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1. Diverse RNA viruses of parasitic nematodes can elicit antibody responses in vertebrate hosts

Author

Quek, Shannon, Hadermann, Amber, Wu, Yang, De Coninck, Lander, Hegde, Shrilakshmi, Boucher, Jordan R., Cresswell, Jessica, Foreman, Ella, Steven, Andrew, LaCourse, E. James, Ward, Stephen A., Wanji, Samuel, Hughes, Grant L., Patterson, Edward I., Wagstaff, Simon C., Turner, Joseph D., Parry, Rhys H., Kohl, Alain, Heinz, Eva, Otabil, Kenneth Bentum, Matthijnssens, Jelle, Colebunders, Robert, and Taylor, Mark J.

Published
2024
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3. Pathological response following neoadjuvant immune checkpoint inhibitors in patients with hepatocellular carcinoma: a cross-trial, patient-level analysis

Author

D'Alessio, Antonio, Stefanini, Bernardo, Blanter, Julia, Adegbite, Benjamin, Crowley, Fionnuala, Yip, Vincent, Slater, Sarah, Fulgenzi, Claudia Angela Maria, Celsa, Ciro, Manfredi, Giulia Francesca, Pai, Madhava, Goldin, Robert D, Ward, Stephen C, Fiel, Maria Isabel, Shu, Daniel H, Su, Yung-Yeh, Cortellini, Alessio, Baretti, Marina, Anders, Robert, Yarchoan, Mark, Hsu, Chiun, Marron, Thomas U, and Pinato, David J

Published
2024
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4. Physiological status monitoring and dynamic risk prediction for operators in extreme environments

Author

Ward, Stephen

Subjects
Physiological monitoring, Extreme environments
Abstract

Extreme environments are inherently dangerous places where there are high risks of injury, illness, and mortality to people who enter these arenas for occupational or vocational reasons. Mountaineers are one such group who are regularly exposed to extremely low temperatures, high wind speeds, high ultra-violet radiation, and low availability of oxygen. One solution to mitigating the risks posed to mountaineers is through the use of physiological monitoring systems. Physiological monitoring can provide an early insight into physiological disregulation, and allow for interventions to be realised in response to observed changes in an individual's physiological state [1]. Laboratory or in-hospital devices are not suitable for deployment in harsh environments, therefore wearable devices are a popular alternative [2]. There is a vast array of devices which can measure an extensive range of physiological parameters; common metrics include heart rate, respiratory rate, and temperature. Wearable devices have been shown to be effective and non-intrusive on the subjects' activities. Accordingly, they are the preferred option in extreme environments as they allow for non-invasive, continual evaluation of a user's metrics [3]. The overall aim of this strategy is to reduce injury, mortality, and the morbidity of people operating within these environments. This, in turn, may increase the efficiency and effectiveness of the operations they are involved in. Despite the promise of physiological monitoring and extensive research into the field, significant challenges still persist. These challenges prevent the routine wide scale adoption of physiological monitoring and mitigation systems from being implemented to protect the people operating in hostile environments. Various authors have identified automated data quantification as the most significant factor preventing the widespread use of physiological monitoring systems [4]-[7]. This thesis addresses this challenge through the development of the EXTReme Environment Risk Evaluation and MItigation Framework Score (EXTREMIS) which provides context to the physiological data collected via wearable sensors. The inclusion of acceleration and physiological sensors provides the ability for meaningful interpretation which takes into account the activities being completed and their respective physical demands. Thus, detecting more true incidences of negative health status, and reducing the incidence of false alarms. The EXTREMIS framework utilises accelerometer data from body worn sensors, and supervised machine learning techniques to classify the activity of the user, and therefore allow for contextual analysis of measured physiological parameters. The approach of automated activity classification of simulated mountaineering specific activities through the use of accelerometers was validated in a controlled laboratory setting. The optimal number and location of accelerometers was established, and the effect on classifier performance of equipment states was quantified. A significant effect of external activity required equipment (12kg rucksack, and mountaineering boots) was noted, and an important conclusion from this research is the need to consider this additional equipment when designing activity classification models for use in extreme environments. Failure to do so will result in poor performance of the activity classifier. This result is potentially significant to fields far beyond mountaineering and extreme environments, and should be considered in any activity classification problem where extra equipment is utilised. This optimised accelerometer configuration, discovered in the initial investigations, was then tested in a mountain environment where additional challenges such as, terrain surfaces and equipment variations were considered. Finally, simultaneous physiological measurements were collected and the EXTREMIS framework was evaluated against existing clinical tools for detecting negative health states. The National Early Warning Score (NEWS) [8], which is a prominent aggregate scoring system for captured physiological measurements, was chosen as a suitable comparison measure. The findings of the study demonstrate that there was a significant main effect of the type of activity being completed on mean heart rate (p < 0.001), mean respiratory rate (p < 0.001), and mean temperature (p < 0.001). This variation further reinforces the need to dynamically evaluate physiological metrics in relation to the activities being completed. As direct evaluation was not possible, the proposed EXTREMIS framework was evaluated against the clinically validated NEWS framework. When both evaluation frameworks are considered, the mean aggregate scores produced by both frameworks over the sessions were significantly different (p < 0.001), NEWS = 7.17(±1.33), EXTREMIS = 3.27(±1.70). Similarly, both frameworks produced significantly different scores for each activity (p < 0.001). The NEWS framework consistently overestimates the risk due to the omission of physiological loading, and therefore provides operational limiting restrictions on non-negative health events. 81.69% of total trial time was designated a 'High' risk state by the NEWS framework, which would indicate the need for immediate intervention despite physiological metrics being in normal ranges for the activities being completed and there being no occurrences of untoward events. EXTREMIS with 5.84% of total trial time was designated a 'High' risk state, was shown to more closely represent the lower risk state associated with the evaluated physiological measurands expected due to the metabolic demands of the activities being completed. The main contribution of this body of research is a novel framework which allows for meaningful evaluation of activities based on their respective physiological demands. This is the first time relative metabolic intensities have been utilised to set expected intensity ratings for recognised activities, and adaptable thresholds defined. This new approach produces more meaningful parameter evaluations, better reflecting the health status of the user, and thus reducing the incidence of false alarms. The EXTREMIS framework provides an immediate solution to a current problem and retains the flexibility to be incrementally optimised and improved with further testing and inclusion of state of the art technologies and practices.

Published
2022
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5. Intratumoral dendritic cell–CD4+ T helper cell niches enable CD8+ T cell differentiation following PD-1 blockade in hepatocellular carcinoma

Author

Magen, Assaf, Hamon, Pauline, Fiaschi, Nathalie, Soong, Brian Y., Park, Matthew D., Mattiuz, Raphaël, Humblin, Etienne, Troncoso, Leanna, D’souza, Darwin, Dawson, Travis, Kim, Joel, Hamel, Steven, Buckup, Mark, Chang, Christie, Tabachnikova, Alexandra, Schwartz, Hara, Malissen, Nausicaa, Lavin, Yonit, Soares-Schanoski, Alessandra, Giotti, Bruno, Hegde, Samarth, Ioannou, Giorgio, Gonzalez-Kozlova, Edgar, Hennequin, Clotilde, Le Berichel, Jessica, Zhao, Zhen, Ward, Stephen C., Fiel, Isabel, Kou, Baijun, Dobosz, Michael, Li, Lianjie, Adler, Christina, Ni, Min, Wei, Yi, Wang, Wei, Atwal, Gurinder S., Kundu, Kunal, Cygan, Kamil J., Tsankov, Alexander M., Rahman, Adeeb, Price, Colles, Fernandez, Nicolas, He, Jiang, Gupta, Namita T., Kim-Schulze, Seunghee, Gnjatic, Sacha, Kenigsberg, Ephraim, Deering, Raquel P., Schwartz, Myron, Marron, Thomas U., Thurston, Gavin, Kamphorst, Alice O., and Merad, Miriam

