Disparities in Nicotine Addictiveness and Cancer Harm Perceptions Among U.S. Adults: A Trend Analysis Using the Health Information National Trends Survey.

INTRODUCTION: Recent research has found widespread misperceptions about nicotine. This study tests perceptions among U.S. adults with respect to nicotine addictiveness and cancer harm, while distinguishing between nicotine misperceptions (ie an incorrect response) and "don't know" (DK) responses. AIMS AND METHODS: Data from three cycles of the Health Information National Trends Survey, fielded in 2015, 2017, and 2019 were merged for analysis. Weighted multinominal logistic regression models were conducted where nicotine addictiveness and cancer harm beliefs (DK, incorrect, and correct responses) were regressed on survey year and demographic variables. We also tested for interactions between survey year and demographic variables to assess if previously identified disparities had evolved during these years. RESULTS: Analyses showed lower odds of misperceptions about nicotine addictiveness, but higher odds of misperceptions about nicotine cancer harm in 2019 compared to 2015. There was no change in DK responses during these years. Disparities by sociodemographics and tobacco use status were observed, mostly for cancer harm. Survey year significantly interacted with age in the model for cancer harm, which was driven primarily by increased incorrect responses and decreased DK responses over time among the youngest age group (18-34 years). There were no significant interactions between survey year and race and ethnicity or level of educational attainment. CONCLUSIONS: Disparities in nicotine addictiveness and cancer harm perceptions reflect the uneven distribution of knowledge in the U.S. adult population. Nicotine cancer harm misperceptions are increasing and educational efforts to address this misperception are warranted. IMPLICATIONS: Future educational efforts targeting nicotine addictiveness beliefs may benefit by focusing on DK responders. The growing trend of misperceptions of nicotine's role in cancer harm may negatively impact perceptions about nicotine replacement therapy and low nicotine content cigarettes. Future efforts should focus on correcting nicotine cancer harm misperception, particularly among young adults.

Mapping Uncharted Terrain: A Systematic Review of Complementary and Integrative Health Communication Using Observational Data in Biomedical Settings.

Complementary and integrative health (CIH) use is diverse and highly prevalent worldwide. Prior research of CIH communication in biomedical encounters address safety, efficacy, symptom management, and overall wellness. Observational methods are rarely used to study CIH communication and avoid recall bias, preserve ecological validity, and contextualize situated clinical communication. Following PRISMA guidelines, we systematically reviewed studies at the intersection of social scientific observational research and findings about CIH communication between clinicians, patients, and caregivers in biomedical settings. We identified international, peer-reviewed publications from seven databases between January 2010 and December 2020. Titles and abstracts were first screened for inclusion, then full studies were coded using explicit criteria. We used a standard checklist was modified to assess article quality. Ten of 11,793 studies examined CIH communication using observational methods for CIH communication in biomedical settings. Studies used a range of observational techniques, including participant and non-participant observation, which includes digital audio or video recordings. Results generated two broad sets of findings, one focused on methodological insights and another on CIH communication. Despite methodological and topic similarities, included studies addressed CIH communication as a process and as proximal and intermediate health outcomes. We recommend how observational studies of CIH communication can better highlight relationships between communication processes and health outcomes. Current research using observational methods offers an incomplete picture of CIH communication in biomedical settings. Future studies should standardize how observational techniques are reported to enhance consistency and comparability within and across biomedical settings to improve comparability.

Human PLD structures enable drug design and characterization of isoenzyme selectivity.

