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8. An experimental study of the role of subsurface plumbing on geothermal discharge

Author

Namiki, A, Ueno, Y, Hurwitz, S, Manga, M, Munoz-Saez, C, and Murphy, F

Subjects
plumbing system, eruption styles, geyser, fumarole, boiling spring, hot spring, Geochemistry & Geophysics, Earth Sciences, Physical Sciences
Abstract

In order to better understand the diverse discharge styles and eruption intervals observed at geothermal features, we performed three series of laboratory experiments with differing plumbing geometries. A single, straight conduit that connects a hot water bath (flask) to a vent (funnel) can originate geyser-like periodic eruptions, continuous discharge like a boiling spring, and fumarole-like steam discharge, depending on the conduit length and radius. The balance between the heat loss from the conduit walls and the heat supplied from the bottom determines whether and where water can condense which in turn controls discharge style. Next, we connected the conduit to a cold water reservoir through a branch, simulating the inflow from an external water source. Colder water located at a higher elevation than a branching point can flow into the conduit to stop the boiling in the flask, controlling the periodicity of the eruption. When an additional branch is connected to a second cold water reservoir, the two cold reservoirs can interact. Our experiments show that branching allows new processes to occur, such as recharge of colder water and escape of steam from side channels, leading to greater variation in discharge styles and eruption intervals. This model is consistent with the fact that eruption duration is not controlled by emptying reservoirs. We show how differences in plumbing geometries can explain various discharge styles and eruption intervals observed in El Tatio, Chile, and Yellowstone, USA.

Published
2016

11. Radioactivity Backgrounds in ZEPLIN-III

Author

Araujo, H. M., Akimov, D. Yu., Barnes, E. J., Belov, V. A., Bewick, A., Burenkov, A. A., Currie, V. Chepel. A., DeViveiros, L., Edwards, B., Ghag, C., Hollingsworth, A., Horn, M., Kalmus, G. E., Kobyakin, A. S., Kovalenko, A. G., Lebedenko, V. N., Lindote, A., Lopes, M. I., Luscher, R., Majewski, P., Neves, A. StJ. Murphy. F., Paling, S. M., da Cunha, J. Pinto, Preece, R., Quenby, J. J., Reichhart, L., Scovell, P. R., Silva, C., Solovov, V. N., Smith, N. J. T., Smith, P. F., Stekhanov, V. N., Sumner, T. J., Thorne, C., and Walker, R. J.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment
Abstract

We examine electron and nuclear recoil backgrounds from radioactivity in the ZEPLIN-III dark matter experiment at Boulby. The rate of low-energy electron recoils in the liquid xenon WIMP target is 0.75$\pm$0.05 events/kg/day/keV, which represents a 20-fold improvement over the rate observed during the first science run. Energy and spatial distributions agree with those predicted by component-level Monte Carlo simulations propagating the effects of the radiological contamination measured for materials employed in the experiment. Neutron elastic scattering is predicted to yield 3.05$\pm$0.5 nuclear recoils with energy 5-50 keV per year, which translates to an expectation of 0.4 events in a 1-year dataset in anti-coincidence with the veto detector for realistic signal acceptance. Less obvious background sources are discussed, especially in the context of future experiments. These include contamination of scintillation pulses with Cherenkov light from Compton electrons and from $\beta$ activity internal to photomultipliers, which can increase the size and lower the apparent time constant of the scintillation response. Another challenge is posed by multiple-scatter $\gamma$-rays with one or more vertices in regions that yield no ionisation. If the discrimination power achieved in the first run can be replicated, ZEPLIN-III should reach a sensitivity of $\sim 1 \times 10^{-8}$ pb$\cdot$year to the scalar WIMP-nucleon elastic cross-section, as originally conceived., Comment: 12 pages, 5 figures

Published
2011
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17. Imagine How Good That Feels: The Impact of Anticipated Positive Emotions on Motivation for Reward Activities

Author

Heise, M, Werthmann, J, Murphy, F, Tuschen-Caffier, B, Renner, F, Heise, M [0000-0003-2650-8681], Werthmann, J [0000-0002-2312-1249], Murphy, Fionnuala [0000-0001-9180-0174], Renner, F [0000-0002-1692-449X], Apollo - University of Cambridge Repository, and Murphy, F [0000-0001-9180-0174]

Subjects
Motivation, Prospective mental imagery, Clinical Psychology, Episodic simulation, Major depression, Guided imagery, Experimental and Cognitive Psychology, Behavioral activation
Abstract

