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Importance: Mogamulizumab is a monoclonal antibody against CCR4 approved for treatment for mycosis fungoides (MF) and Sézary syndrome (SS). Mogamulizumab-associated rash (MAR) is difficult to differentiate from cutaneous MF or SS, which can lead to unnecessary discontinuation of drug use because of concern for severe drug reaction or incorrect presumption of disease relapse or progression in the skin., Objective: To examine the most common clinical presentations of MAR in patients with MF or SS and the diagnostic and management challenges., Design, Setting, and Participants: This retrospective case series assessed patients from a multidisciplinary cutaneous lymphoma clinic and supportive oncodermatology clinic at a major academic referral center who had a diagnosis of MF or SS and received mogamulizumab from January 1, 2013, to January 1, 2020. Treatment was followed by new or worsening rash with skin biopsy results compatible with drug eruption determined by clinicopathologic correlation and molecular testing to exclude active malignant disease., Exposures: At least 1 dose of mogamulizumab., Main Outcomes and Measures: Mogamulizumab-associated rash was characterized by clinical features, including time to onset, clinical presentation, histopathologic features, and management approach., Results: The study included 19 patients with MF or SS who developed MAR (median age, 65 years; age range, 38-82 years; 10 [52.6%] male). Median time to MAR onset was 119 days (range, 56 days to 3.8 years). Patients with MAR exhibited 4 predominant clinical presentations: (1) folliculotropic MF-like scalp plaques with alopecia, (2) papules and/or plaques, (3) photoaccentuated dermatitis, and (4) morbilliform or erythrodermic dermatitis. The most common anatomical region involved was the head and neck, including the scalp. Histopathologic findings were variable and did not correspond to primary clinical morphologic findings. Immunohistochemistry and T-cell clonality ancillary testing were helpful to distinguish MAR from disease. Most patients with MAR (14 of 19) discontinued mogamulizumab treatment; however, no life-threatening severe cutaneous adverse drug reactions occurred, and the decision for drug therapy cessation was usually multifactorial. Four patients were treated again with mogamulizumab with no life-threatening drug-related events. Approaches to management of MAR include topical corticosteroids, systemic corticosteroids, and/or methotrexate., Conclusions and Relevance: This case series found that mogamulizumab-associated rash had a heterogeneous clinical presentation with variable and delayed onset in patients with MF or SS. Mogamulizumab-associated rash exhibited a predilection for the head and neck and was difficult to clinically distinguish from relapse or progression of disease. Recognition of the most common clinical presentations can help prevent unnecessary discontinuation of mogamulizumab treatment. The presence of MAR does not necessitate permanent discontinuation of or avoidance of retreatment with mogamulizumab.

Rash is one of the most common adverse events observed with mogamulizumab, an anti-C-C chemokine receptor 4 monoclonal antibody approved for previously treated mycosis fungoides (MF) and Sezary syndrome (SS). Given the nonspecific clinical presentations of this rash, histopathologic distinction from MF/SS is critical for informing clinical management. We performed a comprehensive characterization of the histopathologic findings in mogamulizumab-associated rash (MAR) with the integration of high-throughput sequencing of T-cell receptor (TCR) genes. Fifty-two biopsy specimens from 19 patients were evaluated retrospectively. Three major histologic reaction patterns were identified: spongiotic/psoriasiform dermatitis (33/52), interface dermatitis (11/52), and granulomatous dermatitis (8/52). Almost half of the specimens (21/52) showed at least 2 of these reaction patterns concurrently. Dermal eosinophils were not a consistent feature, being present in only half (27/52) of specimens and prominent in only 3. Features mimicking MF/SS, including lymphocyte exocytosis, lamellar fibroplasia, and adnexal involvement, were commonly seen but tended to be focal and mild. In 38/43 specimens with available immunohistochemistry, intraepidermal lymphocytes demonstrated a CD4:CD8 ratio ≤1 : 1. Low background levels of the patient's previously identified MF/SS-associated TCR sequence(s) were demonstrated in 20/46 specimens analyzed by high-throughput sequencing of TCR. We conclude that MAR may demonstrate diverse histologic features. Findings that may distinguish MAR from MF/SS include the inverted or normalized CD4:CD8 ratio within intraepidermal lymphocytes and demonstration of absent or nondominant levels of disease-associated TCR sequences. Correlation with the clinical findings and immunohistochemical and molecular characterization of the patient's MF/SS before mogamulizumab, when possible, may facilitate recognition of MAR.

