Integrated multimodal cell atlas of Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 donors with varying AD pathologies. This cohort includes 33 male donors and 51 female donors, with an average age at time of death of 88 years. We used quantitative neuropathology to place donors along a disease pseudoprogression score. Pseudoprogression analysis revealed two disease phases: an early phase with a slow increase in pathology, presence of inflammatory microglia, reactive astrocytes, loss of somatostatin+ inhibitory neurons, and a remyelination response by oligodendrocyte precursor cells; and a later phase with exponential increase in pathology, loss of excitatory neurons and Pvalb+ and Vip+ inhibitory neuron subtypes. These findings were replicated in other major AD studies.

Enhancer AAVs for targeting spinal motor neurons and descending motor pathways in rodents and macaque.

Experimental access to cell types within the mammalian spinal cord is severely limited by the availability of genetic tools. To enable access to lower motor neurons (LMNs) and LMN subtypes, which function to integrate information from the brain and control movement through direct innervation of effector muscles, we generated single cell multiome datasets from mouse and macaque spinal cords and discovered putative enhancers for each neuronal population. We cloned these enhancers into adeno-associated viral vectors (AAVs) driving a reporter fluorophore and functionally screened them in mouse. The most promising candidate enhancers were then extensively characterized using imaging and molecular techniques and further tested in rat and macaque to show conservation of LMN labeling. Additionally, we combined enhancer elements into a single vector to achieve simultaneous labeling of upper motor neurons (UMNs) and LMNs. This unprecedented LMN toolkit will enable future investigations of cell type function across species and potential therapeutic interventions for human neurodegenerative diseases.

The transcriptomic and spatial organization of telencephalic GABAergic neuronal types.

The telencephalon of the mammalian brain comprises multiple regions and circuit pathways that play adaptive and integrative roles in a variety of brain functions. There is a wide array of GABAergic neurons in the telencephalon; they play a multitude of circuit functions, and dysfunction of these neurons has been implicated in diverse brain disorders. In this study, we conducted a systematic and in-depth analysis of the transcriptomic and spatial organization of GABAergic neuronal types in all regions of the mouse telencephalon and their developmental origins. This was accomplished by utilizing 611,423 single-cell transcriptomes from the comprehensive and high-resolution transcriptomic and spatial cell type atlas for the adult whole mouse brain we have generated, supplemented with an additional single-cell RNA-sequencing dataset containing 99,438 high-quality single-cell transcriptomes collected from the pre- and postnatal developing mouse brain. We present a hierarchically organized adult telencephalic GABAergic neuronal cell type taxonomy of 7 classes, 52 subclasses, 284 supertypes, and 1,051 clusters, as well as a corresponding developmental taxonomy of 450 clusters across different ages. Detailed charting efforts reveal extraordinary complexity where relationships among cell types reflect both spatial locations and developmental origins. Transcriptomically and developmentally related cell types can often be found in distant and diverse brain regions indicating that long-distance migration and dispersion is a common characteristic of nearly all classes of telencephalic GABAergic neurons. Additionally, we find various spatial dimensions of both discrete and continuous variations among related cell types that are correlated with gene expression gradients. Lastly, we find that cortical, striatal and some pallidal GABAergic neurons undergo extensive postnatal diversification, whereas septal and most pallidal GABAergic neuronal types emerge simultaneously during the embryonic stage with limited postnatal diversification. Overall, the telencephalic GABAergic cell type taxonomy can serve as a foundational reference for molecular, structural and functional studies of cell types and circuits by the entire community.

Measuring Relationship Influences on Romantic Couples' Cancer-Related Behaviors During the COVID-19 Pandemic: Protocol for a Longitudinal Online Study of Dyads and Cancer Survivors.

