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3. "Wimps need not apply!" : constructing video game developer identity

Author

Marks, K. D.

Subjects
300
Abstract

Having emerged from the self-taught hacker culture of 1980s home-computing, contemporary video game development is now a mainstream global business. Since the industry has managed to gain respectability without sacrificing credibility, it is widely perceived as both financially and intrinsically rewarding, and so has therefore become an aspirational graduate career choice. Despite such desirability, however, there is a considerable lack of diversity amongst the workforce, which consists almost entirely of young white men. Women are particularly poorly represented, not only in relation to overall employee numbers, but also in terms of their distribution across both job roles and the corporate hierarchy. Although conforming to stereotypical expectations, it is apparent that this cannot simply be attributed to inherent sex differences in ability or preference. In addition, a number of online exposés have revealed that, despite having a positive public image, extreme working hours are endemic within the industry. Rather counterintuitively, it appears that employees choose to adopt such working practices, rather than being made to. This thesis considers how such problematic issues are interrelated through the existence of a particular workplace culture, and suggests that it is both a cause and a consequence of them. In particular, it is proposed that the extreme working practices within video game development provide traditionally marginalised male groups with a resource for the social performance of a locally hegemonic form of masculine gender identity. Consequently, this suggests that there is a significant incentive for those benefiting from such masculine resources to protect them, which is likely to result in an industry culture that is hostile to feminine women. By examining the discourse within a number of social interactions that naturally occur at the interface between the industry and the public, this thesis considers how the maintenance of such a masculine version of 'reality' is carried out in practice. Particular attention is paid to the way in which the utilisation of dichotomous categorical stereotypes to manage local interactional issues acts to further propagate such constructs as global resources for use in future interactions. Most significantly, the application of a novel method of visual analysis to metaphorical representations of video game developers suggests that recruitment advertisements act to conflate masculinity and competence. Employees who fail to perform masculinity through the adoption of extreme working practices are therefore likely to be regarded as technically incompetent. As a consequence, women who wish to maintain their femininity will either not enter the industry at all, or remain in low status positions. Since the few women that do progress must behave like stereotypical men in order to attain positions of power, they are then unlikely to regard the culture as problematic or seek to reform it. The self-reinforcing nature of such a workplace culture offers an explanation as to why stand-alone interventions have so far had little impact on either work/life balance or female underrepresentation, and suggests that such issues cannot be addressed by simply seeking to impose a critical mass of women into the industry. Instead, it is proposed that interventions should treat these issues as mutually reinforcing, and therefore directly tackle the way in which they are linked by an industry culture that is maintained through the ongoing reproduction of various problematic discourses relating to dichotomous categorical stereotypes.

Published
2013

4. The BABAR detector

Author

Aubert, B, Bazan, A, Boucham, A, Boutigny, D, De Bonis, I, Favier, J, Gaillard, JM, Jeremie, A, Karyotakis, Y, Le Flour, T, Lees, JP, Lieunard, S, Petitpas, P, Robbe, P, Tisserand, V, Zachariadou, K, Palano, A, Chen, GP, Chen, JC, Qi, ND, Rong, G, Wang, P, Zhu, YS, Eigen, G, Reinertsen, PL, Stugu, B, Abbott, B, Abrams, GS, Amerman, L, Borgland, AW, Breon, AB, Brown, DN, Button-Shafer, J, Clark, AR, Dardin, S, Day, C, Dow, SF, Fan, Q, Gaponenko, I, Gill, MS, Goozen, FR, Gowdy, SJ, Gritsan, A, Groysman, Y, Hernikl, C, Jacobsen, RG, Jared, RC, Kadel, RW, Kadyk, J, Karcher, A, Kerth, LT, Kipnis, I, Kluth, S, Kral, JF, Lafever, R, LeClerc, C, Levi, ME, Lewis, SA, Lionberger, C, Liu, T, Long, M, Luo, L, Lynch, G, Luft, P, Mandelli, E, Marino, M, Marks, K, Matuk, C, Meyer, AB, Minor, R, Mokhtarani, A, Momayezi, M, Nyman, M, Oddone, PJ, Ohnemus, J, Oshatz, D, Patton, S, Pedrali-Noy, M, Perazzo, A, Peters, C, Pope, W, Pripstein, M, Quarrie, DR, Rasson, JE, Roe, NA, Romosan, A, Ronan, MT, Shelkov, VG, Stone, R, Strother, PD, Telnov, AV, von der Lippe, H, Weber, TF, Wenzel, WA, Zizka, G, Bright-Thomas, PG, Hawkes, CM, Kirk, A, Knowles, DJ, and O'Neale, SW

Subjects
hep-ex, Nuclear & Particles Physics, Astronomical and Space Sciences, Atomic, Molecular, Nuclear, Particle and Plasma Physics, Other Physical Sciences
Abstract

BABAR, the detector for the SLAC PEP-II asymmetric e+e- B Factory operating at the γ(4S) resonance, was designed to allow comprehensive studies of CP-violation in B-meson decays. Charged particle tracks are measured in a multi-layer silicon vertex tracker surrounded by a cylindrical wire drift chamber. Electromagnetic showers from electrons and photons are detected in an array of CsI crystals located just inside the solenoidal coil of a superconducting magnet. Muons and neutral hadrons are identified by arrays of resistive plate chambers inserted into gaps in the steel flux return of the magnet. Charged hadrons are identified by dE/dx measurements in the tracking detectors and by a ring-imaging Cherenkov detector surrounding the drift chamber. The trigger, data acquisition and data-monitoring systems, VME- and network-based, are controlled by custom-designed online software. Details of the layout and performance of the detector components and their associated electronics and software are presented. © 2002 Elsevier Science B.V. All rights reserved.

Published
2002

5. OP0015 CD38HI CYTOTOXIC CD8 T CELLS ARE EXPANDED FOLLOWING CHECKPOINT BLOCKADE AND CHARACTERIZE THE T CELL INFILTRATE IN CHECKPOINT INHIBITOR-ASSOCIATED ARTHRITIS

Author

Singaraju, A., primary, Marks, K. E., additional, Wang, R., additional, Shakib, L., additional, Dunlap, G., additional, Cunningham-Bussel, A., additional, Greisen, S. R., additional, Chen, L., additional, Tirpack, A., additional, Fein, M., additional, Adejoorin, I., additional, Todd, D., additional, Macfarlane, L., additional, Goodman, S., additional, Dicarlo, E., additional, Massarotti, E., additional, Sparks, J., additional, Jonsson, A. H., additional, Brenner, M., additional, Postow, M., additional, Chan, K. K., additional, Bass, A., additional, Rao, D., additional, and Donlin, L., additional

Published
2023
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6. Measurement of CP-Violating Asymmetries in B0 Decays to CP Eigenstates

