A randomized phase 3b study evaluating the safety and efficacy of risankizumab in adult patients with moderate-to-severe plaque psoriasis with non-pustular palmoplantar involvement.

BACKGROUND: In plaque psoriasis, palmoplantar areas are more difficult to treat. OBJECTIVE: Evaluate the safety and efficacy of risankizumab (RZB) versus placebo (PBO) for the treatment of palmoplantar psoriasis. METHODS: Patients were randomized to RZB or PBO for 16 weeks followed by RZB through week 52. The primary and secondary end points were achievement of palmoplantar Investigator's Global Assessment of "clear" or "almost clear" with ≥2-point reduction from baseline (ppIGA 0/1), achievement of ≥75%, ≥90%, and 100% improvement in Palmoplantar Psoriasis Area and Severity Index (PPASI 75, PPASI 90, PPASI 100) and achievement of static Physician Global Assessment of "clear" or "almost clear" with ≥2-point reduction from baseline (sPGA 0/1) at week 16. Safety was based on treatment-emergent adverse events. RESULTS: RZB demonstrated significant efficacy compared to PBO at week 16 in the patients achieving ppIGA 0/1 (33.3% vs 16.1% [P = .006]), PPASI 75 (42.5% vs 14.9% [P < .001]), PPASI 90 (27.6% vs 5.7% [P < .001]), sPGA 0/1 (32.2% vs 11.5% [P < .001]), and PPASI 100 (17.2% vs 1.1% [P < .001]). Results improved through week 52 with no new safety signals. LIMITATION: No biologic comparator. CONCLUSIONS: RZB demonstrated good tolerance and efficacy in palmoplantar psoriasis.

Experimental, theoretical, and astrochemical modelling investigation of the gas-phase reaction between the amidogen radical (NH2) and acetaldehyde (CH3CHO) at low temperatures.

The first experimental study of the low-temperature kinetics of the gas-phase reaction of NH2 with acetaldehyde (CH3CHO) has been performed. Experiments were carried out using laser-flash photolysis and laser-induced fluorescence spectroscopy to create and monitor the temporal decay of NH2 in the presence of CH3CHO. Low temperatures relevant to the interstellar medium were achieved using a pulsed Laval nozzle expansion. Rate coefficients were measured over the temperature and pressure range of 29-107 K and 1.4-28.2 × 1016 molecules per cm3, with the reaction exhibiting a negative temperature dependence and a positive pressure dependence. The yield of CH3CO from the reaction has also been determined at 67.1 and 35.0 K, by observing OH produced from the reaction of CH3CO with added O2. Ab initio calculations of the potential energy surface (PES) were combined with Rice-Rampsberger-Kessel-Marcus (RRKM) calculations to predict rate coefficients and branching ratios over a broad range of temperatures and pressures. The calculated rate coefficients were shown to be sensitive to the calculated density of states of the stationary points, which in turn are sensitive to the inclusion of hindered rotor potentials for several of the vibrational frequencies. The experimentally determined rate coefficients and yields have been used to fit the calculated PES, from which low-pressure limiting rate coefficients relevant to the ISM were determined. These have been included in a single-point dark cloud astrochemical model, in which the reaction is shown to be a potential source of gas-phase CH3CO radicals under dark cloud conditions.

Experimental and Theoretical Investigation of the Reaction of NH2 with NO at Very Low Temperatures.

The first experimental study of the low-temperature kinetics of the gas-phase reaction between NH2 and NO has been performed. A pulsed laser photolysis-laser-induced fluorescence technique was used to create and monitor the temporal decay of NH2 in the presence of NO. Measurements were carried out over the temperature range of 24-106 K, with the low temperatures achieved using a pulsed Laval nozzle expansion. The negative temperature dependence of the reaction rate coefficient observed at higher temperatures in the literature continues at these lower temperatures, with the rate coefficient reaching 3.5 × 10-10 cm3 molecule-1 s-1 at T = 26 K. Ab initio calculations of the potential energy surface were combined with rate theory calculations using the MESMER software package in order to calculate and predict rate coefficients and branching ratios over a wide range of temperatures, which are largely consistent with experimentally determined literature values. These theoretical calculations indicate that at the low temperatures investigated for this reaction, only one product channel producing N2 + H2O is important. The rate coefficients determined in this study were used in a gas-phase astrochemical model. Models were run over a range of physical conditions appropriate for cold to warm molecular clouds (10 to 30 K; 104 to 106 cm-3), resulting in only minor changes (<1%) to the abundances of NH2 and NO at steady state. Hence, despite the observed increase in the rate at low temperatures, this mechanism is not a dominant loss mechanism for either NH2 or NO under dark cloud conditions.

