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Published: 14 July 2020

The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research

Nathalie Percie du Sert 1 ,
Viki Hurst 1 ,
Amrita Ahluwalia 2 , 3 ,
Sabina Alam 4 ,
Marc T. Avey 5 ,
Monya Baker 6 ,
William J. Browne 7 ,
Alejandra Clark 8 ,
Innes C. Cuthill 9 ,
Ulrich Dirnagl 10 ,
Michael Emerson 11 ,
Paul Garner 12 ,
Stephen T. Holgate 13 ,
David W. Howells 14 ,
Natasha A. Karp 15 ,
Stanley E. Lazic 16 ,
Katie Lidster 17 ,
Catriona J. MacCallum 18 ,
Malcolm Macleod 19 ,
Esther J. Pearl 1 ,
Ole H. Petersen 20 ,
Frances Rawle 21 ,
Penny Reynolds 22 ,
Kieron Rooney 23 ,
Emily S. Sena 19 ,
Shai D. Silberberg 24 ,
Thomas Steckler 25 &
Hanno Würbel 26

BMC Veterinary Research volume 16 , Article number: 242 ( 2020 ) Cite this article

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Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the “ARRIVE Essential 10,” which constitutes the minimum requirement, and the “Recommended Set,” which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.

Why good reporting is important

In recent years, concerns about the reproducibility of research findings have been raised by scientists, funders, research users, and policy makers [ 1 , 2 ]. Factors that contribute to poor reproducibility include flawed study design and analysis, variability and inadequate validation of reagents and other biological materials, insufficient reporting of methodology and results, and barriers to accessing data [ 3 ]. The bioscience community has introduced a range of initiatives to address the problem, from open access and open practices to enable the scrutiny of all aspects of the research [ 4 , 5 ] through to study preregistration to shift the focus towards robust methods rather than the novelty of the results [ 6 , 7 ], as well as resources to improve experimental design and statistical analysis [ 8 , 9 , 10 ].

Transparent reporting of research methods and findings is an essential component of reproducibility. Without this, the methodological rigour of the studies cannot be adequately scrutinised, the reliability of the findings cannot be assessed, and the work cannot be repeated or built upon by others. Despite the development of specific reporting guidelines for preclinical and clinical research, evidence suggests that scientific publications often lack key information and that there continues to be considerable scope for improvement [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Animal research is a good case in point, where poor reporting impacts on the development of therapeutics and irreproducible findings can spawn an entire field of research, or trigger clinical studies, subjecting patients to interventions unlikely to be effective [ 2 , 19 , 20 ].

In an attempt to improve the reporting of animal research, the ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were published in 2010. The guidelines consist of a checklist of the items that should be included in any manuscript that reports in vivo experiments, to ensure a comprehensive and transparent description [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. They apply to any area of research using live animal species and are especially pertinent to describe comparative research in the laboratory or other formal test setting. The guidelines are also relevant in a wider context, for example, for observational research, studies conducted in the field, and where animal tissues are used. In the 10 years since publication, the ARRIVE guidelines have been endorsed by more than a thousand journals from across the life sciences. Endorsement typically includes advocating their use in guidance to authors and reviewers. However, despite this level of support, recent studies have shown that important information as set out in the ARRIVE guidelines is still missing from most publications sampled. This includes details on randomisation (reported in only 30–40% of publications), blinding (reported in only approximately 20% of publications), sample size justification (reported in less than 10% of publications), and animal characteristics (all basic characteristics reported in less than 10% of publications) [ 11 , 31 , 32 ].

Evidence suggests that 2 main factors limit the impact of the ARRIVE guidelines. The first is the extent to which editorial and journal staff are actively involved in enforcing reporting standards. This is illustrated by a randomised controlled trial at PLOS ONE , designed to test the effect of requesting a completed ARRIVE checklist in the manuscript submission process. This single editorial intervention, which did not include further verification from journal staff, failed to improve the disclosure of information in published papers [ 33 ]. In contrast, other studies using shorter checklists (primarily focused on experimental design) with more editorial follow-up have shown a marked improvement in the nature and detail of the information included in publications [ 34 , 35 , 36 ]. It is likely that the level of resource required from journals and editors currently prohibits the implementation of all the items of the ARRIVE guidelines.

The second issue is that researchers and other individuals and organisations responsible for the integrity of the research process are not sufficiently aware of the consequences of incomplete reporting. There is some evidence that awareness of ARRIVE is linked to the use of more rigorous experimental design standards [ 37 ]; however, researchers are often unfamiliar with the much larger systemic bias in the publication of research and in the reliability of certain findings and even of entire fields [ 33 , 38 , 39 , 40 ]. This lack of understanding affects how experiments are designed and grant proposals prepared, how animals are used and data recorded in the laboratory, and how manuscripts are written by authors or assessed by journal staff, editors, and reviewers.

Approval for experiments involving animals is generally based on a harm–benefit analysis, weighing the harms to the animals involved against the benefits of the research to society. If the research is not reported in enough detail, even when conducted rigorously, the benefits may not be realised, and the harm–benefit analysis and public trust in the research are undermined [ 41 ]. As a community, we must do better to ensure that, where animals are used, the research is both well designed and analysed as well as transparently reported. Here, we introduce the revised ARRIVE guidelines, referred to as ARRIVE 2.0. The information included has been updated, extended, and reorganised to facilitate the use of the guidelines, helping to ensure that researchers, editors, and reviewers—as well as other relevant journal staff—are better equipped to improve the rigour and reproducibility of animal research.