Phospholipase D enzymes (PLDs) are ubiquitous phosphodiesterases that produce phosphatidic acid (PA), a key second messenger and biosynthetic building block. Although an orthologous bacterial Streptomyces sp. strain PMF PLD structure was solved two decades ago, the molecular basis underlying the functions of the human PLD enzymes (hPLD) remained unclear based on this structure due to the low homology between these sequences. Here, we describe the first crystal structures of hPLD1 and hPLD2 catalytic domains and identify novel structural elements and functional differences between the prokaryotic and eukaryotic enzymes. Furthermore, structure-based mutation studies and structures of inhibitor-hPLD complexes allowed us to elucidate the binding modes of dual and isoform-selective inhibitors, highlight key determinants of isoenzyme selectivity and provide a basis for further structure-based drug discovery and functional characterization of this therapeutically important superfamily of enzymes.

Estimating misclassification errors in the reporting of maternal mortality in national civil registration vital statistics systems: A Bayesian hierarchical bivariate random walk model to estimate sensitivity and specificity for multiple countries and years with missing data.

Civil registration vital statistics (CRVS) systems provide data on maternal mortality that can be used for monitoring trends and to inform policies and programs. However, CRVS maternal mortality data may be subject to substantial reporting errors due to misclassification of maternal deaths. Information on misclassification is available for selected countries and periods only. We developed a Bayesian hierarchical bivariate random walk model to estimate sensitivity and specificity for multiple populations and years and used the model to estimate misclassification errors in the reporting of maternal mortality in CRVS systems. The proposed Bayesian misclassification (BMis) model captures differences in sensitivity and specificity across populations and over time, allows for extrapolations to periods with missing data, and includes an exact likelihood function for data provided in aggregated form. Validation exercises using maternal mortality data suggest that BMis is reasonably well calibrated and improves upon the CRVS-adjustment approach used until 2018 by the UN Maternal Mortality Inter-Agency Group (UN-MMEIG) to account for bias in CRVS data resulting from misclassification error. Since 2019, BMis is used by the UN-MMEIG to account for misclassification errors when estimating maternal mortality using CRVS data.

Information Avoidance, Self-affirmation, and Intentions to Receive Genomic Sequencing Results Among Members of an African Descent Cohort.

BACKGROUND: Information avoidance tendencies have been found to be associated with lower intentions to pursue medically actionable genomic sequencing results, but less so among individuals who engage more in spontaneous self-affirmation. Yet these results were obtained with a largely non-Hispanic White, high-SES cohort. PURPOSE: To assess these variables, their magnitude, and their associations in an African-descent cohort as part of the same ClinSeq® exome sequencing program. METHODS: Participants reported levels of spontaneous self-affirmation, information avoidance, and intentions to receive three types of results - medically actionable, non-medically actionable, and carrier status as part of a baseline survey. RESULTS: Relative to the original, non-Hispanic White cohort, those in the African-descent cohort had higher levels of spontaneous self-affirmation and lower intentions of learning about carrier genomic results; they reported comparable levels of information avoidance and intentions to receive other results. Information avoidance was negatively associated with intention to receive non-actionable results in the African-descent cohort, as found in the initial cohort, with no moderating effect of spontaneous self-affirmation. Information avoidance, spontaneous self-affirmation, and their interaction were not associated with intentions to receive actionable results (contrary to findings in the initial cohort), or carrier results. CONCLUSIONS: Individuals of African descent may engage in relatively more spontaneous self-affirmation, and do not appear to engage in more information avoidance. Their information avoidance tendencies were associated with pursuit of non-actionable sequencing results, with no moderating effect of self-affirmation, and were not associated with pursuit of actionable results or carrier results.

Discrimination, identity connectedness and tobacco use in a sample of sexual and gender minority young adults.

