarty P, Morrison J, Morton D, Moshayedi P, Mosley J, Moustafa M, Munshi K, Murray A, Mustafa J, Nadar V, Naidu R, Nalley J, Navy S, Neil L, Neutel JM, Niblack P, Nicely V, Nicolai M, Nijmeh G, Nikas A, Nikyar A, Nixon S, Norman L, Noto G, Nour K, Nugent A, Ocman B, Odegard A, Olsen S, Ortiz-Carrasquillo R, Ossino N, Paez H, Palchick B, Paliwal Y, Pannell R, Parfait V, Partridge J, Patel B, Patel R, Patel M, Patel S, Paysor C, Pena A, Pereira S, Perez M, Perez A, Perkins H, Perry B, Peters P, Phillippi C, Phillips A, Phillips A, Piacente R, Pintado M, Pish R, Pitt W, Poling T, Pomposini D, Poock J, Potts J, Poudrier R, Prior J, Pritchard C, Purighalla R, Quddusi K, Quinones J, Quinton D, Radin M, Radojcsics B, Rajput B, Rama B, Ramos M, Rauch R, Raynes K, Reber AM, Reddy J, Reeves M, Reilly K, Renaud K, Resnick H, Reyes R, Richardson M, Riethof M, Riser J, Rodero M, Rodriguez Araya E, Roper L, Rozeman P, Ruder D, Runquist L, Sack G, Saint-Jacques H, Salfity M, Sall N, Sam K, Samal A, Sanchez D, Santiago J Jr, Savignano C, Saylor R, Scheffel M, Schifferdecker B, Schindler E, Schneider P, Schneider R, Schnitzler R, Schrager B, Schwartz A, Scott R, Seals A, Shah AV, Shah A, Shatsky K, Shayani S, Shealy N, Sheets L, Shelley J, Shepard P, Shetty S, Silver K, Simon M, Singh K, Singh N, Sizemore BC, Skatrud L, Slayton C, Slimak V, Sloane G, Smallwood B, Smith P, Smith M, Smith T, Smith G, Smith B, Smith W, Smith M, Smith J, Smith J, Soca Y, Sofley C, Sopko K, Sosa-Padilla M, Sotolongo R, Sprinkle B, Srivastava S, Starzec M, Steinhoff J, Stelly L, Stinson J, Stoddard M, Stoltz S, Stone B, Stover T, Strain J, Strugatsky S, Stys T, Suleman A, Sullivan P, Tamez W, Tandon N, Teltser M, Terry PS, Terry K, Tessmar C, Thekkoott D, Thomas D, Thomas DM, Thompson E, Thompson J, Thornton A, Tjaden T, Tobias C, Topper J, Tran A, Treasure C, Trenkamp P, Trevino M, Tsou L, Tuholske C, Uy W, Vahtel M, Vaid B, Valenzuela M, Vance A, Vandam J, Vanhecke T, Vanness WC III, Vargas R, Vaz S, Vazquez Tanus J, Veerina K, Vega J, Vento A, Vijay N, Voelker F, Vogt E, Vold D, Vora K, Wade RD, Wadell C, Waksman R, Walker K, Walker K, Wallace K, Warren M, Washam M, Watson B, Webel R, Wells T, West M, Whitaker J, White J, White C, White A, White A, Wilhoit G, Wilkins M, Willingham K, Wilson S, Wilson V, Wise J, Woodall S, Woods A, Wright J, Wu J, Xu ZJ, Yarows S, Young A, Younis L, Zarate J, Zebrack J, Zhang W, Zieve F, Zineldine A, Ridker, P. M., Everett, B. M., Thuren, T., Macfadyen, J. G., Chang, W. H., Ballantyne, C., FONSECA E PIRES, CARLOS EDUARDO, Nicolau, J., Koenig, W., Anker, S. D., Kastelein, J. J. P., Cornel, J. H., Pais, P., Pella, D., Genest, J., Cifkova, R., Lorenzatti, A., Forster, T., Kobalava, Z., Vida-Simiti, L., Flather, M., Shimokawa, H., Ogawa, H., Dellborg, M., Rossi, P. R. F., Troquay, R. P. T., Libby, P., Glynn R., J, CANTOS Trial, Group, Perrone, Filardi, P, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, and ACS - Atherosclerosis & ischemic syndromes
