963 results on '"K Gallagher"'
Search Results
2. 'Once more, with feeling': no difference in outcomes between patients discharged on oral versus intravenous antibiotics for orthopedic infections in a propensity score matched cohort at a US medical center
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Julie Gray, Russell J. Benefield, Chanah K. Gallagher, Heather Cummins, and Laura K. Certain
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Infectious and parasitic diseases ,RC109-216 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Objective: To compare outcomes between patients discharged on intravenous (IV) versus oral (PO) antibiotics for the treatment of orthopedic infections, after creation of an IV-to-PO guideline, at a single academic medical center in the United States. Methods: This was a retrospective, propensity score matched, cohort study of adult patients hospitalized for orthopedic infections from September 30, 2020, to April 30, 2022. Patients discharged on PO antibiotics were matched to patients discharged on IV antibiotics. The primary outcome was one-year treatment failure following discharge. Secondary outcomes were incidence of 60-day treatment failure, adverse drug events (ADE), readmissions, infectious disease clinic “no-show” rates, and emergency department (ED) encounters. Results: Ninety PO-treated patients were matched to 90 IV-treated patients. Baseline characteristics were similar in the two groups after matching. There was no significant difference in the proportions of patients on PO versus IV antibiotics experiencing treatment failure at one year (26% vs 31%, P = .47). There were no significant differences for any secondary outcomes: treatment failure within 60 days (13% vs 14%, P = 1.00), ADE (13% vs 11%, P = .82), unplanned readmission (17% vs 21%, P = .57), or ED encounters (9% vs 18%, P = .54). Survival analyses identified no significant differences in time-to-event between PO and IV treatment for any of the outcomes assessed. Conclusions: There were no appreciable differences in outcomes between patients discharged on PO compared to IV regimens. Antimicrobial stewardship interventions to increase prescribing of PO antibiotics for the treatment of orthopedic infections should be encouraged.
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- 2024
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3. Reviewing the role of machine learning and artificial intelligence for remote attestation in 5G+ networks.
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Shannon K. Gallagher, Austin Whisnant, Anton Dimov Hristozov, and Amit Vasudevan
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- 2022
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4. A comparative study of diagnostic performance and work experience of radiologists in three countries interpreting digital breast tomosynthesis.
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Elly K. Gallagher, Phuong Dung Trieu, Ziba Gandomkar, Tong Li, Masoumeh Gity, Patrick C. Brennan, Sarah Lewis 0001, and Seyedamir Tavakoli Taba
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- 2023
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5. Pathologic complete response and survival after neoadjuvant chemotherapy in cT1-T2/N0 HER2+ breast cancer
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Selena J. An, Emilie D. Duchesneau, Paula D. Strassle, Katherine Reeder-Hayes, Kristalyn K. Gallagher, David W. Ollila, Stephanie M. Downs-Canner, and Philip M. Spanheimer
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Women with small HER2+ breast cancers may have excellent prognosis with adjuvant single-agent chemotherapy and HER2-targeted therapy. The role of de-escalated therapy in the neoadjuvant setting, however, remains uncertain. We conducted a cohort study of adult women with T1-2/cN0 HER2+ breast cancer diagnosed 2013–2016 in the National Cancer Database treated with neoadjuvant chemotherapy (NAC) and HER2-targeted therapy. Factors associated with pathologic complete response (pCR) and overall survival were examined. In total, 6994 patients were included, 32% cT1 and 68% cT2. Multi-agent NAC was given to 90% of women while single-agent NAC was given to 10% of women. pCR was achieved in 46% of cT2 patients and 43% of cT1, and in 46% of patients treated with multi-agent versus 38% single agent. Patients receiving multi-agent chemotherapy were younger, had fewer comorbidities, and had higher cT stage and grade. In all patients, pCR was associated with improved survival (p
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- 2022
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6. Branching Process Models to Identify Risk Factors for Infectious Disease Transmission.
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Shannon K. Gallagher and Dean Follmann
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- 2022
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7. Ionic requirements for the active ileal bile salt transport system
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K Gallagher, J Mauskopf, J T Walker, and L Lack
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sodium ion ,mannitol ,choline chloride ,taurocholate ,taurodehydrocholate ,Biochemistry ,QD415-436 - Abstract
Taurocholate transport by everted ileal gut sacs was studied in physiological media containing graded amounts of sodium ions. Significant uphill transport of taurocholate was observed when the bulk of NaCl was replaced by osmotic equivalents of mannitol or choline chloride. Seventy-seven percent of control transport activity was observed when 36 milliequivalents per liter of Na+ were present in the incubation medium with mannitol acting as the isosmotic replacement, and 74% of the control transport was retained when 31 milliequivalents per liter of Na+ were present in the incubation medium with choline chloride acting as the osmotic replacement. Lowering the Na+ concentration to 19 milliequivalents per liter (i.e., 84% replacement of Na+) still allowed for 69% of the uphill transport observed in the control incubations. Taurodehydrocholate transport by ileal everted sacs was more sensitive to decreased Na+ concentrations; 29% of control transport was observed at 31 milliequivalents per liter of Na+. A kinetic analysis comparing the transport of taurocholate with taurodehydrocholate, the triketo analogue, at different concentrations of Na+ indicated that the apparent affinity of the transport system for Na+ is greater in the presence of taurocholate than in the presence of taurodehydrocholate. The ability of taurodehydrocholate to depress taurocholate transport is less in media of low Na+ concentration. Finally, in vivo intestinal perfusion studies demonstrated that the depression of taurocholate absorption, following Na+ removal, is reversible. These results are in agreement with the idea that Na+ has a physiological role in intestinal bile salt transport, and that the affinities of the anionic bile salt and the sodium cation for the transport system appear to be cooperative in that one enhances the binding of the other.
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- 1976
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8. Quantifying previous SARS-CoV-2 infection through mixture modelling of antibody levels
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C. Bottomley, M. Otiende, S. Uyoga, K. Gallagher, E. W. Kagucia, A. O. Etyang, D. Mugo, J. Gitonga, H. Karanja, J. Nyagwange, I. M. O. Adetifa, A. Agweyu, D. J. Nokes, G. M. Warimwe, and J. A. G. Scott
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Science - Abstract
The proportion of a population that has previously been infected by a pathogen is typically estimated using antibody thresholds adjusted for sensitivity and specificity. Here, the authors present a model-based alternative to threshold methods which accounts for antibody waning and other sources of spectrum bias.
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- 2021
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9. FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036
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Steven P. Angus, Timothy J. Stuhlmiller, Gaurav Mehta, Samantha M. Bevill, Daniel R. Goulet, J. Felix Olivares-Quintero, Michael P. East, Maki Tanioka, Jon S. Zawistowski, Darshan Singh, Noah Sciaky, Xin Chen, Xiaping He, Naim U. Rashid, Lynn Chollet-Hinton, Cheng Fan, Matthew G. Soloway, Patricia A. Spears, Stuart Jefferys, Joel S. Parker, Kristalyn K. Gallagher, Andres Forero-Torres, Ian E. Krop, Alastair M. Thompson, Rashmi Murthy, Michael L. Gatza, Charles M. Perou, H. Shelton Earp, Lisa A. Carey, and Gary L. Johnson
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes. Motif analysis of lapatinib-responsive genomic regions implicated the pioneer transcription factor FOXA1 as a mediator of adaptive responses. Lapatinib in combination with FOXA1 depletion led to dysregulation of enhancers, impaired adaptive upregulation of HER3, and decreased proliferation. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. This highlights the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy.
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- 2021
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10. Modelling the effects of ice transport and sediment sources on the form of detrital thermochronological age probability distributions from glacial settings
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M. Bernard, P. Steer, K. Gallagher, and D. Lundbek Egholm
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Dynamic and structural geology ,QE500-639.5 - Abstract
The impact of glaciers on the Quaternary evolution of mountainous landscapes remains controversial. Although in situ or bedrock low-temperature thermochronology offers insights on past rock exhumation and landscape erosion, the method also suffers from potential biases due to the difficulty of sampling bedrock buried under glaciers. Detrital thermochronology attempts to overcome this issue by sampling sediments at e.g. the catchment outlet, a component of which may originate from beneath the ice. However, detrital age distributions not only reflect the catchment exhumation, but also spatially variable patterns and rates of surface erosion and sediment transport. In this study, we use a new version of a glacial landscape evolution model, iSOSIA, to address the effect of erosion and sediment transport by ice on the form of synthetic detrital age distributions. Sediments are tracked as Lagrangian particles formed by bedrock erosion, and their transport is restricted to ice or hillslope processes, neglecting subglacial hydrology, until they are deposited. We base our model on the Tiedemann Glacier (British Columbia, Canada), which has simple morphological characteristics, such as a linear form and no connectivity to large tributary glaciers. Synthetic detrital age distributions are generated by specifying an erosion history, then sampling sediment particles at the frontal moraine of the modelled glacier. Results show that sediment sources, reflecting different processes such as glacier and hillslope erosion, can have distinct bedrock age distribution signatures, and estimating such distributions should help to identify predominant sources in the sampling site. However, discrepancies between the detrital and bedrock age distributions occur due to (i) the selective storage of a large proportion of sediments in small tributary glaciers and in lateral moraines, (ii) the large range of particle transport times due to varying transport lengths and strong variability of glacier ice velocity, (iii) the heterogeneous pattern of erosion, and (iv) the advective nature of glacier sediment transport along ice streamlines. This last factor leads to a poor lateral mixing of particle detrital signatures inside the frontal moraine, and then local sampling of the frontal moraine is likely to reflect local sources upstream. Therefore, sampling randomly across the moraine is preferred for a more representative view of the catchment age distribution. Finally, systematic comparisons between synthetic (U-Th)/He and fission track detrital ages, with different bedrock age-elevation profiles and different relative age uncertainties, show that the nature of the age-elevation relationship and age uncertainties largely control the ability to track sediment sources in the detrital record. However, depending on the erosion pattern spatially, qualitative first-order information may still be extracted from a thermochronological system with high uncertainties (>30 %). Overall, our results demonstrate that detrital age distributions in glaciated catchments are strongly impacted not only by erosion and exhumation but also by sediment transport processes and their spatial variability. However, when combined with bedrock age distributions, detrital thermochronology offers a novel means to constrain the transport pattern and time of sediment particles.
