Confidence in beliefs about pain predicts expectancy effects on pain perception and anticipatory processing in right anterior insula.

Psychological factors play a major role in exacerbating chronic pain. Effective self-management of pain is often hindered by inaccurate beliefs about the nature of pain which lead to a high degree of emotional reactivity. Probabilistic models of perception state that greater confidence (certainty) in beliefs increases their influence on perception and behavior. In this study, we treat confidence as a metacognitive process dissociable from the content of belief. We hypothesized that confidence is associated with anticipatory activation of areas of the pain matrix involved with top-down modulation of pain. Healthy volunteers rated their beliefs about the emotional distress that experimental pain would cause, and separately rated their level of confidence in this belief. Confidence predicted the influence of anticipation cues on experienced pain. We measured brain activity during anticipation of pain using high-density EEG and used electromagnetic tomography to determine neural substrates of this effect. Confidence correlated with activity in right anterior insula, posterior midcingulate and inferior parietal cortices during the anticipation of pain. Activity in the right anterior insula predicted a greater influence of anticipation cues on pain perception, whereas activity in right inferior parietal cortex predicted a decreased influence of anticipatory cues. The results support probabilistic models of pain perception and suggest that confidence in beliefs is an important determinant of expectancy effects on pain perception.

Modulation of pain ratings by expectation and uncertainty: Behavioral characteristics and anticipatory neural correlates.

Expectations about the magnitude of impending pain exert a substantial effect on subsequent perception. However, the neural mechanisms that underlie the predictive processes that modulate pain are poorly understood. In a combined behavioral and high-density electrophysiological study we measured anticipatory neural responses to heat stimuli to determine how predictions of pain intensity, and certainty about those predictions, modulate brain activity and subjective pain ratings. Prior to receiving randomized laser heat stimuli at different intensities (low, medium or high) subjects (n=15) viewed cues that either accurately informed them of forthcoming intensity (certain expectation) or not (uncertain expectation). Pain ratings were biased towards prior expectations of either high or low intensity. Anticipatory neural responses increased with expectations of painful vs. non-painful heat intensity, suggesting the presence of neural responses that represent predicted heat stimulus intensity. These anticipatory responses also correlated with the amplitude of the Laser-Evoked Potential (LEP) response to painful stimuli when the intensity was predictable. Source analysis (LORETA) revealed that uncertainty about expected heat intensity involves an anticipatory cortical network commonly associated with attention (left dorsolateral prefrontal, posterior cingulate and bilateral inferior parietal cortices). Relative certainty, however, involves cortical areas previously associated with semantic and prospective memory (left inferior frontal and inferior temporal cortex, and right anterior prefrontal cortex). This suggests that biasing of pain reports and LEPs by expectation involves temporally precise activity in specific cortical networks.

Modulation of pain processing in hyperalgesia by cognitive demand.

The relationship between pain and cognitive function is of theoretical and clinical interest, exemplified by observations that attention-demanding activities reduce pain in chronically afflicted patients. Previous studies have concentrated on phasic pain, which bears little correspondence to clinical pain conditions. Indeed, phasic pain is often associated with differential or opposing effects to tonic pain in behavioral, lesion, and pharmacological studies. To address how cognitive engagement interacts with tonic pain, we assessed the influence of an attention-demanding cognitive task on pain-evoked neural responses in an experimental model of chronic pain, the capsaicin-induced heat hyperalgesia model. Using functional magnetic resonance imaging (fMRI), we show that activity in the orbitofrontal and medial prefrontal cortices, insula, and cerebellum correlates with the intensity of tonic pain. This pain-related activity in medial prefrontal cortex and cerebellum was modulated by the demand level of the cognitive task. Our findings highlight a role for these structures in the integration of motivational and cognitive functions associated with a physiological state of injury. Within the limitations of an experimental model of pain, we suggest that the findings are relevant to understanding both the neurobiology and pathophysiology of chronic pain and its amelioration by cognitive strategies.

Empathy for pain involves the affective but not sensory components of pain.

Our ability to have an experience of another's pain is characteristic of empathy. Using functional imaging, we assessed brain activity while volunteers experienced a painful stimulus and compared it to that elicited when they observed a signal indicating that their loved one--present in the same room--was receiving a similar pain stimulus. Bilateral anterior insula (AI), rostral anterior cingulate cortex (ACC), brainstem, and cerebellum were activated when subjects received pain and also by a signal that a loved one experienced pain. AI and ACC activation correlated with individual empathy scores. Activity in the posterior insula/secondary somatosensory cortex, the sensorimotor cortex (SI/MI), and the caudal ACC was specific to receiving pain. Thus, a neural response in AI and rostral ACC, activated in common for "self" and "other" conditions, suggests that the neural substrate for empathic experience does not involve the entire "pain matrix." We conclude that only that part of the pain network associated with its affective qualities, but not its sensory qualities, mediates empathy.