Introducing ARRIVE 2.0

In ARRIVE 2.0, we have improved the clarity of the guidelines, prioritised the items, added new information, and generated the accompanying Explanation and Elaboration (E&E) document to provide context and rationale for each item [ 42 ] (also available at https://www.arriveguidelines.org ). New additions comprise inclusion and exclusion criteria, which are a key aspect of data handling and prevent the ad hoc exclusion of data [ 43 ]; protocol registration, a recently emerged approach that promotes scientific rigour and encourages researchers to carefully consider the experimental design and analysis plan before any data are collected [ 44 ]; and data access, in line with the FAIR Data Principles (Findable, Accessible, Interoperable, Reusable) [ 45 ]. Additional file 1 summarises the changes.

The most significant departure from the original guidelines is the classification of items into 2 prioritised groups, as shown in Tables 1 and 2 . There is no ranking of the items within each group. The first group is the “ARRIVE Essential 10,” which describes information that is the basic minimum to include in a manuscript, as without this information, reviewers and readers cannot confidently assess the reliability of the findings presented. It includes details on the study design, the sample size, measures to reduce subjective bias, outcome measures, statistical methods, the animals, experimental procedures, and results. The second group, referred to as the “Recommended Set,” adds context to the study described. This includes the ethical statement, declaration of interest, protocol registration, and data access, as well as more detailed information on the methodology such as animal housing, husbandry, care, and monitoring. Items on the abstract, background, objectives, interpretation, and generalisability also describe what to include in the more narrative parts of a manuscript.

Revising the guidelines has been an extensive and collaborative effort, with input from the scientific community carefully built into the process. The revision of the ARRIVE guidelines has been undertaken by an international working group—the authors of this publication—with expertise from across the life sciences community, including funders, journal editors, statisticians, methodologists, and researchers from academia and industry. We used a Delphi exercise [ 46 ] with external stakeholders to maximise diversity in fields of expertise and geographical location, with experts from 19 countries providing feedback on each item, suggesting new items, and ranking items according to their relative importance for assessing the reliability of research findings. This ranking resulted in the prioritisation of the items of the guidelines into the 2 sets. Demographics of the Delphi panel and full methods and results are presented in Additional files 2 and 3 . Following their publication on BioRxiv, the revised guidelines and the E&E were also road tested with researchers preparing manuscripts describing in vivo studies, to ensure that these documents were well understood and useful to the intended users. This study is presented in Additional files 4 and 5 .

While reporting animal research in adherence to all 21 items of ARRIVE 2.0 represents best practice, the classification of the items into 2 groups is intended to facilitate the improved reporting of animal research by allowing an initial focus on the most critical issues. This better allows journal staff, editors, and reviewers to verify that the items have been adequately reported in manuscripts. The first step should be to ensure compliance with the ARRIVE Essential 10 as a minimum requirement. Items from the Recommended Set can then be added over time and in line with specific editorial policies until all the items are routinely reported in all manuscripts. ARRIVE 2.0 are fully compatible with and complementary to other guidelines that have been published in recent years. By providing a comprehensive set of recommendations that are specifically tailored to the description of in vivo research, they help authors reporting animal experiments adhere to the National Institutes of Health (NIH) standards [ 43 ] and the minimum standards framework and checklist (Materials, Design, Analysis and Reporting [MDAR] [ 47 ]). The revised guidelines are also in line with many journals’ policies and will assist authors in complying with information requirements on the ethical review of the research [ 48 , 49 ], data presentation and access [ 50 , 51 , 52 ], statistical methods [ 51 , 52 ], and conflicts of interest [ 53 , 54 ].

Although the guidelines are written with researchers and journal editorial policies in mind, it is important to stress that researchers alone should not have to carry the responsibility for transparent reporting. Funders, institutions, and publishers’ endorsement of ARRIVE has been instrumental in raising awareness to date; they now have a key role to play in building capacity and championing the behavioural changes required to improve reporting practices. This includes embedding ARRIVE 2.0 in appropriate training, workflows, and processes to support researchers in their different roles. While the primary focus of the guidelines has been on the reporting of animal studies, ARRIVE also has other applications earlier in the research process, including in the planning and design of in vivo experiments. For example, requesting a description of the study design in line with the guidelines in funding or ethical review applications ensures that steps to minimise experimental bias are considered at the beginning of the research cycle [ 55 ].

Transparent reporting is clearly essential if animal studies are to add to the knowledge base and inform future research, policy, and clinical practice. ARRIVE 2.0 prioritises the reporting of information related to study reliability. This enables research users to assess how much weight to ascribe to the findings and, in parallel, promotes the use of rigorous methodology in the planning and conduct of in vivo experiments [ 37 ], thus increasing the likelihood that the findings are reliable and, ultimately, reproducible.

The intention of ARRIVE 2.0 is not to supersede individual journal requirements but to promote a harmonised approach across journals to ensure that all manuscripts contain the essential information needed to appraise the research. Journals usually share a common objective of improving the methodological rigour and reproducibility of the research they publish, but different journals emphasise different pieces of information [ 56 , 57 , 58 ]. Here, we propose an expert consensus on information to prioritise. This will provide clarity for authors, facilitate transfer of manuscripts between journals, and accelerate an improvement of reporting standards.

Concentrating the efforts of the research and publishing communities on the ARRIVE Essential 10 items provides a manageable approach to evaluate reporting quality efficiently and assess the effect of interventions and policies designed to improve the reporting of animal experiments. It provides a starting point for the development of operationalised checklists to assess reporting, ultimately leading to the build of automated or semi-automated artificial intelligence tools that can detect missing information rapidly [ 59 ].

Improving reporting is a collaborative endeavour, and concerted effort from the biomedical research community is required to ensure maximum impact. We welcome collaboration with other groups operating in this area, as well as feedback on ARRIVE 2.0 and our implementation strategy.

Availability of data and materials

All data and supporting information are available at https://osf.io/unc4j/ .

