A Phase 3b Study for Management of Ocular Side Effects in Patients with Epidermal Growth Factor Receptor-Amplified Glioblastoma Receiving Depatuxizumab Mafodotin.

INTRODUCTION: The Understanding New Interventions with GBM ThErapy (UNITE) study was designed to assess the effect of prophylaxis for ocular side effects (OSEs) in patients with glioblastoma receiving the antibody-drug conjugate (ADC) depatuxizumab mafodotin. UNITE (NCT03419403) was a phase 3b, open-label, randomized, exploratory study performed at 18 research sites in 5 countries. METHODS: The study enrolled adult patients with epidermal growth factor receptor-amplified, histologically confirmed, newly diagnosed supratentorial glioblastoma or grade IV gliosarcoma, and a Karnofsky Performance Status ≥70, receiving depatuxizumab mafodotin. All patients were administered depatuxizumab mafodotin during concurrent radiotherapy and temozolomide and with adjuvant temozolomide. Ninety patients were to be randomized (1:1:1) to OSE prophylactic treatments with each depatuxizumab mafodotin infusion: (a) standard steroid eye drops, (b) standard steroid eye drops plus vasoconstrictor eye drops and cold compress, or (c) enhanced steroids plus vasoconstrictor eye drops and cold compress. A Corneal Epitheliopathy Adverse Event (CEAE) scale was devised to capture symptoms, grade OSEs (scale of 0-5), and inform ADC dose modifications. The primary endpoint was the frequency of a required change in OSE management due to inadequate control of OSEs, defined as decline from baseline in visual acuity (using logarithm of the minimum angle of resolution [LogMAR] scale) or a Grade ≥3 CEAE event, in the worst eye in the first 8 weeks of treatment; unless otherwise specified, the treatment period refers to both the chemoradiation and adjuvant phases. RESULTS: The UNITE study was stopped early after interim analysis of separate phase III trial showed no difference in survival from depatuxizumab mafodotin. Forty patients were randomized (38 received depatuxizumab mafodotin). Overall, 23 patients experienced inadequate control of OSEs that required change in OSE management within 8 weeks of treatment, with 21 (70.0%) experiencing ≥+0.3 change on LogMAR scale in baseline-adjusted visual acuity and 12 reporting a grade ≥3 CEAE. There were no definitive differences among prophylactic treatments. CONCLUSIONS: The premature cessation of the study precludes definitive conclusions regarding the OSE prophylaxis strategies. No new clinically significant safety findings were noted. Despite these limitations, this study highlights the need for novel assessment tools to better understand and mitigate OSEs associated with ADCs.

An empirically based power primer for laboratory aggression research.

Recent reviews suggest that, like much of the psychological literature, research studies using laboratory aggression paradigms tend to be underpowered to reliably locate commonly observed effect sizes (e.g., r = ~.10-.20, Cohen's d = ~0.20-0.40). In an effort to counter this trend, we provide a "power primer" that laboratory aggression researchers can use as a resource when planning studies using this methodology. Using simulation-based power analyses and effect size estimates derived from recent literature reviews, we provide sample size recommendations based on type of research question (e.g., main effect vs. two-way vs. three-way interactions) and correlations among predictors. Results highlight the large number of participants that must be recruited to reach acceptable (~80%) power, especially for tests of interactions where the recommended sample sizes far exceed those typically employed in this literature. These discrepancies are so substantial that we urge laboratory aggression researchers to consider a moratorium on tests of three-way interactions. Although our results use estimates from the laboratory aggression literature, we believe they are generalizable to other lines of research using behavioral tasks, as well as psychological science more broadly. We close by offering a series of best practice recommendations and reiterating long-standing calls for attention to statistical power as a basic element of study planning.

Examining the conceptual and empirical distinctiveness of Agreeableness and "dark" personality items.

