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. 
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...

Mandour, A. S., Farag, A., Helal, M. A. Y. et al. 2023. Non-invasive assessment of the intraventricular pressure using novel color M-mode echocardiography in animal studies: Current status and future perspectives in veterinary medicine. Animals 13(15), 2452.

The assessment of diastolic function has received great interest in order to comprehend its crucial role in the pathophysiology of heart failure and for the early identification of cardiac events. Silent changes in the intraventricular...

Turcu, M.-C., Paștiu, A. I., Bel, L.-V. et al. 2023. Minimally invasive sampling methods for molecular sexing of wild and companion birds. Animals 13(21), 3417.

Birds are highly social and must be paired in order to increase their welfare. Most bird species are monomorphic; therefore, molecular sexing helps provide appropriate welfare for birds. Moreover, early sex determination can be of...

Alizadeh, E. A., Graf, K., Schiwon, J. et al. 2023. Thirty years of telemetry-based data acquisition for cardiovascular drug safety evaluation: Applications and optimization. Journal of Pharmacological and Toxicological Methods 122, 107279.

Conducting safety evaluations of new drugs using conscious animals has been a specialty of our working group for thirty years. In this article, we review the various technical challenges and solutions dealt with over the...

Broche, N., Mouri, K., Suzumura, T. et al. 2023. Measuring short-term changes in stress-associated salivary analytes in free-ranging Japanese macaques (Macaca fuscata). Primates 64(4), 439–449.

Monitoring short-term changes of endocrine responses in non-human primates living in wild populations is a challenge. Saliva contains enzymes, steroids, and various analytes that can be broadly useful for helping us understand physiological responses to...

Hube, D., van Meegen, C., Herbrandt, S. et al. 2023. Hair corticosterone concentration as a potential stress marker in pet rabbits. Veterinary Record 193(9), e3464.

Background As a prey species, rabbits tend to hide their illnesses and injuries. Consequently, pet rabbit owners often do not notice that their pet may be suffering. Methods Data on the housing and health of...

Arfuso, F., Acri, G., Piccione, G. et al. 2022. Eye surface infrared thermography usefulness as a noninvasive method of measuring stress response in sheep during shearing: Correlations with serum cortisol and rectal temperature values. Physiology & Behavior 250, 113781.

During shearing, animals’ welfare is adversely affected and acute stress occurs. Once animal perceives a threat, it develops behavioral, autonomic, endocrine or immune responses to maintain homeostasis. This study aimed to investigate the usefulness of...

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...

Kishida, T., Motokawa, Y., Yokoi, R. et al. 2022. Less invasive, simultaneous, and continuous measurements of locomotor activity and body temperature using the nano tag® small accelerometer device in cynomolgus monkeys. Journal of Pharmacological and Toxicological Methods 118, 107224.

Locomotor activity and body temperature evaluations of cynomolgus monkeys are useful to understand the effects of drugs on the central nervous system. Here, we describe a simple, inexpensive, and less invasive evaluation method using the...

MacRae, A. M., McGreevy, P., Daros, R. R. et al. 2021. Can eye surface temperature be used to indicate a stress response in harbour seals (Phoca vitulina)? Animal Welfare 30(1), 91-100.

Infra-red thermography (IRT) is increasingly being used to estimate physiological stress responses in animals via changes in eye surface temperature. The aim of this study was to determine whether eye temperature of harbour seals (Phoca...

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...

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...

Anderson, J., Kaplan-Stein, S., Adolph, S. et al. 2020. Assessment of non-contact infrared thermometer measurement sites in birds. Journal of Applied Animal Welfare Science 23(2), 131-139.

The standard method of obtaining body temperature in a bird can be a stressful event, making routine evaluations challenging. Twenty-eight privately owned birds in good health were enrolled in the study to compare digital and...

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...

Sutherland, M. A., Worth, G. M., Dowling, S. K. et al. 2020. Evaluation of infrared thermography as a non-invasive method of measuring the autonomic nervous response in sheep. PLOS ONE 15(5): e0233558.

Eye temperature measured using infrared thermography (IRT) can be used as a non-invasive measure of autonomic nervous system (ANS) activity in cattle. The objective of this study was to evaluate if changes in eye temperature...

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...

X. Hui, Kan, E. C. 2019. No-touch measurements of vital signs in small conscious animals. Science Advances 5, eaau0169.

Measuring the heartbeat and respiration of small conscious animals is important for assessing their health and behavior, but present techniques such as electrocardiogram (ECG), ultrasound, and auscultation rely on close skin contact with the animal...

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...

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...

Sawyer, G., Webster, D., Narayan, E. 2019. Measuring wool cortisol and progesterone levels in breeding maiden Australian merino sheep (Ovis aries). PLOS ONE 14(4), e0214734.

Hormonal assessment tools are important for determining the reproductive success of production animals. This study used non-invasive wool assessment to quantify changes in progesterone and cortisol levels in reproducing female merino sheep. Wool samples were...

Broche Jr., N., Takeshita, R. S. C., Mouri, K. et al. 2019. Salivary alpha-amylase enzyme is a non-invasive biomarker of acute stress in Japanese macaques (Macaca fuscata). Primates volume 60(6), 547–558.

Salivary alpha-amylase (sAA) enzyme functions as a digestive enzyme in many species that consume starch in their diet. Human studies have also revealed that sAA enzyme activity levels are positively correlated with the release of...

Kalliokoski, O., Jellestad, F. K., Murison, R. 2019. A systematic review of studies utilizing hair glucocorticoids as a measure of stress suggests the marker is more appropriate for quantifying short-term stressors. Scientific Reports 9, 11997.

Quantitating glucocorticoids (GCs) in hairs is a popular method for assessing chronic stress in studies of humans and animals alike. The cause-and-effect relationship between stress and elevated GC levels in hairs, sampled weeks later, is...

France, L. K., Vermillion, M. S., Garrett, C. M. 2018. Comparison of direct and indirect methods of measuring arterial blood pressure in healthy male rhesus macaques (Macaca mulatta). JAALAS 57(1), 64-69.

Blood pressure is a critical parameter for evaluating cardiovascular health, assessing effects of drugs and procedures, monitoring physiologic status during anesthesia, and making clinical decisions. The placement of an arterial catheter is the most direct...