Source: KANSAS STATE UNIV submitted to NRP
DETERMINATION OF THE OPTIMAL ANALGESIC REGIMEN FOR GOATS WITH LAMENESS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
ACTIVE
Funding Source
Reporting Frequency
Annual
Accession No.
1022696
Grant No.
2020-67015-31456
Cumulative Award Amt.
$496,000.00
Proposal No.
2019-06202
Multistate No.
(N/A)
Project Start Date
Jun 1, 2020
Project End Date
May 31, 2025
Grant Year
2020
Program Code
[A1251]- Animal Health and Production and Animal Products: Animal Well-Being
Recipient Organization
KANSAS STATE UNIV
(N/A)
MANHATTAN,KS 66506
Performing Department
Clinical Sciences
Non Technical Summary
Lameness in goats is a painful condition with serious health and welfare implications. Currently, there are limited data available regarding analgesic drug therapy in goats because validated methods of pain assessment are needed for US FDA to approve these medications. Goals for this project are to: deliver facial grimace and pressure mat gait analysis methods to objectively assess lameness pain in goats; enhance the management of lameness pain by providing dose, route, duration, frequency and withhold period recommendations for pain relieving drugs in goats; and assure consumer safety by characterizing milk and edible tissue depletion kinetics to be used to establish appropriate withholding intervals. Knowledge gained from this proposal will address current animal welfare concerns by delivering methods to assess animals for pain, fill voids in the literature regarding pharmacologic interventions, and characterize milk and edible tissue depletion kinetics following pharmacologic interventions. These activities will maintain consumer confidence in the production practices of meat and dairy goat systems.
Animal Health Component
75%
Research Effort Categories
Basic
25%
Applied
75%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
31538201020100%
Goals / Objectives
Specific Aim 1: To refine an amphotericin B lameness model and optimize a behavioral ethogram in goats. We have evaluated two different lameness models in goats. Amphotericin B induced the most consistent lameness, but the dose used resulted in lameness that was too severe. Our hypothesis is that an alternative dose of amphotericin B injected into the distal interphalangeal joint will produce a more consistent lameness that is maintained for the entire study period. This will deliver a lameness model and outcome assessment methods that can be used to test pharmacological interventions in goats.Specific Aim 2: To determine the most efficacious therapeutic regimen for controlling pain associated with induced lameness. The pharmacokinetics of multiple NSAIDs have been described by our research group and others. However the clinical efficacy of NSAIDs controlling pain associated with lameness has not been investigated. Our goal is to test the clinical efficacy of three NSAID regimens at three different dosages (low, medium, high doses) to define those that are most effective in controlling lameness pain.Specific Aim 3: To characterize the milk and edible tissue (meat and offal) residue depletion kinetics of the most efficacious therapeutic drug regimen in goats. There are limited data in the published literature describing the milk and tissue deletion of NSAIDs in goats as use of these drugs fall under the Minor Use - Minor Species designation. Determination of the milk and edible tissue depletion profiles will assist entities like the Food Animal Residue Avoidance Databank (FARAD) in achieving its goal of providing scientifically-based recommendations regarding safe withdrawal intervals of drugs and chemicals in food-producing animals.
Project Methods
Specific Aim 1:Study Animals: Twenty-four castrated male, Boer or Boer-cross goats will be randomly allocated into one of four treatment groups (n = 6 goats/treatment).Treatment Groups: Treatment groups for Specific Aim 1TreatmentDose (mg)VolumeLameness#/groupHigh dose-Low volumeAmphotericin B100.5 mlYESn = 6High dose-High volumeAmphotericin B101 mlYESn = 6Low dose-Low volumeAmphotericin B50.5 mlYESn = 6ControlSalinen/a1 mlNOn = 6Lameness induction: Lameness will be induced by injecting the dose of amphotericin B into the left hind limb lateral distal interphalangeal joint (intra-articular space). Goats enrolled as non-lame controls will undergo the same procedures as those in the treatment groups with the exception of sterile saline being injected into the distal interphalangeal joint.Sampling: The outcome variables of interest that will be assessed for this specific aim will be (1) visual lameness scores; (2) plasma cortisol concentrations; (3) plasma substance P concentrations; (4) infrared thermography of the lateral rear feet; (5) mechanical nociception threshold tests of the lateral rear feet; (6) facial grimace score; (7) behavior analysis; and (8) pressure mat gait analysis. Outcome variables will be assessed at each time point.Tissue amphotericin B residue: In order to confirm animals injected with amphotericin B into the distal interphalangeal joint do not have violative tissue residues; animals enrolled into the lameness groups will be euthanized and edible tissue harvested to determine tissue amphotericin B concentrations. Tissue amphotericin B concentrations will be determined using liquid chromatography coupled with mass spectrometry (UPLC-MS/MS). Tissue drug concentrations will be analyzed using the tolerance limit method published by the FDA to estimate a meat withhold time as done in previous studies.Statistical Analysis: Data will be analyzed using generalized linear mixed models. Treatment, time, and their interactions will be used as fixed effects, whereas goat is a random effect and the