Psychopathy and alexithymia in female offenders.

Determined the comorbidity of psychopathy and alexithymia in 37 female inmates of a medium-security prison. The authors also investigated the association between psychopathy and alexithymia with the use of affective language in response to questions about an emotional event, and with their propensity for violence. The extent of psychopathy and alexithymia were assessed with the Hare Psychopathy Checklist—Revised (PCL-R) and the Toronto Alexithymia Scale (TAS), respectively. Using standard cutoff scores, 30% were identified as psychopaths, and 32% as alexithymics. Three Ss were both psychopaths and alexithymics. The correlation between PCL-R and TAS total scores was not significant, but the socially deviant impulsive factor of the PCL-R significantly correlated with the TAS items that reflect inability to discriminate feelings and bodily sensations. Alexithymia, but not psychopathy, was negatively related to measures of affective speech content. Both psychopathy and alexithymia were associated with a history of violence. In spite of several manifest similarities, psychopathy and alexithymia appear to be different clinical constructs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synthesis and evaluation of 1-amino-6-halo-β-carbolines as antimalarial and antiprion agents

Malaria is one of the world's most devastating parasitic diseases, causing almost one million deaths each year. Growing resistance to classical antimalarial drugs, such as chloroquine, necessitates the discovery of new therapeutic agents for successful control of this global disease. Here, we report the synthesis of some 6-halo-β-carbolines as analogues of the potent antimalarial natural product, manzamine A, retaining its heteroaromatic core whilst providing compounds with much improved synthetic accessibility. Two compounds displayed superior activity to chloroquine itself against a resistant Plasmodium falciparum strain, identifying them as promising leads for future development. Furthermore, in line with previous reports of similarities in antimalarial and antiprion effects of aminoaryl-based antimalarial agents, the 1-amino-β-carboline libraries were also found to possess significant bioactivity against a prion-infected cell line.     

Structure-activity relationship refinement and further assessment of indole-3-glyoxylamides as a lead series against prion disease

Structure–activity relationships within the indole‐3‐glyoxylamide series of antiprion agents have been explored further, resulting in discovery of several new compounds demonstrating excellent activity in a cell line model of prion disease (EC₅₀ <10 nM ). After examining a range of substituents at the para‐position of the N‐phenylglyoxylamide moiety, five‐membered heterocycles containing at least two heteroatoms were found to be optimal for the antiprion effect. A number of modifications were made to probe the importance of the glyoxylamide substructure, although none were well tolerated. The most potent compounds did, however, prove largely stable towards microsomal metabolism, and the most active library member cured scrapie‐infected cells indefinitely on administration of a single treatment. The present results thereby confirm the indole‐3‐glyoxylamides as a promising lead series for continuing in vitro and in vivo evaluation against prion disease.     

Improved 2,4‐Diarylthiazole‐Based Antiprion Agents: Switching the Sense of the Amide Group at C5 Leads to an Increase in Potency

Amide derivatives of 2,4‐diarylthiazole‐5‐carboxylic acids were synthesised and tested for efficacy in a cell line model of prion disease. A number of compounds demonstrating antiprion activity were thereby identified from the screening libraries, showing improved potency and reproducibility of results relative to amide derivatives of the related 2,4‐diphenyl‐5‐aminothiazole, which have been documented previously. Thus, 'switching' the sense of the amide bond at thiazole C5 revealed a more promising lead series of potential prion disease therapeutics. Furthermore, 3,5‐diaryl‐1,2,4‐thiadiazoles isolated as by‐products during library synthesis provided a handful of additional examples possessing an antiprion effect, thereby augmenting the set of newly identified active compounds. Evaluation of binding to cellular prion protein (PrP^C) showed only weak affinities at best, suggesting that the newly identified antiprion agents do not mediate their biological effect through direct interaction with PrP^C.     

A multi-faceted approach to forecasting broadband demand andtraffic

When forecasting the development of new services, it is advisable to look closely at user demand and the way it is developing, to understand what is driving the changes in demand. Because of the varied nature of these new services, a number of different approaches to forecasting their demand can be applied. The growth in new services, as modeled in this optimistic scenario, leads to a massive increase in the volume of traffic carried by the network. This is not due solely to the growth in the number of terminals, but also to the availability of bandwidth at reasonable prices. The services would still exist if they had to operate over ISDN, but once ATM starts to be used, the available bandwidth allows application designers to incorporate the features and offer the response times needed to provide truly usable applications. This, in turn, reinforces the growth in demand