Author

Aubert, B, Boutigny, D, De Bonis, I, Gaillard, J-M, Jeremie, A, Karyotakis, Y, Lees, JP, Robbe, P, Tisserand, V, Palano, A, Chen, GP, Chen, JC, Qi, ND, Rong, G, Wang, P, Zhu, YS, Eigen, G, Reinertsen, PL, Stugu, B, Abbott, B, Abrams, GS, Borgland, AW, Breon, AB, Brown, DN, Button-Shafer, J, Cahn, RN, Clark, AR, Dardin, S, Day, C, Dow, SF, Elioff, T, Fan, Q, Gaponenko, I, Gill, MS, Goozen, FR, Gowdy, SJ, Gritsan, A, Groysman, Y, Jacobsen, RG, Jared, RC, Kadel, RW, Kadyk, J, Karcher, A, Kerth, LT, Kipnis, I, Kluth, S, Kolomensky, Yu G, Kral, JF, Lafever, R, LeClerc, C, Levi, ME, Lewis, SA, Lionberger, C, Liu, T, Long, M, Lynch, G, Marino, M, Marks, K, Meyer, AB, Mokhtarani, A, Momayezi, M, Nyman, M, Oddone, PJ, Ohnemus, J, Oshatz, D, Patton, S, Perazzo, A, Peters, C, Pope, W, Pripstein, M, Quarrie, DR, Rasson, JE, Roe, NA, Romosan, A, Ronan, MT, Shelkov, VG, Stone, R, Telnov, AV, von der Lippe, H, Weber, T, Wenzel, WA, Zisman, MS, Bright-Thomas, PG, Harrison, TJ, Hawkes, CM, Kirk, A, Knowles, DJ, O'Neale, SW, Watson, AT, Watson, NK, Deppermann, T, Koch, H, Krug, J, Kunze, M, Lewandowski, B, Peters, K, Schmuecker, H, Steinke, M, Andress, JC, and Barlow, NR

Subjects
BABAR Collaboration, hep-ex, Mathematical Sciences, Physical Sciences, Engineering, General Physics
Abstract

We present measurements of time-dependent CP-violating asymmetries in neutral B decays to several CP eigenstates. The measurement uses a data sample of 23x10(6) Upsilon(4S)-->BbarB decays collected by the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we find events in which one neutral B meson is fully reconstructed in a CP eigenstate containing charmonium and the flavor of the other neutral B meson is determined from its decay products. The amplitude of the CP-violating asymmetry, which in the standard model is proportional to sin2beta, is derived from the decay time distributions in such events. The result is sin2beta = 0.34+/-0.20 (stat)+/-0.05 (syst).

Published
2001

12. Exclusive enteral nutrition: An optimal care pathway for use in children with active luminal Crohn's disease

Author

Burgess, D, McGrath, KH, Watson, C, Collins, T, Brown, S, Marks, K, Dehlsen, K, Herbison, K, Landorf, E, Benn, L, Fox, J, Liew, M, Burgess, D, McGrath, KH, Watson, C, Collins, T, Brown, S, Marks, K, Dehlsen, K, Herbison, K, Landorf, E, Benn, L, Fox, J, and Liew, M

Abstract

AIM: Exclusive enteral nutrition (EEN) is recommended as a first-line therapy for active luminal paediatric Crohn's disease, by many contemporary consensus guidelines. However, EEN protocols vary internationally. A key enabler for the use of EEN therapy has been identified as the standardisation of protocols. The aim of this study was to develop an optimal care pathway for use of EEN in children with active luminal Crohn's disease. METHODS: A working group of 11 paediatric gastroenterology dietitians and one paediatric gastroenterologist from Australia and New Zealand was convened to develop a standard optimal care pathway. Seven key areas were identified; clinical indications, workup assessments, EEN prescription, monitoring, food reintroduction, partial enteral nutrition and maintenance enteral nutrition. Recent literature was reviewed, assessed according to the National Health and Medical Research Council guidelines, and consensus statements were developed and voted on. Consensus opinion was used where literature gaps existed. RESULTS: A total of nineteen consensus statements from the seven key areas were agreed upon. The consensus statements informed the optimal care pathway for children with active luminal undertaking EEN in Australia and New Zealand. CONCLUSION: This study developed an EEN optimal care pathway to facilitate standardisation of clinical care for children with active luminal Crohn's disease, and hopefully improve clinical outcomes and identify areas for future research.

Published
2022

15. POS0402 CLONALLY EXPANDED CD38hi CYTOTOXIC CD8 T CELLS DEFINE THE T CELL INFILTRATE IN CHECKPOINT INHIBITOR-ASSOCIATED ARTHRITIS

Author

Wang, R., primary, Singaraju, A., additional, Marks, K. E., additional, Shakib, L., additional, Dunlap, G., additional, Cunningham-Bussel, A., additional, Greisen, S. R., additional, Chen, L., additional, Tirpack, A., additional, Fein, M., additional, Todd, D., additional, Macfarlane, L., additional, Goodman, S., additional, Dicarlo, E., additional, Massarotti, E., additional, Sparks, J., additional, Hamnvik, O. P., additional, Min, L., additional, Jonsson, A. H., additional, Brenner, M., additional, Chan, K. K., additional, Bass, A., additional, Donlin, L., additional, and Rao, D., additional

Published
2022
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16. POS1224 RHEUMATOID ARTHRITIS DISEASE ACTIVITY ASSESSED BY PATIENT-REPORTED OUTCOMES AND FLOW CYTOMETRY BEFORE AND AFTER AN ADDITIONAL DOSE OF COVID-19 VACCINE

Author

Tedeschi, S., primary, Stratton, J., additional, Ellrodt, J., additional, Whelan, M. G., additional, Hayashi, K., additional, Yoshida, K., additional, Chen, L., additional, Adejoorin, I., additional, Marks, K. E., additional, Jonsson, A. H., additional, Rao, D., additional, and Solomon, D., additional

Published
2022
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24. Large-scale discovery of novel genetic causes of developmental disorders

