@article{khan_mondino_russell_case_fefer_woods_olby_gruen_2023, title={A novel task of canine olfaction for use in adult and senior pet dogs}, volume={13}, ISSN={["2045-2322"]}, url={https://europepmc.org/articles/PMC9908929}, DOI={10.1038/s41598-023-29361-x}, abstractNote={Abstract}, number={1}, journal={SCIENTIFIC REPORTS}, author={Khan, Michael Z. and Mondino, Alejandra and Russell, Katharine and Case, Beth and Fefer, Gilad and Woods, Hope and Olby, Natasha and Gruen, Margaret}, year={2023}, month={Feb} }
 @article{mondino_khan_case_giovagnoli_thomson_lascelles_gruen_olby_2023, title={Activity patterns are associated with fractional lifespan, memory, and gait speed in aged dogs}, volume={13}, ISSN={["2045-2322"]}, url={https://europepmc.org/articles/PMC9929073}, DOI={10.1038/s41598-023-29181-z}, abstractNote={Abstract}, note={PMID: 36788306; PMCID: PMC9929073.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Mondino, Alejandra and Khan, Michael and Case, Beth and Giovagnoli, Sara and Thomson, Andrea and Lascelles, B. Duncan X. and Gruen, Margaret and Olby, Natasha}, year={2023}, month={Feb} }
 @article{templeton_fefer_case_roach_azcarate-peril_gruen_callahan_olby_2023, title={Longitudinal Analysis of Canine Oral Microbiome Using Whole Genome Sequencing in Aging Companion Dogs}, volume={13}, ISSN={["2076-2615"]}, DOI={10.3390/ani13243846}, abstractNote={Aged companion dogs have a high prevalence of periodontal disease and canine cognitive dysfunction syndrome (CCDS) and the two disorders are correlated. Similarly, periodontal disease and Alzheimer’s Disease are correlated in people. However, little is known about the oral microbiota of aging dogs. The goal of this project was to characterize the longitudinal changes in oral microbiota in aged dogs. Oral swabs were taken from ten senior client-owned dogs on 2–3 occasions spanning 24 months and they underwent whole genome shotgun (WGS) sequencing. Cognitive status was established at each sampling time. A statistically significant increase in alpha diversity for bacterial and fungal species was observed between the first and last study visits. Bacteroidetes and proteobacteria were the most abundant bacterial phyla. Porphyromonas gulae was the most abundant bacterial species (11.6% of total reads). The species Lactobacillus gasseri had a statistically significant increase in relative abundance with age whereas Leptotrichia sp. oral taxon 212 had a statistically significant positive longitudinal association with cognition score. There is an increased fungal and bacterial alpha diversity in aging dogs over time and nearly universal oral dysbiosis. The role of the oral microbiota, particularly Leptotrichia and P. gulae and P. gingivalis, in aging and CCDS warrants further investigation.}, number={24}, journal={ANIMALS}, author={Templeton, Ginger B. and Fefer, Gilad and Case, Beth C. and Roach, Jeff and Azcarate-Peril, M. Andrea and Gruen, Margaret E. and Callahan, Benjamin J. and Olby, Natasha J.}, year={2023}, month={Dec} }
 @article{khan_mondino_russell_case_fefer_woods_olby_gruen_2023, title={Relationship between engagement with the impossible task, cognitive testing, and cognitive questionnaires in a population of aging dogs}, volume={9}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2022.1052193}, abstractNote={IntroductionThe aim of this study was to evaluate the engagement of aging dogs with a cognitively challenging and potentially frustrating task (the impossible task). Based on previous observations, we predicted that dogs showing signs of cognitive impairment in other cognitive tests and owner-completed questionnaires would show reduced engagement with the task.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Khan, Michael Z. and Mondino, Alejandra and Russell, Katharine and Case, Beth and Fefer, Gilad and Woods, Hope and Olby, Natasha J. and Gruen, Margaret E.}, year={2023}, month={Jan} }
 @article{mondino_khan_case_fefer_panek_gruen_olby_2023, title={Winning the race with aging: age-related changes in gait speed and its association with cognitive performance in dogs}, volume={10}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2023.1150590}, abstractNote={IntroductionIn humans, gait speed is a crucial component in geriatric evaluation since decreasing speed can be a harbinger of cognitive decline and dementia. Aging companion dogs can suffer from age-related mobility impairment, cognitive decline and dementia known as canine cognitive dysfunction syndrome. We hypothesized that there would be an association between gait speed and cognition in aging dogs.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Mondino, Alejandra and Khan, Michael and Case, Beth and Fefer, Gilad and Panek, Wojciech K. and Gruen, Margaret E. and Olby, Natasha J.}, year={2023}, month={Jun} }
