Differential Fc-Receptor Engagement Drives an Anti-tumor Vaccinal Effect.

Passively administered anti-tumor monoclonal antibodies (mAbs) rapidly kill tumor targets via FcγR-mediated cytotoxicity (ADCC), a short-term process. However, anti-tumor mAb treatment can also induce a vaccinal effect, in which mAb-mediated tumor death induces a long-term anti-tumor cellular immune response. To determine how such responses are generated, we utilized a murine model of an anti-tumor vaccinal effect against a model neoantigen. We demonstrate that FcγR expression by CD11c(+) antigen-presenting cells is required to generate anti-tumor T cell responses upon ADCC-mediated tumor clearance. Using FcγR-humanized mice, we demonstrate that anti-tumor human (h)IgG1 must engage hFcγRIIIA on macrophages to mediate ADCC, but also engage hFcγRIIA, the sole hFcγR expressed by human dendritic cells (DCs), to generate a potent vaccinal effect. Thus, while next-generation anti-tumor antibodies with enhanced binding to only hFcγRIIIA are now in clinical use, ideal anti-tumor antibodies must be optimized for both cytotoxic effects as well as hFcγRIIA engagement on DCs to stimulate long-term anti-tumor cellular immunity.

Type I and type II Fc receptors regulate innate and adaptive immunity.

Antibodies produced in response to a foreign antigen are characterized by polyclonality, not only in the diverse epitopes to which their variable domains bind but also in the various effector molecules to which their constant regions (Fc domains) engage. Thus, the antibody's Fc domain mediates diverse effector activities by engaging two distinct classes of Fc receptors (type I and type II) on the basis of the two dominant conformational states that the Fc domain may adopt. These conformational states are regulated by the differences among antibody subclasses in their amino acid sequence and by the complex, biantennary Fc-associated N-linked glycan. Here we discuss the diverse downstream proinflammatory, anti-inflammatory and immunomodulatory consequences of the engagement of type I and type II Fc receptors in the context of infectious, autoimmune, and neoplastic disorders.

Prenatal negative affectivity and trauma-related distress predict mindful parenting during toddler age: Examining parent-infant bonding as a mechanism.

Despite findings demonstrating the importance of parental present-centered awareness, factors undermining mindful parenting have received less attention. Increasingly, evidence points to parental psychopathology as a salient risk factor for parenting difficulties. Thus, the goal of the present study was to investigate specific dimensions of parental trauma-related distress and general negative affectivity during pregnancy as predictors of mindful parenting during toddler age. Parental psychopathology, parent-infant bonding, and mindful parenting were assessed in a sample of heterosexual couples (N = 159) across four waves of data collection spanning pregnancy to child age two. Data were analyzed using path analysis within a dyadic framework. Results demonstrated the unique impact of maternal trauma-related distress during pregnancy (e.g., intrusions and avoidance) on facets of mindful parenting more than two years later. Further, among both mothers and fathers, general negative affectivity common across internalizing disorders undermined mindful parenting through impaired parent-infant bonding. Findings highlight the need for early intervention efforts that incorporate mindfulness strategies to reduce subthreshold symptoms of prenatal psychopathology, promote healthy bonding, and improve parental awareness and self-regulation, thereby enhancing the overall parent-child relationship.

Risk for trauma-related distress following difficult childbirth: Trajectories of traumatic intrusions across 2 years postpartum.

There is heightened risk for maternal posttraumatic stress disorder (PTSD) during the perinatal period. However, it is unclear whether pregnancy and childbirth uniquely contribute to PTSD symptoms above and beyond elevations in negative affectivity that commonly occur among postpartum women (e.g., irritability, fatigue, depressed mood) and past trauma exposure. The present study explored the associations between childbirth stressors and trauma-related distress (TRD; intrusion and avoidance symptoms) across the 2 years following childbirth in a community sample of women (n = 159). Maternal TRD was assessed at pregnancy and four additional timepoints across 2 years postpartum. At pregnancy, mothers completed surveys measuring exposure to trauma and pregnancy-related anxiety. They also reported on pregnancy and childbirth complications across the first 6 months postpartum. Consistent with predictions, labor/delivery complications uniquely predicted increased maternal intrusions during the first 6 months postpartum above and beyond past trauma exposure. Furthermore, growth mixture models identified a subset of women with intrusion symptoms that persisted up to 2 years postpartum and, on average, exceeded the screening threshold for PTSD. Women who experienced greater labor complications were more likely to exhibit this clinical profile relative to low, stable symptoms. Findings highlight the importance of ongoing screening for TRD across the first 2 years postpartum, particularly among women who experience greater labor/delivery complications.

