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12. Viral and antiretroviral dynamics in HIV mother-to-child transmission fluids (VADICT) – Protocol and data analysis plan for a cohort study

Author

Olagunju, Adeniyi, Anweh, Damien, Okafor, Ogechi, Dickinson, Laura, Richman, Douglas, Owen, Andrew, and Adejuyigbe, Ebunoluwa

Subjects
HIV/AIDS, Clinical Research, Pediatric Research Initiative, Prevention, Genetics, Perinatal Period - Conditions Originating in Perinatal Period, Pediatric AIDS, Genetic Testing, Patient Safety, Infectious Diseases, Pediatric, Infection, Reproductive health and childbirth, Good Health and Well Being
Abstract

Background: Pregnancy and polymorphisms in drug disposition genes alter the clearance of key antiretrovirals used as part of regimens for prevention of mother-to-child transmission of HIV (PMTCT). The clinical significance of these in women initiating therapy late in pregnancy has not been investigated. The primary objective of the Viral and Antiretroviral Dynamics in HIV Mother-To-Child Transmission Fluids (VADICT) study is to investigate viral and antiretroviral dynamics in matrices associated with mother-to-child transmission (MTCT) (plasma, genital fluid and breastmilk) in women (stratified by CYP2B6 genotypes) who initiate antiretroviral therapy (ART) before or early in pregnancy versus late in pregnancy or early postpartum. Methods: A cohort of HIV-1 infected women who initiated ART containing 600 mg efavirenz before or early in pregnancy (n = 120), during the third trimester (n = 60), or early postpartum (n = 60) will be studied.  Eligible patients will be recruited from four hospitals in Benue State, North Central Nigeria and followed until the end of breastfeeding. Procedures at follow up visits will include sample collection for drug quantification and HIV-1 RNA and DNA in plasma, genital fluid and breastmilk; adherence monitoring; and newborn and infant assessment. Using newborn exposure to maternal efavirenz at birth for validation, prenatal pharmacogenetics of efavirenz will be explored using physiologically-based pharmacokinetic modelling. Three integrated methods will be used to monitor patterns and correlates of adherence across pregnancy and the breastfeeding period. A population pharmacokinetic-pharmacodynamic model will be developed to describe the observed data and simulate what to expect in women initiating ART containing 400 mg efavirenz (recently approved for non-pregnant adults) late in pregnancy or early postpartum. Discussion: This study will help in understanding residual MTCT in women receiving ART and reasons for the rise in MTCT risk during the breastfeeding period. Trial registration: ClinicalTrials.gov: NCT03284645 (15/09/2017)

Published
2023

39. Correction: Favipiravir and/or nitazoxanide: a randomized, double-blind, placebo-controlled trial of early therapy in COVID-19 in health workers, their household members, and patients treated at IMSS (FANTAZE)

Author

Smith, Tania A., Hoyo-Vadillo, Carlos, Adom, Akosua Agyeman, Favari-Perozzi, Liliana, Gastine, Silke, Dehbi, Hakim-Moulay, Villegas-Lara, Beatriz, Mateos, Eduardo, González, Yessica Sara Pérez, Navarro-Gualito, Maria D., Cruz-Carbajal, Alejandra S., Cortes-Vazquez, Miguel A., Bekker-Méndez, Carolina, Aguirre-Alvarado, Charmina, Aguirre-Gil, Gisela, Delgado-Pastelin, Lucero, Owen, Andrew, Lowe, David, Standing, Joseph, and Escobedo, Jorge

Published
2023
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41. FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2

Author

Brevini, Teresa, Maes, Mailis, Webb, Gwilym J., John, Binu V., Fuchs, Claudia D., Buescher, Gustav, Wang, Lu, Griffiths, Chelsea, Brown, Marnie L., Scott, III, William E., Pereyra-Gerber, Pehuén, Gelson, William T. H., Brown, Stephanie, Dillon, Scott, Muraro, Daniele, Sharp, Jo, Neary, Megan, Box, Helen, Tatham, Lee, Stewart, James, Curley, Paul, Pertinez, Henry, Forrest, Sally, Mlcochova, Petra, Varankar, Sagar S., Darvish-Damavandi, Mahnaz, Mulcahy, Victoria L., Kuc, Rhoda E., Williams, Thomas L., Heslop, James A., Rossetti, Davide, Tysoe, Olivia C., Galanakis, Vasileios, Vila-Gonzalez, Marta, Crozier, Thomas W. M., Bargehr, Johannes, Sinha, Sanjay, Upponi, Sara S., Fear, Corrina, Swift, Lisa, Saeb-Parsy, Kourosh, Davies, Susan E., Wester, Axel, Hagström, Hannes, Melum, Espen, Clements, Darran, Humphreys, Peter, Herriott, Jo, Kijak, Edyta, Cox, Helen, Bramwell, Chloe, Valentijn, Anthony, Illingworth, Christopher J. R., Dahman, Bassam, Bastaich, Dustin R., Ferreira, Raphaella D., Marjot, Thomas, Barnes, Eleanor, Moon, Andrew M., Barritt, IV, Alfred S., Gupta, Ravindra K., Baker, Stephen, Davenport, Anthony P., Corbett, Gareth, Gorgoulis, Vassilis G., Buczacki, Simon J. A., Lee, Joo-Hyeon, Matheson, Nicholas J., Trauner, Michael, Fisher, Andrew J., Gibbs, Paul, Butler, Andrew J., Watson, Christopher J. E., Mells, George F., Dougan, Gordon, Owen, Andrew, Lohse, Ansgar W., Vallier, Ludovic, and Sampaziotis, Fotios