OBJECTIVE: A growing research literature has focused on what have been termed "dark" personality traits/constructs. More recently, the "dark factor" of personality has been proposed as a unifying framework for this research. To date, little work has rigorously investigated whether the traits/constructs investigated in the context of the dark factor can be captured by existing models of normative personality, namely Agreeableness from the Five-factor Model. Thus, the "dark factor" may be an instance of the "jangle" fallacy, where two constructs with different names are in fact the same construct. METHOD: We used a preregistered approach that made use of bass-ackward factor analysis, structural equation modeling, and nomological network analysis to investigate the distinction between the D factor and Agreeableness. RESULTS: Agreeableness and the D factor were similar in their coverage of antagonistic personality content, strongly negatively related (latent r = -.90), and showed near perfect profile dissimilarity (rICC  = -.99). CONCLUSIONS: The results suggested that the D factor can be understood as the opposite pole of Agreeableness (i.e., antagonism) and not as a distinct construct. We discuss the implications for researchers interested in continuing to advance the study of antagonistic personality traits.

Exploring Gender Differences in Machiavellianism Using a Measurement Invariance Approach.

Research suggests that men and women differ on mean levels of Dark Triad personality constructs such as Machiavellianism, but few studies have investigated whether or not these differences are due to actual latent trait differences or bias in measurement. Further, recent research suggests important challenges associated with existing measures of MACH in terms of overlap with psychopathy and matching expert descriptions. The present study took a recently developed measure of Machiavellianism (the Five Factor Machiavellianism Inventory; FFMI), based on the five-factor model, and examined its invariance across gender. Strong (or scalar) factorial invariance was established, indicating that latent factor means can be compared between men and women using this measure. Mean-level differences showed that men had higher levels of latent factors related to antagonism and social dominance. In terms of total score, men reported significantly higher mean levels of Machiavellianism. The findings of the present study lend support to the notion that mean level differences in Machiavellianism across gender are not artifacts of measurement bias.

Development and Validation of the Super-Short Form of the Five Factor Machiavellianism Inventory (FFMI-SSF).

Previous findings have showed that existing measures of Machiavellianism often fail to distinguish Machiavellianism from another construct in the Dark Triad (i.e., psychopathy) and do not align with theoretical descriptions. To rectify this, a 52-item measure (i.e., FFMI) was developed to measure traits that are the most theoretically relevant to Machiavellianism using the Five-Factor model of personality. The aim of the current study is to develop a briefer version of the FFMI that can be used in situations in which efficiency is critical. Using data collected from three samples (total N = 1,945), we developed a 15-item measure of Machiavellianism (i.e., FFMI-SSF) that was shown to be similarly effective as the FFMI in capturing core personality traits relevant to Machiavellianism and distinguishing Machiavellianism from psychopathy and narcissism.

Using item-level analyses to better understand the consequences of partialing procedures: An example using the Dark Triad.

OBJECTIVE: Partialing procedures are frequently used in psychological research. The present study sought to further explore the consequences of partialing, focusing on the replicability of partialing-based results. METHOD: We used popular measures of the Dark Triad (DT; Machiavellianism, narcissism, and psychopathy) to explore the replicability of partialing procedures. We examined whether the residual content of popular DT scales is similar to the residual content of DT scales derived from separate samples based on relations with individual items from the IPIP-NEO-120, allowing for a finer-grained analysis of residual variable content. RESULTS: Profiles were compared using three sample sizes (Small N = 156-157, Moderate N = 313-314, Large N = 627-628) randomly drawn from a large MTurk sample (N = 1,255). There was low convergence between original and residual DT scales within samples. Additionally, results showed that the content of residual Dirty Dozen scales was not similar across samples. Comparable results were found for short Dark Triad-Machiavellianism, but only in the moderate and small samples. CONCLUSION: The results indicate that there are important issues that arise when using partialing procedures, including replicability issues surrounding residual variables. Reasons for the observed results are discussed and further research examining the replicability of residual-based results is recommended.

Vulnerable Narcissism Is (Mostly) a Disorder of Neuroticism.

