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255 results on '"Larder, B."'

1. Modified Friedmann equations via conformal Bohm -- De Broglie gravity

Author

Gregori, G., Reville, B., and Larder, B.

Subjects
General Relativity and Quantum Cosmology, Astrophysics - Cosmology and Nongalactic Astrophysics, High Energy Physics - Phenomenology
Abstract

We use an alternative interpretation of quantum mechanics, based on the Bohmian trajectory approach, and show that the quantum effects can be included in the classical equation of motion via a conformal transformation on the background metric. We apply this method to the Robertson-Walker metric to derive a modified version of Friedmann's equations for a Universe consisting of scalar, spin-zero, massive particles. These modified equations include additional terms that result from the non-local nature of matter and appear as an acceleration in the expansion of the Universe. We see that the same effect may also be present in the case of an inhomogeneous expansion., Comment: Accepted for publication in ApJ

Published
2019
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3. Prediction and inference of dynamics in quantum plasmas

Author

Larder, B, Norreys, P, Graziani, F, and Gregori, G

Subjects
Quantum Physics, Plasma Physics, Materials Science, Warm Dense Matter
Abstract

Quantum plasmas arise in a range of physical contexts, from planetary interiors to Inertial Confinement Fusion experiments. We require sophisticated numerical approaches to find the structural and dynamic properties of these complex, many-body quantum systems; diverse in accuracy and applicability, these computational approaches each have their own strengths and (often ignored) weaknesses. By combining existing techniques with newly developed algorithms, this thesis addresses some weaknesses that are common to many state-of-the-art calculation methods for quantum plasmas, and opens up paths to calculating properties that were not previously accessible. The focus of the thesis is a method based on Bohmian mechanics for dynamic structure calculations; alongside this, stochastic gradient Markov Chain Monte Carlo methods are developed for inferring plasma properties from experimental data.

Published
2020

18. An update to the HIV-TRePS system: The development and evaluation of new global and local computational models to predict HIV treatment outcomes, with or without a genotype

Author

Revell, A. D., Wang, D., Wood, R., Morrow, C., Tempelman, H., Hamers, R. L., Reiss, P., van Sighem, A. I., Nelson, M., Montaner, J. S. G., Lane, H. C., Larder, B. A., Harrigan, R., de Wit, T. R., Hamers, R., Sigaloff, K., Agan, B., Marconi, V., Wegner, S., Sugiura, W., Zazzi, M., Kaiser, R., Schuelter, E., Streinu-Cercel, A., Alvarez-Uria, G., Gatell, J., Lazzari, E., Gazzard, B., Pozniak, A., Mandalia, S., Webster, D., Smith, C., Ruiz, L., Clotet, B., Staszewski, S., Torti, C., Lane, C., Metcalf, J., Perez-Elias, M. -J., Vella, S., Dettorre, G., Carr, A., Norris, R., Hesse, K., Vlahakis, E., Barth, R., Hoffmann, C., Ene, L., Dragovic, G., Diaz, R., Sucupira, C., Sued, O., Cesar, C., Madero, J. S., Emery, S., Cooper, D., Baxter, J., Monno, L., Picchio, G., Debethune, M. -P., Khabo, P., Ledwaba, L., Global Health, Infectious diseases, Amsterdam institute for Infection and Immunity, Amsterdam Public Health, and Internal medicine

Subjects
0301 basic medicine, Microbiology (medical), Genotype, Anti-HIV Agents, 030106 microbiology, Human immunodeficiency virus (HIV), Antiretroviral Therapy, HIV Infections, Biology, medicine.disease_cause, Bioinformatics, Algorithms, Health Resources, Humans, Models, Statistical, ROC Curve, Software, South Africa, Treatment Outcome, Viral Load, Antiretroviral Therapy, Highly Active, Computer Simulation, 03 medical and health sciences, 0302 clinical medicine, Models, Statistics, medicine, Pharmacology (medical), Highly Active, 030212 general & internal medicine, Hiv treatment, Genotyping, Original Research, Pharmacology, Computational model, Statistical, Random forest, Regimen, Infectious Diseases, Test set
Abstract

Objectives: Optimizing antiretroviral drug combination on an individual basis in resource-limited settings is challenging because of the limited availability of drugs and genotypic resistance testing. Here, we describe our latest computational models to predict treatment responses, with or without a genotype, and compare the potential utility of global and local models as a treatment tool for South Africa. Methods: Global random forest models were trained to predict the probability of virological response to therapy following virological failure using 29 574 treatment change episodes (TCEs) without a genotype, 3179 of which were from South Africa and were used to develop local models. In addition, 15 130 TCEs including genotypes were used to develop another set of models. The 'no-genotype' models were tested with an independent global test set (n = 1700) plus a subset from South Africa (n = 222). The genotype models were tested with 750 independent cases. Results: The global no-genotype models achieved area under the receiver-operating characteristic curve (AUC) values of 0.82 and 0.79 with the global and South African tests sets, respectively, and the South African models achieved AUCs of 0.70 and 0.79. The genotype models achieved an AUC of 0.84. The global no-genotype models identified more alternative, locally available regimens that were predicted to be effective for cases that failed their new regimen in the South African clinics than the local models. Both sets of models were significantly more accurate predictors of outcomes than genotyping with rules-based interpretation. Conclusions: These latest global models predict treatment responses accurately even without a genotype, out-performed the local South African models and have the potential to help optimize therapy, particularly in resource-limited settings.