Effect of indium-doped interlayer on the strain relief in GaN films grown on Si(111)

Crack-free GaN films have been achieved by inserting an Indoped low-temperature (LT) AlGaN interlayer grown on silicon by metalorganic chemical vapor deposition. The relationship between lattice constants c and a obtained by X-ray diffraction analysis shows that indium doping interlayer can reduce the stress in GaN layers. The stress in GaN decreases with increasing trimethylindium (TMIn) during interlayer growth. Moreover, for a smaller TMIn flow, the stress in GaN decreases dramatically when In acts as a surfactant to improve the crystallinity of the AlGaN interlayer, and for a larger TMIn flow, the stress will increase again. The decreased stress leads to smoother surfaces and fewer cracks for GaN layers by using an In-doped interlayer than by using an undoped interlayer. In doping has been found to enhance the lateral growth and reduce the growth rate of the c face. It can explain the strain relief and cracks reduction in GaN films. (C) 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison and combination of several stress relief methods for cubic boron nitride films deposited by ion beam assisted deposition

Cubic boron nitride (c-BN) films were prepared by ion beam assisted deposition (IBAD) technique, and the stresses were primary estimated by measuring the frequency shifts in the infrared-absorption peaks of c-BN samples. To test the possible effects of other factors, dependencies of the c-BN transversal optical mode position on film thickness and c-BN content were investigated. Several methods for reducing the stress of c-BN films including annealing, high temperature deposition, two-stage process, and the addition of a small amount of Si were studied, in which the c-BN films with similar thickness and cubic phase content were used to evaluate the effects of the various stress relief methods. It was shown that all the methods can reduce the stress in c-BN films to various extents. Especially, the incorporation of a small amount of Si (2.3 at.%) can result in a remarkable stress relief from 8.4 to similar to 3.6 GPa whereas the c-BN content is nearly unaffected, although a slight degradation of the c-BN crystallinity is observed. The stress can be further reduced down below I GPa by combination of the addition of Si with the two-stage deposition process. (c) 2008 Elsevier B.V. All rights reserved.

AlGaN layers grown on AlGaN buffer layer and GaN buffer layer using strain-relief interlayers - art. no. 68410S

We investigated AlGaN layers grown by metalorganic chemical vapor deposition (MOCVD) on high temperature (HT-)GaN and AlGaN buffer layers. On GaN buffer layer, there are a lot of surface cracking because of tensile strain in subsequent AlGaN epilayers. On HT-AlGaN buffer layer, not only cracks but also high densities rounded pits present, which is related to the high density of coalescence boundaries in HT-AlGaN growth process.The insertion of interlayer (IL) between AlGaN and the GaN pseudosubstrate can not only avoid cracking by modifying the strain status of the epilayer structure, but also improved Al incorporation efficiency and lead to phase-separation. And we also found the growth temperature of IL is a critical parameter for crystalline quality of subsequent AlGaN epilayer. Low temperature (LT-) A1N IL lead to a inferior quality in subsequent AlGaN epilayers.

Boundary effect of relief structure on crystallization of diblock copolymer in thin films

In this Letter, crystal growth of a symmetric crystalline-amorphous diblock copolymer, poly(styrene-b-epsilon-caprolactone) (PS-b-PCL), in thin films was investigated by atomic force microscopy (AFM), Relief structures of holes and islands were formed during annealing the film at the molten state, and the in situ observation of subsequent crystal growth at room temperature indicated that the crystals were preferred to occur at the edge of holes or islands and grew into the interior area. It was concluded that the stretched PCL blocks at the edge of relief structures, caused by material transportation or deformation of the interface, could act as nucleation agents during polymer crystallization. The crystal growth rate of individual lamellae varied both from lamellae to lamellae and in time, but the area occupied by crystals increased constantly with time. At 22 degreesC, the growth rate was 1.2 x 10(-2) mum(2)/min with the scan size 2 x 2 mum(2).

Development of process control methodology for tracking the quality and safety of pain, agitation and sedation management in critical care units