Author

Fitzgerald, T. W., Gerety, S. S., Jones, W. D., van Kogelenberg, M., King, D. A., McRae, J., Morley, K. I., Parthiban, V., Al-Turki, S., Ambridge, K., Barrett, D. M., Bayzetinova, T., Clayton, S., Coomber, E. L., Gribble, S., Jones, P., Krishnappa, N., Mason, L. E., Middleton, A., Miller, R., Prigmore, E., Rajan, D., Sifrim, A., Tivey, A. R., Ahmed, M., Akawi, N., Andrews, R., Anjum, U., Archer, H., Armstrong, R., Balasubramanian, M., Banerjee, R., Baralle, D., Batstone, P., Baty, D., Bennett, C., Berg, J., Bernhard, B., Bevan, A. P., Blair, E., Blyth, M., Bohanna, D., Bourdon, L., Bourn, D., Brady, A., Bragin, E., Brewer, C., Brueton, L., Brunstrom, K., Bumpstead, S. J., Bunyan, D. J., Burn, J., Burton, J., Canham, N., Castle, B., Chandler, K., Clasper, S., Clayton-Smith, J., Cole, T., Collins, A., Collinson, M. N., Connell, F., Cooper, N., Cox, H., Cresswell, L., Cross, G., Crow, Y., DʼAlessandro, M., Dabir, T., Davidson, R., Davies, S., Dean, J., Deshpande, C., Devlin, G., Dixit, A., Dominiczak, A., Donnelly, C., Donnelly, D., Douglas, A., Duncan, A., Eason, J., Edkins, S., Ellard, S., Ellis, P., Elmslie, F., Evans, K., Everest, S., Fendick, T., Fisher, R., Flinter, F., Foulds, N., Fryer, A., Fu, B., Gardiner, C., Gaunt, L., Ghali, N., Gibbons, R., Pereira, Gomes S. L., Goodship, J., Goudie, D., Gray, E., Greene, P., Greenhalgh, L., Harrison, L., Hawkins, R., Hellens, S., Henderson, A., Hobson, E., Holden, S., Holder, S., Hollingsworth, G., Homfray, T., Humphreys, M., Hurst, J., Ingram, S., Irving, M., Jarvis, J., Jenkins, L., Johnson, D., Jones, D., Jones, E., Josifova, D., Joss, S., Kaemba, B., Kazembe, S., Kerr, B., Kini, U., Kinning, E., Kirby, G., Kirk, C., Kivuva, E., Kraus, A., Kumar, D., Lachlan, K., Lam, W., Lampe, A., Langman, C., Lees, M., Lim, D., Lowther, G., Lynch, S. A., Magee, A., Maher, E., Mansour, S., Marks, K., Martin, K., Maye, U., McCann, E., McConnell, V., McEntagart, M., McGowan, R., McKay, K., McKee, S., McMullan, D. J., McNerlan, S., Mehta, S., Metcalfe, K., Miles, E., Mohammed, S., Montgomery, T., Moore, D., Morgan, S., Morris, A., Morton, J., Mugalaasi, H., Murday, V., Nevitt, L., Newbury-Ecob, R., Norman, A., OʼShea, R., Ogilvie, C., Park, S., Parker, M. J., Patel, C., Paterson, J., Payne, S., Phipps, J., Pilz, D. T., Porteous, D., Pratt, N., Prescott, K., Price, S., Pridham, A., Procter, A., Purnell, H., Ragge, N., Rankin, J., Raymond, L., Rice, D., Robert, L., Roberts, E., Roberts, G., Roberts, J., Roberts, P., Ross, A., Rosser, E., Saggar, A., Samant, S., Sandford, R., Sarkar, A., Schweiger, S., Scott, C., Scott, R., Selby, A., Seller, A., Sequeira, C., Shannon, N., Sharif, S., Shaw-Smith, C., Shearing, E., Shears, D., Simonic, I., Simpkin, D., Singzon, R., Skitt, Z., Smith, A., Smith, B., Smith, K., Smithson, S., Sneddon, L., Splitt, M., Squires, M., Stewart, F., Stewart, H., Suri, M., Sutton, V., Swaminathan, G. J., Sweeney, E., Tatton-Brown, K., Taylor, C., Taylor, R., Tein, M., Temple, I. K., Thomson, J., Tolmie, J., Torokwa, A., Treacy, B., Turner, C., Turnpenny, P., Tysoe, C., Vandersteen, A., Vasudevan, P., Vogt, J., Wakeling, E., Walker, D., Waters, J., Weber, A., Wellesley, D., Whiteford, M., Widaa, S., Wilcox, S., Williams, D., Williams, N., Woods, G., Wragg, C., Wright, M., Yang, F., Yau, M., Carter, N. P., Parker, M., Firth, H. V., FitzPatrick, D. R., Wright, C. F., Barrett, J. C., and Hurles, M. E.

Published
2015
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38. Results from the STAR TPC system test

Author

Betts, W., Bieser, F., Bossingham, R., Botlo, M., Cherney, M., Chrin, J., Colarco, P., Crawford, H., Dao, K., Diaz, H., Greiner, D.E., Greiner, L., Hjort, E.L., Jacobson, S., Jared, R.C., Judd, E., Klein, S.R., Lebedev, A.N., LeVine, M.J., Lindenstruth, V., Lisa, M.A., Marks, K., McParland, C., McShane, T.S., Meier, J., Nguyen, M.T., Olson, D.L., Sakrejda, I., Schambach, J., Scheetz, R.A., Stone, N.T.B., Tull, C.E., Visser, G., Vu, C., Wieman, H., and Yee, E.

Subjects
United States. Brookhaven National Laboratory -- Equipment and supplies, Semiconductor nuclear counters -- Design and construction, Nuclear track detectors -- Design and construction, Ion accelerators -- Equipment and supplies, Business, Electronics, Electronics and electrical industries
Abstract

A system test of various components of the Solenoidal Tracker at RHIC (STAR) detector, operating in concert, has recently come on-line. Communication between a major sub-detector, a sector of the Time Projection Chamber (TPC), and the trigger, data acquisition and slow controls systems has been established, enabling data from cosmic ray muons to be collected. First results from an analysis of the TPC data are presented. These include measurements of system noise, electronic parameters such as amplifier gains and pedestal values, and tracking resolution for cosmic ray muons and laser induced ionization tracks. A discussion on the experience gained in integrating the different components for the system test is also given.

Published
1997

39. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Author

Dennis, M, Mead, G, Forbes, J, Graham, C, Hackett, M, Hankey, GJ, House, A, Lewis, S, Lundström, E, Sandercock, P, Innes, K, Williams, C, Drever, J, Mcgrath, A, Deary, A, Fraser, R, Anderson, R, Walker, P, Perry, D, Mcgill, C, Buchanan, D, Chun, Y, Dinsmore, L, Maschauer, E, Barugh, A, Mikhail, S, Blair, G, Hoeritzauer, I, Scott, M, Fraser, G, Lawrence, K, Shaw, A, Williamson, J, Burgess, D, Macleod, M, Morales, D, Sullivan, F, Brady, M, French, R, Van Wijck, F, Watkins, C, Proudfoot, F, Skwarski, J, Mcgowan, D, Murphy, R, Burgess, S, Rutherford, W, Mccormick, K, Buchan, R, Macraild, A, Paulton, R, Fazal, A, Taylor, P, Parakramawansha, R, Hunter, N, Perry, J, Bamford, J, Waugh, D, Veraque, E, Bedford, C, Kambafwile, M, Idrovo, L, Makawa, L, Smalley, P, Randall, M, Thirugnana-Chandran, T, Hassan, A, Vowden, R, Jackson, J, Bhalla, A, Rudd, A, Tam, CK, Birns, J, Gibbs, C, Lee Carbon, L, Cattermole, E, Marks, K, Cape, A, Hurley, L, Kullane, S, Smyth, N, Eglinton, C, Wilson, J, Giallombardo, E, Frith, A, Reidy, P, Pitt, M, Sykes, L, Dellafera, D, Croome, V, Kerwood, L, Hancevic, M, Narh, C, Merritt, C, Duffy, J, Cooke, D, Willson, J, Ali, A, Naqvi, A, Kamara, C, Dennis, M, Mead, G, Forbes, J, Graham, C, Hackett, M, Hankey, GJ, House, A, Lewis, S, Lundström, E, Sandercock, P, Innes, K, Williams, C, Drever, J, Mcgrath, A, Deary, A, Fraser, R, Anderson, R, Walker, P, Perry, D, Mcgill, C, Buchanan, D, Chun, Y, Dinsmore, L, Maschauer, E, Barugh, A, Mikhail, S, Blair, G, Hoeritzauer, I, Scott, M, Fraser, G, Lawrence, K, Shaw, A, Williamson, J, Burgess, D, Macleod, M, Morales, D, Sullivan, F, Brady, M, French, R, Van Wijck, F, Watkins, C, Proudfoot, F, Skwarski, J, Mcgowan, D, Murphy, R, Burgess, S, Rutherford, W, Mccormick, K, Buchan, R, Macraild, A, Paulton, R, Fazal, A, Taylor, P, Parakramawansha, R, Hunter, N, Perry, J, Bamford, J, Waugh, D, Veraque, E, Bedford, C, Kambafwile, M, Idrovo, L, Makawa, L, Smalley, P, Randall, M, Thirugnana-Chandran, T, Hassan, A, Vowden, R, Jackson, J, Bhalla, A, Rudd, A, Tam, CK, Birns, J, Gibbs, C, Lee Carbon, L, Cattermole, E, Marks, K, Cape, A, Hurley, L, Kullane, S, Smyth, N, Eglinton, C, Wilson, J, Giallombardo, E, Frith, A, Reidy, P, Pitt, M, Sykes, L, Dellafera, D, Croome, V, Kerwood, L, Hancevic, M, Narh, C, Merritt, C, Duffy, J, Cooke, D, Willson, J, Ali, A, Naqvi, A, and Kamara, C