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0301 basic medicine ,030204 cardiovascular system & hematology ,law.invention ,0302 clinical medicine ,c-reactive protein ,Randomized controlled trial ,law ,Cardiovascular Disease ,middle aged ,double-blind method ,antibodies ,Myocardial infarction ,humans ,Stroke ,interleukin-1beta ,biology ,Antibodies, Monoclonal ,drug ,General Medicine ,Lipid ,Aged ,anti-inflammatory agents ,monoclonal ,humanized ,atherosclerosis ,cardiovascular diseases ,dose-response relationship ,female ,incidence ,infections ,lipids ,male ,myocardial infarction ,neutropenia ,secondary prevention ,stroke ,Anti-Inflammatory Agent ,aged ,Editorial ,Atherosclerosi ,Monoclonal ,Human ,medicine.drug ,medicine.medical_specialty ,Neutropenia ,Antibodies, Monoclonal, Humanized ,Infections ,Placebo ,antibodies, monoclonal ,dose-response relationship, drug ,infection ,medicine (all) ,03 medical and health sciences ,Internal medicine ,medicine ,Dose-Response Relationship, Drug ,business.industry ,Antiinflammatory Therapy, Canakinumab, for Atherosclerotic Disease ,C-reactive protein ,medicine.disease ,Surgery ,Canakinumab ,030104 developmental biology ,biology.protein ,business - Abstract
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.)
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- 2017
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21. Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13
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Hall, N., Pain, A., Berriman, M., Churcher, C., Harris, B., Harris, D., Mungall, K., Bowman, S., Atkin, R., Baker, S., Barron, A., Brooks, K., Buckee, C. O., Burrows, C., Cherevach, I., Chillingworth, C., Chillingworth, T., Christodoulou, Z., Clark, L., Clark, R., Corton, C., Cronin, A., Davies, R., Davis, P., Dear, P., Dearden, F., Doggett, J., Feltwell, T., Goble, A., Goodhead, I., Gwilliam, R., Hamlin, N., Hance, Z., Harper, D., Hauser, H., Hornsby, T., Holroyd, S., Horrocks, P., Humphray, S., Jagels, K., James, K. D., Johnson, D., Kerhornou, A., Knights, A., Konfortov, B., Kyes, S., Larke, N., Lawson, D., Lennard, N., Line, A., Maddison, M., McLean, J., Mooney, P., Moule, S., Murphy, L., Oliver, K., Ormond, D., Price, C., Quail, M. A., Rabbinowitsch, E., Rajandream, M.-A., Rutter, S., Rutherford, K. M., Sanders, M., Simmonds, M., Seeger, K., Sharp, S., Smith, R., Squares, R., Squares, S., Stevens, K., Taylor, K., Tivey, A., Unwin, L., Whitehead, S., Woodward, J., Sulston, J. E., Craig, A., Newbold, C., and Barrell, B. G.
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Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Author(s): N. Hall (corresponding author) [1]; A. Pain [1]; M. Berriman [1]; C. Churcher [1]; B. Harris [1]; D. Harris [1]; K. Mungall [1]; S. Bowman [1, 2]; R. Atkin [...]
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- 2002
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22. Disseminated Mycobacterium genavense with pulmonary nodules in a kidney transplant recipient: case report and review of the literature
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Doggett, J. S. and Strasfeld, L.
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- 2011
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23. Cytochrome b Drug Resistance Mutation Decreases Babesia Fitness in the Tick Stages But Not the Mammalian Erythrocytic Cycle.
