Objective To measure the effect of free access to the scientific literature on article downloads and citations.Design Randomised controlled trial.Setting 11 journals published by the American ...Physiological Society.Participants 1619 research articles and reviews.Main outcome measures Article readership (measured as downloads of full text, PDFs, and abstracts) and number of unique visitors (internet protocol addresses). Citations to articles were gathered from the Institute for Scientific Information after one year.Interventions Random assignment on online publication of articles published in 11 scientific journals to open access (treatment) or subscription access (control).Results Articles assigned to open access were associated with 89% more full text downloads (95% confidence interval 76% to 103%), 42% more PDF downloads (32% to 52%), and 23% more unique visitors (16% to 30%), but 24% fewer abstract downloads (−29% to −19%) than subscription access articles in the first six months after publication. Open access articles were no more likely to be cited than subscription access articles in the first year after publication. Fifty nine per cent of open access articles (146 of 247) were cited nine to 12 months after publication compared with 63% (859 of 1372) of subscription access articles. Logistic and negative binomial regression analysis of article citation counts confirmed no citation advantage for open access articles.Conclusions Open access publishing may reach more readers than subscription access publishing. No evidence was found of a citation advantage for open access articles in the first year after publication. The citation advantage from open access reported widely in the literature may be an artefact of other causes.
Reducing exposure to obesogens is a strategy for preventing obesity.
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•There is an expanding global obesity pandemic.•Ubiquitous environmental chemicals called obesogens play a vital ...role in the obesity pandemic.•Exposure to obesogens occurs throughout the life course from before conception until death.•Development is the most sensitive time for obesogens to impact future weight gain across the lifespan and generations.•Obesogens can act via epigenetic mechanisms.•There is a need to expand understanding of the obesogen paradigm to clinicians and consumers.
Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The obesogen hypothesis posits that exposure to endocrine disruptors and other chemicals can alter the development and function of the adipose tissue, liver, pancreas, gastrointestinal tract, and brain, thus changing the set point for control of metabolism. Obesogens can determine how much food is needed to maintain homeostasis and thereby increase the susceptibility to obesity. The most sensitive time for obesogen action is in utero and early childhood, in part via epigenetic programming that can be transmitted to future generations. This review explores the evidence supporting the obesogen hypothesis and highlights knowledge gaps that have prevented widespread acceptance as a contributor to the obesity pandemic. Critically, the obesogen hypothesis changes the narrative from curing obesity to preventing obesity.
Synthesis of phosphonooxymethyl derivatives of ravuconazole, 2 (BMS-379224) and 3 (BMS-315801) and their biological evaluation as potential water-soluble prodrugs of ravuconazole are described. The ...phosphonooxymethyl ether analogue 2 (BMS-379224) and N-phosphonooxymethyl triazolium salt 3 (BMS-315801) were both prepared from ravuconazole (1) and bis-tert-butyl chloromethylphosphate, but under two different conditions. Both derivatives were highly soluble in water and converted to the parent in alkaline phosphatase, and also in vivo (rat). However, BMS-315801 was found to be less stable than BMS-379224 in water at neutral pH. BMS-379224 (2) has proved to be one of the most promising prodrugs of ravuconazole that we tested, and it is currently in clinical evaluation as an intravenous formulation of the broad spectrum antifungal azole, ravuconazole.
We have previously shown that appropriate modification of the benzocycloheptapyridine tricyclic ring system can provide potent farnesyl protein transferase (FPT) inhibitors with good cellular ...activity. Our laboratories have also established that incorporation of either pyridinylacetyl N-oxide or 4-N-carboxamidopiperidinylacetyl moieties results in pharmacokinetically stable inhibitors that are orally efficacious in nude mice. We now demonstrate that further elaboration of the tricyclic ring system by introducing a bromine atom at the 7- or the 10-position of the 3-bromo-8-chlorotricyclic ring system provides compounds that have superior potency and selectivity in FPT inhibition. These compounds have good serum levels and half-lives when given orally to rodents and primates. In vitro and in vivo evaluation of a panel of these inhibitors has led to identification of 15 (SCH 66336) as a highly potent (IC50 = 1.9 nM) antitumor agent that is currently undergoing human clinical trials.
High efficiency quantum well GaAs solar cells have been successfully applied in commercial multijunction concentrator cells to increase the absorption in the infrared and provide variability of the ...absorption edge to optimise energy harvesting. Multiple quantum well (MQW) top cells can further improve the performance of multijunction solar cells since the absorption edge of top and middle subcells can be tuned with the MQWs to maximize the efficiency. Also, our simulations show that photon coupling resulting from the radiative dominance of the MQW top cell can make the multijunction cell less sensitive to variations in the incoming spectrum, thus further improving energy harvesting. New results on the characterisation of a novel MQW top cell will be presented along with electro- and photo-luminescence studies relevant to the photonic coupling.
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