Lead stimulus modality change and the attentional modulation of the acoustic and electrical blink reflex

Two experiments investigated the effects of the sensory modality of the lead and of the blink-eliciting stimulus during lead stimulus modality change on blink modulation at lead intervals of 2500 and 3500 ins. Participants were presented with acoustic, visual, or tactile change stimuli after habituation training with lead stimuli from the same or a different sensory modality. In Experiment 1, latency and magnitude of the acoustic blink were facilitated during a change to acoustic or visual lead stimuli, but not during a change to tactile lead stimuli. After habituation to acoustic lead stimuli, blink magnitude was smaller during tactile change stimuli than during habituation stimuli. The latter finding was replicated in Experiment 2 in which blink was elicited by electrical stimulation of the trigeminal nerve. The consistency of the findings across different combinations of lead stimulus and blink-eliciting stimulus modalities does not support a modality-specific account of attentional blink modulation. Rather, blink modulation during generalized orienting reflects modality non-specific processes, although modulation may not always be found during tactile lead stimuli. (C) 2002 Elsevier Science B.V. All rights reserved.

Latent inhibition and schizophrenia: Pavlovian conditioning of autonomic responses

Latent inhibition (LI) is an important model for understanding cognitive deficits in schizophrenia, Disruption of LI is thought to result from an inability to ignore irrelevant stimuli. The study investigated LI in schizophrenic patients by using Pavlovian conditioning of electrodermal responses in a complete within-subject design. Thirty-two schizophrenic patients, ( 16 acute. unmedicated and 16 medicated patients) and 16 healthy control subjects (matched with respect to age and gender) participated in the study. The experiment consisted of two stages: preexposure and conditioning. During preexposure two visual stimuli were presented, one of which served as the to-be-conditioned stimulus (CSp +) and the other one was the not-to-be-conditioned stimulus (CSp -) during the following conditioning ( = acquisition). During acquisition. two novel visual stimuli (CSn + and CSn -) were introduced. A reaction time task was used as the unconditioned stimulus (US). LI was defined as the difference in response differentiation observed between proexposed and non-preexposed sets of CS + and CS -. During preexposure. the schizophrenic patients did not differ in electrodermal responding from the control subjects, neither concerning the extent of orienting nor the course of habituation. The exposure to novel stimuli at the beginning of the acquisition elicited reduced orienting responses in unmedicated patients compared to medicated patients and control subjects, LI was observed in medicated schizophrenic patients and healthy controls. but not in acute unmedicated patients. Furthermore LI was found to be correlated with the duration of illness: it was attenuated in patients who had suffered their first psychotic episode. (C) 2002 Elsevier Science B.V. All rights reserved.

Effect of varying levels of mental workload on startle eyeblink modulation

Previous research using punctuate reaction time and counting tasks has found that the startle eyeblink reflex is sensitive to attentional demands. The present experiment explored whether startle eyeblink is also modulated during a complex continuous task and is sensitive to different levels of mental workload. Participants (N=14) performed a visual horizontal tracking task either alone (single-task condition) or in combination with a visual gauge monitoring task (multiple-task condition) for three minutes. On some task trials, the startle eyeblink reflex was elicited by a noise burst. Results showed that startle eyeblink was attenuated during both tasks and that the attenuation was greater during the multiple-task condition than during the single-task condition. Subjective ratings, endogenous eyeblink rate, heart period, and heart period variability provided convergent validity of the workload manipulations. The findings suggest that the startle eyeblink is sensitive to the workload demands associated with a continuous visual task. The application of startle eyeblink modulation as a workload metric and the possibility that it may be diagnostic of workload demands in different stimulus modalities is discussed.

Should we debrief and counsel people who have had psychological shock?

