Therapy With Allogeneic Severe Acute Respiratory Syndrome Coronavirus-2-Specific T Cells for Persistent Coronavirus Disease 2019 in Immunocompromised Patients.

We administered severe acute respiratory syndrome coronavirus-2 viral-specific T cells (VSTs) under emergency investigational new drug applications to 6 immunocompromised patients with persistent coronavirus disease 2019 (COVID-19) and characterized clinical and virologic responses. Three patients had partial responses after failing other therapies but then died. Two patients completely recovered, but the role of VSTs in recovery was unclear due to concomitant use of other antivirals. One patient had not responded to 2 courses of remdesivir and experienced sustained recovery after VST administration. The use of VSTs in immunocompromised patients with persistent COVID-19 requires further study.

ALVR109, an off-the-shelf partially HLA matched SARS-CoV-2-specific T cell therapy, to treat refractory severe COVID-19 pneumonia in a heart transplant patient: Case report.

An unvaccinated adult male heart transplant recipient patient with recalcitrant COVID-19 due to SARS-CoV-2 delta variant with rising nasopharyngeal quantitative viral load was successfully treated with ALVR109, an off-the-shelf SARS-CoV-2-specific T cell therapy. Background immunosuppression included 0.1 mg/kg prednisone, tacrolimus, and mycophenolate mofetil 1 gm twice daily for historical antibody-mediated rejection. Prior therapies included remdesivir, corticosteroids, and tocilizumab, with requirement for high-flow nasal oxygen. Lack of clinical improvement and acutely rising nasopharyngeal viral RNA more than 3 weeks into illness prompted the request of ALVR109 through an emergency IND. The day following the first ALVR109 infusion, the patient's nasopharyngeal SARS-CoV-2 RNA declined from 7.43 to 5.02 log10 RNA copies/ml. On post-infusion day 4, the patient transitioned to low-flow oxygen. Two subsequent infusions of ALVR109 were administered 10 and 26 days after the first; nasopharyngeal SARS-CoV-2 RNA became undetectable on Day 11, and he was discharged the following day on low-flow oxygen 5 weeks after the initial diagnosis of COVID-19. The clinical and virologic improvements observed in this patient following administration of ALVR109 suggest a potential benefit that warrants further exploration in clinical trials.

Pharmacokinetic Interactions between the Hepatitis C Virus Inhibitors Elbasvir and Grazoprevir and HIV Protease Inhibitors Ritonavir, Atazanavir, Lopinavir, and Darunavir in Healthy Volunteers.

The combination of the hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor elbasvir and the NS3/4A protease inhibitor grazoprevir is a potent, once-daily therapy indicated for the treatment of chronic HCV infection in individuals coinfected with human immunodeficiency virus (HIV). We explored the pharmacokinetic interactions of elbasvir and grazoprevir with ritonavir and ritonavir-boosted HIV protease inhibitors in three phase 1 trials. Drug-drug interaction trials with healthy participants were conducted to evaluate the effect of ritonavir on the pharmacokinetics of grazoprevir (n = 10) and the potential two-way pharmacokinetic interactions of elbasvir (n = 30) or grazoprevir (n = 39) when coadministered with ritonavir-boosted atazanavir, lopinavir, or darunavir. Coadministration of ritonavir with grazoprevir increased grazoprevir exposure; the geometric mean ratio (GMR) for grazoprevir plus ritonavir versus grazoprevir alone area under the concentration-time curve from 0 to 24 h (AUC0-24) was 1.91 (90% confidence interval [CI]; 1.31 to 2.79). Grazoprevir exposure was markedly increased with coadministration of atazanavir-ritonavir, lopinavir-ritonavir, and darunavir-ritonavir, with GMRs for grazoprevir AUC0-24 of 10.58 (90% CI, 7.78 to 14.39), 12.86 (90% CI, 10.25 to 16.13), and 7.50 (90% CI, 5.92 to 9.51), respectively. Elbasvir exposure was increased with coadministration of atazanavir-ritonavir, lopinavir-ritonavir, and darunavir-ritonavir, with GMRs for elbasvir AUC0-24 of 4.76 (90% CI, 4.07 to 5.56), 3.71 (90% CI, 3.05 to 4.53), and 1.66 (90% CI, 1.35 to 2.05), respectively. Grazoprevir and elbasvir had little effect on atazanavir, lopinavir, and darunavir pharmacokinetics. Coadministration of elbasvir-grazoprevir with atazanavir-ritonavir, lopinavir-ritonavir, or darunavir-ritonavir is contraindicated, owing to an increase in grazoprevir exposure. Therefore, HIV treatment regimens without HIV protease inhibitors should be considered for HCV/HIV-coinfected individuals who are being treated with elbasvir-grazoprevir.