 @article{nakanishi_lascelles_allen_case_gearing_enomoto_2022, title={A Pilot, Open-Label Study to Evaluate the Efficacy of Intra-Articular Administration of a Caninized TNF Receptor Fc Fusion Protein as a Treatment for Osteoarthritis-Associated Joint Pain}, volume={9}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2022.836709}, abstractNote={Tumor necrosis factor-α (TNF-α) is a potential target for osteoarthritis (OA) treatment. In several recent clinical studies in human OA, anti-TNF-α therapy showed promising results; however, these were open-label and based on patient-reported outcome measures. In this study, we developed a caninized TNF-α receptor-Fc (caTNFR-Fc) fusion protein and conducted a non-randomized, open-label, pilot study in dogs with OA using objectively measured ground reaction forces and activity. The aims of the study were to assess the efficacy of the intra-articular (IA) injection of the caTNFR-Fc fusion protein as a treatment for OA pain, and additionally to evaluate TNF concentrations in synovial fluid (SF) between joints with/without OA in dogs. Dogs (n = 12) with single-limb lameness due to single joint appendicular OA were recruited. All dogs received caTNFR-Fc fusion protein injection into the affected joint under sedation. Objective kinetic gait analysis using force plate was performed prior to (baseline), and at 14- and 28-days following treatment. Additionally, SF samples were collected from OA joints (n = 69) and non-OA joints (n = 79) in a different cohort of dogs and TNF-α were measured using enzyme-linked immunosorbent assay. No significant treatment effects on the limb use, activity, and the questionnaire were found. The concentration of TNF-α was significantly higher in OA joints than in healthy joints (p = 0.0019), but TNF-α was detected in only 10/69 OA samples. The IA injection of caTNFR-Fc fusion protein provided no benefit in terms of objective limb use and activity data in dogs with OA in this pilot study. Although the SF concentration of TNF-α was significantly higher in OA joints, few OA joints had measurable TNF-α. Collectively, the data indicate TNF-α may not be a good therapeutic target in canine OA.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Nakanishi, Aoi and Lascelles, B. Duncan X. and Allen, Julie and Case, Beth and Gearing, David and Enomoto, Masataka}, year={2022}, month={Jun} }
 @article{fefer_khan_panek_case_gruen_olby_2022, title={Relationship between hearing, cognitive function, and quality of life in aging companion dogs}, volume={8}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.16510}, DOI={10.1111/jvim.16510}, abstractNote={Abstract}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Fefer, Gilad and Khan, Michael Z. and Panek, Wojciech K. and Case, Beth and Gruen, Margaret E. and Olby, Natasha J.}, year={2022}, month={Aug} }
 @article{fefer_panek_khan_singer_westermeyer_mowat_murdoch_case_olby_gruen_2022, title={Use of Cognitive Testing, Questionnaires, and Plasma Biomarkers to Quantify Cognitive Impairment in an Aging Pet Dog Population}, volume={87}, ISSN={["1875-8908"]}, DOI={10.3233/JAD-215562}, abstractNote={Background: Aging dogs may suffer from canine cognitive dysfunction syndrome (CCDS), a condition in which cognitive decline is associated with amyloid pathology and cortical atrophy. Presumptive diagnosis is made through physical examination, exclusion of systemic/metabolic conditions, and completion of screening questionnaires by owners. Objective: This study aimed to determine whether cognitive function could be quantified in aging pet dogs, and to correlate cognitive testing with validated questionnaires and plasma neurofilament light chain (pNfL) concentration. Methods: Thirty-nine dogs from fifteen breeds were recruited (9.3 to 15.3 years). Owners completed the Canine Dementia Scale (CADES) and Canine Cognitive Dysfunction Rating scale (CCDR). Executive control and social cues were tested, and pNfL was measured with single molecule array assay. Comparisons were made between cognitive testing scores, CADES, CCDR scores, and pNfL. Results: CADES scoring classified five dogs as severe CCDS, six as moderate, ten as mild, and eighteen as normal. CCDR identified seven dogs at risk of CCDS and thirty-two as normal. Cognitive testing was possible in the majority of dogs, although severely affected dogs were unable to learn tasks. CADES score correlated with sustained attention duration (r = –0.47, p = 0.002), inhibitory control (r = –0.51, p = 0.002), detour (r = –0.43, p = 0.001), and pNfL (r = 0.41, p = 0.025). Concentration of pNfL correlated with inhibitory control (r = –0.7, p≤0.001). The CCDR scale correlated with performance on inhibitory control (r = –0.46, p = 0.005). Conclusion: Our findings suggest that a multi-dimensional approach using a combination of questionnaires, specific cognitive tests, and pNfL concentration can be used to quantify cognitive decline in aging pet dogs.}, number={3}, journal={JOURNAL OF ALZHEIMERS DISEASE}, author={Fefer, Gilad and Panek, Wojciech K. and Khan, Michael Z. and Singer, Matthew and Westermeyer, Hans D. and Mowat, Freya M. and Murdoch, David M. and Case, Beth and Olby, Natasha J. and Gruen, Margaret E.}, year={2022}, pages={1367–1378} }