Abstract

Background: Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods: FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings: Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation: Fluoxetine 20 mg given daily for 6 months after acute stroke does

Published
2019

40. Benefit of Early versus Deferred Antiretroviral Therapy on Progression of Liver Fibrosis among People with HIV in the START Randomized Trial

Author

Dharan, NJ, Neuhaus, J, Rockstroh, JK, Peters, L, Gordin, F, Arenas-Pinto, A, Emerson, C, Marks, K, Hidalgo, J, Sarmento-Castro, R, Stephan, C, Kumarasamy, N, Emery, S, Matthews, GV, Dharan, NJ, Neuhaus, J, Rockstroh, JK, Peters, L, Gordin, F, Arenas-Pinto, A, Emerson, C, Marks, K, Hidalgo, J, Sarmento-Castro, R, Stephan, C, Kumarasamy, N, Emery, S, and Matthews, GV

Abstract

The role of antiretroviral therapy (ART) in reducing or contributing to liver fibrosis in persons with human immunodeficiency virus (HIV) is unclear. We evaluated participants in the Strategic Timing of AntiRetroviral Treatment (START) trial for liver fibrosis using the AST to Platelet Ratio Index (APRI) and Fibrosis-4 Index (FIB-4), and assessed for a benefit of early versus delayed ART on liver fibrosis progression. ART-naïve persons with high CD4 counts (>500 cells/µL) from 222 clinical sites in 35 countries were randomized to receive ART either at study enrollment (immediate treatment arm) or when their CD4 count fell below 350 cells/µL (deferred treatment arm). The following outcomes were evaluated: fibrosis (APRI > 0.5 or FIB-4 > 1.45), significant fibrosis (APRI > 1.5 or FIB-4 > 3.25), hepatic flare, and resolution of elevated APRI and FIB-4 scores. Of the 4,684 enrolled into the START study, 104 did not have APRI or FIB-4 results and were excluded. Among 4,580 participants (2,273 immediate treatment; 2,307 deferred treatment), the median age was 36 years, 26.9% were female, and 30.4% were black. Three percent had an alcoholism or substance abuse history, 6.4% had hepatitis B and/or C, and 1.1% had significant fibrosis at baseline. The median CD4 count was 651, and 5.3% had HIV RNA ≤ 200. Immediate arm participants were at lower risk of developing increased fibrosis scores than deferred arm participants (hazard ratio [HR] = 0.66; 95% confidence interval [CI] = 0.57-0.78; P < 0.001) and more likely to have resolution of elevated baseline scores (HR 1.6; 95% CI 1.3-1.9; P < 0.001). Conclusions: Significant liver fibrosis was rare among ART-naïve HIV-positive persons with high CD4 counts. Our findings suggest a benefit of early ART in preventing the development of liver fibrosis.

Published
2019

43. Indication of non-thermal contribution to visible femtosecond laser-induced CO oxidation on Ru(0001).

Author

Öberg, H., Gladh, J., Marks, K., Ogasawara, H., Nilsson, A., Pettersson, L. G. M., and Öström, H.

Subjects
FEMTOSECOND lasers, OXIDATION of carbon monoxide, RUTHENIUM, LASER pulses, DESORPTION, DENSITY functional theory, ADSORBATES
Abstract

We studied CO oxidation on Ru(0001) induced by 400 nm and 800 nm femtosecond laser pulses where we find a branching ratio between CO oxidation and desorption of 1:9 and 1:31, respectively, showing higher selectivity towards CO oxidation for the shorter wavelength excitation. Activation energies computed with density functional theory show discrepancies with values extracted from the experiments, indicating both a mixture between different adsorbed phases and importance of non-adiabatic effects on the effective barrier for oxidation. We simulated the reactions using kinetic modeling based on the two-temperature model of laser-induced energy transfer in the substrate combined with a friction model for the coupling to adsorbate vibrations. This model gives an overall good agreement with experiment except for the substantial difference in yield ratio between CO oxidation and desorption at 400 nm and 800 nm. However, including also the initial, non-thermal effect of electrons transiently excited into antibonding states of the O-Ru bond yielded good agreement with all experimental results. [ABSTRACT FROM AUTHOR]

Published
2015
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44. The albumin-bilirubin grade uncovers the prognostic relationship between hepatic reserve and immune dysfunction in HIV-associated hepatocellular carcinoma

Author

Pinato, DJ, Sharma, R, Citti, C, Platt, H, Ventura-Cots, M, Allara, E, Chen, T-Y, Dalla Pria, A, Jain, M, Mínguez, B, Kikuchi, L, Kaufman West, E, Merli, M, Kaplan, DE, Hasson, H, Marks, K, Nelson, M, Núñez, M, Aytaman, A, Bower, M, Bräu, N, Liver Cancer In HIV Study Group, Pinato, DJ [0000-0002-3529-0103], Ventura-Cots, M [0000-0001-9513-2855], Núñez, M [0000-0002-8187-2171], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, Carcinoma, Hepatocellular, Coinfection, Liver Neoplasms, Bilirubin, HIV Infections, Middle Aged, Prognosis, Liver Function Tests, Humans, Female, Biomarkers, Serum Albumin, Aged, Neoplasm Staging, Retrospective Studies
Abstract

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease. AIM: To evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection. METHODS: Using uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group. Patients who underwent liver transplantation were excluded. RESULTS: A total of 387 patients, predominantly HCV co-infected (78%) with balanced representation of all Barcelona Clinic Liver Cancer (BCLC) stages (A = 33%, B = 18%, C = 37%, D = 12%) were recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median duration of 8.8 years. The albumin-bilirubin grade identified significant differences in median survival of 97 months for grade 1 (95% CI 13-180 months), 17 months for grade 2 (95% CI 11-22 months) and 6 months for grade 3 (95% CI 4-9 months, P < .001). A more advanced albumin-bilirubin grade correlated with lower CD4 counts (464/373/288 cells/mm3 for grades 1/2/3) and higher HIV viraemia (3.337/8.701/61.845 copies/mL for grades 1/2/3, P < .001). CONCLUSIONS: In this large, multi-center retrospective study, the albumin-bilirubin grade highlights the interplay between liver reserve and immune dysfunction as prognostic determinants in HIV-associated HCC.