Design: Randomised controlled trial of psychological debriefing. Setting: A British teaching hospital (the Radcliffe Hospital, Oxford). Patients: 66 men and 40 women, aged 17–69 years, admitted to hospital after a motor vehicle accident. Most had been the driver of a car. Median admission duration was four days for the 52 control patients and eight days for the 54 who underwent the intervention. Interventions: A debriefing of about one hour on Day 2 of admission, encouraging patients to describe the accident and express their emotions, followed by a cognitive appraisal which included describing common reactions to traumatic experiences and suggesting a range of people who might be able to assist in the future, including the patient's general practitioner. 91 patients were assessed at four months and 61 were assessed at three years. Control patients had no debriefing or counselling. Main outcome measures: Impact of Event Scale (IES, which focuses on intrusive thoughts and avoidance of similar situations to the event); Brief Symptom Inventory (BSI, a measure of 53 symptoms); and other questions related to physical pain and functional activities. Main results: At four months there was still considerable psychological morbidity among the patients who were followed up. There was a significant difference (P < 0.05) in changes of IES between the 42 who received the intervention, in whom it increased from 15 (standard deviation [SD], 15) to 16 (SD, 15), and the 49 controls, in whom it fell from 15 (SD, 12) to 13 (SD, 14). Similarly, two subscales of the BSI score changed significantly between the intervention group, among whom it deteriorated from 0.5 (SD, 0.5) to 0.6 (SD, 0.8), and the control s, in whom it hardly changed from 0.4 (SD, 0.3) to 0.4 (SD, 0.4). Among the 61 patients followed for three years, the 30 randomised to receive the intervention were significantly worse, by self-report, both psychologically and physically. Their mean IES score deteriorated from a baseline of 15 (SD, 14) to 16 (SD, 18). In comparison, scores for the 31 control patients improved from 16 (SD, 12) to 13 (SD, 17). The difference in change was significant (P < 0.05). Among all patients with high initial scores, these decreased among the controls but not among those receiving the intervention. Conclusion: Psychological counselling should only be used in the context of trials rather than routine care.

Parenteral and mucosal delivery of a novel multi-epitope M protein-based group A streptococcal vaccine construct: investigation of immunogenicity in mice

Primary vaccine strategies against group A streptococci (GAS) have focused on the M protein-the target of opsonic antibodies important for protective immunity. We have previously reported protection of mice against GAS infection following parenteral delivery of a multi-epitope vaccine construct, referred to as a heteropolymer. This current report has assessed mucosal (intranasal (i.n.) and oral) delivery of the heteropolymer in mice with regard to the induction and specificity of mucosal and systemic antibody responses, and compared this to parenteral delivery. GAS-specific IgA responses were detected in saliva and gut upon i.n. and oral delivery of the heteropolymer co-administered with cholera toxin B subunit, respectively. High titre serum IgG responses were elicited to the heteropolymer following all routes of delivery when administered with adjuvant. Moreover, as with parenteral delivery, serum IgG antibodies were detected to the individual heteropolymer peptides following i.n. but not oral delivery. These data support the potential of the i.n. route in the mucosal delivery of a GAS vaccine. (C) 2002 Elsevier Science Ltd. All rights reserved.

Colony-stimulating factor-1 suppresses responses to CpG DNA and expression of toll-like receptor 9 but enhances responses to lipopolysaccharide in murine macrophages

During bacterial infections, the balance between resolution of infection and development of sepsis is dependent upon the macrophage response to bacterial products. We show that priming of murine bone marrow-derived macrophages (BMMs) with CSF-1 differentially regulates the response to two such stimuli, LPS and immunostimulatory (CpG) DNA. CSF-1 pretreatment enhanced IL-6, IL-12, and TNF-alpha production in response to LPS but suppressed the same response to CpG DNA. CSF-1 also regulated cytokine gene expression in response to CpG DNA and LPS; CpG DNA-induced IL-12 p40, IL-12 p35, and TNF-alpha mRNAs were all suppressed by CSF-1 pretreatment. CSF-1 pretreatment enhanced LPS-induced IL-12 p40 mRNA but not TNF-alpha and IL-12 p35 mRNAs, suggesting that part of the priming effect is posttranscriptional. CSF-1 pretreatment also suppressed CpG DNA-induced nuclear translocation of NF-kappaB and phosphorylation of the mitogen-activated protein kinases p38 and extracellular signal-related kinases-1/2 in BMMs, indicating that early events in CpG DNA signaling were regulated by CSF-1. Expression of Toll-like receptor (TLR)9, which is necessary for responses to CpG DNA, was markedly suppressed by CSF-1 in both BMMs and thioglycolate-elicited peritoneal macrophages. CSF-1 also down-regulated expression of TLR1, TLR2, and TLR6, but not the LPS receptor, TLR4, or TLR5. Hence, CSF-1 may regulate host responses to pathogens through modulation of TLR expression. Furthermore, these results suggest that CSF-1 and CSF-1R antagonists may enhance the efficacy of CpG DNA in vivo.