Objective: To develop sedation, pain, and agitation quality measures using process control methodology and evaluate their properties in clinical practice. Design: A Sedation Quality Assessment Tool was developed and validated to capture data for 12-hour periods of nursing care. Domains included pain/discomfort and sedation-agitation behaviors; sedative, analgesic, and neuromuscular blocking drug administration; ventilation status; and conditions potentially justifying deep sedation. Predefined sedation-related adverse events were recorded daily. Using an iterative process, algorithms were developed to describe the proportion of care periods with poor limb relaxation, poor ventilator synchronization, unnecessary deep sedation, agitation, and an overall optimum sedation metric. Proportion charts described processes over time (2 monthly intervals) for each ICU. The numbers of patients treated between sedation-related adverse events were described with G charts. Automated algorithms generated charts for 12 months of sequential data. Mean values for each process were calculated, and variation within and between ICUs explored qualitatively. Setting: Eight Scottish ICUs over a 12-month period. Patients: Mechanically ventilated patients. Interventions: None. Measurements and Main Results: The Sedation Quality Assessment Tool agitation-sedation domains correlated with the Richmond Sedation Agitation Scale score (Spearman [rho] = 0.75) and were reliable in clinician-clinician (weighted kappa; [kappa] = 0.66) and clinician-researcher ([kappa] = 0.82) comparisons. The limb movement domain had fair correlation with Behavioral Pain Scale ([rho] = 0.24) and was reliable in clinician-clinician ([kappa] = 0.58) and clinician-researcher ([kappa] = 0.45) comparisons. Ventilator synchronization correlated with Behavioral Pain Scale ([rho] = 0.54), and reliability in clinician-clinician ([kappa] = 0.29) and clinician-researcher ([kappa] = 0.42) comparisons was fair-moderate. Eight hundred twenty-five patients were enrolled (range, 59-235 across ICUs), providing 12,385 care periods for evaluation (range 655-3,481 across ICUs). The mean proportion of care periods with each quality metric varied between ICUs: excessive sedation 12-38%; agitation 4-17%; poor relaxation 13-21%; poor ventilator synchronization 8-17%; and overall optimum sedation 45-70%. Mean adverse event intervals ranged from 1.5 to 10.3 patients treated. The quality measures appeared relatively stable during the observation period. Conclusions: Process control methodology can be used to simultaneously monitor multiple aspects of pain-sedation-agitation management within ICUs. Variation within and between ICUs could be used as triggers to explore practice variation, improve quality, and monitor this over time

Irish Times coverage of Irish relief and development nongovernmental organisations, legitimacy and accountability, 1994-2009: analysis and implications for the role of nongovernmental organisations

The overall aim of this study was to investigate the extent to which and ways in which Irish relief and development nongovernmental organisations (NGOs) were linked with the concepts of legitimacy and accountability in Irish Times newspaper coverage between 1994 and 2009. This research was based on a quantitative content analysis of 215 Irish Times articles and the results were analysed using statistical methods. Key findings of the research included that NGO accountability received significantly more coverage than NGO legitimacy, "principal-agent" approaches to NGO accountability received significantly more coverage than "stakeholder" approaches to NGO accountability, and questioning of NGOs based on either their accountability or legitimacy was very limited. It is suggested that these findings may indicate both a failure by Irish NGOs to promote "development literacy" and global solidarity among the Irish public, and a limited degree of "development literacy" and global solidarity among the Irish public.

An investigation into mechanisms of visceral pain in rodents

Visceral pain is a debilitating symptom of irritable bowel syndrome (IBS), a disorder affecting up to 30% of adults. A better understanding of the mechanisms underlying visceral hypersensitivity may facilitate development of more targeted therapies, improving the quality of life of these individuals. The studies performed in this thesis were designed to investigate important factors of visceral pain, including early-life manipulations, genetic predisposition and sex hormones. Maternal separation (MS) consistently reproduces visceral hypersensitivity and altered anxiety-like behaviours in rats, symptoms associated with IBS. It has been found that 5-HT2B receptor antagonism blocks visceral pain but no difference in relative 5-HT2B receptor mRNA expression was found in hippocampus, amygdala and colon. The neuronal activation patterns of prefrontal cortex and amygdala of MS rats were then investigated. MS animals are characterised by differential activation of the prefrontal cortex (anterior cingulate cortex (ACC), infralibic cortex, prelimbic cortex) as well as the central nucleus of the amygdala (CeA). Genetic factors also contribute to pain syndromes such as IBS. We utilised the Wistar Kyoto (WKY) rat, a stress-sensitive strain, as an animal model of brain-gut axis dysfunction. WKY rats have a lower expression of the glutamate transporter EAAT2 and mGlu4 receptor in the ACC. Another early-life factor that can increase susceptibility to functional gastrointestinal symptoms later life is disruption of the gut microbiota, thus early-life antibiotic treatment was used to assess this effect. Antibiotic treatment induced visceral hypersensitivity in adulthood and may be related to observed reductions in spinal cord alpha-2A adrenoreceptor (adra2A) mRNA. Lastly, we investigated sex differences in visceral sensitivity. EAAT1 & 2 mRNA levels are lower in females, potentially increasing glutamatergic concentration at the symaptic level. Moreover, NR1 and NR2B subunits mRNA of NMDA receptor were increased in caudal ACC of females. These findings may account for sex differences in visceral sensitivity.