Published
2016
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19. Development of Phenotypic and Genotypic Resistance to Antiretroviral Therapy in the UNAIDS HIV Drug Access Initiative -- Uganda [International Conference on AIDS (13th: 2000: Durban, South Africa)]

Author

Weidle, PJ | Sozi, C. | Mwebaze, R. | Bahendeka, S. | Moss, V. | Rukondo, G. | Katabira, E. | Downing, R. | Hertogs, K. | Larder, B. | Respess, R. | Ochola, D. | Samb, B. | Lackritz, Eve, Weidle, PJ | Sozi, C. | Mwebaze, R. | Bahendeka, S. | Moss, V. | Rukondo, G. | Katabira, E. | Downing, R. | Hertogs, K. | Larder, B. | Respess, R. | Ochola, D. | Samb, B. | Lackritz, Eve, Weidle, PJ | Sozi, C. | Mwebaze, R. | Bahendeka, S. | Moss, V. | Rukondo, G. | Katabira, E. | Downing, R. | Hertogs, K. | Larder, B. | Respess, R. | Ochola, D. | Samb, B. | Lackritz, Eve, and Weidle, PJ | Sozi, C. | Mwebaze, R. | Bahendeka, S. | Moss, V. | Rukondo, G. | Katabira, E. | Downing, R. | Hertogs, K. | Larder, B. | Respess, R. | Ochola, D. | Samb, B. | Lackritz, Eve

Abstract

(DLPS) 5571095.0156.026, http://name.umdl.umich.edu/5571095.0156.026, http://quod.lib.umich.edu/t/text/accesspolicy.html, Where applicable, subject to copyright. Other restrictions on distribution may apply. Please go to http://www.umdl.umich.edu/ for more information.

Published
2000

21. Closing in on HIV drug resistance

Author

Larder, B and Stammers, D

Subjects
food and beverages
Abstract

The structure of a catalytic complex of HIV-1 reverse transcriptase helps rationalize resistance mechanisms for nucleoside analog drugs.

Published
1999

22. Computational models that predict response to HIV therapy can reduce virological failure and therapy costs in resource-limited settings

Author

Revell, A, primary, Wang, D, additional, Alvarez-Uria, G, additional, Streinu-Cercel, A, additional, Ene, L, additional, Wensing, A, additional, Hamers, R, additional, Morrow, C, additional, Wood, R, additional, Tempelman, H, additional, Dewolf, F, additional, Nelson, M, additional, Montaner, J, additional, Lane, H, additional, and Larder, B, additional

Published
2012
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23. Biochemical mechanism of human immunodeficiency virus type 1 reverse transcriptase resistance to stavudine

Author

Lennerstrand, Johan, Stammers, D K, Larder, B A, Lennerstrand, Johan, Stammers, D K, and Larder, B A

Abstract

We have found a close correlation between viral stavudine (d4T) resistance and resistance to d4T-triphosphate at the human immunodeficiency virus type 1 reverse transcriptase (RT) level. RT from site-directed mutants with 69S-XX codon insertions and/or conventional zidovudine resistance mutations seems to be involved in an ATP-dependent resistance mechanism analogous to pyrophosphorolysis, whereas the mechanism for RT with the Q151M or V75T mutation appears to be independent of added ATP for reducing binding to d4T-triphosphate.

Published
2001
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24. Correlation between viral resistance to zidovudine and resistance at the reverse transcriptase level for a panel of human immunodeficiency virus type 1 mutants

Author

Lennerstrand, Johan, Hertogs, K, Stammers, D K, Larder, B A, Lennerstrand, Johan, Hertogs, K, Stammers, D K, and Larder, B A

Abstract

Using a large panel of human immunodeficiency virus type 1 site-directed mutants, we have observed a higher correlation than has previously been demonstrated between zidovudine (AZT)-triphosphate resistance data at the reverse transcriptase (RT) level and corresponding viral AZT resistance. This enhanced-resistance effect at the RT level was seen with ATP and to a lesser extent with PP(i) when ATP was added at physiological concentrations. The ATP-dependent mechanism (analogous to pyrophosphorolysis) appears to be dominant in the mutants bearing the D67N and K70R or 69 insertion mutations, whereas the Q151M mutation seems independent of ATP for decreased binding to AZT-triphosphate.