 @article{hoel_templeton_fefer_case_shah_gruen_olby_2021, title={Sustained Gaze Is a Reliable In-home Test of Attention for Aging Pet Dogs}, volume={8}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2021.819135}, abstractNote={Canine Cognitive Dysfunction Syndrome (CCDS) is a syndrome of progressive cognitive decline comparable to Alzheimer's Disease. The sustained gaze test captures attention loss associated with CCDS in laboratory settings, and adapting the sustained gaze test for use by owners at home could greatly increase the data generated on CCDS. We hypothesized that it would be feasible for owners to perform the sustained gaze test at home, and that results would be reliable over repeated trials. Training materials were developed and dog owners underwent training and performed the test in triplicate at weekly intervals for 3 weeks. Gaze videos and a CAnine DEmentia Scale (CADES) questionnaire were submitted each week. Videos were examined for inclusion and duration of gaze was recorded. One observer repeated video assessments twice, 1 week apart; five different observers assessed videos once. Outcome measures included the relationship between CADES and gaze duration, test-retest reliability of owner-performed sustained gaze testing, and intra- and inter-rater reliability. Twenty dogs aged 7–15.5 years completed testing. The majority of videos were acceptable (162/183). Within dog test-retest reliability was excellent (ICC = 0.96). Intra- and interobserver reliability for determining video validity for inclusion were substantial (k = 0.76 and 0.78, respectively); for duration of gaze these were excellent (ICC = 0.99 and 0.96, respectively). Gaze duration was significantly associated with CADES (p = 0.0026). We conclude that owners can perform the sustained gaze test at home and that data generated are reliable and correlate to CADES, a validated measure of dementia.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Hoel, Jane A. and Templeton, Ginger B. and Fefer, Gilad and Case, Beth C. and Shah, Anshu and Gruen, Margaret E. and Olby, Natasha J.}, year={2021}, month={Dec} }
 @article{gruen_case_robertson_campbell_korpivaara_2020, title={Evaluation of repeated dosing of a dexmedetomidine oromucosal gel for treatment of noise aversion in dogs over a series of noise events}, volume={187}, ISSN={["2042-7670"]}, url={https://doi.org/10.1136/vr.106046}, DOI={10.1136/vr.106046}, abstractNote={Background Noise aversion is a common behavioural disorder in dogs; affected dogs show fear behaviours in response to noise stimuli. Pharmacological treatment is effective for many dogs; clinical reports suggest anxiolytic treatment lowers the need for treatment over time. We aimed to evaluate the effect of dexmedetomidine oromucosal gel for dogs with noise aversion over a series of noise events. Furthermore, we evaluated burden of care for owners of dogs with noise aversion via questionnaire. Methods Owners of enrolled dogs completed records for 10 noise events indicating whether their dog received dexmedetomidine gel and pretreatment and post-treatment anxiety scores; adverse events were noted. Owners were queried about burden of care. Results Twenty-two client-owned dogs completed recordings for 10 events. Logistic regression results showed a significant effect for time of event with decreased probability of receiving treatment for subsequent events (OR=0.75, P=0.0017). Within an event, significant improvement in anxiety was seen (median improvement 11 points; paired Wilcoxon; P<0.0001). We found overall burden of care was manageable, yet many owners agreed with statements regarding frustration (42 per cent), stress (46 per cent), guilt (42 per cent) and sadness (75 per cent) about their dog’s condition. Conclusions Repeated use of dexmedetomidine gel for noise events resulted in decreased need for administration. Burden of care is important to discuss with clients.}, number={12}, journal={VETERINARY RECORD}, publisher={Wiley}, author={Gruen, Margaret and Case, Beth C. and Robertson, James B. and Campbell, Sharon and Korpivaara, Mira Elina}, year={2020}, month={Dec} }
 @article{muller_gaines_gruen_case_arrufat_innes_lascelles_2016, title={Evaluation of Clinical Metrology Instrument in Dogs with Osteoarthritis}, volume={30}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.13923}, DOI={10.1111/jvim.13923}, abstractNote={BackgroundIn veterinary clinical pain studies, there is a paucity of data on test‐retest variability in Clinical Metrology Instruments (CMIs), and it is unknown whether CMIs should be administered using independent (respondents not permitted to see previous answers) or dependent (respondents shown previous answers) interviewing.}, number={3}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Muller, C. and Gaines, B. and Gruen, M. and Case, B. and Arrufat, K. and Innes, J. and Lascelles, B.D.X.}, year={2016}, month={Mar}, pages={836–846} }