Evaluating the HCR-20V3 violence risk assessment measure with mentally disordered offenders and civil psychiatric patients in China.

The current prospective risk assessment study evaluated the application of the Chinese translation of the Historical-Clinical-Risk Management-20 Version 3 (HCR-20V3 ) in a sample of 152 offenders with mental disorders and civil psychiatric patients. The ratings of the presence and relevance of risk factors were compared, as well as summary risk ratings (SRRs), both across offenders and civil psychiatric patients, and across male and female sub-samples. Interrater reliability was consistently "excellent" for the presence and relevance of risk factors and for SRRs. Concurrent validity analyses indicated that HCR-20V3 was strongly correlated with Violence Risk Scale (from r = 0.53 to 0.71). The results of predictive validity analyses provided strong support for the bivariate associations between the main indices of HCR-20V3 and violence within 6 weeks, 7-24 weeks, and 6 months; SRRs added incrementally to both relevance and presence ratings across three follow-up lengths.

The reaction between HgBr and O3: kinetic study and atmospheric implications.

The rate constants of many reactions currently considered to be important in the atmospheric chemistry of mercury remain to be measured in the laboratory. Here we report the first experimental determination of the rate constant of the gas-phase reaction between the HgBr radical and ozone, for which a value at room temperature of k(HgBr + O3) = (7.5 ± 0.6) × 10-11 cm3 molecule s-1 (1σ) has been obtained. The rate constants of two reduction side reactions were concurrently determined: k(HgBr + O) = (5.3 ± 0.4) × 10-11 cm3 molecule s-1 and k(HgBrO + O) = (9.1 ± 0.6) × 10-11 cm3 molecule s-1. The value of k(HgBr + O3) is slightly lower than the collision number, confirming the absence of a significant energy barrier. Considering the abundance of ozone in the troposphere, our experimental rate constant supports recent modelling results suggesting that the main atmospheric fate of HgBr is reaction with ozone to form BrHgO.

Predictive validity of the SAVRY, YLS/CMI, and PCL:YV is poor for intimate partner violence perpetration among adolescent offenders.

OBJECTIVE: Despite advances in developing structured risk assessment instruments, there is currently no instrument to assess and manage the risk of intimate partner violence perpetration among adolescents. Given the empirical link between many forms of antisocial behavior, we tested whether structured tools commonly used by professionals to evaluate adolescents' risk of engaging in general violence and offending could be used to identify adolescents at risk for perpetrating intimate partner violence. HYPOTHESES: Because researchers have not yet examined whether risk assessment tools for general violence and offending predict intimate partner violence perpetration, we did not have a priori hypotheses regarding the predictive validity of these tools for this purpose. METHOD: Research assistants rated 156 adjudicated youth on the Structured Assessment of Violence Risk in Youth (SAVRY), Youth Level of Service/Case Management Inventory (YLS/CMI), and Psychopathy Checklist: Youth Version (PCL:YV) and recorded charges for intimate partner violence perpetration, any violent reoffending, and any reoffending over a 2-year follow-up period. RESULTS: Receiver operating characteristic analysis indicated that total scores and summary risk ratings on the SAVRY and YLS/CMI and total scores on the PCL:YV were significantly predictive of any violent reoffending and any reoffending, with moderate to large effect sizes, but were nonsignificantly associated with intimate partner violence perpetration. Further, penalized logistic regression analysis indicated that the SAVRY, YLS/CMI, and PCL:YV did not significantly add incremental validity to age, gender, race/ethnicity, and prior intimate partner violence perpetration and victimization for predicting future intimate partner violence perpetration. CONCLUSIONS: These findings suggest that the SAVRY, YLS/CMI, and PCL:YV could have limitations for assessing and managing intimate partner violence perpetration among adolescents. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Long-Term Safety and Efficacy of Adalimumab in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis.

PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III). PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or who discontinued the study after meeting treatment failure criteria (active uveitis). METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤ 362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose. MAIN OUTCOME MEASURES: Long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related systemic corticosteroids. RESULTS: At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry. Mean daily dose of systemic corticosteroids was reduced from 9.4 ± 17.1 mg/day at week 0 (n = 359) to 1.5 ± 3.9 mg/day at week 150 (n = 181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest were infections (n = 275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively. CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab.