INTRODUCTION: Studies show that tobacco use among sexual and gender minority (SGM) populations is disproportionately higher than heterosexual or cisgender populations. However, few studies have examined tobacco use among SGM subgroups by race/ethnicity or associations between SGM-specific discrimination and connection to SGM identity and tobacco use. METHODS: This study analysed survey data from 11 313 SGM (gay, lesbian, bisexual, other sexual minority or gender minority) young adults in the USA and reported current cigarette, e-cigarette, other tobacco (cigar, smokeless tobacco, hookah) and polytobacco use. We used multinomial logistic regression to estimate associations between (a) SGM subgroup, race/ethnicity, SGM-specific discrimination and SGM identity connection and (b) each tobacco use outcome (vs never use of tobacco). We conducted postestimation testing to assess predicted probabilities of tobacco use against the sample average. RESULTS: Lesbian females (particularly black lesbian females) had higher-than-average probability of polytobacco use. White bisexual and lesbian participants had higher-than-average probability of cigarette and e-cigarette use, respectively. Higher levels of discrimination were associated with polytobacco use. Higher levels of identity connectedness were protective against certain tobacco use behaviours among gender minority participants and participants with high levels of discrimination experience. CONCLUSIONS: We found variations in tobacco use by SGM subgroups overall and by race/ethnicity. Discrimination may be a risk factor for certain tobacco use behaviours. However, SGM identity connectedness may be protective against tobacco use among gender minority individuals and individuals experiencing SGM-specific discrimination. These findings can inform targeted approaches to reach SGM subgroups at greater risk of tobacco use.

Proteomic Characterization of the Dynamics of Ischemic Stroke in Mice.

Novel therapies and biomarkers are needed for the treatment of acute ischemic stroke (AIS). This study aimed to provide comprehensive insights into the dynamic proteome changes and underlying molecular mechanisms post-ischemic stroke. TMT-coupled proteomic analysis was conducted on mouse brain cortex tissue from five time points up to 4 weeks poststroke in the distal hypoxic-middle cerebral artery occlusion (DH-MCAO) model. We found that nearly half of the detected proteome was altered following stroke, but only ∼8.6% of the changes were at relatively large scales. Clustering on the changed proteome defined four distinct expression patterns characterized by temporal and quantitative changes in innate and adaptive immune response pathways and cytoskeletal and neuronal remodeling. Further analysis on a subset of 309 "top hits", which temporally responded to stroke with relatively large and sustained changes, revealed that they were mostly secreted proteins, highly correlated to different cortical cytokines, and thereby potential pharmacodynamic biomarker candidates for inflammation-targeting therapies. Closer examination of the top enriched neurophysiologic pathways identified 57 proteins potentially associated with poststroke recovery. Altogether, our study generated a rich dataset with candidate proteins worthy of further validation as biomarkers and/or therapeutic targets for stroke. The proteomics data are available in the PRIDE Archive with identifier PXD025077.

Geospatial indicators of exposure, sensitivity, and adaptive capacity to assess neighbourhood variation in vulnerability to climate change-related health hazards.

BACKGROUND: Although the frequency and magnitude of climate change-related health hazards (CCRHHs) are likely to increase, the population vulnerabilities and corresponding health impacts are dependent on a community's exposures, pre-existing sensitivities, and adaptive capacities in response to a hazard's impact. To evaluate spatial variability in relative vulnerability, we: 1) identified climate change-related risk factors at the dissemination area level; 2) created actionable health vulnerability index scores to map community risks to extreme heat, flooding, wildfire smoke, and ground-level ozone; and 3) spatially evaluated vulnerability patterns and priority areas of action to address inequity. METHODS: A systematic literature review was conducted to identify the determinants of health hazards among populations impacted by CCRHHs. Identified determinants were then grouped into categories of exposure, sensitivity, and adaptive capacity and aligned with available data. Data were aggregated to 4188 Census dissemination areas within two health authorities in British Columbia, Canada. A two-step principal component analysis (PCA) was then used to select and weight variables for each relative vulnerability score. In addition to an overall vulnerability score, exposure, adaptive capacity, and sensitivity sub-scores were computed for each hazard. Scores were then categorised into quintiles and mapped. RESULTS: Two hundred eighty-one epidemiological papers met the study criteria and were used to identify 36 determinant indicators that were operationalized across all hazards. For each hazard, 3 to 5 principal components explaining 72 to 94% of the total variance were retained. Sensitivity was weighted much higher for extreme heat, wildfire smoke and ground-level ozone, and adaptive capacity was highly weighted for flooding vulnerability. There was overall varied contribution of adaptive capacity (16-49%) across all hazards. Distinct spatial patterns were observed - for example, although patterns varied by hazard, vulnerability was generally higher in more deprived and more outlying neighbourhoods of the study region. CONCLUSIONS: The creation of hazard and category-specific vulnerability indices (exposure, adaptive capacity and sensitivity sub-scores) supports evidence-based approaches to prioritize public health responses to climate-related hazards and to reduce inequity by assessing relative differences in vulnerability along with absolute impacts. Future studies can build upon this methodology to further understand the spatial variation in vulnerability and to identify and prioritise actionable areas for adaptation.

