Refinement Database

Database on Refinement of Housing, Husbandry, Care, and Use of Animals in Research

This database, created in 2000, is updated every four months with newly published scientific articles, books, and other publications related to improving or safeguarding the welfare of animals used in research.

Tips for using the database:

  • This landing page displays all of the publications in the database.
  • Use the drop-down menus to filter these publications by Animal Type, Setting, and/or Topic.
  • Clicking on a parent category (e.g., Rodent) will include publications relating to all the items in that category (e.g., Chinchilla, Gerbil, Guinea Pig, etc.).
  • You may also add a keyword to further narrow your search.
  • Please note that at this time, only publications dated 2010 or later (with some exceptions) can be filtered by Animal Type and Topic, and only publications dated 2020 or later (with some exceptions) can be filtered by Setting. Most publications older than 2010 can only be searched by keyword. 
Bozzay, J. D., Walker, P. F., Atwood, R. E. et al. 2023. Development, refinement, and characterization of a nonhuman primate critical care environment. PLOS ONE 18(3), e0281548.

Systemic inflammatory response remains a poorly understood cause of morbidity and mortality after traumatic injury. Recent nonhuman primate (NHP) trauma models have been used to characterize the systemic response to trauma, but none have incorporated...

Danforth, M. D., Clyde, V. L., Jourdan, B. et al. 2023. Blood pressure monitoring in zoologically managed bonobos (Pan paniscus). American Journal of Primatology 85(3), e23474.

In response to the growing evidence that hypertension may play a significant role in the development of cardiovascular disease (CVD) in bonobos, the Great Ape Heart Project established a finger blood pressure (BP) monitoring protocol...

Higham, J. P., Cooper, E. B., Whalen, C. et al. 2023. Urinary cytokine measurements do not reflect surgery-induced inflammation in rhesus macaques. American Journal of Primatology 85(8), e23506.

Measurement of the health and disease status of free-ranging primates is often limited by a lack of available biomarkers of immune activation and inflammation that can be applied noninvasively via the measurement of urine or...

Gilberto, D., Michener, M., Smith, B. et al. 2022. Chronic collection of cerebrospinal fluid from rhesus macaques (Macaca mulatta) with cisterna magna ports: Update on refinements. Comparative Medicine 72(1), 45-49.

More than 20 y ago, we developed an animal model for chronic and continuous collection of cerebrospinal fluid (CSF) from conscious rhesus macaques. Since our previous publication in 2003, we have successfully implanted 168 rhesus...

Schilling, A.-K., Mazzamuto, M. V., Romeo, C. 2022. A review of non-invasive sampling in wildlife disease and health research: What’s new? Animals 12(13), 1719.

In the last decades, wildlife diseases and the health status of animal populations have gained increasing attention from the scientific community as part of a One Health framework. Furthermore, the need for non-invasive sampling methods...

Edes, A. N., Zimmerman, D., Jourdan, B. et al. 2022. Value ranges and clinical comparisons of serum DHEA-S, IL-6, and TNF-α in western lowland gorillas. Animals 12(19), 2705.

Physiological data can provide valuable information about the health and welfare of animals. Unfortunately, few validated assays and a lack of information on species-typical levels of circulating biomarkers for wildlife make the measurement, interpretation, and...

Prior, H., Holbrook, M. 2021. Strategies to encourage the adoption of social housing during cardiovascular telemetry recordings in non-rodents. Journal of Pharmacological and Toxicological Methods 108, 106959.

The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) is working with industry to promote social housing during cardiovascular telemetry recordings within non-rodent safety pharmacology and toxicology studies. Following surveys...

Chmurska-Gąsowska, M., Sowińska, N., Pałka, S. et al. 2021. Non-invasive measurement of thyroid hormones in domestic rabbits. Animals 11(5), 1194.

Thyroid hormones are essential for metabolism, energy homeostasis and reproduction. Hormones can be measured in various biological source materials: blood, feces, urine, saliva and others. The aim of our study was to verify usefulness of...

Stow, R., Kendrick, J., Ibbotson, N. et al. 2021. A new group housing approach for non-human primate metabolism studies. Journal of Pharmacological and Toxicological Methods 107, 106947.

Understanding the absorption, distribution, metabolism and excretion (ADME) of candidate drugs in preclinical species is an integral part of the safety and efficacy evaluation in drug development. For this purpose, the housing of single animals...

Yolles, J. N., Lee-Stubbs, R. B. 2021. Comparison of direct and indirect methods of measuring arterial blood pressure in healthy, anesthetized African green monkeys (Chlorocebus aethiops). JAALAS 60(2), 229-237.

Quantitative blood pressure measurement is a critical parameter for assessing cardiovascular health, monitoring physiologic status under anesthesia, and making clinical decisions. The placement of an arterial catheter is the most accurate way to measure blood...

Houser, L. A., Ramsey, C., de Carvalho, F. M. et al. 2021. Improved training and semen collection outcomes using the closed box chair for macaques. Animals 11(8), 2384.

Collaborative semen collection in monkeys is a valuable tool in research, animal collection management, and conservation efforts. To obtain samples, monkeys are often restrained in open restraint chairs (ORC) with the “pole and collar” technique...

Prior, H., Blunt, H., Crossman, L. et al. 2021. Refining procedures within regulatory toxicology studies: Improving animal welfare and data. Animals 11(11), 3057.

