ORCID Profile
0000-0003-2146-9054
Current Organisation
UNSW Sydney
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Publisher: Frontiers Media SA
Date: 17-07-2014
Publisher: Elsevier BV
Date: 10-1985
Publisher: Springer Science and Business Media LLC
Date: 2002
Publisher: Elsevier
Date: 2013
Publisher: Elsevier BV
Date: 2004
Publisher: SAGE Publications
Date: 30-08-2018
Abstract: The objective of this article is to validate the Lupus Impact Tracker (LIT), a disease-specific patient-reported outcome (PRO) tool, in systemic lupus erythematosus (SLE) patients in a multi-ethnic Australian cohort. Patients attending the Monash Lupus Clinic were asked to complete the LIT, a 10-item PRO. Psychometric testing assessing criterion validity, construct validity, test-retest reliability (TRT) and internal consistency reliability (ICR) were performed. We compared the LIT scores across patient characteristics, and correlations between LIT scores and SLEDAI-2k, PGA, and SLICC-SDI were examined. LIT data were obtained from 73 patients. Patients were 84% female with a median age of 41 years, and 34% were Asian. The cohort had mild-moderate disease activity with a median (IQR) Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2k) of 4 (IQR 2–6). The median LIT score was 32.5 (IQR 17.5–50). LIT demonstrated criterion validity against SLEDAI-2k and SDI. Construct validity assessed by confirmatory factor analysis demonstrated an excellent fit (Goodness of fit index 0.95, Comparative Fit Index 1, Root Mean Square Error of Approximation .0001). The LIT demonstrated TRT with an overall intraclass correlation coefficient of 0.986 (95% CI 0.968–0.995). ICR was demonstrated with a Cronbach’s alpha of 0.838. Patients with disability, low socioeconomic status, or higher disease activity had significantly worse LIT scores. The LIT demonstrated properties consistent with its being valid in this population. Lower socioeconomic status appears to have a significant impact on patient-reported health-related quality of life in SLE.
Publisher: SAGE Publications
Date: 03-2007
Publisher: American Psychological Association (APA)
Date: 1983
Publisher: American Psychological Association (APA)
Date: 2005
Publisher: Elsevier BV
Date: 03-1990
Publisher: Cambridge University Press (CUP)
Date: 2001
Publisher: Informa UK Limited
Date: 10-05-2016
Publisher: Elsevier BV
Date: 07-2015
Publisher: Elsevier BV
Date: 04-2007
DOI: 10.1016/J.BRAT.2006.07.005
Abstract: Previous research has shown that D-cycloserine (DCS) facilitates extinction of Pavlovian fear conditioning in rats and enhances exposure therapy in humans. The aim of this study was to test the effect of DCS on extinction of fear conditioning in humans. In three experiments, 238 participants were given either DCS (50 or 500 mg) or placebo 2-3 h before extinction training following a differential shock conditioning paradigm. Clear extinction and recovery (return of fear) effects were observed on both skin conductance and self-reported shock expectancy measures in three studies. DCS had no influence on these effects. The same pattern was observed when the analysis was restricted to aware participants or to good conditioners, when fear-relevant cues (pictures of snakes) were used as the conditioned stimuli, or when analysis was restricted to heightened snake-fearful participants. These results suggest that DCS may not enhance the extinction, or prevent the recovery, of learned fear in a differential Pavlovian conditioning paradigm in humans. Further experimental research is needed to better understand the mechanisms underlying the therapeutic effects of DCS.
Publisher: Springer Science and Business Media LLC
Date: 27-10-2016
Publisher: Informa UK Limited
Date: 06-2006
Publisher: Informa UK Limited
Date: 08-1993
Publisher: American Psychological Association (APA)
Date: 06-2021
DOI: 10.1037/EMO0000739
Publisher: Springer Science and Business Media LLC
Date: 06-10-2016
DOI: 10.1038/SREP34604
Abstract: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the development of autoantibodies to nuclear antigens and inflammatory responses mediated by multiple cytokines. Although previous studies have determined clinical associations between SLE and the anti-inflammatory cytokines IL-10 and IL-37, their role in the disease, or their potential as biomarkers, remains unclear. We examined serum levels of IL-10 and IL-37 in a large cohort of SLE patients, with detailed longitudinal clinical data. We demonstrate a statistically significant association of serum IL-10 with disease activity, with higher levels in active compared to inactive disease. High first visit IL-10 was predictive of high subsequent disease activity patients with IL-10 in highest quartile at first visit were 3.6 times more likely to have active disease in subsequent visits. Serum IL-37 was also higher in SLE patients compared to control, and was strongly associated with Asian ethnicity. However, IL-37 was not statistically significantly associated with disease activity. IL-37 was significantly reduced in patients with organ damage but this association was attenuated in multivariable analysis. The data suggest that IL-10, but not IL-37, may have potential as a biomarker predictive for disease activity in SLE.
Publisher: Elsevier BV
Date: 2015
Publisher: Springer Science and Business Media LLC
Date: 16-11-2006
Publisher: Elsevier BV
Date: 03-2008
DOI: 10.1016/J.BIOPSYCH.2007.11.011
Abstract: Pilot research has suggested that D-cycloserine (DCS) enhances treatment outcomes for anxiety disorders when employed as an adjunct to exposure therapy (ET). The aim of this study was to determine whether 50 mg of DCS enhances ET for social anxiety disorder (SAD) according to a comprehensive set of symptom and life impairment measures. In a randomized double-blind placebo-controlled trial, we administered 50 mg of DCS or placebo in combination with ET to 56 participants who met primary diagnosis for SAD. Participants administered DCS reported greater improvement on measures of symptom severity, dysfunctional cognitions, and life-impairment from SAD in comparison with placebo-treated participants. Effect sizes were mostly in the medium range. Results also indicated that the amount of adaptive learning about one's ability to give speeches in front of an audience interacted with DCS to enhance treatment outcome. This study shows that the administration of DCS before ET enhances treatment outcomes for SAD. Results also provide the first preliminary evidence to suggest that DCS moderates the relationship between a reduction in negative appraisals about one's speech performance and improvement in overall SAD symptoms.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 09-2015
Publisher: Elsevier BV
Date: 03-2015
Publisher: BMJ
Date: 08-04-2015
Publisher: American Psychological Association (APA)
Date: 04-2023
DOI: 10.1037/XAN0000351
Publisher: SAGE Publications
Date: 05-2006
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.BRAINRES.2014.06.008
Abstract: Dysfunction of the hypothalamic-pituitary-adrenal axis, particularly the glucocorticoid receptor, is a commonly implicated link between stress and psychopathology. GR abnormalities are frequently reported in depression, and these anomalies must be resolved before depressive symptoms remit. This biological finding is rendered clinically relevant by the knowledge that only select antidepressants alter GR function. The relationship between GR dysfunction and other diseases associated with psychiatric stress, such as post-traumatic stress disorder (PTSD) and fibromyalgia, is also documented. However, as laboratory constraints limit the utility of GR testing, other measures of GR activity, such as levels of GR-induced genes, may have greater clinical value. In this review, glucocorticoid-induced leucine zipper (GILZ), a product of GR-initiated gene transcription, will be discussed in the context of GR dysfunction in psychopathology.