Published
2023
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6. Precision Medicine in Nephrology: An Integrative Framework of Multidimensional Data in the Kidney Precision Medicine Project

Author

Lake, Blue, Zhang, Kun, Lecker, Stewart, Morales, Alexander, Bogen, Steve, Amodu, Afolarin A., Beck, Laurence, Henderson, Joel, Ilori, Titlayo, Maikhor, Shana, Onul, Ingrid, Schmidt, Insa, Verma, Ashish, Waikar, Sushrut, Yadati, Pranav, Yu, Guanghao, Colona, Mia R., McMahon, Gearoid, Hacohen, Nir, Greka, Anna, Hoover, Paul J., Marshall, Jamie L., Aulisio, Mark, Bush, William, Chen, Yijiang, Crawford, Dana, Madabhushi, Anant, Viswanathan, Vidya S., Bush, Lakeshia, Cooperman, Leslie, Gadegbeku, Crystal, Herlitz, Leal, Jolly, Stacey, Nguyen, Jane, O’Malley, Charles, O’Toole, John, Palmer, Ellen, Poggio, Emilio, Spates-Harden, Kassandra, Sedor, John, Sendrey, Dianna, Taliercio, Jonathan, Appelbaum, Paul, Balderes, Olivia, Barasch, Jonathan, Berroue, Cecilia, Bomback, Andrew, Canetta, Pietro A., D’Agati, Vivette, Kiryluk, Krzysztof, Kudose, Satoru, Mehl, Karla, Sabatello, Maya, Shang, Ning, de Pinho Gonçalves, Joana, Lardenoije, Roy, Migas, Lukasz, Van de Plas, Raf, Rennke, Helmut, Azeloglu, Evren, Campbell, Kirk, Coca, Steven, He, Cijang, He, John, Iyengar, Srinivas Ravi, Lefferts, Seanee, Nadkarni, Girish, Patel, Marissa, Tokita, Joji, Ward, Stephen, Xiong, Yuguang, Verdoes, Abraham, Sabo, Angela, Barwinska, Daria, Gisch, Debora Lidia, Williams, James, Kelly, Katherine, Dunn, Kenneth, Asghari, Mahla, Eadon, Michael, Ferkowicz, Michael, Dagher, Pierre, Ferreira, Ricardo Melo, Winfree, Seth, Bledsoe, Sharon, Wofford, Stephanie, El-Achkar, Tarek, Sutton, Timothy, Bowen, William, Cheng, Ying-Hua, Slade, Austen, Record, Elizabeth, Cheng, Yinghua, Borner, Katy, Herr, Bruce, Jain, Yashvardhan, Quardokus, Ellen, Atta, Mohamed, Bernard, Lauren, Menez, Steven, Parikh, Chirag, Corona Villalobos, Celia Pamela, Wang, Ashley, Wen, Yumeng, Xu, Alan, Chen, Sarah, Donohoe, Isabel, Johansen, Camille, Rosas, Sylvia, Sun, Jennifer, Ardayfio, Joseph, Bebiak, Jack, Campbell, Taneisha, Fox, Monica, Knight, Richard, Koewler, Robert, Pinkeney, Roy, Saul, John, Shpigel, Anna, Prasad, Pottumarthi, Madhavan, Sethu M., Parikh, Samir, Rovin, Brad, Shapiro, John P., Anderton, Christopher, Lukowski, Jessica, Pasa-Tolic, Ljiljana, Velickovic, Dusan, Oliver, George, Mao, Weiguang, Sealfon, Rachel, Troyanskaya, Olga, Pollack, Ari, Goltsev, Yury, Ginley, Brandon, Anjani, Kavya, Laszik, Zoltan G., Mukatash, Tariq, Nolan, Garry, Beyda, David, Bracamonte, Erika, Brosius, Frank, Campos, Baltazar, Marquez, Nicole, Mendoza, Katherine, Scott, Raymond, Thajudeen, Bijin, Tsosie, Rebecca, Woodhead, Gregory, Saunders, Milda, Alloway, Rita R., Lee, Paul J., Rike, Adele, Shi, Tiffany, Woodle, E. Steve, Bjornstad, Petter, Hsieh, Elena, Kendrick, Jessica, Pyle, Laura, Thurman, Joshua, Vinovskis, Carissa, Wrobel, Julia, Lucarelli, Nicholas, Sarder, Pinaki, Bui, James, Carmona-Powell; Ron Gaba, Eunice, Kelly, Tanika, Lash, James, Meza, Natalie, Redmond, Devona, Renteria, Amada, Ricardo, Ana, Setty, Suman, Srivastava, Anand, Alakwaa, Fadhl, Ascani, Heather, Balis, Ul, Bitzer, Markus, Blanc, Victoria, Bonevich, Nikki, Conser, Ninive, Demeke, Dawit, Dull, Rachel, Eddy, Sean, Frey, Renee, Hartman, John, He, Yongqun Oliver, Hodgin, Jeffrey, Kretzler, Matthias, Lienczewski, Chrysta, Luo, Jinghui, Mariani, Laura, McCown, Phillip, Menon, Rajasree, Nair, Viji, Otto, Edgar, Reamy, Rebecca, Rose, Michael, Schaub, Jennifer, Steck, Becky, Wright, Zachary, Coleman, Alyson, Henderson-Brown; Jerica Berge, Dorisann, Caramori, Maria Luiza, Adeyi, Oyedele, Nachman, Patrick, Safadi, Sami, Flanagan, Siobhan, Ma, Sisi, Klett, Susan, Wolf, Susan, Harindhanavudhi, Tasma, Rao, Via, Bream, Peter, Froment, Anne, Kelley, Sara, Mottl, Amy, Chaudhury; Evan Zeitler, Prabir Roy, Bender, Filitsa, Elder, Michele, Gilliam, Matthew, Hall, Daniel E., Kellum, John A., Murugan, Raghavan, Palevsky, Paul, Rosengart, Matthew, Tan, Roderick, Tublin, Mitchell, Winters, James, Bansal, Shweta, Montellano, Richard, Pamreddy, Annapurna, Sharma, Kumar, Venkatachalam, Manjeri, Ye, Hongping, Zhang, Guanshi, Basit, Mujeeb, Cai, Qi, Hendricks, Allen, Hedayati, Susan, Kermani, Asra, Lee, Simon C., Ma, Shihong, Miller, Richard Tyler, Moe, Orson W., Park, Harold, Patel, Jiten, Pillai, Anil, Sambandam, Kamalanathan, Torrealba, Jose, Toto, Robert D., Vazquez, Miguel, Wang, Nancy, Wen, Natasha, Zhang, Dianbo, Alpers, Charles, Berglund, Ashley, Berry, Brooke, Blank, Kristina, Brown, Keith, Carson, Jonas, Daniel, Stephen, de Boer, Ian H., Dighe, Ashveena L., Dowd, Frederick, Grewenow, Stephanie M., Himmelfarb, Jonathan, Hoofnagle, Andrew, Jefferson, Nichole, Larson, Brandon, Limonte, Christine, McClelland, Robyn, Mooney, Sean, Nam, Yunbi, Park, Christopher, Phuong, Jimmy, Rezaei, Kasra, Roberts, Glenda, Sarkisova, Natalya, Shankland, Stuart, Snyder, Jaime, Stutzke, Christy, Tuttle, Katherine, Wangperawong, Artit, Wilcox, Adam, Williams, Kayleen, Young, Bessie, Allen, Jamie, Caprioli, Richard M., de Caestecker, Mark, Djambazova, Katerina, Dufresne, Martin, Farrow, Melissa, Fogo, Agnes, Sharman, Kavya, Spraggins, Jeffrey, Basta, Jeannine, Conlon, Kristine, Diettman, Sabine M., Gaut, Joseph, Kaushal, Madhurima, Jain, Sanjay, Knoten, Amanda, Minor, Brittany, Nwanne, Gerald, Vijayan, Anitha, Zhang, Bo, Arora, Tanima, Cantley, Lloyd, Victoria Castro, Angela M., Kakade, Vijayakumar, Moeckel, Gilbert, Moledina, Dennis, Shaw, Melissa, Wilson, Francis P., El-Achkar, Tarek M., and Eadon, Michael T.