Abbreviations

Animal Research: Reporting of In Vivo Experiments

Findable, Accessible, Interoperable, Reusable

Explanation and Elaboration

Materials, Design, Analysis and Reporting

National Institutes of Health

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Acknowledgements

We would like to thank the members of the expert panel for the Delphi exercise and the participants of the road testing for their time and feedback. We are grateful to the DelphiManager team for advice and use of their software. We would like to acknowledge the late Doug Altman’s contribution to this project; Doug was a dedicated member of the working group and his input to the guidelines’ revision has been invaluable. This article was originally published in Plos Biology https://doi.org/10.1371/journal.pbio.3000410 under a CC-BY license.

This work was supported by the National Centre of the Replacement, Refinement & Reduction on Animals in Research (NC3Rs, https://www.nc3rs.org.uk/ ). NPdS, KL, VH, and EJP are employees of the NC3Rs. Supporting information.

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NPdS: conceptualisation, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, resources, supervision, visualisation, writing – original draft, writing – review and editing; VH: data curation, investigation, methodology, project administration, resources, writing – original draft, writing – review and editing; SEL, EJP: writing – review and editing; KL: investigation, project administration, writing – review and editing; AA, SA, MTA, MB, WJB, AC, ICC, UD, ME, PG, STH, DWH, NAK, CJMcC, MMcL, OHP, FR, PR, KR, ESS, SDS, TS, HW: investigation, methodology, resources, writing – original draft, writing – review and editing. The author(s) read and approved the final manuscript.

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AA: editor in chief of the British Journal of Pharmacology. WJB, ICC and ME: authors of the original ARRIVE guidelines. WJB: serves on the Independent Statistical Standing Committee of the funder CHDI foundation. AC: Senior Editor, PLOS ONE. AC, CJM, MMcL and ESS: involved in the IICARus trial. ME, MMcL and ESS: have received funding from NC3Rs. ME: sits on the MRC ERPIC panel. STH: chair of the NC3Rs board, trusteeship of the BLF, Kennedy Trust, DSRU and CRUK, member of Governing Board, Nuffield Council of Bioethics, member Science Panel for Health (EU H2020), founder and NEB Director Synairgen, consultant Novartis, Teva and AZ, chair MRC/GSK EMINENT Collaboration. VH, KL, EJP and NPdS: NC3Rs staff, role includes promoting the ARRIVE guidelines. SEL and UD: on the advisory board of the UK Reproducibility Network, CJMcC: shareholdings in Hindawi, on the publishing board of the Royal Society, on the EU Open Science policy platform. UD, MMcL, NPdS, CJMcC, ESS, TS and HW: members of EQIPD. MMcL: member of the Animals in Science Committee, on the steering group of the UK Reproducibility Network. NPdS and TS: associate editors of BMJ Open Science. OHP: vice president of Academia Europaea, editor in chief of Function, senior executive editor of the Journal of Physiology, member of the Board of the European Commission’s SAPEA (Science Advice for Policy by European Academies). FR: NC3Rs board member, shareholdings in GSK. FR and NAK: shareholdings in AstraZeneca. PR: member of the University of Florida Institutional Animal Care and Use Committee, editorial board member of Shock. ESS: editor in chief of BMJ Open Science. SDS: role is to provide expertise and does not represent the opinion of the NIH. TS: shareholdings in Johnson & Johnson. SA, MTA, MB, PG, DWH, and KR declared no conflict of interest.

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Additional file 1..

Noteworthy changes in ARRIVE 2.0. This table recapitulates noteworthy changes in the ARRIVE guidelines 2.0, compared to the original ARRIVE guidelines published in 2010.

Additional file 2.

Delphi methods and results. Methodology and results of the Delphi study that was used to prioritise the items of the guidelines into the ARRIVE Essential 10 and Recommended Set.

Additional file 3.

Delphi data. Tabs 1, 2, and 3: Panel members’ scores for each of the ARRIVE items during rounds 1, 2, and 3, along with descriptive statistics. Tab. 4: Qualitative feedback, collected from panel members during round 1, on the importance and the wording of each item. Tab. 5: Additional items suggested for consideration in ARRIVE 2.0; similar suggestions were grouped together before processing. Tab. 6: Justifications provided by panel members for changing an item’s score between round 1 and round 2.

Additional file 4.

Road testing methods and results. Methodology used to road test the revised ARRIVE guidelines and E&E (as published in preprint) and how this information was used in the development of ARRIVE 2.0.

Additional file 5.

Road testing data. Tab 1: Participants’ demographics and general feedback on the guidelines and the E&E preprints. Tab 2: Outcome of each manuscript’s assessment and justifications provided by participants for not including information covered in the ARRIVE guidelines.

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Percie du Sert, N., Hurst, V., Ahluwalia, A. et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. BMC Vet Res 16 , 242 (2020). https://doi.org/10.1186/s12917-020-02451-y

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Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research

* E-mail: [email protected]

Affiliation The National Centre for the Replacement, Refinement and Reduction of Animals in Research, London, United Kingdom

Affiliation School of Veterinary Science, University of Bristol, Bristol, United Kingdom

Affiliation School of Biological Sciences, University of Bristol, Bristol, United Kingdom

Affiliation National Heart and Lung Institute, Imperial College London, United Kingdom

Affiliation Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom

Carol Kilkenny,
William J. Browne,
Innes C. Cuthill,
Michael Emerson,
Douglas G. Altman

Published: June 29, 2010

https://doi.org/10.1371/journal.pbio.1000412
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Citation: Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research. PLoS Biol 8(6): e1000412. https://doi.org/10.1371/journal.pbio.1000412

Copyright: © 2010 Kilkenny et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This project was initiated, funded, and led by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).

Competing interests: The authors have declared that no competing interests exist.

