Developing a theory of the emotional impact of auditory hallucinations: an exploratory study

This research examines recent developments in the cognitive model of auditory hallucinations ("voices") in people with psychoses. Following the research of Chadwick and Birchwood (1994), data are presented on the behavioural, cognitive and affective responses to persistent voices of thirty participants with psychoses. After testing the reliability of their interview, data is then compared to that of the Chadwick and Birchwood (1994) sample. In addition, the research aimed to develop the cognitive model of the emotional impact of voices by examining further possible associations with participants' self-evaluations, hypothesising that these evaluations are associated with the affective response. The cognitive assessment of voices shows reasonable inter-rater and test re-test reliability. Compared to the Chadwick and Birchwood (1994) sample, the present sample had a greater proportion of negative affective responses to voices. regardless of their beliefs about the voices' benevolence or malevolence. Participants in this sample were less likely to endorse the voices' omnipotence or omniscience. Similarities were shown in behavioural responses and factors reported as proof of the voices' potential power. Although it was not possible to explore the associations between the content of voices, affective responses, self-evaluations and distress due to a preponderance of negative affective responses in this sample, nevertheless, it was possible to describe these responses. Participants in this sample had a predominantly negative content to their voices. Those who were able to access a personal meaning were found to have, predominantly, negative personal meanings, low self esteem and moderate distress as measured by standardised instruments

Immune Evasion in Glioma

Glioblastoma multiforme (GBM) is the most common form of primary brain cancer and the current prognosis for patients is poor. New therapies are required that target the invasive cells that are characteristic of GBM. GBM is infiltrated by immune cells but, as with other cancers, immune evasion pathways minimise productive anti-tumour immunity. Natural killer (NK) cells are able to recognise and kill tumour cells and are being developed for the immunotherapy of other cancers. The aim of this work was to analyse the interaction between human NK cells and GBM cells in vivo and in vitro, as a prerequisite to future NK cell based immunotherapy of GBM. Analysis of the cell surface phenotype for GBM infiltrating NK and T cells revealed that the tumour microenvironment exerts localised immune evasion mechanisms which downregulate activation receptors and upregulate inhibitory receptors. The interaction of NK cells with patient-derived GBM stem cells, which are thought to be responsible for recurrent disease, was investigated in vitro. A high-throughput, multiplex flow cytometry-based screen of tumour cells revealed the expression of a number of cell surface molecules that regulate NK cell activation. Furthermore, GBM cells were more susceptible to NK cell lysis in vitro compared to a non-cancerous neural progenitor cell line, revealing specificity in the NK cell response. Furthermore, this screen identified potential mechanisms by which GBM might evade immune surveillance in vivo. Targeting these pathways and restoring functional immune surveillance provides a potential route for future immunotherapy of this disease. However, GBM patients often experience cerebral oedema and are treated with immunosuppressive corticosteroids, such as dexamethasone; this induces a similar immunosuppressed phenotype to that observed with the GBM infiltrating NK cells, and inhibits their lytic function. Gene expression profiling identified the transcription factor c-Myc as a key regulator of NK cell activation and as a hub for the immunosuppressive action of steroids and the immunosuppressive cytokine TGF-β. The demonstration that therapeutic steroids target the same pathway as TGF-β and induce immunosuppression has important implications for the use of steroids in patients undergoing immunotherapy

Roles and responsibilities in understanding, accepting and adapting to an uncertain chronic illness trajectory

The aim of this qualitative study was to explore the lived experience of chronic illness during and beyond diagnosis within the context of relationships between patients, family carers and service providers. Findings focus on the ways in which people with chronic illness and their family carers became aware of the prognostic limits of medical information, and the psycho-social processes involved in managing the uncertainty inherent in the illness trajectory within a context of creating and maintaining relationships with favourite members of staff. This has implications for the current policy imperative for self-care and challenges the assumption that biographical support and self-care are mutually exclusive concepts. Findings suggest that it is necessary to combine the promotion of independence with recognition of the importance of continuity of carer across the illness trajectory. This has implications for the introduction of case managers for people with complex chronic illness. Humanism was adopted as an organisational framework that called for primacy to be given to the voices of patients, children and family carers. Symbolic interactionism informed the interpretive premise that this study is only one representation of multiple realities, and grounded theory was used to guide the iterative process of data collection and analysis. Data were collected in two phases; phase one in a general hospital setting with stroke patients, phase two in a special school for physically disabled children with a variety of chronic illnesses. In phase one, observation and interviews were held with stroke patients (n = 9) and their family carers (n = 10) during the hospital stay and following discharge from hospital. Emerging themes influenced the design of a qualitative questionnaire used with service providers (n = 31) to explore contributions to care and interpretations of progress. In phase two the study was extended to explore perceptions held by physically disabled children (n = 12) in a special school setting and their informal carers (n = 16) about the lived experience of chronic illness. Observation and interviews were used with children, based on photographs they had taken. Data from service providers (n = 42) working within special education were collected using questionnaires. Data taken from different diagnostic and age groups were compared to explore commonalities and differences in representations of chronic illness. Common themes emerged that cut across diagnostic groups and service responses to those groups. The themes are presented in this thesis as three interdependent psycho-social processes intended to manage the uncertainty inherent within the illness trajectory. The processes of understanding, accepting and adapting to uncertainty emerged as central categories. Chronic uncertainty was managed via processes of information management, making comparisons with others, making biographical comparisons with one's self, and maintaining continuity of carer. Findings contribute to increased understanding of the processes of care available to people coping with chronic illness within a multiprofessional context. The innovative nature of this study informs knowledge on several aspects of research into the chronic illness experience, namely, methods of data collection with vulnerable people, practitioner-research, managing multiple pathology, the `expert patient', chronicity, and specialist care outcomes