Pharmacokinetics of elbasvir and grazoprevir in subjects with end-stage renal disease or severe renal impairment.

PURPOSE: To describe the phase 1 and population pharmacokinetic investigations that support dosing recommendations for elbasvir/grazoprevir (EBR/GZR) in hepatitis C virus-infected people with advanced chronic kidney disease. METHODS: This was an open-label, two-part, multiple-dose trial (MK-5172 PN050; NCT01937975) in 24 non-HCV-infected participants with end-stage renal disease (ESRD) or severe renal impairment who received once-daily EBR 50 mg and GZR 100 mg for 10 days. Population pharmacokinetic analyses from the phase 3 C-SURFER study (PN052, NCT02092350) were also conducted. RESULTS: When comparing haemodialysis (HD) and non-HD days in participants with ESRD, geometric mean ratios (GMRs) (90% confidence intervals [CIs]) for EBR and GZR AUC0-24 were 1.14 (1.08-1.21) and 0.97 (0.87-1.09). When comparing ESRD and healthy participants, GMRs (90% CIs) for EBR and GZR AUC0-24 were 0.99 (0.75-1.30) and 0.83 (0.56-1.22) on HD days, and 0.86 (0.65-1.14) and 0.85 (0.58-1.25) on non-HD days. GMRs (90% CIs) for AUC0-24 in participants with severe renal impairment relative to healthy controls were 1.65 (1.09-2.49) for GZR and 1.86 (1.38-2.51) for EBR. In population modelling of data from C-SURFER, absolute geometric means of steady-state EBR AUC0-24 were 2.78 and 3.07 µM*h (HD and non-HD recipients) and GZR AUC0-24 were 1.80 and 2.34 µM*h (HD and non-HD recipients). CONCLUSIONS: EBR/GZR represents an important treatment option for HCV infection in people with severe renal impairment and those with ESRD. No dosage adjustment of EBR/GZR is required in people with any degree of renal impairment, including those receiving dialysis.

Assessment of drug interaction potential between the HCV direct-acting antiviral agents elbasvir/grazoprevir and the HIV integrase inhibitors raltegravir and dolutegravir.

BACKGROUND: Elbasvir/grazoprevir is a once-daily fixed-dose combination therapy for the treatment of chronic HCV infection, including HCV/HIV coinfection. OBJECTIVES: To evaluate the pharmacokinetic interaction of elbasvir and grazoprevir with raltegravir or dolutegravir. METHODS: Three open-label trials in healthy adult participants were conducted. In the raltegravir trials, participants received a single dose of raltegravir 400 mg, a single dose of elbasvir 50 mg or grazoprevir 200 mg, and raltegravir with either elbasvir or grazoprevir. In the dolutegravir trial, participants received a single dose of dolutegravir 50 mg alone or co-administered with once-daily elbasvir 50 mg and grazoprevir 200 mg. RESULTS: The raltegravir AUC0-∞ geometric mean ratio (GMR) (90% CI) was 1.02 (0.81-1.27) with elbasvir and 1.43 (0.89-2.30) with grazoprevir. Dolutegravir AUC0-∞ GMR (90% CI) was 1.16 (1.00-1.34) with elbasvir and grazoprevir. The elbasvir AUC0-∞ GMR (90% CI) was 0.81 (0.57-1.17) with raltegravir and 0.98 (0.93-1.04) with dolutegravir. The grazoprevir AUC0-24 GMR (90% CI) was 0.89 (0.72-1.09) with raltegravir and 0.81 (0.67-0.97) with dolutegravir. CONCLUSIONS: Elbasvir or grazoprevir co-administered with raltegravir or dolutegravir resulted in no clinically meaningful drug-drug interactions and was generally well tolerated. These results support the assertion that no dose adjustments for elbasvir, grazoprevir, raltegravir or dolutegravir are needed for co-administration in HCV/HIV-coinfected people.

A Brief History of Psychological Theory, Research, and Treatment With Adult Male Sex Offenders.