During the development of potential new medicines or agrochemicals, an assessment of the safety profile to humans and environmental species is conducted using a range of different in silico and in vitro techniques in conjunction...

Edes, A. N., Brand, C. M. 2021. Age, sex, and inflammatory markers predict chronic conditions, cardiac disease, and mortality among captive western lowland gorillas (Gorilla gorilla gorilla). Primates 62(6), 931-943.

In humans, inflammatory markers predict health risks. As great apes experience many similar conditions, measuring inflammation may provide valuable health information. We examined four serum inflammatory markers in zoo-housed gorillas (n = 48): albumin, CRP, IL-6, and...

Bertho, J.-M., Ancelet, S., Denais-Laliève, D. et al. 2020. Humane endpoints in severe irradiation experiments using non-human primates: A retrospective analysis. Scandinavian Journal of Laboratory Animal Science 46(1).

A retrospective statistical study has been performed in order to identify the biological, clinical and behavioural variables that could potentially predict the survival status of irradiated non-human primates (NHP) and to refine the future use...

Zemanova, M. A. 2020. Towards more compassionate wildlife research through the 3Rs principles: Moving from invasive to noninvasive methods. Wildlife Biology 2020(1), no page numbers.

Research in ecology and wildlife biology remains crucial for increasing our knowledge and improving species management and conservation in the midst of the current biodiversity crisis. However, obtaining information on population status often involves invasive...

Plangsangmas, T., Brown, J., Thitaram, C. et al. 2020. Circadian rhythm of salivary immunoglobulin A and associations with cortisol as a stress biomarker in captive Asian elephants (Elephas maximus). Animals 10(1), 157.

Salivary immunoglobulin A (sIgA) has been proposed as a potential indicator of welfare for various species, including Asian elephants, and may be related to adrenal cortisol responses. This study aimed to distinguish circadian rhythm effects...

Hambrecht, S., Oerke, A.‐K., Heistermann, M. et al. 2020. Diurnal variation of salivary cortisol in captive African elephants (Loxodonta africana) under routine management conditions and in relation to a translocation event. Zoo Biology 39(3), 186–196.

The present study assessed the diurnal variation in salivary cortisol in captive African elephants during routine management (baseline) and in relation to a potential stressor (translocation) to evaluate to what extent acute stress may affect...

Reinhardt, V. (ed.) 2020. It’s Okay to Cry - Discussions by the Laboratory Animal Refinement & Enrichment Forum [LAREF], Volume V. Animal Welfare Institute, Washington, DC.

This is the 5th volume of selected discussions that took place on the electronic Laboratory Animal Refinement & Enrichment Forum between February 2016 and December 2019. The forum was created in October 2002; it allows...

Cloutier Barbour, C., Danforth, M. D., Murphy, H. et al. 2020. Monitoring great ape heart health through innovative electrocardiogram technology: Training methodologies and welfare implications. Zoo Biology 39(6), 443-447.

Assessing and treating cardiovascular disease (or heart disease) is a growing concern for institutions housing great apes, as it is a major cause of mortality in all four taxa managed in human care. As part...

McFarland, R., Barrett, L., Fuller, A. et al. 2020. Infrared thermography cannot be used to approximate core body temperature in wild primates. American Journal of Primatology 82, e23204.

Understanding the physiological processes that underpin primate performance is key if we are to assess how a primate might respond when navigating new and changing environments. Given the connection between a mammal's ability to thermoregulate...

Murphy, A. M., Ross, C. N., Bliss‐Moreau, E. 2019. Noninvasive cardiac psychophysiology as a tool for translational science with marmosets. American Journal of Primatology 81(9), e23037.

The importance of marmosets for comparative and translational science has grown in recent years because of their relatively rapid development, birth cohorts of twins, family social structure, and genetic tractability. Despite this, they remain understudied...

Kumar, V., Pradheeps, M., Kokkiligadda, A. et al. 2019. Non-invasive assessment of physiological stress in captive Asian elephants. Animals 9(8), 553.

Asian elephant (Elephas maximus) populations, both in the wild and in captivity, have been continually declining over the decades. The present study examined the physiological stress response of captive Asian elephants in relation to body...

Association of Primate Veterinarians. 2019. Association of Primate Veterinarians’ Position Statement: Cerebrospinal fluid aspiration for nonhuman primates in biomedical research. JAALAS 58(4), 428-429.

The Association of Primate Veterinarians (APV) recognizes that CSF collection may be required for both clinical and research purposes in nonhuman primates (NHP). Because there are inherent risks associated with the technique, the laboratory animal...

Edwards, K. L., Miller, M. A., Carlstead, K. et al. 2019. Relationships between housing and management factors and clinical health events in elephants in North American zoos. PLOS ONE 14(6), e0217774.

Elephants experience a number of health issues that can contribute to their well-being and survival. In managed populations, housing conditions and management practices can influence individual health, so potential risk factors associated with morbidity or...

Ishizuka, S., Kawamoto, Y., Toda, K. et al. 2019. Bonobos’ saliva remaining on the pith of terrestrial herbaceous vegetation can serve as non-invasive wild genetic resources. Primates 60(1), 7–13.

Evaluating the genetic diversity of natural populations of endangered species is important for conservation. Although the genetic analysis of wildlife usually requires collecting DNA non-invasively, the variety of non-invasive DNA sampling methods is limited for...