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Attentional control theory suggests that heightened anxiety, whether due to trait or state factors, causes an increased vulnerability to distraction even when the distracters are emotionally neutral. Recent passive oddball studies appear to support this theory in relation to the distraction caused by emotionally neutral sounds. However such studies have manipulated emotional state via the content of task stimuli, thus potentially confounding changes in emotion with differences in task demands. To identify the effect of anxiety on the distraction caused by emotionally neutral sounds, 50 participants completed a passive oddball task requiring emotionally neutral sounds to be ignored. Crucially, state anxiety was manipulated independent of the task stimuli (via unrelated audiovisual stimuli) thus removing confounds relating to task demands. Neither state or trait anxiety was found to influence the susceptibility to distraction by emotionally neutral sounds. These findings contribute to the ongoing debate concerning the impact of emotion on attention.

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Both psychological stress and predictive signals relating to expected sensory input are believed to influence perception, an influence which, when disrupted, may contribute to the generation of auditory hallucinations. The effect of stress and semantic expectation on auditory perception was therefore examined in healthy participants using an auditory signal detection task requiring the detection of speech from within white noise. Trait anxiety was found to predict the extent to which stress influenced response bias, resulting in more anxious participants adopting a more liberal criterion, and therefore experiencing more false positives, when under stress. While semantic expectation was found to increase sensitivity, its presence also generated a shift in response bias towards reporting a signal, suggesting that the erroneous perception of speech became more likely. These findings provide a potential cognitive mechanism that may explain the impact of stress on hallucination-proneness, by suggesting that stress has the tendency to alter response bias in highly anxious individuals. These results also provide support for the idea that top-down processes such as those relating to semantic expectation may contribute to the generation of auditory hallucinations.

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Life expectancy in multiple myeloma has significantly increased. However, a high incidence of chemotherapy induced peripheral neuropathy (CIPN) can negatively influence quality of life during this period. This study applied functional magnetic resonance imaging (fMRI) to compare areas associated with central pain processing in patients with multiple myeloma who had chemotherapy induced peripheral neuropathy (MM-CIPN) with those from healthy volunteers (HV). Twenty-four participants (n = 12 MM-CIPN, n = 12 HV) underwent Blood Oxygen Level-Dependent (BOLD) fMRI at 3T whilst noxious heat-pain stimuli were applied to the foot and then thigh. Patients with MM-CIPN demonstrated greater activation during painful stimulation in the precuneus compared to HV (p = 0.014, FWE-corrected). Patients with MM-CIPN exhibited hypo-activation of the right superior frontal gyrus compared to HV (p = 0.031, FWE-corrected). Significant positive correlation existed between the total neuropathy score (reduced version) and activation in the frontal operculum (close to insular cortex) during foot stimulation in patients with MM-CIPN (p = 0.03, FWE-corrected; adjusted R2 = 0.87). Painful stimuli delivered to MM-CIPN patients evoke differential activation of distinct cortical regions, reflecting a unique pattern of central pain processing compared with healthy volunteers. This characteristic activation pattern associated with pain furthers the understanding of the pathophysiology of painful chemotherapy induced peripheral neuropathy. Functional MRI provides a tool for monitoring cerebral changes during anti-cancer and analgesic treatment.

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OBJECTIVE: Cognitive models of psychosis suggest that anomalous experiences alone do not always lead to clinical psychosis, with appraisals and responses to experiences being central to understanding the transition to "need for care". METHODS: The appraisals and response styles of Clinical (C; n = 28) and Nonclinical (NC; n = 34) individuals with psychotic experiences were compared following experimental analogues of thought interference (Cards Task) and auditory hallucinations (Virtual Acoustic Space Paradigm). RESULTS: The groups were matched in terms of their psychotic experiences. As predicted, the C group scored higher than the NC group on maladaptive appraisals following both tasks, rated the experience as more personally significant, and was more likely to incorporate the experimental setup into their ongoing experiences. The C group also appraised the Cards Task as more salient, distressing, and threatening; this group scored higher on maladaptive-and lower on adaptive-response styles, than the NC group on both tasks. CONCLUSIONS: The findings are consistent with cognitive models of psychosis, with maladaptive appraisals and response styles characterizing the C group only. Clinical applications of both tasks are suggested to facilitate the identification and modification of maladaptive appraisals.

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PURPOSE: It is uncertain whether smoking has an independent dose-related adverse effect on mortality in critically ill patients. This study assessed whether the intensity of smoking history, measured in pack-years, has a dose-related effect on mortality in critically ill patients. METHODS: In this multicentre cohort study data were collected from six tertiary intensive care units (ICU) in Australia and New Zealand. RESULTS: Of the 8,962 patients considered in the study, data on patients' smoking status and smoking history were available from 5,063 and 2,865 patients, respectively. Male gender, and chronic respiratory, liver and cardiovascular diseases were over-represented among smokers compared to non-smokers. Smokers had a higher risk of requiring mechanical ventilation and dying in hospital than non-smokers (10.7% vs. 6.7%, p=0.001), particularly after emergency admission. Smokers also had a longer ICU stay than non-smokers (mean 3.2 days, interquartile range 0.8-3.2 vs. 2.8 days, interquartile range 0.8-2.9; p=0.024). After adjusting for age, gender, elective surgical admission, severity of acute illness, and severe chronic illnesses, the intensity of smoking history remained significantly associated with the risk of dying in hospital. This was in a relatively linear fashion (odds ratio 1.08 per 10 pack-years increment, 95% confidence interval 1.02-1.15; p=0.02). Further grouping of smokers into active smokers and ex-smokers, or including patients with unknown smoking status in the sensitivity analyses did not change the association between the intensity of smoking history and mortality. CONCLUSIONS: Smoking has a dose-related adverse effect on mortality of critically ill patients after adjusting for other confounders.