Published
2018
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45. Twenty-Five Years of Progress in Sea Floor Mapping by Satellite Altimetry

Author

Smith, W., Sandwell, D., Marks, K., and Ole Baltazar Andersen

Abstract

Although ships equipped with deep-water multi-beam echo-sounding (MBES) swath mapping systems and satellite (GPS) navigation have been around for the last 25 years, they rarely collect data in unexplored ocean areas. The most accurate and detailed sea floor sounding data are mostly confined to shallow coastal areas around developed countries, and a few deepwater areas that have been the focus of particular efforts (such as the search for the missing Malasia Airlines flight MH370 aircraft). Almost all the global ocean floor area lies more than a few hundred kilometers from the nearest GPS-navigated MBES data, and global ocean floor depth models must rely on older, low-tech single-wide-beam echo soundings recorded on analog scrolls and often positioned with only celestial navigation (most of the available data in the remote oceans was collected prior to 1965). If the ocean floor area is divided into squares one nautical mile (1.85 km) on a side, and all data, both GPS-MBES and old, low-tech data, are combined, only 8 percent of squares have any data at all. For this reason, global ocean floor mapping relies on satellite altimetry to guide the interpolation of gaps in unmapped areas. The largest variations in sea surface topography are time-invariant and exhibit geoid height anomalies produced by the Earth's gravity field. At high wavenumber (full wavelengths approximately 10 to 160 km) these anomalies are usually correlated with sea floor topography, but can also arise from sub-seafloor tectonic structure buried beneath seafloor sediment. Resolving anomalies at this scale requires satellite altimeter profiles of sea surface height along a dense network of ground tracks, so that the inter-track spacing adequately samples scales as short as 5 km or less. The first altimeter mission to yield a dense network oftracks was the European Space Agency's ERS-1 mission, completed in March of 1995. Marine gravity maps made from these data were exhibited at the Spring 1995 Americal Geophysical Union meeting, and this may have prompted the U.S. Navy to release the Geosat dense track data, collected in 1985-86 but classified Secret until July 1995. Some southern ocean Geosat data had been previously released in 1990 and 1992, allowing algorithm development for bathymetric estimation from dense track altimetry. After the 1990s there was a long period with no new dense-track altimetry, and so seafloor mapping made incremental improvements as geodesists learned to improve the along-track resolution at high wavenumber using specialized retrackers and high-data-rate filters designed to extract the seafloor topography signal. With CryoSat-2 in a long-repeat orbit since 2010, and the Jason-1, Jason-2, and SARAL/AltiKa missions also going into dense-track orbits at the end of their primary missions, there is now a rennaissance in seafloor mapping. Efforts are underway to see how manypreviously uncharted seamounts may be found, and how much resolution may be squeezed out of the newer mission data.

Published
2018

46. Finding Diagnostically Useful Patterns in Quantitative Phenotypic Data

Author

Aitken, Stuart, primary, Firth, Helen V., additional, McRae, Jeremy, additional, Halachev, Mihail, additional, Kini, Usha, additional, Parker, Michael J., additional, Lees, Melissa M., additional, Lachlan, Katherine, additional, Sarkar, Ajoy, additional, Joss, Shelagh, additional, Splitt, Miranda, additional, McKee, Shane, additional, Németh, Andrea H., additional, Scott, Richard H., additional, Wright, Caroline F., additional, Marsh, Joseph A., additional, Hurles, Matthew E., additional, FitzPatrick, David R., additional, Fitzgerald, T.W., additional, Gerety, S.S., additional, Jones, W.D., additional, van Kogelenberg, M., additional, King, D.A., additional, McRae, J., additional, Morley, K.I., additional, Parthiban, V., additional, Al-Turki, S., additional, Ambridge, K., additional, Barrett, D.M., additional, Bayzetinova, T., additional, Clayton, S., additional, Coomber, E.L., additional, Gribble, S., additional, Jones, P., additional, Krishnappa, N., additional, Mason, L.E., additional, Middleton, A., additional, Miller, R., additional, Prigmore, E., additional, Rajan, D., additional, Sifrim, A., additional, Tivey, A.R., additional, Ahmed, M., additional, Akawi, N., additional, Andrews, R., additional, Anjum, U., additional, Archer, H., additional, Armstrong, R., additional, Balasubramanian, M., additional, Banerjee, R., additional, Barelle, D., additional, Batstone, P., additional, Baty, D., additional, Bennett, C., additional, Berg, J., additional, Bernhard, B., additional, Bevan, A.P., additional, Blair, E., additional, Blyth, M., additional, Bohanna, D., additional, Bourdon, L., additional, Bourn, D., additional, Brady, A., additional, Bragin, E., additional, Brewer, C., additional, Brueton, L., additional, Brunstrom, K., additional, Bumpstead, S.J., additional, Bunyan, D.J., additional, Burn, J., additional, Burton, J., additional, Canham, N., additional, Castle, B., additional, Chandler, K., additional, Clasper, S., additional, Clayton-Smith, J., additional, Cole, T., additional, Collins, A., additional, Collinson, M.N., additional, Connell, F., additional, Cooper, N., additional, Cox, H., additional, Cresswell, L., additional, Cross, G., additional, Crow, Y., additional, D’Alessandro, P.M., additional, Dabir, T., additional, Davidson, R., additional, Davies, S., additional, Dean, J., additional, Deshpande, C., additional, Devlin, G., additional, Dixit, A., additional, Dominiczak, A., additional, Donnelly, C., additional, Donnelly, D., additional, Douglas, A., additional, Duncan, A., additional, Eason, J., additional, Edkins, S., additional, Ellard, S., additional, Ellis, P., additional, Elmslie, F., additional, Evans, K., additional, Everest, S., additional, Fendick, T., additional, Fisher, R., additional, Flinter, F., additional, Foulds, N., additional, Fryer, A., additional, Fu, B., additional, Gardiner, C., additional, Gaunt, L., additional, Ghali, N., additional, Gibbons, R., additional, Pereira, S.L. Gomes, additional, Goodship, J., additional, Goudie, D., additional, Gray, E., additional, Greene, P., additional, Greenhalgh, L., additional, Harrison, L., additional, Hawkins, R., additional, Hellens, S., additional, Henderson, A., additional, Hobson, E., additional, Holden, S., additional, Holder, S., additional, Hollingsworth, G., additional, Homfray, T., additional, Humphreys, M., additional, Hurst, J., additional, Ingram, S., additional, Irving, M., additional, Jarvis, J., additional, Jenkins, L., additional, Johnson, D., additional, Jones, D., additional, Jones, E., additional, Josifova, D., additional, Joss, S., additional, Kaemba, B., additional, Kazembe, S., additional, Kerr, B., additional, Kini, U., additional, Kinning, E., additional, Kirby, G., additional, Kirk, C., additional, Kivuva, E., additional, Kraus, A., additional, Kumar, D., additional, Lachlan, K., additional, Lam, W., additional, Lampe, A., additional, Langman, C., additional, Lees, M., additional, Lim, D., additional, Lowther, G., additional, Lynch, S.A., additional, Magee, A., additional, Maher, E., additional, Mansour, S., additional, Marks, K., additional, Martin, K., additional, Maye, U., additional, McCann, E., additional, McConnell, V., additional, McEntagart, M., additional, McGowan, R., additional, McKay, K., additional, McKee, S., additional, McMullan, D.J., additional, McNerlan, S., additional, Mehta, S., additional, Metcalfe, K., additional, Miles, E., additional, Mohammed, S., additional, Montgomery, T., additional, Moore, D., additional, Morgan, S., additional, Morris, A., additional, Morton, J., additional, Mugalaasi, H., additional, Murday, V., additional, Nevitt, L., additional, Newbury-Ecob, R., additional, Norman, A., additional, O’Shea, R., additional, Ogilvie, C., additional, Park, S., additional, Parker, M.J., additional, Patel, C., additional, Paterson, J., additional, Payne, S., additional, Phipps, J., additional, Pilz, D.T., additional, Porteous, D., additional, Pratt, N., additional, Prescott, K., additional, Price, S., additional, Pridham, A., additional, Proctor, A., additional, Purnell, H., additional, Ragge, N., additional, Rankin, J., additional, Raymond, L., additional, Rice, D., additional, Robert, L., additional, Roberts, E., additional, Roberts, G., additional, Roberts, J., additional, Roberts, P., additional, Ross, A., additional, Rosser, E., additional, Saggar, A., additional, Samant, S., additional, Sandford, R., additional, Sarkar, A., additional, Schweiger, S., additional, Scott, C., additional, Scott, R., additional, Selby, A., additional, Seller, A., additional, Sequeira, C., additional, Shannon, N., additional, Sharif, S., additional, Shaw-Smith, C., additional, Shearing, E., additional, Shears, D., additional, Simonic, I., additional, Simpkin, D., additional, Singzon, R., additional, Skitt, Z., additional, Smith, A., additional, Smith, B., additional, Smith, K., additional, Smithson, S., additional, Sneddon, L., additional, Splitt, M., additional, Squires, M., additional, Stewart, F., additional, Stewart, H., additional, Suri, M., additional, Sutton, V., additional, Swaminathan, G.J., additional, Sweeney, E., additional, Tatton-Brown, K., additional, Taylor, C., additional, Taylor, R., additional, Tein, M., additional, Temple, I.K., additional, Thomson, J., additional, Tolmie, J., additional, Torokwa, A., additional, Treacy, B., additional, Turner, C., additional, Turnpenny, P., additional, Tysoe, C., additional, Vandersteen, A., additional, Vasudevan, P., additional, Vogt, J., additional, Wakeling, E., additional, Walker, D., additional, Waters, J., additional, Weber, A., additional, Wellesley, D., additional, Whiteford, M., additional, Widaa, S., additional, Wilcox, S., additional, Williams, D., additional, Williams, N., additional, Woods, G., additional, Wragg, C., additional, Wright, M., additional, Yang, F., additional, Yau, M., additional, Carter, N.P., additional, Parker, M., additional, Firth, H.V., additional, FitzPatrick, D.R., additional, Wright, C.F., additional, Barrett, J.C., additional, and Hurles, M.E., additional

