Valerian does not appear to reduce symptoms for patients with chronic insomnia in general practice using a series of randomised n-of-I trials

Objectives: To investigate the effectiveness of valerian for the management of chronic insomnia in general practice. Design: Valerian versus placebo in a series of n-of-1 trials, in Queensland, Australia. Results: Of 42 enrolled patients, 24 (57%) had sufficient data for inclusion into the n-of-1 analysis. Response to valerian was fair for 23 (96%) participants evaluating their 'energy level in the previous day' but poor or modest for all 24 (100%) participants' response to 'total sleep time' and for 23 (96%) participants' response to 'number of night awakenings' and 'morning refreshment'. As a group, the proportion of treatment successes ranged from 0.35 (95% CI 0.23, 0.47) to 0.55 (95% CI 0.43, 0.67) for the six elicited outcome sleep variables. There was no significant difference in the number (P = 0.06), distribution (P = 1.00) or severity (P = 0.46) of side effects between valerian and placebo treatments. Conclusions: Valerian was not shown to be appreciably better than placebo in promoting sleep or sleep-related factors for any individual patient or for all patients as a group. (C) 2003 Elsevier Ltd. All rights reserved.

T cells signaled by NF-kappa B- dendritic cells are sensitized not anergic to subsequent activation

Paradoxically, while peripheral self-tolerance exists for constitutively presented somatic self Ag, self-peptide recognized in the context of MHC class II has been shown to sensitize T cells for subsequent activation. We have shown that MHC class II(+)CD86(+)CD40(-) DC, which can be generated from bone marrow in the presence of an NF-kappaB inhibitor, and which constitutively populate peripheral tissues and lymphoid organs in naive animals, can induce Ag-specific tolerance. In this study, we show that CD40(-) human monocyte-derived dendritic cells (DC), generated in the presence of an NF-kappaB inhibitor, signal phosphorylation of TCRzeta, but little proliferation or IFN-gamma in vitro. Proliferation is arrested in the G(1)/G(0) phase of the cell cycle. Surprisingly, responding T cells are neither anergic nor regulatory, but are sensitized for subsequent IFN-gamma production. The data indicate that signaling through NF-kappaB determines the capacity of DC to stimulate T cell proliferation. Functionally, NF-kappaB(-)CD40(-)class II+ DC may either tolerize or sensitize T cells. Thus, while CD40(-) DC appear to prime or prepare T cells, the data imply that signals derived from other cells drive the generation either of Ag-specific regulatory or effector cells in vivo.

Glutamate transporter localization does not correspond to the temporary functional recovery and late degeneration after acute ocular ischemia in rats

Purpose: To determine whether the localization of retinal glutamate transporters is affected by retinal ischaemia and whether their ability to transport glutamate decreases with the progression of ischemic retinal and optic nerve degeneration. Methods: Retinal ischemia was induced in rats by acutely increasing the intraocular pressure (IOP, 110 mmHg/60 min). Reperfusion was permitted for periods up to 60 days post-ischemia. Functional evaluation was performed by monitoring the pupil light reflexes (PLRs) and electroretinograms (flash, flicker ERG and oscillatory potentials). Glutamate transporter localization and D-aspartate (glutamate analogue) uptake were assessed by immunohistochemistry. Results: Intense immunoreactivity for the retinal glutamate transporters (GLAST, GLT1, EAAC1 and EAAT5) was observed at all time points after the insult, despite severe retinal degeneration. D-aspartate was also normally accumulated in the ischemic retinas. Ten days post-operatively the PLR ratio (ratio = indirect/direct PLR = 34 +/- 7(.)5%) was significantly less than the pre-operative value (pre-op = 76(.)7 +/- 2 (.)6%, p < 0(.)05). However, 25 and 35 days post-operatively PLR ratios did not differ significantly from pre-operative values (44(.)4 +/- 6(.)9 and 53(.)8 +/- 9(.)6%, p > 0(.)05). Forty-five and 60 days post-operatively the PLR ratio declined again and was significantly lower than the pre-operative value (33(.)8 + 8(.)7 and 26(.)2 + 8(.)9%, p < 0(.)05). Statistical analysis revealed that all tested ERG components had significantly higher values at 32, but not at 42 and 58 days post-operatively when compared to the first time point recorded post-operatively (10 days). Conclusions: While retinal glutamate transport is compromised during an acute ischemic insult, consequent retinal recovery and degeneration are not due to a change in the excitatory amino acid transporter localization or D-aspartate (glutamate analogue) uptake. Rat retina and optic nerve are capable of spontaneous, but temporary, functional recovery after an acute ischemic insult. (C) 2004 Elsevier Ltd. All rights reserved.

Snakes and cats in the flower bed: Fast detection is not specific to pictures of fear-relevant animals

The observation that snakes and spiders are found faster among flowers and mushrooms than vice versa and that this search advantage is independent of set size supports the notion that fear-relevant stimuli are processed preferentially in a dedicated fear module. Experiment I replicated the faster identification of snakes and spiders but also found a set size effect in a blocked, but not in a mixed-trial, sequence. Experiment 2 failed to find faster identification of snake and spider deviants relative to other animals among flowers and mushrooms and provided evidence for a search advantage for pictures of animals, irrespective of their fear relevance. These findings suggest that results from the present visual search task cannot support the notion of preferential processing of fear relevance.