Abbreviations: ARRIVE, Animals in Research: Reporting In Vivo Experiments; NC3Rs, National Centre for the Replacement, Refinement and Reduction of Animals in Research

In the last decade the number of bioscience journals has increased enormously, with many filling specialised niches reflecting new disciplines and technologies. The emergence of open-access journals has revolutionised the publication process, maximising the availability of research data. Nevertheless, a wealth of evidence shows that across many areas, the reporting of biomedical research is often inadequate, leading to the view that even if the science is sound, in many cases the publications themselves are not “fit for purpose,” meaning that incomplete reporting of relevant information effectively renders many publications of limited value as instruments to inform policy or clinical and scientific practice [1] – [21] . A recent review of clinical research showed that there is considerable cumulative waste of financial resources at all stages of the research process, including as a result of publications that are unusable due to poor reporting [22] . It is unlikely that this issue is confined to clinical research [2] – [14] , [16] – [20] .

Failure to describe research methods and to report results appropriately therefore has potential scientific, ethical, and economic implications for the entire research process and the reputation of those involved in it. This is particularly true for animal research, one of the most controversial areas of science. The largest and most comprehensive review of published animal research undertaken to date, to our knowledge, has highlighted serious omissions in the way research using animals is reported [5] . The survey, commissioned by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), a UK Government-sponsored scientific organisation, found that only 59% of the 271 randomly chosen articles assessed stated the hypothesis or objective of the study, and the number and characteristics of the animals used (i.e., species/strain, sex, and age/weight). Most of the papers surveyed did not report using randomisation (87%) or blinding (86%) to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods fully described them and presented the results with a measure of precision or variability [5] . These findings are a cause for concern and are consistent with reviews of many research areas, including clinical studies, published in recent years [2] – [22] .

Good Reporting Is Essential for Peer Review and to Inform Future Research

Scrutiny by scientific peers has long been the mainstay of “quality control” for the publication process. The way that experiments are reported, in terms of the level of detail of methods and the presentation of key results, is crucial to the peer review process and, indeed, the subsequent utility and validity of the knowledge base that is used to inform future research. The onus is therefore on the research community to ensure that their research articles include all relevant information to allow in-depth critique, and to avoiding duplicating studies and performing redundant experiments. Ideally scientific publications should present sufficient information to allow a knowledgeable reader to understand what was done, why, and how, and to assess the biological relevance of the study and the reliability and validity of the findings. There should also be enough information to allow the experiment to be repeated [23] . The problem therefore is how to ensure that all relevant information is included in research publications.

Using Reporting Guidelines Measurably Improves the Quality of Reporting

Evidence provided by reviews of published research suggests that many researchers and peer reviewers would benefit from guidance about what information should be provided in a research article. The CONSORT Statement for randomised controlled clinical trials was one of the first guidelines developed in response to this need [24] , [25] . Since publication, an increasing number of leading journals have supported CONSORT as part of their instructions to authors [26] , [27] . As a result, convincing evidence is emerging that CONSORT improves the quality and transparency of reports of clinical trials [28] , [29] .

Following CONSORT, many other guidelines have been developed—there are currently more than 90 available for reporting different types of health research, most of which have been published in the last ten years (see http://www.equator-network.org and references [30] , [31] ). Guidelines have also been developed to improve the reporting of other specific bioscience research areas including metabolomics and gene expression studies [32] – [37] . Several organisations support the case for improved reporting and recommend the use of reporting guidelines, including the International Committee of Medical Journal Editors, the Council of Science Editors, the Committee on Publication Ethics, and the Nuffield Council for Bioethics [38] – [41] .

Improving the Reporting of Animal Experiments—The ARRIVE Guidelines

Most bioscience journals currently provide little or no guidance on what information to report when describing animal research [42] – [50] . Our review found that 4% of the 271 journal articles assessed did not report the number of animals used anywhere in the methods or the results sections [5] . Reporting animal numbers is essential so that the biological and statistical significance of the experimental results can be assessed or the data reanalysed, and is also necessary if the experimental methods are to be repeated. Improved reporting of these and other details will maximise the availability and utility of the information gained from every animal and every experiment, preventing unnecessary animal use in the future. To address this, we led an initiative to produce guidelines for reporting animal research. The guidelines, referred to as ARRIVE (Animals in Research: Reporting In Vivo Experiments), have been developed using the CONSORT Statement as their foundation [24] , [25] .

The ARRIVE guidelines consist of a checklist of 20 items describing the minimum information that all scientific publications reporting research using animals should include, such as the number and specific characteristics of animals used (including species, strain, sex, and genetic background); details of housing and husbandry; and the experimental, statistical, and analytical methods (including details of methods used to reduce bias such as randomisation and blinding). All the items in the checklist have been included to promote high-quality, comprehensive reporting to allow an accurate critical review of what was done and what was found.

Consensus and consultation are the corner-stones of the guideline development process [51] . To maximise their utility, the ARRIVE guidelines have been prepared in consultation with scientists, statisticians, journal editors, and research funders. We convened an expert working group, comprising researchers and statisticians from a range of disciplines, and journal editors from Nature Cell Biology , Science , Laboratory Animals , and the British Journal of Pharmacology (see Acknowledgments). At a one-day meeting in June 2009, the working group agreed the scope and broad content of a draft set of guidelines that were then used as the basis for a wider consultation with the scientific community, involving researchers, and grant holders and representatives of the major bioscience funding bodies including the Medical Research Council, Wellcome Trust, Biotechnology and Biological Sciences Research Council, and The Royal Society (see Table 1 ). Feedback on the content and wording of the items was incorporated into the final version of the checklist. Further feedback on the content utility of the guidelines is encouraged and sought.