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- 2020
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11. Outcomes of gynecologic cancer surgery during the COVID-19 pandemic: an international, multicenter, prospective CovidSurg-Gynecologic Oncology Cancer study
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Nepogodiev, Dmitri, Siaw-Acheampong, Kwabena, Benson, Ruth A., Bywater, Edward, Chaudhry, Daoud, Dawson, Brett E., Evans, Jonathan P., Glasbey, James C., Gujjuri, Rohan R., Heritage, Emily, Jones, Conor S., Kamarajah, Sivesh K., Khatri, Chetan, Khaw, Rachel A., Keatley, James M., Knight, Andrew, Lawday, Samuel, Li, Elizabeth, Mann, Harvinder S., Marson, Ella J., McLean, Kenneth A., Mckay, Siobhan C., Mills, Emily C., Pellino, Gianluca, Picciochi, Maria, Taylor, Elliott H., Tiwari, Abhinav, Simoes, Joana FF., Trout, Isobel M., Venn, Mary L., Wilkin, Richard JW., Bhangu, Aneel, Abbott, Tom EF., Abukhalaf, Sadi, Adamina, Michel, Ademuyiwa, Adesoji O., Agarwal, Arnav, Akkulak, Murat, Alameer, Ehab, Alderson, Derek, Alakaloko, Felix, Albertsmeier, Markus, Alser, Osaid, Alshaar, Muhammad, Alshryda, Sattar, Arnaud, Alexis P., Augestad, Knut Magne, Ayasra, Faris, Azevedo, José, Bankhead-Kendall, Brittany K., Barlow, Emma, Beard, David, Blanco-Colino, Ruth, Brar, Amanpreet, Minaya-Bravo, Ana, Breen, Kerry A., Bretherton, Chris, Buarque, Igor Lima, Burke, Joshua, Caruana, Edward J., Chaar, Mohammad, Chakrabortee, Sohini, Christensen, Peter, Cox, Daniel, Cukier, Moises, Cunha, Miguel F., Davidson, Giana H., Desai, Anant, Di Saverio, Salomone, Drake, Thomas M., Edwards, John G., Elhadi, Muhammed, Emile, Sameh, Farik, Shebani, Fiore, Marco, Fitzgerald, J Edward, Ford, Samuel, Garmanova, Tatiana, Gallo, Gaetano, Ghosh, Dhruva, Ataíde Gomes, Gustavo Mendonça, Grecinos, Gustavo, Griffiths, Ewen A., Gruendl, Magdalena, Halkias, Constantine, Harrison, Ewen M., Hisham, Intisar, Hutchinson, Peter J., Hwang, Shelley, Isik, Arda, Jenkinson, Michael D., Jonker, Pascal, MA Kaafarani, Haytham, Keller, Debby, Kolias, Angelos, Kruijff, Schelto, Lawani, Ismail, Lederhuber, Hans, Leventoglu, Sezai, Litvin, Andrey, Loehrer, Andrew, Löffler, Markus W., Lorena, Maria Aguilera, Modolo, Maria Marta, Major, Piotr, Martin, Janet, Mashbari, Hassan N., Mazingi, Dennis, Metallidis, Symeon, Mohan, Helen M., Moore, Rachel, Moszkowicz, David, Moug, Susan, Ng-Kamstra, Joshua S., Maimbo, Mayaba, Negoi, Ionut, Niquen, Milagros, Ntirenganya, Faustin, Olivos, Maricarmen, Oussama, Kacimi, Outani, Oumaima, Parreno-Sacdalanm, Marie Dione, Pata, Francesco, Perez Rivera, Carlos Jose, Pinkney, Thomas D., van der Plas, Willemijn, Pockney, Peter, Qureshi, Ahmad, Radenkovic, Dejan, Ramos-De la Medina, Antonio, Richards, Toby, Roberts, Keith, Roslani, April C., Rutegård, Martin, Segura-Sampedro, Juan José, Santos, Irène, Satoi, Sohei, Sayyed, Raza, Schache, Andrew, Schnitzbauer, Andreas A., Seyi-Olajide, Justina O., Sharma, Neil, Shaw, Catherine A., Shaw, Richard, Shu, Sebastian, Soreide, Kjetil, Spinelli, Antonino, Stewart, Grant D., Sund, Malin, Sundar, Sudha, Tabiri, Stephen, Townend, Philip, Tsoulfas, Georgios, van Ramshorst, Gabrielle H., Vidya, Raghavan, Vimalachandran, Dale, Warren, Oliver J., Wedderburn, Duane, Wright, Naomi, Booth, Lesley, Barker, Neil, Cooke, Shirley, Doré, Suzanne, Horwood, Nigel, Runigamugabo, Emmy, Weir, Carrie Tierney, Dajti I, Albania, C, Allemand, LA, Boccalatte, M, Figari, M, Lamm, J, Larrañaga, C, Marchitelli, F, Noll, D, Odetto, M, Perrotta, J, Saadi, L, Zamora, Ballester, A.M., KE, Tapper, N, Zeff, JI, Valenzuela, C, Alurralde, J, Anastasio, Perez de Nucci A, Apas, EL, Caram, D, Eskinazi, JP, Mendoza, M, Usandivaras, R, Badra, A, Esteban, JS, García, PM, García, JI, Gerchunoff, Lucchini, S.M., NIgra, M.A., L, Vargas, T, Hovhannisyan, A, Stepanyan, CE, Vasey, EGR, Watson, C, Ip, J, Kealey, CSH, Lim, S, Sengupta, S, Ward, E, Wong, T, Gould, R, Gourlay, B, Griffiths, S, Gananadha, M, McLaren, J, Cecire, N, Joshi, S, Salindera, A, Sutherland, JH, Ahn, G, Charlton, S, Chen, N, Gauri, R, Hayhurst, S, Jang, F, Jia, C, Mulligan, W, Yang, G, Ye, H, Zhang, M, Ballal, D, Gibson, D, Hayne, H, McMillan, J, Moss, MJ, Pugliese, T, Richards, YTN, Seow, A, Thian, P, Viswambaram, UG, Vo, J, Bennetts, T, Bright, Brooke-Smith, M., R, Fong, B, Gricks, L, Huang, YH, Lam, A, Nathan, Ong, B.S., E, Ooi, M, Szpytma, D, Watson, K, Bagraith, S, Caird, E, Chan, C, Dawson, D, Ho, N, Hui, S, Izwan, E, Jeyarajan, S, Jordan, R, Liang, A, Lim, GJ, Nolan, A, Oar, D, Parker, H, Puhalla, A, Quennell, L, Rutherford, C, Sommerville, P, Townend, Papen M, Von, M, Wullschleger, AC, Dawson, A, Drane, A, Blatt, D, Cope, N, Egoroff, M, Fenton, J, Gani, N, Lott, P, Pockney, N, Shugg, M, Elliott, D, Phung, D, Phan, D, Townend, C, Bong, J, Gundara, A, Frankel, S, Bowman, GR, Guerra, N, Gerns, S, McGeorge, A, Riddell, M, Roberts, N, Rukin, J, Bolt, K, Buddingh, Dudi-Venkata, N.N., S, Jog, HM, Kroon, T, Sammour, R, Smith, C, Stranz, M, Batstone, K, Lah, W, McGahan, D, Mitchell, A, Morton, A, Pearce, G, Sheahan, B, Swinson, A, Waldron, P, Walker, N, Alam, S, Banting, L, Chong, P, Choong, S, Clatworthy, D, Foley, A, Fox, MW, Hii, B, Knowles, J, Mack, M, Read, A, Rowcroft, G, Wright, EWY, Lun, M, Lanner, J, Burtscher, Trivik-Barrientos, F., I, Königsrainer, M, Bauer, C, Freyschlag, M, Kafka, F, Messner, D, Öfner, I, Tsibulak, S, Holawe, M, Zimmermann, K, Emmanuel, M, Grechenig, R, Gruber, M, Harald, L, Öhlberger, J, Presl, A, Wimmer, İ, Namazov, E, Samadov, D, Barker, R, Boyce, S, Corbin, A, Doyle, A, Eastmond, R, Gill, A, Haynes, S, Millar, M, O’Shea, G, Padmore, N, Paquette, E, Phillips, John S, St., K, Walkes, J, Abeloos, Backer T, De, Ceulaer J, De, C, Dick, Diez-Fraile, A., P, Lamoral, C, Spaas, W, Ceelen, P, Pattyn, D, Van de putte, Nieuwenhove Y, Van, Ramshorst G, Van, Willaert, W., Bazzett-Matabele, L., SP, Chiyapo, Ramogola-Masire, D., G, Ramontshonyana, A, Seiphetlheng, P, Vuylsteke, EA, Abdallah, Júnior S, Aguiar, G, Baiocchi, GB, Carvalho, FJF, Coimbra, LP, Kowalski, F, Makdissi, N, Marques, T, Marques, Santos S, Soares Dos, Gonçalves B, Tirapelli, JG, Vartanian, Reis R, Dos, P, Camara, Lima RK, De, Giustina E, Della, PV, Hoffmann, A, Gatti, C, Nardi, R, Oliva, L, Nacif, Ferro C, Carvalho, Ataíde G, Gomes Mendonça, Buarque I, Lima, A, Lira dos Santos Leite, Pol-Fachin, L., Bezerra T, Santos, Ramos da Silva A, Maylson, de Araújo Silvestre D, Windson, Barros A, Vieira, L, Campbell, Cicco R, De, I, Cecconello, P, Gregorio, Lima L, Pontual, Junior U, Ribeiro, FR, Takeda, RM, Terra, Teixeira M, Faccini, Kulcsar, M.A.V., LL, Matos, KS, Nunes, G, Laporte, M, Salem, Awada J, Barakat, TR, Ijichi, NJ, Kim, A, Marreiro, B, Muller, R, Nunes, B, Bodanese, ER, Eidt, JC, Isoton, Vieira da Cunha M, Lemos, de Sampaio L, Regina, C, Vendrame, M, Zeni, JA, Zortéa, MR, Zortéa, M, Sokolov, B, Kidane, S, Srinathan, A, Munro, L, Helyer, D, McKeen, M, Boutros, NG, Caminsky, G, Ghitulescu, G, Jamjoum, J, Moon, J, Pelletier, T, Vanounou, S, Wong, D, Cheng, SD, MacNeil, J, Martin, S, Dumitra, A, Kouyoumdjian, S, Schmid, J, Spicer, A, Agarwal, A, Brar, J, Dada, A, Dare, U, Hameed, F, Osman, B, Johnston, C, Russell, G, Groot, A, Persad, H, Pham, M, Wood, M, Ko, L, Rajendran, S, Demyttenaere, R, Garfinkle, C, Brown, A, Karimuddin, N, Lee, J, Liu, Kia T, Madani, Phang, P.T., M, Raval, K, Tom, Abou-Khalil, J., A, Martel, C, Nessim, J, Stevenson, Riyami S, Al, K, Bali, D, Bigam, K, Dajani, A, Dell, MM, Modolo, Nieto P, Ramirez, R, Sepulveda, A, Molero, A, Bolbaran, I, Ruiz, F, Heredia, F, Bellolio, N, Besser, E, Grasset, JO, Guaman, M, Inzunza, MJ, Irarrázaval, C, Jarry, Martinic M, Quintana, Altamirano C, Riquoir, Manqui CA, Romero, Esquide M, Ruiz, Añazco C, Vargas, A, Almeciga, A, Fletcher, A, Merchan, T, Quijano, D, Sanabria, Arias-Amézquita, F., C, Cétares, Murgueitio N, Cortes, Gomez-Mayorga, J.L., Herrera-Almario, G., J, Rodriguez, P, Iglesias, LO, Puentes, JA, Calvache, Orozco-Chamorro, C.M., DA, Rojas, Sánchez-Gómez, A., M, Abadia, J, Acosta, Aristizabal J, Angel, A, Bonilla, L, Caicedo, Quiroz PH, Calderon, Bonilla S, Cervera, S, Diaz, H, Facundo, Mora M, Garcia, O, Guevara, L, Guzman, Mora DR, Herrera, Ramirez LJ, Jimenez, C, Lehmann, E, Manrique, I, Mariño, M, Medina, Morales RE, Pinilla, A, Puerto, Horta J, Puerto, M, Quintero, Ferro M, Rey, A, Saénz, D, Santana, W, Serrano, O, Suescun, Sanchez LM, Trujillo, Cuasquen BG, Velasquez, Quevedo J , Bogota, Mendoza, G, Bačić, D, Karlović, D, Kršul, M, Zelić, I, Luksic, M, Mamic, I, Bacic, B, Bakmaz, I, Ćoza, E, Dijan, Z, Katusic, J, Mihanovic, D, Morović, I, Rakvin, H, Almezghwi, K, Arslan, H, Besim, A, Özant, N, Özçay, K, Frantzeskou, N, Gouvas, G, Kokkinos, P, Papatheodorou, I, Pozotou, O, Stavrinidou, A, Yiallourou, L, Martinek, M, Skrovina, M, Straka, I, Szubota, M, Peteja, J, Žatecký, V, Javurkova, J, Klat, S, Antony, T, Avlund, KD, Berg, M, Borre, P, Christensen, MC, Elkjær, A, Ernst, SK, Fensman, M, Haldrup, JL, Harbjerg, LH, Iversen, Jensen, P.T., TD, Jeppesen, DW, Kjaer, HØ, Kristensen, N, Lund, Axelsen S, Maigaard, M, Mekhael, N, Mikic, EB, Ostenfeld, AL, Ebbehøj, P, Krarup, N, Schlesinger, H, Smith, S, Batista, A, Crespo, PJ, Díaz, R, Rivas, Rodriguez-Abreu, J., N, Tactuk, Kassas M, El, W, Omar, A, Tawheed, M, Talaat, A, Abdelsamed, AY, Azzam, H, Salem, A, Seleim, A, Abdelmajeed, M, Abdou, NE, Abosamak, Sayed M, A.L., F, Ashoush, R, Atta, E, Elazzazy, M, Elnemr, Hewalla ME, Elsayed, I, Elsherbini, E, Essam, M, Ewedah, I, Ghallab, E, Hassan, M, Ibrahim, M, Metwalli, M, Mourad, Qatora, M.S., M, Ragab, A, Sabry, H, Saifeldin, A, Samih, Abdelaal A, Samir, S, Shehata, K, Shenit, D, Attia, N, Kamal, N, Osman, Abbas, A.M., Elazeem HAS, Abd, Abd-Elkariem, A.Y., MM, Abdelkarem, S, Alaa, M, Ashraf, A, Ayman, MG, Azizeldine, H, Elkhayat, Mashhour A, Emad, M, Gaber, HM, Hamza, I, Hawal, HF, Hetta, Ali A, K., S, M.elghazaly, MM, Mohammed, FA, Monib, Nageh, M.A., A, Saad, MM, Saad, M, Shahine, EA, Yousof, A, Youssef, El-Deeb, M., M, Fawzy, G, Ghaly, M, Ibraheem, A, Eldaly, E, Esmail, M, ElFiky, A, Nabil, M, Alrahawy, A, Sakr, H, Soliman, H, Soltan, G, Amira, I, Sallam, M, Sherief, A, Sherif, A, Abdelrahman, H, Aboulkassem, R, Hamdy, A, Morsi, G, Sherif, H, Abdeldayem, Salama