OBJECTIVE: Increasing attention has been paid to the distinction between the dimensions of narcissistic grandiosity and vulnerability. We examine the degree to which basic traits underlie vulnerable narcissism, with a particular emphasis on the importance of Neuroticism and Agreeableness. METHOD: Across four samples (undergraduate, online community, clinical-community), we conduct dominance analyses to partition the variance predicted in vulnerable narcissism by the Five-Factor Model personality domains, as well as compare the empirical profiles generated by vulnerable narcissism and Neuroticism. RESULTS: These analyses demonstrate that the lion's share of variance is explained by Neuroticism (65%) and Agreeableness (19%). Similarity analyses were also conducted in which the extent to which vulnerable narcissism and Neuroticism share similar empirical networks was tested using an array of criteria, including self-, informant, and thin slice ratings of personality; interview-based ratings of personality disorder and pathological traits; and self-ratings of adverse events and functional outcomes. The empirical correlates of vulnerable narcissism and Neuroticism were nearly identical (MrICC = .94). Partial analyses demonstrated that the variance in vulnerable narcissism not shared with Neuroticism is largely specific to disagreeableness-related traits such as distrustfulness and grandiosity. CONCLUSIONS: These findings demonstrate the parsimony of using basic personality to study personality pathology and have implications for how vulnerable narcissism might be approached clinically.

Translating the Transdiagnostic: Aligning Assessment Practices With Research Advances.

Researchers and clinicians working within the Diagnostic and Statistical Manual of Mental Disorders: Fifth Edition, Text Rev (DSM-5-TR) framework face a difficult question: what does it mean to have an evidence-based assessment of a nonevidence-based diagnostic construct? Alternative nosological approaches conceptualize psychopathology as (a) hierarchical, allowing researchers to move between levels of description and (b) dimensional, eliminating artificial dichotomies between disorders and the dichotomy between mental illness and mental well-being. In this article, we provide an overview of ongoing efforts to develop validated measures of transdiagnostic nosologies (i.e., the Hierarchical Taxonomy of Psychopathology; HiTOP) with applications for measurement-based care. However, descriptive models like HiTOP, which summarize patterns of covariation among psychopathology symptoms, do not address dynamic processes underlying the problems associated with psychopathology. Ambulatory assessment, well-suited to examine such dynamic processes, has also developed rapidly in recent decades. Thus, the goal of the current article is twofold. First, we provide a brief overview of developments in constructing valid measures of the HiTOP model as well as developments in ambulatory assessment practices. Second, we outline how these parallel developments can be integrated to advance measurement-based treatment. We end with a discussion of some major challenges for future research to address to integrate advances more fully in transdiagnostic and ambulatory assessment practices.

Examining the structure of personality dysfunction.

Personality impairment is a core feature of personality disorders in both current (i.e., Diagnostic and Statistical Manual of Mental Disorders, fifth edition [DSM-5] personality disorders, International Classification of Diseases,11th revision personality disorders) and emerging (i.e., DSM-5's alternative model of personality disorders) models of psychopathology. Yet, despite its importance within clinical nosology, attempts to identify its optimal lower-order structure have yielded inconsistent findings. Given its presence in diagnostic models, it is important to better understand its empirical structure across a variety of instantiations. To the degree that impairment is multifaceted, various factors may have different nomological networks and varied implications for assessment, diagnosis, and treatment. Therefore, participants were recruited from two large public universities in the present preregistered study (N = 574) to explore the construct's structure with exploratory "bass-ackward" factor analyses at the item level. Participants completed over 250 items from six commonly used measures of personality dysfunction. Criterion variables in its nomological network were also collected (e.g., general and pathological personality traits, internalizing/externalizing behavior, and personality disorders) using both self- and informant-reports. These factor analyses identified four lower-order facets of impairment (i.e., negative self-regard, disagreeableness, intimacy problems, and lack of direction), all of which showed moderate to strong overlap with traits from both general and pathological models of personality. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Characterizing Stress Processes by Linking Big Five Personality States, Traits, and Day-to-Day Stressors.

The accumulation of day-to-day stressors can impact mental and physical health. How people respond to stressful events is a key mechanism responsible for the effects of stress, and individual differences in stress responses can either perpetuate or prevent negative consequences. Most research on daily stress processes has focused on affective responses to stressors, but stress responses can involve more than just affect (e.g., behavior, cognitions). Additionally, most research has studied the role of neuroticism in shaping those responses, but many other individual differences are associated with stress. In this study, we more broadly characterized daily stress processes by expanding the nomological networks of stress responses to include Big Five personality states. We also linked those stress responses to all Big Five traits, as well as individual differences in stress variety, severity, and controllability. We studied a sample of participants (N = 1,090) who reported on stressful events, their appraisal of events in terms of severity and controllability, and their Big Five personality states daily for 8-10 days (N = 8,870 observations). Multi-level structural equation models were used to separate how characteristics of the perceived stressful situation and characteristics of the person play into daily stress processes. Results showed that (1) all Big Five personality states shift in response to perceived stress, (2) all Big Five personality traits relate to average levels of perceived stress variety, severity, and controllability, (3) individual differences in personality and average perceived stress variety and perceived severity relate to the strength of personality state responses to daily stress, albeit in a more limited fashion. Our results point to new pathways by which stressors affect people in everyday life and begin to clarify processes that may explain individual differences in risk or resilience to the harmful effects of stress.

