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INTRODUCTION: Hereditary factor X deficiency is a rare bleeding disorder, with limited treatment options. This paper describes the approach to pre-clinical development and characterization of a high-purity plasma-derived factor X concentrate, to achieve orphan drug marketing authorization for the treatment of hereditary factor X deficiency. METHODS: A chromatographic process was developed, to purify factor X from human plasma for fractionation. The product was characterized using in vitro, in vivo and ex vivo tests for potency, purity, thrombogenicity, immunogenicity, toxicity and stability. RESULTS: The production process complied with good pharmaceutical manufacturing practice. It achieved 6000-fold purification and 100-fold concentration of the factor X protein compared to human plasma. The factor X protein was 94%-96% pure. Other residual plasma proteins were well below levels in plasma, minimizing potential interference in hemostasis after therapeutic administration. Effective virus-reduction during manufacture, and the absence of thrombogenicity, toxicity and immunogenic potential were confirmed, addressing the main safety concerns historically associated with plasma-derived therapeutics. The freeze-dried product remained stable between +2°C and +30°C for at least three years. After reconstitution with water for injections, the factor X activity was maintained for at least 48 h at +18°C to +22°C. CONCLUSION: Targeted pre-clinical development of the first highly-purified concentrate to treat hereditary factor X deficiency is described. Following international guidelines for nonclinical safety testing, particular strategies were adopted for unmodified products derived from human blood plasma. This approach may also be relevant to the development of other ultra-orphan medicinal products.
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Deficiencia del Factor X , Factor X , Humanos , Factor X/uso terapéutico , Deficiencia del Factor X/tratamiento farmacológico , Deficiencia del Factor X/complicaciones , Hemorragia/complicaciones , Plasma , Preparaciones FarmacéuticasRESUMEN
BACKGROUND: Burn inhalation injury (BII) is a major cause of burn-related mortality and morbidity. Despite published practice guidelines, no consensus exists for the best strategies regarding diagnosis and management of BII. A modified DELPHI study using the RAND/UCLA (University of California, Los Angeles) Appropriateness Method (RAM) systematically analysed the opinions of an expert panel. Expert opinion was combined with available evidence to determine what constitutes appropriate and inappropriate judgement in the diagnosis and management of BII. METHODS: A 15-person multidisciplinary panel comprised anaesthetists, intensivists and plastic surgeons involved in the clinical management of major burn patients adopted a modified Delphi approach using the RAM method. They rated the appropriateness of statements describing diagnostic and management options for BII on a Likert scale. A modified final survey comprising 140 statements was completed, subdivided into history and physical examination (20), investigations (39), airway management (5), systemic toxicity (23), invasive mechanical ventilation (29) and pharmacotherapy (24). Median appropriateness ratings and the disagreement index (DI) were calculated to classify statements as appropriate, uncertain, or inappropriate. RESULTS: Of 140 statements, 74 were rated as appropriate, 40 as uncertain and 26 as inappropriate. Initial intubation with ≥ 8.0 mm endotracheal tubes, lung protective ventilatory strategies, initial bronchoscopic lavage, serial bronchoscopic lavage for severe BII, nebulised heparin and salbutamol administration for moderate-severe BII and N-acetylcysteine for moderate BII were rated appropriate. Non-protective ventilatory strategies, high-frequency oscillatory ventilation, high-frequency percussive ventilation, prophylactic systemic antibiotics and corticosteroids were rated inappropriate. Experts disagreed (DI ≥ 1) on six statements, classified uncertain: the use of flexible fiberoptic bronchoscopy to guide fluid requirements (DI = 1.52), intubation with endotracheal tubes of internal diameter < 8.0 mm (DI = 1.19), use of airway pressure release ventilation modality (DI = 1.19) and nebulised 5000IU heparin, N-acetylcysteine and salbutamol for mild BII (DI = 1.52, 1.70, 1.36, respectively). CONCLUSIONS: Burns experts mostly agreed on appropriate and inappropriate diagnostic and management criteria of BII as in published guidance. Uncertainty exists as to the optimal diagnosis and management of differing grades of severity of BII. Future research should investigate the accuracy of bronchoscopic grading of BII, the value of bronchial lavage in differing severity groups and the effectiveness of nebulised therapies in different severities of BII.