subject of repeated measures. Statistical significance will be set at p≤0.05.Specific Aim 2:Study Animals: Forty-four castrated male, Boer or Boer-cross goats will be used so that each goat is enrolled two times utilizing both rear limbs. The goats will be randomly allocated into one of 11 treatment groups (n = 8 goats/treatment).Study design and treatment groups: A cross-over, dose titration study design will be used so that an appropriate study power can be obtained while reducing the total number of animals required for research. Each animal will be utilized two times, with a rest period between study replicates to allow for full lameness recovery and treatment washout. Goats will be randomly allocated into treatment groups based on the limb (left hind or right hind) to be induced prior to lameness induction. A group of goats will be randomly selected to serve as non-lame controls.To determine the optimal non-steroidal anti-inflammatory drug (NSAID) regimen for controlling pain associated with lameness, three NSAID compounds at three different doses will be investigated. Two control groups will be utilized, a positive (lame) control and negative (non-lame) control. The treatment groups will be as follows:TDF-Low: lameness induction + transdermal flunixin at 3.3 mg/kg topically + oral placeboTDF-Med: lameness induction + transdermal flunixin at 4.2 mg/kg topically + oral placeboTDF-High: lameness induction + transdermal flunixin at 5 mg/kg topically + oral placeboFIR-Low: lameness induction + firocoxib at 0.5 mg/kg orally + topical placeboFIR-Med: lameness induction + firocoxib at 1.0 mg/kg orally + topical placeboFIR-High: lameness induction + firocoxib at 2.0 mg/kg orally + topical placeboMEL-Low: lameness induction + meloxicam at 1.0 mg/kg orally + topical placeboMEL-Med: lameness induction + meloxicam at 2.0 mg/kg orally + topical placeboMEL-High: lameness induction + meloxicam at 3.0 mg/kg orally + topical placebo+Con: lameness induction + placebo control orally + topical placebo-Con: sham lameness induction + placebo control orally + topical placeboLameness induction: Lameness will be induced by injecting the dose of amphotericin B into the left hind limb lateral distal interphalangeal joint (intra-articular space). Goats enrolled as non-lame controls will undergo the same procedures as those in the treatment groups with the exception of sterile saline being injected into the distal interphalangeal joint.Sampling: The outcome variables of interest that will be assessed for this specific aim will be (1) visual lameness scores; (2) plasma cortisol concentrations; (3) plasma substance P concentrations; (4) infrared thermography of the lateral rear feet; (5) mechanical nociception threshold tests of the lateral rear feet; (6) facial grimace score; (7) behavior analysis; and (8) pressure mat gait analysis. Outcome variables will be assessed at each time point.Statistical Analysis: Data will be analyzed using generalized linear mixed models. Treatment, time, and their interactions will be used as fixed effects, whereas goat is a random effect and the subject of repeated measures. Statistical significance will be set at p≤0.05.Specific Aim 3a: Study Animals: Ten female Nubian dairy goats will be enrolled to meet the guidelines set forth by the FDA Guidance for Industry "General Principles for Evaluating the Human Food Safety of New Animal Drugs Used in Food-Producing Animals".Treatment Groups: Goats will be administered three doses at 24 hour intervals, of the analgesic drug found to be most efficacious in controlling pain associated with lameness in Specific Aim 2.Sampling: The study will be conducted using the methods outlined in the Food and Drug Administration (FDA) Guidance for Industry (GFI) #207.Sample Analysis: Milk and plasma samples will be analyzed for drug concentrations using the liquid chromatography coupled with mass spectrometry (UPLC-MS/MS).Data Analysis: The drug concentrations in milk data will be analyzed using the tolerance limit method recommended by FDA to estimate a milk discard time as we have done in previous studies.Specific Aim 3b: Study Animals: Twenty Boer or Boer-cross goats, 10 male and 10 female, weighing approximate 22 kilograms will be enrolled. All goats will be determined to be free of disease and will not have received the test NSAID 30 days prior to enrollment. The number of animals enrolled is consistent with the recommendations of FDA GFI # 207.Treatment Groups: Goats will be administered three doses at 24 hour intervals, of the analgesic drug found to be most efficacious in controlling pain associated with lameness in Specific Aim 2.Sampling: The study will be conducted using the methods outlined in the US Food and Drug Administration (FDA) Guidance for Industry (GFI) #207 (Studies to Evaluate the Metabolism and Residue Kinetics of Veterinary Drugs In Food Producing Animals: Marker Residue Depletion Studies to Establish Product Withdrawal Periods). A total of four (4) goats will be euthanized and tissue samples harvested at each of five (5) time points. The final time points used to harvest animals will be determined based on the optimal drug regimen found to be most efficacious for controlling pain associated with lameness in Specific Aim 2. Tissues to be collected at each predetermined time point include muscle, liver, kidney, and fat per FDA Guidance for Industry #207.Statistical Analysis: Tissue samples will be analyzed for drug concentrations using liquid chromatography coupled with mass spectrometry (UPLC-MS/MS) methods.Data Analysis: Tissue drug concentrations will be analyzed using the tolerance limit method published by the FDA to estimate a meat withhold time as we did in our recent studies.