Published
2024
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7. A large-scale retrospective study enabled deep-learning based pathological assessment of frozen procurement kidney biopsies to predict graft loss and guide organ utilization

Author

Yi, Zhengzi, Xi, Caixia, Menon, Madhav C., Cravedi, Paolo, Tedla, Fasika, Soto, Alan, Sun, Zeguo, Liu, Keyu, Zhang, Jason, Wei, Chengguo, Chen, Man, Wang, Wenlin, Veremis, Brandon, Garcia-barros, Monica, Kumar, Abhishek, Haakinson, Danielle, Brody, Rachel, Azeloglu, Evren U., Gallon, Lorenzo, O’Connell, Philip, Naesens, Maarten, Shapiro, Ron, Colvin, Robert B., Ward, Stephen, Salem, Fadi, and Zhang, Weijia

Published
2024
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8. Impact of pre-transplant immune checkpoint inhibitor use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis

Author

Rezaee-Zavareh, Mohammad Saeid, Yeo, Yee Hui, Wang, Tielong, Guo, Zhiyong, Tabrizian, Parissa, Ward, Stephen C., Barakat, Fatma, Hassanein, Tarek I., Dave, Shravan, Ajmera, Veeral, Bhoori, Sherrie, Mazzaferro, Vincenzo, Chascsa, David M.H., Liu, Margaret C., Aby, Elizabeth S., Lake, John R., Sogbe, Miguel, Sangro, Bruno, Abdelrahim, Maen, Esmail, Abdullah, Schmiderer, Andreas, Chouik, Yasmina, Rudolph, Mark, Sohal, Davendra, Giudicelli, Heloise, Allaire, Manon, Akce, Mehmet, Guadagno, Jessica, Tow, Clara Y., Massoumi, Hatef, De Simone, Paolo, Kang, Elise, Gartrell, Robyn D., Martinez, Mercedes, Paz-Fumagalli, Ricardo, Toskich, Beau B., Tran, Nguyen H., Solino, Gabriela Azevedo, Poltronieri Pacheco, Dra Mariana, Kalman, Richard S., Agopian, Vatche G., Mehta, Neil, Parikh, Neehar D., Singal, Amit G., and Yang, Ju Dong

Published
2024
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9. Signal transduction in leukocytes and endothelial cells

Author

Ward, Stephen

Abstract

This collection of published primary papers, reviews and commentaries spans over 30 years of research. Collectively, they describe a body of work that has used interdisciplinary pharmacological, biochemical, cellular, molecular and genetic approaches to better understand the signal transduction events in leukocytes and epithelial cells that contribute to either immune activation and inflammation, cancer, metaplasia and/or morphogenesis Ultimately, this has been with a view to the identification of new drug targets and developing new therapies primarily for inflammatory disease, but also for cancer and regenerative medicine. The papers presented demonstrate how my laboratory initially explored how antigen receptors, chemokines and cytokines control activation of T lymphocytes, key cells in the adaptive immune system. The strategy was to rigorously interrogate T lymphocyte biology at the fundamental level of biochemical signal transduction, with particular focus on the nature and functional relevance of receptor-operated calcium mobilisation and phosphoinositide lipid metabolism in human lymphocytes and leukemic T cell lines. Eventually, I became focussed on phosphoinositide 3-kinase (PI3K)-dependent signalling and associated functional events in leukocytes. My interests developed further to explore: (i) the role of PI3K in functional events downstream of inflammatory mediators in colonic epithelial cells and their relevance to colitis and Crohn's disease; (ii) signaling mechanisms involved in Barrett's Metaplasia, a pathogenic condition characterized by replacement of stratified squamous epithelium of the distal oesophagus by columnar epithelium; (iii) the role of PI3K in embryonic lung branching morphogenesis, a key developmental process for the formation of many epithelial organs and (iv) novel post-translational protein modifications such as glycation and methylation. More recently it has become clear that activation state of the PI3K pathway is correlated to a poor prognosis particularly in breast cancer patients. Given that PI3K inhibitors have entered the clinic for cancer, prognostic novel quantitative fluorescent microscopy methodology has been developed that identifies cancers in which PI3K is activated. Such approaches could be used in personalised medicine to better identify patients who would benefit from PI3K inhibitor treatment.

Published
2021

10. Global proteomic analysis of plasma from mice infected with Plasmodium berghei ANKA using two dimensional gel electrophoresis and matrix assisted laser desorption ionization-time of flight mass spectrometry

Author

Kokwaro Gilbert O, Gitau Evelyn N, Newton Charles RJC, and Ward Stephen A

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background A global proteomic strategy was used to identify proteins, which are differentially expressed in the murine model of severe malaria in the hope of facilitating future development of novel diagnostic, disease monitoring and treatment strategies. Methods Mice (4-week-old CD1 male mice) were infected with Plasmodium berghei ANKA strain, and infection allowed to establish until a parasitaemia of 30% was attained. Total plasma and albumin depleted plasma samples from infected and control (non-infected) mice were separated by two-dimensional gel electrophoresis (2-DE). After staining, the gels were imaged and differential protein expression patterns were interrogated using image analysis software. Spots of interest were then digested using trypsin and the proteins identified using matrix-assisted laser desorption and ionization-time of flight (MALDI-TOF) mass spectrometry (MS) and peptide mass fingerprinting software. Results Master gels of control and infected mice, and the corresponding albumin depleted fractions exhibited distinctly different 2D patterns comparing control and infected plasma, respectively. A wide range of proteins demonstrated altered expression including; acute inflammatory proteins, transporters, binding proteins, protease inhibitors, enzymes, cytokines, hormones, and channel/receptor-derived proteins. Conclusions Malaria-infection in mice results in a wide perturbation of the host serum proteome involving a range of proteins and functions. Of particular interest is the increased secretion of anti-inflammatory and anti apoptotic proteins.

Published
2011
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11. Sequence and gene expression of chloroquine resistance transporter (pfcrt) in the association of in vitro drugs resistance of Plasmodium falciparum

Author

Bray Patrick G, Owen Andrew, Johnson David, Mungthin Mathirut, Ward Stephen A, Chaijaroenkul Wanna, and Na-Bangchang Kesara

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Plasmodium falciparum chloroquine resistance (CQR) transporter protein (PfCRT) is known to be the important key of CQR. Recent studies have definitively demonstrated a link between mutations in the gene pfcrt and resistance to chloroquine in P. falciparum. Although these mutations are predictive of chloroquine resistance, they are not quantitatively predictive of the degree of resistance. Methods In this study, a total of 95 recently adapted P. falciparum isolates from Thailand were included in the analysis. Parasites were characterized for their drug susceptibility phenotypes and genotypes with respect to pfcrt. From the original 95 isolates, 20 were selected for complete pfcrt sequence analysis. Results Almost all of the parasites characterized carried the previously reported mutations K76T, A220S, Q271E, N326S, I356T and R371I. On complete sequencing, isolates were identified with novel mutations at K76A and E198K. There was a suggestion that parasites carrying E198K were less resistant than those that did not. In addition, pfcrt and pfmdr1 gene expression were investigated by real-time PCR. No relationship between the expression level of either of these genes and response to drug was observed. Conclusion Data from the present study suggest that other genes must contribute to the degree of resistance once the resistance phenotype is established through mutations in pfcrt.