Fisheries management impacts on target species status.

Fisheries management systems around the world are highly diverse in their design, operation, and effectiveness at meeting objectives. A variety of management institutions, strategies, and tactics are used across disparate regions, fishing fleets, and taxonomic groups. At a global level, it is unclear which particular management attributes have greatest influence on the status of fished populations, and also unclear which external factors affect the overall success of fisheries management systems. We used expert surveys to characterize the management systems by species of 28 major fishing nations and examined influences of economic, geographic, and fishery-related factors. A Fisheries Management Index, which integrated research, management, enforcement, and socioeconomic attributes, showed wide variation among countries and was strongly affected by per capita gross domestic product (positively) and capacity-enhancing subsidies (negatively). Among 13 management attributes considered, three were particularly influential in whether stock size and fishing mortality are currently in or trending toward desirable states: extensiveness of stock assessments, strength of fishing pressure limits, and comprehensiveness of enforcement programs. These results support arguments that the key to successful fisheries management is the implementation and enforcement of science-based catch or effort limits, and that monetary investment into fisheries can help achieve management objectives if used to limit fishing pressure rather than enhance fishing capacity. Countries with currently less-effective management systems have the greatest potential for improving long-term stock status outcomes and should be the focus of efforts to improve fisheries management globally.

Cancer communication research in the era of genomics and precision medicine: a scoping review.

Effective use of genetic and genomic data in cancer prevention and treatment depends on adequate communication with patients and the public. Although relevant empirical work has emerged, the scope and outcomes of this communication research have not been characterized. We conducted a comprehensive scoping review of recent published research (2010-2017) on communication of cancer-related genetic and genomic testing (CGT) information. Searches in six databases revealed 9243 unique records; 513 papers were included. Most papers utilized an observational quantitative design; fewer utilized an experimental design. More attention has been paid to outcomes of CGT results disclosure than to decision making regarding CGT uptake or the process of results disclosure. Psychosocial outcomes were most common across studies. This literature has a strong focus on BRCA1/2, with few papers focused on Lynch syndrome or next-generation technologies. Women, Caucasians, older adults, and those of higher socioeconomic status were overrepresented. Research gaps identified include the need for studies on the process of CGT communication; examining behavioral, decision making, and communication outcomes; and inclusion of diverse populations. Addressing these gaps can help improve the use of genomics in cancer control and reduce disparities in access to and use of CGT.

Item Development and Performance of Tobacco Product and Regulation Perception Items for the Health Information National Trends Survey.