I, Abdelkader, M, Balabel, Y, Fayed, AE, Sherif, R, Elmorsi, S, Emile, B, Refky, S, Abd-elsalam, H, Badr, M, Elbahnasawy, M, Elzoghby, M, Essa, Badr S, Gamal, A, Ghoneim, O, Hamad, M, Hamada, M, Hammad, A, Hawila, Morsy, M.S., S, Salman, S, Sarsik, K, Bekele, JH, Kauppila, E, Sarjanoja, O, Helminen, H, Huhta, C, Beyrne, L, Jouffret, L, Lugans, Marie-Macron, L., E, Chouillard, Simone B, De, F, Fredon, A, Roux, J, Bettoni, S, Dakpé, B, Devauchelle, N, Lavagen, S, Testelin, S, Boucher, R, Breheret, A, Gueutier, A, Kahn, Kün-Darbois, J., A, Barrabe, Z, Lakkis, A, Louvrier, S, Manfredelli, P, Mathieu, A, Chebaro, V, Drubay, M, El amrani, C, Eveno, K, Lecolle, G, Legault, L, Martin, G, Piessen, FR, Pruvot, S, Truant, P, Zerbib, Q, Ballouhey, B, Barrat, L, Fourcade, J, Laloze, H, Salle, A, Taibi, J, Tricard, J, Usseglio, D, Bergeat, A, Merdrignac, Roy B, Le, LO, Perotto, A, Scalabre, H, Gornes, C, Vaysse, K, Vergriete, A, Aimé, A, Ezanno, B, Malgras, AP, Arnaud, E, Fustec, V, Lavoue, C, Tesson, P, Bouche, S, Tzedakis, E, Cotte, O, Glehen, J, Lifante, L, 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Burnside, Cadwell-Sneath, S., K, Gajjar, C, Gan, C, Grundy, K, Hallam, K, Hassell, M, Hawari, A, Joshi, H, Khout, K, Konstantinidi, Lee, R.X.N., D, Nunns, R, Schiemer, T, Walton, H, Weaver, L, Whisker, K, Williamson, ME, Ahmed, SI, Bukhari, B, Illingworth, S, Kanthasamy, E, Knights, SL, Ong, R, Pujari, KHM, Tan, R, Vanker, M, Michel, S, Patil, S, Ravindran, J, Sarveswaran, L, Scott, I, Biliatis, M, Edmond, E, King, O, Babawale, D, Hodgson, M, Ismail, J, Khan, U, Lokman, YC, Phan, M, Almond, A, Bhangu, O, Breik, LD, Cato, YA, Chowdhury, A, Desai, S, Ford, E, Griffiths, M, Idle, M, Kamal, K, Karia, A, Kisiel, R, Kulkarni, JKC, Mak, T, Martin, P, Nankivell, A, Parente, S, Parmar, Pathanki, A.M., L, Phelan, P, Praveen, S, Saeed, N, Sharma, J, Singh, G, Solomou, WC, Soon, A, Stevens, F, Tirotta, C, Topham, I, Ughratdar, D, Vijayan, K, Ballantyne, L, Barker, K, Chapman, M, Charalambous, C, Chianakwalam, C, English, J, Evans, A, Fell, D, Frimpong, C, Halkias, R, Iyer, R, Merh, G, Neagu, S, Nikolaou, A, Poddar, V, Pronisceva, V, Reddy, N, Williams, L, Alakandy, P, Bhattathiri, J, Brown, M, Canty, E, Day, A, Geddes, A, Grivas, S, Hassan, S, Lammy, P, Littlechild, C, Maseland, C, Mathieson, J, McCaul, J, McMahon, R, O’Kane, George E, St., N, Suttner, W, Taylor, E, Tilling, W, English, S, Kaul, AH, Khan, F, Khan, A, Mansuri, S, Mukherjee, M, Sarigul, KL, Tan, P, Vulliamy, A, Woodham, YH, Yang, A, Adiamah, H, Brewer, A, Chowdhury, D, Humes, J, Jackman, A, Koh, Lewis-Lloyd, C., A, Navarro, O, Oyende, J, Reilly, R, Vohra, D, Worku, P, Cool, G, Cribb, K, Shepherd, C, Bisset, S, Moug, R, Chadha, N, Elson, R, Galleano, G, Faulkner, A, Langone, Z, Panayi, P, Saleh, F, Tuminello, C, Underwood, G, Brixton, L, Findlay, T, Klatte, A, Majkowska, J, Manson, R, Potter, Al-Khyatt, W., A, Bhalla, Z, Chia, P, Daliya, A, Goyal, E, Grimley, A, Hamad, FL, Malcolm, JCK, Ng, A, Phillips, E, Theophilidou, S, Williams, J, Bowden, N, Campain, I, Daniels, G, Fowler, J, John, L, Massey, F, McDermott, J, McGrath, A, McLennan, M, Ng, J, Pascoe, N, Rajaretnam, N, Angamuthu, S, Bulathsinhala, S, Chowdhury, B, Davidson, G, Fusai, J, Gilliland, C, Hart, Salinas C, Hidalgo, J, Knowles, N, Machairas, R, Mirnezami, T, Pissanou, JM, Pollok, DA, Raptis, F, Soggiu, H, Tzerbinis, M, Varcada, S, Xyda, A, Beamish, E, Davies, R, Foulkes, D, Magowan, H, Nassa, R, Ooi, C, Price, L, Smith, F, Solari, A, Tang, G, Williams, Kahar NN, Abd, Al-Tamimi, Y., A, Bacon, N, Beasley, J, Catto, LH, Chan, D, Chew, M, Crank, N, Ilenkovan, M, Macdonald, B, Narice, O, Rominiyi, S, Saad, S, Sinha, A, Thompson, I, Varley, P, Brennan, T, Drake, EM, Harrison, G, Linder, J, Mayes, R, McGregor, R, Pasricha, RJE, Skipworth, V, Zamvar, P, Hawkin, T, Raymond, O, Ryska, R, Baron, D, Dunne, S, Gahunia, C, Halloran, N, Howes, R, McKinney, F, McNicol, K, Rajput, J, Russ, R, Sutton, P, Szatmary, JR, Tan, P, Whelan, A, Anzak, A, Banerjee, O, Fuwa, F, Hughes, Jayasinghe, J.D., C, Knowles, HM, Kocher, Silva I, Leal, FS, Ledesma, A, Minicozzi, L, Navaratne, P, Patki, R, Rahman, R, Ramamoorthy, C, Sohrabi, C, Tanabalan, M, Thaha, B, Thakur, M, Venn, V, Yip, R, Baumber, J, Parry, S, Evans, L, Jeys, G, Morris, M, Parry, N, Ahmadi, G, Aresu, Barrett-Brown, Z.M., A, Coonar, Yates H, Durio, D, Gearon, J, Hogan, M, King, A, Peryt, IS, Pradeep, M, Adishesh, R, Atherton, K, Baxter, M, Brocklehurst, M, Chaudhury, N, Krishnamohan, J, McAleer, G, Owens, E, Parkin, P, Patkar, I, Phang, A, Aladeojebi, M, Ali, B, Barmayehvar, A, Gaunt, M, Gowda, E, Halliday, M, Kitchen, F, Mansour, P, Nanjaiah, D, Zakai, Abbassi-Ghadi, N., H, Assalaarachchi, A, Currie, M, Flavin, A, Frampton, M, Hague, C, Hammer, J, Hopper, J, Horsnell, S, Humphries, A, Kamocka, TK, Madhuri, S, Preston, P, Singh, J, Stebbing, A, Tailor, D, Walker, E, Coomber, S, Jaunoo, L, Kennedy, A, Airey, J, Bunni, R, Crowley, K, Fairhurst, J, Frost, R, George, S, Lee, S, Mitchell, J, Phull, S, Richards, F, Aljanadi, A, Campbell, A, Glass, I, Hraishawi, M, Jones, C, McIlmunn, S, McIntosh, P, Mhandu, C, O’Donnell, R, Turkington, Al-Ishaq, Z., S, Bhasin, AS, Bodla, A, Burahee, A, Crichton, El-Ghobashy, A., R, Fossett, N, Pigadas, E, Rahman, D, Snee, R, Vidya, N, Yassin, D, Fountain, Hasan, M.T., K, Karabatsou, R, Laurente, O, Pathmanaban, C, Barlow, D, Ding, J, Foster, L, Longstaff, Brett-Miller, C., FE, Buruiana, A, Al-mukhtar, J, Edwards, A, Giblin, C, Kelty, M, Lee, G, Lye, T, Newman, A, Sharkey, C, Steele, Shah N, Sureshkumar, E, Whitehall, J, Blair, A, Lakhiani, Parry-Smith, W., B, Sahu, R, Athwal, A, Baker, L, Jones, C, Konstantinou, S, Ramcharan, J, Vatish, R, Wilkin, A, Alzetani, K, Amer, A, Badran, HV, Colvin, M, Ethunandan, GK, Sekhon, Z, Shakoor, H, Shields, R, Singh, T, Talbot, F, Wensley, S, Lawday, A, Lyons, S, Newman, E, Chung, R, Hagger, A, Hainsworth, I, Hunt, A, Karim, H, Owen, A, Ramwell, G, Santhirakumaran, J, Smelt, C, Tan, P, Vaughan, K, Williams, C, Baker, A, Davies, J, Gossage, M, Kelly, W, Knight, S, Bromage, J, Hall, V, Kaushik, M, Rudic, N, Vallabh, Y, Zhang, G, Harris, G, James, C, Kang, DJ, Lin, AD, Rajgor, T, Royle, R, Scurrah, B, Steel, LJ, Watson, D, Choi, R, Hutchison, V, Luoma, HJ, Marcus, R, May, A, Menon, B, Pramodana, L, Webber, A, Hayes, R, Jones, G, Sivarajah, M, Smith, A, Smrke, D, Strauss, FAM, Abouelela, IA, Aneke, P, Asaad, B, Brown, J, Collis, S, Duff, A, Khan, F, Moura, M, Taylor, B, Wadham, H, Warburton, T, Elmoslemany, Jenkinson, M.D., CP, Millward, R, Zakaria, S, Mccluney, C, Parmar, S, Shah, J, Allison, Babar, M.S., J, Bowen, B, Collard, S, Goodrum, K, Lau, M, Sargent, R, Scott, E, Thomas, H, Whitmore, D, Balasubramaniam, B, Jayasankar, S, Kapoor, A, Ramachandran, C, Semple, A, Elhamshary, SMB, Imam, K, Kapriniotis, V, Kasivisvanathan, J, Lindsay, Rakhshani-Moghadam, S., N, Beech, M, Chand, L, Green, N, Kalavrezos, H, Kiconco, R, McEwen, C, Schilling, D, Sinha, J, Pereca, S, Chopra, D, Egbeare, R, Thomas, S, Arumugam, B, Ibrahim, K, Khan, T, Combellack, G, Hill, S, Jones, M, Kornaszewska, M, Mohammed, G, Tahhan, V, Valtzoglou, N, Blencowe, P, Eskander, K, Gash, L, Gourbault, M, Hanna, TA, Maccabe, B, Main, J, Olivier, C, Newton, S, Roswadowski, N, Ryan, E, Teh, D, West, H, Al-omishy, M, Baig, H, Bates, Taranto G, Di, K, Dickson, N, Dunne, C, Gill, D, Howe, D, Jeevan, A, Khajuria, Martin-Ucar, A., K, McEvoy, P, Naredla, S, Robertson, M, Sait, DR, Sarma, S, Shanbhag, T, Shortland, S, Simmonds, J, Skillman, N, Tewari, G, Walton, Akhtar, M.A., A, Brunt, J, McIntyre, K, Milne, MM, Rashid, A, Sgrò, KE, Stewart, A, Turnbull, Abou-Foul, A.K., G, Gossedge, S, O’Donnell, F, Oldfield, S, Thomson, Gonzalez M, Aguilar, S, Talukder, C, Boyle, D, Fernando, K, Gallagher, A, Laird, D, Tham, M, Bath, P, Basnyat, H, Davis, P, Montauban, A, Shrestha, K, Agarwal, T, Arif, C, Magee, T, Nambirajan, S, Powell, R, Vinayagam, I, Flindall, A, Hanson, V, Mahendran, S, Green, M, Lim, L, MacDonald, V, Miu, L, Onos, K, Sheridan, R, Young, F, Alam, O, Griffiths, C, Houlden, VS, Kolli, AK, Lala, S, Leeson, R, Peevor, Z, Seymour, E, Consorti, R, Gonzalez, R, Grolman, Kwan-Feinberg, R., T, Liu, O, Merzlikin, Francisco, San, A, Brown, Z, Cooper, S, Hirji, J, Jolissaint, D, Mahvi, B, Okafor, CP, Raut, V, Roxo, A, Salim, S, Bessen, L, Chen, L, Dagrosa, K, Fay, C, Fleischer, R, Hasson, E, Henderson, M, Leech, A, Loehrer, C, Markey, J, Paydarfar, K, Rosenkranz, K, Telma, N, Tocci, Wilkinson-Ryan, I., M, Bokenkamp, K, Brown, D, Fleming, C, Heron, C, Hill, H, Kay, E, Leede, K, McElhinney, KA, Olson, EC, Osterberg, C, Riley, P, Srikanth, J, Barbour, D, Blazer, GA, DiLalla, O, Fayanju, ES, Hwang, R, Kahmke, H, Kazaure, A, Lazarides, W, Lee, M, Lidsky, C, Menendez, D, Moris, J, Plichta, MC, Pradhan, L, Puscas, HE, Rice, D, Rocke, L, Rosenberger, R, Scheri, Smith, B.D., Stang, M.T., L, Tolnitch, K, Turnage, J, Visgauss, FS, Walton, T, Watts, S, Zani, J, Farma, K, Cardona, MC, Russell, J, Clark, D, Kwon, N, Goel, J, Kronenfeld, B, Bigelow, E, Etchill, Gabre-Kidan, A., H, Jenny, A, Kent, MR, Ladd, C, Long, H, Malapati, A, Margalit, S, Rapaport, J, Rose, K, Stevens, L, Tsai, D, Vervoort, P, Yesantharao, A, Dehal, D, Klaristenfeld, K, Huynh, H, Kaafarani, L, Naar, M, Qadan, L, Brown, I, Ganly, JE, Mullinax, N, Alpert, C, Gillezeau, Miles DDS MD, F.A.C.S.B.A., E, Taioli, DE, Cha, E, Gleeson, C, Horn, U, Sarpel, N, Gusani, J, Hazelton, J, Maines, JS, Oh, A, Ssentongo, P, Ssentongo, A, Bhama, K, Colling, M, Najarian, M, Azam, A, Choudhry, W, Marx, Y, Abedin, G, Arzumanov, R, Chokshi, S, Gabrilovich, N, Glass, E, Kalyoussef, Parvin-Nejad, F.P., D, Roden, J, Stein, Suarez-Ligon, A., G, Tsui, K, Zhao, J, Fleming, A, Fuson, J, Gigliotti, A, Ovaitt, Y, Ying, MK, Abel, V, Andaya, K, Bigay, Boeck, M.A., H, Chern, C, Corvera, El-Sayed, I., A, Glencer, P, Ha, Hamilton, B.C.S., C, Heaton, K, Hirose, Jablons, D.M., KS, Kirkwood, LZ, Kornblith, JR, Kratz, RH, Lee, PN, Miller, EK, Nakakura, Nunez-Garcia, B., RJ, O’Donnell, D, Ozgediz, P, Park, B, Robinson, A, Sarin, B, Sheu, MG, Varma, KC, Wai, R, Wustrack, MJ, Xu, M, Zimel, D, CA) Beswick, J, Goddard, J, Manor, J, Song, Springs/Loveland, Denver/Colorado, A, Cioci, W, Pavlis, K, Rakoczy, G, Ruiz, R, Saberi, T, Fullmer, C, Gaskill, N, Gross, K, Kiong, CL, Roland, SN, Zafar, M, Abdallah, A, Abouassi, E, Aigbivbalu, M, Almasri, J, Eid, B, George, G, Kulkarni, H, Marwan, M, Mehdi, Andrés M, San, J, Sundaresan, SG, Aoun, VS, Ban, HH, Batjer, K, Bosler, J, Caruso, B, Sumer, D, Abbott, A, Acher, T, Aiken, J, Barrett, E, Foley, PB, Schwartz, AT, Hawkins, A, Maiga, NM, Ruzgar, M, Sion, S, Ullrich, J, Laufer, S, Scasso, Al-Naggar, H., Al-Shehari, M., A, Almassaudi, M, Alsayadi, R, Alsayadi, M, Nahshal, S, Shream, S, AL-Ameri, M, Aldawbali, Fotopoulou, Christina, Khan, Tabassum, Bracinik, Juraj, Glasbey, James, Abu-Rustum, Nadeem, Chiva, Luis, Fagotti, Anna, Fujiwara, Keiichi, Ghebre, Rahel, Gutelkin, Murat, Konney, Thomas O., Ng, Joseph, Pareja, Rene, Kottayasamy Seenivasagam, Rajkumar, Sehouli, Jalid, Surappa, Shylasree T.S., and Leung, Elaine