Published
2011
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12. Molecular Signatures of Glomerular Neovascularization in a Patient with Diabetic Kidney Disease

Author

Ferkowicz, Michael J., Verma, Ashish, Barwinska, Daria, Melo Ferreira, Ricardo, Henderson, Joel M., Kirkpatrick, Mary, Silva, Paolo S., Steenkamp, Devin W., Phillips, Carrie L., Waikar, Sushrut S., Sutton, Timothy A., Lake, Blue, Zhang, Kun, Lecker, Stewart, Morales, Alexander, Stillman, Isaac, Bogen, Steve, Amodu, Afolarin A., Beck, Laurence, Henderson, Joel, Ilori, Titlayo, Maikhor, Shana, Onul, Ingrid, Schmidt, Insa, Verma, Ashish, Waikar, Sushrut, Yadati, Pranav, Yu, Guanghao, Colona, Mia R., McMahon, Gearoid, Weins, Astrid, Hacohen, Nir, Greka, Anna, Hoover, Paul J., Marshall, Jamie L., Aulisio, Mark, Bush, William, Chen, Yijiang, Crawford, Dana, Madabhushi, Anant, Viswanathan, Vidya S., Bush, Lakeshia, Cooperman, Leslie, Gadegbeku, Crystal, Herlitz, Leal, Jolly, Stacey, Nguyen, Jane, O’Malley, Charles, O’Toole, John, Palmer, Ellen, Poggio, Emilio, Spates-Harden, Kassandra, Sedor, John, Sendrey, Dianna, Taliercio, Jonathan, Appelbaum, Paul, Balderes, Olivia, Barasch, Jonathan, Berroue, Cecilia, Bomback, Andrew, Canetta, Pietro A., D’Agati, Vivette, Kiryluk, Krzysztof, Kudose, Satoru, Mehl, Karla, Sabatello, Maya, Shang, Ning, Varela, German, de Pinho Gonçalves, Joana, Lardenoije, Roy, Migas, Lukasz, Van de Plas, Raf, Barisoni, Laura, Rennke, Helmut, Azeloglu, Evren, Campbell, Kirk, Coca, Steven, He, Cijang, He, John, Iyengar, Srinivas Ravi, Lefferts, Seanee, Nadkarni, Girish, Patel, Marissa, Tokita, Joji, Ward, Stephen, Xiong, Yuguang, Verdoes, Abraham, Sabo, Angela, Barwinska, Daria, Gisch, Debora Lidia, Williams, James, Kelly, Katherine, Dunn, Kenneth, Asghari, Mahla, Eadon, Michael, Ferkowicz, Michael, Dagher, Pierre, Ferreira, Ricardo Melo, Winfree, Seth, Bledsoe, Sharon, Wofford, Stephanie, El-Achkar, Tarek, Sutton, Timothy, Bowen, William, Cheng, Ying-Hua, Slade, Austen, Record, Elizabeth, Cheng, Yinghua, Borner, Katy, Herr, Bruce, Jain, Yashvardhan, Quardokus, Ellen, Atta, Mohamed, Bernard, Lauren, Menez, Steven, Parikh, Chirag, Corona Villalobos, Celia Pamela, Wang, Ashley, Wen, Yumeng, Xu, Alan, Chen, Sarah, Donohoe, Isabel, Johansen, Camille, Rosas, Sylvia, Sun, Jennifer, Ardayfio, Joseph, Bebiak, Jack, Brown, Keith, Campbell, Taneisha, Fox, Monica, Hayashi, Lynda, Jefferson, Nichole, Richard Knight, Jennifer Jones, Koewler, Robert, Pinkeney, Roy, Saul, John, Shpigel, Anna, Stutzke, Christy, Prasad, Pottumarthi, Madhavan, Sethu M., Parikh, Samir, Rovin, Brad, Shapiro, John P., Anderton, Christopher, Lukowski, Jessica, Pasa-Tolic, Ljiljana, Velickovic, Dusan, Oliver, George, Mao, Weiguang, Sealfon, Rachel, Troyanskaya, Olga, Wong, Aaron, Pollack, Ari, Goltsev, Yury, Ginley, Brandon, Lutnick, Brendon, Anjani, Kavya, Laszik, Zoltan G., Mukatash, Tariq, Nolan, Garry, Beyda, David, Bracamonte, Erika, Brosius, Frank, Campos, Baltazar, Marquez, Nicole, Mendoza, Katherine, Scott, Raymond, Thajudeen, Bijin, Tsosie, Rebecca, Woodhead, Gregory, Saunders, Milda, Alloway, Rita R., Lee, Paul J., Rike, Adele, Shi, Tiffany, Woodle, E. Steve, Bjornstad, Petter, Hsieh, Elena, Kendrick, Jessica, Pyle, Laura, Thurman, Joshua, Vinovskis, Carissa, Wrobel, Julia, Lucarelli, Nicholas, Sarder, Pinaki, Bui, James, Carmona-Powell, Eunice, Gaba, Ron, Kelly, Tanika, Lash, James, Meza, Natalie, Redmond, Devona, Renteria, Amada, Ricardo, Ana, Setty, Suman, Srivastava, Anand, Alakwaa, Fadhl, Ascani, Heather, Balis, Ul, Bitzer, Markus, Blanc, Victoria, Bonevich, Nikki, Conser, Ninive, Demeke, Dawit, Dull, Rachel, Eddy, Sean, Frey, Renee, Hartman, John, He, Yongqun Oliver, Hodgin, Jeffrey, Kretzler, Matthias, Lienczewski, Chrysta, Luo, Jinghui, Mariani, Laura, McCown, Phillip, Menon, Rajasree, Nair, Viji, Otto, Edgar, Reamy, Rebecca, Rose, Michael, Schaub, Jennifer, Steck, Becky, Wright, Zachary, Coleman, Alyson, Henderson-Brown, Dorisann, Berge, Jerica, Caramori, Maria Luiza, Adeyi, Oyedele, Nachman, Patrick, Safadi, Sami, Flanagan, Siobhan, Ma, Sisi, Klett, Susan, Wolf, Susan, Harindhanavudhi, Tasma, Rao, Via, Bream, Peter, Froment, Anne, Kelley, Sara, Mottl, Amy, Roy-Chaudhury, Prabir, Zeitler, Evan, Bender, Filitsa, Elder, Michele, Gilliam, Matthew, Hall, Daniel E., Kellum, John A., Murugan, Raghavan, Palevsky, Paul, Rosengart, Matthew, Tan, Roderick, Tublin, Mitchell, Winters, James, Bansal, Shweta, Montellano, Richard, Pamreddy, Annapurna, Sharma, Kumar, Venkatachalam, Manjeri, Ye, Hongping, Zhang, Guanshi, Basit, Mujeeb, Cai, Qi, Hendricks, Allen, Hedayati, Susan, and Asra

Published
2024
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13. Glycerol: An unexpected major metabolite of energy metabolism by the human malaria parasite

Author

Bray Patrick G, Fisher Nicholas, Roslaini Abd, Al-Helal Mohammed, Lian Lu-Yun, Ward Stephen A, and Biagini Giancarlo A

