"One a Day Keeps the Prison Away": Understanding the Experiences of Individuals Convicted of Sexual Offences Receiving Anti-Androgens for the Treatment of Problematic Sexual Arousal.

Problematic sexual arousal (PSA) is an umbrella term to describe a range of clinical presentations related to excessive sexual thinking (e.g., sexual preoccupation) and sexual behavior (e.g., hypersexuality). Although such concepts are known to affect sexual recidivism among individuals convicted of sexual offences, PSA is not routinely or directly targeted in offending behavior programs in England and Wales. However, in recent years, there have been moves to incorporate pharmacological interventions for addressing this among people with sexual offence histories. Although some work to understand the experiences of those taking SSRI medication for this purpose has emerged, little is known about the experiences of service users taking anti-androgen medication. In this study, we interviewed all individuals in prison taking anti-androgens for the treatment of problematic sexual arousal following convictions for sexual offences in England at the time of data collection (N = 10). Using a phenomenologically oriented thematic analysis, we established themes pertaining to "Differing needs: Motivations for treatment," "Medication as a risk management strategy," and how the medication helped the men in their pursuit of "Discovering a 'new me'." This work contributes important knowledge to inform the development of ethical and effective prescribing of anti-androgen medication with this population and offer recommendations for both future research and the development of clinical practice.

Mediating role for metacognitive processes in the relationship between schizotypy and anxiety and depression symptoms.

Introduction: Depression and anxiety symptoms are highly prevalent in schizophrenia-spectrum disorders and are commonly associated with schizotypy in non-clinical samples. However, it remains unclear what factors could be contributing to the relationships between schizotypy and anxiety and depression symptoms. Using path analysis, we explored the complex interplay between schizotypy, metacognitive beliefs, cognitive insight, and symptoms of emotional distress.Methods: Self-report data of schizotypy, metacognitive beliefs, cognitive insight, depression, and anxiety symptoms were collected from 344 participants from a predominantly student sample.Results: Path analysis confirmed unique associations between schizotypy dimensions, metacognitive beliefs, and cognitive insight. Furthermore, negative beliefs about worry mediated the link between the schizotypy dimensions, unusual experiences, cognitive disorganisation, and introvertive anhedonia and both depression and anxiety symptoms. Lack of cognitive confidence also mediated the relationship between cognitive disorganisation and depression symptoms. Finally, the cognitive insight subcomponent self-reflectiveness mediated the relationship between unusual experiences and cognitive disorganisation and anxiety.Conclusions: This study significantly furthers our understanding of the complex relationship between schizotypy, metacognitive processes, and emotional distress. Our findings also provide support for interventions which modify metacognitive beliefs and self-reflectiveness, which may prove beneficial for treatment in clinical settings.

"I've Got the Energy to Change, But I Haven't Got the Energy for This Kinda Therapy": A Qualitative Analysis of the Motivations Behind Democratic Therapeutic Community Drop-Out for Men With Sexual Convictions.

Prison-based democratic therapeutic communities (TCs) provide an alternative to mainstream prison, where prisoners can work on psychological difficulties and address offending behavior. Research demonstrates TCs are effective at reducing reoffending rates for residents who stay in therapy 18+ months, and those who drop out of TCs offend at a significantly higher rate than those who complete therapy. Thus, it is important to reduce attrition in TCs. No research has yet explored the explanations for TC drop out offered by those with sexual convictions. The present study uses Interpretive Phenomenological Analysis to qualitatively explore the accounts of men with sexual convictions (n = 7) who dropped out of a TC in a UK prison. Results highlight that issues surrounding external responsivity, therapeutic relationships, and treatment readiness were salient in the participants' accounts of drop out. This research has implications for TCs seeking to better understand and address attrition of people with sexual convictions.

psiCLIP reveals dynamic RNA binding by DEAH-box helicases before and after exon ligation.

RNA helicases remodel the spliceosome to enable pre-mRNA splicing, but their binding and mechanism of action remain poorly understood. To define helicase-RNA contacts in specific spliceosomal states, we develop purified spliceosome iCLIP (psiCLIP), which reveals dynamic helicase-RNA contacts during splicing catalysis. The helicase Prp16 binds along the entire available single-stranded RNA region between the branchpoint and 3'-splice site, while Prp22 binds diffusely downstream of the branchpoint before exon ligation, but then switches to more narrow binding in the downstream exon after exon ligation, arguing against a mechanism of processive translocation. Depletion of the exon-ligation factor Prp18 destabilizes Prp22 binding to the pre-mRNA, suggesting that proofreading by Prp22 may sense the stability of the spliceosome during exon ligation. Thus, psiCLIP complements structural studies by providing key insights into the binding and proofreading activity of spliceosomal RNA helicases.