Publisher: SAGE Publications
Date: 13-08-2013
Abstract: Systemic lupus erythematosus (SLE), an autoimmune condition with erse clinical manifestations, is reported to have different expression in populations of different ancestry. Most previous studies compared patients of different ethnic groups from geographically distinct cohorts. In our study, we aimed to characterize disease manifestations in patients of different ethnic groups from a single centre, and studied patterns of disease activity over time. Demographics, baseline disease characteristics and autoantibody profiles, and disease activity (SLEDAI) measured at each visit, were captured from all consenting patients prospectively followed between 2007 and 2011 in an urban teaching hospital lupus clinic. Ethnicity was self-reported. Asian ethnicity was significantly associated with more clinically severe SLE. Time-adjusted mean SLEDAI ( p = 0.01) and maximum SLEDAI ( p = 0.0018) were significantly higher in Asian patients. Asians were more likely to have renal disease (OR 2.9, 95% CI 1.4–5.98 p = 0.004) and persistently active disease (PAD) (OR 2.14, 95% CI 1.05–4.38, p = 0.04). Asian lupus patients also had a significantly higher proportion of autoantibody positivity to anti-dsDNA, anti-RNP, anti-Sm, anti-Ro and anti-La, as well as increased likelihood of hypocomplementaemia and immunosuppressant use. In this single-cohort study, Asian ethnicity was found to be associated with increased SLE disease activity. This suggests significant inter-ethnic genetic contributions to the regulation of autoimmune responses and disease severity in SLE.
Publisher: Proceedings of the National Academy of Sciences
Date: 03-04-2023
Abstract: In iduals differ in their sensitivity to the adverse consequences of their actions, leading some to persist in maladaptive behaviors. Two pathways have been identified for this insensitivity: a motivational pathway based on excessive reward valuation and a behavioral pathway based on autonomous stimulus–response mechanisms. Here, we identify a third, cognitive pathway based on differences in punishment knowledge and use of that knowledge to suppress behavior. We show that distinct phenotypes of punishment sensitivity emerge from differences in what people learn about their actions. Exposed to identical punishment contingencies, some people (sensitive phenotype) form correct causal beliefs that they use to guide their behavior, successfully obtaining rewards and avoiding punishment, whereas others form incorrect but internally coherent causal beliefs that lead them to earn punishment they do not like. Incorrect causal beliefs were not inherently problematic because we show that many in iduals benefit from information about why they are being punished, revaluing their actions and changing their behavior to avoid further punishment (unaware phenotype). However, one condition where incorrect causal beliefs were problematic was when punishment is infrequent. Under this condition, more in iduals show punishment insensitivity and detrimental patterns of behavior that resist experience and information-driven updating, even when punishment is severe (compulsive phenotype). For these in iduals, rare punishment acted as a “trap,” inoculating maladaptive behavioral preferences against cognitive and behavioral updating.
Publisher: American Psychological Association (APA)
Date: 07-2022
DOI: 10.1037/XAN0000327
Publisher: Cambridge University Press (CUP)
Date: 04-2009
Publisher: SAGE Publications
Date: 11-1981
Publisher: American Psychological Association (APA)
Date: 04-2022
DOI: 10.1037/XAN0000320
Abstract: Inhibitory learning after feature negative training (A+/AB-) is typically measured by combining the Feature B with a separately trained excitor (e.g., C) in a summation test. Reduced responding to C is taken as evidence that B has properties directly opposite to those of C. However, in human causal learning, transfer of B's inhibitory properties to another excitor is modest and depends on in idual differences in inferred causal structure. Here we ask whether instead of opposing processes, a summation test might instead be thought of in terms of generalization. Using an allergist task, we tested whether inhibitory transfer would be influenced by similarity. We found that transfer was greater when the test stimuli were from the same semantic category as the training stimuli (Experiments 1 and 2) and when the test excitor had previously been associated with the same outcome (Experiment 3). We also found that the similarity effect applied across all self-reported causal structures. We conclude it may be more helpful to consider transfer of inhibition as a form of conceptual generalization rather than the arithmetic summation of opposing processes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Publisher: American Psychological Association (APA)
Date: 11-1996
Publisher: Wiley
Date: 07-1996
Publisher: Wiley
Date: 28-03-2014
DOI: 10.1002/ART.38299
Abstract: Myeloperoxidase (MPO) is implicated as a local mediator of tissue damage when released extracellularly in many chronic inflammatory diseases. The purpose of this study was to explore the role of endogenous MPO in experimental rheumatoid arthritis (RA). K/BxN serum-transfer arthritis was induced in C57BL/6 wild-type (WT) and MPO knockout (MPO(-/-) ) mice, and disease development was assessed. MPO activity was measured in joint tissues from mice with or without K/BxN arthritis. Collagen-induced arthritis (CIA) was induced in WT and MPO(-/-) mice, and disease development and immune responses were examined. MPO expression was assessed in synovial biopsy s les from patients with active RA, and the effect of MPO on synovial fibroblasts was tested in vitro. MPO was up-regulated in the joints of mice with K/BxN arthritis, and MPO deficiency attenuated the severity of the disease without affecting circulating cytokine levels. In CIA, MPO(-/-) mice had enhanced CD4+ T cell responses and reduced frequency of regulatory T cells in the lymph nodes and spleen, as well as augmented interleukin-17A and diminished interferon-γ secretion by collagen-stimulated splenocytes, without an effect on circulating anticollagen antibody levels. Despite enhanced adaptive immunity in secondary lymphoid organs, CIA development was attenuated in MPO(-/-) mice. Intracellular and extracellular MPO was detected in the synovium of patients with active RA, and human MPO enhanced the proliferation and decreased the apoptosis of synovial fibroblasts in vitro. MPO contributes to the development of arthritis despite suppressing adaptive immunity in secondary lymphoid organs. This suggests distinct effects of local MPO on arthritogenic effector responses.
