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...

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...

Beeby, N., Baden, A. L., Higham, J. P. 2023. Urinary C-peptide and total triiodothyronine as energetic biomarkers for studies of lemurs. American Journal of Primatology 85(12), e23563.

Measuring energy balance and energy metabolism can provide crucial information for understanding the ecological and behavioral drivers of an animal’s energetic and physiological condition. Both urinary C-peptide (uCP) of insulin and urinary total triiodothyronine (uTT3)...

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...

Barton, J. C., Didier, M. D., Silvestrini, P. et al. 2022. A noninvasive method of temperature measurement using a noncontact handheld infrared thermometer fails to correlate with rectal temperature in dogs and cats. Journal of the American Veterinary Medical Association 260(7), 752-757.

OBJECTIVE: To perform a retrospective, multicenter observational study that compares the agreement of rectal temperature with the temperature measured with noncontact infrared thermometer (NCIT) in a population of dogs and cats. ANIMALS: 168 dogs and...

van der Laan, J. E., Vinke, C. M., Arndt, S. S. 2022. Evaluation of hair cortisol as an indicator of long-term stress responses in dogs in an animal shelter and after subsequent adoption. Scientific Reports 12(1), 5117.

Shelter dogs are exposed to a variety of stressors. Among non-invasive techniques, hair cortisol concentration (HCC) is suggested an easy to collect biomarker for giving insight into long-term stress responses. We evaluated HCC as an...

van der Laan, J. E., Vinke, C. M., Arndt, S. S. 2022. Evaluation of hair cortisol as an indicator of long-term stress responses in dogs in an animal shelter and after subsequent adoption. Scientific Reports 12(1), 5117.

Shelter dogs are exposed to a variety of stressors. Among non-invasive techniques, hair cortisol concentration (HCC) is suggested an easy to collect biomarker for giving insight into long-term stress responses. We evaluated HCC as an...

Reicher, V., Bálint, A., Újváry, D. et al.2022. Non-invasive sleep EEG measurement in hand raised wolves. Scientific Reports 12(1), 9792.

Sleep research greatly benefits from comparative studies to understand the underlying physiological and environmental factors affecting the different features of sleep, also informing us about the possible evolutionary changes shaping them. Recently, the domestic dog...

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...

Takeshita, R. S. C. 2022. Validation of an enzyme immunoassay for measurement of fecal dehydroepiandrosterone sulfate in gibbons and siamangs. Zoo Biology 41(6), 544–553.

Monitoring wildlife stress levels is essential to ensure their quality of life in captivity or in the wild. One promising method to assess the stress response is the comeasurement of glucocorticoids (GC) and dehydroepiandrosterone sulfate...

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...

Koshman, Y. E., Wilsey, A. S., Bird, B. M. et al. 2021. Automated blood sampling in canine telemetry studies: Enabling enhanced assessments of cardiovascular liabilities and safety margins. Journal of Pharmacological and Toxicological Methods 109, 107066.

Introduction: A successful integration of automated blood sampling (ABS) into the telemetry instrumented canine cardiovascular model is presented in this study. This combined model provides an efficient means to quickly gain understanding of potential effects...

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...

Wang, P., Ma, Y., Liang, F. et al. 2020. Non-contact vital signs monitoring of dog and cat using a UWB radar. Animals 10(2), 205.

As pets are considered members of the family, their health has received widespread attention. Since pets cannot talk and complain when they feel uncomfortable, monitoring vital signs becomes very helpful in disease detection, as well...

Boers, K. L., Allender, M. C., Novak, L. J. et al. 2020. Assessment of hematologic and corticosterone response in free-living eastern box turtles (Terrapene carolina carolina) at capture and after handling. Zoo Biology 39(1), 13-22.

Hematology is a common tool for wildlife health assessments. Manual leukocyte counts are required in reptiles, however, disagreement between quantification methods has been observed in some chelonians. This study determined agreement between two methods of...

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...

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...

Lensen, C. M. M., Moons, C. P. H., Diederich, C. 2015. Saliva sampling in dogs: How to select the most appropriate procedure for your study. Journal of Veterinary Behavior 10(6), 504-512.

Saliva sampling is an easy, noninvasive method to assess short-term physiological changes, and as such is a valuable addition to behavioral studies in dogs. Different methods for collecting saliva samples in dogs have been reported...

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...

Packer, R. M. A., Davies, A. M., Volk, H. A. 2019. What can we learn from the hair of the dog? Complex effects of endogenous and exogenous stressors on canine hair cortisol. PLOS ONE 14(5), e0216000.

Hair is an emerging biological matrix in which to measure chronic HPA axis activity, offering a longer term view into an animal’s life. We explored effects of exogenous (e.g. lifestyle, medications, social environment) and endogenous...

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...