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https://doi.org/10.1371/journal.pbio.1000412.t001

The ARRIVE guidelines (see Table 2 ) can be applied to any area of bioscience research using laboratory animals, and the inherent principles apply not only to reporting comparative experiments but also to other study designs. Laboratory animal refers to any species of animal undergoing an experimental procedure in a research laboratory or formal test setting. The guidelines are not intended to be mandatory or absolutely prescriptive, nor to standardise or formalise the structure of reporting. Rather they provide a checklist that can be used to guide authors preparing manuscripts for publication, and by those involved in peer review for quality assurance, to ensure completeness and transparency.

https://doi.org/10.1371/journal.pbio.1000412.t002

Improved Reporting Will Maximise the Output of Published Research

These guidelines were developed to maximise the output from research using animals by optimising the information that is provided in publications on the design, conduct, and analysis of the experiments. The need for such guidelines is further illustrated by the systematic reviews of animal research that have been carried out to assess the efficacy of various drugs and interventions in animal models [8] , [9] , [13] , [52] – [55] . Well-designed and -reported animal studies are the essential building blocks from which such a systematic review is constructed. The reviews have found that, in many cases, reporting omissions, in addition to the limitations of the animal models used in the individual studies assessed in the review, are a barrier to reaching any useful conclusion about the efficacy of the drugs and interventions being compared [2] , [3] .

Driving improvements in reporting research using animals will require the collective efforts of authors, journal editors, peer reviewers, and funding bodies. There is no single simple or rapid solution, but the ARRIVE guidelines provide a practical resource to aid these improvements. The guidelines will be published in several leading bioscience research journals simultaneously [56] – [60] , and publishers have already endorsed the guidelines by including them in their journal Instructions to Authors subsequent to publication. The NC3Rs will continue to work with journal editors to extend the range of journals adopting the guidelines, and with the scientific community to disseminate the guidelines as widely as possible ( http://www.nc3rs.org.uk/ARRIVE ).

Acknowledgments

The NC3Rs gratefully acknowledges the expertise and advice that all the contributors have given to developing the guidelines. We would particularly like to acknowledge the contribution of the other members of NC3Rs Reporting Guidelines Working Group (note that the working group members and authors who contributed to these guidelines were advising in their personal capacity and their input does not necessarily represent the policy of the organisations with which they are associated): Professor David Balding, Department of Epidemiology & Public Health, Imperial College, London UK; Dr Colin Dunn Editor Laboratory Animals (Royal Society of Medicine press); Dr. Stella Hurtley, Senior Editor Science ; Professor Ian McGrath Editor-in-Chief British Journal of Pharmacology (Wiley Blackwell publishers); and Dr. Clare Stanford, Department of Psychopharmacology, University College, London UK. We would also like to thank NC3Rs grant holders, the Medical Research Council, Biotechnology and Biological Sciences Research Council, Wellcome Trust, Parkinson's Disease Society, British Heart Foundation and their grant holders and funding committee members who provided feedback on the guidelines; and Dr. Kathryn Chapman and Dr. Vicky Robinson (both NC3Rs) for their help with the manuscript.

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Animal research: reporting in vivo experiments: the ARRIVE guidelines

Collaborators.

NC3Rs Reporting Guidelines Working Group : Doug Altman , David Balding , William Browne , Innes Cuthill , Colin Dunn , Michael Emerson , Stella Hurtley , Ian McGrath , Clare Stanford

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1 The National Centre for the Replacement, Refinement and Reduction of Animals in Research, London, UK. [email protected]
PMID: 20649561
PMCID: PMC2936830
DOI: 10.1111/j.1476-5381.2010.00872.x

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Improving planning, design, reporting and scientific quality of animal experiments by using the Gold Standard Publication Checklist, in addition to the ARRIVE guidelines. Hooijmans CR, de Vries R, Leenaars M, Curfs J, Ritskes-Hoitinga M. Hooijmans CR, et al. Br J Pharmacol. 2011 Mar;162(6):1259-60. doi: 10.1111/j.1476-5381.2010.01128.x. Br J Pharmacol. 2011. PMID: 21091655 Free PMC article.

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Appendix Animal Research: Reporting In Vivo Experiments: The ARRIVE Guidelines 7

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ITEM		RECOMMENDATION
	1	Provide as accurate and concise a description of the content of the article as possible.
	2	Provide an accurate summary of the background, research objectives, including details of the species or strain of animal used, key methods, principal findings and conclusions of the study.

Background	3
Objectives	4	Clearly describe the primary and any secondary objectives of the study, or specific hypotheses being tested.

Ethical statement	5	Indicate the nature of the ethical review permissions, relevant licences (e.g. Animal [Scientific Procedures] Act 1986), and national or institutional guidelines for the care and use of animals, that cover the research.
Study design	6	For each experiment, give brief details of the study design including: A time-line diagram or flow chart can be useful to illustrate how complex study designs were carried out.
Experimental procedures	7	For each experiment and each experimental group, including controls, provide precise details of all procedures carried out. For example:
Experimental animals	8
Housing and husbandry	9	Provide details of:
Sample size	10
Allocating animals to experimental groups	11
Experimental outcomes	12	Clearly define the primary and secondary experimental outcomes assessed (e.g. cell death, molecular markers, behavioural changes).
Statistical methods	13

Baseline data	14	For each experimental group, report relevant characteristics and health status of animals (e.g. weight, microbiological status, and drug or test naïve) prior to treatment or testing. (This information can often be tabulated).
Numbers analysed	15
Outcomes and estimation	16	Report the results for each analysis carried out, with a measure of precision (e.g. standard error or confidence interval).
Adverse events	17

Interpretation/scientific implications	18	.
Generalisability/translation	19	Comment on whether, and how, the findings of this study are likely to translate to other species or systems, including any relevance to human biology.
Funding	20	List all funding sources (including grant number) and the role of the funder(s) in the study.

The guidelines are intended to

Improve reporting of research using animals.

Guide authors as to the essential information to include in a manuscript, and not be absolutely prescriptive.