Mental imagery in bipolar affective disorder versus unipolar depression: Investigating cognitions at times of ‘positive’ mood

AbstractBackgroundCompared to unipolar depression (UD), depressed mood in bipolar disorder (BD) has been associated with amplified negative mental imagery of the future (‘flashforwards’). However, imagery characteristics during positive mood remain poorly explored. We hypothesise first, that unlike UD patients, the most significant positive images of BD patients will be ‘flashforwards’ (rather than past memories). Second, that BD patients will experience more frequent (and more ‘powerful’) positive imagery as compared to verbal thoughts and third, that behavioural activation scores will be predicted by imagery variables in the BD group.MethodsBD (n=26) and UD (n=26) patients completed clinical and trait imagery measures followed by an Imagery Interview and a measure of behavioural activation.ResultsCompared to UD, BD patients reported more ‘flashforwards’ compared to past memories and rated their ‘flashforwards’ as more vivid, exciting and pleasurable. Only the BD group found positive imagery more ‘powerful’, (preoccupying, ‘real’ and compelling) as compared to verbal thoughts. Imagery-associated pleasure predicted levels of drive and reward responsiveness in the BD group.LimitationsA limitation in the study was the retrospective design. Moreover pathological and non-pathological periods of “positive” mood were not distinguished in the BD sample.ConclusionsThis study reveals BD patients experience positive ‘flashforward’ imagery in positive mood, with more intense qualities than UD patients. This could contribute to the amplification of emotional states and goal directed behaviour leading into mania, and differentiate BD from UD

Influence of vitamin C and vitamin E on redox signalling:implications for exercise adaptations

The exogenous antioxidants vitamin C (ascorbate) and vitamin E (α-tocopherol) often blunt favourable cell signalling responses to exercise, suggesting that redox signalling contributes to exercise adaptations. Current theories posit that this antioxidant paradigm interferes with redox signalling by attenuating exercise-induced reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation. The well-documented in vitro antioxidant actions of ascorbate and α-tocopherol and characterisation of the type and source of the ROS/RNS produced during exercise theoretically enables identification of the redox-dependent mechanism responsible for the blunting of favourable cell signalling responses to exercise. This review aimed to apply this reasoning to determine how the aforementioned antioxidants might attenuate exercise-induced ROS/RNS production. The principal outcomes of this analysis are (1) neither antioxidant is likely to attenuate nitric oxide signalling either directly (reaction with nitric oxide) or indirectly (reaction with derivatives, e.g. peroxynitrite) (2) neither antioxidant reacts appreciably with hydrogen peroxide, a key effector of redox signalling (3) ascorbate but not α-tocopherol has the capacity to attenuate exercise-induced superoxide generation and (4) alternate mechanisms, namely pro-oxidant side reactions and/or reduction of bioactive oxidised macromolecule adducts, are unlikely to interfere with exercise-induced redox signalling. Out of all the possibilities considered, ascorbate mediated suppression of superoxide generation with attendant implications for hydrogen peroxide signalling is arguably the most cogent explanation for blunting of favourable cell signalling responses to exercise. However, this mechanism is dependent on ascorbate accumulating at sites rich in NADPH oxidases, principal contributors to contraction mediated superoxide generation, and outcompeting nitric oxide and superoxide dismutase isoforms. The major conclusions of this review are: (1) direct evidence for interference of ascorbate and α-tocopherol with exercise-induced ROS/RNS production is lacking (2) theoretical analysis reveals that both antioxidants are unlikely to have a major impact on exercise-induced redox signalling and (3) it is worth considering alternate redox-independent mechanisms

Decision support for risk prioritisation of environmental health hazards in a UK city.