Differences between staff groups in perception of risk assessment and risk management of inappropriate sexual behaviour in patients with traumatic brain injury.

This research explored staff perceptions of risk assessment and management of inappropriate sexual behaviour (ISB) displayed in patients following a Traumatic Brain Injury (TBI). The primary focus was to determine differences in perceptions between qualified (N = 40) and direct care staff (N = 47). Vignettes depicting ISB displayed by a male following a TBI were rated. The vignettes varied in behaviour (intimate versus non-contact) and age of the victim (child versus adult). Ratings for causal explanations (poor management, attention seeking, negative emotion and education), attributions (need for action and increase awareness) and emotions were analysed alongside risk assessment and management variables. Intimate contact ISB and ISB directed towards a child were perceived to be more serious and in need of intervention. Direct care staff perceived ISB to be due to sexual motivations, poor emotion control and to seek attention. They elicited greater negative emotions and based their judgements of risk on seriousness. On the other hand, qualified staff were more concerned about implementing interventions based on the risk of recurrence. Differences between staff groups could cause conflict regarding the assessment and management of ISB in TBI. Training to increase awareness of the behaviour could minimise differences and produce greater cohesion within clinical practise.

Postcatalytic spliceosome structure reveals mechanism of 3'-splice site selection.

Introns are removed from eukaryotic messenger RNA precursors by the spliceosome in two transesterification reactions-branching and exon ligation. The mechanism of 3'-splice site recognition during exon ligation has remained unclear. Here we present the 3.7-angstrom cryo-electron microscopy structure of the yeast P-complex spliceosome immediately after exon ligation. The 3'-splice site AG dinucleotide is recognized through non-Watson-Crick pairing with the 5' splice site and the branch-point adenosine. After the branching reaction, protein factors work together to remodel the spliceosome and stabilize a conformation competent for 3'-splice site docking, thereby promoting exon ligation. The structure accounts for the strict conservation of the GU and AG dinucleotides at the 5' and 3' ends of introns and provides insight into the catalytic mechanism of exon ligation.

High-frequency gamblers show increased resistance to extinction following partial reinforcement.

Behaviours that have been rewarded intermittently persist for longer during periods of non-reward than behaviours that have been rewarded continuously. This classic phenomenon is known as the partial reinforcement extinction effect. For decades it has been generally understood that this phenomenon is fundamental to the persistence of gambling in the absence of winning. One obvious, yet untested hypothesis arising from this is that persistent (here, high-frequency) gamblers might be more sensitive to partial reinforcement contingencies. Therefore, our aim was to test the hypothesis that compared to low-frequency gamblers, high-frequency gamblers would show greater resistance to extinction following partial reinforcement in a computer based experiment. Participants were 19 high-frequency gamblers and 21 low-frequency gamblers, all healthy non-smokers aged between 18 and 52. Following partial or continuous reinforcement, persistence of responding in extinction was measured as the number of times a target response was made. After partial reinforcement, high-frequency gamblers made the target response a greater number of times in extinction (compared to low-frequency gamblers). Moreover, the partial reinforcement extinction effect was larger in high-frequency gamblers than in low-frequency gamblers. It remains to be seen whether increased sensitivity to partial reinforcement is a cause or effect of persistent gambling. Nevertheless, the present study represents an important first step in investigating the role of simple partial reinforcement contingencies in determining resistance to extinction in gamblers, the importance of which, whilst hitherto recognised, has never been demonstrated experimentally.

Effects of a neurotensin analogue (PD149163) and antagonist (SR142948A) on the scopolamine-induced deficits in a novel object discrimination task.

Various lines of evidence suggest a role in cognition for the endogenous neuropeptide, neurotensin, involving an interaction with the central nervous system cholinergic pathways. A preliminary study has shown that central administration of neurotensin enhances spatial and nonspatial working memory in the presence of scopolamine, a muscarinic receptor antagonist which induces memory deficits. Utilizing similar methods, the present study employed a two-trial novel object discrimination task to determine the acute effect of a neurotensin peptide analogue with improved metabolic stability, PD149163, on recognition memory in Lister hooded rats. Consistent with previous findings with neurotensin, animals receiving an intracerebroventricular injection of PD149163 (3 microg) significantly discriminated the novel from familiar object during the choice trial. In addition, a similar dose of PD149163 restored the scopolamine-induced deficit in novelty recognition. The restoration effect on scopolamine-induced amnesia produced by PD149163 was blocked by SR142948A, a nonselective neurotensin receptor antagonist, at a dose of 1 mg/kg (intraperitonial) but not at 0.1 mg/kg. In conclusion, the present results confirm a role for neurotensin in mediating memory processes, possibly via central cholinergic mechanisms.

