Brian Wynne

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This paper surveys and interprets the attitudes of scientists to the use of flux adjustments in climate projections with coupled Atmosphere Ocean General Circulation Models. The survey is based largely on the responses of 19 climate modellers to several questions and a discussion document circulated in 1995. We interpret the responses in terms of the(More)
Dolutegravir (DTG), an unboosted HIV integrase inhibitor (INI), is metabolized by UGT1A1 and to a minor extent by CYP3A. Renal elimination of unchanged DTG is very low (< 1 %). As renal impairment may affect pharmacokinetics (PK), even for drugs primarily metabolized or secreted in bile, this study investigated the effect of renal impairment on the PK of(More)
For infectious disease dynamical models to inform policy for containment of infectious diseases the models must be able to predict; however, it is well recognised that such prediction will never be perfect. Nevertheless, the consensus is that although models are uncertain, some may yet inform effective action. This assumes that the quality of a model can be(More)
All commercially available integrase inhibitors are 2-metal binders and may be affected by co-administration with metal cations. The purpose of this study was to evaluate the effect of calcium and iron supplements on dolutegravir pharmacokinetics and strategies (dose separation and food) to attenuate the effects if significant reductions in dolutegravir(More)
AIMS The aim was to evaluate the effect of boceprevir and telaprevir on dolutegravir pharmacokinetics (PK); the effect of dolutegravir on boceprevir and telaprevir PK was assessed through comparison with historical data for each hepatitis C virus (HCV) drug's prescribing information alone. METHODS This was a single-centre, randomized, open-label,(More)
INTRODUCTION Dolutegravir (DTG) is an HIV integrase strand transfer inhibitor approved for use in combination with other antiretrovirals for the treatment of HIV-infection in adults and adolescents. Metformin is a drug frequently used in diabetic HIV-infected patients, which requires titration to optimize dosing. In vitro, DTG inhibits organic cation(More)
Dolutegravir (DTG) is primarily metabolized by UGT1A1 with CYP3A as a minor route. Carbamazepine (CBZ) is a potent inducer of these enzymes; thus, the effect of oral extended-release CBZ on DTG pharmacokinetics (PK) was evaluated to provide dose recommendation when co-administered. This was a single-center, open-label, fixed-sequence, crossover study in(More)
BACKGROUND Daclatasvir (DCV) is an NS5A replication complex inhibitor recently approved for chronic hepatitis C virus treatment. METHODS To assess drug interactions between the HIV integrase strand transfer inhibitor dolutegravir (DTG) and DCV, subjects were randomized into 1 of 2 sequences in an open-label, 3-period, crossover study. Subjects received(More)