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Malaria is a global health emergency, and yet our understanding of the energy metabolism of the principle causative agent of this devastating disease, Plasmodium falciparum, remains rather basic. Glucose was shown to be an essential nutritional requirement nearly 100 years ago and since this original observation, much of the current knowledge of Plasmodium energy metabolism is based on early biochemical work, performed using basic analytical techniques (e.g. paper chromatography), carried out almost exclusively on avian and rodent malaria. Data derived from malaria parasite genome and transcriptome studies suggest that the energy metabolism of the parasite may be more complex than hitherto anticipated. This study was undertaken in order to further characterize the fate of glucose catabolism in the human malaria parasite, P. falciparum. Methods Products of glucose catabolism were determined by incubating erythrocyte-freed parasites with D-[1-13C] glucose under controlled conditions and metabolites were identified using 13C-NMR spectroscopy. Results Following a 2 h incubation of freed-P. falciparum parasites with 25 mM D-[1-13C] glucose (n = 4), the major metabolites identified included; [3-13C] lactate, [1,3-13C] glycerol, [3-13C] pyruvate, [3-13C] alanine and [3-13C] glycerol-3-phosphate. Control experiments performed with uninfected erythrocytes incubated under identical conditions did not show any metabolism of D-[1-13C] glucose to glycerol or glycerol-3-phosphate. Discussion The identification of glycerol as a major glucose metabolite confirms the view that energy metabolism in this parasite is more complex than previously proposed. It is hypothesized here that glycerol production by the malaria parasite is the result of a metabolic adaptation to growth in O2-limited (and CO2 elevated) conditions by the operation of a glycerol-3-phosphate shuttle for the re-oxidation of assimilatory NADH. Similar metabolic adaptations have been reported previously for other microaerobic/anaerobic organisms, such as yeast, rumen protozoa and human parasitic protozoa. Conclusion These data highlight the need to re-evaluate the carbon and redox balance of this important human pathogen, ultimately leading to a better understanding of how the parasite is able to adapt to the variable environments encountered during parasite development and disease progression.

Published
2009
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18. In vitro antimalarial drug susceptibility in Thai border areas from 1998–2003

Author

Mungthin Mathirut, Na Bangchang Kesara, Chaijaroenkul Wanna, and Ward Stephen A

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background The Thai-Myanmar and Thai-Cambodia borders have been historically linked with the emergence and spread of Plasmodium falciparum parasites resistant to antimalarial drugs. Indeed, the areas are often described as harbouring multi-drug resistant parasites. These areas of Thailand have experienced significant changes in antimalarial drug exposure patterns over the past decade. This study describes the in vitro antimalarial susceptibility patterns of 95 laboratory-adapted P. falciparum isolates, collected between 1998 and 2003,. Methods Ninety five P. falciparum isolates were collected from five sites in Thailand between 1998 and 2003. After laboratory adaptation to in vitro culture, the susceptibility of these parasites to a range of established antimalarial drugs (chloroquine [CQ], mefloquine [MQ], quinine [QN] and dihydroartemisinin [DHA]) was determined by the isotopic microtest. Results Mefloquine (MQ) sensitivity remained poorest in areas previously described as MQ-resistant areas. Sensitivity to MQ of parasites from this area was significantly lower than those from areas reported to harbour moderate (p = 0.002) of low level MQ resistance (p = 000001). Importantly for all drugs tested, there was a considerable range in absolute parasite sensitivities. There was a weak, but statistically positive correlation between parasite sensitivity to CQ and sensitivity to both QN and MQ and a positive correlation between MQ and QN. In terms of geographical distribution, parasites from the Thai-Cambodia were tended to be less sensitive to all drugs tested compared to the Thai-Myanmar border. Parasite sensitivity to all drugs was stable over the 6-year collection period with the exception of QN. Conclusion This study highlights the high degree of variability in parasite drug sensitivity in Thailand. There were geographical differences in the pattern of resistance which might reflect differences in drug usage in each area. In contrast to many other studies there were weak, but statistically significant positive, correlations between sensitivity to CQ and sensitivity to MQ and QN. Over the six years of sample collection, parasite sensitivity appears to have stabilized to these drugs in these sites.

Published
2005
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20. Towards a roadmap for space-based observations of the land sector for the UNFCCC global stocktake

Author

Ochiai, Osamu, Poulter, Benjamin, Seifert, Frank Martin, Ward, Stephen, Jarvis, Ian, Whitcraft, Alyssa, Sahajpal, Ritvik, Gilliams, Sven, Herold, Martin, Carter, Sarah, Duncanson, Laura Innice, Kay, Heather, Lucas, Richard, Wilson, Sylvia N., Melo, Joana, Post, Joanna, Briggs, Stephen, Quegan, Shaun, Dowell, Mark, Cescatti, Alessandro, Crisp, David, Saatchi, Sassan, Tadono, Takeo, Steventon, Matt, and Rosenqvist, Ake

Published
2023
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21. The Role of PI3K Isoforms in Autoimmune Disease

Author

Ward, Stephen G., Ahmed, Rafi, Series Editor, Akira, Shizuo, Series Editor, Casadevall, Arturo, Series Editor, Galan, Jorge E., Series Editor, Garcia-Sastre, Adolfo, Series Editor, Malissen, Bernard, Series Editor, Rappuoli, Rino, Series Editor, and Dominguez-Villar, Margarita, editor

Published
2022
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29. The art of the circus : an exploration of the circus within its social, historical, and cultural contexts

Author

Ward, Stephen Edgar

Subjects
Drama
Abstract

The Collins English dictionary gives a definition of circus as 'a travelling company of entertainers, such as acrobats, clowns, trapeze artists, and trained animals'; 'a public performance given by such a company'; 'an arena, usually tented, in which such a performance is held'. Yet these are just physical descriptions of a far more complex subject. The circus is difficult to define because it seems to embody so many paradoxes. It can be magical and entertaining but it can also be subversive and political. It is ephemeral yet deeply embedded within our popular culture. Its perceived 'otherness', in terms of its unfamiliar social structure and life-style, creates an existence beyond the norm. Yet the circus reflects our daily lives and struggles in the way that it confronts risk and danger. It is both old and new at the same time; old skills being reworked and presented within a contemporary world. The circus is an eclectic art form that exists in conjunction with other art forms. This paper supports and academically complements the body of published work by the author on aspects of the circus, and explicates a theory implicit within that work. The published work is intended to provide scholarly but accessible information primarily for a non-academic audience. It explores how the circus, as a distinct art form, has developed from primitive roots to current practices, and attempts to place it within its social, historical, and cultural contexts. This paper will focus on the justifications for circus to be accepted as a legitimate art form. It will examine how circus developed initially with exhibitions of equitation; how it constantly adapted and re-invented itself to meet the needs of a changing society; and how it has evolved into the multi-faceted art form of today. Several important issues will be covered but the limitations of this paper will preclude any detailed discussion, and will be addressed fully in subsequent papers.