PURPOSE OF REVIEW: The goal of this paper is to provide a history of psychological theories, research, and treatment of male sex offenders from the onset of modern approaches that emerged in the 1960s up to the present time. The questions addressed in this paper primarily concern the reasons and justifications for the observed changes. RECENT FINDINGS: Current conceptualizations of the motivations of sex offenders are quite comprehensive with a central focus on deficits in attachment and coping skills. Research now provides an empirical foundation for the issues to be addressed in treatment and for the manner in which treatment is delivered. Advances in theory and research have brought the field of sex offender treatment to the point where the empirical bases point to a structure that, if followed, seem likely to achieve the goal of reduced recidivism.

Diagnostic Issues in the Paraphilias.

PURPOSE OF REVIEW: To examine the empirical bases underlying the diagnoses of the paraphilias. We address issues concerning the reliability of these diagnoses and their implications for etiology, treatment, and prognosis. RECENT FINDINGS: Research on these issues with the paraphilias is quite limited except for those paraphilics whose interests lead them to sexually offend. Even among these clients, research has, for the most part, failed to distinguish those who meet criteria for a paraphilia from those who do not, thereby limiting the possibility of drawing firm conclusions regarding the value of a paraphilic diagnosis. Speculations regarding the etiology of the paraphilias are for the most part limited to those who sexually offend and these theories do not distinguish those who do, or do not, meet paraphilic criteria. Treatment of sex offenders, when effective, appears to have the same impact regardless of whether or not clients meet criteria for a paraphilia. In terms of prognosis, it was only among untreated child molesters that a paraphilic diagnosis (in this case "pedophilia") predicted long-term outcome. In the face of these problems, we suggest a dimensional approach to diagnoses may represent an improvement over the current categorical model.

No Pharmacokinetic Interactions Between Elbasvir or Grazoprevir and Buprenorphine/Naloxone in Healthy Participants and Participants Receiving Stable Opioid Agonist Therapy.

The aims of these phase I trials were to evaluate the pharmacokinetic interaction between elbasvir (EBR) or grazoprevir (GZR) and buprenorphine/naloxone (BUP/NAL). Trial 1 was a single-dose trial in healthy participants. Trial 2 was a multiple-dose trial in participants on BUP/NAL maintenance therapy. Coadministration of EBR or GZR with BUP/NAL had minimal effect on the pharmacokinetics of BUP/NAL, EBR, and GZR. The geometric mean ratios (GMRs (90% CI)) for BUP, norbuprenorphine, and NAL AUC0-∞ were 0.98 (0.89-1.08), 0.97 (0.86-1.09), and 0.88 (0.78-1.00) in the presence/absence of EBR; 0.98 (0.81-1.19), 1.13 (0.97-1.32), and 1.10 (0.82-1.47) in the presence/absence of GZR. The GMRs (90% CI) for EBR and GZR AUC0-∞ in the absence/presence of BUP/NAL were 1.22 (0.98-1.52) and 0.86 (0.63-1.18). In conclusion, no dose adjustment for BUP/NAL, EBR, or GZR is required for patients with HCV infection receiving EBR/GZR and BUP/NAL maintenance therapy.

No Pharmacokinetic Interactions Between Elbasvir or Grazoprevir and Methadone in Participants Receiving Maintenance Opioid Agonist Therapy.

We conducted two phase I trials to evaluate the pharmacokinetic interactions between elbasvir (EBR), grazoprevir (GZR), and methadone (MK-8742-P010 and MK-5172-P030) in non-hepatitis C virus (HCV)-infected participants on methadone maintenance therapy. Coadministration of EBR or GZR with methadone had no clinically meaningful effect on EBR, GZR, or methadone pharmacokinetics. The geometric mean ratios (GMRs) for R- and S-methadone AUC0-24 were 1.03 (90% confidence interval (CI), 0.92-1.15) and 1.09 (90% CI, 0.94-1.26) in the presence/absence of EBR; and 1.09 (90% CI, 1.02-1.17) and 1.23 (90% CI, 1.12-1.35) in the presence/absence of GZR. The GMRs for EBR and GZR AUC0-24 in participants receiving methadone relative to a healthy historical cohort not receiving methadone were 1.20 (90% CI, 0.94-1.53) and 1.03 (90% CI, 0.76-1.41), respectively. These results indicate that no dose adjustment is required for individuals with HCV infection receiving stable methadone therapy and the EBR/GZR fixed-dose regimen.

Pharmacokinetics and Tolerability of Letermovir Coadministered With Azole Antifungals (Posaconazole or Voriconazole) in Healthy Subjects.