Funder: Albert-Ludwigs-Universität Freiburg im Breisgau (1016), Background Disease burden and unsatisfactory treatment outcomes call for innovation in treatments of depression. Prospective mental imagery, i.e. future-directed voluntary imagery-based thought, about potentially-rewarding activities may offer a mechanistically-informed intervention that targets deficits in reward processing, a core clinical feature of depression. We propose that the previously described impact of prospective mental imagery on motivation for everyday activities is facilitated by affective forecasting, i.e. predictions about an individual’s emotional response to the imagined activities. Methods Participants (N = 120) self-nominated six activities to engage in over the following week and were randomized to either: (1) an affective forecasting imagery condition (n = 40); (2) a neutral process imagery condition (n = 40); or (3) a no-imagery control condition (n = 40). Results As predicted, increases in motivation ratings from pre to post experimental manipulation were significantly higher following affective forecasting imagery compared to both neutral process imagery (d = 0.62) and no-imagery (d = 0.91). Contrary to predictions, the number of activities participants engaged in did not differ between conditions. Conclusions Results provide initial evidence for a potentially important role of affective forecasting in prospective mental imagery. We discuss how these findings can inform future research aiming to harness prospective mental imagery’s potential for clinical applications.

Published
2022

20. Within-diver variability in venous gas emboli (VGE) following repeated dives.

Author

Doolette, David J. and Murphy, F. Gregory

Abstract

Introduction: Venous gas emboli (VGE) are widely used as a surrogate endpoint instead of decompression sickness (DCS) in studies of decompression procedures. Peak post-dive VGE grades vary widely following repeated identical dives but little is known about how much of the variability in VGE grades is proportioned between-diver and within-diver. Methods: A retrospective analysis of 834 man-dives on six dive profiles with post-dive VGE measurements was conducted under controlled laboratory conditions. Among these data, 151 divers did repeated dives on the same profile on two to nine occasions separated by at least one week (total of 693 man-dives). Data were analysed for between- and within-diver variability in peak post-dive VGE grades using mixed-effect models with diver as the random variable and associated intraclass correlation coefficients. Results: Most divers produced a wide range of VGE grades after repeated dives on the same profile. The intraclass correlation coefficient (repeatability) was 0.33 indicating that 33% of the variability in VGE grades is between-diver variability; correspondingly, 67% of variability in VGE grades is within-diver variability. DCS cases were associated with an individual diver's highest VGE grades and not with their lower VGE grades. Conclusions: These data demonstrate large within-diver variability in VGE grades following repeated dives on the same dive profile and suggest there is substantial within-diver variability in susceptibility to DCS. Post-dive VGE grades are not useful for evaluating decompression practice for individual divers. [ABSTRACT FROM AUTHOR]

Published
2023
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21. L'anglais en IFSI : Lexique des appareils / systèmes corporels

Author

Murphy, F. C., Murphy, F. C., Murphy, F. C., and Murphy, F. C.

Abstract

Français-anglais / Anglais-français Ce lexique bilingue, destiné avant tout aux étudiants en IFSI et aux infirmiers, s’adresse également à tous les autres professionnels de la santé qui désirent exercer à l’étranger. Les + : Llivre pratique, utile et facile à consulter L’outil indispensable de ceux qui veulent approfondir leur connaissance du français ou de l’anglais dans l’exercice de leur profession.

Published
2022

24. New perspectives on targeted therapy in ovarian cancer

Author

Coward JIG, Middleton K, and Murphy F

Subjects
Gynecology and obstetrics, RG1-991
Abstract

Jermaine IG Coward,1–3 Kathryn Middleton,1 Felicity Murphy1 1Mater Health Services, Raymond Terrace, South Brisbane, QLD, Australia; 2Inflammtion and Cancer Therapeutics Group, Mater Research, University of Queensland, Translational Research Institute, Woolloongabba, Brisbane, QLD, Australia; 3School of Medicine, University of Queensland, Brisbane, QLD, Australia Abstract: Epithelial ovarian cancer remains the most lethal gynecologic malignancy. During the last 15 years, there has been only marginal improvement in 5 year overall survival. These daunting statistics are compounded by the fact that despite all subtypes exhibiting striking heterogeneity, their systemic management remains identical. Although changes to the scheduling and administration of chemotherapy have improved outcomes to a degree, a therapeutic ceiling is being reached with this approach, resulting in a number of trials investigating the efficacy of targeted therapies alongside standard treatment algorithms. Furthermore, there is an urge to develop subtype-specific studies in an attempt to improve outcomes, which currently remain poor. This review summarizes the key studies with antiangiogenic agents, poly(adenosine diphosphate [ADP]-ribose) inhibitors, and epidermal growth factor receptor/human epidermal growth factor receptor family targeting, in addition to folate receptor antagonists and insulin growth factor receptor inhibitors. The efficacy of treatment paradigms used in non-ovarian malignancies for type I tumors is also highlighted, in addition to recent advances in appropriate patient stratification for targeted therapies in epithelial ovarian cancer. Keywords: antiangiogenic therapy, high-grade serous, low grade ovarian cancer, PARP inhibition, cancer-related inflammation