Published
2001
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25. HIV drug susceptibility and treatment response to mega-HAART regimen in patients from the Frankfurt HIV cohort

Author

UCL, Miller, V, Cozzi-Lepri, Alessandro, Hertogs, K, Gute, P, Larder, B, Bloor, S, Klauke, S, Rabenau, H, Phillips, Andrew, Staszewski, S, UCL, Miller, V, Cozzi-Lepri, Alessandro, Hertogs, K, Gute, P, Larder, B, Bloor, S, Klauke, S, Rabenau, H, Phillips, Andrew, and Staszewski, S

Abstract

Objective: To assess the relationship between viral susceptibility at baseline and virological response in human immunodeficiency virus (HIV)-infected patients treated with multi-drug salvage regimens after multiple previous treatment failures. Design: Retrospective analysis of 50 patients from the Frankfurt HIV cohort who had received treatment with a minimum of six drugs, and for whom a sample for baseline viral phenotyping was available. Methods: Viral drug susceptibility was measured retrospectively from stored samples using the Antivirogram, a recombinant virus assay based method. Virological response was defined as a viral load of <400 copies/ml at week 24. For analysis of treatment response, drop-outs were dealt with in two ways, either as failures (DAF) or censored (DAC). Several logistical regression models were applied to identify predictors of response, including baseline virus load, number of new drugs and phenotypic sensitivity scores. Results: At baseline, drug resistance was extensive: 96% of patients had viruses resistant to at least one drug class and 32% had viruses resistant to all three drug classes. In the DAF analysis, 39 patients experienced virological failure. In the DAC analysis, eight were censored and 31 patients experienced virological failure. In multivariate models that adjust for baseline viral load, the number of new drugs and total phenotypic sensitivity scores, the baseline viral load and phenotypic sensitivity score remained significantly associated with virological outcome, whereas in those adjusted for baseline viral load, the number of new drugs, NRTI phenotypic sensitivity score and PI phenotypic sensitivity score, only the latter remained significantly associated with virological outcome. Both the DAF and DAC analyses produced similar results. In all models used, virological failure was shown to be significantly associated with baseline viral load and phenotypic sensitivity score. Conclusions: In this retrospective analysis b

Published
2000

31. Laboratory Guidelines for the Practical Use of HIV Drug Resistance Tests in Patient Follow-Up

Author

Vandamme, A-M, primary, Houyez, F, additional, Bànhegyi, D, additional, Clotet, B, additional, De Schrijver, G, additional, De Smet, KAL, additional, Hall, WW, additional, Harrigan, R, additional, Hellmann, N, additional, Hertogs, K, additional, Holtzer, C, additional, Larder, B, additional, Pillay, D, additional, Race, E, additional, Schmit, J-C, additional, Schuurman, R, additional, Shulse, E, additional, Sönnerborg, A, additional, and Miller, V, additional

Published
2001
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32. A Family of Insertion Mutations between Codons 67 and 70 of Human Immunodeficiency Virus Type 1 Reverse Transcriptase Confer Multinucleoside Analog Resistance

Author

Larder, B. A., primary, Bloor, S., additional, Kemp, S. D., additional, Hertogs, Kurt, additional, Desmet, R. L., additional, Miller, V., additional, Sturmer, M., additional, Staszewski, S., additional, Ren, J., additional, Stammers, D. K., additional, Stuart, D. I., additional, and Pauwels, R., additional

Published
1999
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33. Prospective Longitudinal Analysis of Viral Load and Surrogate Markers in Relation to Clinical Progression in HIV Type 1-Infected Persons

Author

BRUISTEN, S.M., primary, FRISSEN, P.H.J., additional, VAN SWIETEN, P., additional, HARRIGAN, P.R., additional, KINGHORN, I., additional, LARDER, B., additional, WEIGEL, H.M., additional, DE VRIES, E., additional, REGEZ, R.M., additional, HENRICHS, J.H., additional, KOOT, M., additional, and HUISMAN, J.G., additional

Published
1997
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34. Human immunodeficiency virus type 1 drug susceptibility during zidovudine (AZT) monotherapy compared with AZT plus 2',3'-dideoxyinosine or AZT plus 2',3'-dideoxycytidine combination therapy. The protocol 34,225-02 Collaborative Group

Author

Larder, B A, primary, Kohli, A, additional, Bloor, S, additional, Kemp, S D, additional, Harrigan, P R, additional, Schooley, R T, additional, Lange, J M, additional, Pennington, K N, additional, and St Clair, M H, additional

Published
1996
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45. The growth and characterization of crystals of human immunodeficiency virus (HIV) reverse transcriptase

Author

Jones, E.Y., primary, Stuart, D.I., additional, Garman, E.F., additional, Griest, R., additional, Phillips, D.C., additional, Taylor, G.L., additional, Matsumoto, O., additional, Darby, G., additional, Larder, B., additional, Lowe, D., additional, Powell, K., additional, Purifoy, D., additional, Ross, C.K., additional, Somers, D., additional, Tisdale, M., additional, and Stammers, D.K., additional

Published
1993
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