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- 2022
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12. Multi-omic Dissection of Oncogenically Active Epiproteomes Identifies Drivers of Proliferative and Invasive Breast Tumors
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John A. Wrobel, Ling Xie, Li Wang, Cui Liu, Naim Rashid, Kristalyn K. Gallagher, Yan Xiong, Kyle D. Konze, Jian Jin, Michael L. Gatza, and Xian Chen
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Science - Abstract
Summary: Proliferative and invasive breast tumors evolve heterogeneously in individual patients, posing significant challenges in identifying new druggable targets for precision, effective therapy. Here we present a functional multi-omics method, interaction-Correlated Multi-omic Aberration Patterning (iC-MAP), which dissects intra-tumor heterogeneity and identifies in situ the oncogenic consequences of multi-omics aberrations that drive proliferative and invasive tumors. First, we perform chromatin activity-based chemoproteomics (ChaC) experiments on breast cancer (BC) patient tissues to identify genetic/transcriptomic alterations that manifest as oncogenically active proteins. ChaC employs a biotinylated small molecule probe that specifically binds to the oncogenically active histone methyltransferase G9a, enabling sorting/enrichment of a G9a-interacting protein complex that represents the predominant BC subtype in a tissue. Second, using patient transcriptomic/genomic data, we retrospectively identified some G9a interactor-encoding genes that showed individualized iC-MAP. Our iC-MAP findings represent both new diagnostic/prognostic markers to identify patient subsets with incurable metastatic disease and targets to create individualized therapeutic strategies. : Biological Sciences; Cancer Systems Biology; Cancer Subject Areas: Biological Sciences, Cancer Systems Biology, Cancer
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- 2019
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13. Willingness: Human Rights Crises and State Response in Mexico
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Alejandro Anaya-Muñoz and Janice K. Gallagher
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Sociology and Political Science ,Political Science and International Relations ,Geography, Planning and Development - Abstract
States targeted by human rights criticism usually do something—whether ratifying treaties, passing laws, establishing institutions, prosecuting perpetrators, or shifting discourse. But how do we know how coordinated, comprehensive, and effective these actions are? This article proposes five questions to assess how willing a state is to take the steps necessary to meaningfully respond to human rights crises. It applies this approach to two human rights crises in Mexico: femicides and violence against women, and disappearances. This approach effectively differentiates state responses that initially appear similar, demonstrating that the Mexican government has been more willing to address violence against women and femicides than disappearances. An explanation for this difference in outcomes points to a combination of factors related to the underlying preferences of the government involved, the characteristics of victims, and the specific human right being violated.
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- 2023
14. Sandtank-ML: An Educational Tool at the Interface of Hydrology and Machine Learning
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Lisa K. Gallagher, Jill M. Williams, Drew Lazzeri, Calla Chennault, Sebastien Jourdain, Patrick O’Leary, Laura E. Condon, and Reed M. Maxwell
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hydrology ,machine learning ,education ,hydrological modeling ,Hydraulic engineering ,TC1-978 ,Water supply for domestic and industrial purposes ,TD201-500 - Abstract
Hydrologists and water managers increasingly face challenges associated with extreme climatic events. At the same time, historic datasets for modeling contemporary and future hydrologic conditions are increasingly inadequate. Machine learning is one promising technological tool for navigating the challenges of understanding and managing contemporary hydrological systems. However, in addition to the technical challenges associated with effectively leveraging ML for understanding subsurface hydrological processes, practitioner skepticism and hesitancy surrounding ML presents a significant barrier to adoption of ML technologies among practitioners. In this paper, we discuss an educational application we have developed—Sandtank-ML—to be used as a training and educational tool aimed at building user confidence and supporting adoption of ML technologies among water managers. We argue that supporting the adoption of ML methods and technologies for subsurface hydrological investigations and management requires not only the development of robust technologic tools and approaches, but educational strategies and tools capable of building confidence among diverse users.
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- 2021
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15. Effects of climate on salmonid productivity: A global meta‐analysis across freshwater ecosystems
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Brian K. Gallagher, Sarah Geargeoura, and Dylan J. Fraser
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Global and Planetary Change ,Ecology ,Climate Change ,Animals ,Environmental Chemistry ,Fresh Water ,Seasons ,Ecosystem ,Salmonidae ,General Environmental Science - Abstract
Salmonids are of immense socio-economic importance in much of the world, but are threatened by climate change. This has generated a substantial literature documenting the effects of climate variation on salmonid productivity in freshwater ecosystems, but there has been no global quantitative synthesis across studies. We conducted a systematic review and meta-analysis to gain quantitative insight into key factors shaping the effects of climate on salmonid productivity, ultimately collecting 1321 correlations from 156 studies, representing 23 species across 24 countries. Fisher's Z was used as the standardized effect size, and a series of weighted mixed-effects models were compared to identify covariates that best explained variation in effects. Patterns in climate effects were complex and were driven by spatial (latitude, elevation), temporal (time-period, age-class), and biological (range, habitat type, anadromy) variation within and among study populations. These trends were often consistent with predictions based on salmonid thermal tolerances. Namely, warming and decreased precipitation tended to reduce productivity when high temperatures challenged upper thermal limits, while opposite patterns were common when cold temperatures limited productivity. Overall, variable climate impacts on salmonids suggest that future declines in some locations may be counterbalanced by gains in others. In particular, we suggest that future warming should (1) increase salmonid productivity at high latitudes and elevations (especially60° and1500 m), (2) reduce productivity in populations experiencing hotter and dryer growing season conditions, (3) favor non-native over native salmonids, and (4) impact lentic populations less negatively than lotic ones. These patterns should help conservation and management organizations identify populations most vulnerable to climate change, which can then be prioritized for protective measures. Our framework enables broad inferences about future productivity that can inform decision-making under climate change for salmonids and other taxa, but more widespread, standardized, and hypothesis-driven research is needed to expand current knowledge.
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- 2022
16. Racial‐ethnic variations in phyllodes tumors among a multicenter United States cohort
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Amanda L. Nash, Samantha M. Thomas, Suniti N. Nimbkar, Tina J. Hieken, Kandice K. Ludwig, Lisa K. Jacobs, Megan E. Miller, Kristalyn K. Gallagher, Jasmine Wong, Heather B. Neuman, Jennifer Tseng, Taryn E. Hassinger, Tari A. King, E. Shelley Hwang, James W. Jakub, and Laura H. Rosenberger
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Oncology ,Surgery ,General Medicine - Abstract
Previous studies have identified racial-ethnic differences in the diagnostic patterns and recurrence outcomes of women with phyllodes tumors (PT). However, these studies are generally limited in size and generalizability. We therefore sought to explore racial-ethnic differences in age, tumor size, subtype, and recurrence in a large US cohort of women with PT.We performed an 11-institution retrospective review of women with PT from 2007 to 2017. Differences in age at diagnosis, tumor size and subtype, and recurrence-free survival according to race-ethnicity.Women of non-White race or Hispanic ethnicity were younger at the time of diagnosis with phyllodes tumor. Non-Hispanic Other women had a larger proportion of malignant PT. There were no differences in recurrence-free survival in our cohort.Differences in age, tumor size, and subtype were small. Therefore, the workup of young women with breast masses and the treatment of women with PT should not differ according to race-ethnicity. These conclusions are supported by our finding that there were no differences in recurrence-free survival.
