"I just can't go back": Challenging Places for Older Americans since the COVID-19 Pandemic Onset.

During the pandemic, many older adults felt 'out of place' in their home, work, and community spaces with potentially long-term consequences for health and wellbeing. Using national data from the COVID-19 Coping Study, thematic analysis of online long-answer responses (n = 1171; mean age 68 years; 71% female; 93% non-Hispanic White; 86% with at least a 4-year college degree; data collected April-June 2022) identified four themes regarding why particular places are challenging since the pandemic onset: (1) viral exposure fears, (2) frustrating regulations, (3) uncomfortable and hostile social dynamics, and (4) 'out of place' negative emotions. Participants also shared how they continuously address or adapt to place-based challenges through lifestyle adjustments and coping strategies. Novel findings may inform multi-scalar policymaking and interventions to support wellbeing in later life in times of stress and instability.

Altered place engagement since COVID-19: A multi-method study of community participation and health among older americans.

Little is known about longer-term changes to community participation since the COVID-19 pandemic onset and potential implications for health and wellbeing in later life. This multi-method investigation analyzes national data from the COVID-19 Coping Study. Statistical analyses of survey data (n = 1,630; mean age 67.9 years; data collected April/May 2022) identified that adults residing in the US still tended to stay inside their homes more often since the pandemic onset. Overall, participants decreased their engagement with amenities such as eateries, gyms, and arts and cultural sites. Reflexive thematic analysis of semi-structured in-depth interviews (n = 57; mean age 70.7 years; data collected May-July 2021) identified altered community participation with perceived long-term impacts on physical, mental, and social health and wellbeing. The results provide novel insights about the critical nature of 'third places' to support later life, and policy implications to strengthen community environments. Investment in outdoor, well-ventilated, and distanced third places may support wellbeing.

Identity Development and Disruption in Older Adults During COVID-19: A Longitudinal, Mixed-Methods Study.

OBJECTIVES: Disruptive life events, such as the coronavirus disease 2019 (COVID-19) pandemic, may trigger adjustment and revision of older adults' identities. This mixed-methods study explored how older adults perceived their identities changing as a result of the pandemic, and how such identity dynamics related to pandemic-related events and well-being. METHODS: Participants included 2,248 older adults who participated in the longitudinal COVID-19 Coping Study spanning from April/May 2020 to April/May 2021. Mean age was 67.8 years, 70% were women, and 93% were White. We used qualitative thematic analysis to identify the ways the pandemic affected participants' identities. We then investigated the association between identity themes and testing positive for COVID-19, having a friend or family member hospitalized or dying due to COVID-19, or being vaccinated. Finally, we tested whether identity disruption was associated with 12-month trajectories of well-being (including life satisfaction, loneliness, depressive symptoms, anxiety, and self-rated health) using latent growth curve models. RESULTS: Some participants reported positive identity themes, such as rethinking and revising priorities and realization of strength and resilience. Others indicated harmful effects, including identity disruption. Individuals reporting identity disruption had worse well-being at baseline and remained consistently worse over time. DISCUSSION: Findings highlight that identity remains malleable in later life and that stressful events like the COVID-19 pandemic may trigger positive adaptive identity processes, but can also cause identity disruption that is associated with persistently worse well-being over time.

Neighborhood Built Environments and Health in Later Life: A Literature Review.

Objectives: This literature review aims to assess the current state of the field linking neighborhood environments to later-life health and wellbeing. Methods: We used electronic databases (e.g., PubMed, Google Scholar, and ProQuest) to search for studies published between 2010 and 2022 examining associations between neighborhood built environmental variables and later-life physical, cognitive, mental, and social health outcomes. Results: Among 168 studies reviewed, the majority were quantitative (n = 144) and cross-sectional (n = 122). Neighborhood environmental variables significantly associated with later-life health outcomes included population density/rurality, walkability/street connectivity, access to services and amenities, neighborhood quality and disorder, and parks/green/blue/open space. Neighborhoods operated through behavioral and biological pathways including hazardous exposures, affective states (e.g., stress and restoration), and lifestyle (e.g., exercise, socialization, and diet). Discussion: Neighborhoods and healthy aging research is a burgeoning interdisciplinary and international area of scholarship. Findings can inform upstream community interventions and strengthen clinical care.

