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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The pharmacological management of women with bipolar disorder in the perinatal period is challenging. This population has a high recurrence rate, but some medications can be a concern in pregnancy and breastfeeding. Little is known about prescribing practices in perinatal services, and the impact of medication on recurrence rates.
The aims of this study are: 1) to describe the use of medication in women with bipolar disorder in the perinatal period and 2) to evaluate the impact of medication on the rate of postpartum recurrence.
Clinical data were collected from pregnant women with a diagnosis of bipolar disorder in the nine participating centres in the UK and who were not experiencing an episode of illness entering the postpartum period. Using a proforma, data were collected for the period between conception and three months postpartum: sociodemographic, reproductive, the severity of illness, medication and recurrence.
Data were analysed for association using χ2 tests and logistic regression.
In this sample of 167 women, 91 (55%) were taking medication at delivery: 62 (37%) antipsychotics, 41 (25%) antidepressants, and 25 (15%) mood stabilisers. In 12 cases medication was reduced before delivery. Of those who were taking medication at delivery six decreased of stopped after delivery and one increased the dose. 42% of women in this sample experienced a recurrence, with 30% of the sample experiencing a manic/psychotic episode. There was no significant association between taking medication and recurrence χ 2(1) = 0.07, p = 0.79. There continued to be no association in a multivariable analysis when adjusted for parity, severity (previous admissions, age at first treatment, bipolar subtype), type of medication during pregnancy and immediate postpartum changes aOR 0.33 95%CI [0.03; 3.40], p = 0.35.
A high number of women with bipolar disorder are taking medication before delivery and in the majority, antipsychotics are prescribed. The postnatal recurrence rate in both medicated and unmedicated women is high. These results are in line with existing literature. Further work is needed in larger samples to provide clinical guidance for women and their clinicians.
Managing risk is central to clinical care, yet most research focuses on patient perception, as opposed to how risk is enacted within the clinical setting by healthcare professionals.
To explore how surgical risk is perceived, encountered, and managed by congenital cardiac surgeons.
Semi-structured interviews were conducted with 20 congenital cardiac surgeons representing every unit across England and Wales. All interviews were transcribed verbatim, with analysis based on the constant comparative approach.
Three themes were identified, reflecting the interactions between personal, institutional, and political context in which risk is encountered and managed. First, “communicating risk” highlights the complexity and variability in methods employed by surgeons to balance legal/moral obligations with parental need and expectations. Universally, surgeons described the need for flexibility in their approach in order to meet the needs of individual patients. Second, “scrutiny and accountability” captures the spectrum of opinion arising from the binary nature of the outcomes collated and the way in which they are perceived to be interpreted. Third, “nature of the job” highlights the personal and professional implications of conveying and managing risk and the impact of recent policy changes on the way this is enacted.
Variations in approaches to communicating risk demonstrate a lack of consensus, compounded by insufficient evidence to determine or monitor a “best-care” approach. With current surgical outcomes suggesting little room for increasing survival rates, future care needs should shift to the “soft skills” in order to continue to drive improvements in parental and patient experience.
Impulsive and compulsive problem behaviours are associated with a variety of mental disorders. Latent phenotyping indicates the expression of impulsive and compulsive problem behaviours is predominantly governed by a transdiagnostic ‘disinhibition’ phenotype. In a cohort of 117 individuals, recruited as part of the Neuroscience in Psychiatry Network (NSPN), we examined how brain functional connectome and network properties relate to disinhibition. Reduced functional connectivity within a subnetwork of frontal (especially right inferior frontal gyrus), occipital and parietal regions was linked to disinhibition. Findings provide insights into neurobiological pathways underlying the emergence of impulsive and compulsive disorders.
Nonsuicidal self-injury (NSSI) is prevalent among adolescents and research is needed to clarify the mechanisms which contribute to the behavior. Here, the authors relate behavioral neurocognitive measures of impulsivity and compulsivity to repetitive and sporadic NSSI in a community sample of adolescents.
