96 research outputs found

    Neuropsychological functioning and jumping to conclusions in delusions

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    Background: It has been consistently demonstrated that delusions are related to jumping to conclusions (JTC), a data-gathering bias and potential candidate endophenotype of psychosis. Recent research suggests that JTC may be a marker of treatment response. However, we know little about the factors contributing to the occurrence of this reasoning bias. This study investigated the relationship between JTC and hypothesised deficits in working memory, employing standard well-validated neuropsychological tests, in people with current delusions. Method: One hundred and twenty six people with schizophrenia spectrum psychosis and current delusions were assessed for current symptoms, and tested for JTC. We compared performance on tests of working memory in those with the reasoning bias and those without. Results: As expected, 30–40% of this sample of people with current delusions showed the JTC bias. There were no differences in premorbid IQ between those with and without the JTC reasoning bias. However, the performance of the JTC group was significantly worse on tests of working memory. Conclusions: The JTC data-gathering bias is associated with impairments in working memory. New non-pharmacological interventions for people with delusions, designed to improve data gathering, may benefit from incorporating strategies to overcome deficits in working memory

    IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell responses against malaria liver stages.

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    CD4+ T cells are crucial to the development of CD8+ T cell responses against hepatocytes infected with malaria parasites. In the absence of CD4+ T cells, CD8+ T cells initiate a seemingly normal differentiation and proliferation during the first few days after immunization. However, this response fails to develop further and is reduced by more than 90%, compared to that observed in the presence of CD4+ T cells. We report here that interleukin-4 (IL-4) secreted by CD4+ T cells is essential to the full development of this CD8+ T cell response. This is the first demonstration that IL-4 is a mediator of CD4/CD8 cross-talk leading to the development of immunity against an infectious pathogen

    Measuring reasoning in paranoia: development of the Fast and Slow Thinking questionnaire

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    Paranoid thoughts are common across the psychosis continuum. It is well established that reasoning biases (conceived as an overreliance on fast thinking and lack of willingness and/or ability to engage in slow thinking) contribute to paranoia. Targeted therapies have shown promise in improving reasoning in order to reduce paranoia. Psychometrically robust and easy-to-use measures of these thinking styles will assist research and clinical practice. Existing assessments include experimental tasks that are complex to administer or self-report measures that have limitations in comprehensively assessing cognitive biases in paranoia. We have developed the first questionnaire to assess fast and slow thinking biases related to paranoid thoughts, and here report on its evaluation. In study 1, we generated, evaluated, and extracted items reflecting reasoning, and assessed their reliability and validity in a non-clinical sample (n = 209). In study 2, we replicated the factor analysis and psychometric evaluation in a clinical sample (n = 265). The resultant Fast and Slow Thinking (FaST) questionnaire consists of two 5-item scales reflecting fast and slow thinking and is therefore brief and suitable for use in both research and clinical practice. The fast thinking scale is reliable and valid. Reliability and criterion validity of the slow scale shows promise. It had limited construct validity with objective reasoning assessments in the clinical group, possibly due to impaired meta-cognitive awareness of slow thinking. We recommend the FaST questionnaire as a new tool for improving understanding of reasoning biases in paranoia and supporting targeted psychological therapies

    Evidence for Trait Related Theory of Mind Impairment in First Episode Psychosis Patients and Its Relationship with Processing Speed: A 3 Year Follow-up Study

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    This study aimed to confirm whether first-episode psychosis patients present a stable trait impairment in theory of mind (ToM) and to examine the potential relationship between ToM and clinical symptomatology and neurocognition. Patients with a first episode of psychosis (N = 160) and healthy controls (N = 159) were assessed with an extensive neuropsychological test battery, which included a mental state decoding task known as "The Reading the Mind in the Eyes" (Eyes test), at baseline and reassessed after 1 and 3 years. The clinical group performed below healthy controls on the Eyes test while not showing test-retest differences between baseline and follow-up administrations. Analyses revealed age, education and premorbid IQ as potential moderators. Poorer performance on the Eyes test was not linked to clinical symptomatology but was associated with greater neurocognitive deficit, particularly related to processing speed. The persistence of ToM deficits in patients suggests that there are trait related metalizing impairments in first episode psychosis. This study shows the influence of processing speed and moderator variables on efficient ToM.This work was supported by the Instituto de Salud Carlos III (FISCP07/00008andPI14/00918) and Fundación Instituto de Investigación Marqués de Valdecilla. No pharmaceutical industry has participated in the study