INTRODUCTION: Emerging tobacco products have become increasingly popular, and the US Food and Drug Administration extended its authority to all products meeting the definition of a tobacco product in 2016. These changes may lead to shifts in public perceptions about tobacco products and regulation, and national surveys are attempting to assess these perceptions at the population level. This article describes the item development and cognitive interviewing of the tobacco product and regulation perception items included in two tobacco-focused cycles of the Health Information National Trends Survey (HINTS-FDA), referred to as HINTS-FDA. METHODS: Cognitive interviewing was used to investigate how respondents comprehended and responded to tobacco product and regulation perception items. Adult participants (n = 20) were selected purposively to oversample current tobacco users and were interviewed in two iterative rounds. Weighted descriptive statistics from the fielded HINTS-FDA surveys (N = 5474) were also calculated. RESULTS: Items were generally interpreted as intended, and participants meaningfully discriminated between tobacco products when assessing addiction perceptions. Response selection issues involved inconsistent reporting among participants with little knowledge or ambivalent opinions about either government regulation or tobacco products and ingredients, which resolved when a "don't know" response option was included in the survey. The fielded survey found that a non-negligible proportion of the population do not have clear perceptions of emerging tobacco products or government regulation. CONCLUSIONS: A "don't know" response option is helpful for items assessing many emerging tobacco products but presents several analytic challenges that should be carefully considered. Multiple items assessing specific tobacco product and regulation perception items are warranted in future surveys. IMPLICATIONS: The findings from this study can serve as a foundation for future surveys that assess constructs related to emerging tobacco products, harm perceptions across multiple tobacco products, and tobacco-related government regulatory activities. The data provide unique insight into item-specific motivation for selecting a "don't know" response option for tobacco survey items.

An Update on Cognitive Therapy for the Management of Chronic Pain: a Comprehensive Review.

PURPOSE OF REVIEW: Psychological approaches to the management of chronic pain have proven to be very effective in allowing patients to better manage their symptoms and with overall functioning. RECENT FINDINGS: Cognitive functional therapy (CFT) is centered on a three-step process, beginning with cognitive training, then progressing to functional movement training and exposure with control, and ending with physical activity and lifestyle changes. Cognitive behavioral therapy (CBT) as a technique focuses on identifying and changing maladaptive behaviors, thought patterns, and situations that contribute to psychiatric dysfunction, which may lead to further progression of pain. The purpose of this review is to provide a comprehensive update of recent advances in the use of both CFT and CBT for the management of chronic pain conditions.

Using graphic text-messaging to promote smoking cessation among first-generation Chinese and Korean male immigrants.

First-generation Chinese and Korean male immigrants in the United States are at high risk for tobacco use. This study pilot-tested a graphic, native-language text-messaging intervention to promote smoking cessation among these groups. First-generation Chinese and Korean male immigrant smokers (N = 71) were recruited from the Washington DC area. Participants were randomly assigned to one of four conditions based on a between-subjects 2 (graphic plus text or text-only messages) � 2 (quitline information or quitting tips) design. The text-messaging intervention included 30 text messages in total and lasted one month. Participants completed an expired air carbon monoxide (CO) assessment and self-reported measures at both baseline and follow-up. Results show that, from baseline to follow-up, participants' expired air CO levels decreased significantly (P = 0.001). Attitude toward quitting also became more positive (P = 0.028). Compared with text-only messages, graphic text messages produced greater positive changes in quitting attitudes (P = 0.039) and elicited greater fear response (P = 0.005). Compared with quitting tip messages, quitline information resulted in greater regret (P = 0.016) and fear (P = 0.051). These findings suggest that graphic text-messaging can be an effective method to promote smoking cessation among first-generation Chinese and Korean male immigrants.

1,2,4-Triazolsulfone: A novel isosteric replacement of acylsulfonamides in the context of NaV1.7 inhibition.

Recently, the identification of several classes of aryl sulfonamides and acyl sulfonamides that potently inhibit NaV1.7 and demonstrate high levels of selectivity over other NaV isoforms have been reported. The fully ionizable nature of these inhibitors has been shown to be an important part of the pharmacophore for the observed potency and isoform selectivity. The requirement of this functionality, however, has presented challenges associated with optimization toward inhibitors with drug-like properties and minimal off-target activity. In an effort to obviate these challenges, we set out to develop an orally bioavailable, selective NaV1.7 inhibitor, lacking these acidic functional groups. Herein, we report the discovery of a novel series of inhibitors wherein a triazolesulfone has been designed to serve as a bioisostere for the acyl sulfonamide. This work culminated in the delivery of a potent series of inhibitors which demonstrated good levels of selectivity over NaV1.5 and favorable pharmacokinetics in rodents.