BACKGROUND: Research has established the effects of romantic relationships on individuals' morbidity and mortality. However, the interplay between relationship functioning, affective processes, and health behaviors has been relatively understudied. During the COVID-19 pandemic, relational processes may influence novel health behaviors such as social distancing and masking. OBJECTIVE: We describe the design, recruitment, and methods of the relationships, risk perceptions, and cancer-related behaviors during the COVID-19 pandemic study. This study was developed to understand how relational and affective processes influence romantic partners' engagement in cancer prevention behaviors as well as health behaviors introduced or exacerbated by the COVID-19 pandemic. METHODS: The relationships, risk perceptions, and cancer-related behaviors during the COVID-19 pandemic study used online survey methods to recruit and enroll 2 cohorts of individuals involved in cohabiting romantic relationships, including 1 cohort of dyads (n=223) and 1 cohort of cancer survivors (n=443). Survey assessments were completed over 2 time points that were 5.57 (SD 3.14) weeks apart on average. Health behaviors assessed included COVID-19 vaccination and social distancing, physical activity, diet, sleep, alcohol use, and smoking behavior. We also examined relationship factors, psychological distress, and household chaos. RESULTS: Data collection occurred between October 2021 and August 2022. During that time, a total of 926 participants were enrolled, of which about two-thirds were from the United Kingdom (n=622, 67.8%) and one-third were from the United States (n=296, 32.2%); about two-thirds were married (n=608, 66.2%) and one-third were members of unmarried couples (n=294, 32%). In cohorts 1 and 2, the mean age was about 34 and 50, respectively. Out of 478 participants in cohort 1, 19 (4%) identified as Hispanic or Latino/a, 79 (17%) as non-Hispanic Asian, 40 (9%) as non-Hispanic Black or African American, and 306 (64%) as non-Hispanic White; 62 (13%) participants identified their sexual orientation as bisexual or pansexual, 359 (75.1%) as heterosexual or straight, and 53 (11%) as gay or lesbian. In cohort 2, out of 440 participants, 13 (3%) identified as Hispanic or Latino/a, 8 (2%) as non-Hispanic Asian, 5 (1%) as non-Hispanic Black or African American, and 398 (90.5%) as non-Hispanic White; 41 (9%) participants identified their sexual orientation as bisexual or pansexual, 384 (87.3%) as heterosexual or straight, and 13 (3%) as gay or lesbian. The overall enrollment rate for individuals was 66.14% and the overall completion rate was 80.08%. CONCLUSIONS: We discuss best practices for collecting online survey data for studies examining relationships and health, challenges related to the COVID-19 pandemic, recruitment of underrepresented populations, and enrollment of dyads. Recommendations include conducting pilot studies, allowing for extra time in the data collection timeline for marginalized or underserved populations, surplus screening to account for expected attrition within dyads, as well as planning dyad-specific data quality checks. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48516.

Potential role of cannabis in ameliorating observed racialized disparities in cancer pain management.

Cancer-related pain affects a large proportion of all patients with cancer yet remains inadequately managed, particularly among patients from certain racialized backgrounds. Recently, there has been increased research and clinical interest in the use of medical cannabis for cancer pain management, including its potential to ameliorate race-based disparities in cancer pain control. Although medical cannabis is not currently a US Food and Drug Administration-approved treatment option for cancer-related pain, many oncologists discuss and recommend its use with their patients, underscoring the need for researchers and clinicians to proactively identify barriers to cannabis for cancer pain management that may disproportionately affect patients from certain racial groups. In this commentary, we highlight challenges that patients from racialized backgrounds may face when incorporating cannabis into their palliative care regimens and discuss opportunities for researchers and clinicians to address these challenges should medical cannabis become a recommended treatment option for cancer pain management. In particular, we identify challenges at the structural (eg, lack of insurance coverage), clinician (eg, racialized stereotypes regarding addiction and pain), and individual (eg, internalized stigma) levels and emphasize the importance of multilevel approaches in combating these challenges as the evidence base regarding medical cannabis and its potential harms and therapeutic benefits continues to accumulate.

The Association of Context with Reported Self-Efficacy for Cancer-Preventive Behaviors and Perceived Cancer Risk in U.S. Adults from the Midlife in the United States (MIDUS) Study.