    Use of selective serotonin reuptake inhibitors and risk of re-operation due to post-surgical bleeding in breast cancer patients: a Danish population-based cohort study

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    <p>Abstract</p> <p>Background</p> <p>Selective serotonin reuptake inhibitors (SSRI) decrease platelet-function, which suggests that SSRI use may increase the risk of post-surgical bleeding. Few studies have investigated this potential association.</p> <p>Methods</p> <p>We conducted a population-based study of the risk of re-operation due to post-surgical bleeding within two weeks of primary surgery among Danish women with primary breast cancer. Patients were categorised according to their use of SSRI: never users, current users (SSRI prescription within 30 days of initial breast cancer surgery), and former users (SSRI prescription more than 30 days before initial breast cancer surgery). We calculated the risk of re-operation due to post-surgical bleeding within 14 days of initial surgery, and the relative risk (RR) of re-operation comparing SSRI users with never users of SSRI adjusting for potential confounders.</p> <p>Results</p> <p>389 of 14,464 women (2.7%) were re-operated. 1592 (11%) had a history of SSRI use. Risk of re-operation was 2.6% among never users, 7.0% among current SSRI users, and 2.7% among former users. Current users thus had an increased risk of re-operation due to post-operative bleeding (adjusted relative risk = 2.3; 95% confidence interval (CI) = 1.4, 3.9) compared with never users. There was no increased risk of re-operation associated with former use of SSRI (RR = 0.93, 95% CI = 0.66, 1.3).</p> <p>Conclusions</p> <p>Current use of SSRI is associated with an increased risk of re-operation due to bleeding after surgery for breast cancer.</p

    Psychological characteristics of religious delusions

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    Purpose Religious delusions are common and are considered to be particularly difficult to treat. In this study we investigated what psychological processes may underlie the reported treatment resistance. In particular, we focused on the perceptual, cognitive, affective and behavioural mechanisms held to maintain delusions in cognitive models of psychosis, as these form the key treatment targets in cognitive behavioural therapy. We compared religious delusions to delusions with other content. Methods Comprehensive measures of symptoms and psychological processes were completed by 383 adult participants with delusions and a schizophrenia spectrum diagnosis, drawn from two large studies of cognitive behavioural therapy for psychosis. Results Binary logistic regression showed that religious delusions were associated with higher levels of grandiosity (OR 7.5; 95 % CI 3.9–14.1), passivity experiences, having internal evidence for their delusion (anomalous experiences or mood states), and being willing to consider alternatives to their delusion (95 % CI for ORs 1.1–8.6). Levels of negative symptoms were lower. No differences were found in delusional conviction, insight or attitudes towards treatment. Conclusions Levels of positive symptoms, particularly anomalous experiences and grandiosity, were high, and may contribute to symptom persistence. However, contrary to previous reports, we found no evidence that people with religious delusions would be less likely to engage in any form of help. Higher levels of flexibility may make them particularly amenable to cognitive behavioural approaches, but particular care should be taken to preserve self-esteem and valued aspects of beliefs and experiences

    Plasminogen binding and activation at the breast cancer cell surface: the integral role of urokinase activity