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Chiu, Joy E, Renard, Isaline, George, Santosh, Pal, Anasuya C, Alday, P Holland, Narasimhan, Sukanya, Riscoe, Michael K, Doggett, J Stone, Mamoun, Choukri Ben, and Ben Mamoun, Choukri
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TICK infestations ,CYTOCHROME b ,DRUG resistance ,BABESIA ,PARASITE life cycles ,TICKS ,MOSQUITO vectors ,BABESIOSIS diagnosis ,ANTIPROTOZOAL agents ,PROTOZOA ,BABESIOSIS ,RESEARCH ,GENETIC mutation ,ANIMAL experimentation ,RESEARCH methodology ,EVALUATION research ,COMPARATIVE studies ,RESEARCH funding ,QUINOLONE antibacterial agents ,PARASITES ,ERYTHROCYTES ,HEMOPROTEINS ,PHARMACODYNAMICS ,INFECTIOUS disease transmission - Abstract
Human babesiosis is an emerging tick-borne malaria-like illness caused by Babesia parasites following their development in erythrocytes. Here, we show that a mutation in the Babesia microti mitochondrial cytochrome b (Cytb) that confers resistance to the antibabesial drug ELQ-502 decreases parasite fitness in the arthropod vector. Interestingly, whereas the mutant allele does not affect B. microti fitness during the mammalian blood phase of the parasite life cycle and is genetically stable as parasite burden increases, ELQ-502-resistant mutant parasites developing in the tick vector are genetically unstable with a high rate of the wild-type allele emerging during the nymphal stage. Furthermore, we show that B. microti parasites with this mutation are transmitted from the tick to the host, raising the possibility that the frequency of Cytb resistance mutations may be decreased by passage through the tick vector, but could persist in the environment if present when ticks feed. [ABSTRACT FROM AUTHOR]
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- 2022
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24. Comparison of Identical Technology: Automation versus Manual
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Colavecchia, C, Naguit, I, Visvalingam, R, Doggett, J, Callum, J, and Coovadia, A S
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- 2003
25. Targeted Structure-Activity Analysis of Endochin-like Quinolones Reveals Potent Qi and Qo Site Inhibitors of Toxoplasma gondii and Plasmodium falciparum Cytochrome bc(1) and Identifies ELQ-400 as a Remarkably Effective Compound against Acute Experimental Toxoplasmosis
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McConnell, Erin V., Bruzual, Igor, Pou, Sovitj, Winter, Rolf, Dodean, Rozalia A., Smilkstein, Martin J., Krollenbrock, Alina, Nilsen, Aaron, Zakharov, Lev N., Riscoe, Michael K., and Doggett, J. Stone
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Molecular Structure ,Phenyl Ethers ,Plasmodium falciparum ,Antiprotozoal Agents ,Drug Resistance ,Quinolones ,Article ,Electron Transport Complex III ,Mice ,Structure-Activity Relationship ,parasitic diseases ,Drug Discovery ,Animals ,Humans ,Malaria, Falciparum ,Toxoplasma ,Cells, Cultured ,Toxoplasmosis - Abstract
Cytochrome bc(1) inhibitors have been broadly studied as human and veterinary medicines, and agricultural fungicides. For the most part, cytochrome bc(1) inhibitors compete with ubiquinol at the ubiquinol oxidation (Qo) site or with ubiquinone at the quinone reduction (Qi) site. 4(1H)-Quinolones with 3-position substituents may inhibit either site based on quinolone ring substituents. 4(1H)-Quinolones that inhibit the Qi site are highly effective against toxoplasmosis, malaria and babesiosis and do not inhibit human cytochrome bc(1). We tested a series of 4(1H)-Quinolones against wild-type and drug resistant strains of Toxplasma gondii and Plasmodium falciparum. These experiments identified very potent compounds that inhibit T. gondii proliferation at picomolar concentrations. The most potent compounds target the Qo site, and for these compounds, an alkyl side chain confers potency against T. gondii greater than that of bulkier side chains. Our experiments also show that substituents on the quinolone ring influenced selectivity between T. gondii and P. falciparum and between Qo and Qi site-mediated activity. Comparison of the parasite cytochrome b sequences identified amino acids that are associated with drug resistance in P. falciparum that exist naturally in wild-type T. gondii. These underlying differences may influence drug susceptibility. Finally, a Qo site active 4(1H)-quinolone-3-diarylether tested in a murine model of toxoplasmosis was superior to atovaquone, resulting in survival from Type I strain T. gondii infection. These experiments identify highly effective compounds for toxoplasmosis and provide valuable insight into the structure-activity relationship of cytochrome bc(1) inhibitors.
