A phase 1 study of nivolumab in combination with interferon-gamma for patients with advanced solid tumors.

This phase I, dose-escalation trial evaluates the safety of combining interferon-gamma (IFN-γ) and nivolumab in patients with metastatic solid tumors. Twenty-six patients are treated in four cohorts assessing increasing doses of IFN-γ with nivolumab to evaluate the primary endpoint of safety and determine the recommended phase two dose (RP2D). Most common adverse events are low grade and associated with IFN-γ. Three dose limiting toxicities are reported at the highest dose cohorts. We report only one patient with any immune related adverse event (irAE). No irAEs ≥ grade 3 are observed and no patients require corticosteroids. The maximum tolerated dose of IFN-γ is 75 mcg/m2, however based on a composite of safety, clinical, and correlative factors the RP2D is 50 mcg/m2. Exploratory analyses of efficacy in the phase I cohorts demonstrate one patient with a complete response, and five have achieved stable disease. Pre-planned correlative assessments of circulating immune cells demonstrate intermediate monocytes with increased PD-L1 expression correlating with IFN-γ dose and treatment duration. Interestingly, post-hoc analysis shows that IFN-γ induction increases circulating chemokines and is associated with an observed paucity of irAEs, warranting further evaluation. ClinicalTrials.gov Trial Registration: NCT02614456.

The Effect of Hypervigilance on the Relationship Between Sexual Victimization and Gait.

Two studies investigated the relationship between hypervigilance, vulnerable gait cues, and a history of sexual victimization. In Study 1 (N = 130), gait was coded for traits relating to vulnerability where half of the sample was unaware of being videotaped (Unaware condition) and the other half was aware (Aware condition) to induce hypervigilance (between-subjects design). Gait was associated with a history of victimization, but only in the Unaware condition. A mediation analysis found that perceived impact of victimization mediated the association between victimization and vulnerable gait. In Study 2, female university students (N = 62) were measured on their victimization history and hypervigilance. Walking styles of participants were coded for the presence of vulnerability cues in both an Unaware and Aware condition (within-subjects design). A regression analysis revealed an association between hypervigilance and a reduced change in walking style between the two conditions. More notably, hypervigilance was found to moderate the relationship between sexual victimization and vulnerable gait but not violent victimization and vulnerable gait. These results suggest that hypervigilance may be an adaptive response that reduces perceived vulnerability in sexually victimized women.

Explaining dehumanization among children: the interspecies model of prejudice.

Although many theoretical approaches have emerged to explain prejudices expressed by children, none incorporate outgroup dehumanization, a key predictor of prejudice among adults. According to the Interspecies Model of Prejudice, beliefs in the human-animal divide facilitate outgroup prejudice through fostering animalistic dehumanization (Costello & Hodson, 2010). In the present investigation, White children attributed Black children fewer 'uniquely human' characteristics, representing the first systematic evidence of racial dehumanization among children (Studies 1 and 2). In Study 2, path analyses supported the Interspecies Model of Prejudice: children's human-animal divide beliefs predicted greater racial prejudice, an effect explained by heightened racial dehumanization. Similar patterns emerged among parents. Furthermore, parent Social Dominance Orientation predicted child prejudice indirectly through children's endorsement of a hierarchical human-animal divide and subsequent dehumanizing tendencies. Encouragingly, children's human-animal divide perceptions were malleable to an experimental prime highlighting animal-human similarity. Implications for prejudice interventions are considered.

Psychopathy and victim selection: the use of gait as a cue to vulnerability.

Previous research has shown that victims display characteristic body language, specifically in their walking style (Grayson & Stein, 1981). Individuals scoring higher on the interpersonal/affective aspects of psychopathy (Factor 1) are more accurate at judging victim vulnerability simply from viewing targets walking (Wheeler, Book, & Costello, 2009). The present study examines the relation between psychopathy and accuracy in assessing victim vulnerability in a sample of inmates from a maximum security penitentiary in Ontario, Canada. Forty-seven inmates viewed short video clips of targets walking and judged how vulnerable each target was to victimization. Higher Factor 1 psychopathy scores (as measured by the PCL-R; Hare 2003) were positively related to accuracy in judging victim vulnerability. Contrary to research with noninstitutional participants (Wheeler et al., 2009), inmates higher on Factor 1 of psychopathy were more likely to rationalize their vulnerability judgments by mentioning the victim's gait. Implications of these findings are discussed.

