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Alice Verstaen,1 Judith T Moskowitz,2 Karin E Snowberg,1 Jennifer Merrilees,3 Glenna A Dowling1 1Department of Physiological Nursing, University of California, San Francisco, San Francisco, CA, 2Department of Medical Social Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, 3UCSF Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA Abstract: Given the increasing number of family caregivers of persons with dementia (PWD) and the associated burden and detriments to both physical and mental health, interventions that aim to improve such outcomes are important. Studies are increasingly demonstrating the unique importance of positive emotions in coping with stress, independent from the impact of negative emotions. However, none have examined the benefits of interventions that target positive emotions for caregivers of individuals with a chronic and debilitating disease such as dementia. This paper presents the design and methods for a randomized controlled trial (RCT) of a positive affect skills intervention for family caregivers of PWD. The RCT is of a skills-based intervention that seeks to increase the frequency and intensity of positive affect in order to improve outcomes such as well-being, coping, and physical and mental health. The skills are delivered by trained facilitators via five one-to-one Internet video sessions with family caregivers of persons diagnosed with dementia (eg, Alzheimer’s disease, vascular dementia, unspecified). The control group is an emotion reporting/waitlist control. Follow-up assessments are conducted post-intervention and at 1, 3, and 6 months post-completion of the intervention. This study promises to be an important and needed step toward improving the lives of caregivers of PWD. Keywords: positive affect, dementia caregiving, coping, intervention, stress, RCT

Abstract Background The long-term effectiveness of immunotherapies against Multiple Myeloma (MM) remains elusive, demonstrated by the inevitable relapse in patients. This underscores the urgent need for an in-depth analysis of the MM tumor-immune microenvironment (TME). Hereto, a representative immunocompetent MM mouse model can offer a valuable approach to study the dynamic changes within the MM-TME and to uncover potential resistance mechanisms hampering effective and durable therapeutic strategies in MM. Methods We generated a comprehensive single-cell RNA-sequencing atlas of the MM-TME in bone marrow and spleen encompassing different stages of disease, using the immunocompetent 5T33MM mouse model. Through comparative analysis, we correlated our murine dataset with the pathogenesis in MM patients by reanalyzing publicly available datasets of human bone marrow samples across various disease stages. Using flow cytometry, we validated the dynamic changes upon disease progression in the 5T33MM model. Furthermore, interesting target populations, as well as the immune-boosting anti-CD40 agonist (αCD40) therapy were tested ex vivo on murine and human primary samples and in vivo using the 5T33MM model. Results In this study, we identified the heterogenous and dynamic changes within the TME of murine and human MM. We found that the MM-TME was characterized by an increase in T cells, accompanied with an exhausted phenotype. Although neutrophils appeared to be rather innocuous at early disease stages, they acquired a pro-tumorigenic phenotype during MM progression. Moreover, conventional dendritic cells (cDCs) showed a less activated phenotype in MM, underscoring the potential of immune-boosting therapies such as αCD40 therapy. Importantly, we provided the first pre-clinical evaluation of αCD40 therapy and demonstrated successful induction of cDC- and T-cell activation, accompanied by a significant short-term anti-tumor response. Conclusions This resource provides a comprehensive and detailed immune atlas of the evolution in human and murine MM disease progression. Our findings can contribute to immune-based patient stratification and facilitate the development of novel and durable (immune) therapeutic strategies in MM.

Abstract To address our climate emergency, “we must rapidly, radically reshape society”—Johnson & Wilkinson, All We Can Save. In science, reshaping requires formidable technical (cloud, coding, reproducibility) and cultural shifts (mindsets, hybrid collaboration, inclusion). We are a group of cross‐government and academic scientists that are exploring better ways of working and not being too entrenched in our bureaucracies to do better science, support colleagues, and change the culture at our organizations. We share much‐needed success stories and action for what we can all do to reshape science as part of the Open Science movement and 2023 Year of Open Science.