This survey of 206 forensic psychologists tested the "filtering" effects of preexisting expert attitudes in adversarial proceedings. Results confirmed the hypothesis that evaluator attitudes toward capital punishment influence willingness to accept capital case referrals from particular adversarial parties. Stronger death penalty opposition was associated with higher willingness to conduct evaluations for the defense and higher likelihood of rejecting referrals from all sources. Conversely, stronger support was associated with higher willingness to be involved in capital cases generally, regardless of referral source. The findings raise the specter of skewed evaluator involvement in capital evaluations, where evaluators willing to do capital casework may have stronger capital punishment support than evaluators who opt out, and evaluators with strong opposition may work selectively for the defense. The results may provide a partial explanation for the "allegiance effect" in adversarial legal settings such that preexisting attitudes may contribute to partisan participation through a self-selection process.

The knowledge of experts presumably affects their credibility and the degree to which the trier of fact agrees with them. However, specific effects of demonstrated knowledge are largely unknown. In this experiment, we manipulated a forensic expert's level of knowledge in a mock-trial paradigm. We tested the influence of low versus high expert knowledge on mock juror perceptions of expert credibility, on agreement with the expert, and on sentencing. We also tested expert gender as a potential moderator. Knowledge effects were statistically significant; however, these differences carried little practical utility in predicting mock jurors' ultimate decisions. Contrary to the hypotheses that high knowledge would yield increased credibility and agreement, knowledge manipulations influenced only perceived expert likeability. The low-knowledge expert was perceived as more likeable than the high-knowledge counterpart, a paradoxical finding. No significant differences across expert gender were found. Implications for conceptualizing expert witness knowledge and credibility and their potential effects on juror decision-making are discussed., (© 2015 American Academy of Psychiatry and the Law.)

This review of women's participation in the legal system as expert witnesses examines the empirical literature on the perceived credibility and persuasiveness of women compared with men experts. The effects of expert gender are complex and sometimes depend on the circumstances of the case. Some studies find no differences, some find favorable effects for women and others for men, and still others find that expert gender interacts with other circumstances of the case. The findings are interpreted through social role theory and the role incongruity theory of prejudice. Future directions for research are identified and implications are considered for attorneys who select and prepare expert witnesses. Suggestions for men's and women's behavior as expert witnesses are provided., (Copyright © 2014 John Wiley & Sons, Ltd.)

In this study, we examined how manipulations of likeability and knowledge affected mock jurors' perceptions of female and male expert witness credibility (n = 290). Our findings extend the person-perception literature by demonstrating how warmth and competence overlap with existing conceptions of likeability and knowledge in the psycholegal domain. We found that experts high in likeability, knowledge, or both were perceived equally positively, regardless of gender, in a death penalty sentencing context. Gender differences emerged when the expert was low in likeability or knowledge. In these conditions the male expert was perceived more positively than the comparable female expert. Although intermediate judgments (e.g., perceptions of credibility) were affected by our manipulations, ultimate decisions (e.g., sentencing) were not. Implications for theory and practice are discussed.

The 64-item Hare Self-Report Psychopathy Scale (Hare SRP; Paulhus, Neumann, & Hare, in press ) is the most recent revision of the SRP, which has undergone numerous iterations. Little research has been conducted with this new edition; therefore, the goal of this study was to elucidate the factor structure as well as the criterion-related, convergent, and discriminant validity of the measure in a large sample of college students (N = 602). Confirmatory factor analyses revealed that the best fitting model was the original 4-factor model proposed by the authors of the Hare SRP (compared to a 1-factor, 2-factor, and 4-factor random model). The 4-factor model revealed superior fit for the data relative to the other alternative models. In addition, we elaborated on the psychometric properties of this 4-factor model in this sample. The Hare SRP total and factor scores evidenced good internal reliability as well as promising criterion-related, convergent, and discriminant validity in terms of predicting scores on conceptually relevant external criteria. Implications for theory and future research are discussed.