Be flexible to accommodate reporting a wide range of research areas and experimental protocols.

Promote reproducible, transparent, accurate, comprehensive, concise, logically ordered, well written manuscripts.

Improve the communication of the research findings to the broader scientific community.

The guidelines are NOT intended to

Promote uniformity, stifle creativity, or encourage authors to adhere rigidly to all items in the checklist. Some of the items may not apply to all studies, and some items can be presented as tables/figure legends or flow diagrams (e.g. the numbers of animals treated, assessed and analysed).

Be a guide for study design and conduct. However, some items on the checklist, such as randomisation, blinding and using comparator groups, may be useful when planning experiments as their use will reduce the risk of bias and increase the robustness of the research.

What kind of research areas do the guidelines apply to?

The guidelines will be most appropriate for comparative studies, where two or more groups of experimental animals are being compared; often one or more of the groups may be considered as a control. They apply also to studies comparing different drug doses, or, for example, where a single animal is used as its own control (within–subject experiment).

Most of the recommendations also apply to studies that do not have a control group.

The guidelines are suitable for any area of bioscience research where laboratory animals are used.

Who are the guidelines aimed at?

Novice and experienced authors

Journal editors

Peer reviewers

Funding bodies

How might these guidelines be used?

The guidelines provide a checklist for those preparing or reviewing a manuscript intended for publication.

Acknowledgements

The NC3Rs gratefully acknowledges the expertise and advice that all the contributors have given to developing the guidelines. We would particularly like to acknowledge the contribution of the NC3Rs Reporting Guidelines Working Group † – Professor Doug Altman, Centre for Statistics in Medicine, University of Oxford UK, Professor David Balding, Department of Epidemiology & Public Health, Imperial College, London UK, Professor William Browne, Department of Clinical Veterinary Science, University of Bristol UK, Professor Innes Cuthill, School of Biological Sciences, University of Bristol UK, Dr Colin Dunn, Editor Laboratory Animals (Royal Society of Medicine press), Dr Michael Emerson, National Heart and Lung Institute, Imperial College, London UK, Dr Stella Hurtley, Senior Editor Science, Professor Ian McGrath, Editor-in-Chief British Journal of Pharmacology (Wiley Blackwell Publishers) and Dr Clare Stanford, Department of Psychopharmacology, University College, London UK. We would also like to thank NC3Rs grant holders, the Medical Research Council, Biotechnology and Biological Sciences Research Council (BBSRC), Wellcome Trust, Parkinson’s Disease Society, British Heart Foundation and their grant holders and funding committee members who provided feedback on the guidelines; and Kathryn Chapman and Vicky Robinson (both NC3Rs) for their help with the manuscript.

The reporting guidelines project was funded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).

Reprinted with permission from the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research ( www .nc3rs.org.uk ). Originally published in PLoS Biology, June 2010 (volume 8, issue 6).

Please note that the working group members who contributed to these guidelines were advising in their personal capacity and their input does not necessarily represent the policy of the organisations with which they are associated.

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In Vitro and in vivo characterization of nasal pH-Responsive in-situ hydrogel of Candesartan-loaded invasomes as a potential stroke treatment

Original Article
Published: 11 September 2024

Cite this article

Shaimaa El-Housiny 1 ,
Amr Gamal Fouad ORCID: orcid.org/0000-0002-0082-4160 2 , 9 ,
Rana El-Bakry 3 ,
Randa Mohammed Zaki 4 , 5 ,
Obaid Afzal 6 ,
Fatma I. Abo El-Ela 7 &
Maha M. Ghalwash 8

Candesartan (CDN) is a useful anti-stroke medication because it lowers blood pressure, inflammation, oxidative stress, angiogenesis and apoptosis. However, CDN has limited efficacy due to its low solubility and poor bioavailability. This study set out to develop nasal pH-responsive in situ hydrogel of CDN-loaded invasomes a (PRHCLI) for enhancing CDN’s release, penetration, bioavailability, and effectiveness as a possible treatment for stroke. Based on the results of the pre-formulation investigation, the optimum CLI formulation for intravasomal delivery of CDN was determined to be 3% of phospholipid, 0.16% of cholesterol, 3% of ethanol, and 1% of cineole. The optimum formulation significantly enhanced CDN permeation and release by 2.06-fold and 59.06%, respectively. The CLI formulation was added to a mixture of chitosan (0.67%w/v) and glyceryl monooleate (0.27%v/v) to develop PRHCLI. The PRHCLI formulation enhanced the release and permeation of CDN relative to free CDN by 2.15 and 2.76 folds, respectively. An experimental rat stroke model was utilized for in vivo studies to evaluate the bioavailability, effectiveness, and toxicity of the PRHCLI formulation. The nasal PRHCLI drops increased the CDN’s bioavailability by 3.20-fold compared to oral free CDN. Increased grip strength and decreased flexion, spontaneous motor activity, and Morris Water Maze scores in comparison to oral free CDN showed that nasal PRHCLI drops have better anti-stroke activity. The toxicity evaluation revealed the safety of nasal PRHCLI. Hence, nasal PRHCLI drops may represent a promising avenue as a stroke therapy.

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Acknowledgements

This study is supported via funding from Prince sattam bin Abdulaziz University project number (PSAU/2024/R/1445).

