Conceptual and Empirical Issues in Pedohebephilic Interest

Male sexual attraction to children is central for understanding and preventing sexual offending against children. The current research aimed to examine conceptual and empirical issues in how we understand, treat, and measure pedohebephilic interests in men with histories of sexual offences. Chapter 2 and 3 presents a taxometric analysis of phallometric measures of pedophilic interest. The results of the taxometric analysis indicated that pedophilic interest is distributed as three latent categories. In post-hoc analyses, the three categories were characterized as having non-pedophilic, non-preferentially pedophilic, and preferentially pedophilic interest. Chapter 4 presents a meta-analysis of research examining the effect of interventions in reducing pedophilic arousal in men with histories of sexual offences against children. The results of the meta-analysis suggest that behavioural and pharmacological interventions were associated with significant decreases in sexual arousal. Some of these interventions showed magnitudes of change that were greater than estimated natural history processes and men in some of these interventions showed posttreatment levels of arousal comparable to non-offending men. Men with the highest levels of pretreatment pedophilic arousal demonstrated the greatest amount of change over the course of treatment. In contrast, no intervention approaches were associated with increases in arousal to adults. Chapter 5 examined convergent and predictive validity in three measures of pedophilic interest. The results indicate that a phallometric test and the Violence Risk Scale-Sexual Offense version’s (VRS-SO) Sexual Deviance factor showed convergence, while the Screening Scale for Pedophilic Interest (SSPI) demonstrated somewhat less convergence with the other measures. Similarly, the phallometric test and the Sexual Deviance factor of the VRS-SO were predictive of sexual recidivism and the VRS-SO remained a significant predictor after controlling for static risk. The SSPI was not predictive of sexual recidivism. Within the phallometric test, the predictive validity of different latent structural models of pedophilic interest were examined. Across the models, a dimensional model and a trichotomous model received the most support, with the latter remaining predictive of sexual recidivism after controlling for static risk. Taken together, the results identify the need for replication studies examining latent structure in pedophilic interest, demonstrate the potential for treatment to help improve men’s ability to regulate their sexual arousal, and provide further validity evidence for measures of pedophilic interest

Taking the Pulse: perceptions of crime trends and community safety and support for crime control methods in the Canadian Prairies

The present study analyzed crime survey data extracted from the 2012 Saskatchewan Taking the Pulse survey on a sample of 1,700 adult Saskatchewan residents. The focus was on examining perceptions of crime trends, perceived effectiveness of various methods for controlling crime, and their sociodemographic correlates. The majority of survey respondents perceived crime in general to be on the rise (37%) or to have not changed at all (48%) over the last three years. Individuals who perceived crime to have decreased were significantly more likely to support alternatives to punishment as effective methods for reducing crime, while individuals who perceived crime to be on the rise were twice as likely to support the use of punitive methods. Perceptions of community safety were unrelated to preference for one crime reduction method over another. Education level was inversely related to crime trend perceptions (r = -.14) and preference for punitive methods to reduce crime (r = -.20). Finally, the results of logistic regression indicated higher levels of education, higher income, and perceptions of crime decreasing were all uniquely associated with a preference for alternatives to punishment in reducing crime. In these analyses, younger age was predictive of a preference for alternatives in reducing youth crime, while urban residential setting was associated with a preference for alternatives to punishment in reducing crime in general

Coibamide A Induces mTOR-Independent Autophagy and Cell Death in Human Glioblastoma Cells

Coibamide A is an N-methyl-stabilized depsipeptide that was isolated from a marine cyanobacterium as part of an International Cooperative Biodiversity Groups (ICBG) program based in Panama. Previous testing of coibamide A in the NCI in vitro 60 cancer cell line panel revealed a potent anti-proliferative response and "COMPARE-negative" profile indicative of a unique mechanism of action. We report that coibamide A is a more potent and efficacious cytotoxin than was previously appreciated, inducing concentration-and time-dependent cytotoxicity (EC₅₀<100 nM) in human U87-MG and SF-295 glioblastoma cells and mouse embryonic fibroblasts (MEFs). This activity was lost upon linearization of the molecule, highlighting the importance of the cyclized structure for both anti-proliferative and cytotoxic responses. We show that coibamide A induces autophagosome accumulation in human glioblastoma cell types and MEFs via an mTOR-independent mechanism; no change was observed in the phosphorylation state of ULK1 (Ser-757), p70 S6K1 (Thr-389), S6 ribosomal protein (Ser-235/236) and 4EBP-1 (Thr-37/46). Coibamide A also induces morphologically and biochemically distinct forms of cell death according to cell type. SF-295 glioblastoma cells showed caspase-3 activation and evidence of apoptotic cell death in a pattern that was also seen in wild-type and autophagy-deficient (ATG5-null) MEFs. In contrast, cell death in U87-MG glioblastoma cells was characterized by extensive cytoplasmic vacuolization and lacked clear apoptotic features. Cell death was attenuated, but still triggered, in Apaf-1-null MEFs lacking a functional mitochondria-mediated apoptotic pathway. From the study of ATG5-null MEFs we conclude that a conventional autophagy response is not required for coibamide A-induced cell death, but likely occurs in dying cells in response to treatment. Coibamide A represents a natural product scaffold with potential for the study of mTOR-independent signaling and cell death mechanisms in apoptotic-resistant cancer cells

The evidence base for circulating tumour DNA blood-based biomarkers for the early detection of cancer: a systematic mapping review

