Within the hindbrain region, neural crest cell migration is organized into three streams that follow the segmentation of the neuroepithelium into distinct rhombomeric compartments. Although the streaming of neural crest cells is known to involve signals derived from the neuroepithelium, the molecular properties underlying this process are poorly understood. Here, we have mapped the expression of the signaling component of two secreted class III Semaphorins, Semaphorin (Sema) 3A and Sema 3F, at time points that correspond to neural crest cell migration within the hindbrain region of the chick. Both Semaphorins are expressed within rhombomeres at levels adjacent to crest-free mesenchyme and expression of the receptor components essential for Semaphorin activity by neural crest cells suggests a function in restricting neural crest cell migration. By using bead implantation and electroporation in ovo, we define a role for both Semaphorins in the maintenance of neural crest cell streams in proximity to the neural tube.
This study evaluates the editorial policies of a randomized sample of English language peer-reviewed journals that publish original research involving the use of animals. The aim is to identify whether journals have editorial policies relating to the use of animals in the research that they are prepared to publish and whether any policies are likely to promote animal welfare and dissemination of information on the 3Rs (reduction, refinement, replacement) within the scientific community. The results demonstrate that a significant proportion of journals publishing original research involving animals do not have any editorial policy relating to the use of animals. Of those journals that do have policies the majority simply request that the research be carried out in accordance with standard regulatory requirements. This paper aims to provide editors and publishers with the information they need to review their own editorial policies to ensure they are fulfilling their potential to promote animal welfare and dissemination of the 3Rs.
The HAARP guidelines aim to set a global minimum standard for reporting results from and details of research experiments using animals. Their adoption would contribute to more transparency in research and improve reproducibility.
A meeting on Contemporary Topics in Zebrafish Husbandry and Care was held in the United Kingdom in 2014, with the aim of providing a discussion forum for researchers, animal technologists, and veterinarians from academia and industry to share good practice and exchange ideas. Presentation topics included protocols for optimal larval rearing, implementing the 3Rs (replacement, reduction, and refinement) in large-scale colony management, and environmental enrichment. The audience also participated in a survey of current practice relating to practical husbandry, cryopreservation, and the provision of enrichment.
Background Only a small proportion of preclinical research (research performed in animal models prior to clinical trials in humans) translates into clinical benefit in humans. Possible reasons for the lack of translation of the results observed in preclinical research into human clinical benefit include the design, conduct, and reporting of preclinical studies. There is currently no formal domain-based assessment of the clinical relevance of preclinical research. To address this issue, we have developed a tool for the assessment of the clinical relevance of preclinical studies, with the intention of assessing the likelihood that therapeutic preclinical findings can be translated into improvement in the management of human diseases. Methods We searched the EQUATOR network for guidelines that describe the design, conduct, and reporting of preclinical research. We searched the references of these guidelines to identify further relevant publications and developed a set of domains and signalling questions. We then conducted a modified Delphi-consensus to refine and develop the tool. The Delphi panel members included specialists in evidence-based (preclinical) medicine specialists, methodologists, preclinical animal researchers, a veterinarian, and clinical researchers. A total of 20 Delphi-panel members completed the first round and 17 members from five countries completed all three rounds. Results This tool has eight domains (construct validity, external validity, risk of bias, experimental design and data analysis plan, reproducibility and replicability of methods and results in the same model, research integrity, and research transparency) and a total of 28 signalling questions and provides a framework for researchers, journal editors, grant funders, and regulatory authorities to assess the potential clinical relevance of preclinical animal research. Conclusion We have developed a tool to assess the clinical relevance of preclinical studies. This tool is currently being piloted.
A round table discussion was held during the LAVA-ESLAV-ECLAM conference on Reproducibility of Animal Studies on the 25th of September 2017 in Edinburgh. The aim of the round table was to discuss how to enhance the rate at which the quality of reporting animal research can be improved. This signed statement acknowledges the efforts that participant organizations have made towards improving the reporting of animal studies and confirms an ongoing commitment to drive further improvements, calling upon both academics and laboratory animal veterinarians to help make this cultural change. Main text On Monday 25th September 2017 a round table meeting funded by LAL was held to discuss how to enhance the rate at which the quality of reporting animal research can be improved. This meeting took place during the LAVA-ESLAV-ECLAM conference on reproducibility in animal studies in Edinburgh. It was attended by individuals & organisations proactively working on this issue across Europe including research funders (MRC, Wellcome Trust, ZonMw), journals (EMBO, F1000Research, PLOS ONE, BMJ Open Science, BMC, British Journal of Pharmacology (BJP), The Lancet, Laboratory Animals) & others including ESLAV, EQUATOR, CAMARADES, SYRCLE, Responsible Research in Practice. NIHR were also present to share learning from the perspective of a funder of later phase clinical research. All reiterated a commitment to drive improvements in the quality of animal research reporting to improve reproducibility, and call upon both academics and laboratory animal veterinarians to help drive this cultural change. In our experience relevant and useful training in
Background Personalised medicine is a medical model that aims to provide tailor-made prevention and treatment strategies for defined groups of individuals. The concept brings new challenges to the translational step, both in clinical relevance and validity of models. We have developed a set of recommendations aimed at improving the robustness of preclinical methods in translational research for personalised medicine. Methods These recommendations have been developed following four main steps: (1) a scoping review of the literature with a gap analysis, (2) working sessions with a wide range of experts in the field, (3) a consensus workshop, and (4) preparation of the final set of recommendations. Results Despite the progress in developing innovative and complex preclinical model systems, to date there are fundamental deficits in translational methods that prevent the further development of personalised medicine. The literature review highlighted five main gaps, relating to the relevance of experimental models, quality assessment practices, reporting, regulation, and a gap between preclinical and clinical research. We identified five points of focus for the recommendations, based on the consensus reached during the consultation meetings: (1) clinically relevant translational research, (2) robust model development, (3) transparency and education, (4) revised regulation, and (5) interaction with clinical research and patient engagement. Here, we present a set of 15 recommendations aimed at improving the robustness of preclinical methods in translational research for personalised medicine. Conclusions Appropriate preclinical models should be an integral contributor to interventional clinical trial success rates, and predictive translational models are a fundamental requirement to realise the dream of personalised medicine. The implementation of these guidelines is ambitious, and it is only through the active involvement of all relevant stakeholders in this field that we will be able to make an impact and effectuate a change which will facilitate improved translation of personalised medicine in the future.
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