Expressive suppression is a response-focused regulatory strategy aimed at concealing the outward expression of emotion that is already underway. Expressive suppression requires the integration of interoception, proprioception, and social awareness to guide behavior in alignment with personal and interpersonal goals-all processes known to involve the insular cortex. Frontotemporal dementia (FTD) provides a useful patient model for studying the insula's role in socioemotional regulation. The insula is a key target of early atrophy in FTD, causing patients to lose the ability to represent the salience of internal and external conditions and to use these representations to guide behavior. We examined a sample of 59 patients with FTD, 52 patients with Alzheimer's disease (AD), and 38 neurologically healthy controls. Subjects viewed 2 disgust-eliciting films in the laboratory. During the first film, subjects were instructed to simply watch (emotional reactivity trial); during the second, they were instructed to hide their emotions (expressive suppression trial). Structural images from a subsample of participants (n = 42; 11 FTD patients, 11 AD patients, and 20 controls) were examined in conjunction with behavior. FreeSurfer was used to quantify regional gray matter volume in 41 empirically derived neural regions in both hemispheres. Of the 3 groups studied, FTD patients showed the least expressive suppression and had the smallest insula volumes, even after controlling for age, gender, and emotional reactivity. Among the brain regions examined, the insula was the only significant predictor of expressive suppression ability, with lower insula gray matter volume in both hemispheres predicting less expressive suppression. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

We examined age-related changes in emotional behavior in a sample of middle-aged and older long-term married couples over a 13-year period. Data were collected at 3 waves, each occurring 5 to 6 years apart. For the present study, only couples who participated in all 3 waves were examined (n = 87). Couples were either in the middle-aged group (40-50 years old, married at least 15 years) or the older group (60-70 years old, married at least 35 years). At each wave, couples engaged in 15-min unrehearsed conversations about an area of disagreement in their marriage. Emotional behaviors during the conversation were objectively coded using the Specific Affect Coding System. Latent growth curve analyses revealed that, for both husbands and wives, negative emotional behavior (primarily belligerence, defensiveness, fear/tension, and whining) decreased and positive emotional behavior (primarily humor, enthusiasm, and validation) increased with age. Findings generalized across middle-aged and older cohorts and levels of marital satisfaction. These findings support theories that suggest that positive emotion increases and negative emotion decreases with age, expanding upon previous findings by examining objectively coded emotional behaviors longitudinally in an interpersonal context. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

IntroductionCaring for a spouse with dementia can be extremely challenging. Many caregivers experience profound declines in well-being; however, others remain healthy.ObjectiveThis study determined whether the personal pronouns used in interactions between persons with dementia (PWDs) and their spousal caregivers were associated with caregiver well-being.MethodsFifty-eight PWDs and their spousal caregivers engaged in a 10-min conversation about an area of disagreement in a laboratory setting. Verbatim transcripts of the conversation were coded using text analysis software, and caregivers and PWDs each received scores for (a) I-pronouns, (b) you-pronouns, and (c) we-pronouns. Caregivers' well-being was assessed using a composite measure of depression, anxiety, burden, and strain.ResultsResults revealed that less use of we-pronouns by caregivers and PWDs and greater use of I-pronouns by PWDs were -associated with lower caregiver well-being.ConclusionsThese findings indicate that less use of pronouns that refer to the couple (we-pronouns used by either partner) and greater use of pronouns that refer to the PWD (I-pronouns used by the PWD) are indicative of caregivers at heightened risk for lower well-being.

ObjectiveProviding care for a spouse with dementia is associated with an increased risk for poor mental health. To determine whether this vulnerability in caregivers is related to the expression of positive emotion, we examined 57 patients with Alzheimer's disease and behavioral variant frontotemporal dementia and their spouses as they discussed a marital conflict.MethodFacial behavior during the discussion was objectively coded to identify Duchenne (i.e., genuine) smiles and non-Duchenne (i.e., polite) smiles. Caregiver mental health was measured using the Medical Outcomes Survey.ResultsGreater expression of Duchenne smiles by patients was associated with better caregiver mental health, even when accounting for covariates (i.e., diagnosis, patient cognitive functioning, and caregiver marital satisfaction). Greater expression of non-Duchenne smiles by patients was associated with worse caregiver health, but only when covariates were entered in the model. Expression of Duchenne and non-Duchenne smiles by caregivers was not associated with caregiver mental health.DiscussionPatients' expression of Duchenne and non-Duchenne smiles may reveal important aspects of the emotional quality of the patient-caregiver relationship that influence caregiver burden and mental health.