Background: Cancer is one of the leading causes of death in the United States. It is critical to understand the associations among multilevel determinants of cancer prevention and control behaviors. This study examined associations of neighborhood factors with perceived risk of cancer and self-efficacy for reducing cancer risk. Methods: Cross-sectional analyses included 2324 U.S. adults from the Midlife in the U.S. Wave 3. Participants completed surveys of neighborhood environment (perceived neighborhood trust and safety, built environment conditions, social integration), perceived cancer risk and cancer prevention efficacy. Multivariate linear regressions examined associations of neighborhood context with risk perceptions and self-efficacy. Results: In the model that adjusted for sociodemographic characteristics, better perceived neighborhood trust and safety were associated with lower perceived cancer risk. In fully adjusted models for sociodemographic characteristics and contextual factors, higher perceptions of neighborhood trust and safety were associated with higher cancer prevention self-efficacy. Perceptions of better built neighborhood conditions and higher social integration were significantly associated with lower perceived cancer risk and higher perceived cancer prevention efficacy. Conclusions: Perceptions of neighborhood context may play a role in shaping psychosocial factors such as perceived cancer risk and self-efficacy, even after controlling for robust predictors of these perceptions.

Synergistic Opportunities for Affective Science and Behavior Change.

Behavior change can be challenging to facilitate and achieve. Behavior change frameworks largely focus on social cognitive determinants, omitting affective determinants or including them in a superficial way. However, evidence points to the role of affect in decision-making and behavior, particularly when the behavior at focus for change is affectively pleasant or when the behavior to be facilitated is affectively unpleasant. This paper identifies challenges and opportunities to further affective science by using behavior change as a context and, relatedly, to further the science of behavior change by leveraging theoretical and methodological innovations in affective science.

Affective Science Research: Perspectives and Priorities from the National Institutes of Health.

Affective science is a broad and burgeoning field, and the National Institutes of Health (NIH) support research on a similarly broad range of topics. Across NIH, funding is available for basic, translational, and intervention research, including research in non-human animals, healthy populations, and those with or at risk for disease. Multiple NIH Institutes and Centers have specific programs devoted to topics within the affective science umbrella. Here, we introduce the funding priorities of these six: the National Cancer Institute (NCI), National Center for Complementary and Integrative Health (NCCIH), National Institute of Mental Health (NIMH), National Institute on Aging (NIA), National Institute on Drug Abuse (NIDA), and National Institute on Minority Health and Health Disparities (NIMHD). We then discuss overlapping themes and offer a perspective on promising research directions.

Integrated multimodal cell atlas of Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive and stereotyped accumulation of protein aggregates, but the underlying molecular and cellular mechanisms driving AD progression and vulnerable cell populations affected by disease remain coarsely understood. The current study harnesses single cell and spatial genomics tools and knowledge from the BRAIN Initiative Cell Census Network to understand the impact of disease progression on middle temporal gyrus cell types. We used image-based quantitative neuropathology to place 84 donors spanning the spectrum of AD pathology along a continuous disease pseudoprogression score and multiomic technologies to profile single nuclei from each donor, mapping their transcriptomes, epigenomes, and spatial coordinates to a common cell type reference with unprecedented resolution. Temporal analysis of cell-type proportions indicated an early reduction of Somatostatin-expressing neuronal subtypes and a late decrease of supragranular intratelencephalic-projecting excitatory and Parvalbumin-expressing neurons, with increases in disease-associated microglial and astrocytic states. We found complex gene expression differences, ranging from global to cell type-specific effects. These effects showed different temporal patterns indicating diverse cellular perturbations as a function of disease progression. A subset of donors showed a particularly severe cellular and molecular phenotype, which correlated with steeper cognitive decline. We have created a freely available public resource to explore these data and to accelerate progress in AD research at SEA-AD.org.

SIO-ASCO guideline on integrative medicine for cancer pain management: implications for racial and ethnic pain disparities.

