PREPARE: guidelines for planning animal research and testing

There is widespread concern about the quality, reproducibility and translatability of studies involving research animals. Although there are a number of reporting guidelines available, there is very little overarching guidance on how to plan animal experiments, despite the fact that this is the logical place to start ensuring quality. In this paper we present the PREPARE guidelines: Planning Research and Experimental Procedures on Animals: Recommendations for Excellence. PREPARE covers the three broad areas which determine the quality of the preparation for animal studies: formulation, dialogue between scientists and the animal facility, and quality control of the various components in the study. Some topics overlap and the PREPARE checklist should be adapted to suit specific needs, for example in field research. Advice on use of the checklist is available on the Norecopa website, with links to guidelines for animal research and testing, at https://norecopa.no/PREPARE

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of sufferingwithin commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Experimental investigation of single carbon compounds under hydrothermal conditions

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 70 (2006): 446-460, doi:10.1016/j.gca.2005.09.002.The speciation of carbon in subseafloor hydrothermal systems has direct implications for the maintenance of life in present day vent ecosystems and possibly the origin of life on early Earth. Carbon monoxide is of particular interest because it represents a key reactant during the abiotic synthesis of reduced carbon compounds via Fischer-Tropsch-type processes. Laboratory experiments were conducted to constrain reactions that regulate the speciation of aqueous single carbon species under hydrothermal conditions and determine kinetic parameters for the oxidation of CO according to the water water-gas shift reaction (CO2 + H2 = CO + H2O). Aqueous fluids containing added CO2, CO, HCOOH, NaHCO3, NaHCOO, and H2 were heated at 150, 200, and 300°C and 350 bar in flexible cell hydrothermal apparatus, and the abundance of carbon compounds were monitored as a function of time. Variations in fluid chemistry suggest that the reduction of CO2 to CH3OH under aqueous conditions occurs via a stepwise process that involves the formation of HCOOH, CO, and possibly CH2O, as reaction intermediaries. Kinetic barriers that inhibit the reduction of CH3OH to CH4 allow the accumulation of reaction intermediaries in solution at high concentrations regulated by metastable equilibrium. Reaction of CO2 to form CO involves a two-step process in which CO2 initially undergoes a reduction step to HCOOH which subsequently dehydrates to form CO. Both reactions proceed readily in either direction. A preexponential factor of 1.35 x 106 s-1 and an activation energy of 102 KJ mol-1 were retrieved from the experimental results for the oxidation of CO to CO2. Reactions rates amongst single carbon compounds during the experiments suggests SCO2 (CO2 + HCO3- + CO3=), CO, SHCOOH (HCOOH + HCOO-), and CH3OH may reach states of redox-dependent metastable thermodynamic equilibrium in subseafloor and other hydrothermal systems. The abundance of CO under equilibrium conditions, which in turn may influence the likelihood for abiotic synthesis via Fischer-Tropsch-type processes, is strongly dependent on temperature, the total carbon content of the fluid, and host-rock lithology. If crustal residence times following the mixing of high-temperature hydrothermal fluids with cool seawater are sufficiently long, reequilibration of aqueous carbon can result in the generation of additional reduced carbon species such as HCOOH and CH3OH and the consumption of H2. The present study suggests that abiotic reactions involving aqueous carbon compounds in hydrothermal systems are sufficiently rapid to influence metabolic pathways utilized by organisms that inhabit vent environments.This study was supported by the National Science Foundation grant #OCE-0136954, the Office of Basic Energy Sciences, U.S. Department of Energy grant #DEFG0297ER14746, and by NASA Exobiology grant #NAG5-7696 and Origins grant #NNG04GG23G

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Developing a collaborative agenda for humanities and social scientific research on laboratory animal science and welfare.

Improving laboratory animal science and welfare requires both new scientific research and insights from enquiry in the humanities and social sciences. Whilst scientific research provides evidence to replace, reduce and refine procedures involving laboratory animals (the ‘3Rs’), work in the humanities and social sciences can help understand the social, economic and cultural processes that enhance or impede humane ways of knowing and working with laboratory animals. However, communication across these disciplinary perspectives is currently limited, and they frame questions, generate results, engage users, and seek to influence policy in different ways. To facilitate dialogue and future research at this interface, we convened an interdisciplinary group of 45 life scientists, social scientists, humanities scholars, non-governmental organisations and policy-makers to generate a collaborative research agenda. This drew on other agenda-setting exercises in science policy, using a collaborative and deliberative approach for the identification of research priorities. Participants were recruited from across the community, invited to submit research questions and vote on their priorities. They then met at an interactive workshop in the UK, discussed all 136 questions submitted, and collectively defined the 30 most important issues for the group. The output is a collaborative future agenda for research in the humanities and social sciences on laboratory animal science and welfare. The questions indicate a demand for new research in the humanities and social sciences to inform emerging discussions and priorities on the governance and practice of laboratory animal research, including around: international harmonisation, openness and public engagement, ‘cultures of care’, harm-benefit analysis and the future of the 3Rs. The process underlines the value of interdisciplinary exchange for improving mutual understanding of different research cultures and identifies ways of enhancing the effectiveness of future research at the interface between the humanities, social sciences, science and science policy

The Role of the Three Rs in Improving the Planning and Reproducibility of Animal Experiments

Efforts to improve the design of animal studies have tended to focus on the more mathematical aspects, such as randomization, blocking and statistical analysis. There are, however, many other factors that affect the data from preclinical studies. To improve validity, scientists must collaborate closely with the animal facility involved as soon as the decision to use animals has been made. Such discussions will also help to improve animal welfare, as well as any health and safety issues. A large number of guidelines have been produced over the last 20 years for reporting results in the scientific literature. Comprehensive guidelines for planning animal experiments have been produced more recently, to fulfill this need. These will be described in this paper. A commitment to improving animal welfare, scientific quality, staff care and transparency for all stakeholders will also foster a culture of care around animal research, which benefits all parties. All the Three Rs of Russell and Burch (Replacement, Reduction and Refinement) play a role in the planning and reproducibility of research and testing which may involve animals