 @article{orlando_case_thomson_griffith_sherman_2016, title={Use of oral trazodone for sedation in cats: a pilot study}, volume={18}, ISSN={["1532-2750"]}, DOI={10.1177/1098612x15587956}, abstractNote={ObjectivesResistance to transportation and stressful veterinary visits are major causes for a decrease in feline veterinary care. Few options exist for oral sedatives to reduce cats’ anxiety prior to veterinary visits. The purpose of this study was to evaluate the safety and efficacy of oral trazodone for use as a single dose agent for sedation in cats.}, number={6}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Orlando, Jillian M. and Case, Beth C. and Thomson, Andrea E. and Griffith, Emily and Sherman, Barbara L.}, year={2016}, month={Jun}, pages={476–482} }
 @article{knazovicky_helgeson_case_gruen_maixner_lascelles_2016, title={Widespread somatosensory sensitivity in naturally occurring canine model of osteoarthritis}, volume={157}, ISSN={0304-3959}, url={http://dx.doi.org/10.1097/j.pain.0000000000000521}, DOI={10.1097/j.pain.0000000000000521}, abstractNote={Abstract Osteoarthritis (OA)-associated pain is a leading cause of disability. Central sensitization (CS), as a result of OA, is recognized as an important facet of human patients' chronic pain and has been measured in people using quantitative sensory testing (QST) testing. The spontaneous canine OA model has been suggested as a good translational model, but CS has not been explored in this model. In this study, QST was performed on dogs with and without spontaneous hip or stifle OA to determine whether OA is associated with CS in this model. Mechanical (von Frey and blunt pressure) and thermal (hot and cold) sensory thresholds obtained in dogs with chronic OA-associated pain (n = 31) were compared with those of normal dogs (n = 23). Dogs were phenotyped and joint-pain scored, and testing was performed at the OA-affected joint, cranial tibial muscle, and dorsal metatarsal region. QST summary data were evaluated using mixed-effect models to understand the influence of OA status and covariates, and dogs with OA and control dogs were compared. The presence of OA was strongly associated with hyperalgesia across all QST modalities at the index joint, cranial tibial muscle, and metatarsal site. Mechanical QST scores were significantly moderately negatively correlated with total joint-pain scores. The spontaneous canine OA model is associated with somatosensory sensitivity, likely indicative of CS. These data further validate the canine spontaneous OA model as an appropriate model of the human OA pain condition.}, number={6}, journal={PAIN}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Knazovicky, David and Helgeson, Erika S. and Case, Beth and Gruen, Margaret E. and Maixner, William and Lascelles, B. Duncan X.}, year={2016}, month={Jun}, pages={1325–1332} }
 @article{lascelles_knazovicky_case_freire_innes_drew_gearing_2015, title={A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain}, volume={11}, ISSN={["1746-6148"]}, url={https://dx.doi.org/10.1186/s12917-015-0413-x}, DOI={10.1186/s12917-015-0413-x}, abstractNote={There is a critical need for proven drugs other than non-steroidal anti-inflammatory drugs for treatment of degenerative joint disease (DJD) pain in dogs. Antibodies against nerve growth factor (NGF) are analgesic in rodent models and in humans with DJD. This pilot study aimed to evaluate the efficacy of a novel caninised anti-NGF antibody (NV-01) for the treatment of DJD pain in dogs. In a randomized, parallel group, stratified, double masked, placebo controlled, proof of principle clinical pilot study design, 26 dogs with DJD received NV-01 (200 mcg/kg IV) or placebo on day 0 (D0). In addition to objective accelerometry measures, owners completed clinical metrology instruments (Client-Specific Outcome Measures [CSOM], Canine Brief Pain Inventory [CBPI] and Liverpool Osteoarthritis in Dogs Index [LOAD]) on D0, D14 and D28. CBPI subscales (pain severity [PS] and pain interference [PI]), CSOM and LOAD scores were evaluated within and between groups for change over time. Recognized success/failure criteria were applied and success compared between groups. CBPI PS and PI scores significantly improved in the NV-01 group (PS: D0-14, P = 0.012 and D0-28, P = 0.019; PI: D0-14, P = 0.012 and D0-28, P = 0.032) but not in the placebo group. CSOM scores showed similar patterns with a significant difference between within-group changes at D14 and D28 (P = 0.038 and P = 0.009, respectively), and significantly more successes at D28 (P = 0.047). LOAD scores significantly improved in the NV-01 group (D0-14, P = 0.004 and D0-28, P = 0.002) but not in the placebo group. There were significant differences between the groups for change in LOAD score at D14 (P = 0.014) and D28 (P = 0.033). No side effects were noted. Activity in the NV-01 group increased over the study period compared to placebo (P = 0.063) and the difference between the groups for change in activity over the time period 9am-5pm (8 hours) was significant (P = 0.006). These pilot data demonstrate a positive analgesic effect of anti-NGF antibody in dogs suffering from chronic pain. The magnitude of the effect appeared identical to that expected with an NSAID.}, number={1}, journal={BMC VETERINARY RESEARCH}, publisher={BioMed Central}, author={Lascelles, B. Duncan X. and Knazovicky, David and Case, Beth and Freire, Mila and Innes, John F. and Drew, Alexander C. and Gearing, David P.}, year={2015}, month={Apr} }