Adaptation is not required to explain the long-term response of axons to molecular gradients

It has been suggested that growth cones navigating through the developing nervous system might display adaptation, so that their response to gradient signals is conserved over wide variations in ligand concentration. Recently however, a new chemotaxis assay that allows the effect of gradient parameters on axonal trajectories to be finely varied has revealed a decline in gradient sensitivity on either side of an optimal concentration. We show that this behavior can be quantitatively reproduced with a computational model of axonal chemotaxis that does not employ explicit adaptation. Two crucial components of this model required to reproduce the observed sensitivity are spatial and temporal averaging. These can be interpreted as corresponding, respectively, to the spatial spread of signaling effects downstream from receptor binding, and to the finite time over which these signaling effects decay. For spatial averaging, the model predicts that an effective range of roughly one-third of the extent of the growth cone is optimal for detecting small gradient signals. For temporal decay, a timescale of about 3 minutes is required for the model to reproduce the experimentally observed sensitivity.

Factor structure of the Mood and Anxiety Symptom Questionnaire does not generalize to an anxious/depressed sample

Objective: The tripartite model of anxiety and depression has been proposed as a representation of the structure of anxiety and depression symptoms. The Mood and Anxiety Symptom Questionnaire (MASQ) has been put forwards as a valid measure of the tripartite model of anxiety and depression symptoms. This research set out to examine the factor structure of anxiety and depression symptoms in a clinical sample to assess the MASQ's validity for use in this population. MethodsThe present study uses confirmatory factor analytic methods to examine the psychometric properties of the MASQ in 470 outpatients with anxiety and mood disorder. Results: The results showed that none of the previously reported two-factor, three-factor or five-factor models adequately fit the data, irrespective of whether items or subscales were used as the unit of analysis. Conclusions: It was concluded that the factor structure of the MASQ in a mixed anxiety/depression clinical sample does not support a structure consistent with the tripartite model. This suggests that researchers using the MASQ with anxious/depressed individuals should be mindful of the instrument's psychometric limitations.

Using cohort studies to estimate mortality among injecting drug users that is not attributable to AIDS

Background: Injecting drug use (IDU) and associated mortality appear to be increasing in many parts of the world. IDU is an important factor in HIV transmission. In estimating AIDS mortality attributable to IDU, it is important to take account of premature mortality rates from other causes to ensure that AIDS related mortality among injecting drug users (IDUs) is not overestimated. The current review provides estimates of the excess non-AIDS mortality among IDUs. Method: Searches were conducted with Medline, PsycINFO, and the Web of Science. The authors also searched reference lists of identified papers and an earlier literature review by English et al (1995). Crude. mortality rates (CMRs) were derived from data on the number of deaths, period of follow UP, and number of participants. In estimating the all-cause mortality, two rates were calculated: one that included all cohort studies identified in the search, and one that only included studies that reported on AIDS deaths in their cohort. This provided lower and upper mortality rates, respectively. Results: The current paper derived weighted mortality rates based upon cohort studies that included 179 885 participants, 1 219 422 person-years of observation, and 16 593 deaths. The weighted crude AIDS mortality rate from studies that reported AIDS deaths was approximately 0.78% per annum. The median estimated non-AIDS mortality rate was 1.08% per annum. Conclusions: Illicit drug users have a greatly increased risk of premature death and mortality due to AIDS forms a significant part of that increased risk; it is, however, only part of that risk. Future work needs to examine mortality rates among IDUs in developing countries, and collect data on the relation between HIV and increased mortality due to all causes among this group.

Reaction time facilitation by acoustic task-irrelevant stimuli is not related to startle

Previous research has been interpreted to suggest that the startle reflex mediates the RT facilitation observed if intense, accessory acoustic stimuli are presented coinciding with the onset of a visual imperative stimulus in a forewarned simple RT task. The present research replicated this finding as well as the facilitation of startle observed during the imperative stimulus. It failed, however, to find any relationship between the size of the blink startle reflex elicited by the accessory acoustic stimuli, which differed in intensity and rise time, and RT or RT facilitation observed on trials with accessory acoustic stimuli. This finding suggests that the RT facilitation is not mediated by the startle reflex elicited by the accessory acoustic stimuli. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

Liberal Democracy and the Inferior 'Other'Other’: Could the peace liberal democracy promises to bring not extend to ‘Others’?

Advocates of liberal democracy argue that its principles and practices contribute directly to peace (at both inter-state and domestic levels). They rely on ideals such as the rule of law, institutional checks and balances on power, an ethos of tolerance, and free market economics to deliver the liberal peace. Liberals, however, overlook three important features embedded in the construction of liberal democracy which can serve to facilitate political violence: 1) the fixed and thus non-negotiable nature of liberal democracy’s core principles, 2) the inferior manner in which it conceives ‘Other’ social orders that do not share its core principles, and 3) the urge to proselytise Others. Together, these constitutive qualities can facilitate moves by leaders of Other groups to argue that liberal democracy threatens ‘their’ preferred identity, and thus its promised peaceful outcomes can be put in doubt.

Implicit learning is not subject to blocking

Explicit (aware) learning has been shown to evidence certain characteristics, such as extinction, blocking, occasion setting, and reliance on context. These characteristics have not been assessed in implicit (unaware) learning. The current study investigated whether implicit learning is subject to blocking. Participants completed a cued reaction time task, where they watched rapid presentations of a random sequence of 8 pairs of shapes, and responded to two target shapes. One target was always preceded by a cue. The experimental group completed a pretraining phase where half the cue, one shape, was followed by the target. Both experimental and control groups completed a training phase where both elements of the cue, two shapes, were followed by the target. Both aware and unaware participants evidenced learning, whereby responding was faster for cued than uncued targets. Aware participants in the experimental group responded faster to targets preceded by the pretrained element than by the other element of the cue. Control and unaware experimental participants were faster to respond to targets preceded by either element of the cue. As blocking was only evident in aware participants, but implicit learning was observed in all participants, it is concluded that implicit learning is not subject to blocking.