Progress 06/01/23 to 05/31/24

Outputs
Target Audience:Our target audience represents several constituencies. Foremost, our work is designed to be applicable to veterinary professionals and animal scientists. Veterinary professionals and livestock producers have a great deal of interest in this research as it will provide information for an optimal analgesia for lame goats. Animal scientists in industry and academia are targeted because our work may produce significant advances for animal welfare during livestock production. The research will provide goat producers and veterinarians with practical strategies to provide analgesia to lame goats. These strategies will also ultimately be paired with data so veterinarians can provide appropriate meat and milk withholding intervals for goats being treated with analgesics. To best communicate the value of the research to a broad audience, our group will participate in national and regional conference proceedings and publication of findings in peer-reviewed journals. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This project provided professional training and development for Mikaela Weeder. Mikaela Weeder is a graduate student at Kansas State University College of Veterinary Medicine. This grant provided resources for her to completeresearch required for her PhD.This project provided her opportunities to work on labratory assays, including ELISAs, RIAs, and LCMS methodolgy. It also allowed her to plan and complete multiple studies from beginning to end. This work also allowed her first and second manuscripts for the peer revision process. Through this process, she had both manuscripts accepted for publication in Translational Animal Science and in JAVMA. How have the results been disseminated to communities of interest?The results from Specific aim 1 have been published in Translational Animal Science for communities of interest. The castration paper was presented at AABP 2023 in an oral format. It was also presented at KSU CVM Phi Zeta Day 2023 in an oral format. It will be presented at WBC 2024 in poster format. The castration paper was published online and in printSpring of 2024 in JAVMA. The results from Specific aim 2 have been presented in a poster format at KSU CVM Phi Zeta Day 2024. Data will be published upon data analysis completion. What do you plan to do during the next reporting period to accomplish the goals?Atissue residue study to determine the tissue withdrawalintervals for meloxicam was completed in Spring 2024. Results are waiting to be analyzed. The milk residue study to determine the withdrawal interval for meloxicam in milk is set to be completed in Summer 2024 in collborationwith Langston University.