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DESC1 was identified using gene-expression analysis between squamous cell carcinoma of the head and neck and normal tissue. It belongs to the type II transmembrane multidomain serine proteinases (TTSPs), an expanding family of serine proteinases, whose members are differentially expressed in several tissues. The biological role of these proteins is currently under investigation, although in some cases their participation in specific functions has been reported. This is the case for enteropeptidase, hepsin, matriptase and corin. Some members, including DESC1, are associated with cell differentiation and have been described as tumor markers. TTSPs belong to the type II transmembrane proteins that display, in addition to a C-terminal trypsin-like serine proteinase domain, a differing set of stem domains, a transmembrane segment and a short N-terminal cytoplasmic region. Based on sequence analysis, the TTSP family is subdivided into four subfamilies: hepsin/transmembrane proteinase, serine (TMPRSS); matriptase; corin; and the human airway trypsin (HAT)/HAT-like/DESC subfamily. Members of the hepsin and matriptase subfamilies are known structurally and here we present the crystal structure of DESC1 as a first member of the HAT/HAT-like/DESC subfamily in complex with benzamidine. The proteinase domain of DESC1 exhibits a trypsin-like serine proteinase fold with a thrombin-like S1 pocket, a urokinase-type plasminogen activator-type S2 pocket, to accept small residues, and an open hydrophobic S3/S4 cavity to accept large hydrophobic residues. The deduced substrate specificity for DESC1 differs markedly from that of other structurally known TTSPs. Based on surface analysis, we propose a rigid domain association for the N-terminal SEA domain with the back site of the proteinase domain.

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BACKGROUND: Schizophrenia is associated with widespread cognitive deficits that have an impact on social function. Modafinil promotes wakefulness and is reported to enhance cognition. AIMS: To study the acute effects of modafinil administration upon brain activity and cognitive performance in people with chronic schizophrenia. METHOD: In a randomised double-blind placebo-controlled crossover design, 19 patients received either modafinil (100 mg) or placebo prior to undertaking a working memory task with functional magnetic resonance imaging. RESULTS: Seventeen patients completed the study and another underwent acute relapse 4 days post-drug. Modafinil administration was associated with significantly greater activation in the anterior cingulate cortex during the working memory task. The anterior cingulate cortex signal correlated with cognitive performance, although only a subset of patients exhibited 'enhancement'. CONCLUSIONS: Modafinil modulates anterior cingulate cortex function in chronic schizophrenia but its beneficial cognitive effects may be restricted to a subset of patients requiring further characterisation.

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OBJECTIVE: This study probed the ability of people with chronic schizophrenia to control their behavior in time by requiring them to deliberately vary responses within the temporal domain (i.e., to avoid regular inter-response intervals). METHODS: Thirteen schizophrenia patients performed single finger movements (at moments of their own choosing) in an event-related functional magnetic resonance imaging paradigm. Their performance was computed using the coefficient of variation of inter-response interval duration. RESULTS: Task performance was positively correlated with activation of left lateral prefrontal cortex. Post hoc analyses revealed an inverse correlation between activation in this region and severity of attentional impairment. CONCLUSION: These findings implicate left lateral prefrontal cortex in the modulation of the temporal response space in schizophrenia and imply greater attentional (executive) impairment among those who fail to modulate their behavior in time.

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An organism may use misinformation, knowingly (through deception) or unknowingly (as in the case of camouflage), to gain advantage in a competitive environment. From an evolutionary perspective, greater tactical deception occurs among primates closer to humans, with larger neocortices. In humans, the onset of deceptive behaviours in childhood exhibits a developmental trajectory, which may be regarded as 'normal' in the majority and deficient among a minority with certain neurodevelopmental disorders (e.g. autism). In the human adult, deception and lying exhibit features consistent with their use of 'higher' or 'executive' brain systems. Accurate detection of deception in humans may be of particular importance in forensic practice, while an understanding of its cognitive neurobiology may have implications for models of 'theory of mind' and social cognition, and societal notions of responsibility, guilt and mitigation. In recent years, functional neuroimaging techniques (especially functional magnetic resonance imaging) have been used to study deception. Though few in number, and using very different experimental protocols, studies published in the peer-reviewed literature exhibit certain consistencies. Attempted deception is associated with activation of executive brain regions (particularly prefrontal and anterior cingulate cortices), while truthful responding has not been shown to be associated with any areas of increased activation (relative to deception). Hence, truthful responding may comprise a relative 'baseline' in human cognition and communication. The subject who lies may necessarily engage 'higher' brain centres, consistent with a purpose or intention (to deceive). While the principle of executive control during deception remains plausible, its precise anatomy awaits elucidation.

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Stimulation of the Drosophila immune response activates NF-kappaB and JNK signaling pathways. For example, infection by Gram-negative bacteria induces the Imd signaling pathway, leading to the activation of the NF-kappaB-like transcription factor Relish and the expression of a battery of genes encoding antimicrobial peptides. Bacterial infection also activates the JNK pathway, but the role of this pathway in the immune response has not yet been established. Genetic experiments suggest that the Drosophila homolog of the mammalian MAPK kinase kinase, TAK1 (transforming growth factor beta-activated kinase 1), activates both the JNK and NF-kappaB pathways following immune stimulation. In this report, we demonstrate that Drosophila TAK1 functions as both the Drosophila IkappaB kinase-activating kinase and the JNK kinase-activating kinase. However, we found that JNK signaling is not required for antimicrobial peptide gene expression but is required for the activation of other immune inducible genes, including Punch, sulfated, and malvolio. Thus, JNK signaling appears to play an important role in the cellular immune response and the stress response.

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