Publisher: Wiley
Date: 22-07-2014
DOI: 10.1038/ICB.2014.56
Abstract: The hypothalamic-pituitary-adrenal (HPA) axis is an important regulator of the stress response. In healthy in iduals, the HPA axis maintains an equilibrium, ensuring that endogenous glucocorticoid (GC) levels remain within the normal range. However, hypofunction of the HPA axis may have a role in the development of inflammatory diseases, such as rheumatoid arthritis (RA). Glucocorticoid-induced leucine zipper (GILZ) is an anti-inflammatory protein, the expression of which is upregulated by GC. Although GILZ mediates the anti-inflammatory effects of GC, it may not be associated with the adverse effects that are frequently caused by exogenous GC administration. This has raised interest in GILZ potentiation as a therapeutic approach in diseases such as RA, which may mimic the anti-inflammatory effects of GC without causing harmful side effects. This review will outline the involvement of the HPA axis in RA, as a prelude to highlighting emerging evidence regarding the role of GILZ in inflammation control and RA.
Publisher: American Psychological Association (APA)
Date: 2015
DOI: 10.1037/XAN0000042
Abstract: Much of contemporary associative learning research is focused on understanding how and when the associative history of cues affects later learning about those cues. Very little work has investigated the effects of the associative history of outcomes on human learning. Three experiments extended the "learned irrelevance" paradigm from the animal conditioning literature to examine the influence of an outcome's prior predictability on subsequent learning of relationships between cues and that outcome. All 3 experiments found evidence for the idea that learning is biased by the prior predictability of the outcome. Previously predictable outcomes were readily associated with novel predictive cues, whereas previously unpredictable outcomes were more readily associated with novel nonpredictive cues. This finding highlights the importance of considering the associative history of outcomes, as well as cues, when interpreting multistage designs. Associative and cognitive explanations of this certainty matching effect are discussed.
Publisher: Elsevier BV
Date: 04-1989
Publisher: Elsevier BV
Date: 10-2000
Publisher: American Psychological Association (APA)
Date: 10-1983
Publisher: Elsevier BV
Date: 08-2006
Publisher: The American Association of Immunologists
Date: 12-2016
Abstract: Ag s ling is a key process in dendritic cell (DC) biology. DCs use constitutive macropinocytosis, receptor-mediated endocytosis, and phagocytosis to capture exogenous Ags for presentation to T cells. We investigated the mechanisms that regulate Ag uptake by DCs in the steady-state and after a short-term LPS exposure in vitro and in vivo. We show that the glucocorticoid-induced leucine zipper protein (GILZ), already known to regulate effector versus regulatory T cell activation by DCs, selectively limits macropinocytosis, but not receptor-mediated phagocytosis, in immature and recently activated DCs. In vivo, the GILZ-mediated inhibition of Ag uptake is restricted to the CD8α+ DC subset, which expresses the highest GILZ level among splenic DC subsets. In recently activated DCs, we further establish that GILZ limits p38 MAPK phosphorylation, providing a possible mechanism for GILZ-mediated macropinocytosis control. Finally, our results demonstrate that the modulation of Ag uptake by GILZ does not result in altered Ag presentation to CD4 T cells but impacts the efficiency of cross-presentation to CD8 T cells. Altogether, our results identify GILZ as an endogenous inhibitor of macropinocytosis in DCs, the action of which contributes to the fine-tuning of Ag cross-presentation.
Publisher: Springer Science and Business Media LLC
Date: 20-08-2013
Abstract: Glucocorticoids have broad-ranging and powerful anti-inflammatory and immunomodulatory effects. Unsurprisingly, therefore, glucocorticoids are widely and persistently used to treat a large number of inflammatory diseases, including rheumatoid arthritis (RA), despite the well-described adverse effects of these drugs. Annexin A1 is a glucocorticoid-induced molecule that is known to replicate many of the described anti-inflammatory effects of glucocorticoids. In addition to the well-documented roles of this protein in neutrophil function, emerging evidence suggests that annexin A1 is involved in the modulation of T-cell function and the adaptive immune responses relevant to RA. Interest in annexin A1 was renewed after the delineation of the receptors for this protein. This breakthrough also led to advances in our understanding of anti-inflammatory annexin A1 mimetic peptides and agonistic compounds targeting these receptors, particularly those specific for the receptor N-formyl peptide receptor 2 (FPR2). Herein, we review the current knowledge of the biological activities of annexin A1 and their relevance to RA pathogenesis. We also discuss the potential of annexin A1 mimics and strategies aimed at potentiating annexin A1 signalling to become viable approaches to minimizing glucocorticoid use in RA and other inflammatory disorders.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2014
Publisher: Wiley
Date: 28-07-2014
DOI: 10.1002/ART.38689
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.BETH.2015.09.004
Abstract: Intolerance of Uncertainty (IU) has gained increasing interest as a vulnerability factor for worry in Generalized Anxiety Disorder and other emotional disorders. We extended the procedure of Grupe and Nitschke (2011) to compare threat processing in High IU (n=29) and Low IU (n=26) participants. Participants viewed four cues: two reference cues that preceded aversive pictures on 100% or 0% of trials, and a target cue that preceded aversive pictures on 50% of trials (Uncertain condition). Participants were instructed about these probabilities in advance. In addition, we surprised participants with a second target cue that also preceded aversive pictures on 50% of trials but that had not been mentioned in the instructions (Ambiguous condition). Results provided preliminary evidence that High IU participants showed greater online threat expectancy, postexperimental covariation estimates and negative mood for the target cues compared to the reference cues. The results also suggest that among high IU in iduals, ambiguity, rather than uncertainty per se, may be a particularly powerful trigger for biased threat appraisal and negative affect. Clinically, the results suggest that patients with high IU may benefit from interventions to help them calibrate the degree of risk in situations involving ambiguous threat.