Letermovir is a human cytomegalovirus terminase inhibitor for cytomegalovirus infection prophylaxis in hematopoietic stem cell transplant recipients. Posaconazole (POS), a substrate of glucuronosyltransferase and P-glycoprotein, and voriconazole (VRC), a substrate of CYP2C9/19, are commonly administered to transplant recipients. Because coadministration of these azoles with letermovir is expected, the effect of letermovir on exposure to these antifungals was investigated. Two trials were conducted in healthy female subjects 18 to 55 years of age. In trial 1, single-dose POS 300 mg was administered alone, followed by a 7-day washout; then letermovir 480 mg once daily was given for 14 days with POS 300 mg coadministered on day 14. In trial 2, on day 1 VRC 400 mg was given every 12 hours; on days 2 and 3, VRC 200 mg was given every 12 hours, and on day 4 VRC 200 mg. On days 5 to 8, letermovir 480 mg was given once daily. Days 9 to 12 repeated days 1 to 4 coadministered with letermovir 480 mg once daily. In both trials, blood samples were collected for the assessment of the pharmacokinetic profiles of the antifungals, and safety was assessed. The geometric mean ratios (90%CIs) for POS+letermovir/POS area under the curve and peak concentration were 0.98 (0.83, 1.17) and 1.11 (0.95, 1.29), respectively. Voriconazole+letermovir/VRC area under the curve and peak concentration geometric mean ratios were 0.56 (0.51, 0.62) and 0.61 (0.53, 0.71), respectively. All treatments were generally well tolerated. Letermovir did not affect POS pharmacokinetics to a clinically meaningful extent but decreased VRC exposure. These results suggest that letermovir may be a perpetrator of CYP2C9/19-mediated drug-drug interactions.

Pharmacokinetics, Safety, and Tolerability of Single-Dose Elbasvir in Participants with Hepatic Impairment.

BACKGROUND: The combination of elbasvir and grazoprevir is approved for the treatment of hepatitis C virus genotype 1 or 4 infection. OBJECTIVE: To evaluate the pharmacokinetics and safety of single-dose elbasvir 50 mg in participants with hepatic impairment. METHODS: Participants with mild, moderate, or severe hepatic impairment and age-, sex-, and weight-matched healthy controls were enrolled in a 3-part, open-label, sequential-panel, single-dose pharmacokinetic study. Blood samples were collected to assess pharmacokinetics. Safety and tolerability were assessed throughout the study. RESULTS: Thirty-four participants were enrolled: eight with mild hepatic impairment, 11 with moderate hepatic impairment, seven with severe hepatic impairment, and eight healthy matched controls. Participants with mild, moderate, and severe hepatic impairment demonstrated a numeric, but not statistically significant, decrease in elbasvir exposure compared with controls, with a mean 39, 28, and 12% decrease in area under the concentration-time curve from time 0 extrapolated to infinity, as well as a 42, 31, and 42% decrease in maximum plasma concentration (C max), respectively. The observed median time to C max was similar in participants with hepatic impairment and controls. Single-dose administration of elbasvir was well tolerated. CONCLUSIONS: The pharmacokinetics of elbasvir after a single, oral 50-mg dose were not clinically meaningfully altered in non-HCV-infected participants with mild, moderate, or severe hepatic dysfunction. However, since elbasvir is currently available only as part of a fixed-dose combination with grazoprevir, the fixed-dose combination should not be administered to patients with moderate or severe hepatic impairment, due to the significantly increased plasma grazoprevir exposures in those populations.

No clinically meaningful pharmacokinetic interaction between the hepatitis C virus inhibitors elbasvir and grazoprevir and the oral contraceptives ethinyl estradiol and levonorgestrel.