Published
2015

27. List of Contributors

Author

Abbas, B., primary, Abreu, A., additional, Adams, R., additional, Adolfsson-Erici, M., additional, Afonso, A., additional, Afonso-Olivares, C., additional, Agirbas, E., additional, Aguiló, J.M., additional, Airoldi, L., additional, Aksoy, H., additional, Albentosa, M., additional, Alcaro, L., additional, Aliani, S., additional, Al-Maslamani, I., additional, Alomar, C., additional, Altin, D., additional, Álvarez, E., additional, Amaral-Zettler, L.A., additional, Amato, E., additional, Anderson, A., additional, Andrady, A.L., additional, Andrius, G., additional, Angel, D., additional, Ariese, F., additional, Arp, H.P., additional, Asensio, M., additional, Assidqi, K., additional, Avio, C.G., additional, Aytan, U., additional, Bahri, T., additional, Baini, M., additional, Bakir, A., additional, Ball, H., additional, Baranyi, C., additional, Barboza, L.G.A., additional, Barg, U., additional, Bargelloni, L., additional, Barras, H., additional, Barrera, C., additional, Barria, P., additional, Barrows, A., additional, Barth, A., additional, Batel, A., additional, Baztan, J., additional, Baztan, P., additional, Beiras, R., additional, Benedetti, M., additional, Berber, A.A., additional, Berber, N., additional, Bergmann, M., additional, Berlino, M., additional, Berrow, S., additional, Bessa, F., additional, Besseling, E., additional, Beyer, B., additional, Binaglia, M., additional, Bizjak, T., additional, Bjorndal, K.A., additional, Blust, R., additional, Boertien, M., additional, Bolten, A.B., additional, Booth, A.M., additional, Bounoua, B., additional, Bourseau, P., additional, Brahimi, N., additional, Bramini, M., additional, Brennholt, N., additional, Breuninger, E., additional, Bried, J., additional, Broderick, A., additional, Broglio, E., additional, Browne, M.A., additional, Bruzaud, S., additional, Buceta, J., additional, Buchinger, S., additional, Budimir, S., additional, Budzin-ski, H., additional, Butter, E., additional, Cachot, J., additional, Caetano, M., additional, Callaghan, A., additional, Camedda, A., additional, Capella, S., additional, Cardelli, L., additional, Carpentieri, S., additional, Carrasco, A., additional, Carriço, R., additional, Caruso, A., additional, Cassone, A.-L., additional, Castillo, A., additional, Castro, R.O., additional, Catarino, A.I., additional, Cazenave, P.W., additional, Çelik, İ., additional, Cerralbo, P., additional, César, G., additional, Chouinard, O., additional, Chubarenko, I., additional, Chubarenko, I.P., additional, Cicero, A.M., additional, Clarindo, G., additional, Clarke, B., additional, Clérandeau, C., additional, Clüsener-Godt, M., additional, Codina-García, M., additional, Cole, M., additional, Collard, F., additional, Collignon, A., additional, Collins, T., additional, Compa, M., additional, Conan, P., additional, Constant, M., additional, Cordier, M., additional, Courtene-Jones, W., additional, Cousin, X., additional, Covelo, P., additional, Cózar, A., additional, Crichton, E., additional, Crispi, O., additional, Cronin, M., additional, Croot, P.L., additional, Cruz, M.J., additional, d’Errico, G., additional, Dâmaso, C., additional, Das, K., additional, de Alencastro, L.F., additional, de Araujo, F.V., additional, de Boer, J.F., additional, de Lucia, G.A., additional, Debeljak, P., additional, Dehaut, A., additional, Deudero, S., additional, Devrieses, L., additional, Di Vito, S., additional, Díaz, A., additional, Donohue, J., additional, Doumenq, P., additional, Doyle, T.K., additional, Dris, R., additional, Druon, J.-N., additional, Duarte, C.M., additional, Duflos, G., additional, Dumontier, M., additional, Duncan, E., additional, Dussud, C., additional, Eckerlebe, A., additional, Egelkraut-Holtus, M., additional, Eidsvoll, D.P., additional, Ek, C., additional, Elena, S., additional, Elineau, A., additional, Enevoldsen, H., additional, Eppe, G., additional, Eriksen, M., additional, Ernsteins, R., additional, Espino, M., additional, Estévez-Calvar, N., additional, Ewins, C., additional, Fabre, P., additional, Faimali, M., additional, Fattorini, D., additional, Faure, F., additional, Ferrando, S., additional, Ferreira, J.C., additional, Ferreira-da-Costa, M., additional, Fileman, E., additional, Fischer, M., additional, Fortunato, A.B., additional, Fossi, M.C., additional, Foulon, V., additional, Frank, A., additional, Frenzel, M., additional, Frère, L., additional, Frias, J.P.G.L., additional, Frick, H., additional, Froneman, P.W., additional, Gabet, V.M., additional, Gabrielsen, G.W., additional, Gago, J., additional, Gajst, T., additional, Galgani, F., additional, Gallinari, M., additional, Galloway, T.S., additional, Gamarro, E.G., additional, Gambardella, C., additional, Garaventa, F., additional, Garcia, S., additional, Garrabou, J., additional, Garrido, P., additional, Gary, S.F., additional, Gasperi, J., additional, Gaze, W., additional, Geertz, T., additional, Gelado-Caballero, M.D., additional, George, M., additional, Gercken, J., additional, Gerdts, G., additional, Ghiglione, J.