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Quemaduras , Lesión Pulmonar , Humanos , Acetilcisteína , Quemaduras/terapia , Respiración Artificial , Heparina , AlbuterolRESUMEN
In the UK, the first 'lockdown' of the COVID-19 pandemic necessitated a rapid shift to online learning and digital technologies in Higher Education (HE). While the situation was unprecedented, extant literature on online learning suggested there would be challenges, opportunities, and benefits to this transition, and we sought to understand these via a case study of one UK HEI department at this time. To draw out in-depth and nuanced accounts of this (at time of investigation-unstudied) scenario, qualitative data were collected via semi-structured online interview or written reflection. To explore, identify and understand the experiences from both sides, and with a diverse sample, we purposively recruited both staff (n = 10) and students (n = 12), from various roles and backgrounds, including those with additional learning and/or mental health needs. The 'bricolage' data were analysed inductively, utilising a latent reflexive approach, and organised into a framework around five core themes: 'methods and means of engagement'; 'learning maintenance, destruction and construction'; 'remote education and resource accessibility and literacy'; 'support and communication'; and 'life and learning: responses, adaptations and impacts'. Within these, a range of challenges, successes and, most importantly, future learning and innovation outcomes were identified by staff and students, particularly relevant to working with and supporting students with additional needs in the online learning forum. These discoveries informed a set of practical recommendations, provided here in Box 1, for (rapid implementation of) online learning (in times of stress).
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BACKGROUND: Schizophrenia is a complex, heterogeneous disorder, with highly variable treatment outcomes, and relatively little is known about what is important to patients. The aim of the study was to understand treatment outcomes informal carers perceive to be important to people with schizophrenia. METHOD: Qualitative interview study with 34 individuals and 8 couples who care for a person with schizophrenia/schizoaffective disorder. Interviews were transcribed verbatim and analysed by a thematic framework based approach. RESULTS: Carers described well-recognised outcomes of importance, alongside more novel outcomes relating to: Safety (of the patient/others); insight (e.g. into non-reality of psychotic phenomena); respite from fear, distress or pain; socially acceptable behaviour; getting out of the house; attainment of life milestones; changes in personality and/or temperament; reduction of vulnerability to stress; and several aspects of physical health. CONCLUSIONS: These findings have the potential to inform the development of patient- or carer- focused outcome measures that take into account the full range of domains that carers feel are important for patients.
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Actitud Frente a la Salud , Cuidadores/psicología , Esquizofrenia/terapia , Adulto , Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Investigación Cualitativa , Resultado del TratamientoRESUMEN
OBJECTIVE: Conduct a deep exploration of the outcomes that matter to people with a diagnosis of schizophrenia and understand from their perspective how these outcomes can be achieved. SAMPLE AND METHODS: In-depth qualitative interviews were conducted with 22 people with a diagnosis of schizophrenia. Interviews were analysed using thematic frameworks, and a realist informed theories of change approach. RESULTS: Our study revealed the potential causal relationships between the context of a person's life, short-term goals and long-term outcomes. We provide a nuanced and detailed exploration of outcomes that matter for people with schizophrenia in relation to self-defined well-being. Achieving life milestones, feeling safe and outcomes related to improved physical health along with employment, a positive sense of self and psychosocial outcomes, were highly valued. For short- and long-term outcomes to be achieved, individuals required medication with minimal side-effects, cognitive behavioural therapy, family/social support and meaningful activities in their lives. Well-being was influenced by life context and short- and long-term outcomes, but in a circular nature also framed what short-term goals could be achieved. CONCLUSIONS: Working with people with a diagnosis of schizophrenia to identify and achieve better outcomes will necessitate a person-centred approach. This will require an appreciation of the relationship between the statutory and non-statutory resources that are available and a consideration of an individual's current well-being status. This approach acknowledges personal strengths and encourages ownership of goals and supports self-management.