Retrospective radiological analysis to establish anatomical variation in angulation between medial canthus and the middle turbinate, for optimal positioning of Lester Jones Lacrimal bypass tubes in treatment of Epiphora.

PURPOSE: To determine the optimum angle for placement of Lester Jones lacrimal bypass tube using fixed radiological markers on CT scan head with axial and coronal cuts, as well as analysing the anatomical variation and range of angulation between individuals within our local population. METHODS: A retrospective radiological study conducted on a randomly selected sample of 384 adult patients in a UK Teaching Hospital. The angle between the medial canthus and the middle turbinate was measured on CT scans of the head using fixed radiological anatomical landmarks and analysed using the IMPAX software. Patients with orbital or nasal fractures, as well as those with history of surgical procedures involving the facial bones, were excluded. The accuracy of our measurements was validated using three dimensional (3D) CT head reconstruction technology. RESULTS: Analysis of the results showed a range of angulation between 28-45 degrees, with a mean angle of 36.99 ± 4.78 SD. There was no significant correlation found when comparing the different age groups using the One Way ANOVA test. Furthermore, a non-significant correlation was found between males and females when their mean angles were compared using the independent t-test. CONCLUSION: Our study showed that the ideal angle for insertion of Lester Jones tube would be between 30-45 degrees, with a mean of 37 degrees. No significant correlation was found between the age of the patient and the ideal angle of insertion of Lester Jones tube. Moreover, no significant difference was found in the angle measurements between males and females.

The Relative Importance of Psychopathy Features as Predictors of Externalizing Behaviors in Youth: A Multimethod Examination.

Research in youth psychopathy has focused heavily on the affective features (i.e., callous-unemotional [CU] traits) given robust links to severe and chronic forms of externalizing behaviors. Recently, there have been calls to expand the scope of work in this area to examine the importance of other interpersonal (i.e., antagonism) and behavioral (i.e., disinhibition) features of psychopathy. In the present study, we apply an under-utilized statistical approach (i.e., dominance analysis) to assess the relative importance of CU traits, antagonism, and disinhibition in the prediction of externalizing behaviors in youth, cross-sectionally and at 9-month follow-up. Using a multi-informant (youth- and parent-report), multi-method (questionnaire, ecological momentary assessment [EMA]) preregistered approach in a diverse sample of clinically referred youth (Mage = 12.60 years, SD = .95 years, 47% female; 61% racial/ethnic minority), we found youth- and parent-reported psychopathy features accounted for a significant proportion of variance in externalizing behavior cross-sectionally and longitudinally. However, results provided limited support for our preregistered hypotheses. While antagonism and disinhibition had larger general dominance weights relative to CU traits for both youth- and parent-report, most differences were non-significant. Thus, the interpersonal, affective, and behavioral psychopathy features could not be distinguished from one another in terms of their importance in the prediction of externalizing behavior, assessed cross-sectionally or longitudinally. Taken together, the results highlight promising avenues for future research on the relative importance of youth psychopathy features.

Moderation effects in personality disorder research.

Tests of statistical interactions (or tests of moderation effects) in personality disorder research are a common way for researchers to examine nuanced hypotheses relevant to personality pathology. However, the nature of statistical interactions makes them difficult to reliably detect in many research scenarios. The present study used a flexible, simulation-based approach to estimate statistical power to detect trait-by-trait interactions common to psychopathy research using the Triarchic model of Psychopathy and the Psychopathic Personality Inventory. Our results show that even above-average sample sizes in these literatures (e.g., N = 428) provide inadequate power to reliably detect trait-by-trait interactions, and the sample sizes needed to detect interaction effect sizes in realistic scenarios are extremely large, ranging from 1,300 to 5,200. The implications for trait-by-trait interactions in psychopathy are discussed, as well as how the present findings might generalize to other areas of personality disorder research. We provide recommendations for how to design research studies that can provide informative tests of interactions in personality disorder research, but also highlight that a more realistic option is to abandon the traditional approach when testing for interaction effects and adopt alternative approaches that may be more productive. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Entropion-ectropion: the influence of axial globe length on lower eyelid malposition.