Published
2019

33. Neoadjuvant clinical trials provide a window of opportunity for cancer drug discovery

Author

Marron, Thomas U., Galsky, Matthew D., Taouli, Bachir, Fiel, Maria Isabel, Ward, Stephen, Kim, Edward, Yankelevitz, David, Doroshow, Deborah, Guttman-Yassky, Emma, Ungar, Benjamin, Mehandru, Saurabh, Golas, Benjamin J., Labow, Daniel, Sfakianos, John, Nair, Sujit S., Chakravarty, Dimple, Buckstein, Michael, Song, Xiaoyu, Kenigsberg, Effi, Gnjatic, Sacha, Brown, Brian D., Sparano, Joseph, Tewari, Ashutosh, Schwartz, Myron, Bhardwaj, Nina, and Merad, Miriam

Published
2022
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35. Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial

Author

Marron, Thomas U, Fiel, Maria Isabel, Hamon, Pauline, Fiaschi, Nathalie, Kim, Edward, Ward, Stephen C, Zhao, Zhen, Kim, Joel, Kennedy, Paul, Gunasekaran, Ganesh, Tabrizian, Parissa, Doroshow, Deborah, Legg, Meredith, Hammad, Ashley, Magen, Assaf, Kamphorst, Alice O, Shareef, Muhammed, Gupta, Namita T, Deering, Raquel, Wang, Wei, Wang, Fang, Thanigaimani, Pradeep, Mani, Jayakumar, Troncoso, Leanna, Tabachnikova, Alexandra, Chang, Christie, Akturk, Guray, Buckup, Mark, Hamel, Steven, Ioannou, Giorgio, Hennequin, Clotilde, Jamal, Hajra, Brown, Haley, Bonaccorso, Antoinette, Labow, Daniel, Sarpel, Umut, Rosenbloom, Talia, Sung, Max W, Kou, Baijun, Li, Siyu, Jankovic, Vladimir, James, Nicola, Hamon, Sara C, Cheung, Hung Kam, Sims, Jennifer S, Miller, Elizabeth, Bhardwaj, Nina, Thurston, Gavin, Lowy, Israel, Gnjatic, Sacha, Taouli, Bachir, Schwartz, Myron E, and Merad, Miriam

Published
2022
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36. Exploring Consumer Experiences of Barriers and Enablers to Accessing Rehabilitation That Meets Their Needs: The Rehabilitation Choices Study, Part 2—Consumer Perspectives.

Author

Mason, Gillian, Ribbons, Karen, Bailey, Lucy, O'Malley, Adrian, Ward, Tracy, Ward, Stephen, Pollack, Michael, Walker, Frederick R., Nilsson, Michael, and Hodyl, Nicolette

Subjects
HEALTH services accessibility, HEALTH attitudes, QUALITATIVE research, PATIENT safety, RESEARCH funding, REHABILITATION, INTERVIEWING, QUESTIONNAIRES, PATIENT-family relations, DECISION making, DESCRIPTIVE statistics, THEMATIC analysis, CAREGIVERS, CHRONIC diseases, RESEARCH methodology, MEDICAL needs assessment, COMPARATIVE studies, CAREGIVER attitudes, PATIENTS' attitudes
Abstract

Introduction: Improved access to rehabilitation is highlighted as a key pathway to achieving the World Health Organisation's (WHO) goal of ensuring healthy lives and promoting well‐being for all (Sustainable Development Goal 3). This article is the second in a two‐part series outlining the findings from the Rehabilitation Choices study, which aimed to identify how health professionals and consumers in Australia are informed to make decisions about rehabilitation, and their experience with barriers and enablers to accessing that rehabilitation. In this study, we present the perspectives of consumers with different health conditions and a range of experiences with rehabilitation services. Methods: This was a qualitative study using focus groups and semi‐structured interviews. People with self‐reported lived experience of rehabilitation and carers were recruited using maximum variation sampling. Thematic analysis of data was conducted using an inductive approach. Results: Fifty‐six consumers with diverse lived experiences of rehabilitation (19–80 years, 49 patients, 7 carers) participated in focus groups and interviews to discuss how they sourced information about rehabilitation and their experiences of what made it hard or easy to access rehabilitative care to meet their needs. Four themes were produced from the data: (1) service‐centricity of options limits access, (2) access is the patient's responsibility, (3) enabling decision‐making about rehabilitation with appropriate information and (4) provision of a psychologically safe environment. Conclusions: Any planned (re)design of services to improve consumer access to rehabilitation should consider the themes identified in this study. This will ensure that consumers are provided with rehabilitation options that suit their holistic and unique needs beyond consideration of their medical diagnoses, and are actively supported to navigate this access, provided with information to help them make informed choices and provided a psychologically safe environment to engage effectively with rehabilitation. Patient or Public Contribution: Three consumer research partners with lived experience of rehabilitation as patients or carers were core team members. They were involved in the design and implementation of the recruitment and communications strategies, design of the interview approach and discussion guide, contributed to the interpretation and contextualisation of findings and writing of this manuscript and are included as co‐authors (A. O., T. W. and S. W.). [ABSTRACT FROM AUTHOR]

Published
2024
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37. Single‐cell RNA sequencing data identify a conserved population of metallothionein‐expressing macrophages that may be ubiquitous in vital human organs.

Author

Daccache, Joseph A., Eng, Francis, Cao, Lei, Ma, Ning, Ward, Stephen C., Schiano, Thomas, Miller, Mark, Herron, Daniel, Azzara, Anthony V., Pullen, Steven S., Guarnieri, Paolo, Aloman, Costica, and Branch, Andrea D.

Subjects
ORGANS (Anatomy), IMMUNOHISTOCHEMISTRY techniques, GENE expression, ALVEOLAR macrophages, MYELOID cells
Abstract

The article in Clinical & Translational Discovery identifies a rare population of metallothionein-expressing macrophages present in all vital human organs. Using single-cell RNA sequencing data, the study characterizes these macrophages in the liver, kidney, and lung, highlighting their gene expression patterns and potential functional roles. Immunohistochemistry techniques confirm the presence of these macrophages in human liver tissue, suggesting a role in neoangiogenesis. The research sets the stage for further studies on the functional role of these macrophages in tissue homeostasis and remodeling. [Extracted from the article]

Published
2024
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38. A Phase 1, Randomized, Double‐Blind, Placebo‐Controlled, Single Ascending Dose Trial of AWZ1066S, an Anti‐Wolbachia Candidate Macrofilaricide.

Author

Devereux, Graham, Bula, Marcin, Tripp, Karen, Fitzgerald, Richard, Eraut, Nicola, Alam, Muhammad Salman, Moriyama, Tomoyuki, Shinkyo, Raku, Walker, Lauren, Wang, Duolao, Gusovsky, Fabian, van der Velde, Jeannette, Turner, Joseph D., Hong, Weiqian David, O'Neill, Paul M., Taylor, Mark J., and Ward, Stephen A.

Subjects
NEGLECTED diseases, LYMPHATIC diseases, ONCHOCERCIASIS, FILARIASIS, LIVER enzymes
Abstract

AWZ1066S has been developed as a potential treatment for the neglected tropical diseases lymphatic filariasis and onchocerciasis. AWZ1066S targets the Wolbachia bacterial endosymbiont present in the causative nematode parasites. This phase 1, first‐in‐human study aimed to assess the safety and pharmacokinetics of AWZ1066S in healthy human participants. In a randomized double‐blind, placebo‐controlled, single ascending dose study, healthy adults received a single oral dose of AWZ1066S (or placebo) and were followed up for 10 days. The planned single doses of AWZ1066S ranged from 100 to 1600 mg, and each dose was administered to a cohort of 8 participants (6 AWZ1066S and 2 placebo). In total 30 people participated, 18 (60%) female, median age 30.0 years (minimum 20, maximum 61). The cohorts administered 100, 200, 300, and 400 mg of AWZ1066S progressed unremarkably. After single 700‐mg doses all 4 participants developed symptoms of acute gastritis and transient increases in liver enzymes. The severity of these adverse events ranged from mild to severe, with 1 participant needing hospital admission. Pharmacokinetic analysis indicated that AWZ1066S is rapidly absorbed with predictable pharmacokinetics. In conclusion, safety concerns prevented this study from reaching the human exposures needed for AWZ1066S to be clinically effective against lymphatic filariasis and onchocerciasis. [ABSTRACT FROM AUTHOR]

Published
2024
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40. Examining the Judean Scribal Tendencies in the Psalms of Papyrus Amherst 63, with Col. XII, 11¬–19 as a Test Case

Author

Ward, Stephen Elliott

Subjects
Near Eastern studies, Aramaic, Demotic, Papyrus Amherst 63, Psalm 20
Abstract

Papyrus Amherst 63, also known as the “Mystery Papyrus,” has been a difficult manuscript to study. This document is written in Demotic script and Aramaic language. This creates a quandary among scholars. The difficulty is that the script (Demotic) and the language (Aramaic) are incongruent. This difficulty has hampered the study of this manuscript. This text is understudied and there are also only a handful of scholars who have thoroughly worked on this text. At this point, there are only two published editions of this text. This dissertation explores the Judean scribalism of this unique document through sociolinguistics. While there are various West Asian cultures present, this dissertation focuses on the Judean presence. Papyrus Amherst 63 col. xii lines 11–19 lay at the crux of this study and serve as the test case displaying the Judean scribal tendencies. This text has parallels with Psalm 20 of the Hebrew Bible, which makes this document important for understanding the West Asian community present in Egypt and its development. This dissertation provides a unique look into the West Asian community and the influences that are present in and outside of Egypt. This dissertation aims to uncover the Judean scribal tendencies that lay beneath the difficulties of this manuscript and will also explore the literary devices that are present that demonstrate Judean scribalism.