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- 2022
17. Noninferiority testing with censoring when the event rate is low
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Shannon K. Gallagher, Jing Wang, Keith Lumbard, Lori E. Dodd, and Michael Proschan
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Statistics and Probability ,Epidemiology ,Humans ,Computer Simulation ,Probability - Abstract
The PREDICT TB trial tests noninferiority of an abbreviated treatment regimen (arm A) vs a conventional treatment regimen (arm C). Treatment trials of drug-susceptible tuberculosis are expected to have low event rates (ie, relapse probabilities around 3-5%). We examine the question of what is the "best" way to test for noninferiority in a setting with low event rates. In a series of simulations supported by theoretical arguments, we examine operating characteristics of five tests, including normal approximation, exact, and simulation-based tests. Two of these tests are constructed from Kaplan-Meier based-estimators, which account for variable follow-up time (and those lost to follow-up). We evaluate the effect of loss to follow-up via simulations. We also examine the results of the five tests on a data set similar to PREDICT TB, the REMoxTB trial. We find that the normal approximation tests perform well, albeit with small type I error rate inflation. We also find that the Kaplan-Meier methods generally have larger power than the other tests, especially when there is between 10-30% loss to follow-up.
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- 2022
18. A Rare Pediatric Case of Anti-melanoma Differentiation-associated Gene 5 Rapidly Progressive Interstitial Lung Disease
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K. Gallagher, R. Ortenberg, and D. Toprak
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- 2023
19. The role of bariatric surgery in liver transplantation: timing and type
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Danial Safavi, Ben Creavin, Tom K. Gallagher, and Michael E. Kelly
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Treatment Outcome ,Non-alcoholic Fatty Liver Disease ,Gastrectomy ,Humans ,Bariatric Surgery ,Female ,Surgery ,Obesity ,Liver Transplantation ,Obesity, Morbid ,Retrospective Studies - Abstract
Introduction The rise in obesity worldwide has shifted the indications for liver transplantation (LT), with non-alcoholic steatohepatitis (NASH) being the second most common indication for transplantation. There remains an underestimation of cirrhosis being attributed to NASH. Bariatric surgery (BS) is a reliable solution to overcome obesity and its associated comorbidities. The role of BS in LT has been investigated by different studies; however, the type of BS and timing of LT need further investigation. Methods A systemic review examining the role of BS in LT patients was performed. After selection of the studies based on inclusion and exclusion criteria, data extraction was performed by two independent reviewers. Primary outcomes included patient and graft survival. Results From a total of 2374 articles, five met the prefined criteria. One hundred sixty-two patients had both BS + LT and 1426 underwent LT alone. The percentage of female patients in the BS + LT and LT cohorts was 75% and 35% respectively. The average age in BS + LT and LT cohorts was 43.05 vs. 56.22 years respectively. Patients undergoing BS had comparable outcomes in terms of overall patient survival, graft survival and post-operative morbidity compared to LT alone. When comparing BMI change in patients with prior versus simultaneous BS + LT, no significant difference was found. Conclusion BS and LT patients achieve comparable outcomes to general LT populations. Further studies examining simultaneous BS + LT are needed to answer questions concerning patient selection and timing of surgery.
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- 2022
20. Are we choosing wisely? Drivers of preoperative MRI use in breast cancer patients
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Eric Brown, Amanda Mendiola, Melissa Lazar, Naveenraj L. Solomon, David W. Ollila, Marissa Howard-McNatt, Edward A. Levine, Anees B. Chagpar, Sonali V Pandya, Elisabeth Dupont, Carlos Garcia-Cantu, Mary Murray, Kristalyn K. Gallagher, Andrew Fenton, Jennifer Gass, Sharon S. Lum, Akiko Chiba, Laura Walters, and Jukes P. Namm
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Male ,medicine.medical_specialty ,Multivariate analysis ,medicine.medical_treatment ,Breast Neoplasms ,Mastectomy, Segmental ,law.invention ,Breast cancer ,Randomized controlled trial ,Patient age ,law ,Preoperative Care ,medicine ,Breast-conserving surgery ,Humans ,Breast ,Stage (cooking) ,Neoadjuvant therapy ,Tumor histology ,business.industry ,General Medicine ,medicine.disease ,Magnetic Resonance Imaging ,Neoadjuvant Therapy ,Female ,Surgery ,Radiology ,business - Abstract
Factors contributing to the use of preoperative MRI remain poorly understood.Data from a randomized controlled trial of stage 0-3 breast cancer patients undergoing breast conserving surgery between 2016 and 2018 were analyzed.Of the 396 patients in this trial, 32.6% had a preoperative MRI. Patient age, race, ethnicity, tumor histology, and use of neoadjuvant therapy were significant predictors of MRI use. On multivariate analysis, younger patients with invasive lobular tumors were more likely to have a preoperative MRI. Rates also varied significantly by individual surgeon (p 0.001); in particular, female surgeons (39.9% vs. 24.0% for male surgeons, p = 0.001) and those in community practice (58.9% vs. 14.2% for academic, p 0.001) were more likely to order preoperative MRI. Rates declined over the two years of the study, particularly among female surgeons.Preoperative MRI varies with patient age and tumor histology; however, there remains variability by individual surgeon.
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- 2022
21. Computer Vision Analysis of Specimen Mammography to Predict Margin Status
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Kevin A Chen, Kathryn E Kirchoff, Logan R Butler, Alexa D Holloway, Muneera R Kapadia, Kristalyn K Gallagher, and Shawn M Gomez
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Intra-operative specimen mammography is a valuable tool in breast cancer surgery, providing immediate assessment of margins for a resected tumor. However, the accuracy of specimen mammography in detecting microscopic margin positivity is low. We sought to develop a deep learning-based model to predict the pathologic margin status of resected breast tumors using specimen mammography. A dataset of specimen mammography images matched with pathology reports describing margin status was collected. Models pre-trained on radiologic images were developed and compared with models pre-trained on non-medical images. Model performance was assessed using sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). The dataset included 821 images and 53% had positive margins. For three out of four model architectures tested, models pre-trained on radiologic images outperformed domain-agnostic models. The highest performing model, InceptionV3, showed a sensitivity of 84%, a specificity of 42%, and AUROC of 0.71. These results compare favorably with the published literature on surgeon and radiologist interpretation of specimen mammography. With further development, these models could assist clinicians with identifying positive margins intra-operatively and decrease the rate of positive margins and re-operation in breast-conserving surgery.
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- 2023
22. Scaling and Flow Similarity Considerations to Develop a 1/40th Scale Aerodynamic Model of a Longwall Coal Mine for Methane Hazards Investigation
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H. Pinheiro, A. Juganda, N. Sandoval, F Wilson, K. Gallagher, G. Bogin, and J. Brune
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Control and Systems Engineering ,Mechanical Engineering ,Materials Chemistry ,Metals and Alloys ,General Chemistry ,Geotechnical Engineering and Engineering Geology - Published
- 2022
23. An X-ray investigation of stereoselectivity in the interactions of [Co(en)3]3+ with [Co(ox)3]3− (en is ethane-1,2-diamine and ox is oxalate)
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Megan K. Gallagher, Jonathan Baker, Robert Black, Allen G. Oliver, and A. Graham Lappin
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Inorganic Chemistry ,Materials Chemistry ,Physical and Theoretical Chemistry ,Condensed Matter Physics - Abstract
The X-ray structure of racemic tris(ethane-1,2-diamine-κ2 N,N′)cobalt(III) tris(oxalato-κ2 O 1,O 2)cobaltate(III) pentahydrate, [Co(C2H8N2)3][Co(C2O4)3]·5H2O or [Co(en)3][Co(ox)3]·5H2O, has been determined. Hydrogen-bonding interactions along the C 3-axis of the [Co(en)3]3+ cation with the [Co(ox)3]3− anion are heterochiral, while those perpendicular to this axis are homochiral. Implications for the interpretation of chiral discriminations and induction in electron-transfer reactions in solution are discussed.
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- 2022
24. Crystal structure of tris(trans-1,2-diaminocyclohexane-κ2N,N′)cobalt(III) trichloride monohydrate
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Megan K. Gallagher, Allen G. Oliver, and A. Graham Lappin
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crystal structure ,cobalt(III) ,1,2-diaminocyclohexane ,coordination complex ,hydrogen-bonding patterns ,Crystallography ,QD901-999 - Abstract
The synthesis of the title hydrated complex salt, [Co(C6H14N2)3]Cl3·H2O, from racemic trans-1,2-diaminocyclohexane and [CoCl(NH3)5]Cl2 and its structural characterization are presented in this paper. The product was synthesized in the interest of understanding the hydrogen-bonding patterns of coordination complexes. Previous characterizations of the product in the I-42d space group have not yielded coordinates; thus, this paper provides the first coordinates for this complex in this space group. The octahedrally coordinated cation adopts twofold rotation symmetry, with outer-sphere chloride counter-ions and solvent water molecules forming a hydrogen-bonded network with amine H atoms.
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- 2016
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25. Prospective Evaluation of Radar-Localized Reflector–Directed Targeted Axillary Dissection in Node-Positive Breast Cancer Patients after Neoadjuvant Systemic Therapy
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Kristalyn K, Gallagher, Kathleen, Iles, Cherie, Kuzmiak, Raphael, Louie, Kandace P, McGuire, and David W, Ollila
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Radar ,Sentinel Lymph Node Biopsy ,Axilla ,Humans ,Lymph Node Excision ,Breast Neoplasms ,Female ,Surgery ,Lymph Nodes ,Neoadjuvant Therapy ,Neoplasm Staging - Abstract
This is a prospective, single-institution study to evaluate feasibility and accuracy of radar-localized reflector (RLR)-targeted axillary dissection (TAD) in node-positive breast cancer patients after neoadjuvant systemic therapy (NST).Patients with biopsy-proven T1-2, N1-3 disease were eligible. Before NST, a marker clip and/or RLR was placed into the positive node. After NST, RLR was inserted if not placed previously. All patients underwent RLR TAD followed by axillary lymph node dissection (ALND). Primary end points of the trial were feasibility of RLR TAD and false negative rate (FNR).Between 2017 and 2021, 101 patients with N1-3 disease underwent NST. Five patients withdrew from the study, 1 was ineligible, and there were 9 technical failures, thus our final study cohort comprised 86 patients. RLR TAD was performed with probe guidance and confirmed with intraoperative specimen radiograph. After RLR TAD, ALND was performed. Median number of RLR TAD nodes removed was 2 (range 1-10), and the RLR TAD nodes remained positive in 56 patients. Median number of ALND nodes removed was 18 (range 4-46). Accounting for 9 technical failures, feasibility was 90%. All technical failures occurred with attempted placement of RLR after NST. Feasibility rate was 100% when RLR placement occurred at diagnosis. Of the evaluable 86 patients, RLR TAD accurately predicted axillary status in 83 patients, with FNR of 5.1%.We demonstrate high accuracy of RLR TAD, especially when RLR is placed before NST. For patients who present with N1-3 disease, this is another step towards axillary surgery de-escalation strategies.
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- 2022
26. Sociodemographic and Clinical Predictors of Neoadjuvant Chemotherapy in cT1-T2/N0 HER2-Amplified Breast Cancer
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Emilie D. Duchesneau, Selena J. An, Paula D. Strassle, Katherine E. Reeder-Hayes, Kristalyn K. Gallagher, David W. Ollila, Stephanie M. Downs-Canner, and Philip M. Spanheimer
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Adult ,Sentinel Lymph Node Biopsy ,Breast Neoplasms ,Article ,Neoadjuvant Therapy ,Oncology ,Chemotherapy, Adjuvant ,Axilla ,Humans ,Lymph Node Excision ,Female ,Surgery ,Lymph Nodes ,Mastectomy - Abstract
The optimal treatment strategy for small node-negative human epidermal growth factor receptor 2-positive (HER2+) breast cancer remains controversial. Neoadjuvant chemotherapy may risk overtreatment, whereas surgery first fails to identify patients with residual disease in need of escalated adjuvant systemic therapy. We investigated patient characteristics associated with receipt of neoadjuvant chemotherapy.Adult women with cT1-T2/N0, HER2+ breast cancer between 2013 and 2017 in the National Cancer Database who underwent surgery within 8 months of diagnosis were included. Patients were classified as receiving neoadjuvant chemotherapy versus a surgery-first approach. We assessed the sociodemographic and clinical predictors of neoadjuvant chemotherapy versus surgery first and associations between neoadjuvant chemotherapy and breast cancer treatments using multivariable regression models.We identified 56,784 women, of whom 12,758 (22%) received neoadjuvant chemotherapy, 29,139 (53%) received adjuvant chemotherapy, 12,907 (24%) received no chemotherapy, and 1980 were missing chemotherapy information. After adjustment, cT2 stage was the strongest predictor of neoadjuvant chemotherapy compared with surgery first. Younger age and later diagnosis year were positively associated with receipt of neoadjuvant chemotherapy. In contrast, hormone receptor positivity, Black race, rural county, and government-funded or no health insurance were inversely associated with neoadjuvant chemotherapy. In multivariable analyses, patients who received neoadjuvant chemotherapy were more likely to have a mastectomy (vs. lumpectomy) and sentinel lymph node biopsy or no nodal surgery (vs. axillary lymph node dissection). Patients who received neoadjuvant chemotherapy were more likely to receive multi-agent (vs. single-agent) chemotherapy than those who received adjuvant chemotherapy.Substantial differences in the utilization of neoadjuvant chemotherapy exist in women with HER2+ breast cancer, which reflect both clinical parameters and disparities. Optimal treatment strategies should be implemented equitably across sociodemographic groups.