PURPOSE: To evaluate the effect of axial globe length and other biometry parameters on age-related lower eyelid malposition. METHODS: Consecutive patients with involutional lower eyelid malposition underwent preoperative biometry with Zeiss IOL Master and Hertel's exophthalmometer prior to surgery. Patients with other causes of eyelid malposition and thyroid eye disease were excluded. GraphPad InStat was used for t test and chi-square statistical analysis. RESULTS: Data on 57 eyelids of 52 Caucasian patients were collected. There were 28 ectropions and 29 entropions. The mean axial globe length in the ectropion group (23.5 mm, standard deviation ± 0.9) was significantly longer than in the entropion group (22.7 mm, standard deviation ± 1.03) (p = 0.008). There was significant sex predilection, with entropion more common in women and ectropion more common in men (p = 0.03). The mean axial globe projection in the ectropion group was 16.6 mm (standard deviation ± 2.4) and in the entropion group was 14.6 mm (standard deviation ± 2.7) (p = 0.002). There was no statistical difference in age, keratometry, amount of astigmatism, and cylinder axis. CONCLUSION: Involutional eyelid malposition directly correlates with axial globe length with the ectropion group having lengthier eyes compared with the entropion group. Hence, axial globe length could be an influential factor in the onset of involutional eyelid malposition.

Reliability of Differential Item Functioning in Alcohol Use Disorder: Bayesian Meta-Analysis of Criteria Discrimination Estimates.

Numerous studies leverage item response theory (IRT) methods to examine measurement characteristics of alcohol use disorder (AUD) diagnostic criteria. Less work has examined the consistency of AUD IRT parameter estimates, an essential step for establishing measurement invariance, making statements about symptom diagnosticity, and validating the theoretical construct. A Bayesian meta-analysis of IRT discrimination values for AUD criteria across 33 independent samples (Total N = 321,998) revealed that overall consistency of AUD criteria discriminations was low (generalized intraclass correlation range = .105-.249). However, specific study characteristics accounted for substantial variability, suggesting that the unreliability is partially systematic. We replicated evidence of differential item functioning (DIF) via established factors (e.g., age, gender), but the magnitudes were small compared with DIF associated with assessment instrument. These results offer practical recommendations regarding which instruments to use when specific AUD criteria are of interest and which criteria are most sensitive when comparing demographic groups.

Agreeableness explains the factor structure of the Self-Report Psychopathy Scale, Fourth Edition.

The five-factor model (FFM) is a general personality model that has been frequently studied in its relation to psychopathy (Lynam & Miller, 2015; Widiger & Lynam, 1998) with ample evidence that Antagonism (low Agreeableness) plays a core role in the conceptualization of psychopathy. The present study examined the relations between the Self-Report Psychopathy Scale, Fourth Edition (SRP-4; Paulhus et al., 2014), one of the most commonly used self-report measures of psychopathy and the FFM. Using a preregistered analytical approach, we found that all 4 subscales and the total score of the SRP-4 are positively correlated with all facets of Antagonism and that Antagonism accounts for the overlap between SRP-4 subscales, as introducing these facets to a hierarchical regression reduced the overlap between subscales by more than 50%. Adding Conscientious to the model did not account for further reduction in overlap between the factors. Finally, a structural equation model showed the latent correlation between Antagonism and psychopathy as captured by the SRP-4 to be effectively 1.0, again highlighting the role of Antagonism in the SRP-4's conceptualization of psychopathy. The results were consistent across 2 large samples (Ns of 627 and 628). This study suggests the SRP-4 is assessing Antagonism and showcases the primary role of Antagonism in psychopathy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Antagonism in Daily Life: An Exploratory Ecological Momentary Assessment Study.