Published
2019
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48. The B AB AR detector

Author

Aubert, B., Bazan, A., Boucham, A., Boutigny, D., De Bonis, I., Favier, J., Gaillard, J.-M., Jeremie, A., Karyotakis, Y., Le Flour, T., Lees, J.P., Lieunard, S., Petitpas, P., Robbe, P., Tisserand, V., Zachariadou, K., Palano, A., Chen, G.P., Chen, J.C., Qi, N.D., Rong, G., Wang, P., Zhu, Y.S., Eigen, G., Reinertsen, P.L., Stugu, B., Abbott, B., Abrams, G.S., Amerman, L., Borgland, A.W., Breon, A.B., Brown, D.N., Button-Shafer, J., Clark, A.R., Dardin, S., Day, C., Dow, S.F., Fan, Q., Gaponenko, I., Gill, M.S., Goozen, F.R., Gowdy, S.J., Gritsan, A., Groysman, Y., Hernikl, C., Jacobsen, R.G., Jared, R.C., Kadel, R.W., Kadyk, J., Karcher, A., Kerth, L.T., Kipnis, I., Kluth, S., Kral, J.F., Lafever, R., LeClerc, C., Levi, M.E., Lewis, S.A., Lionberger, C., Liu, T., Long, M., Luo, L., Lynch, G., Luft, P., Mandelli, E., Marino, M., Marks, K., Matuk, C., Meyer, A.B., Minor, R., Mokhtarani, A., Momayezi, M., Nyman, M., Oddone, P.J., Ohnemus, J., Oshatz, D., Patton, S., Pedrali-Noy, M., Perazzo, A., Peters, C., Pope, W., Pripstein, M., Quarrie, D.R., Rasson, J.E., Roe, N.A., Romosan, A., Ronan, M.T., Shelkov, V.G., Stone, R., Strother, P.D., Telnov, A.V., von der Lippe, H., Weber, T.F., Wenzel, W.A., Zizka, G., Bright-Thomas, P.G., Hawkes, C.M., Kirk, A., Knowles, D.J., O'Neale, S.W., Watson, A.T., Watson, N.K., Deppermann, T., Koch, H., Krug, J., Kunze, M., Lewandowski, B., Peters, K., Schmuecker, H., Steinke, M., Andress, J.C., Barlow, N.R., Bhimji, W., Chevalier, N., Clark, P.J., Cottingham, W.N., De Groot, N., Dyce, N., Foster, B., Mass, A., McFall, J.D., Wallom, D., Wilson, F.F., Abe, K., Hearty, C., McKenna, J.A., Thiessen, D., Camanzi, B., Harrison, T.J., McKemey, A.K., Tinslay, J., Antohin, E.I., Blinov, V.E., Bukin, A.D., Bukin, D.A., Buzykaev, A.R., Dubrovin, M.S., Golubev, V.B., Ivanchenko, V.N., Kolachev, G.M., Korol, A.A., Kravchenko, E.A., Mikhailov, S.F., Onuchin, A.P., Salnikov, A.A., Serednyakov, S.I., Skovpen, Yu.I., Telnov, V.I., Yushkov, A.N., Booth, J., Lankford, A.J., Mandelkern, M., Pier, S., Stoker, D.P., Zioulas, G., Ahsan, A., Arisaka, K., Buchanan, C., Chun, S., Faccini, R., MacFarlane, D.B., Prell, S.A., Rahatlou, Sh., Raven, G., Sharma, V., Burke, S., Callahan, D., Campagnari, C., Dahmes, B., Hale, D., Hart, P.A., Kuznetsova, N., Kyre, S., Levy, S.L., Long, O., Lu, A., May, J., Richman, J.D., Verkerke, W., Witherell, M., Yellin, S., Beringer, J., DeWitt, J., Dorfan, D.E., Eisner, A.M., Frey, A., Grillo, A.A., Grothe, M., Heusch, C.A., Johnson, R.P., Kroeger, W., Lockman, W.S., Pulliam, T., Rowe, W., Sadrozinski, H., Schalk, T., Schmitz, R.E., Schumm, B.A., Seiden, A., Spencer, E.N., Turri, M., Walkowiak, W., Wilder, M., Williams, D.C., Chen, E., Dubois-Felsmann, G.P., Dvoretskii, A., Hanson, J.E., Hitlin, D.G., Kolomensky, Yu.G., Metzler, S., Oyang, J., Porter, F.C., Ryd, A., Samuel, A., Weaver, M., Yang, S., Zhu, R.Y., Devmal, S., Geld, T.L., Jayatilleke, S., Jayatilleke, S.M., Mancinelli, G., Meadows, B.T., Sokoloff, M.D., Bloom, P., Broomer, B., Erdos, E., Fahey, S., Ford, W.T., Gaede, F., van Hoek, W.C., Johnson, D.R., Michael, A.K., Nauenberg, U., Olivas, A., Park, H., Rankin, P., Roy, J., Sen, S., Smith, J.G., Wagner, D.L., Blouw, J., Harton, J.L., Krishnamurthy, M., Soffer, A., Toki, W.H., Warner, D.W., Wilson, R.J., Zhang, J., Brandt, T., Brose, J., Dahlinger, G., Dickopp, M., Dubitzky, R.S., Eckstein, P., Futterschneider, H., Kocian, M.L., Krause, R., Müller-Pfefferkorn, R., Schubert, K.R., Schwierz, R., Spaan, B., Wilden, L., Behr, L., Bernard, D., Bonneaud, G.R., Brochard, F., Cohen-Tanugi, J., Ferrag, S., Fouque, G., Gastaldi, F., Matricon, P., Mora de Freitas, P., Renard, C., Roussot, E., T'Jampens, S., Thiebaux, C., Vasileiadis, G., Verderi, M., Anjomshoaa, A., Bernet, R., Di Lodovico, F., Muheim, F., Playfer, S., Swain, J.E., Falbo, M., Bozzi, C., Dittongo, S., Folegani, M., Piemontese, L., Ramusino, A.C., Treadwell, E., Anulli, F., Baldini-Ferroli, R., Calcaterra, A., de Sangro, R., Falciai, D., Finocchiaro, G., Patteri, P., Peruzzi, I.M., Piccolo, M., Xie, Y., Zallo, A., Bagnasco, S., Buzzo, A., Contri, R., Crosetti, G., Fabbricatore, P., Farinon, S., Lo Vetere, M., Macri, M., Minutoli, S., Monge, M.R., Musenich, R., Pallavicini, M., Parodi, R., Passaggio, S., Pastore, F.C., Patrignani, C., Pia, M.G., Priano, C., Robutti, E., Santroni, A., Bartoldus, R., Dignan, T., Hamilton, R., Mallik, U., Cochran, J., Crawley, H.B., Fischer, P.A., Lamsa, J., McKay, R., Meyer, W.T., Rosenberg, E.I., Albert, J.N., Beigbeder, C., Benkebil, M., Breton, D., Cizeron, R., Du, S., Grosdidier, G., Hast, C., Höcker, A., Lacker, H.M., LePeltier, V., Lutz, A.M., Plaszczynski, S., Schune, M.H., Trincaz-Duvoid, S., Truong, K., Valassi, A., Wormser, G., Alford, O., Behne, D., Bionta, R.M., Bowman, J., Brigljević, V., Brooks, A., Dacosta, V.A., Fackler, O., Fujino, D., Harper, M., Lange, D.J., Mugge, M., O'Connor, T.G., Olson, H., Ott, L., Parker, E., Pedrotti, B., Roeben, M., Shi, X., van