Kinetic Study of the Reactions PO + O2 and PO2 + O3 and Spectroscopy of the PO Radical.

The kinetics of the reactions of PO with O2 and PO2 with O3 were studied at temperatures ranging from ∼190 to 340 K, using a pulsed laser photolysis-laser induced fluorescence technique. For the reaction of PO + O2, there is evidence of both a two- and three-body exit channel, producing PO2 + O and PO3, respectively. Potential energy surfaces of both the PO + O2 and PO2 + O3 systems were calculated using electronic structure theory and combined with RRKM calculations to explain the observed pressure and temperature dependences. For PO + O2, at pressures typical of a planetary upper atmosphere where meteoric ablation of P will occur, the reaction is effectively pressure independent with a yield of PO2 + O of >99%; the rate coefficient can be expressed by log10(k, 120-500 K, cm3 molecule-1 s-1) = -13.915 + 2.470 log10(T) - 0.5020(log10(T))2, with an uncertainty of ±10% over the experimental temperature range (191-339 K). With increasing pressure, the yield of PO3 increases, reaching ∼90% at a pressure of 1 atm and T = 300 K. For PO2 + O3, k(188-339 K) = 3.7 × 10-11 exp(-1131/T) cm3 molecule-1 s-1, with an uncertainty of ±26% over the stated temperature range. Laser-induced fluorescence spectra of PO over the wavelength range 245-248 nm were collected and simulated using pgopher to obtain new spectroscopic constants for the ground and v = 1 vibrational levels of the X2Π and A2Σ+ states of PO.

Experimental Study of the Removal of Ground- and Excited-State Phosphorus Atoms by Atmospherically Relevant Species.

The reaction kinetics of the ground and first two excited states of atomic phosphorus, P, with atmospherically relevant species were studied at temperatures ranging from ∼200 to 750 K using a pulsed laser photolysis-laser-induced fluorescence technique. The temperature dependence of the rate coefficients is parametrized as follows (units: cm3 molecule-1 s-1, 1σ errors): k(P(2P)+O2)(189 ≤ T/K ≤ 701) = (7.10 ± 1.03) × 10-12 × (T/298)1.42±0.13 × exp[(374 ± 41)/T]; k(P(2D)+O2)(188 ≤ T/K ≤ 714) = (1.20 ± 0.29) × 10-11 × (T/298)0.821±0.207 × exp[(177 ± 70)/T]; k(P(2D)+CO2)(296 ≤ T/K ≤ 748) = (5.68 ± 0.36) × 10-12 × (T/298)0.800±0.103; k(P(2D)+N2)(188 ≤ T/K ≤ 748) = (1.42 ± 0.03) × 10-12 × (T/298)1.36±0.04; k(P(4S)+O2)(187 ≤ T/K ≤ 732) = (3.08 ± 0.31) × 10-13 × (T/298)2.24±0.29. Electronic structure theory combined with RRKM calculations have been used to explain the unusual temperature dependence of P(4S) + O2. The small pre-exponential factor for the reaction results from a tight steric constraint, together with the requirement that the reaction occurs on doublet rather than sextet electronic surfaces.

Comparing the lexical similarity of the triarchic model of psychopathy to contemporary models of psychopathy.

OBJECTIVE: The triarchic model of psychopathy (Patrick, Fowles, & Krueger, 2009) posits that psychopathic personality comprises three domains: boldness, meanness, and disinhibition. The present study aimed to clarify conceptual overlap between contemporary definitions of psychopathy, with particular emphasis given to the relevance of boldness (i.e., social dominance, venturesomeness, emotional resiliency)-a topic of recent debate. METHOD: Undergraduate students (N = 439) compared the lexical similarity of triarchic domains with two contemporary models of psychopathy: the Comprehensive Assessment of Psychopathic Personality (CAPP; Cooke, Hart, Logan, & Michie, 2012) and the Five-Factor Model of psychopathy (FFM; Widiger & Lynam, 1998). RESULTS: From a content validity perspective, meanness and disinhibition were lexically similar to both the CAPP and FFM psychopathy, whereas boldness was less strongly associated with these models. Meanness showed the strongest lexical similarity in comparison with past prototypicality ratings of the CAPP and FFM psychopathy. CONCLUSIONS: These findings bear implications for defining and comparing conceptualizations of psychopathy that underpin its assessment.