Publisher: Wiley
Date: 25-02-2015
DOI: 10.1002/ART.38966
Abstract: Interferon-α (IFNα)-producing plasmacytoid dendritic cells (PDCs) are implicated in the pathogenesis of systemic lupus erythematosus (SLE). IFNα-related genes are highlighted among SLE susceptibility alleles and are characteristically expressed in the blood of patients with SLE, while in mouse models of lupus, PDC numbers and IFNα production are increased. This study was undertaken to investigate the effects of inhibitors that selectively target different antiapoptotic molecules on the survival of PDCs. PDC numbers, in vitro survival, and expression of antiapoptotic molecules were evaluated in lupus-prone (NZB × NZW)F1 (NZB/NZW) mice. The impact of Bcl-2 antagonists and glucocorticoids on PDCs was evaluated in vitro and in vivo. IFNα production by NZB/NZW mice was evaluated before and after treatment with Bcl-2 antagonists. PDCs, but not lymphoid tissue-resident conventional DCs, largely relied on the antiapoptotic protein Bcl-2 for survival. The enlarged PDC compartment in NZB/NZW mice was associated with selectively prolonged survival and increased Bcl-2 transcription. Functionally, this resulted in enhanced production of IFNα. Bcl-2 inhibitors selectively killed mouse and human PDCs, including PDCs from SLE patients, but not conventional DCs, d ened IFNα production by PDCs, and synergized with glucocorticoids to kill activated PDCs. Enhanced PDC survival is a likely contributing factor to enhanced IFNα production by lupus PDCs. Bcl-2 antagonists potently and selectively kill PDCs and reduce IFNα production. Thus, we believe that they are attractive candidates for treating PDC-associated diseases.
Publisher: Elsevier BV
Date: 04-2015
Publisher: SAGE Publications
Date: 18-08-2016
Publisher: American Psychological Association (APA)
Date: 12-2018
DOI: 10.1037/XLM0000558
Publisher: BMJ
Date: 08-2015
Publisher: American Psychological Association (APA)
Date: 2009
DOI: 10.1037/A0013294
Abstract: P. Perruchet (1985b) showed a double dissociation of conditioned responses (CRs) and expectancy for an airpuff unconditioned stimulus (US) in a 50% partial reinforcement schedule in human eyeblink conditioning. In the Perruchet effect, participants show an increase in CRs and a concurrent decrease in expectancy for the airpuff across runs of reinforced trials conversely, participants show a decrease in CRs and a concurrent increase in expectancy for the airpuff across runs of nonreinforced trials. Three eyeblink conditioning experiments investigated whether the linear trend in eyeblink CRs in the Perruchet effect is a result of changes in associative strength of the conditioned stimulus (CS), US sensitization, or learning the precise timing of the US. Experiments 1 and 2 demonstrated that the linear trend in eyeblink CRs is not the result of US sensitization. Experiment 3 showed that the linear trend in eyeblink CRs is present with both a fixed and a variable CS-US interval and so is not the result of learning the precise timing of the US. The results are difficult to reconcile with a single learning process model of associative learning in which expectancy mediates CRs.
Publisher: Ubiquity Press, Ltd.
Date: 10-03-2023
DOI: 10.5334/JOC.266
Publisher: American Psychological Association (APA)
Date: 08-1998
Publisher: Elsevier BV
Date: 02-2005
Publisher: SAGE Publications
Date: 23-02-2016
Abstract: Can conditioning occur without conscious awareness of the contingency between the stimuli? We trained participants on two separate reaction time tasks that ensured attention to the experimental stimuli. The tasks were then interleaved to create a differential Pavlovian contingency between visual stimuli from one task and an airpuff stimulus from the other. Many participants were unaware of the contingency and failed to show differential eyeblink conditioning, despite attending to a salient stimulus that was contingently and contiguously related to the airpuff stimulus over many trials. Manipulation of awareness by verbal instruction dramatically increased awareness and differential eyeblink responding. These findings cast doubt on dual-system theories, which propose an automatic associative system independent of cognition, and provide strong evidence that cognitive processes associated with awareness play a causal role in learning.
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.BIOPSYCHO.2017.08.056
Abstract: Fear generalisation refers to the spread of conditioned fear to stimuli similar but distinct from the original conditioned stimulus. In this study, participants were presented with repeated pairings of a conditioned stimulus with a shock, in either a single-cue or differential conditioning paradigm. Generalisation of fear was then tested by presenting stimuli that were novel, but similar to the conditioned stimulus along a spatial stimulus dimension. Dependent measures were online shock expectancy ratings and skin conductance level. A erse range of generalisation gradients was observed, and the shape of the gradients for both expectancy ratings and skin conductance responses corresponded with participants' verbally reported rules. The findings point to an important role for cognitively controlled processes in human fear generalisation, and provide support for a single-system learning model. They also highlight the potential importance of cognitive reappraisal in clinical treatments for over-generalised fear.
Publisher: Springer Science and Business Media LLC
Date: 27-04-2015
DOI: 10.1038/NCOMMS7838
Abstract: Histone deacetylase inhibitors (HDACi) are approved for treating certain haematological malignancies, however, recent evidence also illustrates they are modulators of the immune system. In experimental models, HDACi are particularly potent against malignancies originating from the B-lymphocyte lineage. Here we examine the ability of this class of compounds to modify both protective and autoimmune antibody responses. In vitro, HDACi affect B-cell proliferation, survival and differentiation in an HDAC-class-dependent manner. Strikingly, treatment of lupus-prone Mrl/lpr mice with the HDACi panobinostat significantly reduces autoreactive plasma-cell numbers, autoantibodies and nephritis, while other immune parameters remain largely unaffected. Immunized control mice treated with panobinostat or the clinically approved HDACi vorinostat have significantly impaired primary antibody responses, but these treatments surprisingly spare circulating memory B cells. These studies indicate that panobinostat is a potential therapy for B-cell-driven autoimmune conditions and HDACi do not induce major long-term detrimental effects on B-cell memory.
Publisher: SAGE Publications
Date: 08-2008
DOI: 10.1080/17470210701503229
Abstract: A laboratory model was developed to study human avoidance learning. Participants could avoid an electric shock signalled by a 5-s conditioned stimulus (CS) by pressing one of a set of response buttons. Self-reported shock expectancy and skin conductance were recorded during a subsequent 10-s interval before shock. Shock expectancy declined when the correct avoidance response was learned and returned when the response was unavailable. Learning transferred to another shock CS. Parallel effects were observed on skin conductance once performance anxiety was controlled by requiring responding on all trials. Learning was faster when the Pavlovian contingencies were trained before introduction of the instrumental response. The results support a cognitive model of anxiety in which performance of an avoidance response reduces expectancy of an aversive outcome and thereby reduces anxiety.