Survey of depressive symptomatology in brain injury resulting from intimate partner violence.

OBJECTIVE: A high prevalence of depression exists in specific sub-samples of survivors of brain injury (BI) sustained from intimate partner violence (IPV). However, the experience of depression by survivors of IPV-related BI from general civilian populations remains unclear. This study documents the symptom profile of depression reported by individuals who screened positive for sustaining an IPV-related BI. METHODS: 36 individuals who screened positive for possible IPV-related BI completed the Beck Depression Inventory-2nd Edition (BDI-II). Subscales characterizing the nature of the symptoms were created. Frequency and descriptive statistics were calculated for item responses on the BDI-II. Participants were also assigned to high or low symptom severity groups to examine between-group differences. RESULTS: Participants endorsed experiencing somatic symptoms more severely than self-evaluative and affective symptoms. Additionally, self-evaluative and cognitive symptoms correlated with total BDI-II scores for the high symptom severity group but not for the low symptom severity group. CONCLUSIONS: The findings highlight somatic symptoms of depression, in particular as a common experience among survivors of IPV-related BI. Further, self-evaluative and cognitive symptoms may be more sensitive in detecting depression after IPV-related BI. These results may aid in the development of guidelines to better diagnose and treat depression in IPV-related BI.

A Laboratory Test of Alcohol-Related Intimate Partner Aggression: Expectancies Are Not to Blame.

Background: The role of alcohol expectancies and evaluations (i.e., perceived outcomes of drinking and whether these outcomes are desirable) in alcohol-related intimate partner aggression (IPA) has been debated, with some researchers arguing that expectancies fully account for the alcohol-IPA relationship and others suggesting they play a minimal if any role in alcohol-related IPA. In the current study, we examine the impact of expectancies and evaluations on alcohol-related IPA observed in the lab, in order to clarify what impact, if any, alcohol expectancies have on alcohol-related IPA. Consistent with findings from laboratory studies examining general aggression, we expected that individuals who were intoxicated would display greater IPA than individuals who were sober, but that alcohol expectancies and evaluations would be unrelated to in vivo IPA. Method: Participants were 69 dating couples (total N = 138), randomly assigned to consume either an alcohol or placebo beverage. IPA was measured with an in vivo aggression task based on the Taylor Aggression Paradigm. Results: As expected, alcohol intoxication predicted in vivo IPA following provocation (p < .03), whereas alcohol expectancies and evaluations were not related to IPA. Conclusions: These findings provide further support that alcohol expectancies and evaluations play little if any role in alcohol-related IPA. Rather, intoxication likely increases risk for IPA through its physiological effects on perception and thought. Further, treatments targeting alcohol use, rather than beliefs about outcomes of drinking, may have a greater impact on alcohol-related IPA.

Promoting resilience to depression among couples during pregnancy: The protective functions of intimate relationship satisfaction and self-compassion.