"Please don't let me become a statistic in this grocery store": Civic engagement among older Americans since the COVID-19 pandemic onset.

The COVID-19 pandemic disrupted civic life and upended daily routines. Coffee shops, restaurants, recreation centers, parks, and other 'third places' that facilitate communal gathering, interpersonal connection, and meaningful activity closed or operated under tight restrictions. Little is known about longer-term impacts on older adults' civic life since the pandemic's onset. The COVID-19 Coping Study conducted semi-structured interviews in April-July 2021 with 57 adults aged ≥55 across the United States (mean age 71). Reflexive thematic analysis identified heightened sociopolitical tensions and complex community experiences since the pandemic's onset. Participants shared nuanced perceptions of greater physical and emotional distancing, siloed communities, politicized public health adherence, fears of gun violence, and experiences of racial discrimination in shared spaces. Hopeful efforts to re-engage in civic life involved cautious social activities post-vaccination, altered daily routines, and finding a "new normal." The novel results explore how a large sample of racially and socioeconomically diverse older adults perceive and experience American sociopolitical tensions anchored in shared everyday spaces. Results may inform practical opportunities for policymakers and community service providers to strengthen social infrastructure, support wellbeing, and bolster civic life.

The Joys and Stresses of Social Relationships and the Effect on Resiliency During the Covid-19 Pandemic: A National Survey of US Older Adults.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic placed unprecedented stress on older adults. Resiliency could mitigate deleterious effects of pandemic stressors. We described trends in resilience among US adults aged 50-80 years approximately one and half years after the onset of the pandemic, compared with before the pandemic, and evaluated associations between relationships and resilience. RESEARCH DESIGN AND METHODS: Data were from the National Poll on Healthy Aging (N=2,100) in August 2021. Respondents rated their resiliency as compared with before the pandemic (more, about the same, or less) and different types of relationships (spouse/partner, friends, neighbors) as sources of joy and/or stress during the pandemic (a lot, some, very little, and not at all). Multinomial logistic regressions (complete-case analysis) estimated the relationships between each joyful and stressful relationships and resiliency. RESULTS: Most participants reported feeling as resilient as before the pandemic (70.6%) with 14.5% feeling less resilient. More women than men felt less resilient than before the pandemic (16.7% vs. 12.8%, p=0.006). Feeling a lot of stress from one's spouse or neighbors was associated with increased likelihood of feeling less resilient than before the pandemic (OR=3.7; 95% CI: 1.8, 7.7 and OR=4.5; 95% CI: 1.5, 13.9, respectively) which was stronger among women (OR=15.1; 95% CI: 4.8, 45.6) than men (OR=1.03; 95% CI: 0.4, 2.7). DISCUSSION AND IMPLICATIONS: Social relationships may have been more important for women than for men in supporting resiliency during the pandemic. Understanding patterns of resiliency can help to inform policymaking and support the well-being of older adults.

'My neighbourhood is fuzzy, not hard and fast': Individual and contextual associations with perceived residential neighbourhood boundaries among ageing Americans.

Neighborhoods are fluid social and spatial constructs that vary by person and place. How do residential neighborhoods shift as people age? This mixed-method study investigates how perceived neighborhood boundaries and size vary by individual and contextual characteristics. Semi-structured interviews with 125 adults aged 55-92 living in the Minneapolis (Minnesota) metropolitan area suggested that neighborhood boundaries are "fuzzy". Qualitative thematic analysis identified duration of residence and housing stability, race, life-space mobility, social capital, sense of safety, and the built and social environment as key neighborhood determinants. This informed quantitative analyses among 7,811 respondents (mean age 72) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study who self-reported how many blocks composed their neighborhoods. We tested individual and contextual factors identified in the qualitative results as related to perceived neighborhood size. Three-level gamma regression models showed that being older, white, less educated, lower income, less physically and cognitively healthy, less active, less socially supported, and feeling unsafe were significantly associated with smaller self-reported neighborhood sizes. Further, living in less racially diverse, less dense, and less affluent areas were significantly associated with smaller neighborhoods. The mixed-methods findings deepen understanding of scale in neighborhood-based research, inform urban planning interventions, and help understand what "neighborhood" means among diverse aging Americans.