ObjectiveTo test the effects of Life Enhancing Activities for Family Caregivers (LEAF), a 6-week positive emotion regulation intervention, on outcomes of positive emotion, depression, anxiety, and physical health as measured by the Patient-Reported Outcomes Measurement Information System® (PROMIS®).MethodA randomized controlled trial (N = 170) comparing LEAF (N = 86) to an emotion reporting/waitlist condition (N = 84) in dementia caregivers. LEAF was individually delivered online by trained facilitators. Participants in the control condition completed daily online emotion reports and then crossed over into the intervention condition after 6 weeks. The study was registered with Clinicaltrials.gov (NCT01825681) and funded by R01NR014435.ResultsAnalyses of difference in change from baseline to 6 weeks demonstrated significantly greater decreases in PROMIS® depression (d = -.25; p = .02) and Quality of Life in Neurological Disorders (NeuroQOL) anxiety (d = -.33; p < .01), as well as improvements in PROMIS® physical health (d = .24; p = .02) in the intervention condition compared to the emotion reporting/waitlist control. The intervention also showed greater improvements in positive emotion (d = .58; p < .01) and positive aspects of caregiving (d = .36; p < .01). Increases in positive emotion significantly mediated the effect of LEAF on depression over time.ConclusionsThis randomized controlled trial of the online-facilitated positive emotion regulation intervention in dementia caregivers demonstrated small to medium effect sizes on caregiver well-being and shows promise for remotely delivered programs to improve psychological well-being in caregivers of people with dementia and other chronic illnesses. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Given the increasing number of family caregivers of persons with dementia (PWD) and the associated burden and detriments to both physical and mental health, interventions that aim to improve such outcomes are important. Studies are increasingly demonstrating the unique importance of positive emotions in coping with stress, independent from the impact of negative emotions. However, none have examined the benefits of interventions that target positive emotions for caregivers of individuals with a chronic and debilitating disease such as dementia. This paper presents the design and methods for a randomized controlled trial (RCT) of a positive affect skills intervention for family caregivers of PWD. The RCT is of a skills-based intervention that seeks to increase the frequency and intensity of positive affect in order to improve outcomes such as well-being, coping, and physical and mental health. The skills are delivered by trained facilitators via five one-to-one Internet video sessions with family caregivers of persons diagnosed with dementia (eg, Alzheimer's disease, vascular dementia, unspecified). The control group is an emotion reporting/waitlist control. Follow-up assessments are conducted post-intervention and at 1, 3, and 6 months post-completion of the intervention. This study promises to be an important and needed step toward improving the lives of caregivers of PWD.

Abstract People in the Northeast United States have a long history of benefitting from the ocean in many ways, exemplified by the region's important cod and lobster fisheries, coastal tourism and recent expansion of offshore energy. Over the past few decades, the region has become one of the fastest warming spots on the planet, has seen significant growth in coastal populations, and expansion of new sectors into the marine environment, resulting in ecosystem shifts and changes to the supply and distribution of these benefits. With these changes comes a need for measuring ocean health to understand how engagement with the ocean may be affected, and how regional management may need to adapt. To address this need, we tailored the Ocean Health Index framework to the U.S. Northeast region, scoring eight distinct goals for ocean health on a scale of 0 to 100 for 11 sub‐regions over 13 years (2005–2017). All goal scores were averaged resulting in an Ocean Health Index score of 83 for the Northeast in 2017. This score fluctuated by 1 point in either direction (82–84) in the previous 12 years. The lowest scoring goals in 2017 also exhibited the highest volatility since 2005, Food Provision (64) and Resource Access Opportunities (71). The region's highest goal scores came from Livelihoods & Economies (99) and Biodiversity (90) and remained stable during the study period. Clean Waters scores had a steady, significant downward trend since 2005, while Resource Access Opportunities and Aquaculture show the largest improvements. This synthesis of over 50 datasets to create annual aggregate scores provides the public, government and non‐government agencies with an easily digestible summary of how the region is faring in regards to ocean health. Perhaps even more importantly, this synthesis allows for the tracking of trends over time and the ability to quickly identify and prioritize low‐scoring components of ocean health that could benefit from dedicated resources for improvement. As managers plan for the future in a changing Northeast marine region, the ability to track annual changes in ocean health and its respective components is key to making decisions that benefit the entire social‐ecological system. A free Plain Language Summary can be found within the Supporting Information of this article.