Impacts
What was accomplished under these goals? Specific aim 1: This project has been completed and was published in 2023.We were able to create a reproducible lameness model in goats using Amphotericin B. Three different models were tested (high dose-high volume, high dose-low volume, low dose-low volume) alongside a control. The modelthat created transient lameness consistently in goats for a short period of time was the high dose-low volume treatment. A grimace scale was also created during this project, which is the first goat specific grimace scale noted in literature. Specific aim 2: This project has been completed. Data analysis is being finalized before this project is to be submitted for publication and optimal dose/drug is concluded. No adverse reactions were noted in goats given flunixin, firocoxib, or meloxicam at three varying dosages. Specific Aim 3: The edible tissue phase of this project has been completed. Samples have been gathered and are awaiting drug concentration analysis through LCMS methodology.

Publications

  • Type: Journal Articles Status: Published Year Published: 2023 Citation: Weeder MM, Kleinhenz MD, Reppert EJ, Fritz BR, Viscardi AV, Montgomery SR, Martin MS, Curtis AK, Leslie AA, Lou ME, Hall MG, Coetzee JF. Optimal lameness induction model development using amphotericin B in meat goats. Transl Anim Sci. 2023 Sep 2;7(1):txad105. doi: 10.1093/tas/txad105. PMID: 37720823; PMCID: PMC10503652.
  • Type: Journal Articles Status: Published Year Published: 2024 Citation: Weeder, Mikaela & Kleinhenz, Michael & Reppert, Emily & Weaver, Leslie & Johnson, Blaine & Leslie, Alyssa & Smith, Kristen & Curtis, Andrew & Fritz, Bailey & Coetzee, Johann. (2024). Comparison of firocoxib and meloxicam for pain mitigation in goats undergoing surgical castration. Journal of the American Veterinary Medical Association. 1-8. 10.2460/javma.23.10.0575.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2023 Citation: Weeder, Mikaela & Kleinhenz, Michael & Reppert, Emily & Weaver, Leslie & Johnson, Blaine & Leslie, Alyssa & Smith, Kristen & Curtis, Andrew & Fritz, Bailey & Coetzee, Johann. (2023). Comparison of firocoxib and meloxicam for pain mitigation in goats undergoing surgical castration. AABP Proceedings. Vol 56(2).


Progress 06/01/22 to 05/31/23

Outputs
Target Audience:Our target audience represents several constituencies. Foremost, our work is designed to be applicable to veterinary professionals and animal scientists. Veterinary professionals and livestock producers have a great deal of interest in this research as it will provide information for an optimal analgesia for lame goats. Animal scientists in industry and academia are targeted because our work may produce significant advances for animal welfare during livestock production. The research will provide goat producers and veterinarians with practical strategies to provide analgesia to lame goats. These strategies will also ultimately be paired with data so veterinarians can provide appropriate meat and milk withholding intervals for goats being treated with analgesics. To best communicate the value of the research to a broad audience, our group will participate in national and regional conference proceedings and publication of findings in peer-reviewed journals. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Although the primary goals of the project are not intended to provide training and professional development, it has facilitated the recruitment and training of an additional graduate student (Mikaela Weeder) starting at the end of the previous reporting period. She has undergone many hours of professional development via university safety compliance modules and departmental seminars. These all serve to refine her skills as a scientist and support her professional goals. She will also received training from her mentor, fellow graduate students, and collaborators in order to better prepare her to successfully complete her work on the project. Furthermore, the research has accommodated veterinary and undergraduate students in production-relevant learning environments. Training activities have included data collection and analysis, animal manipulations and handling, and experimental design. These opportunities are valuable for students as well as researchers to increase proficiency and collaboration in veterinary research. Other students have received extensive training in animal handling, sampling, and data entry as a result of this project. This training is in line with the professional goals of the students involved. How have the results been disseminated to communities of interest?Preliminary results from the castration study were shared at the Phi Zeta Research Day at Kansas State University. What do you plan to do during the next reporting period to accomplish the goals?Prior to the end of the reporting period, we will have analyzed the data and determine the optimal drug regimen for controlling pain associated with lameness in goats. Determination of a tissue residue profile and withdrawal interval will be undertaken. Goats for the tissue residue study have been procured.

