Doctors refuse space to group fighting drug company influence
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PROVIDER: S-EPMC1226273 | biostudies-literature | 2005 Sep
REPOSITORIES: biostudies-literature
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Project description:Injurious home-cage aggression (fighting) in mice affects both animal welfare and scientific validity. It is arguably the most common potentially preventable morbidity in mouse facilities. Existing literature on mouse aggression almost exclusively examines territorial aggression induced by introducing a stimulus mouse into the home-cage of a singly housed mouse (i.e. the resident/intruder test). However, fighting occurring in mice living together in long-term groups under standard laboratory housing conditions has barely been studied. We performed a point-prevalence epidemiological survey of fighting at a research institution with an approximate 60,000 cage census. A subset of cages was sampled over the course of a year and factors potentially influencing home-cage fighting were recorded. Fighting was almost exclusively seen in group-housed male mice. Approximately 14% of group-housed male cages were observed with fighting animals in brief behavioral observations, but only 14% of those cages with fighting had skin injuries observable from cage-side. Thus simple cage-side checks may be missing the majority of fighting mice. Housing system (the combination of cage ventilation and bedding type), genetic background, time of year, cage location on the rack, and rack orientation in the room were significant risk factors predicting fighting. Of these predictors, only bedding type is easily manipulated to mitigate fighting. Cage ventilation and rack orientation often cannot be changed in modern vivaria, as they are baked in by cookie-cutter architectural approaches to facility design. This study emphasizes the need to invest in assessing the welfare costs of new housing and husbandry systems before implementing them.
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Project description:The current challenge in designing effective drugs against HIV-1 is to find novel candidates with high potency, but with a lower susceptibility to mutations associated with drug resistance. Trying to address this challenge, we developed in our previous study (Ishikita and Warshel, Angew Chem Int Ed Engl 2008; 47:697-700) a novel computational strategy for fighting drug resistance by predicting the likely moves of the virus through constraints on binding and catalysis. This has been based on calculating the ratio between the vitality values ((K(i) k(cat)/K(M))(mutant)/(K(i) k(cat)/K(M))(wild-type)) and using it as a guide for predicting the moves of the virus. The corresponding calculations of the binding affinity, K(i), were carried out using the semi-macroscopic version of the protein dipole Langevin dipole (PDLD/S) in its linear response approximation (LRA) in its β version (PDLD/S-LRA/β). We also calculate the proteolytic efficiency, k(cat)/K(M), by evaluating the transition state (TS) binding free energies using the PDLD/S-LRA/β method. Here we provide an extensive validation of our strategy by calculating the vitality of six existing clinical and experimental drug candidates. It is found that the computationally determined vitalities correlate reasonably well with those derived from the corresponding experimental data. This indicates that the calculated vitality may be used to identify mutations that would be most effective for the survival of the virus. Thus, it should be possible to use our approach in screening for mutations that would provide the most effective resistance to any proposed antiviral drug. This ability should be very useful in guiding the design of drug molecules that will lead to the slowest resistance.
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Project description:BackgroundCreating new therapies often involves drug companies paying healthcare professionals and institutions for research and development (R&D) activities, including clinical trials. However, industry sponsorship can create conflicts of interest (COIs). We analysed approaches to drug company R&D payment disclosure in European countries and the distribution of R&D payments at the country and company level.MethodsUsing documentary sources and a stakeholder survey we identified country- regulatory approaches to R&D payment disclosure. We reviewed company-level descriptions of disclosure practices in the United Kingdom, a country with a major role in Europe's R&D. We obtained country-level R&D payment data from industry trade groups and public authorities and company-level data from eurosfordocs.eu, a publicly available payments database. We conducted content analysis and descriptive statistical analysis.ResultsIn 32 of 37 studied countries, all R&D payments were reported without named recipients, following a self-regulatory approach developed by the industry. The methodological descriptions from 125 companies operating in the United Kingdom suggest that within the self-regulatory approach companies had much leeway in deciding what activities and payments were considered as R&D. In five countries, legislation mandated the disclosure of R&D payment recipients, but only in two were payments practically identifiable and analysable. In 17 countries with available data, R&D constituted 19%-82% of all payments reported, with self-regulation associated with higher shares. Available company-level data from three countries with self-regulation suggests that R&D payments were concentrated by big funders, and some companies reported all, or nearly all, payments as R&D.ConclusionThe lack of full disclosure of R&D payments in countries with industry self-regulation leaves considerable sums of money unaccounted for and potentially many COIs undetected. Disclosure mandated by legislation exists in few countries and rarely enhances transparency practically. We recommend a unified European approach to R&D payment disclosure, including clear definitions and a centralised database.
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Project description:An animal's decision to enter into a fight depends on the interaction between perceived resource value (V) and fighting costs (C). Both could be altered by predictable environmental fluctuations. For intertidal marine animals, such as the sea anemone Actinia equina, exposure to high flow during the tidal cycle may increase V by bringing more food. It may also increase C via energy expenditure needed to attach to the substrate. We asked whether simulated tidal cycles would alter decisions in fighting A. equina We exposed some individuals to still water and others to simulated tidal cycles. To gain insights into V, we measured their startle responses before and after exposure to the treatments, before staging dyadic fights. Individuals exposed to flow present shorter startle responses, suggesting that flowing water indicates high V compared with still water. A higher probability of winning against no-flow individuals and longer contests between flow individuals suggests that increased V increases persistence. However, encounters between flow individuals were less likely to escalate, suggesting that C is not directly related to V. Therefore, predictable environmental cycles alter V and C, but in complex ways.
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