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Estado de Salud , Salud Mental , Medición de Resultados Informados por el Paciente , Esquizofrenia/terapia , Psicología del Esquizofrénico , Adulto , Antipsicóticos/efectos adversos , Cognición , Terapia Cognitivo-Conductual/métodos , Femenino , Objetivos , Conocimientos, Actitudes y Práctica en Salud , Humanos , Relaciones Interpersonales , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Autoimagen , Apoyo SocialRESUMEN
BACKGROUND: North American studies show bipolar disorder is associated with elevated rates of problem gambling; however, little is known about rates in the different presentations of bipolar illness. AIMS: To determine the prevalence and distribution of problem gambling in people with bipolar disorder in the UK. METHOD: The Problem Gambling Severity Index was used to measure gambling problems in 635 participants with bipolar disorder. RESULTS: Moderate to severe gambling problems were four times higher in people with bipolar disorder than in the general population, and were associated with type 2 disorder (OR = 1.74, P = 0.036), history of suicidal ideation or attempt (OR = 3.44, P = 0.02) and rapid cycling (OR = 2.63, P = 0.008). CONCLUSIONS: Approximately 1 in 10 patients with bipolar disorder may be at moderate to severe risk of problem gambling, possibly associated with suicidal behaviour and a rapid cycling course. Elevated rates of gambling problems in type 2 disorder highlight the probable significance of modest but unstable mood disturbance in the development and maintenance of such problems.
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Trastorno Bipolar/complicaciones , Trastorno Depresivo Mayor/complicaciones , Juego de Azar/epidemiología , Adolescente , Adulto , Afecto , Anciano , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Índice de Severidad de la Enfermedad , Distribución por Sexo , Ideación Suicida , Intento de Suicidio , Reino Unido/epidemiología , Adulto JovenRESUMEN
Video gamers can play to negate the psychological impact of stress, which may become problematic when users over-rely on the stress relief potential of gaming. This study used a repeated measures experimental design to investigate the relationships between stress, video gaming, and problematic video gaming behaviours in a convenience sample of 40 students at a UK university. The results indicated that positive affect increased and negative affect decreased, whilst a biological stress measure (instantaneous pulse rate) also decreased after a short video gaming session (t(36) = 4.82, p < 0.001, d = 0.79). The results also suggested that video gaming can act as a short-term buffer against the physiological impact of stress. Further research should focus on testing individuals who have been tested for gaming disorder, as opposed to the general population. Research could also utilise variations of the methodological framework used in this study to examine the intensity of a stress relief effect under different social situations. The study's findings in relation to published works are also discussed.
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In a pre-registered survey linked to this paper (Exploring the relationships between psychological variables and loot box engagement, part 1: pre-registered hypotheses), we confirmed bivariate associations between engagement with loot boxes (purchasable randomized rewards in video games) and measures of problem gambling, problem video gaming, impulsivity, gambling cognitions, experiences of game-related 'flow', psychological distress and reduced wellbeing. However, these variables have complex relationships, so to gain further insights, we analysed the dataset (1495 gamers who purchase loot boxes and 1223 purchasers of non-randomized content) in a series of Bayesian mixed-effects multiple regressions with a zero-inflation component. The results challenge some well-established results in the literature, including associations between loot box engagement and problematic gambling measures, instead suggesting that this relationship might be underpinned by shared variance with problem video gaming and gambling-related cognitions. An entirely novel discovery revealed a complex interaction between experiences of flow and loot box engagement. Distress and wellbeing are both (somewhat contradictorily) predictive of participants engaging with loot boxes, but neither correlate with increasing loot box risky engagement/spend (among those who engage). Our findings unravel some of the nuances underpinning loot box engagement, yet remain consistent with narratives that policy action on loot boxes will have benefits for harm minimization.