Publisher: BMJ
Date: 16-04-2014
DOI: 10.1136/ANNRHEUMDIS-2013-205139
Abstract: The principle of treating-to-target has been successfully applied to many diseases outside rheumatology and more recently to rheumatoid arthritis. Identifying appropriate therapeutic targets and pursuing these systematically has led to improved care for patients with these diseases and useful guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology, dermatology, internal medicine and clinical immunology, and a patient representative, contributed to this initiative. The majority convened on three occasions in 2012-2013. Twelve topics of critical importance were identified and a systematic literature review was performed. The results were condensed and reformulated as recommendations, discussed, modified and voted upon. The finalised bullet points were analysed for degree of agreement among the task force. The Oxford Centre level of evidence (LoE, corresponding to the research questions) and grade of recommendation (GoR) were determined for each recommendation. The 12 systematic literature searches and their summaries led to 11 recommendations. Prominent features of these recommendations are targeting remission, preventing damage and improving quality of life. LoE and GoR of the recommendations were variable but agreement was >0.9 in each case. An extensive research agenda was identified, and four overarching principles were also agreed upon. Treat-to-target-in-SLE (T2T/SLE) recommendations were developed by a large task force of multispecialty experts and a patient representative. It is anticipated that 'treating-to-target' can and will be applicable to the care of patients with SLE.
Publisher: Elsevier BV
Date: 09-2007
DOI: 10.1016/J.JPSYCHIRES.2006.05.006
Abstract: Previous research [Hofmann SG, Meuret AE, Smits JA, Simon NM, Pollack MH, Eisenmenger K, et al. Augmentation of exposure therapy for social anxiety disorder with D-cycloserine. Archives of General Psychiatry 2006 :298-304 Ressler KJ, Rothbaum BO, Tannenbaum L, Anderson P, Graap K, Zimand E, et al. Cognitive enhancers as adjuncts to psychotherapy: use of d-cycloserine in phobic in iduals to facilitate extinction of fear. Archives of General Psychiatry 2004 :1136-44] suggests that d-cycloserine (DCS) facilitates the reduction of clinical fear in humans. We used a well established intervention to evaluate the effectiveness of administering DCS as an adjunct to exposure therapy in a heightened, but sub-clinical, fear population. Over two studies, 100 spider-fearful participants were allocated to DCS or placebo before treatment and were assessed at pre-, immediate post-, and 3.5 weeks post-treatment. Significant treatment effects and return of fear was observed at follow-up, particularly in non-treatment contexts however, both studies failed to demonstrate any enhancing effects of DCS (50 or 500 mg). DCS did not enhance the reduction of spider fears or the generalisation of treatment of a single session of exposure-based therapy. These results suggest that DCS may not enhance loss of non-clinical levels of fear in human populations.
Publisher: BMJ
Date: 24-11-2013
DOI: 10.1136/ANNRHEUMDIS-2012-202545
Abstract: The introduction of biologics, especially tumour necrosis factor (TNF) inhibitors, has revolutionized the management of chronic inflammatory diseases. However, at least one third of patients with these diseases, receiving TNF inhibitors either do not respond to treatment, or lose initial responsiveness. For a significant proportion, improvement of clinical response is achieved after switching to another anti-TNF drug, suggesting a basis for failure unrelated to the therapeutic target itself. A likely explanation for this is immunogenicity, as all biologics are potentially immunogenic, and the resulting anti-drug antibodies (ADAb) can theoretically decrease the efficacy of biologics and/or induce adverse events. Indeed, in these chronic inflammatory diseases, many studies have now established correlations between ADAb formation, low serum drug levels, and the failure or loss of response to anti-TNF antibodies. This article will review key findings related to ADAb, and propose a model wherein monitoring of drug levels and ADAb may be a predictive tool leading to a better choice of biologics. Such an approach could improve chronic inflammatory disease management toward a personalized and more cost-effective approach.
Publisher: Springer Science and Business Media LLC
Date: 25-07-2016
DOI: 10.1038/SREP29909
Abstract: Ethnicity is a key factor impacting on disease severity in SLE, but molecular mechanisms of these associations are unknown. Type I IFN and MIF have each been associated with SLE pathogenesis. We investigated whether increased SLE severity in Asian patients is associated with either MIF or Type I IFN. SLE patients (n = 151) had prospective recording of disease variables. Serum MIF, and a validated composite score of three Type I IFN-inducible chemokines (IFNCK:CCL2, CXCL10, CCL19) were measured. Associations of MIF and IFNCK score with disease activity were assessed, with persistent active disease (PAD) used as a marker of high disease activity over a median 2.6 years follow up. In univariable analysis, MIF, IFNCK score and Asian ethnicity were significantly associated with PAD. Asian ethnicity was associated with higher MIF but not IFNCK score. In multivariable logistic regression analysis, MIF (OR3.62 (95% CI 1.14,11.5), p = 0.03) and Asian ethnicity (OR3.00 (95% CI 1.39,6.46), p 0.01) but not IFNCK were significantly associated with PAD. These results potentially support an effect of MIF, but not Type I IFN, in heightened SLE disease severity in Asian SLE. The associations of MIF and Asian ethnicity with PAD are at least partly independent.
Publisher: Wiley
Date: 06-2013
DOI: 10.1111/IMJ.12070
Abstract: Ethnic differences in both disease susceptibility and expression have been noted in systemic lupus erythematosus (SLE). This review focuses on the evidence of disparities between SLE patients of Asian and Caucasian descent, the two predominant ethnic groups affected by SLE in the Australian context. While epidemiological studies suggest higher rates of SLE among Asian patients, multi-ethnic cohort studies have allowed direct comparison of disease characteristics between different ethnic groups. Such studies suggest that Asians are affected by more severe SLE across several disease parameters, including increased renal involvement, autoantibody positivity, disease activity and damage accumulation. As delineation of these disparities becomes clearer, uncovering the biological basis of such differences poses a significant opportunity to progress understanding of SLE pathogenesis. Understanding ethnic variation in disease provides a platform for an in idualised approach to risk assessment, monitoring and management of SLE.