Concurrent validity of the personality assessment screener in a large sample of offenders.

Mental health problems are disproportionately prevalent in forensic and correctional settings, and there have been numerous attempts to develop screening tools to evaluate individuals in such contexts. This study investigates the clinical utility of the Personality Assessment Screener (PAS; Morey, 1997), a brief self-report measure of risk for emotional and behavioral dysfunction, in a large mixed-gender offender sample (N = 1,658). The PAS is a 22-item measure derived from the Personality Assessment Inventory (PAI; Morey, 1991, 2007), a more comprehensive self-report instrument widely used to assess for psychological disturbances among forensic and correctional populations. We examined the ability of the PAS to concurrently predict clinically significant elevations on the PAI and several other indicators of symptomatology and dysfunction. Collectively, results suggest that PAS total and element (subscale) scores show considerable promise in screening inmates for serious problems with emotional and behavioral functioning, though interpretive ranges used to categorize PAS scores in clinical and community settings may require revision for criminal justice populations. We discuss the applied value of the PAS for detecting specific areas of dysfunction relevant to risk management (e.g., aggression, suicidality) and for concentrating resources on offenders with the most immediate and severe need for psychological services. (PsycINFO Database Record

Physical Effects of Anabolic-androgenic Steroids in Healthy Exercising Adults: A Systematic Review and Meta-analysis.

Many athletes use anabolic-androgenic steroids (AAS) for physical enhancement but the magnitude of these gains and associated adverse effects has not been rigorously quantified. MEDLINE, EMBASE, Cochrane, SPORTDiscus, and PsycINFO were searched to identify randomized placebo-controlled trials of AAS in healthy exercising adults that reported one of the following outcomes: muscular strength, body composition, cardiovascular endurance, or power. Two authors appraised abstracts to identify studies for full-text retrieval; these were reviewed in duplicate to identify included studies. Study quality was assessed using the Cochrane method. Data were extracted in duplicate and pooled using the DerSimonian and Laird random effects model and to calculate the ratio of mean outcome improvement where possible. Pooled standardized mean difference (SMD) in muscle strength between AAS and placebo was 0.27 (95% confidence interval, 0.07-0.47; I = 12.7%; 21 studies). Change in strength was 52% greater in the AAS group compared to placebo. The SMD for change in lean mass between AAS and placebo was 0.62 (95% confidence interval, 0.35-0.89; I = 26%; 14 studies). Due to missing data, fat mass, cardiovascular endurance, power, and adverse effects were summarized qualitatively. Only 13 of 25 studies reported adverse effects including increased low density lipoprotein (LDL), decreased high density lipoprotein (HDL), irritability, and acne. In healthy exercising adults, AAS use is associated with a small absolute increase in muscle strength and moderate increase in lean mass. However, the transparency and completeness of adverse effect reporting varied, most studies were of short duration, and doses studied may not reflect actual use by athletes.

Are adolescent risk assessment tools sensitive to change? A framework and examination of the SAVRY and the YLS/CMI.

Although many adolescent risk assessment tools include an emphasis on dynamic factors, little research has examined the extent to which these tools are capable of measuring change. In this article, we outline a framework to evaluate a tool's capacity to measure change. This framework includes the following: (a) measurement error and reliable change, and (b) sensitivity (i.e., internal, external, and relative sensitivity). We then used this framework to evaluate the Structured Assessment of Violence Risk in Youth (SAVRY) and Youth Level of Service/Case Management Inventory (YLS/CMI). Research assistants conducted 509 risk assessments with 146 adolescents on probation (101 male, 45 female), who were assessed every 3 months over a 1-year period. Internal sensitivity (i.e., change over time) was partially supported in that a modest proportion of youth showed reliable changes over the 3-, 6-, and 12-month follow-ups. External sensitivity (i.e., the association between change scores and reoffending) was also partially supported. In particular, 22% of the associations between change scores and any and violent reoffending were significant at a 6-month follow-up. However, only 1 change score (i.e., peer associations) remained significant after the Bonferroni correction was applied. Finally, relative sensitivity was not supported, as the SAVRY and YLS/CMI was not more dynamic than the Psychopathy Checklist: Youth Version (PCL:YV). Specifically, the 1-year rank-order stability coefficients for the SAVRY, YLS/CMI, and PCL:YV Total Scores were .78, .75, and .76, respectively. Although the SAVRY and YLS/CMI hold promise, further efforts may help to enhance sensitivity to short-term changes in risk. (PsycINFO Database Record

Influence of the HCR-20, LS/CMI, and PCL-R on decisions about parole suitability among lifers.