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Department of Pharmaceutics and Drug Manufacturing, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Cairo, Egypt

Shaimaa El-Housiny

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt

Amr Gamal Fouad

Department of Pharmacology and Toxicology, EL Saleheya EL Gadida University, EL Saleheya El Gadida, Sharkia, Egypt

Rana El-Bakry

Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj, Saudi Arabia

Randa Mohammed Zaki

Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Beni-Suef University, Beni-Suef, Egypt

Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj, Saudi Arabia

Obaid Afzal

Department of Pharmacology, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt

Fatma I. Abo El-Ela

Department of Pharmaceutics and Drug Manufacturing, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt

Maha M. Ghalwash

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Contributions

Shaimaa El-Housiny: Conceptualization, Methodology, Data Curation, Writing - Review & Editing; Randa Mohammed Zaki: Software, Validation, Resources, Writing - Review & Editing; Obaid Afzal: Software, Validation, Resources, Writing - Review & Editing; Rana El-Bakry: Methodology, Formal analysis, Writing - Original Draft; Fatma I. Abo El-Ela: Conceptualization, Methodology, Writing - Original Draft; Maha M. Ghalwash: Conceptualization, Methodology, Writing - Review & Editing; Amr Gamal Fouad: Conceptualization, Methodology, Writing - Original Draft.

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El-Housiny, S., Fouad, A.G., El-Bakry, R. et al. In Vitro and in vivo characterization of nasal pH-Responsive in-situ hydrogel of Candesartan-loaded invasomes as a potential stroke treatment. Drug Deliv. and Transl. Res. (2024). https://doi.org/10.1007/s13346-024-01700-z

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Review Article
Published: 10 September 2024

The role of the haematopoietic stem cell niche in development and ageing

Terri L. Cain ORCID: orcid.org/0000-0002-5590-2103 1 ,
Marta Derecka ORCID: orcid.org/0000-0001-6265-9781 1 &
Shannon McKinney-Freeman ORCID: orcid.org/0000-0001-8061-2557 1

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Haematopoiesis
Haematopoietic stem cells
Stem-cell niche

Blood production depends on rare haematopoietic stem cells (HSCs) and haematopoietic stem and progenitor cells (HSPCs) that ultimately take up residence in the bone marrow during development. HSPCs and HSCs are subject to extrinsic regulation by the bone marrow microenvironment, or niche. Studying the interactions between HSCs and their niche is critical for improving ex vivo culturing conditions and genetic manipulation of HSCs, which is pivotal for improving autologous HSC therapies and transplantations. Additionally, understanding how the complex molecular network in the bone marrow is altered during ageing is paramount for developing novel therapeutics for ageing-related haematopoietic disorders. HSCs are unique amongst stem and progenitor cell pools in that they engage with multiple physically distinct niches during their ontogeny. HSCs are specified from haemogenic endothelium in the aorta, migrate to the fetal liver and, ultimately, colonize their final niche in the bone marrow. Recent studies employing single-cell transcriptomics and microscopy have identified novel cellular interactions that govern HSC specification and engagement with their niches throughout ontogeny. New lineage-tracing models and microscopy tools have raised questions about the numbers of HSCs specified, as well as the functional consequences of HSCs interacting with each developmental niche. Advances have also been made in understanding how these niches are modified and perturbed during ageing, and the role of these altered interactions in haematopoietic diseases. In this Review, we discuss these new findings and highlight the questions that remain to be explored.

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Do haematopoietic stem cells age?

Decoding human fetal liver haematopoiesis

Hematopoietic stem and progenitor cell signaling in the niche

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Acknowledgements

This work was supported by the National Institute of Diabetes and Digestive and Kidney Disease (R01DK116835 and R01DK104028, to S.M.-F.), National Heart, Lung, and Blood Institute (F31HL170678, to T.L.C.), American Lebanese Syrian Associated Charities (to S.M.-F. and M.D.), Leukaemia Research Foundation (to M.D.) and WES Foundation (to M.D.). S.M.-F. is a Scholar of The Leukaemia & Lymphoma Society. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health.

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A key adhesion protein and transcription factor in the Wnt signalling pathway.

(AGM). An embryonic mesodermal region from which haematopoietic stem cells (HSCs) emerge in mammals.

Cytokines produced by adipose tissue that have roles in inflammatory and metabolic signalling.

A mouse model that has significantly reduced white and brown adipose tissue.

(CS). A classification system of 23 stages developed as a standard timeline of human embryonic development.

An aromatic amine that serves as a neurotransmitter, such as dopamine and adrenaline.

A bioinformatics algorithm that predicts cell-to-cell communications via ligand–receptor interactions based on single-cell RNA sequencing (scRNA-seq) or spatial transcriptomics data.

A bioinformatic algorithm that can predict ligand–receptor cellular interactions based on single-cell RNA sequencing (scRNA-seq) expression of the ligands, receptors and associated signalling pathway genes across annotated cellular populations.

A microenvironment on the outer edge of the bone marrow comprising many cell types, including haematopoietic stem cells (HSCs).

Interactions between ligand and receptor pairs occurring on the same cell.

A narrow section of the embryonic mesoderm from which haematopoietic stem cells (HSCs) emerge in zebrafish, and ultimately gives rise to the urogenital systems.

A toxic alkaloid found in some plant species.

A haematological disorder in which there is a clinical decrease in the number of lymphocytes present in the blood.

Enzymes found in the intercellular space that break down extracellular proteins.

Occurs when an individual haematopoietic stem cell (HSC) has an increased relative contribution of myeloid lineage progeny compared with lymphoid lineage progeny.

A group of multipotent stem cells that migrate during development and give rise to large groups of tissues, such as connective tissue, skin pigmentation cells and craniofacial bones.

A regulator of many developmentally relevant processes in a tissue-dependent manner, including cell proliferation and growth.

The transplantation of organs or tissues, such as blood, between two different species.