Published
2023
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42. Epic, idealism, and romanticism

Author

Wynn Owen, Andrew and Perry, Seamus

Subjects
Idealism in literature, Romanticism, Poetry
Abstract

My opening argument is that Romantic aesthetics is grounded in a metaphysics for which epic is a fitting form. This metaphysics presents an ontological picture that endorses a substance monism that either claims mind to be this substance or includes mind as part of some neutral substance. I then argue for what I call 'metaphysical Hegelianism about epic', which is the view that epic's 'inner form', to borrow Georg Lukács's term, is characterised by concern with the limitation of the freedom of individuals by objective reality. Epic is characteristically concerned with two types of limitation particularly: limitation of the will, and limitation of freedom by the presence of other minds. The first of these leads to artistic consideration of the kinds of experience associated with apprehension of questions surrounding free will and determinism. The second leads to artistic consideration of the place of the individual agent in relation to the community. To show the epic's preoccupation with mind-emphasising ontologies and normative models of agency, examples are given from the four main epics I discuss: The Prelude (1798-9, 1805, and 1850 texts), Sordello (first published 1840), Aurora Leigh (first published 1856), and Leaves of Grass (first published 1855). I then ask why epic consideration of these problems can be valuable. With reference to Romantic epistemology, I argue that art can provide knowledge that goes beyond what is possible for propositionally-based knowledge. Consequently, artworks must be experienced for the kinds of unparaphrasable knowledge they contain to be accessed. I suggest that a central function of the scholarship and criticism of art is to assist the experiencer in this experiencing. Finally, I discuss two different ways in which the word 'epic' is sometimes used: to describe the epic form; and to describe the experience of individual works in the epic form that satisfy certain conditions.

Published
2021

44. Publisher Correction: On the issue of transparency and reproducibility in nanomedicine

Author

Leong, Hon S, Butler, Kimberly S, Brinker, C Jeffrey, Azzawi, May, Conlan, Steve, Dufès, Christine, Owen, Andrew, Rannard, Steve, Scott, Chris, Chen, Chunying, Dobrovolskaia, Marina A, Kozlov, Serguei V, Prina-Mello, Adriele, Schmid, Ruth, Wick, Peter, Caputo, Fanny, Boisseau, Patrick, Crist, Rachael M, McNeil, Scott E, Fadeel, Bengt, Tran, Lang, Hansen, Steffen Foss, Hartmann, Nanna B, Clausen, Lauge PW, Skjolding, Lars M, Baun, Anders, Ågerstrand, Marlene, Gu, Zhen, Lamprou, Dimitrios A, Hoskins, Clare, Huang, Leaf, Song, Wantong, Cao, Huiliang, Liu, Xuanyong, Jandt, Klaus D, Jiang, Wen, Kim, Betty YS, Wheeler, Korin E, Chetwynd, Andrew J, Lynch, Iseult, Moghimi, Seyed Moein, Nel, André, Xia, Tian, Weiss, Paul S, Sarmento, Bruno, das Neves, José, Santos, Hélder A, Santos, Luis, Mitragotri, Samir, Little, Steve, Peer, Dan, Amiji, Mansoor M, Alonso, Maria José, Petri-Fink, Alke, Balog, Sandor, Lee, Aaron, Drasler, Barbara, Rothen-Rutishauser, Barbara, Wilhelm, Stefan, Acar, Handan, Harrison, Roger G, Mao, Chuanbin, Mukherjee, Priyabrata, Ramesh, Rajagopal, McNally, Lacey R, Busatto, Sara, Wolfram, Joy, Bergese, Paolo, Ferrari, Mauro, Fang, Ronnie H, Zhang, Liangfang, Zheng, Jie, Peng, Chuanqi, Du, Bujie, Yu, Mengxiao, Charron, Danielle M, Zheng, Gang, and Pastore, Chiara