-F., additional, Gies, E., additional, Gilbert, B., additional, Giménez, L., additional, Glassom, D., additional, Glockzin, M., additional, Godley, B., additional, Goede, K., additional, Goksøyr, A., additional, Gómez, M., additional, Gómez-Parra, A., additional, González-Marco, D., additional, González-Solís, J., additional, Gorbi, S., additional, Gorokhova, E., additional, Gorsky, G., additional, Gosch, M., additional, Grose, J., additional, Guebitz, G.M., additional, Guedes-Alonso, R., additional, Guijarro, B., additional, Guilhermino, L., additional, Gundry, T., additional, Gutow, L., additional, Haave, M., additional, Haeckel, M., additional, Haernvall, K., additional, Hajbane, S., additional, Hamann, M., additional, Hämer, J., additional, Hamm, T., additional, Hansen, B.H., additional, Hardesty, B.D., additional, Harth, B., additional, Hartikainen, S., additional, Hassellöv, M., additional, Hatzky, S., additional, Healy, M.G., additional, Hégaret, H., additional, Henry, T.B., additional, Hermabessiere, L., additional, Hernández-Brito, J.J., additional, Hernandez-Gonzalez, A., additional, Hernandez-Milian, G., additional, Hernd, G., additional, Herrera, A., additional, Herring, C., additional, Herzke, D., additional, Heussner, S., additional, Hidalgo-Ruz, V., additional, Himber, C., additional, Holland, M., additional, Hong, N.-H., additional, Horton, A.A., additional, Horvat, P., additional, Huck, T., additional, Huhn, M., additional, Huvet, A., additional, Iglesias, M., additional, Igor, C., additional, Isachenko, I.A., additional, Ivar do Sul, J-A., additional, Jahnke, A., additional, Janis, B., additional, Janis, K., additional, Janis, U., additional, Jemec, A., additional, Jiménez, J.C., additional, Johnsen, H., additional, Jorgensen, B., additional, Jørgensen, J.H., additional, Jörundsdóttir, H., additional, Jung, Y.-J., additional, Kedzierski, M., additional, Keiter, S., additional, Kershaw, P., additional, Kerhervé, P., additional, Kesy, K., additional, Khan, F., additional, Khatmullina, L.I., additional, Kirby, J., additional, Kiriakoulakis, K., additional, Klein, R., additional, Klunderud, T., additional, Knudsen, C.M.H., additional, Knudsen, T.B., additional, Kochleus, C., additional, Koelmans, A.A., additional, Kögel, T., additional, Koistinen, A., additional, Kopke, K., additional, Korez, Š., additional, Kowalski, N., additional, Kreikemeyer, B., additional, Kroon, F., additional, Krumpen, T., additional, Krzan, A., additional, Kržan, A., additional, Labrenz, M., additional, Lacroix, C., additional, Ladirat, L., additional, Laforsch, C., additional, Lagarde, F., additional, Lahive, E., additional, Lambert, C., additional, Lapucci, C., additional, Lattin, G., additional, Law, K.L., additional, Le Roux, F., additional, Le Souef, K., additional, Le Tilly, V., additional, Lebreton, L., additional, Leemans, E., additional, Lehtiniemi, M., additional, Lenz, M., additional, Leskinen, J., additional, Leslie, H., additional, Leslie, H.A., additional, Levasseur, C., additional, Lewis, C., additional, Licandro, P., additional, Lind, K., additional, Lindeque, P., additional, Lindeque, P.K., additional, Lips, I., additional, Liria, A., additional, Liria-Loza, A., additional, Llinás, O., additional, Loiselle, S.A., additional, Long, M., additional, Lorenz, C., additional, Lorenzo, S.M., additional, Loubar, K., additional, Luna-Jorquera, G., additional, Lusher, A.L., additional, Macchia, V., additional, MacGabban, S., additional, Mackay, K., additional, MacLeod, M., additional, Maes, T., additional, Magaletti, E., additional, Maggiore, A., additional, Magnusson, K., additional, Mahon, A.M., additional, Makorič, P., additional, Mallow, O., additional, Marques, J., additional, Marsili, L., additional, Martí, E., additional, Martignac, M., additional, Martin, J., additional, Martínez, I., additional, Martínez, J., additional, Martinez-Gil, M., additional, Martins, H.R., additional, Matiddi, M., additional, Maximenko, N., additional, Mazlum, R., additional, Mcadam, R., additional, Mcknight, L., additional, McNeal, A.W., additional, Measures, J., additional, Mederos, M.S., additional, Mendoza, J., additional, Meyer, M.S., additional, Miguelez, A., additional, Milan, M., additional, Militão, T., additional, Miller, R.Z., additional, Mino-Vercellio-Verollet, M., additional, Mir, G., additional, Miranda-Urbina, D., additional, Misurale, F., additional, Montesdeoca-Esponda, S., additional, Mora, J., additional, Morgana, S., additional, Moriceau, B., additional, Morin, B., additional, Morley, A., additional, Morrison, L., additional, Murphy, F., additional, Naidoo, T., additional, Näkki, P., additional, Napper, I.E., additional, Narayanaswamy, B.E., additional, Nash, R., additional, Negri, A., additional, Nel, H.A., additional, Nerheim, M.S., additional, Nerland, I.L., additional, Neto, J., additional, Neves, V., additional, Nies, H., additional, Noel, M., additional, Nor, N.H.M., additional, Noren, F., additional, O’ Connell, B., additional, O’ Connor, I., additional, Obbard, J.P., additional, Oberbeckmann, S., additional, Obispo, R., additional, Officer, R., additional, Ogonowski, M., additional, Orbea, A., additional, Ortlieb, M., additional, Osborn, A.M., additional, Ostiategui-Francia, P., additional, Packard, T., additional, Pahl, S., additional, Palatinus, A., additional, Palmqvist, A., additional, Pannetier, P., additional, Panti, C., additional, Parmentier, E., additional, Pasanen, P., additional, Patarnello, T., additional, Pattiaratchi, C., additional, Pauletto, M., additional, Paulus, M., additional, Pavlekovsky, K., additional, Pedersen, H.B., additional, Pedrotti, M.