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Cain, T.L., Derecka, M. & McKinney-Freeman, S. The role of the haematopoietic stem cell niche in development and ageing. Nat Rev Mol Cell Biol (2024). https://doi.org/10.1038/s41580-024-00770-8

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The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) are a checklist of recommendations for the full and transparent reporting of research involving animals - maximising the quality and reliability of published research, and enabling others to better scrutinise, evaluate and reproduce it., standard
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The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) are a checklist of information to include in publications describing animal research. Aims and objectives of the ARRIVE guidelines The guidelines ensure that studies are reported in enough detail to add to the knowledge base. Scientific publications reporting animal research often lack important information, limiting ...
The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research
The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and ...
The ARRIVE guidelines 2.0
To facilitate a step-wise approach to improving reporting, the guidelines are organised into two prioritised sets: ARRIVE Essential 10 These ten items are the basic minimum that must be included in any manuscript describing animal research. Without this information readers and reviewers cannot assess the reliability of the findings.
Reporting animal research: Explanation and elaboration for the ARRIVE
However, evidence shows that the majority of publications fail to include key information and there is significant scope to improve the reporting of studies involving animal research [1-4]. To that end, the UK National Centre for the 3Rs (NC3Rs) published the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines in 2010.
The ARRIVE guidelines 2.0: updated guidelines for reporting animal research
This includes embedding ARRIVE 2.0 in appropriate training, workflows and processes to support researchers in their different roles. While the primary focus of the guidelines has been on the reporting of animal studies, ARRIVE also has other applications earlier in the research process, including in the planning and design of in vivo experiments.
The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research
In an attempt to improve the reporting of animal research, the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were published in 2010. The guidelines consist of a checklist of the items that should be included in any manuscript that reports in vivo experiments, to ensure a comprehensive and transparent description [21-30 ...
The ARRIVE guidelines 2.0: Updated guidelines for reporting animal
The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and ...
The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research
In an attempt to improve the reporting of animal research, the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were published in 2010. The guidelines consist of a checklist of the items that should be included in any manuscript that reports in vivo exper-iments, to ensure a comprehensive and transparent description [21-30].
Reporting animal research: Explanation and elaboration for the ARRIVE
However, evidence shows that the majority of publications fail to include key information and there is significant scope to improve the reporting of studies involving animal research [1-4]. To that end, the UK National Centre for the 3Rs (NC3Rs) published the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines in 2010.
Reporting animal research: Explanation and elaboration for the ARRIVE
This explanation and elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2.0, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature.
PDF The ARRIVE , Marc T Avey4, Monya Baker5 guidelines 2
The ARRIVE guidelines 2.0 Animal Research: Reporting of In Vivo Experiments Nathalie Percie du Sert1, Viki Hurst 1, Amrita Ahluwalia2, Sabina Alam3, Marc T Avey4, Monya Baker5, William J Browne6, Alejandra Clark7, Innes C Cuthill6, Ulrich Dirnagl8, Michael Emerson9, Paul Garner10,
Animal research: reporting in vivo experiments—The ARRIVE Guidelines
Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 8:e1000412 Schulz KF, Altman DG, Moher D, The CONSORT Group (2010) CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. Br Med J 340:c332.
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Animal research: Reporting. in vivo. experiments: The ARRIVE guidelines. Provide as accurate and concise a description of the content of the article as possible. Provide an accurate summary of the background, research objectives, including details of the species or strain of animal used, key methods, principal findings and conclusions of the study.
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The reporting guidelines project was funded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). These guidelines are excerpted (as permitted under the Creative Commons Attribution License [CCAL], with the knowledge and approval of PLoS Biology and the authors) from Kilkenny C, Browne WJ, Cuthill ...
ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments
The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) are a checklist of recommendations to improve the reporting of research involving animals - maximizing the quality and reliability of published research, and enabling others to better scrutinize, evaluate and reproduce it. Read more *NIH encourages the use of the ARRIVE Essential 10 checklist in all publications ...
Animal Research: Reporting In Vivo Experiments: The ARRIVE guidelines
The reporting guidelines project was funded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). These guidelines are excerpted (as permitted under the Creative Commons Attribution License [CCAL], with the knowledge and approval of PLoS Biology and the authors) from Kilkenny C, Browne WJ, Cuthill ...
The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research
The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and ...
Improving Bioscience Research Reporting: The ARRIVE Guidelines for
Abbreviations: ARRIVE, Animals in Research: Reporting In Vivo Experiments; NC3Rs, National Centre for the Replacement, Refinement and Reduction of Animals in Research In the last decade the number of bioscience journals has increased enormously, with many filling specialised niches reflecting new disciplines and technologies.
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Animal research: reporting in vivo experiments: the ARRIVE guidelines. Animal research: reporting in vivo experiments: the ARRIVE guidelines. Animal research: reporting in vivo experiments: the ARRIVE guidelines Br J Pharmacol. 2010 Aug;160(7):1577-9. doi: 10.1111/j.1476-5381.2010.00872.x.
The ARRIVE guidelines 2.0: Updated guidelines for reporting animal
The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and ...
Animal Research: Reporting In Vivo Experiments: The ARRIVE Guidelines
Appendix Animal Research: Reporting In Vivo Experiments: The ARRIVE Guidelines 7. ITEM RECOMMENDATION; TITLE: 1: Provide as accurate and concise a description of the content of the article as possible. ... Animal Research: Reporting In Vivo Experiments: The ARRIVE Guidelines - Guidance for the Description of Animal Research in Scientific ...
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The principle of 3R—to replace, reduce and refine the use of animals in research—was formulated more than 60 years ago (Russell & Burch, 1959).It has been continuously adapted and modified since and found increasing acceptance as the ethical and legal basis for regulating animal experimentation, most prominently in the EU (Parlament & Rat der Europäischen Union).
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The ethics committee of Beni-Suef University, Egypt (BSU-IACUC: 022-414) authorized the in vivo study strategy, which adhered to the ARRIVE criteria. The animal house was equipped with forty two mature male Wistar rats, weighing 200-250 g, and maintained at a temperature of 22 ± 2ºC and a humidity level of 30-70%.
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