Bibber, K., Wenaus, T.J., Wright, D.M., Wuest, C.R., Yamamoto, B., Carroll, M., Cooke, P., Fry, J.R., Gabathuler, E., Gamet, R., George, M., Kay, M., McMahon, S., Muir, A., Payne, D.J., Sloane, R.J., Sutcliffe, P., Touramanis, C., Aspinwall, M.L., Bowerman, D.A., Dauncey, P.D., Eschrich, I., Gunawardane, N.J.W., Martin, R., Nash, J.A., Price, D.R., Sanders, P., Smith, D., Azzopardi, D.E., Back, J.J., Dixon, P., Harrison, P.F., Newman-Coburn, D., Potter, R.J.L., Shorthouse, H.W., Williams, M.I., Vidal, P.B., Cowan, G., George, S., Green, M.G., Kurup, A., Marker, C.E., McGrath, P., McMahon, T.R., Salvatore, F., Scott, I., Vaitsas, G., Brown, D., Davis, C.L., Li, Y., Pavlovich, J., Allison, J., Barlow, R.J., Boyd, J.T., Fullwood, J., Jackson, F., Khan, A., Lafferty, G.D., Savvas, N., Simopoulos, E.T., Thompson, R.J., Weatherall, J.H., Bard, R., Dallapiccola, C., Farbin, A., Jawahery, A., Lillard, V., Olsen, J., Roberts, D.A., Schieck, J.R., Blaylock, G., Flood, K.T., Hertzbach, S.S., Kofler, R., Lin, C.S., Willocq, S., Wittlin, J., Brau, B., Cowan, R., Taylor, F., Yamamoto, R.K., Britton, D.I., Fernholz, R., Houde, M., Milek, M., Patel, P.M., Trischuk, J., Lanni, F., Palombo, F., Bauer, J.M., Booke, M., Cremaldi, L., Kroeger, R., Reep, M., Reidy, J., Sanders, D.A., Summers, D.J., Arguin, J.F., Beaulieu, M., Martin, J.P., Nief, J.Y., Seitz, R., Taras, P., Woch, A., Zacek, V., Nicholson, H., Sutton, C.S., Cartaro, C., Cavallo, N., De Nardo, G., Fabozzi, F., Gatto, C., Lista, L., Piccolo, D., Sciacca, C., Cason, N.M., LoSecco, J.M., Alsmiller, J.R.G., Gabriel, T.A., Handler, T., Heck, J., Iwasaki, M., Sinev, N.B., Caracciolo, R., Colecchia, F., Dal Corso, F., Galeazzi, F., Marzolla, M., Michelon, G., Morandin, M., Posocco, M., Rotondo, M., Santi, S., Simonetto, F., Stroili, R., Torassa, E., Voci, C., Bailly, P., Benayoun, M., Briand, H., Chauveau, J., David, P., De la Vaissière, C., Del Buono, L., Genat, J.-F., Hamon, O., Leruste, Ph., Le Diberder, F., Lebbolo, H., Lory, J., Martin, L., Martinez-Vidal, F., Roos, L., Stark, J., Versillé, S., Zhang, B., Manfredi, P.F., Ratti, L., Re, V., Speziali, V., Frank, E.D., Gladney, L., Guo, Q.H., Panetta, J.H., Angelini, C., Batignani, G., Bettarini, S., Bondioli, M., Bosi, F., Carpinelli, M., Forti, F., Gaddi, A., Gagliardi, D., Giorgi, M.A., Lusiani, A., Mammini, P., Morganti, M., Morsani, F., Neri, N., Profeti, A., Paoloni, E., Raffaelli, F., Rama, M., Rizzo, G., Sandrelli, F., Simi, G., Triggiani, G., Haire, M., Judd, D., Paick, K., Turnbull, L., Wagoner, D.E., Albert, J., Bula, C., Kelsey, M.H., Lu, C., McDonald, K.T., Miftakov, V., Sands, B., Schaffner, S.F., Smith, A.J.S., Tumanov, A., Varnes, E.W., Bronzini, F., Buccheri, A., Bulfon, C., Cavoto, G., del Re, D., Ferrarotto, F., Ferroni, F., Fratini, K., Lamanna, E., Leonardi, E., Mazzoni, M.A., Morganti, S., Piredda, G., Safai Tehrani, F., Serra, M., Voena, C., Waldi, R., Jacques, P.F., Kalelkar, M., Plano, R.J., Adye, T., Claxton, B., Dowdell, J., Egede, U., Franek, B., Galagedera, S., Geddes, N.I., Gopal, G.P., Kay, J., Lidbury, J., Madani, S., Metcalfe, S., Markey, G., Olley, P., Watt, M., Xella, S.M., Aleksan, R., Besson, P., Bourgeois, P., Convert, P., De Domenico, G., de Lesquen, A., Emery, S., Gaidot, A., Ganzhur, S.F., Georgette, Z., Gosset, L., Graffin, P., Hamel de Monchenault, G., Hervé, S., Karolak, M., Kozanecki, W., Langer, M., London, G.W., Marques, V., Mayer, B., Micout, P., Mols, J.P., Mouly, J.P., Penichot, Y., Rolquin, J., Serfass, B., Toussaint, J.C., Usseglio, M., Vasseur, G., Yeche, C., Zito, M., Copty, N., Purohit, M.V., Yumiceva, F.X., Adam, I., Adesanya, A., Anthony, P.L., Aston, D., Bartelt, J., Becla, J., Bell, R., Bloom, E., Boeheim, C.T., Boyarski, A.M., Boyce, R.F., Briggs, D., Bulos, F., Burgess, W., Byers, B., Calderini, G., Chestnut, R., Claus, R., Convery, M.R., Coombes, R., Cottrell, L., Coupal, D.P., Coward, D.H., Craddock, W.W., DeBarger, S., DeStaebler, H., Dorfan, J., Doser, M., Dunwoodie, W., Dusatko, J.E., Ecklund, S., Fieguth, T.H., Freytag, D.R., Glanzman, T., Godfrey, G.L., Haller, G., Hanushevsky, A., Harris, J., Hasan, A., Hee, C., Himel, T., Huffer, M.E., Hung, T., Innes, W.R., Jessop, C.P., Kawahara, H., Keller, L., King, M.E., Klaisner, L., Krebs, H.J., Langenegger, U., Langeveld, W., Leith, D.W.G.S., Louie, S.K., Luitz, S., Luth, V., Lynch, H.L., McDonald, J., Manzin, G., Marsiske, H., Mattison, T., McCulloch, M., McDougald, M., McShurley, D., Menke, S., Messner, R., Morii, M., Mount, R., Muller, D.R., Nelson, D., Nordby, M., O'Grady, C.P., Olavson, L., O'Neill, F.G., Oxoby, G., Paolucci, P., Pavel, T., Perl, J., Pertsova, M., Petrak, S., Putallaz, G., Raines, P.E., Ratcliff, B.N., Reif, R., Robertson, S.H., Rochester, L.S., Roodman, A., Russel, J.J., Sapozhnikov, L., Saxton, O.H., Schietinger, T., Schindler, R.H., Schwiening, J., Sciolla, G., Seeman, J.T., Serbo, V.V., Shapiro, S., Skarpass Sr, K., Snyder, A., Soderstrom, E., Soha, A., Spanier, 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Published
2002
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50. Week 96 results of the randomized, multicentre Maraviroc Switch (MARCH) study