Subjects
Nanoscience & Nanotechnology
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

45. Viral and antiretroviral dynamics in HIV mother-to-child transmission fluids (VADICT) – Protocol and data analysis plan for a cohort study

Author

Olagunju, Adeniyi, Anweh, Damien, Okafor, Ogechi, Dickinson, Laura, Richman, Douglas, Owen, Andrew, and Adejuyigbe, Ebunoluwa

Abstract

Background: Pregnancy and polymorphisms in drug disposition genes alter the clearance of key antiretrovirals used as part of regimens for prevention of mother-to-child transmission of HIV (PMTCT). The clinical significance of these in women initiating therapy late in pregnancy has not been investigated. The primary objective of the Viral and Antiretroviral Dynamics in HIV Mother-To-Child Transmission Fluids (VADICT) study is to investigate viral and antiretroviral dynamics in matrices associated with mother-to-child transmission (MTCT) (plasma, genital fluid and breastmilk) in women (stratified by CYP2B6 genotypes) who initiate antiretroviral therapy (ART) before or early in pregnancy versus late in pregnancy or early postpartum. Methods: A cohort of HIV-1 infected women who initiated ART containing 600 mg efavirenz before or early in pregnancy (n = 120), during the third trimester (n = 60), or early postpartum (n = 60) will be studied.  Eligible patients will be recruited from four hospitals in Benue State, North Central Nigeria and followed until the end of breastfeeding. Procedures at follow up visits will include sample collection for drug quantification and HIV-1 RNA and DNA in plasma, genital fluid and breastmilk; adherence monitoring; and newborn and infant assessment. Using newborn exposure to maternal efavirenz at birth for validation, prenatal pharmacogenetics of efavirenz will be explored using physiologically-based pharmacokinetic modelling. Three integrated methods will be used to monitor patterns and correlates of adherence across pregnancy and the breastfeeding period. A population pharmacokinetic-pharmacodynamic model will be developed to describe the observed data and simulate what to expect in women initiating ART containing 400 mg efavirenz (recently approved for non-pregnant adults) late in pregnancy or early postpartum. Discussion: This study will help in understanding residual MTCT in women receiving ART and reasons for the rise in MTCT risk during the breastfeeding period. Trial registration: ClinicalTrials.gov: NCT03284645 (15/09/2017)

Published
2019

48. Favipiravir and/or nitazoxanide: a randomized, double-blind, placebo-controlled trial of early therapy in COVID-19 in health workers, their household members, and patients treated at IMSS (FANTAZE)

Author

Smith, Tania, Hoyo-Vadillo, Carlos, Adom, Akosua Agyeman, Favari-Perozzi, Liliana, Gastine, Silke, Dehbi, Hakim-Moulay, Villegas-Lara, Beatriz, Mateos, Eduardo, González, Yessica Sara Pérez, Navarro-Gualito, Maria D., Cruz-Carbajal, Alejandra S., Cortes-Vazquez, Miguel A., Bekker-Méndez, Carolina, Aguirre-Alvarado, Charmina, Aguirre-Gil, Gisela, Delgado-Pastelin, Lucero, Owen, Andrew, Lowe, David, Standing, Joseph, and Escobedo, Jorge

Published
2022
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50. Cellular interactions underpinning the immunomodulatory action of mesenchymal stromal cells in models of liver transplant injury

Author

Owen, Andrew Philip

Subjects
617.5, RD Surgery
Abstract

End stage liver disease represents a common end point for a number of disease processes, the only current treatment for which is liver transplantation, but the demand for donor organs exceeds the supply. This has led to the use of more marginal donors with an increase in the rates of complications. Mesenchymal stem/stromal cells (MSC) are a multipotent cell capable of modulating the immune system through a number of different processes and represent a potential therapy in post transplantation liver injury. In this study I describe the prospective isolation and culture expansion of murine MSC. In in vitro assays MSC suppressed T lymphocytes and following stimulus with inflammatory cytokines MSC secreted a number of cytokines including Il-10. In the MDR2-/- model intravenous MSC therapy led to a reduction in liver injury with an increase in restorative macrophages. Subcutaneous administration of MSC showed no beneficial effect. MSC were also tested in a hepatic ischaemia reperfusion injury model where no effect was seen. In summary MSC were able to suppress lymphocyte proliferation and secrete anti-inflammatory cytokines in vitro, and in vivo they were able to reduce liver injury in the MDR2-/- model but not the hepatic ischaemia reperfusion injury mode.

Published
2018

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