-L., additional, Peeken, I., additional, Peeters, D., additional, Peeters, E., additional, Pellegrini, D., additional, Perales, J.A., additional, Perez, E., additional, Perz, V., additional, Petit, S., additional, Pflieger, M., additional, Pham, C.K., additional, Piazza, V., additional, Pinto, M., additional, Planells, O., additional, Plaza, M., additional, Pompini, O., additional, Potthoff, A., additional, Prades, L., additional, Primpke, S., additional, Proietti, M., additional, Proskurowski, G., additional, Puig, C., additional, Pujo-Pay, M., additional, Pullerits, K., additional, Queirós, A.M., additional, Quinn, B., additional, Raimonds, E., additional, Ramis-Pujol, J., additional, Rascher-Friesenhausen, R., additional, Reardon, E., additional, Regoli, F., additional, Reichardt, A.M., additional, Reifferscheid, G., additional, Reilly, K., additional, Reisser, J., additional, Riba, I., additional, Ribitsch, D., additional, Rinnert, E., additional, Rios, N., additional, Rist, S.E., additional, Rivadeneira, M.M., additional, Rivière, G., additional, Robbens, J., additional, Robertson, C.J.R., additional, Rocher, V., additional, Rochman, C.M., additional, Rodrigues, M., additional, Rodriguez, Y., additional, Rodríguez, A., additional, Rodríguez, G., additional, Rodríguez, J.R.B., additional, Rodríguez, S., additional, Rodríguez, Y., additional, Rogan, E., additional, Rojo-Nieto, E., additional, Romeo, T., additional, Ross, P.S., additional, Roveta, A., additional, Rowland, S.J., additional, Ruckstuhl, N.A., additional, Ruiz-Fernández, A-C., additional, Ruiz-Orejón, L.F., additional, Runge, J., additional, Russell, M., additional, Saavedra, C., additional, Saborowski, R., additional, Sahin, B.E., additional, Sailley, S., additional, Sakaguchi-Söder, K., additional, Salaverria, I., additional, Sánchez-Arcilla, A., additional, Sánchez-Nieva, J., additional, Sanderson, W., additional, Santana-Rodríguez, J.J., additional, Santana-Viera, S., additional, Santos, M.B., additional, Santos, M.R., additional, Sanz, M.R., additional, Sardá, R., additional, Savelli, H., additional, Schoeneich-Argent, R., additional, Scholz-Böttcher, B.M., additional, Sciacca, F., additional, Scofield, R.P., additional, Setälä, O., additional, Selenius, M., additional, Sempere, R., additional, Senturk, Y., additional, Shashoua, Y., additional, Sherman, P., additional, Sick, C., additional, Siegel, D., additional, Sierra, J.P., additional, Silva, F., additional, Silvestri, C., additional, Sintija, G., additional, Sire, O., additional, Slat, B., additional, Smit, A., additional, Sobral, P., additional, Sorvari, J., additional, Sosa-Ferrera, Z., additional, Sotillo, M.G., additional, Soudant, P., additional, Speidel, L., additional, Spurgeon, D.J., additional, Steer, M.K., additional, Steindal, C.C., additional, Stifanese, R., additional, Štindlová, A., additional, Stuurman, L., additional, Suaria, G., additional, Suazo, C.G., additional, Sureda, A., additional, Surette, C., additional, Svendsen, C., additional, Syberg, K., additional, Tairova, Z., additional, Talvitie, J., additional, Tassin, B., additional, Tazerout, M., additional, Tekman, M.B., additional, ter Halle, A., additional, Thiel, M., additional, Thomas, K.V., additional, Thompson, R.C., additional, Tinkara, T., additional, Tirelli, V., additional, Tomassetti, P., additional, Toorman, E., additional, Toppe, J., additional, Tornambè, A., additional, Torres, R., additional, Torres-Padrón, M.E., additional, Underwood, A.J., additional, Urbina, M., additional, Usategui-Martín, A., additional, Usta, R., additional, Valdés, L., additional, Valente, A., additional, Valentina, T., additional, van Arkel, K., additional, Van Colen, C., additional, Van Der Hal, N., additional, van Franeker, J.A., additional, Van Herwerden, L., additional, Van Loosdrecht, M., additional, van Oyen, A., additional, Vandeperre, F., additional, Vanderlinden, J-P., additional, Vani, D., additional, Vasconcelos, L., additional, Vega-Moreno, D., additional, Ventero, A., additional, Vethaak, A.D., additional, Vianello, A., additional, Vicioso, M., additional, Vieira, L.R., additional, Viršek, M.K., additional, Vos, M., additional, Wahl, M., additional, Wallace, N., additional, Walton, A., additional, Waniek, J.J., additional, Watts, A., additional, Webster, L., additional, Wesch, C., additional, Whitfield, E., additional, Wichels, A., additional, Wieczorek, A.M., additional, Wilcox, C., additional, Williams, R.J., additional, Wong-Wah-Chung, P., additional, Wright, S., additional, Wyles, K.J., additional, Young, R., additional, Yurtsever, M., additional, Yurtsever, U., additional, Zada, L., additional, Zamani, N.P., additional, and Zampetti, G., additional