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- 2022
27. Branching Process Models to Identify Risk Factors for Infectious Disease Transmission
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Dean Follmann and Shannon K. Gallagher
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Statistics and Probability ,Infectious disease transmission ,Computer science ,Immunology ,Discrete Mathematics and Combinatorics ,Statistics, Probability and Uncertainty ,Branching process - Published
- 2022
28. Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial
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Muhammed O Afolabi, David Ishola, Daniela Manno, Babajide Keshinro, Viki Bockstal, Baimba Rogers, Kwabena Owusu-Kyei, Alimamy Serry-Bangura, Ibrahim Swaray, Brett Lowe, Dickens Kowuor, Frank Baiden, Thomas Mooney, Elizabeth Smout, Brian Köhn, Godfrey T Otieno, Morrison Jusu, Julie Foster, Mohamed Samai, Gibrilla Fadlu Deen, Heidi Larson, Shelley Lees, Neil Goldstein, Katherine E Gallagher, Auguste Gaddah, Dirk Heerwegh, Benoit Callendret, Kerstin Luhn, Cynthia Robinson, Brian Greenwood, Maarten Leyssen, Macaya Douoguih, Bailah Leigh, Deborah Watson-Jones, M Kargbo, E Bockarie, N L James, A Kabbah, A Kamara, K H Koroma, S O Langley, N William, R Kessebeh, T Mooney, L Conteh, E Smout, K Allieu, K Bangura, M S Bangura, M A Bangura, H Jalloh, A B Jalloh, I Kamara, M Kamara, A Konteh, S Koroma, C Marrah, M Sesay, M T Sesay, A T Deen, A Jalloh, R M Kaimbay, D Kain, E L Kamara, M P Kamara, O J Kamara, S L M Kamara, M Kanneh, A H Koroma, D Lahai, I S Mansaray, W S Marah, M J Massaquoi, A Nabie, N S Saidu, I Samai, J N Tengheh, A S Turay, A Fornah, F Sesay, A Sow, E Swaray, F Mansaray, T Ade-Cole, L M Bangura, M L Conteh, A M Koroma, M Koroma, A Sam, T Scott, T Sessie, J-H C Sunders, S I-S Turay, J Weekes, M Sheku, L Gibson, D Kowuor, I Ahamed, W Allieu, D U Kabba, F J Kamara, M S Kebbie, M Pessima, A Wurie, F Bah, A I Bangura, R A S Bangura, L Blango, S Boima, M Conteh, Y Conteh, M L Daramy, O Fofanah, E George, T F Hanson, M I Jalloh, M Kalawa, A M Kamara, F E Kamara, G M Kamara, H M Kamara, P B D Kamara, R T Kamara, R Kamara, D P Kanneh, I Komeh, M Kuyateh, F F Mansaray, M M Mansaray, A B Sillah, M A Tarawally, O S Turya, J B Yawmah, B Leigh, D Watson-Jones, B Greenwood, M H Samai, G F Deen, D Marke, T Sesay, P Piot, P Smith, J Edmunds, S Lees, H Larson, H Weiss, P Wilson, R Phillips, C Maxwell, D Ishola, M Afolabi, F Baiden, P Akoo, K Owusu-Kyei, D Tindanbil, H Bower, J Stuart, O M Bah, B T Rogers, A Serry-Bangura, I B Swaray, A Bangura, I J David, D G M Davies, J A Kallon, A B Kamara, I F Kamara, M M Kamara, F E Morovia, F B Suma, F Thompson, M Murray, O Kakay, F Suma, I Sesay, J Foster, D Manno, K Gallagher, S Cox, N Howard, M Cesay, P Torrani, S Sharma, E Snowden, T Banks, T Harber, J Brown, K Howard, N Melton, S Malcolm, S Welsh, R Eggo, M Jendrossek, C Pearson, K Offergeld, C Ferrault, M Van Alst, N Mahajan, M Van Looveren, S Van Ballaert, T De Cnodder, N Grobler, L Roza, T Liberi, L Armishaw, C Verkleij, T Henrick, A Banaszkiewicz, B Lowe, K Awuondo, H Hafezi, E Hancox, B Kohn, G O Tuda, G Bangura, M T Kroma, L Fofanah, A Pessima, M Rogers, O Sheriff, T W Ajala, J Fangawa, S Foday Jr, I S F Koroma, B Mansaray, H A Mansaray, K Sesay, M K Charles, P C Heroe, M Lamin Karbo, I S Yansaneh, S Gogo Egoeh, A Trye, M Amponsah, L Donelson, T Sylvester, V Owira, G Onyuka, L Nambuchi, A Oburu, D Apollo, L Vandi, N D Alghali, A Bah, I J Bangura, A C Cole, S Fofanah, H U Jalloh, K F N Jalloh, N Jalloh, H U Kabba, J N Kabba, M Kabba, J S Kamara, F Kanjie, A P Kanu, I Kargbo, G Kassa-Koroma, S B Koroma, A Sankoh, T Sankoh, O D Sesay, H Wilhem, C T Williams, I Bangura, Y Ben-Rogers, F J Jamboria, N Kamara, I Kanawah, A T Kargbo, I Swaray, L Amara, I Bundu, H B Jakema, K Kamara, M F Sheku, Q Adeleye, I Akhigbe, R Bakalemwa, N P Chami, L Altmann, B Kamara, K van Roey, P Conteh, M Samura, V Gandie, M Marrah, E Moinina, J Kalokoh, S Bosompem, T Hilton, M O Jusu, P Borboh, A S Brima, A F Y Caulker, A Kallon, B Koroma, R C Macauley, T M D Saquee, H I Williams, A R Bangura, J Fornah, B Idriss, M Sillah, W Mackay, B Aleghen, T Murray, J Edem-Hotah, T Fatorma, F Amara, S Bangura, E Bonnie, M Sannoh, A Donaldson, S Ndingi, D Nyaberi, M Pereira, A Rothwell, V Vy, L Nyallay, A Fombah, S Saidu, T P Dambo, P J Fakaba, M M E Fatorma, R H Freeman, C L Johnson, D B Kogba, A Lahai, W Vincent, N Yambasu, M Bangura, A Tengbeh, R Kabia, A M Nyakoi, M Callaghan, L Enria, and S Lee
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Male ,Modified vaccinia Ankara ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Antibodies, Viral ,medicine.disease_cause ,Injections, Intramuscular ,Drug Administration Schedule ,Sierra Leone ,Sierra leone ,Immunogenicity, Vaccine ,Vaccines, DNA ,Humans ,Medicine ,Ebola Vaccines ,Child ,Reactogenicity ,Heterologous vaccine ,Ebola virus ,Ebola vaccine ,business.industry ,Infant ,Viral Vaccines ,Ebolavirus ,Vaccination ,Regimen ,Infectious Diseases ,Child, Preschool ,Female ,business - Abstract
Summary Background Children account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone. Methods This randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1–17 years were enrolled in three age cohorts (12–17 years, 4–11 years, and 1–3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 1010 viral particles; first dose) followed by MVA-BN-Filo (1 × 108 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov , NCT02509494 . Findings From April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1–3 years after placebo injection to 21% (30 of 144) of children aged 4–11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12–17 years and 4–11 years age cohorts after the first and second dose, and pyrexia in the 1–3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12–17 years (9929 ELISA units [EU]/mL [95% CI 8172–12 064]), in 119 (99%) of 120 aged 4–11 years (10 212 EU/mL [8419–12 388]), and in 118 (98%) of 121 aged 1–3 years (22 568 EU/mL [18 426–27 642]). Interpretation The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1–17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children. Funding Innovative Medicines Initiative 2 Joint Undertaking and Janssen Vaccines & Prevention BV.
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- 2022
29. Type 1 interferon auto-antibodies are elevated in patients with decompensated liver cirrhosis
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Gordon Greville, Sinead Cremen, Shauna O’Neill, Sarah Azarian, Gareth Brady, William McCormack, Olivier Touzelet, David Courtney, Ultan Power, Paul Dowling, Tom K Gallagher, Connor GG Bamford, and Mark W Robinson
- Abstract
Understanding the biological basis of clinical risk factors for severe COVID-19 is required to ensure at-risk patient populations receive appropriate clinical care. Patients with decompensated liver cirrhosis, in particular those classified as Childs-Pugh class B and C, are at increased risk of severe COVID-19 upon infection with SARS-CoV-2. The biological mechanisms underlying this are unknown. We hypothesised this may be due to changes in expression levels of intrinsic antiviral proteins within the serum as well as alterations in the innate immune response to SARS-CoV-2 infection. We identified significant alterations in the serum proteome of patients with more severe liver disease and an increased frequency of auto-antibodies capable of neutralising type I interferons. No difference in SARS-CoV-2 pseudoparticle infection or live SARS-CoV-2 virus infection was observed with serum from decompensated cirrhotic patients. Principal component analysis of the serum proteome identified two main clinical parameters associated with serum proteome changes – aetiology and MELD-Na score. Among patients with MELD-Na scores >20 we detected significant inhibition of IFN-α2b and IFN-α8 signalling but not IFN-β1a, mediated by auto-antibodies. Our results suggest pre-existing neutralising auto-antibodies targeting type I IFN may increase the likelihood of severe COVID-19 in chronic liver disease patients upon SARS-CoV-2 infection and may also be of relevance to other viral infections in this patient population.
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- 2022
30. The role of neo-adjuvant therapy in cholangiocarcinoma: A systematic review
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Sinead Cremen, Michael E. Kelly, and Tom K. Gallagher
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Cancer Research ,Oncology - Abstract
IntroductionCholangiocarcinoma (CCA) is the most common malignancy affecting the biliary tree. The only curative treatment is surgical resection, aiming for negative margins (R0). For those who have locally advanced disease, which is borderline resectable, neoadjuvant chemoradiation presents an opportunity to reduce tumour size and allow for surgical resection. The aim of this review is to establish the role of neoadjuvant therapy in each subtype of CCA and establish its impact on survival.MethodsSearch terms such as ‘neoadjuvant therapy’ and ‘cholangiocarcinoma’ were searched on multiple databases, including Pubmed, Ovid and Embase. They were then reviewed separately by two reviewers for inclusion criteria. 978 studies were initially identified from the search strategy, with 21 being included in this review.Results5,009 patients were included across 21 studies. 1,173 underwent neoadjuvant therapy, 3,818 had surgical resection alone. 359 patients received Gemcitabine based regimes, making it the most commonly utilised regimen for patients CCA and Biliary Tract Cancer (BTC). Data on tolerability of regimes was limited. All included papers were found to have low risk of bias when assessed using The Newcastle Ottawa Scale. Patients who underwent neoadjuvant therapy had a similar median overall survival compared to those who underwent upfront surgery (38.4 versus 35.1 months respectively). Pre-operative CA19-9, microvascular invasion, perineurial invasion and positive lymph nodes were of prognostic significance across BTC and CCA subtypes.ConclusionNeoadjuvant therapy and surgical resection is associated with improved patient outcomes and longer median overall survival compared to therapy and upfront surgery, however heterogeneity between research papers limited the ability to further analyse the significance of these results. Although initial studies are promising, further research is required in order to define suitable treatment protocols and tolerability of neoadjuvant regimes.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42020164781.