Publisher: SAGE Publications
Date: 27-05-2021
Publisher: SAGE Publications
Date: 27-08-2013
Publisher: Informa UK Limited
Date: 08-1994
Publisher: Springer Science and Business Media LLC
Date: 13-06-2006
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.JAUT.2015.05.010
Abstract: Patients with inflammatory autoimmune diseases are routinely treated with synthetic glucocorticoids to suppress immunopathology. A crucial outcome of glucocorticoid exposure is induction of glucocorticoid-induced leucine zipper (GILZ), a protein with multiple functions that include inhibition of key immune cell signalling pathways. Here we report that GILZ maintains a threshold for activation of Th17 responses and IL-17-dependent pathology. GILZ expression was deficient in lesional skin of psoriasis patients and was negatively correlated with the pro-inflammatory cytokines IL-23, IL-17A and IL-22, and with STAT3 expression. Deficiency of GILZ in mice resulted in excessive inflammation and pro-inflammatory cytokine expression in the imiquimod model of psoriasis, and dendritic cells lacking GILZ produced greater IL-1, IL-23 and IL-6 in response to imiquimod stimulation in vitro. These cytokines stimulate Th17 cell differentiation, and we found unchallenged GILZ-deficient mice to have spontaneous production of IL-17A and IL-22 in vivo. We also identified a T cell-intrinsic role for GILZ in limiting Th17 cell formation in vitro in response to Th17-promoting cytokines IL-1β and IL-23. Addition of IL-6 under these conditions suppressed GILZ, allowing T cell proliferation and expression of Th17 genes, whereas exogenous delivery of GILZ using a cell-permeable fusion protein restored regulation of Th17 cell proliferation. Thus, GILZ has a non-redundant function to constrain pathogenic Th17 responses, with clinical implications for psoriasis.
Publisher: Elsevier BV
Date: 04-2015
Publisher: Frontiers Media SA
Date: 11-11-2015
Publisher: BMJ
Date: 11-2016
Publisher: Elsevier BV
Date: 12-2016
Publisher: Elsevier BV
Date: 10-1991
Publisher: Elsevier BV
Date: 09-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2005
Publisher: American Psychological Association (APA)
Date: 2010
DOI: 10.1037/A0018433
Abstract: In 3 experiments, we examined Perruchet, Cleeremans, and Destrebecqz's (2006) double dissociation of cued reaction time (RT) and target expectancy. In this design, participants receive a tone on every trial and are required to respond as quickly as possible to a square presented on 50% of those trials (a partial reinforcement schedule). Participants are faster to respond to the square following many recent tone-square pairings and slower to respond following many tone-alone presentations. Of importance, expectancy of the square is highest when performance on the RT task is poorest-following many tone-alone trials. This finding suggests that RT performance is determined by the strength of a tone-square link and that this link is the product of a non-expectancy-based learning mechanism. The present experiments, however, provide evidence that the speeded RTs are not the consequence of the strengthening and weakening of a tone-square link. Thus, the RT Perruchet effect does not provide evidence for a non-expectancy-based link-formation mechanism.
Publisher: American Psychological Association (APA)
Date: 2012
DOI: 10.1037/A0027385
Abstract: Cues that reliably predict an outcome in an initial phase of training (Phase 1) are learned faster in a second phase of training (Phase 2) than cues that were unreliable in Phase 1. This result is observed despite objectively equal relationships between the cues and the outcomes in Phase 2, and consequently constitutes a nonnormative bias in learning. The present experiments sought to confirm that this learned predictiveness effect is the product of attentional processes (Experiment 1), and to test further whether these processes are under voluntary control or are automatic in nature (Experiment 2). In addition to the usual outcome prediction measure, eye-gaze behavior was also monitored. The results indicated an important role for top-down strategic attentional processes in the learned predictiveness task. In contrast, no evidence for an automatic attentional bias was found.
Publisher: Cambridge University Press (CUP)
Date: 04-2009
Publisher: Springer Science and Business Media LLC
Date: 24-12-2015
Publisher: Springer Science and Business Media LLC
Date: 11-03-2014
Abstract: Systemic lupus erythematosus (SLE) is characterized by multisystem immune-mediated injury in the setting of autoimmunity to nuclear antigens. The clinical heterogeneity of SLE, the absence of universally agreed clinical trial end points, and the paucity of validated therapeutic targets have, historically, contributed to a lack of novel treatments for SLE. However, in 2011, a therapeutic monoclonal antibody that neutralizes the cytokine TNF ligand superfamily member 13B (also known as B-cell-activating factor of the TNF family [BAFF]), belimumab, became the first targeted therapy for SLE to have efficacy in a randomized clinical trial. Because of its specificity, the efficacy of belimumab provides an opportunity to increase understanding of SLE pathophysiology. Although belimumab depletes B cells, this effect is not as powerful as that of other B-cell-directed therapies that have not been proven efficacious in randomized clinical trials. In this article, therefore, we review results suggesting that neutralizing BAFF can have effects on the immune system other than depletion of B cells. We also identify aspects of the BAFF system for which data in relation to SLE are still missing, and we suggest studies to investigate the pathogenesis of SLE and ways to refine anti-BAFF therapies. The role of a related cytokine, TNF ligand superfamily member 13 (also known as a proliferation-inducing ligand [APRIL]) in SLE is much less well understood, and hence this review focuses on BAFF.
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.BIOPSYCHO.2011.05.002
Abstract: Squire et al. have proposed that trace and delay eyeblink conditioning procedures engage separate learning systems: a declarative hippoc al/cortical system associated with conscious contingency awareness, and a reflexive sub-cortical system independent of awareness, respectively (Clark and Squire, 1998 Smith et al., 2005). The only difference between these two procedures is that the conditioned stimulus (CS) and the unconditioned stimulus (US) overlap in delay conditioning, whereas there is a brief interval (e.g., 1s) between them in trace conditioning. In two experiments using the same procedure as Clark and Squire's group, we observed differential conditioning only in participants who showed contingency awareness in a post-experimental questionnaire, with both trace and delay procedures. We interpret these results to suggest that, although there may be multiple brain regions involved in learning, these regions are organized as a coordinated system rather than as separate, independent systems.