Pregnancy, while often marked by joy, may pose considerable risk for depression among parents. Against a backdrop of adverse life events, expectant parents may be even more vulnerable to developing symptoms of depression during the prenatal period. Thus, it is critical to identify sources of resilience that might facilitate a successful transition to parenthood among couples who have a history of adversity. Prior work suggests that interpersonal and intrapersonal factors associated with resilience, such as intimate relationship satisfaction and self-compassion (i.e., self-kindness, common humanity, and mindfulness), have the potential to attenuate prenatal depression among couples with a history of stressful life experiences. We tested this possibility in a sample of 159 couples navigating pregnancy. As predicted, a greater number of prior stressful life experiences was associated with increased depression symptom severity for both mothers and fathers. However, moderation analyses revealed the positive link between cumulative stressful life experiences and depression symptom severity was attenuated among mothers who reported greater self-compassion in the form of feelings of common humanity, and fathers who reported higher levels of intimate relationship satisfaction and self-compassion in the form of mindfulness. Findings suggest enhancing intimate relationship satisfaction and self-compassion among expectant couples may be valuable in attenuating prenatal depression among those with a greater history of adversity.

Associations Between Sexual Objectification and Bystander Efficacy: The Mediating Role of Barriers to Bystander Intervention.

This study examined whether sexual objectification (i.e., reducing someone to a sex object via a disproportionate focus on appearance and sexual characteristics) was associated with decreased confidence in future bystander intervention to reduce the risk for sexual violence (i.e., bystander efficacy) through several barriers to intervention: failing to notice the event, failing to identify the situation as risky, and failing to take responsibility Participants were 1,021 undergraduates (n = 309 men; n = 712 women) who completed self-report measures. Because men frequently perpetrate objectification, whereas women often experience objectification, complementary models were tested with objectification perpetration in men and objectification experiences in women. As expected, for men, each barrier mediated negative associations between objectification perpetration and bystander efficacy. Unexpectedly, for women, each barrier mediated positive associations between objectification experiences and bystander efficacy. Findings underscore important gender differences in associations between sexual objectification and bystander efficacy, as well as potential benefits of helping bystanders recognize the risk for sexual violence and assume responsibility for intervening.

Differential requirements for FcγR engagement by protective antibodies against Ebola virus.

Ebola virus (EBOV) continues to pose significant threats to global public health, requiring ongoing development of multiple strategies for disease control. To date, numerous monoclonal antibodies (mAbs) that target the EBOV glycoprotein (GP) have demonstrated potent protective activity in animal disease models and are thus promising candidates for the control of EBOV. However, recent work in a variety of virus diseases has highlighted the importance of coupling Fab neutralization with Fc effector activity for effective antibody-mediated protection. To determine the contribution of Fc effector activity to the protective function of mAbs to EBOV GP, we selected anti-GP mAbs targeting representative, protective epitopes and characterized their Fc receptor (FcγR) dependence in vivo in FcγR humanized mouse challenge models of EBOV disease. In contrast to previous studies, we find that anti-GP mAbs exhibited differential requirements for FcγR engagement in mediating their protective activity independent of their distance from the viral membrane. Anti-GP mAbs targeting membrane proximal epitopes or the GP mucin domain do not rely on Fc-FcγR interactions to confer activity, whereas antibodies against the GP chalice bowl and the fusion loop require FcγR engagement for optimal in vivo antiviral activity. This complexity of antibody-mediated protection from EBOV disease highlights the structural constraints of FcγR binding for specific viral epitopes and has important implications for the development of mAb-based immunotherapeutics with optimal potency and efficacy.

Does Gratitude Promote Resilience During a Pandemic? An Examination of Mental Health and Positivity at the Onset of COVID-19.

Researchers have emphasized the detrimental effects of COVID-19 on mental health, but less attention has been given to personal strengths promoting resilience during the pandemic. One strength might be gratitude, which supports wellbeing amidst adversity. A two-wave examination of 201 college students revealed anxiety symptom severity increased to a lesser extent from pre-COVID (January-March 2020) to onset-COVID (April 2020) among those who reported greater pre-COVID gratitude. A similar trend appeared for depression symptom severity. Gratitude was also correlated with less negative changes in outlook, greater positive changes in outlook, and endorsement of positive experiences resulting from COVID-19. Thematic analysis showed "strengthened interpersonal connections" and "more time" were the most commonly reported positive experiences. Overall findings suggest gratitude lessened mental health difficulties and fostered positivity at the onset of the pandemic, but more research is needed to determine whether gratitude and other strengths promote resilience as COVID-19 continues.