 @article{sherman_gruen_case_foster_fish_lazarowski_depuy_dorman_2015, title={A test for the evaluation of emotional reactivity in Labrador retrievers used for explosives detection}, volume={10}, ISSN={["1878-7517"]}, DOI={10.1016/j.jveb.2014.12.007}, abstractNote={The United States Marine Corps (USMC) uses Labrador retrievers as improvised explosive device detection dogs (IDDs). Of critical importance is the selection of dogs that are emotionally suited for this highly specialized application. The goal of our study was to develop an emotional reactivity test (ERT) as a screening tool for the selection of IDDs. The ERT included a series of subtasks that expose each dog sequentially to visual, auditory, and experiential stimuli with an associated grading scale used by trained observers to rate individual dog responses. In this study, 16 Labrador retrievers that met initial selection criteria as candidate IDDs were assessed using the ERT, measurement of plasma and salivary cortisol concentrations (pre- and post-ERT), and an independent open-field test of anxiety in response to sound stimuli. Based on the sum of its responses, each dog was assigned an aggregate ERT score. Aggregate ERT scores from independent trained observers were highly concordant [Shrout-Fleiss's intraclass correlation (2,1) = 0.96] suggesting excellent inter-rater reliability. The aggregate ERT scores were also negatively correlated with the dogs' scores on the open-field anxiety test (Spearman rank correlation, n = 16, r = −0.57, P = 0.0214). In addition, there were significant increases in salivary (Wilcoxon signed rank, n = 16, S = 38.5, P = 0.0458) and plasma (Wilcoxon signed rank, n = 16, S = 68, P < 0.0001) cortisol levels after the ERT, compared with baseline, suggesting that exposure to the ERT test elements produced a physiological stress response. We conclude that the ERT is a useful pre-training screening test that can be used to identify dogs with a low threshold of emotional reactivity for rejection, and dogs with a high threshold of emotional reactivity for entry into the IDD training program.}, number={2}, journal={JOURNAL OF VETERINARY BEHAVIOR-CLINICAL APPLICATIONS AND RESEARCH}, author={Sherman, Barbara L. and Gruen, Margaret E. and Case, Beth C. and Foster, Melanie L. and Fish, Richard E. and Lazarowski, Lucia and DePuy, Venita and Dorman, David C.}, year={2015}, pages={94–102} }
 @article{gruen_case_foster_lazarowski_fish_landsberg_depuy_dorman_sherman_2015, title={The use of an open-field model to assess sound-induced fear and anxiety-associated behaviors in Labrador retrievers}, volume={10}, ISSN={["1878-7517"]}, DOI={10.1016/j.jveb.2015.03.007}, abstractNote={Previous studies have shown that the playing of thunderstorm recordings during an open-field task elicits fearful or anxious responses in adult beagles. The goal of our study was to apply this open field test to assess sound-induced behaviors in Labrador retrievers drawn from a pool of candidate improvised explosive devices (IED)-detection dogs. Being robust to fear-inducing sounds and recovering quickly is a critical requirement of these military working dogs. This study presented male and female dogs, with 3 minutes of either ambient noise (Days 1, 3 and 5), recorded thunderstorm (Day 2), or gunfire (Day 4) sounds in an open field arena. Behavioral and physiological responses were assessed and compared to control (ambient noise) periods. An observer blinded to sound treatment analyzed video records of the 9-minute daily test sessions. Additional assessments included measurement of distance traveled (activity), heart rate, body temperature, and salivary cortisol concentrations. Overall, there was a decline in distance traveled and heart rate within each day and over the five-day test period, suggesting that dogs habituated to the open field arena. Behavioral postures and expressions were assessed using a standardized rubric to score behaviors linked to canine fear and anxiety. These fear/anxiety scores were used to evaluate changes in behaviors following exposure to a sound stressor. Compared to control periods, there was an overall increase in fear/anxiety scores during thunderstorm and gunfire sound stimuli treatment periods. Fear/anxiety scores were correlated with distance traveled, and heart rate. Fear/anxiety scores in response to thunderstorm and gunfire were correlated. Dogs showed higher fear/anxiety scores during periods after the sound stimuli compared to control periods. In general, candidate IED-detection Labrador retrievers responded to sound stimuli and recovered quickly, although dogs stratified in their response to sound stimuli. Some dogs were robust to fear/anxiety responses. The results suggest that the open field sound test may be a useful method to evaluate the suitability of dogs for IED-detection training.}, number={4}, journal={JOURNAL OF VETERINARY BEHAVIOR-CLINICAL APPLICATIONS AND RESEARCH}, author={Gruen, Margaret E. and Case, Beth C. and Foster, Melanie L. and Lazarowski, Lucia and Fish, Richard E. and Landsberg, Gary and Depuy, Venita and Dorman, David C. and Sherman, Barbara L.}, year={2015}, pages={338–345} }