PURPOSE: Oral contraceptive pills (OCPs) are an important element of hepatitis C virus (HCV) treatment in women of childbearing potential. These studies evaluated the safety and pharmacokinetic interactions between elbasvir (EBR) and grazoprevir (GZR) and ethinyl estradiol/levonorgestrel (EE/LNG). METHODS: Both studies were open-label, single-site, two-period, fixed-sequence, one-way interaction studies. In period 1, subjects received one tablet of EE/LNG (0.03 mg/0.15 mg). In period 2, subjects received EBR (50 mg once daily) for 13 days or GZR (200 mg once daily) for 10 days, with one tablet of EE/LNG on day 7 (GZR group) or 10 (EBR group). Each study enrolled 20 healthy, nonsmoking adult females. RESULTS: There was no clinically meaningful effect of multiple doses of EBR or GZR on the pharmacokinetics of EE or LNG. Geometric mean ratios (GMRs) for AUC0-∞ and Cmax in the presence and absence of EBR were 1.01 and 1.10 for EE and 1.14 and 1.02 for LNG, with 90% confidence intervals (CIs) that were contained in the interval [0.80, 1.25]. Similarly, the AUC0-∞ and Cmax GMRs in the presence and absence of GZR were 1.10 and 1.05 for EE and 1.23 and 0.93 for LNG, respectively. The 90% CIs for EE AUC0-∞ and for EE and LNG Cmax were contained in the interval [0.80, 1.25]; however, the 90% CI for the LNG AUC0-∞ [1.15, 1.32] slightly exceeded the upper bound. CONCLUSIONS: These results suggest that EBR/GZR can be co-administered to female patients with HCV of childbearing potential who are on OCPs to prevent pregnancy.

Susceptibilities of genotype 1a, 1b, and 3 hepatitis C virus variants to the NS5A inhibitor elbasvir.

Elbasvir is an investigational NS5A inhibitor with in vitro activity against multiple HCV genotypes. Antiviral activity of elbasvir was measured in replicons derived from wild-type or resistant variants of genotypes 1a, 1b, and 3. The barrier to resistance was assessed by the number of resistant colonies selected by exposure to various elbasvir concentrations. In a phase 1b dose-escalating study, virologic responses were determined in 48 noncirrhotic adult men with chronic genotype 1 or 3 infections randomized to placebo or elbasvir from 5 to 50 mg (genotype 1) or 10 to 100 mg (genotype 3) once daily for 5 days. The NS5A gene was sequenced from plasma specimens obtained before, during, and after treatment. Elbasvir suppressed the emergence of resistance-associated variants (RAVs) in vitro in a dose-dependent manner. Variants selected by exposure to high elbasvir concentrations typically encoded multiple amino acid substitutions (most commonly involving loci 30, 31, and 93), conferring high-level elbasvir resistance. In the monotherapy study, patients with genotype 1b had greater reductions in HCV RNA levels than patients with genotype 1a at all elbasvir doses; responses in patients with genotype 3 were generally less pronounced than for genotype 1, particularly at lower elbasvir doses. M28T, Q30R, L31V, and Y93H in genotype 1a, L31V and Y93H in genotype 1b, and A30K, L31F, and Y93H in genotype 3 were the predominant RAVs selected by elbasvir monotherapy. Virologic findings in patients were consistent with the preclinical observations. NS5A-RAVs emerged most often at amino acid positions 28, 30, 31, and 93 in both the laboratory and clinical trial. (The MK-8742 P002 trial has been registered at ClinicalTrials.gov under identifier NCT01532973.).

Psychological Treatment of the Paraphilias: a Review and an Appraisal of Effectiveness.

Initially, this paper notes that treatment for the paraphilias has been most thoroughly described and evaluated within the context of treating sex offenders (i.e., child molesters, rapists, and exhibitionists). We note that the literature does not always carefully distinguish "pedophiles" from other child molesters and that rapists are often identified as having a "Not Otherwise Specified" paraphilia. Both these practices appear problematic. We then outline current approaches to the treatment of sex offenders which have typically been seen as relevant to dealing with all types of paraphilias. The historical emergence of sex offender treatment is noted, leading to an outline of current approaches that address known problematic issues by employing established procedures and by delivering treatment in an empirically based manner. We conclude with a description of evaluations of the effectiveness of these treatment approaches which indicate overall positive outcomes.

A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection.

Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Factor-κB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction. We show that A51R is also critical for VACV replication in vertebrate cells and for pathogenesis in mice. Interestingly, A51R colocalizes with, and stabilizes, host microtubules and also associates with ubiquitin. We show that A51R promotes viral protein stability, possibly by preventing ubiquitin-dependent targeting of viral proteins for destruction. Importantly, our studies reveal exciting new opportunities to study virus-host interactions in experimentally-tractable Lepidopteran systems.

Sexual sadism: current diagnostic vagueness and the benefit of behavioral definitions.