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Receiving digital healthcare consultations for weight management, in place of in-person appointments, has proliferated in recent years, accelerated by the COVID-19 pandemic. The objective of the present study was to investigate patients' experiences of digital weight management services (DWMS) provided by the National Health Service (NHS). Particular emphasis was placed on examining the perceived benefits and limitations of DWMS so as to identify potential means of improving provision. Sixteen patients (eight male; eight female) accessing digital consultations at one of two West Midlands (UK) NHS trusts, participated in semi-structured interviews. Interviews were transcribed verbatim and analysed via thematic analysis. We identified three overarching themes and associated sub-themes that reflect the perceived benefits and limitations of service provision as identified by patients. These were technology acceptability (sub-themes 'challenges', 'requirements/facilitators', and 'beneficial features'); treatment acceptability (sub-themes 'treatment features', 'patient attributes', and 'practitioner skills'); and treatment efficacy (sub-themes 'treatment features', 'patient attributes', and 'practitioner skills'). Themes identified in this study have informed recommendations intended to enhance acceptability of DWMS technology and treatment, potentially encouraging engagement and increasing treatment efficacy. Limitations of the present study and recommendations for further research are also presented.
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COVID-19 , Medicina Estatal , Humanos , Masculino , Femenino , Pandemias , Investigación Cualitativa , Derivación y ConsultaRESUMEN
Loot boxes are purchasable randomized 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, perhaps driven by a range of overlapping psychological processes (e.g. impulsivity, gambling-related cognitions, etc.) It has also been argued that loot box engagement may have negative influences on player financial and psychological wellbeing. We conducted a pre-registered survey of 1495 loot box purchasing gamers (LB cohort) and 1223 gamers who purchase other, non-randomized game content (nLB cohort). Our survey confirms 15 of our 23 pre-registered hypotheses against our primary outcome (risky loot box engagement), establishing associations with problem gambling, problem gaming, impulsivity, gambling cognitions, experiences of game-related 'flow' and specific 'distraction and compulsion' motivations for purchase. Results with hypotheses concerning potential harms established that risky loot box engagement was negatively correlated with wellbeing and positively correlated with distress. Overall, results indicate that any risks from loot boxes are liable to disproportionately affect various 'at risk' cohorts (e.g. those experiencing problem gambling or video gaming), thereby reiterating calls for policy action on loot boxes.
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Loot boxes are purchasable items in video games with a chance-based outcome. They have attracted substantial attention from academics and legislators over recent years, partly because of associations between loot box engagement and problem gambling. Some researchers have suggested that loot boxes may act as a gateway into subsequent gambling and/or problem gambling. However, such "gateway effects" have not been formally investigated. Using a survey of 1102 individuals who both purchase loot boxes and gamble, we found that 19.87% of the sample self-reported either "gateway effects" (loot boxes causally influencing subsequent gambling) or "reverse gateway effects" (gambling causally influencing subsequent loot box engagement). Both subsets of participants had higher scores for problem gambling, problem video gaming, gambling-related cognitions, risky loot boxes engagement, and impulsivity. These individuals also had a tendency for higher loot box and gambling spend; suggesting that potential gateway effects are related to measurable risks and harms. Moreover, the majority of participants reporting gateway effects were under 18 when they first purchased loot boxes. Content analysis of free text responses revealed several reasons for self-reported gateway effects, the most frequent of which were sensation-seeking, normalisation of gambling-like behaviours, and the addictive nature of both activities. Whilst the cross-sectional nature of our findings cannot conclusively establish directions of causality, thus highlighting the need for longitudinal research, we conclude that there is a case for legislation on loot boxes for harm minimisation purposes.