Racial and ethnic disparities in pain management pose major challenges to equitable cancer care delivery. These disparities are driven by complex interactions between patient-, provider-, and system-related factors that resist reductionistic solutions and require innovative, holistic approaches. On September 19, 2022, the Society for Integrative Oncology and the American Society of Clinical Oncology published a joint guideline to provide evidence-based recommendations on integrative medicine for cancer pain management. Integrative medicine, which combines conventional treatments with complementary modalities from cultures and traditions around the world, are uniquely equipped to resonate with diverse cancer populations and fill existing gaps in pain management. Although some complementary modalities, such as music therapy and yoga, lack sufficient evidence to make a specific recommendation, other modalities, such as acupuncture, massage, and hypnosis, demonstrated an intermediate level of evidence, resulting in moderate strength recommendations for their use in cancer pain management. However, several factors may hinder real-world implementation of the Society for Integrative Oncology and the American Society of Clinical Oncology guideline and must be addressed to ensure equitable pain management for all communities. These barriers include, but are not limited to, the lack of insurance coverage for many complementary therapies, the limited diversity and availability of complementary therapy providers, the negative social norms surrounding complementary therapies, the underrepresentation of racial and ethnic subgroups in the clinical research of complementary therapies, and the paucity of culturally attuned interventions tailored to diverse individuals. This commentary examines both the challenges and the opportunities for addressing racial and ethnic disparities in cancer pain management through integrative medicine.

Support-Giving Is Associated With Lower Systemic Inflammation.

BACKGROUND: Support-giving has emerged as a health-relevant social behavior, such that giving more support is associated with better physical health. However, biological mechanisms by which support-giving and health are linked remain unclear. Whether support-giving uniquely relates to health relative to other psychosocial factors is also an open research question. PURPOSE: Two studies test the hypothesis that support-giving is uniquely (over-and-above other psychosocial factors) related to lower systemic inflammation, a biological correlate of health. METHODS: Cross-sectional associations of support-giving with markers of systemic inflammation (i.e., interleukin-6 [IL-6], C-reactive protein [CRP]) were examined in two independent samples of midlife adults (Study 1, n = 746; Study 2, n = 350). RESULTS: Consistent with hypotheses, giving to more social targets (to family and friends, and also volunteering for various causes), but not receiving support from similar targets, was associated with lower IL-6. In conceptual replication and extension with a different measure of support-giving, higher frequency of support-giving behavior was associated with lower IL-6, even after adjusting for social network size and individual differences in social desirability. There were no associations between support-giving and CRP in either sample. CONCLUSIONS: Future research needs to establish causality and directly test mechanistic pathways, but together, findings reaffirm the health-relevance of support-giving behavior and shed light on a promising biological mechanism by which such effects may occur.

Support-giving behavior and health are linked such that more support-giving is related to better health and longevity for the person giving. How such a link occurs, however, is an open question for research. Two cross-sectional studies test the hypothesis that support-giving behavior relates to lower systemic inflammation, a potential biological pathway linking supportive behavior with health. Results of Study 1 show that giving to more social targets (to family and friends, and also volunteering) is associated with lower inflammation. Receiving support was not associated with inflammation. In a replication and extension, Study 2 shows that a greater frequency of giving is also related to lower systemic inflammation, over and above the size of one's social network and individual differences in reporting socially desirable responses. Although more research is needed to establish whether support-giving causes systemic inflammation to change, the current findings highlight a promising pathway by which support-giving behavior benefits health.

Sun protection behavior: health impact, prevalence, correlates and interventions.