Published
2023

46. Protein N-Glycans in Healthy and Sclerotic Glomeruli in Diabetic Kidney Disease

Author

Veličković, Dušan, Shapiro, John P., Parikh, Samir V., Rovin, Brad, Toto, Robert D., Vazquez, Miguel A., Poggio, Emilio D., O'Toole, John F., Sedor, John R., Alexandrov, Theodore, Jain, Sanjay, Bitzer, Markus, Hodgin, Jeffrey, Veličković, Marija, Sharma, Kumar, Anderton, Christopher R., Adeyi, Oyedele A., Alakwaa, Fadhl, Alexandrov, Theodore, Allen, Jamie L., Alpers, Charles E., Alvear, Alison Bunio, Ambekar, Akhil, Ancheta, Joed, Anderton, Christopher R., Angus, Sophia A., Anjani, Kavya, Appelbaum, Paul S., Ardayfio, Joseph, Arora, Tanima, Ascani, Heather K., Asghari, Mahla, El-Achkar, Tarek M., Athar, Humra, Atta, Mohamed G., Aulisio, Mark P., Aw, Stephanie J., Azeloglu, Evren U., Bagne, Cathy A., Balderes, Olivia, Balis, Ulysses G.J., Barasch, Jonathan, Barisoni, Laura, Barwinska, Daria, Basta, Jeannine, Bebiak, Jack, Beck, Laurence H., Berge, Jerica M., Berglund, Ashley C., Bernard, Lauren, Berry, Brooke, Beyda, David H., Bhanushali, Jini Ashok, Bitzer, Markus, Bjornstad, Petter, Blanc, Victoria M., Blank, Kristina N., Bledsoe, Sharon B., Bogen, Steve, Bomback, Andrew S., Bonevich, Nikole, Border, Samuel, Börner, Katy, Bowen, William S., Boys, Charlotte, Bracamonte, Erika R., Bream, Peter R., Brosius, Frank C., Brown, Keith D., Budiman, Tifanny, Bueckle, Andreas, Bui, J.T., James, T., Burg, Ashley R., Burgess, Adam, Bush, Lakeshia, Bush, William S., Cai, Qi, Calixte, Marie Florence, Cameron-Wheeler, Tashas, Campbell, Kirk N, Campbell, Taneisha, Campbell, Catherine, Campos, Baltazar, Canetta, Pietro A., Cantley, Lloyd G, Caramori, M. Luiza, Carmona-Powell, Eunice, Carson, Jonas M, Chan, Lili, Chen, Sarah W, Chen, Yijiang, Cheng, Ying-Hua, Bejarano, Maria Chilo, Choe, Kisurb, Cimino, James G., Coca, Steven G., Coleman, Alyson, Colley, Madeline E., Collie, Mary M., Colona, Mia R., Commander, Clayton W., Conlon, Kristine, Conser, Ninive, Cooperman, Leslie, Corona-Villalobos, Celia P., Crawford, Dana C., Creger, Nathan, Cuevas-Rios, Yarieli, D'Agati, Vivette ., Dagher, Pierre c., de Boer, Ian H., de Caestecker, M.P, de Cos, Marina, Gonçalves, Joana P., Dekker, Matthew, Demeke, Dawit, Dighe, Ashveena L, Ding, Yanli, Djambazova, Katerina V., Donohoe, Isabel, Dowd, Frederick, Drawz, P.E., Dufresne, Martin, Dull, Rachel, Dunn, Kenneth W., Duran, Daniel Damian, Eadon, Michael T, Eddy, Sean, Elder, Michele M, Fallegger, Robin, Farrow, Melissa A, Ferkowicz, Michael, Fine, Derek M., Flanagan, Siobhan M., Fogo, Agnes B., Fox, Monica L., Frey, Renee, Froment, Anne, Gaba, Ron C., Gadegbeku, Crystal A, Gaut, Joseph P., Gehlenborg, Nils, Geraghty, Molly C, Ghag, Reetika, Gilliam, Matthew, Ginley, Brandon, Gisch, Debora, Gordon, Ronald E., Gorman, Brittney L., Greka, Anna, Grewenow, Stephanie M., Gurung, Bhupendra Kumar, Guthrie, Leah, Hacohen, Nir, Haddad, Samuel, Hall, Daniel E., Hansen, Jens, Harindhanavudhi, Tasma, Hartman, John, Hayashi, Lynda, Haydak, Jonathan, He, John Cijiang, He, Yongqun, Hedayati, S. Susan, Henderson, Dori, Henderson, Joel M, Hendricks, Allen R, Henshaw, Asari, Herlitz, Leal, Hernandez, Jeanine, Herr, Bruce W., Himmelfarb, Jonathan, Hodgin, Jeffrey B., Hoofnagle, Andrew N, Horowitz, Carol R., Hsieh, E.W.Y., Huynh, Courtney, Iyengar, Ravi, Jain, Sanjay, Janowczyk, Andrew, Jeffers, Vivian, Jefferson, Nichole M., Jennette, J Charles, Johansen, Camille, Jolly, Stacey, Jones, Christopher J., Jones, Jennifer L., Jones, Kiasha, Joyeux, Cienn N., Ju, Wenjun, Judd, Audra M., Kakade, Vijayakumar R, Kakarla, Dhatri, Kaspari, Rachel R., Kaushal, Madhurima, Keefe, Nicole, Keller, Mark S., Kelley, Sara S., Kellum, John A., Kelly, K. J., Kelly, Tanika N., Kermani, Asra, Kiryluk, Krzysztof, Klett, Susan, Knight, Richard A., Knoten, Amanda, Koch, Gina, Koewler, Robert, Kretzler, Matthias, Kruse, Angela R.S., Küchenhoff, Leonie, Lake, Blue B., Lardenoije, Roy, Larson, Astrid, Larson, Brandon G, Lash, James P., Laszik, Zoltan G., Lecker, Stewart H., Lee, Simon C., Lee, Sora, Lefferts, Sean, Li, Xiang, Lienczewski, Chrysta C, Limonte, Christine P, Lucarelli, Nicholas, Lukowski, Jessica, Lutnick, Brendon, Ma, Shihong, Ma, Sisi, Madabhushi, Anant, Maikhor, Shana, Mao, Weiguang, Mariani, Laura H., Markovic, Marina, Marquez, Nicole, Marshall, Jamie L., McAdams, Meredith C, McClelland, Robyn L., McCown, Phillip J., McMahon, Gearoid Michael, McMurray, Amy, Mehl, Karla, Meliambro, Kristin, Ferreira, Ricardo Melo, Mendoza, Katherine, Menez, Steven, Menon, Rajasree, Meza, Natalie, Migas, Lukasz G., Miller, R. Tyler, Mimar, Sayat, Minor, Brittany C, Mody, Priya, Moeckel, Gilbert W., Moledina, D.G., Molina-Guzman, Jenny, Monroy-Trujillo, Jose M, Morales, Alexander, Moreno, Vanessa, Mottl, Amy K., Mukatash, Tariq, Munar, Dane, Murugan, Raghavan, Nachman, Patrick H., Nadkarni, Girish N, Naglah, Ahmed, Nair, Viji, Nam, Yunbi, Narasimhan, R., Nwanne, Gerald, O'Malley, Charles, O'Toole, John F., Toro, Fernanda Ochoa, Oliver, George (Holt), Onul, Ingrid F, Otto, Edgar A., Palevsky, Paul M., Palmer, Ellen, Pamreddy, Annapurna, Parikh, Chirag R., Parikh, Samir V, Park, Christopher, Park, Harold, Paša-Tolić, Ljiljana, Patel, Jiten, Patel, Marissa, Patlis, Boris S., Paul, Anindya S., Phuong, Jimmy, Pillai, Anil, Pinkeney, Roy, Plisiewicz, Alexa, Poggio, Emilio D, Pollack, Ari, Prasad, Pottumarthi V, Pyle, Laura, Quardokus, Ellen M., Quiroga, Arabela, Ragi, Nagarjunachary, Randhawa, Parmjeet, Randle, Teresa, Rao, Via, Rauchman, Michael, Rauwolf, Nicolas J, Reamy, Rebecca, Record, Elizabeth G., Redmond, Devona, Rennke, Helmut, Renteria, Amada, Rezaei, Kasra A, Rhodes, Rosamond, Ricardo, Ana C., Rice, Samuel, Rivera, Marcelino, Roberts, Glenda V., Rosas, R., Sylvia, E., Rose, Michael P., Rosen, Seymour, Rosenberg, Avi Z., Rosenberg, Michael S., Rosengart, Matthew R., Rovin, Brad H., Roy, Neil, Roy-Chaudhury, Prabir, Rubinsky, Melissa D., Sabo, Angela R., Saez-Rodriguez, Julio, Safadi, Sami, Samari, Imane H., Sanora, Ana Celina, Sarder, Pinaki, Sarkisova, Natalya, Sarwal, Minnie M, Saul, John, Saunders, Milda R., Schaub, Jennifer A., Schmidt, IM, Scott, Raymond, Scroggins, Aaron, Sealfon, Rachel S. G., Sedor, John R., Sendrey, Dianna, Setty, Suman, Shah, Sonya, Shariff, Saad Mohammed, Sharma, Kumar, Shaw, Melissa M., Sigdel, Tara K, Silva, Paolo S., Snyder, Jaime, Snyder, Michelle L., Spates-Harden, Kassandra, Sperati, C. John, Spraggins, Jeffrey M., Srivastava, Anand, Stashevsky, Jennifer, Steck, Becky, Stillman, Isaac E, Stutzke, Christy, Subramanian, Lalita, Sun, Jennifer K., Rajan, Sandhya Sundar, Sutton, Timothy A., Taliercio, Jonathan J, Tan, Roderick, Tanevski, Jovan, Thajudeen, Bijin, Thurman, Joshua M., Tokita, Joji, Torrealba, Jose R., Toto, Robert D, Tout, Haneen, Troyanskaya, Olga G, Tsosie, Rebecca, Turner, Jeffrey M, Tuttle, Katherine R., Ugwuowo, Ugochukwu, Upadhyay, Ashish, Valerius, M. Todd, Van de Plas, Raf, Varela, German, Vazquez, Miguel A., Velickovic, Dusan, Venkatachalam, Manjeri, Verdoes, Abraham, Verma, Ashish, Victoria-Castro, Angela M., Vijayan, Anitha, Villalobos, Alexander, Viloria, Noralinda B., Vinovskis, Carissa, Vita, Tina, Waikar, Sushrut S., Wang, Ashley R., Wang, Bangchen, Wang, Nancy, Wang, Ruikang, Wangperawong, Artit, Ward, Stephen C, Warfield, Curtis, Weins, Astrid, Wen, Natasha, Wen, Yumeng, Wilcox, Adam, Williams, James C., Williams, Kayleen, Williams, Mark E., Wilson, F. Perry, Winfree, Seth, Winters, James, Wofford, Stephanie, Wolf, Susan M., Wong, Aaron, Woodhead, Gregory, Wright, Devin M., Wright, Zach, Wright, Zoe, Wrobel, Julia, Xing, Fuyong, Xu, Alan, Yadati, Pranav, Ye, Hongping, Young, Bessie A., Yu, Guanghao, Mon-Wei Yu, Samuel, Zeinoun, Gabriel, Zeitler, Evan M., Zhang, Bo, Zhang, Guanshi, and Zhang, Yi