Interpersonal distance is central to communication and complex social behaviors but the neural correlates of interpersonal distance preferences are not defined. Previous studies suggest that damage to the orbitofrontal cortex (OFC) is associated with impaired interpersonal behavior. To examine whether the OFC is critical for maintaining appropriate interpersonal distance, we tested two groups of patients with OFC damage: Patients with OFC lesions and patients with behavioral variant frontotemporal dementia. These two groups were compared to healthy controls and to patients with lesions restricted to the dorsolateral prefrontal cortex. Only patients with OFC damage showed abnormal interpersonal distance preferences, which were significantly different from both controls and patients with dorsolateral prefrontal damage. The comfortable distances these patients chose with strangers were significantly closer than the other groups and resembled distances normally used with close others. These results shed light on the role of the OFC in regulating social behavior and may serve as a simple diagnostic tool for dementia or lesion patients.

Objectively coded interpersonal emotional behaviors that emerged during a 15-min marital conflict interaction predicted the development of physical symptoms in a 20-year longitudinal study of long-term marriages. Dyadic latent growth curve modeling showed that anger behavior predicted increases in cardiovascular symptoms and stonewalling behavior predicted increases in musculoskeletal symptoms. Both associations were found for husbands (although cross-lagged path models also showed some support for wives) and were controlled for sociodemographic characteristics (age, education) and behaviors (i.e., exercise, smoking, alcohol consumption, caffeine consumption) known to influence health. Both associations did not exist at the start of the study, but only emerged over the ensuing 20 years. There was some support for the specificity of these relationships (i.e., stonewalling behavior did not predict cardiovascular symptoms; anger behavior did not predict musculoskeletal symptoms; neither symptom was predicted by fear nor sadness behavior), with the anger-cardiovascular relationship emerging as most robust. Using cross-lagged path models to probe directionality of these associations, emotional behaviors predicted physical health symptoms over time (with some reverse associations found as well). These findings illuminate longstanding theoretical and applied issues concerning the association between interpersonal emotional behaviors and physical health and suggest opportunities for preventive interventions focused on specific emotions to help address major public health problems. (PsycINFO Database Record

Disgust is an emotion that helps us deal with potential contamination (Rozin & Fallon, 1987). It produces a distinctive facial expression (e.g., wrinkled nose) and a physiological response that is accompanied by strong visceral sensations (e.g., nausea). Given the important role that the anterior insula plays in processing and integrating visceral information (Craig, 2009), it is likely to be centrally involved in disgust. Despite this, few studies have examined the link between insular degeneration and the experience, physiology, and expression of disgust. We studied a group that was heterogeneous in terms of insular damage: 84 patients with neurodegenerative diseases (i.e., frontotemporal dementia, corticobasal syndrome, progressive supranuclear palsy, Alzheimer's disease) and 29 controls. Subjects viewed films that elicit high levels of disgust and sadness. Emotional reactivity was assessed using self-report, peripheral physiology, and facial behavior. Regional brain volumes (insula, putamen, pallidum, caudate, and amygdala) were determined from structural MRIs using the FreeSurfer method. Results indicated that smaller insular volumes were associated with reduced disgust responding in self-report and physiological reactivity, but not in facial behavior. In terms of the specificity of these findings, insular volume did not predict sadness reactivity, and disgust reactivity was not predicted by putamen, pallidum, and caudate volumes (lower self-reported disgust was associated with smaller amygdala volume). These findings underscore the central role of the insula in the experience and physiology of disgust. (PsycINFO Database Record