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Conducta Adictiva , Juego de Azar , Juegos de Video , Estudios Transversales , Humanos , Conducta ImpulsivaRESUMEN
BACKGROUND 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.
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Conducta Adictiva , Juego de Azar , Juegos de Video , Adulto , Conducta Adictiva/psicología , Estudios Transversales , Empleo , Femenino , Juego de Azar/psicología , Humanos , Masculino , Juegos de Video/psicologíaRESUMEN
Rising dementia incidence is likely to increase pressures on healthcare services, making effective well coordinated care imperative. Yet, barriers to this care approach exist which, we argue, might be understood by focussing on identity dynamics at the frontlines of care. In this article, we draw upon findings from an ethnographic study of healthcare assistants (HCAs) from three dementia wards across one National Health Service mental health trust. Data revealed that the HCAs are a close-knit 'in-group' who share low group status and norms and, often highlight their own expertise in order to promote self worth. HCAs' social identity is considered as a barrier to effective teamwork with strong ingroup behaviour suggested as a consequence of their marginalisation. We explore these findings with reference to social identity theory (Tajfel, 1974; Turner, 1978 ) and discuss implications for delivering multiprofessional and interprofessional care.
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Técnicos Medios en Salud/organización & administración , Demencia/terapia , Eficiencia Organizacional , Relaciones Interprofesionales , Atención al Paciente/métodos , Identificación Social , Antropología Cultural , Actitud del Personal de Salud , Demencia/psicología , Grupos Focales , Humanos , Pacientes Internos , Grupo de Atención al Paciente , Prejuicio , Teoría Psicológica , Autoeficacia , Reino UnidoRESUMEN
INTRODUCTION: Loot boxes are purchasable randomised reward mechanisms in video games. Due to structural and psychological similarities with gambling, there are fears that loot box purchasing may be associated with problematic gambling. Whilst monthly expenditure is typically modest (i.e. < $20), the distribution is highly skewed, with a small number of high-level spenders, sometimes referred to as "whales". It is not known what proportion of industry profits are derived from such players, and whether they are typically wealthy individuals and/or problem gamblers. METHODS: We used structured literature searches to identify surveys of gamers with open-access loot box data. The resulting datasets were aggregated, and correlations between loot box expenditure, problem gambling and earnings investigated using Spearman's rho correlations. RESULTS: The combined open-access data comprised 7,767 loot box purchasers (5,933 with self-report earnings). Secondary analysis of this self-report data confirmed that disproportionate revenue appears to be generated from high-level spenders: the top 5% of spenders (> $100/month) represent half of loot box revenue. Previously reported correlations between problem gambling and loot box expenditure were confirmed, with an aggregate correlation of ρ = 0.34, p < .001. In contrast, there was no significant correlation between loot box spend and earnings ρ = 0.02, p = .10. CONCLUSION: Our secondary analysis suggests that games developers (unwittingly or not) are disproportionately profiting from moderate and high-risk gamblers, rather than high earning customers. Such patterns of spending mirror those observed with gambling revenues, and have implications for harm minimisation and ongoing policy debates around loot boxes.
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Conducta Adictiva , Juego de Azar , Juegos de Video , Animales , Humanos , Recompensa , BallenasRESUMEN
Excessive engagement with (increasingly prevalent) loot boxes within games has consistently been linked with disordered gambling and/or gaming. The importance of recognising and managing potential risks associated with loot box involvement means understanding contributing factors is a pressing research priority. Given that motivations for gaming and gambling have been informative in understanding risky engagement with those behaviours, this qualitative study investigated motivations for buying loot boxes, through in-depth interviews with 28 gamers from across the UK. A reflexive thematic analysis categorised reasons for buying into seven "themes"; opening experience; value of box contents; game-related elements; social influences; emotive/impulsive influences; fear of missing out; triggers/facilitators. These themes are described in detail and discussed in relation to the existing literature and motivation theories. This study contributes to understanding ways in which digital items within loot boxes can be highly valued by purchasers, informing the debate around parallels with gambling. Findings that certain motivations were disproportionately endorsed by participants with symptoms of problematic gambling has potential implications for policy and warrants further study.