 @article{lazarowski_foster_gruen_sherman_case_fish_milgram_dorman_2014, title={Acquisition of a visual discrimination and reversal learning task by Labrador retrievers}, volume={17}, ISSN={["1435-9456"]}, DOI={10.1007/s10071-013-0712-1}, abstractNote={Optimal cognitive ability is likely important for military working dogs (MWD) trained to detect explosives. An assessment of a dog’s ability to rapidly learn discriminations might be useful in the MWD selection process. In this study, visual discrimination and reversal tasks were used to assess cognitive performance in Labrador retrievers selected for an explosives detection program using a modified version of the Toronto General Testing Apparatus (TGTA), a system developed for assessing performance in a battery of neuropsychological tests in canines. The results of the current study revealed that, as previously found with beagles tested using the TGTA, Labrador retrievers (N = 16) readily acquired both tasks and learned the discrimination task significantly faster than the reversal task. The present study confirmed that the modified TGTA system is suitable for cognitive evaluations in Labrador retriever MWDs and can be used to further explore effects of sex, phenotype, age, and other factors in relation to canine cognition and learning, and may provide an additional screening tool for MWD selection.}, number={3}, journal={ANIMAL COGNITION}, author={Lazarowski, Lucia and Foster, Melanie L. and Gruen, Margaret E. and Sherman, Barbara L. and Case, Beth C. and Fish, Richard E. and Milgram, Norton W. and Dorman, David C.}, year={2014}, month={May}, pages={787–792} }
 @article{thrall_maccarini_stauffer_macfall_hauck_snyder_case_linder_lan_mccall_et al._2012, title={Thermal dose fractionation affects tumour physiological response}, volume={28}, ISSN={["0265-6736"]}, DOI={10.3109/02656736.2012.689087}, abstractNote={Purpose: It is unknown whether a thermal dose should be administered using a few large fractions with higher temperatures or a larger number of fractions with lower temperatures. To evaluate this we assessed the effect of administering the same total thermal dose, approximately 30 CEM43T90, in one versus three to four fractions per week, over 5 weeks. Materials and methods: Canine sarcomas were randomised to receive one of the hyperthermia fractionation schemes along with fractionated radiotherapy. Tumour response was based on changes in tumour volume, oxygenation, water diffusion quantified using MRI, and a panel of histological and immunohistochemical end points. Results: There was a greater reduction in tumour volume and water diffusion at the end of therapy in tumours receiving one hyperthermia fraction per week. There was a weak but significant association between improved tumour oxygenation 24 h after the first hyperthermia treatment and extent of volume reduction at the end of therapy. Finally, the direction of change of HIF-1α and CA-IX immunoreactivity after the first hyperthermia fraction was similar and there was an inverse relationship between temperature and the direction of change of CA-IX. There were no significant changes in interstitial fluid pressure, VEGF, vWF, apoptosis or necrosis as a function of treatment group or temperature. Conclusions: We did not identify an advantage to a three to four per week hyperthermia prescription, and response data pointed to a one per week prescription being superior.}, number={5}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Thrall, Donald E. and Maccarini, Paolo and Stauffer, Paul and Macfall, James and Hauck, Marlene and Snyder, Stacey and Case, Beth and Linder, Keith and Lan, Lan and Mccall, Linda and et al.}, year={2012}, pages={431–440} }
 @article{thrall_larue_pruitt_case_dewhirst_2006, title={Changes in tumour oxygenation during fractionated hyperthermia and radiation therapy in spontaneous canine sarcomas}, volume={22}, ISSN={["0265-6736"]}, DOI={10.1080/02656730600836386}, abstractNote={Tumour oxygenation was measured in seven canine soft tissue sarcomas being treated with a fractionated course of radiation and hyperthermia. Measurements obtained during treatment were compared to pre-treatment measurements. The most important finding was an increase in oxygenation in tumours with low pre-treatment oxygenation that persisted throughout treatment. This is an advantageous hyperthermia effect as it may lead to increased radiation cell killing at each fraction. In other tumours, potentially less advantageous changes in oxygenation may be hyperthermia fractionation related and this deserves further investigation.}, number={5}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Thrall, D. E. and Larue, S. M. and Pruitt, A. F. and Case, B. and DeWhirst, M. W.}, year={2006}, month={Aug}, pages={365–373} }