The role of medical social workers in cancer clinical trial teams: A group case study of multidisciplinary perspectives.

INTRODUCTION: Social workers collaborate with a wide range of healthcare providers in clinical trial teams, yet their roles may not always be understood or supported by team members. It is currently unknown how social workers and multidisciplinary team members perceive social workers' roles in the clinical trial context. METHODS: Using a group case-study approach, social workers, core medical team members, and allied healthcare workers (n = 19) completed in-depth interviews to discuss the roles of social workers in a cancer clinical trial setting. FINDINGS: Social workers discussed their role as primarily patient-centered, perceiving themselves to be a counselor, patient advocate, and conduit. They also described areas of perceived limited role contribution. Other members of the multidisciplinary teams viewed the roles of social workers to be focused on being a conduit and coordinator. DISCUSSION: We found discordance in the way that social workers and their team members view the roles of social workers in clinical trials. Our data suggest that structural and interpersonal barriers may prevent social workers from working to the full extent of their license in a clinical trial context. Implications, future research, and suggestions for interventions to more fully integrate social workers into clinical trial settings are discussed.

Discovery of a biarylamide series of potent, state-dependent NaV1.7 inhibitors.

The NaV1.7 ion channel has garnered considerable attention as a target for the treatment of pain. Herein we detail the discovery and structure-activity relationships of a novel series of biaryl amides. Optimization led to the identification of several state-dependent, potent and metabolically stable inhibitors which demonstrated promising levels of selectivity over NaV1.5 and good rat pharmacokinetics. Compound 18, which demonstrated preferential inhibition of a slow inactivated state of NaV1.7, was advanced into a rat formalin study where upon reaching unbound drug levels several fold over the rat NaV1.7 IC50 it failed to demonstrate a robust reduction in nociceptive behavior.

The discovery of benzoxazine sulfonamide inhibitors of NaV1.7: Tools that bridge efficacy and target engagement.

The voltage-gated sodium channel NaV1.7 has received much attention from the scientific community due to compelling human genetic data linking gain- and loss-of-function mutations to pain phenotypes. Despite this genetic validation of NaV1.7 as a target for pain, high quality pharmacological tools facilitate further understanding of target biology, establishment of target coverage requirements and subsequent progression into the clinic. Within the sulfonamide class of inhibitors, reduced potency on rat NaV1.7 versus human NaV1.7 was observed, rendering in vivo rat pharmacology studies challenging. Herein, we report the discovery and optimization of novel benzoxazine sulfonamide inhibitors of human, rat and mouse NaV1.7 which enabled pharmacological assessment in traditional behavioral rodent models of pain and in turn, established a connection between formalin-induced pain and histamine-induced pruritus in mice. The latter represents a simple and efficient means of measuring target engagement.

Primary care physicians' attitudes and beliefs about cancer clinical trials.

BACKGROUND/AIMS: Cancer clinical trials give patients access to state-of-the-art treatments and facilitate the translation of findings into mainstream clinical care. However, patients from racial and ethnic minority groups remain underrepresented in clinical trials. Primary care physicians are a trusted source of information for patients, yet their role in decision-making about cancer treatment and referrals to trial participation has received little attention. The aim of this study was to determine physicians' knowledge, attitudes, and beliefs about cancer clinical trials, their experience with trials, and their interest in appropriate training about trials. METHODS: A total of 613 physicians in the New York City area primarily serving patients from ethnic and racial minority groups were invited via email to participate in a 20-min online survey. Physicians were asked about their patient population, trial knowledge and attitudes, interest in training, and personal demographics. Using calculated scale variables, we used descriptive statistical analyses to better understand physicians' knowledge, attitudes, and beliefs about trials. RESULTS: A total of 127 physicians completed the survey. Overall, they had low knowledge about and little experience with trials. However, they generally had positive attitudes toward trials, with 41.4% indicating a strong interest in learning more about their role in trials, and 35.7% indicating that they might be interested. Results suggest that Black and Latino physicians and those with more positive attitudes and beliefs were more likely to be interested in future training opportunities. CONCLUSION: Primary care physicians may be an important group to target in trying to improve cancer clinical trial participation among minority patients. Future work should explore methods of educational intervention for such interested providers.