Impacts
What was accomplished under these goals? The goats procured for Aim 2 were intact males and needed to be castrated prior to study enrollment. This allowed for a subset to be used to determine the efficacy of two NSAIDs on surgical castration pain. There are currently no approved analgesic drugs for surgical castration in goats. This study sought to examine the effects of firocoxib and meloxicam in goats after surgical castration. Twelve male goats (6-8m) under injectable anesthesia were surgically castrated and administered firocoxib (n=6) or meloxicam (n=6). Treatments were administered at 0, 24 and 48h. Six male goats served as controls (CNTL). Outcome measurements included infrared thermography, visual analog scoring, kinetic gait analysis, and blood plasma. Collection of outcome measures occurred at -24, 4, 8, 24, 48 and 72h. Visual analog scoring for firocoxib and meloxicam were significantly higher at 48hr compared to CNTL (P =0.03). Rear stride length was significantly longer when firocoxib was administered compared to meloxicam and CNTL at 72h (P=0.0006, P=0.0007). Further evaluation of firocoxib and meloxicam is needed after surgical castration in goats, but this data is important to veterinarian and their clients. Study Aim 2 was completed over the summer and fall of 2022. Fifty goats were enrolled onto the study. Lameness was induced using 0.3 mL of amphotericin B at 50 mg/mL, which was the optimal concentration determined in Aim 1. The induction procedure resulted in lameness in 100% of the induced animals. Outcome variables assessed were thermography of the lame and sound rear feet, mechanical nociception threshold tests, visual lameness score, facial grimace scale, and kinetic gait analysis. Outcomes are still being analyzed and will be complete summer 2023 in-order to select the optimal drug and dose for controlling lameness pain. This will allow Aim 3a, determination of tissue residues to be completed summer/fall 2023.

Publications


    Progress 06/01/21 to 05/31/22

    Outputs
    Target Audience:Our target audience represents several constituencies. Foremost, our work is designed to be applicable to veterinary professionals and animal scientists. Veterinary professionals and livestock producers have a great deal of interest in this research as it will provide information for an optimal analgesia for lame goats. Animal scientists in industry and academia are targeted because our work may produce significant advances for animal welfare during livestock production. The research will provide goat producers and veterinarians with practical strategies to provide analgesia to lame goats. These strategies will also ultimately be paired with data so veterinarians can provide appropriate meat and milk withholding intervals for goats being treated with analgesics. To best communicate the value of the research to a broad audience, our group will participate in national and regional conference proceedings and publication of findings in peer-reviewed journals. Changes/Problems:No changes or problems have been encountered during this reporting period. What opportunities for training and professional development has the project provided? Although the primary goals of the project are not intended to provide training and professional development, it has facilitated the recruitment and training of an additional graduate student (Mikaela Weeder) starting at the end of the previous reporting period. She has undergone many hours of professional development via university safety compliance modules and departmental seminars. These all serve to refine her skills as a scientist and support her professional goals. She will also received training from her mentor, fellow graduate students, and collaborators in order to better prepare her to successfully complete her work on the project. Furthermore, the research has accommodated veterinary and undergraduate students in production-relevant learning environments. Training activities have included data collection and analysis, animal manipulations and handling, and experimental design. These opportunities are valuable for students as well as researchers to increase proficiency and collaboration in veterinary research. Other students have received extensive training in animal handling, sampling, and data entry as a result of this project. This training is in line with the professional goals of the students involved. How have the results been disseminated to communities of interest?Preliminary results from the study and development of a goat facial grimace scale were shared at the K-State CVM Phi Zeta Research Symposium and the 14th North American Regional Meeting of ISAE in Davis, CA. A poster describing the goat grimace scale was shared at the 2021 Veterinary Summer Research Scholar program. What do you plan to do during the next reporting period to accomplish the goals?Prior to the end of the reporting period, we will have analyzed all the data and determine an optimal lameness induction model. Goats for the second study have been procured and have been enrolled into one replicate of the Study Aim 2. Completion of Study Aim 2 should be complete in Q4 2022 with analysis complete by Q2 2023.