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- 2018
26. Progress in Arabidopsis genome sequencing and functional genomics
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Wambutt, R, Murphy, G, Volckaert, G, Pohl, T, Düsterhöft, A, Stiekema, W, Entian, K.-D, Terryn, N, Harris, B, Ansorge, W, Brandt, P, Grivell, L, Rieger, M, Weichselgartner, M, de Simone, V, Obermaier, B, Mache, R, Müller, M, Kreis, M, Delseny, M, Puigdomenech, P, Watson, M, Schmidtheini, T, Reichert, B, Portatelle, D, Perez-Alonso, M, Boutry, M, Bancroft, I, Vos, P, Hoheisel, J, Zimmermann, W, Wedler, H, Ridley, P, Langham, S.-A, McCullagh, B, Bilham, L, Robben, J, Van der Schueren, J, Grymonprez, B, Chuang, Y.-J, Vandenbussche, F, Braeken, M, Weltjens, I, Voet, M, Bastiaens, I, Aert, R, Defoor, E, Weitzenegger, T, Bothe, G, Ramsperger, U, Hilbert, H, Braun, M, Holzer, E, Brandt, A, Peters, S, van Staveren, M, Dirkse, W, Mooijman, P, Klein Lankhorst, R, Rose, M, Hauf, J, Kötter, P, Berneiser, S, Hempel, S, Feldpausch, M, Lamberth, S, Van den Daele, H, De Keyser, A, Buysshaert, C, Gielen, J, Villarroel, R, De Clercq, R, Van Montagu, M, Rogers, J, Cronin, A, Quail, M, Bray-Allen, S, Clark, L, Doggett, J, Hall, S, Kay, M, Lennard, N, McLay, K, Mayes, R, Pettett, A, Rajandream, M.-A, Lyne, M, Benes, V, Rechmann, S, Borkova, D, Blöcker, H, Scharfe, M, Grimm, M, Löhnert, T.-H, Dose, S, de Haan, M, Maarse, A, Schäfer, M, Müller-Auer, S, Gabel, C, Fuchs, M, Fartmann, B, Granderath, K, Dauner, D, Herzl, A, Neumann, S, Argiriou, A, Vitale, D, Liguori, R, Piravandi, E, Massenet, O, Quigley, F, Clabauld, G, Mündlein, A, Felber, R, Schnabl, S, Hiller, R, Schmidt, W, Lecharny, A, Aubourg, S, Gy, I, Cooke, R, Berger, C, Monfort, A, Casacuberta, E, Gibbons, T, Weber, N, Vandenbol, M, Bargues, M, Terol, J, Torres, A, Perez-Perez, A, Purnelle, B, Bent, E, Johnson, S, Tacon, D, Jesse, T, Heijnen, L, Schwarz, S, Scholler, P, Heber, S, Bielke, C, Frishmann, D, Haase, D, Lemcke, K, Mewes, H.W, Stocker, S, Zaccaria, P, Mayer, K, Schüller, C, and Bevan, M
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- 2000
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27. Pharmacokinetics and In Vivo Efficacy of Pyrazolopyrimidine, Pyrrolopyrimidine, and 5-Aminopyrazole-4-Carboxamide Bumped Kinase Inhibitors against Toxoplasmosis.
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Hulverson, Matthew A, Bruzual, Igor, McConnell, Erin V, Huang, Wenlin, Vidadala, Rama S R, Choi, Ryan, Arnold, Samuel L M, Whitman, Grant R, McCloskey, Molly C, Barrett, Lynn K, Rivas, Kasey L, Scheele, Suzanne, DeRocher, Amy E, Parsons, Marilyn, Ojo, Kayode K, Maly, Dustin J, Fan, Erkang, Voorhis, Wesley C Van, Doggett, J Stone, and Van Voorhis, Wesley C
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CALCIUM-dependent protein kinase ,TOXOPLASMOSIS ,KINASE inhibitors ,PHARMACOKINETICS ,PROTEIN kinases ,TOXOPLASMA gondii ,ANIMAL experimentation ,COMPARATIVE studies ,HETEROCYCLIC compounds ,RESEARCH methodology ,MEDICAL cooperation ,MICE ,ORAL drug administration ,PROTEINS ,RESEARCH ,EVALUATION research ,CEREBRAL toxoplasmosis ,PROTEIN kinase inhibitors ,IN vitro studies ,CHEMICAL inhibitors ,PHARMACODYNAMICS - Abstract
Bumped kinase inhibitors (BKIs) have been shown to be potent inhibitors of Toxoplasma gondii calcium-dependent protein kinase 1. Pyrazolopyrimidine and 5-aminopyrazole-4-carboxamide scaffold-based BKIs are effective in acute and chronic experimental models of toxoplasmosis. Through further exploration of these 2 scaffolds and a new pyrrolopyrimidine scaffold, additional compounds have been identified that are extremely effective against acute experimental toxoplasmosis. The in vivo efficacy of these BKIs demonstrates that the cyclopropyloxynaphthyl, cyclopropyloxyquinoline, and 2-ethoxyquinolin-6-yl substituents are associated with efficacy across scaffolds. In addition, a broad range of plasma concentrations after oral dosing resulted from small structural changes to the BKIs. These select BKIs include anti-Toxoplasma compounds that are effective against acute experimental toxoplasmosis and are not toxic in human cell assays, nor to mice when administered for therapy. The BKIs described here are promising late leads for improving anti-Toxoplasma therapy. [ABSTRACT FROM AUTHOR]
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- 2019
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28. A technology demonstration facility
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Thomassen, K. I. and Doggett, J. N.