Is the COVID-19 Pandemic a High-Risk Period for College Student Alcohol Use? A Comparison of Three Spring Semesters.

BACKGROUND: There has been widespread concern that the COVID-19 pandemic may be a high-risk time for alcohol use among heavy drinking populations such as college students. Initial efforts to evaluate changes in college drinking have not yet accounted for typical drinking patterns within a semester. METHODS: To fill this gap, we evaluated how college student drinking patterns changed with the onset of restrictions related to the COVID-19 pandemic during spring 2020 relative to spring 2018 and 2019. Participants were 1,365 college students aged 19 and older, including 895 students who reported past-month alcohol use. Daily drinking data were extracted from an online Timeline Followback survey. RESULTS: Negative binomial hurdle models revealed that, with the onset of the COVID-19 pandemic in spring 2020, college student drinkers did not increase their drinking frequency as was typical in late spring semester, and the number of drinks per occasion declined substantially (28% reduction), greater than the change observed from early to late spring 2018 (3% reduction) or spring 2019 (8% increase). This reduction in drinking quantity in spring 2020 was larger for college student drinkers who moved residences because of the pandemic (49% reduction) than students who did not move (21% reduction). Perceptions in pandemic-related changes in drinking also revealed that 83.5% of college student drinkers self-reported that their drinking stayed the same or decreased. CONCLUSIONS: Findings suggest that, on average, college students drank less-not more-during the onset of the COVID-19 pandemic and highlight the importance of living situation in college student drinking behavior. More research is needed to assess alcohol use in other universities, as this information could be utilized in norms-based interventions to further reduce drinking in students who remain at risk.

Site-selective chemoenzymatic glycoengineering of Fab and Fc glycans of a therapeutic antibody.

The N-glycans attached to the Fab and Fc domains play distinct roles in modulating the functions of antibodies. However, posttranslational site-selective modifications of glycans in antibodies and other multiply glycosylated proteins remain a challenging task. Here, we report a chemoenzymatic method that permits independent manipulation of the Fab and Fc N-glycans, using cetuximab as a model therapeutic monoclonal antibody. Taking advantage of the substrate specificity of three endoglycosidases (Endo-S, Endo-S2, and Endo-F3) and their glycosynthase mutants, together with an unexpected substrate site-selectivity of a bacterial α1,6-fucosidase from Lactobacillus casei (AlfC), we were able to synthesize an optimal homogeneous glycoform of cetuximab in which the heterogeneous and immunogenic Fab N-glycans were replaced with a single sialylated N-glycan, and the core-fucosylated Fc N-glycans were remodeled with a nonfucosylated and fully galactosylated N-glycan. The glycoengineered cetuximab demonstrated increased affinity for the FcγIIIa receptor and significantly enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) activity.

IL-15 enhanced antibody-dependent cellular cytotoxicity mediated by NK cells and macrophages.

The goal of cancer immunotherapy is to stimulate the host immune system to attack malignant cells. Antibody-dependent cellular cytotoxicity (ADCC) is a pivotal mechanism of antitumor action of clinically employed antitumor antibodies. IL-15 administered to patients with metastatic malignancy by continuous i.v. infusion at 2 µg/kg/d for 10 days was associated with a 38-fold increase in the number and activation status of circulating natural killer (NK) cells and activation of macrophages which together are ADCC effectors. We investigated combination therapy of IL-15 with rituximab in a syngeneic mouse model of lymphoma transfected with human CD20 and with alemtuzumab (Campath-1H) in a xenograft model of human adult T cell leukemia (ATL). IL-15 greatly enhanced the therapeutic efficacy of both rituximab and alemtuzumab in tumor models. The additivity/synergy was shown to be associated with augmented ADCC. Both NK cells and macrophages were critical elements in the chain of interacting effectors involved in optimal therapeutic responses mediated by rituximab with IL-15. We provide evidence supporting the hypothesis that NK cells interact with macrophages to augment the NK-cell activation and expression of FcγRIV and the capacity of these cells to become effectors of ADCC. The present study supports clinical trials of IL-15 combined with tumor-directed monoclonal antibodies.