Perceptions of self-image and physical appearance: conversations with typically developing youth and youth with idiopathic scoliosis.

PURPOSE: To report how youths, both with and without idiopathic scoliosis (IS), respond to questions about their self-image and perceptions of body shape. An additional purpose is to describe themes that emerged as important to youths with IS to better understand scoliosis from their perspective. METHODS: Descriptive qualitative and quantitative methods were utilized. Subject interviews were conducted, as part of a larger cognitive interviewing study on the Spinal Appearance Questionnaire, using a cross-sectional sample of 76 females between 8 and 16 years of age with IS and who were typically developing (TD), without scoliosis. RESULTS: IS and TD subjects revealed similar findings when asked what makes them look good versus their peers; self-image ratings were also positive. Predominant themes from open-ended responses include physical appearance, feelings, brace wear, and discomfort. CONCLUSION: Self-image and body shape did not differ significantly between groups. The identified themes warrant further exploration as they are significant and important to youth with scoliosis.

Cognitive testing of the spinal appearance questionnaire with typically developing youth and youth with idiopathic scoliosis.

BACKGROUND: The Spinal Appearance Questionnaire (SAQ) underwent initial psychometric studies, which suggested good reliability and discriminative ability. Although the SAQ is used as a self report of appearance, our center was concerned about its use with youth owing to complex words and vague questions. We conducted this cross-sectional study to evaluate the readability, comprehension, and interpretation of items on the SAQ. METHODS: Cognitive interview methodology of 76 youths (8 to 16 y; average age 13) included 31 with scoliosis and 45 typically developing. Subjects were required to read each SAQ item and think aloud to capture cognitive processes about the items and responses. Interviews were audiotaped and transcribed verbatim. Problems were categorized and frequencies for each category were calculated. RESULTS: There were reading and comprehension problems and problems understanding the illustration with every written and pictorial SAQ item, respectively. The percent of subjects who encountered at least one problem ranged from 16% to 96%. Subjects had difficulty with understanding the intent of every SAQ item and with understanding the meaning of specific words such as "prominence" and "flank." The pictorial illustrations for items 2 and 3 were problematic for 58% and 49% of subjects, respectively. The illustrations of the lungs (item 4) and hips (items 4 and 5) were problematic for 42% and 27% of subjects, respectively. These results were consistent regardless of age or diagnoses. CONCLUSION: This study does not support the use of the SAQ as currently used with youth owing to use of complex medical words, vague questions, difficult illustrations, and various interpretations of the intent of many of the items. LEVEL OF EVIDENCE: Not applicable (not an intervention study).

Interpersonal disgust, ideological orientations, and dehumanization as predictors of intergroup attitudes.

Disgust is a basic emotion characterized by revulsion and rejection, yet it is relatively unexamined in the literature on prejudice. In the present investigation, interpersonal-disgust sensitivity (e.g., not wanting to wear clean used clothes or to sit on a warm seat vacated by a stranger) in particular predicted negative attitudes toward immigrants, foreigners, and socially deviant groups, even after controlling for concerns with contracting disease. The mechanisms underlying the link between interpersonal disgust and attitudes toward immigrants were explored using a path model. As predicted, the effect of interpersonal-disgust sensitivity on group attitudes was indirect, mediated by ideological orientations (social dominance orientation, right-wing authoritarianism) and dehumanizing perceptions of the out-group. The effects of social dominance orientation on group attitudes were both direct and indirect, via dehumanization. These results establish a link between disgust sensitivity and prejudice that is not accounted for by fear of infection, but rather is mediated by ideological orientations and dehumanizing group representations. Implications for understanding and reducing prejudice are discussed.