Dissection of Prp8 protein defines multiple interactions with crucial RNA sequences in the catalytic core of the spliceosome.

Current models of the core of the spliceosome include a network of RNA-RNA interactions involving the pre-mRNA and the U2, U5, and U6 snRNAs. The essential spliceosomal protein Prp8 interacts with U5 and U6 snRNAs and with specific pre-mRNA sequences that participate in catalysis. This close association with crucial RNA sequences, together with extensive genetic evidence, suggests that Prp8 could directly affect the function of the catalytic core, perhaps acting as a splicing cofactor. However, the sequence of Prp8 is almost entirely novel, and it offers few clues to the molecular basis of Prp8-RNA interactions. We have used an innovative transposon-based strategy to establish that catalytic core RNAs make multiple contacts in the central region of Prp8, underscoring the intimate relationship between this protein and the catalytic center of the spliceosome. Our analysis of RNA interactions identifies a discrete, highly conserved region of Prp8 as a prime candidate for the role of cofactor for the spliceosome's RNA core.

Prp8p dissection reveals domain structure and protein interaction sites.

We describe a novel approach to characterize the functional domains of a protein in vivo. This involves the use of a custom-built Tn5-based transposon that causes the expression of a target gene as two contiguous polypeptides. When used as a genetic screen to dissect the budding yeast PRP8 gene, this showed that Prp8 protein could be dissected into three distinct pairs of functional polypeptides. Thus, four functional domains can be defined in the 2413-residue Prp8 protein, with boundaries in the regions of amino acids 394-443, 770, and 2170-2179. The central region of the protein was resistant to dissection by this approach, suggesting that it represents one large functional unit. The dissected constructs allowed investigation of factors that associate strongly with the N- or the C-terminal Prp8 protein fragments. Thus, the U5 snRNP protein Snu114p associates with Prp8p in the region 437-770, whereas fragmenting Prp8p at residue 2173 destabilizes its association with Aar2p.

Haloperidol can increase responding to both discrete and contextual cues in trace conditioned rats.

Haloperidol has been shown to enhance attentional selectivity in conditioning procedures. For example, in latent inhibition (LI) it improves animals' ability to treat as irrelevant, stimuli that have previously been presented without consequence. The present study tested whether this finding would generalize to other procedures that present animals with weak predictors. We therefore used a trace conditioning procedure to present rats with a conditioned stimulus (CS) weakened through temporal discontiguity (rather than preexposure in LI) and a flashing light background provided an alternative experimental stimulus. In Experiment 1, a noise CS was paired contiguously (at '0 s') with food or at a 10 s trace interval. In Experiment 2, the trace interval was lengthened to 20 s. In both experiments, haloperidol treatment generally reduced responding in 0 s contiguous groups. By contrast, 0.03 mg/kg haloperidol enhanced conditioning, selectively, to the weakly predictive trace CS, though it was without effect on responding within the trace interval. In addition, again at 0.03 mg/kg, haloperidol significantly increased excitatory conditioning to contextual stimuli in trace groups relative to contiguous groups. At the shorter (10 s) Experiment 1 trace, this result was shown in the extinction test of conditioning to the background stimulus. At the longer (20 s) Experiment 2 trace, this result was shown in the acquisition of responding to the box context in the inter-trial-interval. The demonstration that low dose haloperidol can increase conditioning is novel. This increase was seen selectively with stimuli (both trace-conditioned and contextual) that should have been treated as weak predictors so these results are contrary to what was expected on the basis of haloperidol effects on stimuli weakened through pre-exposure. The possibility that increased contextual conditioning could be relevant to the interpretation of haloperidol-induced enhancement of LI is discounted. However, it is suggested that this result could nonetheless reflect cognitive enhancement.

Intraventricular 5,7-dihydroxytryptamine lesions disrupt acquisition of working memory task rules but not performance once learned.

The serotonergic system is implicated in learning and memory and its disorder, e.g. after 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") abuse. This study examined the effects of widespread depletion of serotonin (5-HT) using intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) on the learning of a working memory task in the dark agouti (DA) rat. The lesion impaired acquisition but not later performance of a nonspatial working memory rule, as measured using nonmatch to sample object recognition in the Y-maze. The lesion had a marginal effect on choice completion times over the course of testing. However, nonspecific effects did not provide a good account of the reduction in choice accuracy as this persisted when completion times were taken into account statistically. Similarly, in a second experiment, the same lesioned rats were slowed in the acquisition of spatial alternation in the T-maze. However, in the open field, there were no comparably long-lasting effects of the serotonergic depletion on line crossings and defecation, only a transient reduction in activity on the first day.Together, these data suggest that the serotonergic system is important in the acquisition of working memory tasks in the rat and that this outcome was unlikely to be the result of nonspecific effects of the lesion.