Computerized laboratory tasks (Affective Go/No-Go, Cambridge Gambling Task, and Probabilistic Reversal Task) were used to evaluate cognitive performance. Participants were adolescents aged 15 to 17 with (n = 50) and without (n = 190) NSSI history, sampled from the ROOTS project which recruited adolescents from secondary schools in Cambridgeshire, UK. NSSI was categorized as sporadic (1-3 instances per year) or repetitive (4 or more instances per year). Analyses were carried out in a series of linear and negative binomial regressions, controlling for age, gender, intelligence, and recent depressive symptoms.
Adolescents with lifetime NSSI, and repetitive NSSI specifically, made significantly more perseverative errors on the Probabilistic Reversal Task and exhibited significantly lower quality of decision making on the Cambridge Gambling Task compared to no-NSSI controls. Those with sporadic NSSI did not significantly differ from no-NSSI controls on task performance. NSSI was not associated with behavioral measures of impulsivity.
Repetitive NSSI is associated with increased behavioral compulsivity and disadvantageous decision making, but not with behavioral impulsivity. Future research should continue to investigate how neurocognitive phenotypes contribute to the onset and maintenance of NSSI, and determine whether compulsivity and addictive features of NSSI are potential targets for treatment.
Public reporting of clinical performance is increasingly used in many countries to improve quality and enhance accountability of the health system. The assumption is that greater transparency will stimulate improvements by clinicians in response to peer pressure, patient choice or competition. The international diffusion of public reporting might suggest greater similarity between health systems. Alternatively, national and local contexts (including health system imperatives, professional power and organisational culture) might continue to shape its form and impact, implying continued divergence. The paper considers public reporting in the USA and England through the lens of Scott's ‘pillars’ institutional framework. The USA was arguably the first country to adopt public reporting systematically in the late 1980s. England is a more recent adopter; it is now being widely adopted through the National Health Service (NHS). Drawing on qualitative data from California and England, this paper compares the behavioural and policy responses to public reporting by health system stakeholders at micro, meso and macro levels and through the intersection of ideas, interests, institutions and individuals through. The interplay between the regulative, normative and cultural-cognitive pillars helps explain the observed patterns of on-going divergence.
Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.
To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.
We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.
Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015–0.017), with carriers being 7.5–7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.
This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.
Rare's 1997 game GoldenEye 007 redefined the first-person shooter genre not only through its mission-based gameplay, improved enemy AI, and architecturally believable level designs, but also how it combined these features to create an internally consistent, believable Bond experience. When the game was remade in 2010, new developers Eurocom had to negotiate intellectual property restrictions and new genre developments to create a game that was both faithful to the beloved original and successful on its own terms. We explore the relationship between these games via the rubrics of adaptive fidelity (how faithfully each game operates as an adaptation of the GoldenEye film) and fictional coherence (how well their own components collaboratively encourage role-play as the character of Bond).
Keywords: first-person shooter; adaptation; GoldenEye 007; role-play; transmedia; James Bond
In 1995, Nintendo approached videogame development company Rare, Ltd. about designing a game based on the then in-production James Bond film GoldenEye (UK/USA: Martin Campbell, 1995) as a platform-exclusive title for their Nintendo 64 console. While the resulting game, GoldenEye 007 (1997), first appeared to be a routine production, comparable to releasing action figures or other merchandise to accompany a movie release, it would ultimately become a surprise critical and commercial success and a landmark both of film-to-videogame adaptation and of the emerging first-person shooter genre. While its multiplayer mode created the biggest stir, its single-player levels are remembered today not only for their innovative mission objectives, enemy behavior, and level design, but for the way these features worked to create an internally consistent, believable Bond experience.
In 2010, another videogame adaptation of GoldenEye appeared, this time developed by Eurocom for the Nintendo Wii. The motivations behind this re-adaptation have very little to do with any lingering popularity for the then fifteen-year old Pierce Brosnan vehicle—instead, it had been the enduring, nostalgia-enriched reputation of the original game that prompted the return of this particular storyline from the Bond canon. A curious double-adaptation, the 2010 game serves as a case study in the adaptation and mutation of intellectual property, as well as the development of the first-person shooter genre, particularly as a medium for storytelling.