Publisher: Elsevier BV
Date: 05-2012
Publisher: Elsevier BV
Date: 05-2003
Publisher: Cold Spring Harbor Laboratory
Date: 09-2004
DOI: 10.1101/LM.79604
Publisher: Informa UK Limited
Date: 08-2004
Publisher: SAGE Publications
Date: 11-07-2013
Abstract: The objective of this study is to determine whether serum concentrations of B cell activating factor from the tumour necrosis factor family (BAFF) and/or a proliferation-inducing ligand (APRIL) are associated with clinical manifestations of systemic lupus erythematosus (SLE). BAFF and APRIL concentrations were quantified using a commercial ELISA in serum s les obtained at the time of clinical assessment in 98 patients, and on 245 s les from 75 of these patients followed prospectively. Serum BAFF was significantly increased, and APRIL decreased, in patients with either renal or central nervous system (CNS) lupus. In contrast, in cross-sectional analysis, there was no correlation between disease activity (SLEDAI-2k) and serum BAFF or APRIL. In longitudinal follow-up, there was no association between changes in serum BAFF or APRIL and changes in SLEDAI-2k, or between baseline serum BAFF or APRIL and subsequent changes in SLEDAI-2k. However, between-visit changes in BAFF were significantly different in patients with increases in SLEDAI-2k ≥ 4, compared to patients whose SLEDAI-2k did not change. Although neither serum BAFF nor APRIL correlated with disease activity in the overall population, elevated serum BAFF and reduced APRIL may be markers of renal and CNS disease in SLE patients.
Publisher: The American Association of Immunologists
Date: 15-05-2015
Abstract: Glucocorticoid (GC)-induced leucine zipper (GILZ) has been shown to mediate or mimic several actions of GC. This study assessed the role of GILZ in self-resolving and GC-induced resolution of neutrophilic inflammation induced by LPS in mice. GILZ expression was increased during the resolution phase of LPS-induced pleurisy, especially in macrophages with resolving phenotypes. Pretreating LPS-injected mice with trans-activator of transcription peptide (TAT)–GILZ, a cell-permeable GILZ fusion protein, shortened resolution intervals and improved resolution indices. Therapeutic administration of TAT-GILZ induced inflammation resolution, decreased cytokine levels, and promoted caspase-dependent neutrophil apoptosis. TAT-GILZ also modulated the activation of the survival-controlling proteins ERK1/2, NF-κB and Mcl-1. GILZ deficiency was associated with an early increase of annexin A1 (AnxA1) and did not modify the course of neutrophil influx induced by LPS. Dexamethasone treatment resolved inflammation and induced GILZ expression that was dependent on AnxA1. Dexamethasone-induced resolution was not altered in GILZ−/− mice due to compensatory expression and action of AnxA1. Our results show that therapeutic administration of GILZ efficiently induces a proapoptotic program that promotes resolution of neutrophilic inflammation induced by LPS. Alternatively, a lack of endogenous GILZ during the resolution of inflammation is compensated by AnxA1 overexpression.
Publisher: American Psychological Association (APA)
Date: 06-2020
DOI: 10.1037/XLM0000779
Publisher: American Psychological Association (APA)
Date: 2022
DOI: 10.1037/XAN0000311
Publisher: American Psychological Association (APA)
Date: 2002
Publisher: American Psychological Association (APA)
Date: 2003
Publisher: Cambridge University Press (CUP)
Date: 09-1993
Publisher: SAGE Publications
Date: 09-2013
DOI: 10.1080/17470218.2012.752854
Abstract: In laboratory contingency learning tasks, people usually give accurate estimates of the degree of contingency between a cue and an outcome. However, if they are asked to estimate the probability of the outcome in the presence of the cue, they tend to be biased by the probability of the outcome in the absence of the cue. This bias is often attributed to an automatic contingency detection mechanism, which is said to act via an excitatory associative link to activate the outcome representation at the time of testing. We conducted 3 experiments to test alternative accounts of contingency bias. Participants were exposed to the same outcome probability in the presence of the cue, but different outcome probabilities in the absence of the cue. Phrasing the test question in terms of frequency rather than probability and clarifying the test instructions reduced but did not eliminate contingency bias. However, removal of ambiguity regarding the presence of additional causes during the test phase did eliminate contingency bias. We conclude that contingency bias may be due to ambiguity in the test question, and therefore it does not require postulation of a separate associative link-based mechanism.
Publisher: Informa UK Limited
Date: 03-2011
Publisher: Springer Science and Business Media LLC
Date: 22-07-2014
Abstract: In the current therapeutic climate, mortality rates from systemic lupus erythematosus (SLE) remain unacceptably high. Although new therapies are on the horizon, pending their emergence and availability, optimization of the currently available therapies is potentially achievable. A 'treat-to-target' approach is now considered routine for many diseases, including rheumatoid arthritis, for which it has substantially improved patient outcomes. The heterogeneity of SLE, as well as lack of universal agreement over methods to measure disease activity and treatment responses, has impeded the development of such an approach for this disease. In this article, the potential benefits of a treatment-target definition are explored, obstacles to the development of a treatment target in SLE are identified, and possible strategies to achieve this goal are discussed.
Publisher: SAGE Publications
Date: 05-1982
Publisher: Elsevier BV
Date: 04-2014
Publisher: Wiley
Date: 12-08-2014
DOI: 10.1111/BPH.12768
Publisher: BMJ
Date: 24-11-2016
DOI: 10.1136/ANNRHEUMDIS-2016-209519
Abstract: Treat-to-target recommendations have identified ‘remission’ as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE. An international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%. The task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions: 1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by …………………. (reference to symptoms, signs, routine labs). 2. For defining remission, a validated index must be used, for ex le, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0 with routine laboratory assessments included, and supplemented with physician's global assessment. 3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics. The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life. The work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.
Publisher: Elsevier BV
Date: 10-2014
Publisher: BMJ
Date: 28-10-2015
Publisher: Springer Science and Business Media LLC
Date: 09-11-2016
Publisher: SAGE Publications
Date: 23-05-2023
Publisher: American Psychological Association (APA)
Date: 02-2019
DOI: 10.1037/XGE0000496
Publisher: SAGE Publications
Date: 10-2002
Publisher: Wiley
Date: 25-05-2015
DOI: 10.1002/ART.39069
Abstract: Mesenchymal stem cells (MSCs) are potent immunosuppressive cells that have shown promise in the treatment of rheumatoid arthritis (RA). Deciphering the intrinsic characteristics of MSCs that correlate with their biologic activity will facilitate their clinical use. Recently, the role of glucocorticoid‐induced leucine zipper (GILZ) in the development of RA has been documented. The aim of this study was to evaluate whether GILZ expression by MSCs may contribute to their therapeutic effect. MSCs were isolated from GILZ‐deficient (GILZ −/− ) mice and wild‐type mice. MSCs (1 × 10 6 cells) were injected twice via the tail vein into mice with collagen‐induced arthritis (CIA). In vitro, we showed that GILZ is a key factor involved in the immunosuppressive potential of MSCs. MSCs derived from GILZ −/− mice did not suppress the proliferation of CD4+ T cells and were less efficient than MSCs derived from WT mice in altering Th17 cell polarization. Thus, we investigated the role of GILZ in an experimental model of arthritis and demonstrated that although WT MSCs significantly reduced paw swelling in arthritic mice, GILZ −/− MSCs did not. Moreover, the magnitude of the effects of GILZ −/− MSCs on Th17 cell frequency was significantly lower than that of WT MSCs. The therapeutic effect of MSCs correlated with the generation of Treg cells bearing the CD4 + RORγt+IL‐17 low IL‐10+ signature, and Th17 cell polarization was GILZ dependent. This study demonstrates that GILZ has an essential role in the therapeutic effectiveness of MSCs in arthritis by favoring Th17 cell polarization toward a regulatory phenotype. Therefore, potentiation of GILZ expression in MSCs could represent a means to enhance their therapeutic effect in autoimmune diseases.