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Qualitative studies have identified a diverse array of motivations for purchasing items within video games through chance-based mechanisms (i.e., "loot boxes"). Given that some individuals-particularly those at risk of disordered gaming and/or gambling-are prone to over-involvement with loot box purchasing, it is important to have a reliable, valid means of measuring the role of different motivations in driving purchasing behaviour. Building on prior qualitative research, this paper reports the development and validation of the "RAFFLE" scale, to measure the Reasons and Facilitators for Loot box Engagement. A 23-item, seven-factor scale was developed through cognitive interviews (n = 25) followed by two surveys of UK-based gamers who purchase loot boxes; analysed via exploratory (n = 503) and confirmatory (n = 1495) factor analysis, respectively. Subscales encompassed "enhancement'; "progression'; "social pressure'; "distraction/compulsion'; "altruism'; "fear of missing out'; and "resale". The scale showed good criterion and construct validity (correlating well with measures of loot box engagement; the risky loot box index (r = 0.63) and monthly self-reported spend (r = 0.38)), and good internal validity (Cronbach's alpha = 0.84). Parallels with, and divergence from, motivations for related activities of gaming and gambling, and alignment with broader theoretical models of motivation, are discussed.
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In order to learn about the behaviours and health experiences of people who gamble on the Internet, we conducted an international online survey with respondents recruited via gambling and gambling-related websites. The mean (SD) age of the 4,125 respondents completing the survey was 35.5 (11.8) years, with 79.1% being male and 68.8% UK residents. Respondents provided demographic details and completed validated psychometric screening instruments for problem gambling, mood disturbances, as well as alcohol and substance misuse, and history of deliberate self harm. We applied latent class analysis to respondents' patterns of regular online gambling activities, and identified subgroups of individuals who used the Internet to gamble in different ways (L (2) = 44.27, bootstrap P = 0.07). We termed the characteristic profiles as 'non-to-minimal gamblers'; 'sports bettors'; 'casino & sports gamblers'; 'lottery players'; and 'multi-activity gamblers'. Furthermore, these subgroups of respondents differed on other demographic and psychological dimensions, with significant inter-cluster differences in proportion of individuals scoring above threshold for problem gambling, mood disorders and substance misuse, and history of deliberate self harm (all Chi (2)s > 23.4, all P-values <0.001). The 'casino & sports' and 'multi-activity-gamblers' clusters had the highest prevalence of mental disorder. Internet gamblers appear to be heterogeneous but composed of several subgroups, differing markedly on both demographic and clinical characteristics.
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Actitud Frente a la Salud , Conducta Adictiva/epidemiología , Juego de Azar/epidemiología , Estado de Salud , Internet/estadística & datos numéricos , Adulto , Conducta Adictiva/psicología , Análisis por Conglomerados , Comorbilidad , Europa (Continente)/epidemiología , Femenino , Juego de Azar/psicología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Índice de Severidad de la Enfermedad , Factores Socioeconómicos , Estrés Psicológico/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
While there has been extensive research into consumption of "traditional" forms of explicit sexual and violent media (within pornography, videogames and movies), the informal exchange and viewing of explicit real-world violent and sexual content via social media is an under-investigated and potentially problematic behaviour. The current study used an online survey (n= 225: 169f, 55m, 1x, mean age 30.61 (SD 12.03)) to explore self-reported reactions to unsolicited explicit violent and sexual content that participants had received from friends or contacts. In line with our predictions based on previous studies of fictional explicit content, we found effects of both gender and prior exposure on these reactions. Specifically, females rated both sexual and violent explicit content as significantly less funny and exciting and more disturbing than males did. Amongst males, those with high previous exposure rated violent content as more exciting than those with lower or no prior experience. Regardless of gender, participants with higher exposure to sexual content rated it as funnier than those with mild or no exposure, and those with higher exposure to violent content rated it as more amusing and more exciting. However, contrary to what desensitization theories would predict, prior exposure did not attenuate how disturbing explicit content (of either a sexual or a violent nature) was rated. Multiple avenues for further investigation emerged from this preliminary cross-sectional study, and we suggest priorities for further qualitative or longitudinal work on this novel topic.