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- 1983
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29. Extended-spectrum antiprotozoal bumped kinase inhibitors: A review.
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Van Voorhis, Wesley C., Doggett, J. Stone, Parsons, Marilyn, Hulverson, Matthew A., Choi, Ryan, Arnold, Samuel L.M., Riggs, Michael W., Hemphill, Andrew, Howe, Daniel K., Mealey, Robert H., Lau, Audrey O.T., Merritt, Ethan A., Maly, Dustin J., Fan, Erkang, and Ojo, Kayode K.
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KINASE inhibitors , *NILOTINIB , *PROTEIN kinase B , *APICOMPLEXA , *PHARMACOKINETICS , *PHOSPHORYLATION - Abstract
Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of parasitic diseases. However, the difficulty of inhibiting parasite protein kinases to the exclusion of host orthologues poses a practical challenge. A possible path around this difficulty is the use of bumped kinase inhibitors for targeting calcium-dependent protein kinases that contain atypically small gatekeeper residues and are crucial for pathogenic apicomplexan parasites' survival and proliferation. In this article, we review efficacy against the kinase target, parasite growth in vitro , and in animal infection models, as well as the relevant pharmacokinetic and safety parameters of bumped kinase inhibitors. [ABSTRACT FROM AUTHOR]
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- 2017
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30. An all-sky set of (B)-V-R photometric calibrators for Schmidt surveys. GSPC2.1: First release
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Bucciarelli, B., García Yus, J., Casalegno, R., Postman, M., Lasker, B.M., Sturch, C., Lattanzi, M.G., McLean, B.J., Costa, E., Falasca, A., Le Poole, R., Massone, G., Potter, M., Rosenberg, A., Borgman, T., Doggett, J., Morrison, J., Pizzuti, A., Pompei, E., Rehner, D., Siciliano, L., and Wolfe, D.
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- 2001
31. Cystic Neutrophilic Granulomatous Mastitis: Association With Gram-Positive Bacilli and Corynebacterium.
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Troxell, Megan L, Gordon, Nicole T, Doggett, J Stone, Ballard, Morgan, Vetto, John T, Pommier, Rodney F, and Naik, Arpana M
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CORYNEBACTERIUM diseases ,MASTITIS ,RESEARCH funding ,GRAM-positive bacterial infections ,DISEASE complications - Abstract
Objectives: To determine whether cystic neutrophilic granulomatous mastitis (CNGM) can be associated with Gram-positive bacilli and CorynebacteriumMethods: We reviewed our experience with 35 granulomatous mastitis patients over a 10-year period, including histologic pattern, Gram stain and other microbiologic data, clinical presentation, treatment and outcome.Results: Biopsies from 19 patients demonstrated CNGM, while 16 patients had other patterns of granulomatous mastitis. Gram-positive organisms were seen within microcystic spaces in 16/19 CNGM, but 0/16 non-CNGM patients (P = .000). Culture or molecular studies demonstrated Corynebacterium species in three, all CNGM. Patients with CNGM were more likely to be younger, of Hispanic ethnicity, and born outside of the United States. Granulomatous mastitis resolved after a protracted course with widely variable treatment (antibiotics, surgery, steroids).Conclusions: Our data further support CNGM as an infectious disease; further study of Corynebacterium-directed therapy in CNGM is needed. [ABSTRACT FROM AUTHOR]- Published
- 2016
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32. Acute Suppurative Thyroiditis.