Publisher: Informa UK Limited
Date: 08-1988
Publisher: Wiley
Date: 24-09-2013
DOI: 10.1002/ART.38090
Publisher: American Psychological Association (APA)
Date: 2012
DOI: 10.1037/A0024411
Abstract: Squire and colleagues have proposed that trace and delay eyeblink conditioning are fundamentally different kinds of learning: trace conditioning requires acquisition of a conscious declarative memory for the stimulus contingencies whereas delay conditioning does not. Declarative memory in trace conditioning is thought to generate conditioned responding through the activation of a conscious expectancy for when the unconditioned stimulus (US) is going to occur. Perruchet (1985) has previously shown that in a 50% partial reinforcement design it is possible to dissociate single cue delay eyeblink conditioning from conscious expectancy for the US by examining performance over runs of reinforced and nonreinforced trials. Clark, Manns, and Squire (2001) claim that this dissociation does not occur in trace eyeblink conditioning. In the present experiment we examined the Perruchet effect for short, moderate, and long trace intervals (600, 1000, and 1400 ms) and for the equivalent interstimulus intervals (ISIs) in a delay conditioning procedure. We found evidence for a dissociation of eyeblink CRs and US expectancy over runs regardless of whether there was a delay or a trace arrangement of cues. The reasons for the Perruchet effect are still unclear, but the present data suggest that it does not depend on a separate nondeclarative system of the type proposed by Squire and colleagues.
Publisher: Elsevier BV
Date: 08-2009
Publisher: Oxford University Press
Date: 25-03-2011
Publisher: Springer Science and Business Media LLC
Date: 10-03-2015
Abstract: Australia is a geographically vast but sparsely populated country with many unique factors affecting the practice of rheumatology. With a population comprising minority Indigenous peoples, a historically European-origin majority population, and recent large-scale migration from Asia, the effect of ethnic ersity on the phenotype of rheumatic diseases such as systemic lupus erythematosus (SLE) is a constant of Australian rheumatology practice. Australia has a strong system of universal healthcare and subsidized access to medications, and clinical and research rheumatology are well developed, but inequitable access to specialist care in urban and regional centres, and the complex disconnected structure of the Australian healthcare system, can hinder the management of chronic diseases.
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.BIOPSYCHO.2011.09.007
Abstract: Two experiments examined competition between an instrumental avoidance response and a Pavlovian safety signal for association with omission of electric shock in a human fear conditioning paradigm. Self-reported shock expectancies and skin conductance responses were consistent with blocking of learning of the instrumental contingency by prior training of the Pavlovian contingency, and vice versa. The results support the idea that a common learning mechanism underlies both Pavlovian and instrumental conditioning. The expectancy data suggest that this learning mechanism is cognitive in nature, and that Pavlovian and instrumental learning involve external and internal attributions, respectively. The procedure may thus serve as a laboratory model for attributional processes involved in the acquisition of threat expectancies in anxiety and anxiety disorders.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.BRAT.2018.05.012
Abstract: Trait anxiety has been widely accepted as a vulnerability factor for the development of anxiety disorders. However, few studies have examined how trait anxiety may affect fear generalisation, which is believed to be a core feature of anxiety disorders. Using a single-cue conditioning paradigm, the current study found a range of discrete generalisation gradients in both expectancy ratings and skin conductance, which were highly consistent with participants' reported abstract rules. Trait anxious participants showed the same level of threat expectancy to the conditioned cue as low anxious participants. However they showed over-generalisation to novel test stimuli, but only when they failed to identify a clear rule. This result suggests that over-generalisation of fear may be a special case of the more general principle that trait anxiety is associated with excessive threat appraisal under conditions of ambiguity.
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.BIOPSYCHO.2016.06.007
Abstract: In the Perruchet effect, there is a concurrent dissociation between participants' conditioned responses (CRs) and their expectancy of the unconditioned stimulus (US) across runs of repeated trials. The effect has been taken as evidence for multiple learning processes, but this conclusion follows only if the CR trend is the result of learning. Two experiments examined the role of US recency in generating the observed CR trend. A standard Perruchet condition was compared with a control condition in which US recency was controlled by presenting the US on every trial. The associative contribution was maintained by varying the temporal relationship between the CS and the US. In both experiments the pattern of CRs seen in the Perruchet condition was absent in the control condition, suggesting that the eyeblink trend in the Perruchet effect may be due to a non-associative performance factor such as priming or sensitization arising from recent US presentations.
Publisher: American Psychological Association (APA)
Date: 2002
Publisher: Wiley
Date: 11-1992
Publisher: American Psychological Association (APA)
Date: 07-1984
Publisher: Cold Spring Harbor Laboratory
Date: 17-06-2013
Abstract: Single-cue delay eyeblink conditioning is presented as a prototypical ex le of automatic, nonsymbolic learning that is carried out by subcortical circuits. However, it has been difficult to assess the role of cognition in single-cue conditioning because participants become aware of the simple stimulus contingency so quickly. In this experiment ( n = 166), we masked the contingency to reduce awareness. We observed a strong relationship between contingency awareness and conditioned responding, with both trace and delay procedures. This finding suggests that explicit associative knowledge and anticipatory behavior are regulated by a coordinated system rather than by functionally and neurally distinct systems.
Publisher: Elsevier BV
Date: 09-2017
No related grants have been discovered for Peter Lovibond.