Convergent and Predictive Associations of Three Measures of Pedophilic Interest.

Pedophilic interest is a central risk factor for sexual offending against children. Multiple measures exist to assess pedophilic interest, and the present study aims to provide validity evidence for three of these measures in a sample of men convicted of sexual offenses. The association between a phallometric test for pedophilic interest, the Screening Scale for Pedophilic Interest (SSPI), and the sexual deviance factor of the Violence Risk Scale-Sexual Offense (VRS-SO) version was examined in a sample of 261 men who participated in sexual violence reduction services. The association between these measures and sexual recidivism, both as sole predictors and while controlling for static risk, was also assessed. The second aim of the study was to examine the validity of different methods for modeling the distribution of pedophilic interests, using phallometric test scores, based on the findings in recent taxometric research. The measures generally showed a positive and moderate relationship with each other and predicted sexual recidivism. However, the SSPI did not significantly predict sexual recidivism, and when controlling for static risk, only the VRS-SO Sexual Deviance factor significantly predicted this outcome. Modeling phallometric test scores continuously and trichotomously produced significant associations with sexual recidivism; however, only a trichotomous model with two levels remained predictive after controlling for static risk. The results are broadly supportive of measures of pedophilic interest and underscore the importance of appropriately modeling the latent structure of pedophilic interest.

Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

Long-term follow-up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis.

Hairy cell leukaemia (HCL) was first described 50 years ago. Median survival was then 4 years. The purine analogues, introduced in the 1980s, transformed this prognosis. We reviewed data retrospectively from 233 patients, treated with pentostatin (n = 188) or cladribine (n = 45), to investigate the current long-term outlook. Median follow-up was 16 years. There were no significant differences in outcome between the two agents. Overall, the complete response (CR) rate was 80% and median relapse-free survival was 16 years. After relapse (n = 79) or non-response (n = 5), 26 patients received pentostatin and 58 cladribine; 69% achieved CR and median relapse-free survival was 11 years. After third-line therapy (n = 23), 50% achieved CR and median relapse-free survival was 6.5 years. However, CRs were equally durable, whether after first, second or third-line therapy. Complete responders and those with both haemoglobin >100 g/l and platelet count >100 x 10(9)/l before treatment had the longest relapse-free survival (P < 0.0001). Patients still in CR at 5 years had only a 25% risk of relapse by 15 years. Outcomes for patients with recurrent disease improved with the monoclonal antibody rituximab, combined with either purine analogue. Overall only eight patients died of HCL-related causes. Patients achieving a CR can expect a normal lifespan.