Modulating IgG effector function by Fc glycan engineering.

IgG antibodies contain a conserved N-glycosylation site on the Fc domain to which a complex, biantennary glycan is attached. The fine structures of this glycan modulate antibody effector functions by affecting the binding affinity of the Fc to diverse Fc receptor family members. For example, core fucosylation significantly decreases antibody-dependent cellular cytotoxicity (ADCC), whereas terminal α2,6-sialylation plays a critical role in the anti-inflammatory activity of human i.v. immunoglobulin therapy. The effect of specific combinations of sugars in the glycan on ADCC remains to be further addressed, however. Therefore, we synthesized structurally well-defined homogeneous glycoforms of antibodies with different combinations of fucosylation and sialylation and performed side-by-side in vitro FcγR-binding analyses, cell-based ADCC assays, and in vivo IgG-mediated cellular depletion studies. We found that core fucosylation exerted a significant adverse effect on FcγRIIIA binding, in vitro ADCC, and in vivo IgG-mediated cellular depletion, regardless of sialylation status. In contrast, the effect of sialylation on ADCC was dependent on the status of core fucosylation. Sialylation in the context of core fucosylation significantly decreased ADCC in a cell-based assay and suppressed antibody-mediated cell killing in vivo. In contrast, in the absence of fucosylation, sialylation did not adversely impact ADCC.

Observing Alcohol Myopia in the Context of a Trauma Film Paradigm: Differential Recall of Central and Peripheral Details.

BACKGROUND: A major tenet of the alcohol myopia model is that intoxication results in a narrowing of attention to the most central environmental cues, at the cost of more peripheral information. Though long hypothesized, no known study of alcohol myopia has demonstrated differential immediate recall of central and peripheral cues using a standardized task. To address this gap, we conducted an alcohol administration study with a clear, standardized focus-a trauma film. METHODS: Ninety-eight female social drinkers completed self-report measures, and then were randomized to consume a placebo beverage, a low dose of alcohol (mean breath alcohol concentration [BrAC] = 0.04%), or a high dose of alcohol (mean BrAC = 0.11%). Participants then moved to a staged room where they viewed a film clip depicting a sexual assault. After leaving the room, participants completed a written free recall task of the film and the room. RESULTS: The distinction between recall of central and peripheral details was supported by confirmatory factor analysis. Consistent with the alcohol myopia model, relative to placebo, a high dose of alcohol led to impaired recall of peripheral (but not central) details. Although the interaction between BrAC and information type (central vs. peripheral) was not statistically significant, simple effects revealed a strong association between BrAC and peripheral information, and no association between BrAC and central information. Bolstering myopia as an explanation for our findings, neither central nor peripheral information correlated with self-reported tendencies to dissociate or distract oneself, or typical alcohol consumption or expectancies. CONCLUSIONS: Alcohol myopia can be observed through an immediate free recall task following a stressful film. Additional research is needed to continue evaluating dose-dependent differential recall in larger samples. This task may be useful for clarifying the role of alcohol myopia in clinical phenomena, such as aggressive behavior and processing traumatic events.

A Longitudinal Examination of Posttraumatic Stress Disorder Symptoms and Risky Sexual Behavior: Evaluating Emotion Dysregulation Dimensions as Mediators.

Posttraumatic stress disorder (PTSD) has been linked to a wide array of risky and health-compromising behaviors, including risky sexual behavior (RSB). Cross-sectional studies reveal positive associations between emotion dysregulation and both PTSD and RSB. This study extended that work by exploring whether intermediate levels of emotion dysregulation across multiple dimensions account for the relation between baseline PTSD symptoms and RSB (i.e., number of vaginal sex partners, number of instances of condomless sex, and number of instances of risky/impulsive sex) 16 months later. Participants were 447 trauma-exposed young adult women from the community (60.0% White; M age = 21.80 years) who completed five assessments (separated by 4-month increments) over a 16-month period. Baseline PTSD symptoms were significantly positively associated with all emotion dysregulation dimensions at 8 months and the number of instances of risky/impulsive sex at 16 months. Further, results revealed significant indirect effects of baseline PTSD symptoms on (1) 16-month vaginal sex partners through both the nonacceptance of negative emotions and difficulties controlling impulsive behaviors when distressed at 8-month and (2) 16-month risky/impulsive sex through difficulties engaging in goal-directed behaviors when distressed at 8 months. Results provide support for the mediating roles of nonacceptance of negative emotions and difficulties controlling behaviors when distressed in the relation between PTSD symptoms and later RSB.