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    INTRODUCTION: The regulation of extracellular proteolytic activity via the plasminogen activation system is complex, involving numerous activators, inhibitors, and receptors. Previous studies on monocytic and colon cell lines suggest that plasmin pre-treatment can increase plasminogen binding, allowing the active enzyme to generate binding sites for its precursor. Other studies have shown the importance of pre-formed receptors such as annexin II heterotetramer. However, few studies have used techniques that exclusively characterise cell-surface events and these mechanisms have not been investigated at the breast cancer cell surface. METHODS: We have studied plasminogen binding to MCF-7 in which urokinase plasminogen activator receptor (uPAR) levels were upregulated by PMA (12-O-tetradecanoylphorbol-13-acetate) stimulation, allowing flexible and transient modulation of cell-surface uPA. Similar experiments were also performed using MDA-MB-231 cells, which overexpress uPAR/uPA endogenously. Using techniques that preserve cell integrity, we characterise the role of uPA as both a plasminogen receptor and activator and quantify the relative contribution of pre-formed and cryptic plasminogen receptors to plasminogen binding. RESULTS: Cell-surface plasminogen binding was significantly enhanced in the presence of elevated levels of uPA in an activity-dependent manner and was greatly attenuated in the presence of the plasmin inhibitor aprotinin. Pre-formed receptors were also found to contribute to increased plasminogen binding after PMA stimulation and to co-localise with uPA/uPAR and plasminogen. Nevertheless, a relatively modest increase in plasminogen-binding capacity coupled with an increase in uPA led to a dramatic increase in the proteolytic capacity of these cells. CONCLUSION: We show that the majority of lysine-dependent plasminogen binding to breast cancer cells is ultimately regulated by plasmin activity and is dependent on the presence of significant levels of active uPA. The existence of a proteolytic positive feedback loop in plasminogen activation has profound implications for the ability of breast cancer cells expressing high amounts of uPA to accumulate a large proteolytic capacity at the cell surface, thereby conferring invasive potential

    SlowMo, a digital therapy targeting reasoning in paranoia, versus treatment as usual in the treatment of people who fear harm from others: study protocol for a randomised controlled trial

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    Background: Paranoia is one of the most common symptoms of schizophrenia-spectrum disorders, and is associated with significant distress and disruption to the person’s life. Developing more effective and accessible psychological interventions for paranoia is a clinical priority. Our research team has approached this challenge in two main ways: firstly, by adopting an interventionist causal approach to increase effectiveness and secondly, by incorporating user-centred inclusive design methods to enhance accessibility and usability. Our resultant new digital intervention, SlowMo, intensively targets a reasoning style associated with paranoia, fast thinking, characterised by jumping to conclusions and belief inflexibility. It consists of an easy-to-use, enjoyable and memorable digital interface. An interactive web-based app facilitates delivery of face-to-face meetings which is then synchronised with an innovative mobile app for use in daily life. Methods/Design: We aim to test the clinical efficacy of SlowMo over 24 weeks to determine the mechanisms through which it reduces paranoia, and to identify participant characteristics that moderate its effectiveness. In a parallel-group randomised controlled trial, with 1:1 allocation, 360 participants with distressing persecutory beliefs will be independently randomised to receive either the SlowMo intervention added to treatment as usual (TAU) or TAU, using randomly varying permuted blocks, stratified by paranoia severity and site. Research workers will be blind to therapy allocation. The primary outcome is paranoia severity over 24 weeks; our hypothesised mechanism of change is reasoning; moderators include negative symptoms and working memory; and secondary outcomes include wellbeing, quality of life, and service use. The accessibility, usability and acceptability of the digital platform will be assessed. Discussion: SlowMo has been developed as the first blended digital therapy to target fears of harm from others through an inclusive design approach. In addition to testing its efficacy, this trial will add to our understanding of psychological mechanisms in paranoia. The study will examine the usability and adherence of a novel digital therapy, including an app for self-management, in a large sample of people affected by severe mental health difficulties

    Structured models of cell migration incorporating molecular binding processes

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    The dynamic interplay between collective cell movement and the various molecules involved in the accompanying cell signalling mechanisms plays a crucial role in many biological processes including normal tissue development and pathological scenarios such as wound healing and cancer. Information about the various structures embedded within these processes allows a detailed exploration of the binding of molecular species to cell-surface receptors within the evolving cell population. In this paper we establish a general spatio-temporal-structural framework that enables the description of molecular binding to cell membranes coupled with the cell population dynamics. We first provide a general theoretical description for this approach and then illustrate it with two examples arising from cancer invasion
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