Among 5,181 inmates indeterminately sentenced to life in California who were evaluated for parole suitability between January 2009 and November 2010, 11% were granted parole. After administration of the HCR-20, LS/CMI, and PCL-R, psychologists judged most inmates (78%) to be at low or moderate risk for future violence. This overall risk rating (ORR) was significantly associated with parole suitability decisions. Moderate to large associations were observed between the ORR and all risk indices. The HCR-20 Clinical and Risk Management scales demonstrated the strongest associations with parole suitability decisions. Among the LS/CMI scales, Procriminal Attitudes and Leisure/Recreation were most predictive of failure to obtain parole. PCL-R scores had little influence on parole suitability decisions beyond the HCR-20 and LS/CMI. Overall, findings suggest parole board members' decisions were consistent with empirically supported practice, in that individuals assessed to be at relatively low risk were far more likely to be granted parole than those assessed to be at moderate or high risk for future violence.

Remorse, psychopathology, and psychopathy among adolescent offenders.

Remorse has long been important to the juvenile justice system. However, the nature of this construct has not yet been clearly articulated, and little research has examined its relationships with other theoretically and forensically relevant variables. The present study was intended to address these issues by examining relationships among remorse, psychopathology, and psychopathy in a sample of adolescent offenders (N = 97) using the theoretically and empirically established framework of guilt and shame (Tangney & Dearing, 2002). Findings indicated that shame was positively related to behavioral features of psychopathy, whereas guilt was negatively related to psychopathic characteristics more broadly. In addition, shame was positively associated with numerous mental health problems whereas guilt was negatively associated with anger, depression, and anxiety. These results provide empirical support for theory that psychopathy is characterized by lack of remorse (e.g., Hare, 1991), and also underscore shame and guilt as potentially important treatment targets for adolescent offenders.

DSM-5 antisocial personality disorder: predictive validity in a prison sample.

Symptoms of antisocial personality disorder (ASPD), particularly remorselessness, are frequently introduced in legal settings as a risk factor for future violence in prison, despite a paucity of research on the predictive validity of this disorder. We examined whether an ASPD diagnosis or symptom-criteria counts could prospectively predict any form of institutional misconduct, as well as aggressive and violent infractions among newly admitted prisoners. Adult male (n = 298) and female (n = 55) offenders were recruited from 4 prison systems across the United States. At the time of study enrollment, diagnostic information was collected using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; APA, 1994) Axis II Personality Disorders (SCID-II; First, Gibbon, Spitzer, Williams, & Benjamin, 1997) supplemented by a detailed review of official records. Disciplinary records were obtained from inmates' respective prisons covering a 1-year period following study enrollment and misconduct was categorized hierarchically as any (general), aggressive (verbal/physical), or violent (physical). Dichotomous ASPD diagnoses and adult symptom-criteria counts did not significantly predict institutional misconduct across our 3 outcome variables, with effect sizes being close to 0 in magnitude. The symptom of remorselessness in particular showed no relation to future misconduct in prison. Childhood symptom counts of conduct disorder demonstrated modest predictive utility. Our results offer essentially no support for the claim that ASPD diagnoses can predict institutional misconduct in prison, regardless of the number of adult symptoms present. In forensic contexts, testimony that an ASPD diagnosis identifies defendants who will pose a serious threat while incarcerated in prison presently lacks any substantial scientific foundation.

Changes in dynamic risk and protective factors for violence during inpatient forensic psychiatric treatment: predicting reductions in postdischarge community recidivism.

Empirical studies have rarely investigated the association between improvements on dynamic risk and protective factors for violence during forensic psychiatric treatment and reduced recidivism after discharge. The present study aimed to evaluate the effects of treatment progress in risk and protective factors on violent recidivism. For a sample of 108 discharged forensic psychiatric patients pre- and posttreatment assessments of risk (HCR-20) and protective factors (SAPROF) were compared. Changes were related to violent recidivism at different follow-up times after discharge. Improvements on risk and protective factors during treatment showed good predictive validity for abstention from violence for short- (1 year) as well as long-term (11 years) follow-up. This study demonstrates the sensitivity of the HCR-20 and the SAPROF to change and shows improvements on dynamic risk and protective factors are associated with lower violent recidivism long after treatment.