Published
2017
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30. Grouping MWCNTs based on their similar potential to cause pulmonary hazard after inhalation a case-study: a case-study

Author

Murphy, F., Jacobsen, N.R., Di Ianni, E., Johnston, H., Braakhuis, H., Peijnenburg, W.J.G.M., Oomen, A., Fernandes, T., and Stone, V.

Abstract

BackgroundThe EU-project GRACIOUS developed an Integrated Approach to Testing and Assessment (IATA) to support grouping high aspect ratio nanomaterials (HARNs) presenting a similar inhalation hazard. Application of grouping reduces the need to assess toxicity on a case-by-case basis and supports read-across of hazard data from substances that have the data required for risk assessment (source) to those that lack such data (target). The HARN IATA, based on the fibre paradigm for pathogenic fibres, facilitates structured data gathering to propose groups of similar HARN and to support read-across by prompting users to address relevant questions regarding HARN morphology, biopersistence and inflammatory potential. The IATA is structured in tiers, allowing grouping decisions to be made using simple in vitro or in silico methods in Tier1 progressing to in vivo approaches at the highest Tier3. Here we present a case-study testing the applicability of GRACIOUS IATA to form an evidence-based group of multiwalled carbon nanotubes (MWCNT) posing a similar predicted fibre-hazard, to support read-across and reduce the burden of toxicity testing.ResultsThe case-study uses data on 15 different MWCNT, obtained from the published literature. By following the IATA, a group of 2 MWCNT was identified (NRCWE006 and NM-401) based on a high degree of similarity. A pairwise similarity assessment was subsequently conducted between the grouped MWCNT to evaluate the potential to conduct read-across and fill data gaps required for regulatory hazard assessment. The similarity assessment, based on expert judgement of Tier 1 assay results, predicts both MWCNT are likely to cause a similar acute in vivo hazard. This result supports the possibility for read-across of sub-chronic and chronic hazard endpoint data for lung fibrosis and carcinogenicity between the 2 grouped MWCNT. The implications of accepting the similarity assessment based on expert judgement of the MWCNT group are considered to stimulate future discussion on the level of similarity between group members considered sufficient to allow regulatory acceptance of a read-across argument.ConclusionThis proof-of-concept case-study demonstrates how a grouping hypothesis and IATA may be used to support a nuanced and evidence-based grouping of ‘similar’ MWCNT and the subsequent interpolation of data between group members to streamline the hazard assessment process.

Published
2022

33. Glycols

Author

Forkner, Matthew W., primary, Robson, John H., additional, Snellings, William M., additional, Martin, A. E., additional, Murphy, F. H., additional, Parsons, T. E., additional, Albin, Brooke A., additional, Burgess, Lloyd M., additional, and Proulx, Grant, additional

Published
2022
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35. Overall survival (OS) with encorafenib (enco) + cetuximab (cetux) in BEACON CRC: Effect of prior therapy for BRAF V600E-mutant metastatic colorectal cancer (mCRC).