"I Can't Take Any Chances": A Mixed Methods Study of Frailty, Isolation, Worry, and Loneliness Among Aging Adults During the COVID-19 Pandemic.

Little is known about how frailty has shaped experiences of living through the COVID-19 pandemic. In this cross-sectional mixed methods study, we analyzed data from the nationwide COVID-19 Coping Study from December 2020 through January 2021 (N = 2094 US adults aged ≥55) to investigate quantitative associations between frailty and the prevalence of physical isolation, worry about COVID-19, and loneliness. Reflexive thematic analysis explored aging adults' lived experiences of frailty during the pandemic. In multivariable-adjusted population-weighted modified Poisson regression models, we found that frailty was associated with increased prevalence of physical isolation, worry about COVID-19, and loneliness. Qualitative experiences of aging with frailty during the pandemic were diverse, and encompassed isolation, worry, and loneliness, as well as coping strategies and resilience. The findings may inform individualized multi-factorial strategies (e.g., physical activity, nutrition, and social interaction) to support well-being among adults aging with frailty during the pandemic.

Neighborhood 'Disamenities': local barriers and cognitive function among Black and white aging adults.

BACKGROUND: This study examined the association between cognitive function and three neighborhood 'disamenities' that may pose local barriers to utilizing community resources and increase risk for cognitive decline. METHOD: Using national data from 21,165 urban- and suburban-dwelling Black and white adults (mean age: 67 years) in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, we assessed global cognitive function through a factor score of five cognitive screening tests. General Additive Mixed Models (GAMM) tested whether residing in areas with more polluting sites, highways, and limited walkability was associated with worse cognitive function. RESULTS: Limited walkability and the presence of polluting sites had a significant negative association with cognitive function after controlling for individual and neighborhood factors. CONCLUSION: Neighborhood disamenities may be linked to cognitive function among aging residents. Identifying neighborhood factors that pose barriers to accessing community resources may inform upstream policy applications to reduce risk for cognitive decline.

Rural/urban differences in mental health and social well-being among older US adults in the early months of the COVID-19 pandemic.

OBJECTIVES: This study seeks to identify differences in mental health and social well-being during the early months of the COVID-19 pandemic among older adults by rural/urban location. METHODS: We use data from the COVID-19 Coping Study, a nation-wide online study of U.S. adults aged 55 and older (n = 6,873) fielded during April-May, 2020. We investigated rural/urban differences in mental health (depressive symptoms and anxiety symptoms) and social well-being (loneliness and social isolation); concern about COVID-19; and types of social participation (e.g. phone/video calls, visits). We also used multivariable logistic regression models to assess the relationship of rurality with mental health, adjusting for socio-demographic correlates, COVID-19 history, and COVID-19 concern. RESULTS: We found similar prevalence of mental health and social well-being outcomes for rural and urban respondents. Rural respondents reported lower concern about COVID-19 and more frequent use of social media than urban respondents. CONCLUSION: Mental health and social well-being did not differ by rural/urban location in the early months of the COVID-19 pandemic. However, rural residents reported less concern about COVID-19 and more use of social media, potentially leading to greater risk of illness from the pandemic in later months.

Can Technology-Based Social Memory Aids Improve Social Engagement? Perceptions of a Novel Memory Aid for Persons With Memory Concerns.

Social withdrawal and isolation are frequently experienced among people with cognitive impairment, Alzheimer's disease, and Alzheimer's disease related dementias. Few assistive technologies exist to support persons with memory concerns' (PWMC) continuing social engagement. This study aimed to understand PWMC and family caregivers' initial perspectives on the feasibility and utility of a wearable technology-based social memory aid. We recruited 20 dyads, presented the memory aid, and conducted semi-structured interviews from June to August 2020 over Zoom video conferencing. Interviews were transcribed and analyzed using thematic analysis. Overall, participants anticipated the technology could reduce socializing-related stress now and in the future for both members of the care dyad. However, certain features of the memory aid (e.g., visitors must have the app), could limit utility, and participants provided recommendations to enhance the tool. Our findings will inform future technology-enabled social memory aid development for PWMC and family caregivers.

Treatment of multiple synchronous canine mast cell tumours using intratumoural tigilanol tiglate.