The principles of the modern foundational economy and its role in renewing citizenship and informing public policy are explored for the first time in this instructive collection. Challenging mainstream social and economic thinking, it shows how foundational economy experiments at different scales can foster radical social innovation through collective, rather than private, consumption. An interdisciplinary group of respected European academics provide case studies of initiatives and interventions around policy cornerstones including housing, food supply and water and waste management. They build a judicious evidence base of the growing relevance of foundational economic thinking and its potential to provide a new political and social outlook on civil society and social justice.
The act of doing policy to or imposing policies on citizens is the cardinal sin of policy practice. As the chapters in this volume have illustrated, to avoid this sin the last half century has witnessed a great experiment that has celebrated and promoted neoliberal principles with the ideas of individual freedom and the sovereign consumer citizen at their core, the great deception being that consumer-citizens are free to choose, don't have policies imposed on them and are free from the stifling confines of bureaucratic states. As the chapters have shown, this is by and large a failed experiment but, despite the economic crisis, the laboratory is still open for business. As processes of financialization have invaded increasing aspects of daily life, the evidence from this volume clearly demonstrates that the effect has been to constrain the autonomy of individuals and weaken the ties of community and solidarity. The loss of collective voice has not been counterbalanced by a stronger individual choice. Moreover, the idea of citizenship has been distorted and used against citizens as large corporations have been able to enjoy the rights of citizenship while evading their duties.
In this concluding chapter we focus on the relationship between the foundational economy and new emerging forms of citizenship. Our starting point is the argument that foundational thinking is necessarily underpinned by the fostering of a new and universalistic model of citizenship, a model that views citizenship as more than a status that brings with it a bundle of rights that one possesses qua citizen, but as something that is also a dynamic part of daily life (Barbera et al, 2018). As a number of the contributors to this volume suggest, this perspective moves beyond citizenship as a collection of rights and responsibilities to emphasize the active and social nature of citizenship where people continually work on, engage with, dispute and argue over their rights and duties. Of course, this is easier said than done, and there is a danger of underestimating the depth of the structural and economic crisis and its effects on the capacities of individual citizens. Moreover, this perspective risks converging with the idea of ‘caring liberalism’ (Jessop et al, 2013: 111) and concentrating on the goal of individual ‘activation’ in terms of self-entrepreneurship and human capital as the main, if not the only, horizon for people's wellbeing.
The ‘foundational economy’ encompasses those goods and services, together with the economic and social relationships that underpin them, that provide the everyday infrastructure of civilized life. A nonexhaustive list includes gas and electricity, water, waste and sewerage, retail food supply, telecommunications, health and social care, housing, education and public transport. Since the 1990s, many of these goods and services have been increasingly incorporated within market logics by policies that promote commodification, privatization and financialization. The failure of these policies and their impact on the daily lives of citizens have been documented in a body of work that has applied foundational thinking to a number of substantive areas of social and economic relations and geographic regions (see Bentham et al, 2013; Barbera et al, 2017, 2018; Foundational Economy Collective, 2018).
This edited collection takes this scholarship further using comparative perspectives on the foundational economy in relation to governance, urban life, welfare critical goods and food systems. We extend theoretical and empirical work on the foundational economy to explore its relevance to key policy areas and to civil society. Addressing a range of substantive areas of concern, individual chapters use case studies at different national and regional levels to illustrate the arguments being developed. In so doing we provide a unique perspective on the relationship between civil society, democracy and the foundational economy.
Our aim is to advance foundational thinking in three key areas. First, we set out detailed evidence on the impact of growth-based and financialized solutions on local democracy, citizenship and civil society and explore alternative approaches to citizenship and social justice that are rooted in the foundational economy. Second, for the first time we provide important comparative perspectives on the development of foundational thinking. And third, we document detailed and critical case studies in core areas of economic and social life.
