Reasoning deficits among illicit drug users are associated with aspects of cannabis use.

Deficits in deductive reasoning have been observed among ecstasy/polydrug users. The present study seeks to investigate dose-related effects of specific drugs and whether these vary with the cognitive demands of the task. One hundred and five participants (mean age 21.33, SD 3.14; 77 females, 28 males) attempted to generate solutions for eight one-model syllogisms and one syllogism for which there was no valid conclusion. All of the one-model syllogisms generated at least one valid conclusion and six generated two valid conclusions. In these six cases, one of the conclusions was classified as common and the other as non-common. The number of valid common inferences was negatively associated with the aspects of short-term cannabis use and with measures of IQ. The outcomes observed were more than simple post-intoxication effects since cannabis use in the 10 days immediately before testing was unrelated to reasoning performance. Following adjustment for multiple comparisons, the number of non-common valid inferences was not significantly associated with any of the drug-use measures. Recent cannabis use appears to impair the processes associated with generating valid common inferences while not affecting the production of non-common inferences. It is possible, therefore, that the two types of inference may recruit different executive resources, which may differ in their susceptibility to cannabis-related effects.

Non-covalent inhibitors of rhinovirus 3C protease.

The first known non-covalent inhibitors of rhinovirus 3C protease (3CP) have been identified through fragment based screening and hit identification activities.

DIVERSet JAG Compounds Inhibit Topoisomerase II and Are Effective Against Adult and Pediatric High-Grade Gliomas.

High-grade gliomas (HGGs) are aggressive primary brain tumors with local invasive growth and poor clinical prognosis in both adult and pediatric patients. Clinical response is compounded by resistance to standard frontline antineoplastic agents, an absence of novel therapeutics, and poor in vitro models to evaluate these. We screened a range of recently identified anticancer compounds in conventional adult, pediatric, and new biopsy-derived HGG models. These in vitro lines showed a range of sensitivity to standard chemotherapeutics, with varying expression levels of the prognostic markers hypoxia-induced factor (HIF) 1α and p53. Our evaluation of lead DIVERSet library compounds identified that JAG-6A, a compound that was significantly more potent than temozolomide or etoposide, was effective against HGG models in two-dimensional and three-dimensional systems; mediated this response by the potent inhibition of topoisomerase Iiα; remained effective under normoxic and hypoxic conditions; and displayed limited toxicity to non-neoplastic astrocytes. These data suggest that JAG-6A could be an alternative topoisomerase IIα inhibitor and used for the treatment of HGG.

Risk perception, fuzzy representations and comparative optimism.

Rather than a unitary value, individuals may represent health risk as a fuzzy entity that permits them to make a number of specific possible estimates. Comparative optimism might be explained by people flexibly, using such a set to derive optimistic risk estimates. Student participants were asked to rate the likelihood of eight harmful alcohol-related outcomes occurring to themselves and to an average student. Participants made either unitary estimates or estimates representing the upper and lower bounds of a set denoting 'realistic probability' estimates. Personal risk estimates were lower when they were made as unitary estimates than those calculated from the mid-points of the bounded estimates. Unitary estimates of personal risk made after the bounded estimates were lower than initial unitary estimates. There were no effects for estimates made with regard to the average student. Risk may be internally represented as a fuzzy set, and comparative optimism may exist partly because this set allows people the opportunity to make optimistic unitary estimates for personal risk within what they see as realistic parameters.

Fuzzy risk perception: correlates of "fuzzy" and specific measures of outcome likelihood in young drinkers.

Promoting informed choices about alcohol use requires understanding the nature of drinkers' risk perceptions and how these influence decision-making. Fuzzy trace theory states that people use imprecise "fuzzy" risk representations, which are based on the broad cognitive and affective meanings of risk-related experiences, whereas traditionally used measures request precise unitary estimations. Fuzzy representations may be less affected by defensive self-enhancement biases inherent in unitary estimates and better predictors of decision outcomes because they better reflect risk-related affect. Conversely, unitary estimates are based in specific experience and should be better associated with objective risk. Fuzziness was operationalized as a bounded range of undergraduate drinkers' lowest and highest "possibly true" estimates of likelihood for eight alcohol-related outcomes on an unmarked scale anchored by the terms "no chance" and "certain." This allowed comparison to unitary estimates and objective alcohol-related risk (Alcohol Use Disorders Identification Test [AUDIT] scores). Consistent with self-enhancement, unitary estimates were lower than bounded estimate midpoints. An accountability manipulation, which reduces self-enhancement, increased unitary but not bounded estimates. These effects were stronger in participants scoring highly on defensive coping. Bounded estimates were better predicted by risk-related affect and they more strongly predicted intention to reduce drinking. Unitary measures were better predicted by AUDIT scores. Accountability manipulations suppress heuristic thought, reduced correlations between bounded estimates and affect and intention, and eliminated unitary and bounded differences in prediction of AUDIT scores. Drinkers prefer fuzzy representations that reflect affective information when making decisions, but improving risk-based decisions may involve combining the best elements of bounded and unitary representations.