Background: The presence of circulating cell-free DNA from tumours in blood (ctDNA) is of major importance to those interested in early cancer detection, as well as to those wishing to monitor tumour progression or diagnose the presence of activating mutations to guide treatment. In 2014, the UK Early Cancer Detection Consortium undertook a systematic mapping review of the literature to identify blood-based biomarkers with potential for the development of a non-invasive blood test for cancer screening, and which identified this as a major area of interest. This review builds on the mapping review to expand the ctDNA dataset to examine the best options for the detection of multiple cancer types. Methods: The original mapping review was based on comprehensive searches of the electronic databases Medline, Embase, CINAHL, the Cochrane library, and Biosis to obtain relevant literature on blood-based biomarkers for cancer detection in humans (PROSPERO no. CRD42014010827). The abstracts for each paper were reviewed to determine whether validation data were reported, and then examined in full. Publications concentrating on monitoring of disease burden or mutations were excluded. Results: The search identified 94 ctDNA studies meeting the criteria for review. All but 5 studies examined one cancer type, with breast, colorectal and lung cancers representing 60% of studies. The size and design of the studies varied widely. Controls were included in 77% of publications. The largest study included 640 patients, but the median study size was 65 cases and 35 controls, and the bulk of studies (71%) included less than 100 patients. Studies either estimated cfDNA levels non-specifically or tested for cancer-specific mutations or methylation changes (the majority using PCR-based methods). Conclusion: We have systematically reviewed ctDNA blood biomarkers for the early detection of cancer. Pre-analytical, analytical, and post-analytical considerations were identified which need to be addressed before such biomarkers enter clinical practice. The value of small studies with no comparison between methods, or even the inclusion of controls is highly questionable, and larger validation studies will be required before such methods can be considered for early cancer detection

Is childhood sexual victimization associated with cognitive distortions, self-esteem, and emotional congruence with children?

The current paper examined the association between childhood sexual victimization (CSV) and constructs thought to be relevant for sexual offending in secondary analyses of three samples of adult males who committed sexual offences against children (N = 16, 28, and 20). Compared to participants who reported no CSV, those who reported CSV exhibited slightly to moderately more cognitive distortions and moderately to largely less negative evaluations of sexual offending against children; slightly to moderately higher self-esteem, positive evaluation of people who commit sexual offences, and identification with people who commit sexual offences against children; and much more emotional congruence with children. Our findings suggest that CSV may be associated with variables presumed to play a role in sexual offending against children. However, given the small sample sizes and other limitations of our studies, our evidence does not permit conclusions regarding causal relationships and any novel findings require replication

Coibamide A Induces mTOR-Independent Autophagy and Cell Death in Human Glioblastoma Cells

Coibamide A is an N-methyl-stabilized depsipeptide that was isolated from a marine cyanobacterium as part of an International Cooperative Biodiversity Groups (ICBG) program based in Panama. Previous testing of coibamide A in the NCI in vitro 60 cancer cell line panel revealed a potent anti-proliferative response and "COMPARE-negative" profile indicative of a unique mechanism of action. We report that coibamide A is a more potent and efficacious cytotoxin than was previously appreciated, inducing concentration- and time-dependent cytotoxicity (EC50<100 nM) in human U87-MG and SF-295 glioblastoma cells and mouse embryonic fibroblasts (MEFs). This activity was lost upon linearization of the molecule, highlighting the importance of the cyclized structure for both anti-proliferative and cytotoxic responses. We show that coibamide A induces autophagosome accumulation in human glioblastoma cell types and MEFs via an mTOR-independent mechanism; no change was observed in the phosphorylation state of ULK1 (Ser-757), p70 S6K1 (Thr-389), S6 ribosomal protein (Ser-235/236) and 4EBP-1 (Thr-37/46). Coibamide A also induces morphologically and biochemically distinct forms of cell death according to cell type. SF-295 glioblastoma cells showed caspase-3 activation and evidence of apoptotic cell death in a pattern that was also seen in wild-type and autophagy-deficient (ATG5-null) MEFs. In contrast, cell death in U87-MG glioblastoma cells was characterized by extensive cytoplasmic vacuolization and lacked clear apoptotic features. Cell death was attenuated, but still triggered, in Apaf-1-null MEFs lacking a functional mitochondria-mediated apoptotic pathway. From the study of ATG5-null MEFs we conclude that a conventional autophagy response is not required for coibamide A-induced cell death, but likely occurs in dying cells in response to treatment. Coibamide A represents a natural product scaffold with potential for the study of mTOR-independent signaling and cell death mechanisms in apoptotic-resistant cancer cells

Emotional Congruence with Children: Are Implicit and Explicit Child-Like Self-Concept and Attitude Toward Children Associated with Sexual Offending Against Children?

Some men convicted of sexual offences against children express an exaggerated affiliation with childhood, ascribe child-like characteristics to themselves, experience strong non-sexual liking of children, and hold positive views of children and childhood. These features are generally called emotional congruence with children. The present study examined child-like self-concept, which is an association of self with children and child-like characteristics, attitude toward children, and general emotional congruence with children as correlates of sexual offending against children and pedophilia. Male participants (18 sexual offenders against unrelated children; 7 incest offenders; 22 non-sexual offenders; 54 students) completed newly developed implicit and explicit measures of child-like self-concept and attitude toward children, as well as more established self-report measures of emotional congruence with children. Assessments of pedophilic interest and sexual recidivism risk were obtained from official file information. Sexual offenders against unrelated children reported higher levels of implicit child-like self-concept and self-reported emotional congruence with children when compared to the other three groups. Implicit child-like self-concept showed a small correlation with emotional congruence measures, whereas implicit attitude toward children was moderately correlated with the emotional congruence measures. Implicit child-like self-concept, implicit attitude toward children, and the emotional congruence measures were associated with greate