The current status of laser applications in dentistry

A range of lasers. is now available for use in dentistry. This paper summarizes key current and emerging applications, for lasers in clinical practice. A major diagnostic application of low power lasers is the detection of caries, using fluorescence elicited from hydroxyapatite or from bacterial by-products. Laser fluorescence is an effective method for detecting and quantifying incipient occlusal and cervical,carious lesions, and with further refinement could be used in the, same manner for proximal lesions. Photoactivated dye techniques have been developed which use low power lasers to elicit a photochemical reaction, Photoactivated dye techniques' can be used to disinfect root canals, periodontal pockets, cavity preparations and sites of peri-implantitis. Using similar principles, more powerful lasers tan be used for photodynamic therapy in the treatment of malignancies of the oral mucosa. Laser-driven photochemical reactions can also be used for tooth whitening. In combination with fluoride, laser irradiation can improve the resistance of tooth structure to demineralization, and this application is of particular benefit for susceptible sites in high caries risk patients. Laser technology for caries' removal, cavity preparation and soft tissue surgery is at a high state of refinement, having had several decades of development up to the present time. Used in conjunction with or as a replacement for traditional methods, it is expected that specific laser technologies will become an essential component of contemporary dental practice over the next decade.

Application of fairness theory to service failures and service recovery

This article presents a fairness theory-based conceptual framework for studying and managing consumers’ emotions during service recovery attempts. The conceptual framework highlights the central role played by counterfactual thinking and accountability. Findings from five focus groups are also presented to lend further support to the conceptual framework. Essentially, the article argues that a service failure event triggers an emotional response in the consumer, and from here the consumer commences an assessment of the situation, considering procedural justice, interactional justice, and distributive justice elements, while engaging in counterfactual thinking and apportioning accountability. More specifically, the customer assesses whether the service provider could and should have done something more to remedy the problem and how the customer would have felt had these actions been taken. The authors argue that during this process situational effort is taken into account when assessing accountability. When service providers do not appear to exhibit an appropriate level of effort, consumers attribute this to the service provider not caring. This in turn leads to the customer feeling more negative emotions, such as anger and frustration. Managerial implications of the study are discussed.

Generation of CTL responses using Kunjin replicon RNA

The Kunjin replicon was used to express a polytope that consisted of seven hepatitis C virus cytotoxic T lymphocyte epitopes and one influenza cytotoxic T lymphocyte epitope for vaccination studies. The self-replicating nature of, and expression from, the ribonucleic acid was confirmed in vitro . Initial vaccinations with one dose of Kun-Poly ribonucleic acid showed that an influenza-specific cytotoxic T lymphocyte response was elicited more efficiently by intradermal inoculation compared with intramuscular delivery. Two micrograms of ribonucleic acid delivered in the ear pinnae of mice was sufficient to elicit a detectable cytotoxic T lymphocyte response 10 days post-vaccination. Further vaccination studies showed that four of the seven hepatitis C virus cytotoxic T lymphocyte epitopes were able to elicit weak cytotoxic T lymphocyte responses whereas the influenza epitope was able to elicit strong, specific cytotoxic T lymphocyte responses following three doses of Kun-Poly ribonucleic acid. These studies vindicate the use of the Kunjin replicon as a vector to deliver encoded proteins for the development of cell-mediated immune responses.

Immunogenicity of recombinant HBsAg/HCV particles in mice pre-immunised with hepatitis B virus-specific vaccine

Due to their spatial structure virus-like particles (VLPs) generally induce effective immune responses. VLPs derived from the small envelope protein (HBsAg-S) of hepatitis B virus (HBV) comprise the HBV vaccine. Modified HBsAs-S VLPs, carrying the immunodominant hypervariable region (HVR1) of the hepatitis C virus (HCV) envelope protein E2 within the exposed 'a'-determinant region (HBsAg/HVR1-VLPs), elicited HVR1-specific antibodies in mice. A high percentage of the human population is positive for anti-HBsAg antibodies (anti-HBs), either through vaccination or natural infection. We, therefore, determined if pre-existing anti-HBs could influence immunisation with modified VLPs. Mice were immunised with a commercial HBV vaccine, monitored to ensure an anti-HBs response, then immunised with HBsAg/HVR1-VLPs. The resulting anti-HVR1 antibody titre was similar in mice with or without pre-existing anti-HBs. This suggests that HBsAg/HVR1-VLPs induce a primary immune response to HVR1 in anti-HBs positive mice and, hence, they may be used successfully in individuals already immunised with the HBV vaccine. (C) 2003 Elsevier Science Ltd. All rights reserved.