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Doggett, J. Stone and Wong, Brian
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- 2014
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33. Emphysematous Pyelonephritis.
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Wong, Brian and Doggett, J. Stone
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- 2014
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34. Emphysematous Cholecystitis.
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Doggett, J. Stone and Wong, Brian
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- 2014
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35. Mucormycosis.
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Doggett, J. Stone and Wong, Brian
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- 2014
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36. Malignant (Necrotizing) Otitis Externa.
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Doggett, J. Stone and Wong, Brian
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- 2014
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37. Necrotizing Soft Tissue Infections.
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Doggett, J. Stone and Wong, Brian
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- 2014
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38. Engineering of beam direct conversion for a 120-kV, 1-MW ion beam
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Barr, W. L, Doggett, J. N, Hamilton, G. W, Kinney, J. D, and Moir, R. W
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Plasma Physics - Abstract
Practical systems for beam direct conversion are required to recover the energy from ion beams at high efficiency and at very high beam power densities in the environment of a high-power neutral-injection system. Such an experiment is now in progress using a 120-kV beam with a maximum total current of 20 A. After neutralization, the H(+) component to be recovered will have a power of approximately 1 MW. A system testing these concepts has been designed and tested at 15 kV, 2 kW in preparation for the full-power tests. The engineering problems involved in the full-power tests affect electron suppression, gas pumping, voltage holding, diagnostics, and measurement conditions. Planning for future experiments at higher power includes the use of cryopumping and electron suppression by a magnetic field rather than by an electrostatic field. Beam direct conversion for large fusion experiments and reactors will save millions of dollars in the cost of power supplies and electricity and will dispose of the charged beam under conditions that may not be possible by other techniques.
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- 1977
39. Discovery, Synthesis, andOptimization of Antimalarial 4(1H)-Quinolone-3-Diarylethers.
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Nilsen, Aaron, Miley, Galen P., Forquer, Isaac P., Mather, Michael W., Katneni, Kasiram, Li, Yuexin, Pou, Sovitj, Pershing, April M., Stickles, Allison M., Ryan, Eileen, Kelly, Jane Xu, Doggett, J. Stone, White, Karen L., Hinrichs, David J., Winter, Rolf W., Charman, Susan A., Zakharov, Lev N., Bathurst, Ian, Burrows, Jeremy N., and Vaidya, Akhil B.
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- 2014
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40. Organic carbon in Antarctic snow.
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Lyons, W. Berry, Welch, Kathleen A., and Doggett, J. Kenneth
- Published
- 2007
- Full Text
- View/download PDF
41. Drugs in development for toxoplasmosis: advances, challenges, and current status
- Author
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Alday PH and Doggett JS
- Subjects
Toxoplasma gondii ,therapeutics ,preclinical medicine ,experimental medicine ,mechanism of action ,Apicomplexa ,Therapeutics. Pharmacology ,RM1-950 - Abstract
P Holland Alday,1 Joseph Stone Doggett1,2 1Division of Infectious Diseases, Oregon Health & Science University, 2Portland Veterans Affairs Medical Center, Portland, OR, USA Abstract: Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis. Keywords: Toxoplasma gondii, therapeutics, preclinical medicine, experimental medicine, mechanism of action, Apicomplexa
- Published
- 2017
42. 285 EMG FEEDBACK VIA VIDEOGAME FOR REHABILITATION OF HEMIPARETIC GAIT
- Author
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Epstein, M., Bardack, A., Bhandari, P., Doggett, J., Gagliolo, N., Graff, S., Li, E., Petro, E., Sailey, M., Salaets, N., Tousley, B., Turner, J., McCombe-Waller, S., Whitall, J., and Abshire, P.
- Published
- 2010
- Full Text
- View/download PDF
43. Shedding some light.
- Author
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Doggett, J.
- Subjects
- *
HUNTING - Abstract
Discusses how hunters can use discarded buck antlers to predict where deer will be found in the fall. Buck deer shed their antlers each winter. Summarizes research supporting the theory of predicting where deer will be.
- Published
- 1992
44. Proud of a peacock.
- Author
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Doggett, J.