 @article{lora-michiels_yu_sanders_poulson_azuma_case_vujaskovic_thrall_charles_dewhirst_2006, title={Extracellular pH and P-31 magnetic resonance spectroscopic variables are related to outcome in canine soft tissue sarcomas treated with thermoradiotherapy}, volume={12}, ISSN={["1078-0432"]}, DOI={10.1158/1078-0432.CCR-05-2669}, abstractNote={Abstract}, number={19}, journal={CLINICAL CANCER RESEARCH}, author={Lora-Michiels, Michael and Yu, Daohai and Sanders, Linda and Poulson, Jean M. and Azuma, Chieko and Case, Beth and Vujaskovic, Zeljko and Thrall, Donald E. and Charles, H. Cecil and Dewhirst, Mark W.}, year={2006}, month={Oct}, pages={5733–5740} }
 @article{hauck_larue_petros_poulson_yu_spasojevic_pruitt_klein_case_thrall_et al._2006, title={Phase I trial of doxorubicin-containing low temperature sensitive liposomes in spontaneous canine tumors}, volume={12}, ISSN={["1078-0432"]}, DOI={10.1158/1078-0432.CCR-06-0226}, abstractNote={Abstract}, number={13}, journal={CLINICAL CANCER RESEARCH}, author={Hauck, Marlene L. and LaRue, Susan M. and Petros, William P. and Poulson, Jean M. and Yu, Daohai and Spasojevic, Ivan and Pruitt, Amy F. and Klein, Allison and Case, Beth and Thrall, Donald E. and et al.}, year={2006}, month={Jul}, pages={4004–4010} }
 @article{case_lewbart_doerr_2005, title={The physiological and behavioural impacts of and preference for an enriched environment in the eastern box turtle (Terrapene carolina carolina)}, volume={92}, ISSN={["1872-9045"]}, DOI={10.1016/j.applanim.2004.11.011}, abstractNote={The physiological and behavioural impact of, as well as preference for, enriched versus barren environments was determined for captive eastern box turtles (Terrapene carolina carolina). Thirty-eight box turtles were randomized to either barren (flat newspaper substrate) or enriched (cypress mulch substrate, shredded paper and a hide box) enclosures for a 1-month period. Complete blood counts, fecal corticosterone, and body weights were measured at the beginning and end of the test period. Activities performed within the two environments were also compared. Turtles in enriched enclosures had a significantly lower heterophil to lymphocyte ratio (H/L) at the end of the treatment period (p = 0.01). Enriched-housed turtles also spent significantly less time engaged in escape behaviour (p < 0.01). There was no significant difference in fecal corticosterone or body weight change between the two treatment groups. At the beginning of the study, each turtle was placed in a preference test system in which it could move freely between a barren and enriched environment. Relative-dwelling time (RDT) was determined for each environment. Turtles showed a distinct preference for the enriched environment (90.9% median RDT, p < 0.01). After the 1-month housing experiment turtles were revaluated for preference to determine if previous housing experience affected choice. Turtles continued to prefer an enriched environment regardless of prior housing conditions (97.6% median RDT, p < 0.01). Results of this study demonstrate that the captive housing environment impacts the physiology and behaviour of box turtles, and suggest housing modifications that encourage typical species-specific behaviour should be provided.}, number={4}, journal={APPLIED ANIMAL BEHAVIOUR SCIENCE}, author={Case, BC and Lewbart, GA and Doerr, PD}, year={2005}, month={Aug}, pages={353–365} }
 @article{thrall_larue_yu_samulski_sanders_case_rosner_azuma_poulson_pruitt_et al._2005, title={Thermal dose is related to duration of local control in canine sarcomas treated with thermoradiotherapy}, volume={11}, number={14}, journal={Clinical Cancer Research}, author={Thrall, D. E. and Larue, S. M. and Yu, D. H. and Samulski, T. and Sanders, L. and Case, B. and Rosner, G. and Azuma, C. and Poulson, J. and Pruitt, A. F. and et al.}, year={2005}, pages={5206–5214} }
 @article{case_hauck_yeager_simkins_serres_schmith_dillberger_page_2000, title={The pharmacokinetics and pharmacodynamics of GW395058, a peptide agonist of the thrombopoietin receptor, in the dog, a large-animal model of chemotherapy-induced thrombocytopenia}, volume={18}, ISSN={["1066-5099"]}, DOI={10.1634/stemcells.18-5-360}, abstractNote={GW395058, a PEGylated peptide agonist of the thrombopoietin receptor, stimulates megakaryocytopoiesis and has previously been shown to increase platelet counts in vivo. The pharmacokinetics and pharmacodynamics of GW395058 were characterized using a randomized, crossover study in a large‐animal model (dog) of chemotherapy‐induced thrombocytopenia.}, number={5}, journal={STEM CELLS}, author={Case, BC and Hauck, ML and Yeager, RL and Simkins, AH and Serres, M and Schmith, VD and Dillberger, JE and Page, RL}, year={2000}, pages={360–365} }