Rapid colour changes in multilayer reflecting stripes in the paradise whiptail, Pentapodus paradiseus

The Paradise whiptail (Pentapodus paradiseus) has distinct reflective stripes on its head and body. The reflective stripes contain a dense layer of physiologically active iridophores, which act as multilayer reflectors. The wavelengths reflected by these stripes can change from blue to red in 0.25 s. Transmission electron microscopy revealed that the iridophore cells contain plates that are, on average, 51.4 nm thick. This thickness produces a stack, which acts as an ideal quarter-wavelength multilayer reflector (equal optical thickness of plates and spaces) in the blue, but not the red, region of the spectrum. When skin preparations were placed into hyposmotic physiological saline, the peak wavelength of the reflected light shifted towards the longer (red) end of the visible spectrum. Hyperosmotic saline reversed this effect and shifted the peak wavelength towards shorter (blue/UV) wavelengths. Norepinephrine (100 mumol l(-1)) shifted the peak wavelength towards the longer end of the spectrum, while adenosine (100 mumol l(-1)) reversed the effects of norepinephrine. The results from this study show that the wavelength changes are elicited by a change of similar to70 nm in the distance between adjacent plates in the iridophore cells.

Cross-protective and Infection-Enhancing Immunity in Mice Vaccinated Against Flaviviruses Belonging to the Japanese Encephalitis Virus Serocomplex

The Japanese encephalitis virus serocomplex is a group of mosquito-borne flaviviruses that cause severe encephalitic disease in humans. The recent emergence of several members of this serocomplex in geographic regions where other closely related flaviviruses are endemic has raised urgent human health issues. Thus, the impact of vaccination against one of these neurotropic virus on the outcome of infection with a second, serologically related virus is unknown. We show here that immunity against Murray Valley encephalitis virus in vaccinated mice can cross-protect but also augment disease severity following challenge with Japanese encephalitis virus. Immunepotentiation of heterologous flavivirus disease was apparent in animals immunized with a 'killed' virus preparation when humoral antiviral immunty of low magnitude was elicited. (C) 2002 Elsevier Science Ltd. All rights reserved.

Provision of 4-1BB ligand enhances effector and memory CTL responses generated by immunization with dendritic cells expressing a human tumor-associated antigen

Up-regulation of receptor-ligand pairs during interaction of an MHC-presented epitope on dendritic cells (DCs) with cognate TCR may amplify, sustain, and drive diversity in the ensuing T cell immune response. Members of the TNF ligand superfamily and the TNFR superfamily contribute to this costimulatory molecule signaling. In this study, we used replication deficient adenoviruses to introduce a model tumor-associated Ag (the E7 oncoprotein of human papillomavirus 16) and the T cell costimulatory molecule 4-IBBL into murine DCs, and monitored the ability of these recombinant DO to elicit E7-directed T cell responses following immunization. Splenocytes from mice immunized with DCs expressing E7 alone elicited E7-directed effector and memory CTL responses. Coexpression of 4-1BBL in these E7-expressing DO increased effector and memory CTL responses when they were used for immunization. 4-1BBL expression up-regulated CD80 and CD86 second signaling molecules in DO. We also report an additive effect of 4-IBBL and receptor activator of NF-kappaB/receptor activator of NF-kappaB ligand coexpression in E7-transduced DC inummogens on E7-directed effector and memory CTL responses and on MHC class II and CD80/86 expression in DCs. Additionally, expression of 4-1BBL in E7-transduced DCs reduced nonspecific T cell activation characteristic of adenovirus vector-associated immunization. The results have generic implications for improved or tumor Ag-expressing DC vaccines by incorporation of exogenous 4-1BBL. There are also specific implications for an improved DC-based vaccine for human papillomavirus 16-associated cervical carcinoma.

Climate of fear in organisational settings: Construct definition, measurement and a test of theory

This paper reports a study that explored a new construct: climate of fear. We hypothesised that climate of fear would vary across work sites within organisations, but not across organisations. This is in contrast a to measures of organisational culture, which were expected to vary both within and across organisations. To test our hypotheses, we developed a new 13-item measure of perceived fear in organisations and tested it in 20 sites across two organisations (N = 209). Culture variables measured were innovative leadership culture, and communication culture. Results were that climate of fear did vary across sites in both organisations, while differences across organisations were not significant, as we anticipated. Organisational culture, however, varied between the organisations, and within one of the organisations. The climate of fear scale exhibited acceptable psychometric properties.