- Subjects
- *
FISHING - Abstract
Recounts the author's experience fishing in southern Venezuela's Orinoco River for big peacock `pavon,' peacock bass. The peacock bass is tough and powerful with rough jaws and a hoary maw.
- Published
- 1991
45. Flipping out.
- Author
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Doggett, J.
- Subjects
- *
FISHING - Abstract
Describes flipping--the art of casting a long, two-handed rod--effectively to catch largemouth fish. Guidelines; Equipment. INSET: Flipping lures.;When flipping fails..
- Published
- 1988
46. Endochin-Like Quinolones Exhibit Promising Efficacy Against Neospora Caninum in vitro and in Experimentally Infected Pregnant Mice
- Author
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Anghel, Nicoleta, Balmer, Vreni, Müller, Joachim, Winzer, Pablo Arnold, Aguado Martinez, Adriana, Roozbehani, Mona, Pou, Sovitj, Nilsen, Aaron, Riscoe, Michael, Doggett, J Stone, and Hemphill, Andrew
- Subjects
630 Agriculture ,570 Life sciences ,biology ,3. Good health - Abstract
We report on the efficacy of selected endochin-like quinolones (ELQs) against tachyzoites grown in human foreskin fibroblasts (HFF), and in a pregnant BALB/c mouse model. Fourteen ELQs were screened against transgenic tachyzoites expressing β-galactosidase (Nc-βgal). Drugs were added concomitantly to infection and the values for 50% proliferation inhibition (IC) were determined after 3 days. Three compounds exhibited IC values below 0.1 nM, 3 ELQs had ICs between 0.1 and 1 nM, for 7 compounds values between 1 and 10 nM were noted, and one compound had an IC of 22.4 nM. Two compounds, namely ELQ-316 and its prodrug ELQ-334 with ICs of 0.66 and 3.33 nM, respectively, were previously shown to display promising activities against experimental toxoplasmosis and babesiosis caused by in mice, and were thus further studied. They were assessed in long-term treatment assays by exposure of infected HFF to ELQs at 0.5 μM concentration, starting 3 h after infection and lasting for up to 17 days followed by release of drug pressure. Results showed that the compounds substantially delayed parasite proliferation, but did not exert parasiticidal activities. TEM of drug treated parasites detected distinct alterations within the parasite mitochondria, but not in other parasite organelles. Assessment of safety of ELQ-334 in the pregnant mouse model showed that the compound did not interfere in fertility or pregnancy outcome. In infected pregnant mice treated with ELQ-334 at 10 mg/kg/day for 5 days, neonatal mortality (within 2 days ) was found in 7 of 44 pups (15.9%), but no postnatal mortality was noted, and vertical transmission was reduced by 49% compared to the placebo group, which exhibited 100% vertical transmission, neonatal mortality in 15 of 34 pups (44%), and postnatal mortality for 18 of the residual 19 pups during the 4 weeks follow-up. These findings encourage more research on the use of ELQs for therapeutic options against infection.
47. Terrestrial time.
- Author
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Doggett, J.
- Subjects
- *
FISHING - Abstract
Gives advice on using artificial `terrestrial' flies to catch fish. Terrestrials can be frogs, turtles, snakes and baby alligators, and they work well as bait in the early summer. Discusses bait presentation and when and where to use terrestrials. INSET: The charge of the light brigade (catching large, silent bass....
- Published
- 1991
48. Bumping bottom for bass.
- Author
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Doggett, J.
- Subjects
- *
BASS fishing - Abstract
Gives advice on how to successfully bottom-bump fish for bass. Worms, impressionistic crawlers and leadhead jigs can be used, and the fishing requires patience and concentration. Types of bait; Different seasons; Water.
- Published
- 1991
49. Fall's finer side.
- Author
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Doggett, J.
- Subjects
- *
BASS fishing - Abstract
Suggests using light tackle and small bait to catch bass under bright autumn conditions with clear water. Spinning tackle; Level-wind tackle; Fly fishing; Bass bugging.
- Published
- 1989
50. Perfectly clear.
- Author
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Doggett, J.
- Subjects
- *
BASS fishing - Abstract
Suggests techniques for bass fishing on a clear day. Potential setbacks and ways to avoid them.
- Published
- 1989
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