Mast cell tumours (MCTs) are common canine skin neoplasia. While they generally occur as single tumours, multiple synchronous MCTs (msMCTs) of de novo/non-metastatic origin are reported in a proportion of the patient population. Where there is no evidence of metastasis or lymphatic spread, MCTs are effectively controlled by surgery and other local therapies. However, treatment of de novo msMCTs can be more challenging, especially when they occur in surgically difficult locations. Here, we report the use of tigilanol tiglate, a novel small molecule registered as a veterinary pharmaceutical for the local treatment of non-metastatic MCTs, in the treatment of patients with msMCTs presenting at three Australian specialist referral centres. We also present a meta-analysis of the literature to provide a better understanding of the prevalence of canine msMCTs. Notably, nine patients with a total of 32 MCTs were treated during the study. A complete response was recorded in 26 (81%) of the individual MCTs on Day 28 after a single tigilanol tiglate injection. Of the 6 initially non-responsive MCTs, one achieved a complete response after a further tigilanol tiglate treatment. A complete response was reported at 6 months in all 22 of the tumours that were evaluable and that had recorded a complete response at Day 84. For the literature meta-analysis, 22 studies were found with prevalence estimates of msMCTs ranging from 3 to 40%; when combined, these studies yielded 3,745 patients with a prevalence of 13% (95% CI 10; 16). Overall, the results demonstrate the utility of intratumoural tigilanol tiglate as an option for the treatment of multiple MCTs where multiple surgical resections would have been required.

Perceptions of societal ageism and declines in subjective memory during the COVID-19 pandemic: Longitudinal evidence from US adults aged ≥55 years.

The cognitive health of older adults since the COVID-19 pandemic onset is unclear, as is the potential impact of pandemic-associated societal ageism on perceived cognition. We investigated associations between perceptions of societal ageism and changes in subjective memory over a 10-month period during the COVID-19 pandemic. We collected longitudinal data from monthly online questionnaires in the nationwide COVID-19 Coping Study of US adults aged ≥55 from April 2020 to January 2021 (N = 4444). We analyzed the data using multivariable longitudinal multilevel models. We identified an overall decline in subjective memory, especially in the initial months of the pandemic. Adults who perceived that societal respect for older adults decreased during the pandemic experienced more rapid declines in their subjective memory. These findings suggest that aging adults perceived a decline in their memory, especially during the initial months of the COVID-19 pandemic. Societal interventions to combat ageism may help improve subjective memory and could decrease risk for cognitive decline among middle-aged and older adults.

Cognability: An Ecological Theory of neighborhoods and cognitive aging.

While a growing body of evidence points to potentially modifiable individual risk factors for dementia, the built and social environments in which people develop and navigate cognitive decline are largely overlooked. This paper proposes a new theoretical concept, Cognability, to conceptualize how supportive an area is to cognitive health among aging residents. Cognability incorporates a constellation of both positive and negative neighborhood features related to physical activity, social interaction and cognitive stimulation in later life. We analyzed data from the REasons for Geographic And Racial Differences in Stroke Study, a national sample of older Black and white adults in the United States (n = 21,151; mean age at assessment = 67; data collected 2006-2017). Generalized additive multilevel models examined how cognitive function varied by neighborhood features. Access to civic and social organizations, recreation centers, fast-food and coffee establishments, arts centers, museums, and highways were significantly associated with cognitive function. Race-, gender-, and education-specific models did not yield substantial improvements to the full-model. Our results suggest that the unequal distribution of amenities and hazards across neighborhoods may help account for considerable inequities observed in cognitive health among older adults. Cognability advances ecological theories of aging through an innovative "whole neighborhood" approach. It aims to identify which specific neighborhood features are most protective of cognitive health among aging adults to inform upstream public health initiatives, community interventions, and policy.

Multimorbidity and Mental Health Trajectories Among Middle-Aged and Older U.S. Adults During the COVID-19 Pandemic: Longitudinal Findings From the COVID-19 Coping Study.