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- 2022
31. External validation of the IDENTIFY risk calculator
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S. Khadhouri, L. Orecchia, R. Banthia, P. Piazza, D. Mak, N. Pyrgidis, P. Narayan, P. Abad Lopez, F. Nawaz, T.T. Thanh, F. Claps, D. Hogan, J. Gomez Rivas, S. Alonso, I. Chibuzo, K. Meghana, T. Anbarasan, K. Gallagher, and V. Kasivisvanathan
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Urology - Published
- 2023
32. Bridging Endocrine Therapy for HR+/HER2- Resectable Breast Cancer: Is it Safe?
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Philip M Spanheimer, David W. Ollila, Kathleen Iles, Madeline Thornton, Kristalyn K. Gallagher, Mya L. Roberson, and Jihye Park
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Adult ,Oncology ,2019-20 coronavirus outbreak ,medicine.medical_specialty ,Bridging (networking) ,Antineoplastic Agents, Hormonal ,Coronavirus disease 2019 (COVID-19) ,Receptor, ErbB-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Breast Neoplasms ,Breast cancer ,Surgical oncology ,Internal medicine ,Pandemic ,North Carolina ,Humans ,Medicine ,Pandemics ,Aged ,Neoplasm Staging ,Probability ,Aged, 80 and over ,business.industry ,Endocrine therapy ,COVID-19 ,General Medicine ,Middle Aged ,medicine.disease ,Neoadjuvant Therapy ,Carcinoma, Intraductal, Noninfiltrating ,Treatment Outcome ,Receptors, Estrogen ,Female ,Receptors, Progesterone ,business - Abstract
Background The COVID-19 pandemic has required new treatment paradigms to limit exposures and optimize hospital resources, including the use of neoadjuvant endocrine therapy (NAET) as bridging therapy for HR+/HER2-invasive tumors and DCIS. While this approach has been used in locally advanced disease, it is unclear how it may affect outcomes in resectable HR+/HER2- tumors. Methods Women ≥18 years diagnosed with in situ (Tis) or non-metastatic HR+/HER2- breast cancer from March-May 2019 and 2020 were included. Fisher’s exact test and two-sample t test were used to compare baseline characteristics and surgical outcomes between strata. Sub-analysis was performed between patients who received primary surgery vs a bridging NAET approach. Results Despite similar clinical characteristics, patients in 2019 were more likely to have a surgery-first approach (75% vs 42%, P-value = .0007), receive surgery sooner (22 vs 29 days, P-value < .001), and within 60 days from diagnosis date (100% vs 85%, P-value = .0301). Neoadjuvant endocrine therapy was a more prevalent approach in 2020 (48% vs 7%, P-value < .0001). Rates of clinical to pathologic up-staging remained consistent across primary surgery vs bridging NAET subgroups ( P-value = .9253). Discussion Pandemic-driven treatment protocols provide a unique opportunity to assess the utility of bridging endocrine therapy for resectable HR+/HER2- tumors. Differences in clinical and pathologic staging were similar across groups and did not appear to be affected by receipt of NAET. Our limited cohort demonstrates this strategic therapeutic avenue can optimize health care utilization and may be a reasonable approach when delaying surgery is preferred.
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- 2021
33. Remdesivir for the Prevention of Invasive Mechanical Ventilation or Death in Coronavirus Disease 2019 (COVID-19): A Post Hoc Analysis of the Adaptive COVID-19 Treatment Trial-1 Cohort Data
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Constance A. Benson, Otto O. Yang, Sarah B Doernberg, Robert Grossberg, Jing Wang, David C. Lye, Philip O Ponce, Cameron R. Wolfe, Richard T. Davey, Shannon K. Gallagher, Lori E. Dodd, Jocelyn Voell, Rekha R. Rapaka, William R. Short, Noreen A. Hynes, and Catharine I. Paules
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Microbiology (medical) ,Mechanical ventilation ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,business.industry ,medicine.medical_treatment ,Infectious Diseases ,Risk groups ,Treatment trial ,Oxygen breathing ,Emergency medicine ,Cohort ,Post-hoc analysis ,medicine ,Treatment effect ,business - Abstract
This post hoc analysis of the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) shows a treatment effect of remdesivir (RDV) on progression to invasive mechanical ventilation (IMV) or death. Additionally, we create a risk profile that better predicts progression than baseline oxygen requirement alone. The highest risk group derives the greatest treatment effect from RDV.
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- 2021
34. Self-regulation in the Kindergarten Classroom: Contributions of Relational and Sociodemographic Factors
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Brittany N. Zakszeski, Emily K. Gallagher, and Bridget V. Dever
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Race (biology) ,Service delivery framework ,education ,Multilevel model ,Closeness ,Ethnic group ,Educational psychology ,General Medicine ,Psychology ,Socioeconomic status ,Disadvantage ,Developmental psychology - Abstract
Prior research suggests that dimensions of the student–teacher relationship are transactionally associated with students’ self-regulation of classroom behavior, an important component of school readiness and success. The current study sought to determine the extent to which associations for student–teacher closeness and conflict with self-regulation (a) vary across kindergarten classrooms and schools and (b) are moderated by individual- (i.e., socioeconomic status, race/ethnicity) and system-level sociodemographic factors (i.e., economic disadvantage level, racial/ethnic composition). These associations were explored using multilevel modeling within a large national, longitudinal dataset including approximately 9990 kindergarteners, 1990 classrooms, and 670 schools. Despite substantial variance in the associations of closeness with self-regulation across classrooms and of conflict with self-regulation across classrooms and schools, results identified no sociodemographic moderators of the relationship–self-regulation associations, suggesting that these factors are universally related and promotive for varying sociodemographic populations; however, results also pointed to several sociodemographic subgroups at increased risk for low relational closeness, high relational conflict, and low self-regulation in the classroom. These findings are discussed in light of issues related to measurement and service delivery in schools.
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- 2021
35. Conclusion
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Janice K. Gallagher
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The concluding chapter reflects on the challenges of studying violence and the reasons the author chose to write a book spanning many levels of analysis, and focused on family members of victims of disappearances. It then summarizes the methodological and conceptual contributions of this book, as well as the implications of its findings. It draws out the implications of these findings for policymakers and funders, and calls for a recognition of the central place of victims of violence in challenging impunity and proposing a series of measures to support, legitimate, and protect their work. It closes by returning to the stories and reflections of Nancy, Juan Carlos, Lucia, and Alfonso.
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- 2022
36. Legal and Political Opportunities of the Uneven State
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Janice K. Gallagher
- Abstract
This chapter shows how victims’ collectives that are engaged in sustained mobilization burrow into the walls of impunity in different, and difficult, political contexts. By taking advantage of their relationships with sympathetic state actors, utilizing divisions both within the state and among the state and its drug trafficking organization allies, and striking out on their own to search for their loved ones, they strategically exploit opportunities to advance their right to truth, justice, and non-recurrence of the disappearances. The discussion is first framed within the literature that helps to explain the interactions between these different actors (state, DTOs, civil society). Next, it looks inside the state-level justice systems to better understand the structures and incentives that shape the behavior of state investigators. Finally, it unpacks three different cases (Tamaulipas, Veracruz, Nuevo León) with differing political opportunities and shows how victims’ collectives adapted their tactics in response—enabling them to erode impunity even in the most inauspicious environments.
- Published
- 2022
37. To What Effect?
- Author
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Janice K. Gallagher
- Abstract
Chapter 6 employs the United Nations Principles to combat impunity to help explain the gains that have been made in terms of rights to justice, truth, reparations, and non-recurrence in Mexico. It discusses the judicial outcomes of sustained mobilization by looking at the achievements and limitations of the leading human rights NGO in Nuevo León as well the judicial status of the cases of the three families profiled in this book. It examines the role of sustained mobilization in the passage of the Victims’ Law (2013), which is focused on reparations to victims, and the Law on Enforced Disappearance (2017), which promises progress on the right to truth and non-recurrence if fully implemented. Finally, it assesses the evolution of the victims’ movement—arguing that advances in available movement resources and repertoires of contention have shifted the accountability terrain for victims of violence in Mexico.
- Published
- 2022
38. State and Civil Society Responses to Disappearances in Mexico
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Janice K. Gallagher
- Abstract
This chapter sets the historical and political context of impunity in Mexico, tracing the shifting terrain of legal and political opportunities for people affected by disappearances. It discusses state-perpetrated disappearances during the Dirty War and the birth of the Mexican human rights movement in response. It shows that after democratization in 2000, advocacy around disappearances was increasingly possible, but the state’s diminishing control over lethal violence, worsened by its weak and decentralized judiciary, overwhelmed Mexico’s legal and political institutions. Mexico’s human rights organizations likewise found themselves unprepared for the unprecedented crisis in lethal violence as the lines between state and non-state perpetrators of violence blurred. This left victims of violence with scarce organizing resources to draw from. In response, a burgeoning of local collectives has occurred in recent years. These collectives form coalition organizations, use social media, hold conferences, and engage in participatory investigations to collectively combat impunity.
- Published
- 2022
39. The Evolution of Legal Consciousness
- Author
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Janice K. Gallagher
- Abstract
This chapter traces the transformation of legal consciousness among the three families profiled as they evolve from apolitical citizens to prominent activists and advocates. By following the claim-making and mobilization trajectories of Nancy, Juan Carlos, and Lucia and Alfonso, we see their understandings of legality evolve along with their abilities to challenge the inner workings of impunity. The chapter progressively puts individual stories in relation with one another—both theoretically, as the ways they think and act begin to converge, and in practice, as they meet each other in the national victims’ movement. Despite their initial divergent legal consciousnesses, sustained mobilization draws them to think more similarly over time—gravitating toward a strategic understanding of the law. As the ways they think converge, they are also drawn to a common contentious repertoire.
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- 2022
40. Introduction
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Janice K. Gallagher
- Abstract
The introductory chapter lays out the question, argument, and empirical strategy of the book and also previews the Mexican context. The book asks, how do people, living in settings marked by normalized rights violations, transform into rights-claiming and, ultimately, rights-bearing citizens? This chapter walks through the argument that as people participate in ongoing mobilization and claim-making over time, (1) their legal consciousness shifts, and with this shift, (2) their ability to challenge impunity is likewise transformed. It posits that despite the apparent impossibility of combating impunity without the state, victims have been able to erode impunity—that is, to bootstrap justice—to a surprising degree. It argues that these processes are best understood with a multi-level, temporally situated perspective, and that this approach provides insight into what has been achieved in the past decade, drawing lessons relevant beyond Mexico about what can be achieved in the struggle against impunity.
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- 2022
41. Bootstrap Justice
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Janice K. Gallagher
- Abstract
How do people living in settings marked by normalized rights violations, transform into rights-claiming and, ultimately, rights-bearing citizens? Bootstrap Justice centers the voices and perspectives of people whose lives have been upended by the disappearance of their loved ones in Mexico. The book argues that as people participate in ongoing mobilization and claim-making over time (1) their legal consciousness— their understandings of the state and of themselves as citizens and political actors—shifts, and that with these shifts, (2) their ability to challenge impunity is likewise transformed. Drawing on over a decade of ethnographic work, Bootstrap Justice offers unique insight into the critical but often overlooked role of informal relationships and dynamics in shaping substantive legal and human rights outcomes. The book presents in-depth analyses of the individuals involved in the daily struggle to find their loved ones, the organizations they form, the social movements they join, and the state- and national-level legal and political contexts that condition what is possible for them to achieve. This multi-level, temporally situated perspective provides unique insight into what has been achieved in the past decade, and draws lessons relevant beyond Mexico about what can be achieved in the struggle against impunity.
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- 2022
42. The Beginnings
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Janice K. Gallagher
- Abstract
This chapter lays the theoretical and empirical foundation for understanding why and how legal consciousness shifts over time. It first reviews the central explanations of why people mobilize, including life circumstances, underlying internal motivations, and the nature of the grievance. It argues for the relevance of how a person thinks—about the law, cooperation, their own sense of agency—in shaping whether and how they mobilize. The chapter then explores the salience of each of these logics in understanding the lives and decisions of the three families of focus before and in the immediate aftermath of their loved ones’ disappearance. Finally, it argues that closely reviewing the details of each disappearance improves insight into how the nature of the disappearance as a particularly cruel grievance shapes mobilization: its impetus for action lies in the ongoing uncertainty and possibility that their loved one’s well-being may be contingent on their own actions.