Despite the application of Self-Efficacy Theory (Bandura, 1977, 2000) to many areas of psychology, there is a lack of research on self-efficacy in the ability to testify in court. The present study fills this gap by incrementally developing the construct of Witness Self-Efficacy and establishing its psychometric properties. Study I features exploratory and confirmatory factor analyses yielding a two-factor Witness Self-Efficacy Scale (WSES). The two components are Poise and Communication Style. Study II uses a second data collection to show that both WSES domains possess convergent, divergent, and predictive validity relations consistent with those expected using an SET framework. Notably, WSES components predicted perceptions of witness credibility and sentencing outcomes above and beyond witness extraversion, general self-efficacy, and general self-confidence. Implications for SET and witness preparation training are discussed. Copyright © 2010 John Wiley & Sons, Ltd., (Copyright © 2010 John Wiley & Sons, Ltd.)

This study sought to identify stigma differences between HIV/AIDS and other sexually transmitted infections (STIs). Interviewees from Alabama, USA (n = 537) rated two types of stigma (damage to social reputation and 'moral weakness') for seven infections ranging from 'nuisance' conditions (e.g. pubic lice) to life-threatening disease (e.g. HIV/AIDS). When asked which of the seven STIs would be most damaging to reputation, 74.8% of respondents chose HIV/AIDS. However, when asked to choose which STI represented moral weakness in infected persons, HIV/AIDS was rated as significantly lower than the other STIs, which suggests that HIV/AIDS is perceived differently than non-HIV STIs. This study addresses the possibility that advances in public awareness of HIV/AIDS have not necessarily been extrapolated into awareness of other STIs. Clinicians should be aware of these high levels of stigma as potential barriers to treatment for all STIs. Public health officials should consider the impact of undifferentiated stigma on STI prevention messages.

This study was conducted to investigate the relationship between expert witness likeability and jurors' judgments of credibility and tendencies in sentencing. Two actors playing expert witnesses were trained to present themselves as high and low in likeability in a standard testimony scenario in the sentencing phase of a capital murder trial. The effects of extraversion and gender of the 210 psychology undergraduates serving as mock jurors attending to expert testimony were also examined. The dependent variables were the jurors' perceptions of the witnesses' credibility and their agreement with the testimony. The likeability of the expert witnesses was found to be significantly related to the jurors' perception of their trustworthiness, but not to their displays of confidence or knowledge or to the mock jurors' sentencing decisions. The women rated highly likeable experts as more credible than the less likeable ones, but the men did not differentiate between the two types. As extraversion increased, the male jurors' agreement with testimony increased, but the female jurors' agreement decreased. The results suggest that likeability can be an important element in the credibility of the source and that attorneys and trial consultants now have an empirical foundation for addressing likeability as part of witness preparation.

Dihydroorotase plays a key role in pyrimidine biosynthesis by catalyzing the reversible interconversion of carbamoyl aspartate to dihydroorotate. Here we describe the three-dimensional structure of dihydroorotase from Escherichia coli determined and refined to 1.7 A resolution. Each subunit of the homodimeric enzyme folds into a "TIM" barrel motif with eight strands of parallel beta-sheet flanked on the outer surface by alpha-helices. Unexpectedly, each subunit contains a binuclear zinc center with the metal ions separated by approximately 3.6 A. Lys 102, which is carboxylated, serves as a bridging ligand between the two cations. The more buried or alpha-metal ion in subunit I is surrounded by His 16, His 18, Lys 102, Asp 250, and a solvent molecule (most likely a hydroxide ion) in a trigonal bipyramidal arrangement. The beta-metal ion, which is closer to the solvent, is tetrahedrally ligated by Lys 102, His 139, His 177, and the bridging hydroxide. L-Dihydroorotate is observed bound to subunit I, with its carbonyl oxygen, O4, lying 2.9 A from the beta-metal ion. Important interactions for positioning dihydroorotate into the active site include a salt bridge with the guanidinium group of Arg 20 and various additional electrostatic interactions with both protein backbone and side chain atoms. Strikingly, in subunit II, carbamoyl L-aspartate is observed binding near the binuclear metal center with its carboxylate side chain ligating the two metals and thus displacing the bridging hydroxide ion. From the three-dimensional structures of the enzyme-bound substrate and product, it has been possible to propose a unique catalytic mechanism for dihydroorotase. In the direction of dihydroorotate hydrolysis, the bridging hydroxide attacks the re-face of dihydroorotate with general base assistance by Asp 250. The carbonyl group is polarized for nucleophilic attack by the bridging hydroxide through a direct interaction with the beta-metal ion. During the cyclization of carbamoyl aspartate, Asp 250 initiates the reaction by abstracting a proton from N3 of the substrate. The side chain carboxylate of carbamoyl aspartate is polarized through a direct electrostatic interaction with the binuclear metal center. The ensuing tetrahedral intermediate collapses with C-O bond cleavage and expulsion of the hydroxide which then bridges the binuclear metal center.