BACKGROUND: There is increasing appreciation of the proportion of the health burden that is attributed to modifiable population exposure to environmental health hazards. To manage this avoidable burden in the United Kingdom (UK), government policies and interventions are implemented. In practice, this procedure is interdisciplinary in action and multi-dimensional in context. Here, we demonstrate how Multi Criteria Decision Analysis (MCDA) can be used as a decision support tool to facilitate priority setting for environmental public health interventions within local authorities. We combine modelling and expert elicitation to gather evidence on the impacts and ranking of interventions. METHODS: To present the methodology, we consider a hypothetical scenario in a UK city. We use MCDA to evaluate and compare the impact of interventions to reduce the health burden associated with four environmental health hazards and rank them in terms of their overall performance across several criteria. For illustrative purposes, we focus on heavy goods vehicle controls to reduce outdoor air pollution, remediation to control levels of indoor radon, carbon monoxide and fitting alarms, and encouraging cycling to target the obesogenic environment. Regional data was included as model evidence to construct a ratings matrix for the city. RESULTS: When MCDA is performed with uniform weights, the intervention of heavy goods vehicle controls to reduce outdoor air pollution is ranked the highest. Cycling and the obesogenic environment is ranked second. CONCLUSIONS: We argue that a MCDA based approach provides a framework to guide environmental public health decision makers. This is demonstrated through an online interactive MCDA tool. We conclude that MCDA is a transparent tool that can be used to compare the impact of alternative interventions on a set of pre-defined criteria. In our illustrative example, we ranked the best intervention across the equally weighted selected criteria out of the four alternatives. Further work is needed to test the tool with decision makers and stakeholders

Quality after the QOF? Before dismantling it, we need a redefined measure of ‘quality’

This is the author accepted manuscript. The final version is available from Royal College of General Practitioners via the DOI in this record.n/aNational Institute for Health Research (NIHR

Loot box engagement: relationships with educational attainment, employment status and earnings in a cohort of 16 000 United Kingdom gamers

© 2022 The Authors. Published by Wiley. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1111/add.15837Background and Aims: Loot boxes are purchasable randomised rewards in video games that share structural and psychological similarities with gambling. Systematic review evidence has established reproducible associations between loot box purchasing and both problem gambling and problem video gaming. We aimed to measure the association between loot box engagement and socioeconomic correlates. Design: The study was a cross-sectional online survey using the recruitment platform, Prolific. Setting: United Kingdom (UK). Participants: A cohort of 16 196 UK adults (18 + years) self-reporting as video gamers. Measurements: Respondents were asked about their game-related purchasing behaviour (including loot boxes), recent monthly spend on loot boxes and gambling engagement (gambling in any form; gambling online; playing ‘social casino’ games). A range of demographic variables were simultaneously captured, including age, sex, ethnicity, earnings, employment and educational attainment. Findings: Overall, 17.16% of gamers in our cohort purchased loot boxes, with a mean self-reported monthly spend of £29.12. These loot box purchasers are more likely to gamble (45.97% gamble) than people who make other types of game-related purchases (on aggregate, 28.13% of non-loot box purchasers gamble), and even greater still than those who do not make any game related purchases (24.38% gamble P < 0.001). Loot box engagement (as binary yes/no or as monthly spend normalised to earnings) was significantly associated with younger age (P < 0.001 and P < 0.001; respectively, for binary yes/no and monthly spend, adjusted for false discovery rate correction), male sex (P < 0.001 and P = 0.025), non-university educational attainment (P < 0.001 and P < 0.001) and unemployment (P = 0.003 and P = < 0.001). Lower earners spent a higher proportion of monthly earnings on loot boxes (P < 0.001). Conclusions: The demographic associations of video game loot box engagement (younger age, male sex, non-university educational attainment and unemployment) mirror those of other addictive and problematic behaviours, including disordered gambling, drug and alcohol misuse.Gamble Aware.Published versio

A randomised double-blinded sham controlled cross-over trial of tined lead sacral nerve stimulation testing for chronic constipation

Objectives Sacral nerve stimulation (SNS) may provide long-term symptom relief to patients suffering from chronic constipation. Patients are currently selected for SNS using a 2-week peripheral nerve evaluation (PNE) comprising stimulation by temporary leads. However, only 40% of test responders receive long-term benefit from treatment meaning that healthcare costs per successfully treated patient are too high. The primary objective was to assess tined-lead testing to predict benefit from SNS for chronic constipation. Patients and methods A randomized double-blind sham-controlled cross-over design evaluated enhanced PNE (ePNE) using tined quadripolar electrode leads over 6 weeks. The design differentiated between patients with discriminate and indiscriminate responses to testing. A score improvement of 25% or more was considered to be a positive response within a stimulation period. The primary outcome was the proportion of patients showing a reduction of at least 0.5 in constipation symptom score at 6 months. Results A total of 45 patients were randomized, of whom 29 (64.4%) were test-phase responders. Of these, 27 were implanted providing permanent SNS. During ePNE, seven (18%) were discriminate responders, 22 (56%) were indiscriminate responders and 10 (26%) were nonresponders. Six patients were withdrawn during the test phase because of infection or noncompliance. At 6 months, there was no significant difference in primary outcome between discriminate and indiscriminate responders (60 vs. 57%, P=0.76). The study was terminated prematurely because of a persistent infection rate of 10 (22%) during ePNE of which nine (20%) were severe. Conclusion ePNE is a poor predictor of treatment response at 6 months. This suggests a strong and persistent placebo response during both SNS PNE and treatment. An extended 6-week PNE poses a high risk of infection