Each chapter addresses different aspects of the foundational economy from a comparative perspective, illustrating key points with case studies. Areas that are considered in detail include the rise of platform capitalism and the so-called sharing economy that extend commodification and value extraction into mundane activities. In contrast, foundational economy thinking can utilize the same technological developments to offer potential alternative forms of social and economic organization through platform cooperativism.
This chapter focuses on the relationship between the foundational economy, citizenship, democracy and social justice. Our argument is that the foundational economy approach is rooted in a conceptualization of citizenship rights and obligations that are derived from human needs, needs that are met through intermediate satisfiers that are contextdependent and responsive to sociotechnical system change – that is, they are socially, culturally and place-specific, and require agreement through continuous political negotiation and dialogue over time. A key area that becomes apparent from this approach is that there is an increasing and damaging asymmetrical relationship between the rights and duties of corporations as legal entities and the stratified rights and duties of individual citizens qua citizens. A second and related point is that while economies are zonal, people, households and groups live in places. Citizen wellbeing is therefore based on the contingent, place-based drivers of income, from jobs, pensions and welfare, and infrastructure, including grounded (housing, utilities, health, education and care), mobility (cars and public transport systems) and social (parks, libraries, community centres).
We begin this chapter by examining the scope of the foundational economy, and proceed to focus on the importance of foundational thinking for critiques of capitalist formations that involve financialization and extraction. We then discuss the relationship between the foundational economy and human needs and capabilities before developing the argument for a moral basis to the foundational economy and how this links to citizenship. We consider how an impoverished form of citizenship has developed, and within the literature on citizenship we delineate the links between the foundational and civil society, citizenship and the commons, focusing in particular on the potential for developing democratic governance and public action. We conclude by arguing that foundational thinking provides a means of linking citizenship to attempts to manage the commons. This proposes a citizenship based on universal human needs and rights to intermediate goods and services combined with recognition of heterogeneity and diversity in economic and social relations. If social relations and institutional arrangements vary contextually across space and time, this then requires innovative solutions based on experimentation at different scales.
The nature and degree of cognitive impairments in schizoaffective disorder is not well established. The aim of this meta-analysis was to characterise cognitive functioning in schizoaffective disorder and compare it with cognition in schizophrenia and bipolar disorder. Schizoaffective disorder was considered both as a single category and as its two diagnostic subtypes, bipolar and depressive disorder.
Following a thorough literature search (468 records identified), we included 31 studies with a total of 1685 participants with schizoaffective disorder, 3357 with schizophrenia and 1095 with bipolar disorder. Meta-analyses were conducted for seven cognitive variables comparing performance between participants with schizoaffective disorder and schizophrenia, and between schizoaffective disorder and bipolar disorder.
Participants with schizoaffective disorder performed worse than those with bipolar disorder (g = −0.30) and better than those with schizophrenia (g = 0.17). Meta-analyses of the subtypes of schizoaffective disorder showed cognitive impairments in participants with the depressive subtype are closer in severity to those seen in participants with schizophrenia (g = 0.08), whereas those with the bipolar subtype were more impaired than those with bipolar disorder (g = −0.23) and less impaired than those with schizophrenia (g = 0.29). Participants with the depressive subtype had worse performance than those with the bipolar subtype but this was not significant (g = 0.25, p = 0.05).
Cognitive impairments increase in severity from bipolar disorder to schizoaffective disorder to schizophrenia. Differences between the subtypes of schizoaffective disorder suggest combining the subtypes of schizoaffective disorder may obscure a study's results and hamper efforts to understand the relationship between this disorder and schizophrenia or bipolar disorder.
The decision to prescribe psychotropic medication is always a matter of weighing up potential risks and benefits but at no time is this more difficult than in pregnancy and the post-partum period. This is because the risks do not only relate to the side-effects for the mother but also potential adverse outcomes for the pregnancy and the child who may be particularly vulnerable during fetal development and breastfeeding. In addition, there is often a degree of uncertainty about what added risks medication may bring compared with no treatment.