The phenomenon of sexual sadism was first scientifically described by Richard von Krafft-Ebing in 1999 as a sexual preference disorder that focuses on the infliction of suffering, pain, or humiliation to achieve sexual gratification. The present article reviews the historical development of the term sexual sadism, including the current descriptive nosology of psychiatric classification. Despite clear definitions that specify the sexual objects, duration, and distress necessary for a disorder, evidence for the diagnostic reliability for sexual sadism in the forensic domain is mixed. We argue that the reliance on the patient's willingness to divulge corresponding violent sexual fantasies is the Achilles' heel of the diagnosis. In an attempt to improve agreement across diagnosticians, we argue for the use of behavioral indicators. We summarize the extant research on the Severe Sexual Sadism Scale (SESAS), which is a file-based observer rating of pertinent crime-scene actions. We conclude that the analysis of crime-scene behavior, as achieved with the SESAS, can provide a useful complement for the clinical diagnosis in forensic psychiatry and psychology.

Viral infection: an evolving insight into the signal transduction pathways responsible for the innate immune response.

The innate immune response is initiated by the interaction of stereotypical pathogen components with genetically conserved receptors for extracytosolic pathogen-associated molecular patterns (PAMPs) or intracytosolic nucleic acids. In multicellular organisms, this interaction typically clusters signal transduction molecules and leads to their activations, thereby initiating signals that activate innate immune effector mechanisms to protect the host. In some cases programmed cell death-a fundamental form of innate immunity-is initiated in response to genotoxic or biochemical stress that is associated with viral infection. In this paper we will summarize innate immune mechanisms that are relevant to viral pathogenesis and outline the continuing evolution of viral mechanisms that suppress the innate immunity in mammalian hosts. These mechanisms of viral innate immune evasion provide significant insight into the pathways of the antiviral innate immune response of many organisms. Examples of relevant mammalian innate immune defenses host defenses include signaling to interferon and cytokine response pathways as well as signaling to the inflammasome. Understanding which viral innate immune evasion mechanisms are linked to pathogenesis may translate into therapies and vaccines that are truly effective in eliminating the morbidity and mortality associated with viral infections in individuals.

Characterization of poxvirus-encoded proteins that regulate innate immune signaling pathways.

Innate immune recognition of pathogens is critical to the prompt control of infections, permitting the host to survive to develop long-term immunity via an adaptive immune response. Poxviruses encode a family of proteins that inhibit signaling by Toll-like receptors to their downstream signaling components, severely limiting nuclear translocation of transcription factors such as IRF3 and NF-κB and thereby decreasing production of host interferons and cytokines. We describe bioinformatics techniques for identifying candidate poxviral inhibitors of the innate immune response based on similarity to the family of proteins that includes A52, A46, and N1. Robust luciferase assays can determine whether a given poxviral gene affects innate immune signaling, and in combination with other approaches can identify the cellular targets of poxviral innate immune evasion genes. Because apoptosis is an innate immune response of the cell to viral infection, assays for identifying poxviral genes that inhibit apoptosis can also be employed. Novel poxviral innate immune inhibitors are being identified via several approaches and these techniques promise to identify further complexities in the way that poxviruses interact with the host innate immune system.

Mindreading abilities in sexual offenders: an analysis of theory of mind processes.

The paper aims to assess the theory of mind (ToM) of sexual offenders. We administered to 21 sexual offenders and to 21 nonoffenders two classical first- and second-order ToM tasks, a selection of six Strange Stories, and a semi-structured interview, the Theory of Mind Assessment Scale (Th.o.m.a.s), which provides a multi-dimensional evaluation of ToM, investigating first- vs. third-person and egocentric vs. allocentric perspectives. Results show that sexual offenders performed worse than controls on second-order ToM tasks, on Strange Stories and on each of the Th.o.m.a.s dimensions, whereas they did as well as the control group on first-order ToM tasks. A detailed analysis of participants' performance on Th.o.m.a.s. showed that sex offenders performed worse on the third-person than on the first-person ToM scale, and worse on the allocentric than on the egocentric perspective; these findings did not apply to the controls. Implications for future research and treatment are discussed.

The importance of individual differences in pornography use: theoretical perspectives and implications for treating sexual offenders.

This article reviews the extant literature regarding pornography's influence on antisocial attitudes, sexual arousal, and sexually aggressive behavior in both noncriminal and criminal samples. The article concludes that when examined in the context of multiple, interacting factors, the findings are highly consistent across experimental and nonexperimental studies and across differing populations in showing that pornography use can be a risk factor for sexually aggressive outcomes, principally for men who are high on other risk factors and who use pornography frequently. Finally, this article presents theoretical implications based on these findings, as well as some clinical implications relevant to the assessment and treatment of sexual offenders.