Background and Objectives: This study aimed to examine the associations between multimorbidity at the COVID-19 pandemic onset and subsequent longitudinal trajectories of depressive symptoms, anxiety symptoms, and loneliness in middle-aged and older adults over a 12-month follow-up. Research Design and Methods: Data were from monthly online questionnaires in the COVID-19 Coping Study of U.S. adults aged ≥55 from April/May 2020 through April/May 2021 (N = 4,024). Multimorbidity was defined as having ≥2 versus <2 chronic conditions at baseline. Mental health outcomes were assessed monthly as depressive symptoms (8-item Center for Epidemiologic Studies Depression scale), anxiety symptoms (5-item Beck Anxiety Inventory), and loneliness (3-item UCLA Loneliness Scale). We used multivariable-adjusted population- and attrition-weighted mixed-effects linear models to examine the longitudinal associations between multimorbidity and mental health symptoms. Results: Multimorbidity at the pandemic onset was associated with elevated depressive (b = 0.37; 95% CI: 0.16-0.59) and anxiety (b = 0.39; 95% CI: 0.15-0.62) symptoms at baseline. Changes in symptoms for all three mental health outcomes were nonlinear over time, with worsening symptoms over the first 6 months of the pandemic (April/May to September/October 2020), followed by improvement in symptoms over the subsequent 6 months (September/October 2020 to April/May 2021). Middle-aged and older adults with multimorbidity experienced faster rates of change in anxiety symptoms and loneliness than those without multimorbidity, with persistently elevated mental health symptomatology throughout the follow-up. Discussion and Implications: Results highlight the unique and persistent mental health risks experienced by middle-aged and older adults with multimorbidity during the COVID-19 pandemic. The observed improvements in symptoms underscore the mental resilience of these individuals, indicating their adaptation to the ongoing pandemic.

Mental health and well-being in times of COVID-19: A mixed-methods study of the role of neighborhood parks, outdoor spaces, and nature among US older adults.

The role of parks and nature to support well-being during the COVID-19 pandemic is uncertain. To examine this topic, we used mixed-methods data collected in April-May 2020 from US adults aged ≥55 in the COVID-19 Coping Study. We quantitatively evaluated the associations between number of neighborhood parks and depression, anxiety, and loneliness; and conducted qualitative thematic analysis of participants' outdoor experiences. Among urban residents, depression and anxiety were inversely associated with the number of neighborhood parks. Thematic analysis identified diverse engagement in greenspaces that boosted physical, mental, and social well-being. The therapeutic potential of outdoor and greenspaces should be considered for interventions during future epidemics.

Acute relationships between mental health and cognitive function during the COVID-19 pandemic: Longitudinal evidence from middle-aged and older US adults.

Background: The acute impacts of COVID-19-related mental health concerns on cognitive function among middle-aged and older adults are unknown. We investigated whether between-person (BP) differences and within-person (WP) changes in loneliness, anxiety, and worry about COVID-19 were related to cognitive function and abilities in a longitudinal cohort of middle-aged and older United States (US) adults over a nine-month period during the COVID-19 pandemic. Methods: Data were from bimonthly questionnaires in the nationwide COVID-19 Coping Study from August/September 2020 through April/May 2021 (N = 2262 adults aged ≥55). Loneliness was assessed with the 3-item UCLA Loneliness Scale, anxiety with the 5-item Beck Anxiety Inventory, and COVID-19 worry on a 5-point Likert-type scale. Cognitive outcomes were assessed with the 6-item Patient Reported Outcomes Measurement Information System (PROMIS®) Cognitive Function and Abilities scales. Marginal structural models incorporating inverse probability of treatment and attrition weights as well as sampling weights estimated the BP and WP relationships between the mental health predictors and PROMIS® cognitive scores over time. Results: In any given month, experiencing a loneliness or anxiety symptom score higher than the sample mean (BP difference) or higher than one's personal mean across the nine-month period (WP change) was negatively associated with cognitive function and abilities in that month. The observed magnitudes of associations were stronger for BP differences than for WP changes and were the strongest for anxiety symptom scale scores. Conclusions: Elevated loneliness and anxiety symptoms, both relative to other adults and to one's usual levels, were acutely associated with worse perceived cognitive function and abilities over a nine-month period during the COVID-19 pandemic in the United States. The long-term impacts of mental health symptoms experienced during the pandemic for population cognitive health should be explored.

Physical isolation and mental health among older US adults during the COVID-19 pandemic: longitudinal findings from the COVID-19 Coping Study.