Rhesus macaques (Macaca mulatta) with self-injurious behavior show less behavioral anxiety during the human intruder test.

Self-injurious behavior (SIB) has been linked to anxiety in the human literature, but relatively few studies have explored this link in rhesus macaques. A widely used behavioral assessment of anxiety, the human intruder test (HIT), employs the mildly stressful stimulus of an unfamiliar experimenter to assess anxious behavior in macaques. The HIT was conducted on 59 (20 male) laboratory housed rhesus macaques, 30 with a record of SIB (10 male). If monkeys with SIB have a more anxious phenotype, they should show stronger reactions to the HIT. However, contrary to our predictions, monkeys with SIB did not show higher levels of anxious behavior compared to controls. They spent significantly less time showing anxious behavior and displayed little aggression in response to the stare of the intruder. SIB and control monkeys did not differ in a range score (number of unique behaviors expressed per phase); however, SIB monkeys had a lower change score (total number of behaviors expressed including repetitions) than controls. In general, monkeys that paced regardless of SIB status, showed a reduction in pacing when the intruder entered the room. Possible explanations for the failure of SIB monkeys to show increased anxiety in the HIT include greater exposure of SIB monkeys to unfamiliar humans because of their condition, evidence for a subtype of SIB which is not anxiety related, and/or the presence of comorbid depressive-like symptoms. Am. J. Primatol. 79:e22569, 2017. © 2016 Wiley Periodicals, Inc.

Responses to the Human Intruder Test are related to hair cortisol phenotype and sex in rhesus macaques (Macaca mulatta).

Measurement of cortisol in hair provides a chronic index of hypothalamic-pituitary-adrenal (HPA) axis activity and has been applied to assessments of temperament (stable behavioral differences between individuals). However, the extent to which chronically high HPA axis activity relates to a correspondingly high degree of behavioral reactivity is as yet unknown. Therefore, the goal of the present experiment was to assess the relationship between hair cortisol and a reactive temperament. We administered the Human Intruder Test (HIT) twice to 145 (80 male) rhesus macaques (Macaca mulatta) in order to assess behavioral reactivity. The HIT presents monkeys with an unfamiliar experimenter and is composed of a Baseline phase (no intruder) followed by three experimental phases in which the orientation of the intruder changes (Profile, Stare, Back). Behavioral responses to the test were videotaped and behaviors thought to reflect a reactive response to the intruder were scored for duration. Hair samples collected within ±1 month of the first HIT session were analyzed for cortisol by enzyme immunoassay. Subjects were assigned to three groups based on hair cortisol concentration: high, intermediate, and low cortisol phenotypes. Monkeys with the high cortisol phenotype were more reactive to the presence of the intruder than those with the low cortisol phenotype: they were more aggressive, scratched more, and spent more time in the back half of the cage. Males yawned significantly more while females spent more time immobile and in the back of the cage. Overall, monkeys with higher hair cortisol demonstrated an exaggerated response to the presence of the human intruder, supporting a relationship between high levels of chronic HPA axis activity and a reactive temperament. These results indicate that high levels of HPA axis activity, which may result from either genetic variation or environmental stress, correspond with heightened behavioral responses to a stressful experience. Am. J. Primatol. 79:e22526, 2017. © 2016 Wiley Periodicals, Inc.