Author

Desai J., Kopetz S., Aderka D., Grothey A., Van Cutsem E., Yaeger R., Wasan H.S., Yoshino T., Ciardiello F., Chantrill L., Tebbutt N., Strickland A., Price T., Karapetis C., Murphy F., Gollerkeri A., Golden A., Edwards M.L., Tabernero J., Desai J., Kopetz S., Aderka D., Grothey A., Van Cutsem E., Yaeger R., Wasan H.S., Yoshino T., Ciardiello F., Chantrill L., Tebbutt N., Strickland A., Price T., Karapetis C., Murphy F., Gollerkeri A., Golden A., Edwards M.L., and Tabernero J.

Abstract

Background: Enco + cetux (doublet) has been approved in the US, EU, and Japan for the treatment of BRAF V600E-mutant mCRC after progression on 1-2 prior regimens. In the BEACON CRC study (NCT02928224), median OS (95% CI) with the doublet was 9.3 months (8.0-11.3) vs 5.9 months (5.1-7.1) with cetux + irinotecan or FOLFIRI (control) in patients (pts) with BRAF V600E-mutant mCRC (HR 0.61 [95% CI: 0.5-0.8]). This post hoc analysis investigates OS by prior therapies to the doublet treatment in pts with BRAF V600E-mutant mCRC from the BEACON CRC study. Methods : OS of pts treated with the doublet or control were compared according to prior treatment with bevacizumab, oxaliplatin or FOLFOXIRI and duration of prior anticancer therapy (ACT). Results : Sixty-four per cent and 55% of pts in the doublet and control arm respectively received prior bevacizumab. Of pts who had one prior therapy, 95% and 88% received prior oxaliplatin and 20% and 14% received prior FOLFOXIRI, respectively. In the doublet arm, pts who had bevacizumab < 4 months before start of study treatment had a median OS of 8.3 months (95% CI: 6.2-11.2); those who had bevacizumab >=4 months prior had a median OS of 10.7 (95% CI: 7.5-17.7). Within each treatment arm, OS was similar regardless of prior treatment with oxaliplatin or FOLFOXIRI. The duration of prior ACT was similar across study arms, ranging from 5.6 to 5.8 months for the first line of ACT. Conclusions : In the BEACON CRC study, pts treated with the doublet for BRAF V600E-mutant mCRC demonstrated similar OS regardless of prior therapies or duration of prior therapy use. This exploratory post hoc analysis provides data that reflect the prior treatment landscape clinicians may face when deciding subsequent treatment regimens for pts with BRAF V600E-mutant mCRC.

Published
2022

36. Molecular correlates of clinical benefit in previously treated patients (pts) with BRAF V600E-mutant metastatic colorectal cancer (mCRC) from the BEACON study.

Author

Desai J., Kopetz S., Murphy D.A., Pu J., Ciardiello F., Grothey A., Van Cutsem E., Wasan H.S., Yaeger R., Yoshino T., Chantrill L., Tebbutt N., Strickland A., Price T., Karapetis C., Murphy F., Donahue A.C., Golden A., Gollerkeri A., Zhu Z., Tabernero J., Desai J., Kopetz S., Murphy D.A., Pu J., Ciardiello F., Grothey A., Van Cutsem E., Wasan H.S., Yaeger R., Yoshino T., Chantrill L., Tebbutt N., Strickland A., Price T., Karapetis C., Murphy F., Donahue A.C., Golden A., Gollerkeri A., Zhu Z., and Tabernero J.

Abstract

Background: In the BEACON study, encorafenib + binimetinib + cetuximab (enco/bini/cetux; triplet) and enco + cetux (doublet) improved OS and ORR vs standard of care in previously treated BRAF V600E-mutant mCRC pts. Molecular profiling of tumours from this study was performed to identify molecular correlates of outcome. Methods : Baseline tumour samples were analysed by whole-exome sequencing (WES) and whole transcriptome sequencing (WTS). BRAF-mutant (BM) and consensus molecular subtypes (CMS) were determined and pathway activities evaluated with gene set variation analysis. Tumour response was evaluated for each subtype. Additional association and interaction analyses between molecular features and outcomes by treatments are ongoing and will be presented. Results : Baseline tumour samples were analysed by WES and/or WTS for 79.2% of pts. Of the 460 pts analysed by WTS (73.7% in the triplet arm, 66.4% in the doublet arm, 67.4% in the control arm), 84.6% were classified as CMS1 or CMS4. Overall 32.2% of pts were classified as BM1 and the majority (84.5%) of these were CMS4. Many of those classified as BM2 (67.8%) were CMS1 (64.7%). In the BM1 and CMS4 tumours, expression of inflammatory response and epithelial mesenchymal transition genes were elevated, and expression of cell cycle genes was reduced. Response rate in pts with CMS4 and/or BM1 tumors was higher in the triplet arm (CMS4: 33.3% [95% CI: 21.7-46.7]; BM1: 33.3% [95% CI: 21.4-47.1]) vs the doublet arm (CMS4: 19.2% [95% CI: 9.6-32.5]; BM1: 14.9% [95% CI: 6.2-28.3]). Conclusions : Molecular characteristics and biological properties observed in BRAF V600E-mutant mCRC suggest a subset of pts with specific molecular features may derive greater clinical benefit from triplet vs doublet therapy. These findings support further investigating the biological landscape in BRAF-mutant mCRC to enable potential hypotheses for pt selection to improve clinical outcome in future studies.