Sun protection behavior can reduce skin cancer risk. This paper provides an overview of skin cancer risk and the complex behavioral options for sun protection, along with a narrative review of research on determinants of, and interventions to promote, sun protection. Gaps and opportunities for future research are also outlined. Evidence supports the effectiveness of sunscreen use, ultraviolet (UV) protection clothing, and shade seeking. However, these behaviors are complex and are often performed in ways that are inadequate for sun protection. Most research examining and targeting determinants of sun protection behavior has focused on sunscreen use, to the exclusion of other strategies, and has largely ignored the complexity of even sunscreen use. Most research and interventions are theory- driven, drawing on social cognitive constructs, but also considering self and social identity and emotion. Multilevel perspectives considering context, environment, policies, and other structural contexts have also been applied to sun protection behavior, but there is a need to combine psychological constructs with factors at other levels to optimize predictive models and intervention effectiveness. Effective sun protection effectively involves complex behaviors and perceived and actual tradeoffs that should be considered, in combination with multilevel determinants, in research predicting and promoting sun safety.

Activation Versus Change as a Principle Underlying Intervention Strategies to Promote Health Behaviors.

BACKGROUND AND PURPOSE: Interventions are effective in promoting health behavior change to the extent that (a) intervention strategies modify targets (i.e., mechanisms of action), and (b) modifying targets leads to changes in behavior. To complement taxonomies that characterize the variety of strategies used in behavioral interventions, we outline a new principle that specifies how strategies modify targets and thereby promote behavior change. We distinguish two dimensions of targets-value (positive vs. negative) and accessibility (activation level)-and show that intervention strategies operate either by altering the value of what people think, feel, or want (target change) or by heightening the accessibility of behavior-related thoughts, feelings, and goals (target activation). METHODS AND RESULTS: We review strategies designed to promote target activation and find that nudges, cue-reminders, goal priming, the question-behavior effect, and if-then planning are each effective in generating health behavior change, and that their effectiveness accrues from heightened accessibility of relevant targets. We also identify several other strategies that may operate, at least in part, via target activation (e.g., self-monitoring, message framing, anticipated regret inductions, and habits). CONCLUSIONS: The Activation Vs. Change Principle (AVCP) offers a theoretically grounded and parsimonious means of distinguishing among intervention strategies. By focusing on how strategies modify targets, the AVCP can aid interventionists in deciding which intervention strategies to deploy and how to combine different strategies in behavioral trials. We outline a research agenda that could serve to further enhance the design and delivery of interventions to promote target activation.

Future-oriented Emotions and Decisions to Receive Genomic Testing Results Among U.S. Adults of African Ancestry.

BACKGROUND: Future-oriented emotions are associated with consequential health decision-making, including genomic testing decisions. However, little is known about the relative role of various future-oriented emotions in such decisions. Moreover, most research on predictors of decision making regarding genomic testing is conducted with white participants. PURPOSE: This study examined the role of future-oriented emotions in decisions to receive genomic testing results in U.S. individuals of African descent. METHODS: We analyzed cross-sectional survey data from a genomic sequencing cohort (N = 408). All participants identified as African, African-American, or Afro-Caribbean (Mage = 56.3, 74.7% female). Participants completed measures assessing anticipatory affect (worry about genetic testing results), anticipated distress (feeling devastated if genetic testing showed an increased risk for fatal disease), and anticipated regret (regretting a decision not to learn results). Outcomes were intentions for learning actionable, nonactionable, and carrier results. RESULTS: Anticipated regret was robustly positively associated with intentions to receive actionable (b = 0.28, p < .001), nonactionable (b = 0.39, p < .001), and carrier (b = 0.30, p < .001) results. Anticipated distress was negatively associated with intentions to receive nonactionable results only (b = -0.16, p < .01). Anticipatory negative affect (worry) was not associated with intentions. At higher levels of anticipated regret, anticipated distress was less strongly associated with intentions to receive nonactionable results (b = 0.14, p = .02). CONCLUSIONS: Our results highlight the role of future-oriented emotions in genomic testing among participants who are typically underrepresented in genomic testing studies and behavioral medicine broadly. Future work should examine whether interventions targeting future-oriented emotions such as anticipated regret may have clinically meaningful effects in genetic counseling in similar cohorts.