Risk for Revictimization Following Interpersonal and Noninterpersonal Trauma: Clarifying the Role of Posttraumatic Stress Symptoms and Trauma-Related Cognitions.

One victimization experience can increase the risk for subsequent victimization, which is known as revictimization. The aims of this study were to build on sexual revictimization research by (a) broadening the understanding of revictimization to interpersonal (and potentially noninterpersonal) trauma generally and (b) gaining specificity in the mechanisms that underlie revictimization. Using a prospective multisite design, an ethnically and racially diverse sample of 453 young women from the community (age range: 18-25 years, 60.7% European American) completed an initial survey and at least one follow-up survey within the subsequent year. Participants completed self-report measures of trauma history, posttraumatic stress symptoms, and maladaptive posttraumatic cognitions. Structural equation models revealed that interpersonal revictimization was observed when controlling for past noninterpersonal trauma, odds ratio (OR) = 2.27, 95% CI [1.23, 4.18], and supported the role of posttraumatic stress symptoms as a mechanism underlying such revictimization, 95% CI of indirect effect (IE) [0.08, 0.51]. Additionally, a history of noninterpersonal trauma (controlling for past interpersonal trauma) increased risk of subsequent interpersonal victimization via posttraumatic stress symptoms, 95% CI of IE [0.01, 0.38]. Notably, however, when maladaptive cognitions were included as mediators in addition to posttraumatic stress symptoms, the only unique indirect effect was for the association between interpersonal trauma and risk of revictimization specifically through perceived threat of harm, 95% CI of IE [0.05, 0.20]. These findings suggest that efforts to reduce interpersonal revictimization should target maladaptive posttraumatic cognitions, particularly perceptions of threat in the environment.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Riesgo de revictimización luego de trauma interpersonal y no interpersonal: Aclarando el rol de los Síntomas de Estrés postraumático y las Cogniciones relacionadas con el Trauma REVICTIMIZACIÓN, TEPT Y COGNICIONES Una experiencia de victimización puede aumentar el riesgo de una subsiguiente victimización, conocida como revictimización. Los objetivos de este estudio fueron desarrollar una investigación sobre la revictimización sexual mediante (a) una comprensión más amplia de la revictimización al trauma interpersonal (y potencialmente no interpersonal) en general, y (b) la obtención de especificidad en los mecanismos que subyacen a la revictimización. Utilizando un diseño multisitio prospectivo, una muestra étnica y racialmente diversa de 453 mujeres jóvenes de la comunidad (rango de edad: 18-25 años, 60.7% europeo-estadounidense) completaron una encuesta inicial y al menos una encuesta de seguimiento dentro del año siguiente. Las participantes completaron medidas de auto reporte del historial de traumas, síntomas de estrés postraumático y cogniciones postraumáticas no adaptativas. Los modelos de ecuaciones estructurales revelaron que se observó una revictimización interpersonal al controlar traumas no interpersonales pasados, odds ratio (OR) = 2.27, IC 95% [1.23, 4.18], y apoyaron el rol de los síntomas de estrés postraumático como un mecanismo subyacente a dicha revictimización, IC del 95% de efecto indirecto (IE) [0.08, 0.51]. Además, un historial de trauma no interpersonal (controlando el trauma interpersonal pasado) incrementó el riesgo de subsecuente victimización interpersonal mediante síntomas de estrés postraumático, IC del 95% de IE [0.01, 0.38]. Sin embargo, notablemente, cuando se incluyeron las cogniciones no adaptativas como mediadores además de los síntomas de estrés postraumático, el único efecto indirecto fue la asociación entre el trauma interpersonal y el riesgo de revictimización, específicamente a través de la percepción de la amenaza de daño, IC del 95% de IE [0.05, 0.20]. Estos hallazgos sugieren que los esfuerzos para reducir la revictimización interpersonal deben dirigirse a las cogniciones postraumáticas no adaptativas, en particular las percepciones de amenaza en el medio ambiente.

Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions.

B cells regulate immune responses by producing antigen-specific antibodies. However, specific B-cell subsets can also negatively regulate T-cell immune responses, and have been termed regulatory B cells. Human and mouse regulatory B cells (B10 cells) with the ability to express the inhibitory cytokine interleukin-10 (IL-10) have been identified. Although rare, B10 cells are potent negative regulators of antigen-specific inflammation and T-cell-dependent autoimmune diseases in mice. How B10-cell IL-10 production and regulation of antigen-specific immune responses are controlled in vivo without inducing systemic immunosuppression is unknown. Using a mouse model for multiple sclerosis, here we show that B10-cell maturation into functional IL-10-secreting effector cells that inhibit in vivo autoimmune disease requires IL-21 and CD40-dependent cognate interactions with T cells. Moreover, the ex vivo provision of CD40 and IL-21 receptor signals can drive B10-cell development and expansion by four-million-fold, and generate B10 effector cells producing IL-10 that markedly inhibit disease symptoms when transferred into mice with established autoimmune disease. The ex vivo expansion and reinfusion of autologous B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies.

Further Validation of a Laboratory Analog Sexual Aggression Task: Associations With Novel Risk Factors for Sexual Violence.

Official crime statistics and self-reports of sexual aggression perpetration are limited by various factors (e.g., lack of reporting, social desirability bias), as well as an inability to use these measures in experimental studies of sexual aggression. To address these issues, Nagayama Hall et al. (1994) developed a laboratory analog measure of sexual aggression, which has received empirical support as a valid measure of sexual aggression proclivity. Here, we seek to replicate these findings and further validate the paradigm by examining sexually aggressive responses in relation to a range of recently emerging predictors of sexual aggression (e.g., sexual objectification, sexual narcissism) as well as participants' perceptions of a female confederate serving as the target of sexual aggression. A sample of 49 undergraduate men completed questionnaires and participated in the sexual aggression analog task. Results of logistic regression analyses supported both criterion and construct validity of the analog task; men who chose the sexually explicit video were more likely to report prior sexual aggression, greater sexual objectification of women, higher sexual narcissism, greater hostile sexism, and higher impersonal dating. These men were also more likely to express dehumanizing beliefs about the female confederate, consider her less intelligent, and believe she was more distressed by the video. These results replicate and extend prior research supporting this paradigm as a valid laboratory-based measure of sexual aggression proclivity that can be used in tandem with validated self-report measures.

Childhood Sexual Abuse and Fear of Abandonment Moderate the Relation of Intimate Partner Violence to Severity of Dissociation.

Betrayal trauma theory proposes a relation between intimate partner violence (IPV) and dissociation, suggesting that dissociation among victims of IPV may function to restrict awareness of abuse in order to preserve attachments perceived as vital. We investigated two factors that may moderate the relation between IPV and dissociation-childhood sexual abuse (CSA) severity and fear of abandonment-among 348 women currently in a relationship. The relation between frequency of IPV (sexual and physical) and dissociation (amnesia and depersonalization) was moderated by CSA severity and fear of abandonment. Specifically, among women with clinically relevant fear of abandonment, the strength of the relation between IPV and dissociation became stronger as CSA severity increased. This study is the first to demonstrate the moderating roles of fear of abandonment and CSA history in the relation between IPV and dissociation among women. Findings suggest that it may be important to target fear of abandonment in interventions with IPV victims who have a CSA history. Results suggest that fear of abandonment warrants greater attention in research on IPV revictimization.