PURPOSE: We investigated the relationships between physical isolation at home during the period when many US states had shelter-in-place orders and subsequent longitudinal trajectories of depression, anxiety, and loneliness in older adults over a 6 month follow-up. METHODS: Data were from monthly online questionnaires with US adults aged ≥ 55 in the nation-wide COVID-19 Coping Study (April through October 2020, N = 3978). Physical isolation was defined as not leaving home except for essential purposes (0, 1-3, 4-6, and 7 days in the past week), measured at baseline (April-May). Outcomes were depressive symptoms (8-item Center for Epidemiological Studies Depression Scale), anxiety symptoms (5-item Beck Anxiety Inventory), and loneliness (3-item UCLA loneliness scale), measured monthly (April-October). Multivariable, population- and attrition-weighted linear mixed-effects models assessed the relationships between baseline physical isolation with mental health symptoms at baseline and over time. RESULTS: Physical isolation (7 days versus 0 days in the past week) was associated with elevated depressive symptoms (adjusted ß = 0.85; 95% CI 0.10-1.60), anxiety symptoms (adjusted ß = 1.22; 95% CI 0.45-1.98), and loneliness (adjusted ß = 1.06; 95% CI 0.51-1.61) at baseline, but not with meaningful rate of change in these mental health outcomes over time. The symptom burden of each mental health outcome increased with increasing past-week frequency of physical isolation. CONCLUSION: During the early COVID-19 pandemic, physical isolation was associated with elevated depressive symptoms, anxiety symptoms, and loneliness, which persisted over time. These findings highlight the unique and persistent mental health risks of physical isolation at home under pandemic control measures.

Who looks on the bright side? Optimistic and pessimistic perceptual-response reflexes over American adulthood.

Research suggests that the way individuals are oriented towards the future is deeply embedded in their psychology, shaping how they perceive and react to opportunities and threats, even at unconscious levels. We argue that exposures to opportunities and threats over the life course can shape future orientation at a deep level, and that word-valence effects to survey questions indicate optimistic and pessimistic "perceptual-response reflexes" that are manifestations of unconscious dispositions. Using data collected over 25 years in the Americans' Changing Lives (ACL) study we analyze variation in word-valence effects by age, birth cohort, gender, and race. The broad adult age-range of the sample and the length of follow-up permits the examination of birth cohorts ranging from the "First Children of the 20th Century" (born before 1917) to "Baby Boomers" (born 1947-1962). We find notable differences in age-graded trends across two overarching birth cohort groups: those who reached high school age before the Supreme Court's landmark Brown vs Board of Education decision in 1954 (i.e., born before 1932) and after (i.e., born in 1932 and later). Age-related trends in optimistic perceptual response diverge notably for women versus men, and for Black versus White Americans. Trends in pessimistic perceptual response differ from trends in optimistic response. For example, in early adulthood Black Americans score higher on both optimistic and pessimistic response patterns than White Americans. Birth-cohort differences in both outcomes vary by gender and race. Those differences are interpreted in terms of changes in political, demographic, and sociocultural contexts.

Developing a translational murine-to-canine pathway for an IL-2/agonist anti-CD40 antibody cancer immunotherapy.

Human and canine sarcomas are difficult to treat soft tissue malignancies with an urgent need for new improved therapeutic options. Local recurrence rates for humans are between 10%-30%, and 30%-40% develop metastases. Outcomes for dogs with sarcoma vary with grade but can be similar. Pet dogs share the human environment and represent human cancer with genetic variation in hosts and tumours. We asked if our murine studies using genetically identical mice and cloned tumour cells were translatable to larger, genetically diverse domestic dogs with naturally occurring tumours, to (i) develop a canine cancer therapeutic, and (ii) to use as a translational pathway to humans. Our murine studies showed that intra-tumoral delivery of interleukin-2 (IL-2) plus an agonist anti-CD40 antibody (Ab) induces long-term curative responses ranging from 30% to 100%, depending on tumour type. We developed an agonist anti-canine-CD40 Ab and conducted a phase I dose finding/toxicology 3 + 3 clinical trial in dogs (n = 27) with soft tissue sarcomas on account of suitability for intratumoral injection and straightforward monitoring. Dogs were treated with IL-2 plus anti-CD40 antibody for 2 weeks. Three dose levels induced tumour regression with minimal side effects, measured by monitoring, haematological and biochemical assays. Importantly, our mouse and canine studies provide encouraging fundamental proof-of-concept data upon which we can develop veterinary and human immunotherapeutic strategies.