Future-oriented emotions (emotions directed toward a future outcome, such as worrying about a future outcome, or expecting to feel distress or regret if a particular outcome occurs) are important predictors of health decisions, including decisions to seek and receive genomic testing results. Understanding how such factors relate to decisions to receive genetic testing results is particularly important in medically-underserved groups such as individuals of African ancestry, who are underrepresented in genomics and behavioral science research. We analyzed survey responses from a genomic sequencing cohort where all 408 participants identified as African, African-American, or Afro-Caribbean, and were asked about their level of worry, anticipated distress, and anticipated regret about results, plus their interest in receiving three types of genomic testing results from the study. We found that participants who expected that they would regret their decision to not learn the results had stronger intentions to receive all three types of results; those who expected to feel distressed by a genetic testing result that showed an increased risk for a fatal disease were less interested in nonactionable genetic testing results specifically. Our results highlight the differing roles of specific types of future-oriented emotions in genomic testing decisions, among participants who are typically underrepresented in this type of research.

Increasing Receptivity to COVID-19 Public Health Messages with Self-Affirmation and Self vs. Other Framing.

There remains an urgent need for effective communication about the importance of widespread adherence to behavioral recommendations to control the COVID-19 pandemic that will also reduce resistance to such guidance. We examined two strategies for COVID-19 communication- (1) self-affirmation (reflecting on a personal value in order to boost self-integrity and reduce defensiveness to potentially threatening information); and (2) manipulating self/other message framing - and moderation of these strategies by COVID-19 risk. 600 participants (Mage = 32.55, 51% female) were recruited for an online study and, after assessment of risk factors for severe COVID-19 infection, were exposed to the experimental manipulations. Three classes of defensive responses were considered as outcomes of interest: reactance, attitudinal responses, and behavioral responses. We found that participants derogated the self-focused message more than the other-focused message. Further, other-focused messaging and/or self-affirmation were more likely to elicit positive responses among individuals at higher risk for COVID-19 complications. Our findings suggest having individuals affirm values prior to viewing COVID-19 messages, and framing messages in terms of the importance of protecting others, may be beneficial strategies for encouraging responsiveness - particularly if the targets of such messages are at risk of COVID-19 complications themselves.

Perceptions and tolerance of uncertainty: relationship to trust in COVID-19 health information and vaccine hesitancy.

The COVID-19 crisis has exposed the public to considerable scientific uncertainty, which may promote vaccine hesitancy among individuals with lower tolerance of uncertainty. In a national sample of US adults in May-June 2020, we examined how both perceptions of uncertainty about COVID-19 and trait-level differences in tolerance of uncertainty arising from various sources (risk, ambiguity, and complexity) are related to vaccine hesitancy-related outcomes, including trust in COVID-19 information, COVID-19 vaccine intentions, and beliefs that COVID-19 vaccines should undergo a longer testing period before being released to the public. Overall, perceptions of COVID-19 uncertainty were not associated with trust in information, vaccine intentions, or beliefs about vaccine testing. However, higher tolerance of risk was associated with lower intentions to get vaccinated, and lower tolerance of ambiguity was associated with lower intentions to get vaccinated and preferring a longer period of vaccine testing. Critically, perceptions of COVID-19 uncertainty and trait-level tolerance for uncertainty also interacted as predicted, such that greater perceived COVID-19 uncertainty was more negatively associated with trust in COVID-19 information among individuals with lower tolerance for risk and ambiguity. Thus, although perceptions of uncertainty regarding COVID-19 may not reduce trust and vaccine hesitancy for all individuals, trait-level tolerance of uncertainty arising from various sources may have both direct and moderating effects on these outcomes. These findings can inform public health communication or other interventions to increase COVID-19 vaccination uptake.

Responsive social support serves important functions in clinical communication: Translating perspectives from relationship science to improve cancer clinical interactions.