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Medios de Comunicación , Literatura Erótica , Conducta Sexual , Medios de Comunicación Sociales , Violencia , Adulto , Estudios Transversales , Femenino , Humanos , MasculinoRESUMEN
The human pentraxin proteins, serum amyloid P component (SAP) and C-reactive protein (CRP) are important in routine clinical diagnosis, SAP for systemic amyloidosis and CRP for monitoring the non-specific acute phase response. They are also targets for novel therapies currently in development but their roles in health and disease are controversial. Thus, both for clinical use and to rigorously elucidate their functions, structurally and functionally intact, pharmaceutical grade preparations of the natural, authentic proteins are required. We report here the production from normal human donor plasma and the characterization of the first such preparations. Importantly, we demonstrate that, contrary to reports using recombinant proteins and less well characterized preparations, neither CRP nor SAP stimulate the release by human peripheral blood mononuclear cells in vitro of any TNFα, IL-6 or IL-8, nor does SAP cause release of IL-1ß or IL-10. Furthermore neither of our preparations was pro-inflammatory in mice in vivo.
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Proteína C-Reactiva/análisis , Citocinas/metabolismo , Leucocitos Mononucleares/metabolismo , Componente Amiloide P Sérico/análisis , Proteínas de Fase Aguda/análisis , Proteínas de Fase Aguda/aislamiento & purificación , Proteínas de Fase Aguda/farmacología , Amiloidosis/sangre , Animales , Proteína C-Reactiva/aislamiento & purificación , Proteína C-Reactiva/farmacología , Células Cultivadas , Cromatografía en Gel , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Componente Amiloide P Sérico/aislamiento & purificación , Componente Amiloide P Sérico/farmacología , Espectrometría de Masa por Ionización de Electrospray , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Gambling can be motivated by both its hedonic value and by attempts to cope with dysphoric or stressful states. Thus, motivations constitute important mechanisms linking mood fluctuations and gambling. However, little is known about how different kinds of affective disturbance, such as mood elevation and dysphoria, motivate gambling behavior. METHODS: To estimate relationships between different mood experiences and gambling motivations, we recruited 4125 Internet gamblers via hyperlinks placed on gambling Web sites. Mean (SD) age of respondents was 35.5 (11.8) years, with 79.1% (3263) being male and 68.8% (2838) UK residents. We collected ratings for 11 gambling motivations. We used principal components analysis, followed by hierarchical linear regression, to model the relationships between motivation factor scores and gambling behavior, depressive symptoms, hypomanic experiences, deliberate self-harm, and alcohol and substance misuse. RESULTS: Gambling to regulate mood, gambling for monetary goals, and gambling for enjoyment were enhanced in individuals at heightened risk of problematic gambling, with mood regulation and enjoyment factors being enhanced in female compared with male problem gamblers. Lowered mood reduced the enjoyment motivation, whereas previous mood elevation enhanced it. Gambling problems alongside previous hypomanic experiences or current dysphoria enhanced gambling to regulate emotional states. CONCLUSIONS: Recent theorizing argues that mood disorders and pathologic gambling may share aspects of pathophysiology. Different forms of emotional disturbance, such as mood elevation and dysphoric states, which confer heightened risk for bipolar disorder and depression, are associated with divergent motivations that might represent distinct pathways into gambling behavior.