 @article{thrall_rosner_azuma_larue_case_samulski_dewhirst_2000, title={Using units of CEM 43 degrees C T-90, local hyperthermia thermal dose can be delivered as prescribed}, volume={16}, ISSN={["1464-5157"]}, DOI={10.1080/026567300416712}, abstractNote={A randomized study was designed in dogs with spontaneous soft tissue sarcomas to gain information about the relationship between hyperthermia dose and outcome. The study compared two levels of thermal dose applied to dogs with heatable tumours, so it was necessary to deliver either a low (2-5 CEM 43°C T90) or high (20-50 CEM 43°C T90) thermal dose as precisely as possible. It was also desirable to have similar numbers of hyperthermia treatments in each thermal dose group. Identification of heatable tumours and randomization to high or low heat dose group was done during the first hyperthermia treatment. This was readily accomplished using mapping of temperatures in thermometry catheters, manual recording of thermal data, and visual inspection of raw thermal data with subsequent adjustment of the duration of the hyperthermia treatment. An analysis of precision of thermal dose delivery was conducted after approximately 50% of projected accrual had been met in a randomized phase III assessment of thermal dose effect. Fifty-four dogs were eligible for randomization; in 48 dogs the tumour was deemed heatable according to predetermined temperature criteria applied during the first heat treatment. Twenty-four dogs were randomized to the high heat dose group, and 24 to the low heat dose group. Median (range) total thermal dose for dogs in the high dose group was 43.5 CEM 43°C T90 (16.4-66.6) compared to 3.2 CEM 43°C T90 (2.1-4.6) for dogs in the low dose group. There was no overlap of thermal doses between groups. Thus, thermal dose could be delivered accurately, being within the predetermined range in 47 of the 48 dogs. Thermal dose quantified as CEM 43°C T50, however, did overlap between groups and the clinical significance of this finding will not be known until outcome data are analysed. Most dogs in both groups received five hyperthermia treatments. Median (range) treatment duration for dogs in the high dose group was 300min (147-692) compared to 111min (51-381) for dogs in the low dose group. Relatively simple but accurate methods of delivering prescribed thermal dose as described herein will aid the translation of clinical hyperthermia from the research setting into more general practice once the characteristics of the relationship between hyperthermia dose and outcome are understood.}, number={5}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Thrall, DE and Rosner, GL and Azuma, C and Larue, SM and Case, BC and Samulski, T and Dewhirst, MW}, year={2000}, month={Sep}, pages={415–428} }
 @article{waddle_fine_case_trogdon_tyczkowska_frazier_page_1999, title={Phase I and pharmacokinetic analysis of high-dose tamoxifen and chemotherapy in normal and tumor-bearing dogs}, volume={44}, ISSN={["0344-5704"]}, DOI={10.1007/s002800050947}, abstractNote={{"Label"=>"PURPOSE", "NlmCategory"=>"OBJECTIVE"} To determine whether tamoxifen plasma concentrations capable of blocking P-glycoprotein (Pgp) in vitro can be safely achieved in dogs and whether doxorubicin pharmacokinetic alterations occur when tamoxifen is coadministered. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} Tamoxifen dose escalation studies were conducted in 7 normal dogs and in 19 tumor-bearing dogs receiving full-dose chemotherapy. Plasma tamoxifen and serum doxorubicin disposition were analyzed for putative drug interactions. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} Steady-state plasma concentrations of tamoxifen and N-desmethyl tamoxifen (NDMT) were 5-10 microM following oral tamoxifen administration at 600 mg/m2 every 12 h for 7 days to normal and tumor-bearing dogs. Mild-moderate gastrointestinal toxicity (diarrhea, anorexia) and reversible neurotoxicity were observed in dogs receiving chemotherapy plus high-dose tamoxifen. Myelosuppression was not affected by combined treatment in tumor-bearing dogs. High-dose tamoxifen decreased the clearance and volume of distribution of full-dose doxorubicin. {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} Concentrations of tamoxifen/ NDMT sufficient to inhibit Pgp may be achieved in dogs receiving full-dose chemotherapy with a moderate but acceptable increase in gastrointestinal toxicity. Tamoxifen affects doxorubicin metabolism in dogs at high doses resulting in increased serum exposure. Pharmacologic manipulation of Pgp expression or function in normal and tumor tissue in dogs may facilitate investigation of novel anticancer treatment strategies in humans.}, number={1}, journal={CANCER CHEMOTHERAPY AND PHARMACOLOGY}, author={Waddle, JR and Fine, RL and Case, BC and Trogdon, ML and Tyczkowska, K and Frazier, D and Page, RL}, year={1999}, month={Jul}, pages={74–80} }
 @article{thrall_larue_powers_page_johnson_george_kornegay_mcentee_levesque_smith_et al._1999, title={Use of whole body hyperthermia as a method to heat inaccessible tumours uniformly: a phase III trial in canine brain masses}, volume={15}, number={5}, journal={International Journal of Hyperthermia}, author={Thrall, D. E. and Larue, S. M. and Powers, B. E. and Page, R. L. and Johnson, J. and George, S. L. and Kornegay, J. N. and McEntee, M. C. and Levesque, D. C. and Smith, M. and et al.}, year={1999}, pages={383–398} }