Published
2024
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47. A Phase 1, Randomized, Double‐Blind, Placebo‐Controlled, Single Ascending Dose Trial of AWZ1066S, an Anti‐WolbachiaCandidate Macrofilaricide

Author

Devereux, Graham, Bula, Marcin, Tripp, Karen, Fitzgerald, Richard, Eraut, Nicola, Alam, Muhammad Salman, Moriyama, Tomoyuki, Shinkyo, Raku, Walker, Lauren, Wang, Duolao, Gusovsky, Fabian, Velde, Jeannette, Turner, Joseph D., Hong, Weiqian David, O'Neill, Paul M., Taylor, Mark J., and Ward, Stephen A.

Abstract

AWZ1066S has been developed as a potential treatment for the neglected tropical diseases lymphatic filariasis and onchocerciasis. AWZ1066S targets the Wolbachiabacterial endosymbiont present in the causative nematode parasites. This phase 1, first‐in‐human study aimed to assess the safety and pharmacokinetics of AWZ1066S in healthy human participants. In a randomized double‐blind, placebo‐controlled, single ascending dose study, healthy adults received a single oral dose of AWZ1066S (or placebo) and were followed up for 10 days. The planned single doses of AWZ1066S ranged from 100 to 1600 mg, and each dose was administered to a cohort of 8 participants (6 AWZ1066S and 2 placebo). In total 30 people participated, 18 (60%) female, median age 30.0 years (minimum 20, maximum 61). The cohorts administered 100, 200, 300, and 400 mg of AWZ1066S progressed unremarkably. After single 700‐mg doses all 4 participants developed symptoms of acute gastritis and transient increases in liver enzymes. The severity of these adverse events ranged from mild to severe, with 1 participant needing hospital admission. Pharmacokinetic analysis indicated that AWZ1066S is rapidly absorbed with predictable pharmacokinetics. In conclusion, safety concerns prevented this study from reaching the human exposures needed for AWZ1066S to be clinically effective against lymphatic filariasis and onchocerciasis.

Published
2024
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50. Building the next pyramid

Author

West, Joseph, Gallagher, Greg, Waters, Kevin, Ward, Stephen, and Ward, Tia

Subjects
Physics - Popular Physics
Abstract

The results of experimental tests of a novel method for moving large (pyramid construction size) stone blocks by rolling them are presented. The method is implemented by tying 12 identical rods of appropriately chosen radius to the faces of the block forming a rough dodecagon prism. Experiments using a 1,000 kg block show that it can be moved across level open ground with a dynamic coefficient of friction of less than 0.06. This value is a factor of five lower than that obtained for dragging the block, and the best values reported for dragging by others, at 0.3. the results are more dramatic than those obtained on smaller scale experiments on a 29.6 kg block, also reported here. For full scale pyramid blocks, the wooden "rods" woudl need to be posts of order 30 cm in diameter, similar in size to those used as masts on ships in the Nile., Comment: 12 pages, 3 figures. arXiv admin note: substantial text overlap with arXiv:1408.3603

Published
2015

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