Author

Pett, SL, Amin, J, Horban, A, Andrade-Villanueva, J, Losso, M, Porteiro, N, Madero, JS, Belloso, W, Tu, E, Silk, D, Kelleher, A, Harrigan, R, Clark, A, Sugiura, W, Wolff, M, Gill, J, Gatell, J, Clarke, A, Ruxrungtham, K, Prazuck, T, Kaiser, R, Woolley, I, Alberto Arnaiz, J, Cooper, D, Rockstroh, JK, Mallon, P, Emery, S, Fisher, M, Rockstroh, J, Stellbrink, J, Merlin, K, Yeung, J, Fsadni, B, Marks, K, Suzuki, K, Rismanto, N, Salomon, H, Rubio, AE, Chibo, D, Birch, C, Swenson, L, Chan, D, Berg, T, Obermeier, M, Schuelter, E, Aragon, SS, Luebke, N, Coughlan, S, Dean, J, Iwatani, Y, Teran, GR, Avila, S, Sirivichayakul, S, Naphassanant, M, Ubolyam, S, Kaye, S, Land, S, Walker, S, Haubrich, R, DeJesus, E, Berthon-Jones, N, Espinosa, N, Courtney-Vega, K, Absar, N, Haskelberg, H, Robson, R, Donaldson, A, Guelman, D, Gambardella, L, Valdovinos, M, Arnaiz, J, Beleta, H, Ramos, N, Targa, M, Späth, B, Boesecke, C, Engelhardt, A, Perry, N, Beckthold, B, Drummond, F, Lefevre, E, Corr, S, Grant, C, Lupo, S, Peroni, L, Sanchez, M, De Paz Sierra, M, Viloria, G, Parlante, A, Bissio, E, Luchetti, P, Confalonieri, V, Warley, E, Vieni, I, Vilas, C, Zarate, A, Mayer, G, Elliot, J, Hagenauer, M, Kelley, M, Pett, SL, Amin, J, Horban, A, Andrade-Villanueva, J, Losso, M, Porteiro, N, Madero, JS, Belloso, W, Tu, E, Silk, D, Kelleher, A, Harrigan, R, Clark, A, Sugiura, W, Wolff, M, Gill, J, Gatell, J, Clarke, A, Ruxrungtham, K, Prazuck, T, Kaiser, R, Woolley, I, Alberto Arnaiz, J, Cooper, D, Rockstroh, JK, Mallon, P, Emery, S, Fisher, M, Rockstroh, J, Stellbrink, J, Merlin, K, Yeung, J, Fsadni, B, Marks, K, Suzuki, K, Rismanto, N, Salomon, H, Rubio, AE, Chibo, D, Birch, C, Swenson, L, Chan, D, Berg, T, Obermeier, M, Schuelter, E, Aragon, SS, Luebke, N, Coughlan, S, Dean, J, Iwatani, Y, Teran, GR, Avila, S, Sirivichayakul, S, Naphassanant, M, Ubolyam, S, Kaye, S, Land, S, Walker, S, Haubrich, R, DeJesus, E, Berthon-Jones, N, Espinosa, N, Courtney-Vega, K, Absar, N, Haskelberg, H, Robson, R, Donaldson, A, Guelman, D, Gambardella, L, Valdovinos, M, Arnaiz, J, Beleta, H, Ramos, N, Targa, M, Späth, B, Boesecke, C, Engelhardt, A, Perry, N, Beckthold, B, Drummond, F, Lefevre, E, Corr, S, Grant, C, Lupo, S, Peroni, L, Sanchez, M, De Paz Sierra, M, Viloria, G, Parlante, A, Bissio, E, Luchetti, P, Confalonieri, V, Warley, E, Vieni, I, Vilas, C, Zarate, A, Mayer, G, Elliot, J, Hagenauer, M, and Kelley, M

Abstract

Objectives: The Maraviroc Switch (MARCH) study week 48 data demonstrated that maraviroc, a chemokine receptor-5 (CCR5) inhibitor, was a safe and effective switch for the ritonavir-boosted protease inhibitor (PI/r) component of a two nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] plus PI/r-based antiretroviral regimen in patients with R5-tropic virus. Here we report the durability of this finding. Methods: MARCH, an international, multicentre, randomized, 96-week open-label switch study, enrolled HIV-1-infected adults with R5-tropic virus who were stable (> 24 weeks) and virologically suppressed [plasma viral load (pVL) < 50 HIV-1 RNA copies/mL]. Participants were randomized to continue their current PI/r-based regimen (PI/r) or to switch to MVC plus two N(t)RTIs (MVC) (1:2 randomization). The primary endpoint was the difference in the proportion with pVL < 200 copies/mL at 96 weeks. The switch arm was defined as noninferior if the lower limit of the 95% confidence interval (CI) for the difference was < −12% in the intention-to-treat (ITT) population. Safety endpoints (the difference in the mean change from baseline or a comparison of proportions) were analysed as key secondary endpoints. Results: Eighty-two (PI/r) and 156 (MVC) participants were randomized and included in the ITT analysis; 71 (87%) and 130 (83%) were in follow-up and on therapy at week 96. At week 96, 89.0% and 90.4% in the PI/r and MVC arms, respectively, had pVL < 50 copies/mL (95% CI -6.6, 10.2). Moreover, in those switching away from PI/r, there were significant reductions in mean total cholesterol (differences 0.31 mmol/L; P = 0.02) and triglycerides (difference 0.44 mmol/L; P < 0.001). Changes in CD4 T-cell count, renal function, and serious and nonserious adverse events were similar in the two arms. Conclusions: MVC as a switch for a PI/r is safe and effective at maintaining virological suppression while having significant lipid benefits over 96 weeks.

Published
2018

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