Published
2022

37. Developing Integrated Approaches for Testing and Assessment (IATAs) in order to support nanomaterial safety

Author

Powell, L.G., Gillies, S., Fernandes, T.F., Murphy, F., Giubilato, E., Cazzagon, V., Hristozov, D., Pizzol, L., Blosi, M., Costa, A.L., Prina-Mello, A., Bouwmeester, H., Sarimveis, H., Janer, G., Stone, V., Powell, L.G., Gillies, S., Fernandes, T.F., Murphy, F., Giubilato, E., Cazzagon, V., Hristozov, D., Pizzol, L., Blosi, M., Costa, A.L., Prina-Mello, A., Bouwmeester, H., Sarimveis, H., Janer, G., and Stone, V.

Abstract

Due to the unique characteristics of nanomaterials (NM) there has been an increase in their use in nanomedicines and innovative medical devices (MD). Although large numbers of NMs have now been developed, comprehensive safety investigations are still lacking. Current gaps in understanding the potential mechanisms of NM-induced toxicity can make it challenging to determine the safety testing necessary to support inclusion of NMs in MD applications. This article provides guidance for implementation of pre-clinical tailored safety assessment strategies with the aim to increase the translation of NMs from bench development to clinical use. Integrated Approaches to Testing and Assessment (IATAs) are a key tool in developing these strategies. IATAs follow an iterative approach to answer a defined question in a specific regulatory context to guide the gathering of relevant information for safety assessment, including existing experimental data, integrated with in silico model predictions where available and appropriate, and/or experimental procedures and protocols for generating new data to fill gaps. This allows NM developers to work toward current guidelines and regulations, while taking NM specific considerations into account. Here, an example IATA for NMs with potential for direct blood contact was developed for the assessment of haemocompatibility. This example IATA brings together the current guidelines for NM safety assessment within a framework that can be used to guide information and data gathering for the safety assessment of intravenously injected NMs. Additionally, the decision framework underpinning this IATA has the potential to be adapted to other testing needs and regulatory contexts.

Published
2022

41. Developing Integrated Approaches for Testing and Assessment (IATAs) in order to support nanomaterial safety

Author

Powell, L. G., primary, Gillies, S., additional, Fernandes, T. F., additional, Murphy, F., additional, Giubilato, E., additional, Cazzagon, V., additional, Hristozov, D., additional, Pizzol, L., additional, Blosi, M., additional, Costa, A. L., additional, Prina-Mello, A., additional, Bouwmeester, H., additional, Sarimveis, H., additional, Janer, G., additional, and Stone, V., additional

Published
2022
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49. Application of Bayesian networks in determining nanoparticle-induced cellular outcomes using transcriptomics

Author

Furxhi, I, Murphy, F, Poland, C, Sheehan, B, Mullins, M, Mantecca, P, Furxhi I., Murphy F., Poland C. A., Sheehan B., Mullins M., Mantecca P., Furxhi, I, Murphy, F, Poland, C, Sheehan, B, Mullins, M, Mantecca, P, Furxhi I., Murphy F., Poland C. A., Sheehan B., Mullins M., and Mantecca P.

Abstract

Inroads have been made in our understanding of the risks posed to human health and the environment by nanoparticles (NPs) but this area requires continuous research and monitoring. Machine learning techniques have been applied to nanotoxicology with very encouraging results. This study deals with bridging physicochemical properties of NPs, experimental exposure conditions and in vitro characteristics with biological effects of NPs on a molecular cellular level from transcriptomics studies. The bridging is done by developing and implementing Bayesian Networks (BNs) with or without data preprocessing. The BN structures are derived either automatically or methodologically and compared. Early stage nanotoxicity measurements represent a challenge, not least when attempting to predict adverse outcomes and modeling is critical to understanding the biological effects of exposure to NPs. The preprocessed data-driven BN showed improved performance over automatically structured BN and the BN with unprocessed datasets. The prestructured BN captures inter relationships between NP properties, exposure condition and in vitro characteristics and links those with cellular effects based on statistic correlation findings. Information gain analysis showed that exposure dose, NP and cell line variables were the most influential attributes in predicting the biological effects. The BN methodology proposed in this study successfully predicts a number of toxicologically relevant cellular disrupted biological processes such as cell cycle and proliferation pathways, cell adhesion and extracellular matrix responses, DNA damage and repair mechanisms etc., with a success rate >80%. The model validation from independent data shows a robust and promising methodology for incorporating transcriptomics outcomes in a hazard and, by extension, risk assessment modeling framework by predicting affected cellular functions from experimental conditions.

Published
2019

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