    Impacts
    What was accomplished under these goals? The study in Aim 1, Optimization of a lameness induction model using amphotericin B in meat goats has been completed. Data analysis is on-going, but projected to be complete within the first quarter of 2022. Twenty-four (24) meat type goats using three varying dosages of amphotericin B (Amp-B). Lameness was produced by an intraarticular injection into the left hind lateral claw distal interphalangeal joint with either a Hi-Hi, Hi-Low, or Low-Low treatment of Amp-B (n=6/group). A saline treatment of 0.5mL was used as a control (n=6). Lameness induction responses was analyzed by infrared thermography at the induced joint (IRT), mechanical-nociception threshold (MNT), visual lameness scoring (VLS), a visual analogue scale (VAS), kinetic gait analysis (PMT), plasma cortisol (CORT), prostaglandin metabolite E (PGE), substance P (Sub P), and facial grimace evaluation. Responses were taken at -24hr, 4hr, 6hr, 12hr, 24hr, 48hr, and 72hr. Of the three amphotericin B treatments, only the Hi-Low group produced lameness in all six treated goats. Lameness failed to develop in 2 Hi-Hi goats and 4 Low-Low goats. Differences between left hind (induced) and right hind (control) MNT values were significantly higher for the three treatment groups compared to the control group of (P=0.002). The High-Low goats had higher VAS measures at 24, 48 and 72 h compared to controls (P=0.02). While each Amp-B treatment was able to produce lameness, the Hi-Low treatment group (Amp-B, 5mg/0.25ml) provided the clearest reproducible lameness induction when compared to other treatments. Goats for Study Aim 2 were procured through the Sheep and Meat Goat Unit at Kansas State. A group of intact bucks of similar size and age were procured, but were not of the size needed for Study Aim 2. A subset (n = 18) were utilized in a comparative NSAID study for surgical castration. The NSAIDs compared were meloxicam at 1 mg/kg and firocoxib at 0.5 mg/kg. The data collection phase took place Q2 2022 so the goats were ready for Q3 enrollment onto Study Aim 2. Study Aim 2 commenced July 2022, and is still underway. The lameness induction protocol determined from Study Aim 1 (Hi-low) has been used on 20 goats with all 20 having a minimum of 3/5 grade lameness. The remaining replicates should be complete in Q3 2022.

    Publications

    • Type: Conference Papers and Presentations Status: Published Year Published: 2022 Citation: M Lou, MD Kleinhenz, EJ Reppert, MG Hall, M Weeder, JF Coetzee, AV Viscardi. Developing a Goat Grimace Scale to assess pain in goats. 14th North American Regional Meeting of ISAE. Davis, CA. 2022


    Progress 06/01/20 to 05/31/21

    Outputs
    Target Audience:Our target audience represents several constituencies. Foremost, our work is designed to be applicable to veterinary professionals and animal scientists. Veterinary professionals and livestock producers have a great deal of interest in this research as it will provide information for an optimal analgesia for lame goats. Animal scientists in industry and academia are targeted because our work may produce significant advances for animal welfare during livestock production. The research will provide goat producers and veterinarians with practical strategies to provide analgesia to lame goats. These strategies will also ultimately be paired with data so veterinarians can provide appropriate meat and milk withholding intervals for To best communicate the value of the research to a broad audience, our group will participate in national and regional conference proceedings and publication of findings in peer-reviewed journals. Changes/Problems:COVID-19 has caused a major delay in starting this project. University shut-downs and furloughs caused a back-log in research at the animal unit delaying study commencement. Further challenges include procuring goats needed for this project. A poor kid crop at the research unit last year as well as lack of market supply made procuring the needed goats difficult. This challenge was overcome via K-State extension agent networks. What opportunities for training and professional development has the project provided?Although the primary goals of the project are not intended to provide training and professional development, it has facilitated the recruitment and training of an additional graduate student (Mikaela Weeder) starting at the end of this reporting period. She has undergone many hours of professional development via university safety compliance modules and departmental seminars. These all serve to refine her skills as a scientist and support her professional goals. She will also received training from her mentor, fellow graduate students, and collaborators in order to better prepare her to successfully complete her work on the project. Furthermore, the research has accommodated veterinary and undergraduate students in production-relevant learning environments. Training activities have included data collection and analysis, animal manipulations and handling, and experimental design. These opportunities are valuable for students as well as researchers to increase proficiency and collaboration in veterinary research. Other students have received extensive training in animal handling, sampling, and data entry as a result of this project. This training is in line with the professional goals of the students involved. How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals?During the next reporting period, our group plans finalize the refinement of the lameness induction model (SA 1) and start work on determining an optimal analgesic regimen (SA 2).

    Impacts
    What was accomplished under these goals? Animals for SA1 have been procured and housed at the research unit.

    Publications