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- 2022
43. Critical Disconnects
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Janice K. Gallagher and Jorge Contesse
- Published
- 2022
44. The ParFlow Sandtank: An interactive educational tool making invisible groundwater visible
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Lisa K. Gallagher, Abram J. Farley, Calla Chennault, Sara Cerasoli, Sébastien Jourdain, Patrick O'Leary, Laura E. Condon, and Reed M. Maxwell
- Subjects
Water Science and Technology - Abstract
Physical aquifer models are a highly effective teaching tool for hydrology education, however they come with inherent limitations that include the high cost to purchase, the static configuration of the model materials, the time required to visualize hydrogeological phenomena, and the effort to reset and clean them over time. To address these and other limitations, we have developed an interactive computer simulation of a physical aquifer model called the ParFlow Sandtank. In this gamified interface, users run the simulation using a familiar web-app like interface with sliders and buttons while learning real hydrologic concepts. Our user interface allows participants to dive into the world of hydrology, understanding assumptions about model parameters such as hydraulic conductivity, making decisions about inputs to groundwater aquifer systems such as pumping rates, visualizing outputs such as stream flow, transport, and saturation, and exploring various factors that impact real environmental systems such as climate change. The ParFlow Sandtank has already been used in a variety of educational settings with more than 9,000 users per year, and we feel this emerging educational tool can be used broadly in educational environments and can be scaled-up to provide greater accessibility for students and educators. Here we present the capabilities and workflow of the ParFlow Sandtank, two use cases, and additional tools and custom templates that have been developed to support and enhance the reach of the ParFlow Sandtank.
- Published
- 2022
45. Diversity, equity, and inclusion in genitourinary clinical trials leading to FDA novel drug approval: An assessment of the FDA center for drug evaluation and research drug trials snapshot
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Asia N. Matthew-Onabanjo, Gabrielle Nortey, Richard S. Matulewicz, Ramsankar Basak, Donna A. Culton, Kimberly N. Weaver, Kristalyn K. Gallagher, Hung-Jui Tan, Tracy L. Rose, Matthew Milowsky, and Marc A. Bjurlin
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Cancer Research ,Oncology - Published
- 2023
46. Suboptimal therapy following breast conserving surgery in triple-negative and HER2-positive breast cancer patients
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Stephanie Downs-Canner, Paula D Strassle, Hyman B. Muss, Jeffrey E. Johnson, Kristalyn K. Gallagher, Guilherme C de Oliveira, David W. Ollila, Chris B. Agala, and Philip M Spanheimer
- Subjects
Adult ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Breast Neoplasms ,Mastectomy, Segmental ,Systemic therapy ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,HER2 Positive Breast Cancer ,medicine ,Breast-conserving surgery ,Humans ,Triple negative ,Triple-negative breast cancer ,Neoplasm Staging ,business.industry ,Cancer ,medicine.disease ,Combined Modality Therapy ,Treatment Outcome ,030104 developmental biology ,Oncology ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Female ,business ,Adjuvant - Abstract
PURPOSE: To assess potential disparities in guideline-concordant care delivery among women with early-stage triple-negative and HER2-positive breast cancer treated with breast conserving therapy. METHODS: Women ≥ 40 years old diagnosed with pT2N0M0 triple-negative or HER2-positive breast cancer treated with primary surgery and axillary staging between 2012 and 2017 were identified using the National Cancer Database (NCDB). The primary outcome was receipt of adjuvant systemic therapy and radiation concordant with current guidelines. Multivariable log-binomial regression was used to assess the prevalence of optimal therapy use across patient and cancer characteristics. Kaplan–Meier curves were used to assess 5-year overall survival. Multivariable Cox proportional hazards regression was used to compare the impact of optimal therapy on 5-year mortality. RESULTS: 11,785 women were included with 7,843 receiving optimal therapy. Receipt of optimal therapy decreased with age even after adjusting for comorbidities and cancer characteristics; other sociodemographic factors were not associated with differences in receipt of optimal therapy. Among patients who did not receive adjuvant systemic therapy, most were not offered the treatment (49%) or refused (40%). Overall 5-year survival was higher among women who received optimal therapy (89% [95% CI 88.0–89.3] vs. 66% [95% CI 62.9–68.5]). Patients who received suboptimal therapy were over twice as likely to die within 5 years of their diagnosis (adjusted HR 2.44, 95% CI 2.12–2.82). CONCLUSION: Age is the primary determinant of the likelihood of a woman to receive optimal adjuvant therapies in high-risk early-stage breast cancer. Patients who did not receive optimal therapy had significantly diminished survival.
- Published
- 2021
47. FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036
- Author
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Gaurav Mehta, Gary L. Johnson, Lynn Chollet-Hinton, Stuart R. Jefferys, Joel S. Parker, Andres Forero-Torres, Timothy J. Stuhlmiller, Ian E. Krop, Xiaping He, Charles M. Perou, Kristalyn K. Gallagher, Noah Sciaky, Daniel R. Goulet, Steven P. Angus, Alastair M. Thompson, Maki Tanioka, J. Felix Olivares-Quintero, Cheng Fan, Lisa A. Carey, Rashmi Krishna Murthy, Darshan Singh, Matthew G. Soloway, H. Shelton Earp, Xin Chen, Jon S. Zawistowski, Patricia A. Spears, Michael L. Gatza, Naim U. Rashid, Michael P. East, and Samantha M. Bevill
- Subjects
0301 basic medicine ,Tumour heterogeneity ,medicine.drug_class ,medicine.medical_treatment ,Lapatinib ,Monoclonal antibody ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Trastuzumab ,medicine ,Pharmacology (medical) ,Radiology, Nuclear Medicine and imaging ,skin and connective tissue diseases ,neoplasms ,RC254-282 ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Pertuzumab ,FOXA1 ,business ,medicine.drug - Abstract
Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes. Motif analysis of lapatinib-responsive genomic regions implicated the pioneer transcription factor FOXA1 as a mediator of adaptive responses. Lapatinib in combination with FOXA1 depletion led to dysregulation of enhancers, impaired adaptive upregulation of HER3, and decreased proliferation. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. This highlights the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy.
- Published
- 2021
48. Human Hepatic CD56bright NK Cells Display a Tissue-Resident Transcriptional Profile and Enhanced Ability to Kill Allogenic CD8+ T Cells
- Author
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Gráinne Jameson, Cathal Harmon, Rhyla Mae Santiago, Diarmaid D. Houlihan, Tom K. Gallagher, Lydia Lynch, Mark W. Robinson, and Cliona O’Farrelly
- Subjects
Immunology ,Immunology and Allergy - Abstract
Liver-resident CD56brightCD16-natural killer (NK) cells are enriched in the human liver and are phenotypically distinct from their blood counterparts. Although these cells are capable of rapid cytotoxic effector activity, their functional role remains unclear. We hypothesise that they may contribute to immune tolerance in the liver during transplantation. RNA sequencing was carried out on FACS sorted NK cell subpopulations from liver perfusates (n=5) and healthy blood controls (n=5). Liver-resident CD56brightCD16+/-NK cells upregulate genes associated with tissue residency. They also upregulate expression ofCD160andLY9, both of which encode immune receptors capable of activating NK cells. Co-expression of CD160 and Ly9 on liver-resident NK cells was validated using flow cytometry. Hepatic NK cell cytotoxicity against allogenic T cells was tested using anin vitroco-culture system of liver perfusate-derived NK cells and blood T cells (n=10-13). In co-culture experiments, hepatic NK cells but not blood NK cells induced significant allogenic T cell death (p=0.0306). Allogenic CD8+T cells were more susceptible to hepatic NK cytotoxicity than CD4+T cells (pbrightNK cells with an anti-CD160 agonist mAb enhanced this cytotoxic response (p=0.0382). Our results highlight a role for donor liver NK cells in regulating allogenic CD8+T cell activation, which may be important in controlling recipient CD8+T cell-mediated rejection post liver-transplant.
- Published
- 2022
49. Risk of pancreatic ductal adenocarcinoma associated with carriage of BRCA1 and/or BRCA2 mutation: A systematic review and meta-analysis
- Author
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Jennifer L. McGarry, Ben Creavin, Michael E. Kelly, and Tom K. Gallagher
- Subjects
BRCA2 Protein ,Pancreatic Neoplasms ,Oncology ,BRCA1 Protein ,Mutation ,Pancreatic Ducts ,Humans ,Surgery ,General Medicine ,Germ-Line Mutation ,Carcinoma, Pancreatic Ductal - Abstract
Germline BRCA1/2 mutations lead to malfunction of DNA damage repair pathways and predispose to pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to synthesise the available research on this topic. Four studies reporting risk ratio (RR) were included in the final meta-analysis to minimise misrepresenting our results by combining separate risk estimates. Our meta-analysis revealed a statistically significant increased risk of PDAC in BRCA carriers overall (RR: 2.65, 95% confidence interval: 1.43-4.91, p = 0.002).
- Published
- 2022
50. Abstract PS1-15: Does breast cancer subtype impact margin status in patients undergoing partial mastectomy?
- Author
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Maria E. Herrera, Edward A. Levine, Ming Xie, Sonali V Pandya, Naveenraj L. Solomon, Alliric I. Willis, Anees B. Chagpar, Andrew Fenton, Brian Yoder, Fangyong Li, David W. Ollila, Marissa Howard-McNatt, Theodore N. Tsangaris, Noreen E. McGowan, Maheswari Senthil, Melissa Lazar, Tara McPartland, Mary Murray, David Edmonson, Hongwei Ma, Carlos Garcia-Cantu, Elisabeth Dupont, Yoana P. Avitan, Kristalyn K. Gallagher, Ricardo Martinez, Eric Brown, Amanda Mendiola, Adam C. Berger, Jukes P. Namm, Victor Haddad, Akiko Chiba, Laura Walters, M Butler, Sharon S. Lum, and Jennifer Gass
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Partial mastectomy ,Cancer ,Breast cancer subtype ,Margin status ,medicine.disease ,Breast cancer ,Internal medicine ,Statistical significance ,Cohort ,medicine ,business ,Neoadjuvant therapy - Abstract
BACKGROUND: It is known that breast cancer subtype (e.g., luminal vs. triple negative (TN)) can affect response to systemic therapy and prognosis; however, it is less well-understood whether these subtypes affect margin status and should therefore alter surgical management. METHODS: Data from two randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. The data were restricted to patients who had invasive carcinoma present in the PM specimen, and in whom data for all three receptors (ER, PR and HER-2) were known. Patients were classified as luminal if they were ER and/or PR+, HER-2 enriched if they were ER and PR negative but HER-2 positive, and TN if they were negative for all three receptors. We evaluated the impact of subtype on the margin status at the time the surgeon had completed their standard PM, prior to randomization to CSM vs. no CSM. Non-parametric statistical analyses were performed using SPSS Version 26. RESULTS: 350 patients were included in this cohort for analysis. The median patient age was 64 (range; 32-94 years) and the median invasive tumor size was 1.2 cm (range; 0.6-8.0 cm). 326 (93.1%) were luminal type, 22 (6.3%) were triple negative, and 2 (0.6%) were HER-2 enriched. Subtype was significantly correlated with race (black patients were more likely to have TN disease than white patients, 22.2% vs. 3.8%, p=0.001), palpability (TN tumors were more likely to be palpable than luminal cancers 54.5% vs. 29.8%, p=0.007) and grade (78.9% of TN cancers were high grade vs. 13.5% of luminal cancers p0.05 for all). While patients with TN and HER-2 enriched tumors were more likely to receive neoadjuvant therapy, this did not reach statistical significance (p=0.117). Surgeons were no more likely to take selective margins on the basis of molecular subtype (p=0.413). In this cohort, the overall positive margin rate was 33.7%. This did not vary based on molecular subtype (positive margin rate: 33.7% for patients with luminal tumors vs. 36.4% for those with TN tumors, p=0.425). On multivariate regression controlling for molecular subtype, race, grade and palpability, the only factor which predicted positive margin status was grade (p=0.005), with high grade tumors being significantly more likely to have a positive margin than low grade tumors, independent of other factors (OR=3.503, 95% CI: 1.638-7.494, p=0.001). CONCLUSION: While molecular subtype correlates with race, tumor grade and palpability, it does not predict margin status. Therefore, molecular subtype should not, independent of other factors, influence surgical decision-making. Citation Format: Andrew Fenton, Elisabeth Dupont, Theodore Tsangaris, Carlos Garcia-Cantu, Marissa Howard-McNatt, Akiko Chiba, Adam Berger, Edward Levine, Jennifer Gass, Kristalyn Gallagher, Sharon Lum, Ricardo Martinez, Alliric Willis, Sonali Pandya, Eric Brown, Amanda Mendiola, Mary Murray, Naveenraj Solomon, Maheswari Senthil, David Ollila, David Edmonson, Melissa Lazar, Jukes Namm, Fangyong Li, Meghan Butler, Noreen McGowan, Maria Herrera, Yoana Avitan, Brian Yoder, Laura Walters, Tara McPartland, Victor Haddad, Hongwei Ma, Ming Xie, Anees Chagpar. Does breast cancer subtype impact margin status in patients undergoing partial mastectomy? [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-15.
- Published
- 2021
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