Patient-clinician interactions are critical to patient-centered care, including in cancer care contexts which are often defined by multiple patient-clinician interactions over an extended period. Research on these dyadic interactions has been guided by perspectives in clinical communication science, but the study of clinical communication has not been fully integrated with perspectives on interpersonal interactions from relationship science research. An overlapping concept in both fields is the concept of responsive socialsupport. In this article, we discuss responsiveness as a concept that offers opportunities for connections between these two disciplines. Next, we focus on how relationship science can be applied to research in clinical settings. We discuss how three areas of relationship science define responsiveness and have potential for extension to clinical communication: (1) (in)visibility of social support, (2) attachment orientations, and (3) shared meaning systems. We also discuss how social biases can impede responsiveness and suggest research avenues to develop ideas and understand potential challenges in connecting these two fields. Many opportunities exist for interdisciplinary theory development that can generate momentum in understanding interpersonal processes in cancer care.

Understanding responses to different types of conflicting information about cancer prevention.

BACKGROUND: Individuals are regularly exposed to conflicting information about health; however, understanding of how individuals respond to different types of conflicting information is limited. METHODS: In total, 1027 US adults were randomly assigned to 1 of 8 conflicting information messages about nutrition and cancer risk, depicting 1/4 conflicting information types (conflict in evidence - sources A and B agree the evidence is mixed; conflict between two expert sources - sources A and B present conflicting evidence about nutrition and cancer risk; conflict within the same expert source - source A changes its own recommendation about the evidence; no conflict control) crossed by 1/2 baseline recommendations with which new information conflicted (limit vs. do not limit red meat intake to reduce cancer risk). RESULTS: Compared to the control, each conflicting information type led to lower perceived scientific consensus about how much red meat one should eat (p < .001); conflict in evidence (p = .004) and between sources (p = .006) led to lower trust in scientists. Intentions to consume red meat more frequently were higher in the conflicting information conditions than control in the group initially told to "limit red meat" and lower in the "do not limit red meat" group (p = .022). Conflict within the same source led to higher perceived scientific consensus compared to conflict in evidence (p = .007) and between sources (p = .013); it also lowered intentions to consume red meat more frequently compared to conflict in evidence, but only in the "do not limit red meat" condition (p = .033). Conflict in evidence (p = .007) and within the same source (p = .013) increased cancer fatalism compared to conflict between sources. CONCLUSIONS: Conflict in scientific evidence and conflict arising from the same expert source (e.g., a changing public health guideline) may have pernicious effects. Future efforts could investigate how best to publicly communicate these instances of scientific conflict to minimize negative impact.

Analysis of the components of cancer risk perception and links with intention and behaviour: A UK-based study.

Risk perception refers to how individuals interpret their susceptibility to threats, and has been hypothesised as an important predictor of intentions and behaviour in many theories of health behaviour change. However, its components, optimal measurement, and effects are not yet fully understood. The TRIRISK model, developed in the US, conceptualises risk perception as deliberative, affective and experiential components. In this study, we aimed to assess the replicability of the TRIRISK model in a UK sample by confirmatory factor analysis (CFA), explore the inherent factor structure of risk perception in the UK sample by exploratory factor analysis (EFA), and assess the associations of EFA-based factors with intentions to change behaviour and subsequent behaviour change. Data were derived from an online randomised controlled trial assessing cancer risk perception using the TRIRISK instrument and intention and lifestyle measures before and after communication of cancer risk. In the CFA analysis, the TRIRISK model of risk perception did not provide a good fit for the UK data. A revised model developed using EFA consisted of two separate "numerical" and "self-reflective" factors of deliberative risk perception, and a third factor combining affective with a subset of experiential items. This model provided a better fit to the data when cross-validated. Using multivariable regression analysis, we found that the self-reflective and affective-experiential factors of the model identified in this study were reliable predictors of intentions to prevent cancer. There were no associations of any of the risk perception factors with behaviour change. This study confirms that risk perception is clearly a multidimensional construct, having identified self-reflective risk perception as a new distinct component with predictive validity for intention. Furthermore, we highlight the practical implications of our findings for the design of interventions incorporating risk perception aimed at behaviour change in the context of cancer prevention.