The effects of nonsteroidal anti-inflammatory agents on superoxide production and granule enzyme release by human polymorphonuclear leukocytes stimulated with either formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe] or immune complexes were investigated. Cytochrome c reduction and the release of lysozyme, beta-glucuronidase, myeloperoxidase and gelatinase were measured. Auranofin, phenylbutazone, sulfasalazine and the phospholipase A2 inhibitor, 4-bromophenacyl bromide, strongly inhibited these responses in fMet-Leu-Phe stimulated cells, at concentrations below 50 microM. Indomethacin, piroxicam, mefenamic acid, primaquine and quinacrine at 50-250 microM were inhibitory. Up to 1 mM ibuprofen and chloroquine inhibited superoxide production but had little effect on degranulation. With cells stimulated by IgG aggregates (immune complexes), up to 1 mM ibuprofen, mefenamic acid and piroxicam did not inhibit either response. Indomethacin, phenylbutazone, sulfasalazine and primaquine inhibited, but considerably higher concentrations were required than with fMet-Leu-Phe. Quinacrine inhibited superoxide production equally well with both stimuli but inhibited enzyme release only with fMet-Leu-Phe. Only auranofin, 4-bromophenacyl bromide, and the weakly effective chloroquine exerted approximately the same effect with both stimuli. D-Penicillamine did not affect enzyme release with either stimulus and interfered in the superoxide assay. Gelatinase release induced by fMet-Leu-Phe was affected to the same extent, or slightly more, than release of the other granule enzymes. With immune complexes, there was only modest inhibition of gelatinase release by any of the drugs at 250-1000 microM. Our results reinforce previous observations that many anti-inflammatory drugs affect neutrophil functions, but their effects vary with stimulus. The relative insensitivity of immune complex-induced responses to most of the drugs must be taken into account when considering their mode of action.

Sulfasalazine is a potent inhibitor of superoxide production and granule enzyme release by stimulated neutrophils, and modulation of these responses may contribute to its anti-inflammatory properties. It is a composite drug consisting of 5-aminosalicylic acid and sulfapyridine joined through an azo linkage. To investigate which functional groups on the molecule are active against neutrophil responses, 5-aminosalicylic acid, sulfapyridine and olsalazine were added to cells stimulated with fMet-Leu-Phe or immune complexes. The inhibitory effects of sulfasalazine on superoxide production, degranulation and neutrophil-mediated collagen degradation were closely mimicked by olsalazine, with the other two compounds having little effect on either function. Thus the azo link appears to be the important structural feature of sulfasalazine that affects neutrophil responses. This suggests that sulfasalazine could be anti-inflammatory in its own right rather than just acting as a source of 5-aminosalicylic acid. Our findings are also a favourable indication for olsalazine (Dipentum), which is currently under trial as an anti-inflammatory agent.

The ability of nonsteroidal antiinflammatory drugs to inhibit neutrophil-mediated degradation of type IV collagen in an in vitro tissue injury model using glomerular basement membrane (GBM) containing immune complexes was investigated. Auranofin (2.5-10 microM), phenylbutazone (50-250 microM), sulfasalazine (250-1,000 microM), and 4-bromophenacyl bromide (5-20 microM) each inhibited up to 70% of the collagen degradation, in parallel with almost complete inhibition of the release of azurophil and specific granule enzymes. These drugs had much less an effect on gelatinase release. Indomethacin and the antimalarials, which inhibited the neutrophil oxidative burst but not degranulation, had little effect on GBM collagen degradation. Our results do not necessarily imply that inhibition of neutrophil-mediated degradation of connective tissue is relevant to the action of nonsteroidal antiinflammatory drugs in vivo; however, using the GBM model system, we have shown that when a drug inhibits granule enzyme release, there is an associated decrease in collagen degradation, whereas inhibition of the oxidative burst has relatively little effect.