Interpersonal Antagonism is one of the major domains of maladaptive personality. Structural-based investigations of Antagonism have generally been consistent in highlighting the more specific antagonistic traits (e.g., manipulativeness, callousness) that underlie the broader domain. However, less work has attempted to merge structural and functional accounts of Antagonism to assess how specific antagonistic traits manifest in daily life. This exploratory study examined how Antagonism and its specific features relate to outcomes assessed using ecological momentary assessment (EMA) methods. Across four independent EMA samples (N range=297-396; total N = 1,365; observations per outcome=5,419-17,735), we investigated how antagonistic traits related to theoretically relevant, EMA-based outcomes (e.g., affect, empathy, coldness-warmth in interpersonal interactions). Results showed robust findings across samples and operationalizations of Antagonism (e.g., Antagonism's relation with negative affect), along with more mixed results (e.g., Antagonism's relation with different measures of empathy). We discuss future research directions for structural and functional accounts of Antagonism.

Untangling the Relation Between Narcissistic Traits and Behavioral Aggression Following Provocation Using an FFM Framework.

Work on narcissism has identified two variants: grandiose and vulnerable. The variants share an antagonistic core, but differ in neuroticism and extraversion. The current study explored how the variants relate to behavioral aggression following provocation. Results showed an interaction between grandiose narcissism and condition, such that grandiose narcissism was positively related to aggression only among those who were provoked, though the magnitude of this interaction was dependent on which measure of grandiose narcissism was used. A similar effect for vulnerable narcissism was not found. Moderated mediation analyses showed that antagonism-related traits were responsible for this relation. For vulnerable narcissism, moderated mediation results showed competing relations among vulnerable narcissism components-neuroticism-related traits were negatively related while antagonism-related traits were positively related. Results are discussed in the context of previous work. Antagonism-related traits, as opposed to traits related to extraversion and neuroticism, are most important in explaining narcissistic aggression.

Triarchic or septarchic?-Uncovering the Triarchic Psychopathy Measure's (TriPM) structure.

The Triarchic Psychopathy Measure (TriPM) is based on a 3-dimensional conceptual model, though few studies have directly tested a 3-factor structure. The current study used a large community sample (N = 1,064, 53% males, Mage = 34) to test the structure of the TriPM via exploratory and confirmatory factor analysis, along with 4 community replication samples from North American and Europe (Ns = 511-603, 33-49% males) and 1 European male offender sample (N = 150). Three of these samples were also used to model the correlations between relevant external correlates and the original TriPM factors versus emergent factors to examine the cost of misspecifying TriPM structure. The model analyses did not support a 3-factor model (comparative fit index = .76, root mean square error of approximation = .08), revealing a number of items with limited statistical information, but uncovered a 7-factor structure (comparative fit index = .92, root mean square error of approximation = .04). From the majority of Boldness, Meanness, and Disinhibition scale items, respectively, emerged 3 factors reflecting Positive Self-Image, Leadership, and Stress Immunity; 2 factors tapping Callousness and Enjoy Hurting; and 2 factors involving Trait Impulsivity and Overt Antisociality. Further, the Enjoy Hurting and Overt Antisociality factors were more strongly correlated with one another than with the other scales from their home domains (Callousness and Impulsivity). All 7 emergent factors were differentially associated with the external correlates, suggesting that the 3 original TriPM factors do not optimally represent the conceptual model underlying the TriPM. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The perils of untested assumptions in theory testing: A reply to Patrick et al. (2020).

We respond to a critique by Patrick et al. (2020) of our recent study (Roy et al., 2020) that raised questions regarding the three-factor model of the Triarchic Psychopathy Measure (TriPM). Roy et al. demonstrated that a replicable model involving seven unidimensional factors accounted for the TriPM items across North American and European general population samples, as well as European male offenders. Despite having access to large TriPM datasets, the Patrick et al. critique relied on tangential analyses of general personality traits, using a single college sample with TriPM data as supplemental. Thus, Patrick et al. ignored findings highlighting multidimensional TriPM scales and the uncertainty they introduce with respect to the larger nomological network of psychopathy. In our reply, we demonstrate additional problems with the three-factor TriPM model and show that the seven-factor model out-performs the three-factor model in predicting correlates of psychopathy. (PsycInfo Database Record (c) 2021 APA, all rights reserved).