TMEM67 is required for the maintenance of the perinuclear actin cap

Meckel-Gruber syndrome (MKS) is a genetically heterogeneous disease characterised by the phenotypic triad of occipital encephalocele, polycystic kidneys, and polydactyly. MKS is classified as a ciliopathy as mutations to the MKS proteins result in dysfunction to the primary cilium. Recent research has expanded the aetiology of MKS, as increasing evidence for non-ciliary roles for the MKS proteins are uncovered. Evidence includes their presence at focal adhesions and a role in controlling extracellular matrix (ECM) morphology. The relative contributions of ciliary and non-ciliary cellular phenotypes to the clinical presentations of MKS are not currently known. This thesis identifies ECM-dependent aberrations to the perinuclear actin cap in MKS patient cells lacking the MKS type 3 transmembrane protein TMEM67, likely contributing to migration defects previously identified in patient cells. Furthermore, GFP-Trap analysis identifies a number of myosins as potential binding partners of TMEM67; a previously unreported association. Analysis of these binding partners reports the top biological processes for TMEM67 as myosin-motor activity and actin-based movement, adding to the potential non-ciliary roles of the protein already reported. By expanding our understanding of the role of ciliopathy proteins outside of the cilium, we better comprehend the aetiology of the diseases, providing an opportunity to find new therapeutic interventions

Major depression and survival in people with cancer

OBJECTIVE: The question of whether depression is associated with worse survival in people with cancer remains unanswered because of methodological criticism of the published research on the topic. We aimed to study the association in a large methodologically robust study. METHODS: We analysed data on 20,582 patients with breast, colorectal, gynaecological, lung and prostate cancers who had attended cancer outpatient clinics in Scotland, UK. Patients had completed two-stage screening for major depression as part of their cancer care. These data on depression status were linked to demographic, cancer and subsequent mortality data from national databases. We estimated the association of major depression with survival for each cancer using Cox regression. We adjusted for potential confounders and interactions between potentially time-varying confounders and the interval between cancer diagnosis and depression screening, and used multiple imputation for missing depression and confounder data. We pooled the cancer-specific results using fixed-effects meta-analysis. RESULTS: Major depression was associated with worse survival for all cancers, with similar adjusted hazard ratios: breast cancer (HR 1.42, 95% CI 1.15-1.75), colorectal cancer (HR 1.47, 95% CI 1.11-1.94), gynaecological cancer (HR 1.36, 95% CI 1.08-1.71), lung cancer (HR 1.39, 95% CI 1.24-1.56), prostate cancer (HR 1.76, 95% CI 1.08-2.85). The pooled hazard ratio was 1.41 (95% CI 1.29-1.54, p<0.001, I2=0%). These findings were not materially different when we only considered the deaths (90%) that were attributed to cancer. CONCLUSIONS: Major depression is associated with worse survival in patients with common cancers. The mechanisms of this association and the clinical implications require further study

Gender, foundation degrees and the knowledge economy

This article questions the concept of ‘education for employment’, which constructs a discourse of individual and societal benefit in a knowledge‐driven economy. Recent policy emphasis in the European Union promotes the expansion of higher education and short‐cycle vocational awards such as the intermediate two‐year Foundation Degree recently introduced into England and Wales. Studies of vocational education and training (VET) and the knowledge economy have focused largely on the governance of education and on the development and drift of policy. Many VET programmes have also been considered for their classed, raced and gendered take‐up and subsequent effect on employment. This article builds on both fields of study to engage with the finer cross‐analyses of gender, social class, poverty, race and citizenship. In its analysis of policy texts the article argues that in spite of a discourse of inclusivity, an expanded higher education system has generated new inequalities, deepening social stratification. Drawing on early analyses of national quantitative data sets, it identifies emerging gendered, classed and raced patterns and considers these in relation to occupationally and hierarchically stratified labour markets, both within and without the knowledge economy

A terminal assessment of stages theory : introducing a dynamic states approach to entrepreneurship

Stages of Growth models were the most frequent theoretical approach to understanding entrepreneurial business growth from 1962 to 2006; they built on the growth imperative and developmental models of that time. An analysis of the universe of such models (N=104) published in the management literature shows no consensus on basic constructs of the approach, nor is there any empirical confirmations of stages theory. However, by changing two propositions of the stages models, a new dynamic states approach is derived. The dynamic states approach has far greater explanatory power than its precursor, and is compatible with leading edge research in entrepreneurship

Living for the weekend: youth identities in northeast England

Consumption and consumerism are now accepted as key contexts for the construction of youth identities in de-industrialized Britain. This article uses empirical evidence from interviews with young people to suggest that claims of `new community' are overstated, traditional forms of friendship are receding, and increasingly atomized and instrumental youth identities are now being culturally constituted and reproduced by the pressures and anxieties created by enforced adaptation to consumer capitalism. Analysis of the data opens up the possibility of a critical rather than a celebratory exploration of the wider theoretical implications of this process

To what extent is behaviour a problem in English schools?:Exploring the scale and prevalence of deficits in classroom climate

The working atmosphere in the classroom is an important variable in the process of education in schools, with several studies suggesting that classroom climate is an important influence on pupil attainment. There are wide differences in the extent to which classroom climate is considered to be a problem in English schools. Some ‘official’ reports suggest that behaviour in schools is ‘satisfactory or better’ in the vast majority of schools; other sources have pointed to behaviour being a serious and widespread problem. The paper details four studies conducted over the past decade which aimed to explore these disparities. The aim of the research was to gain a more accurate insight into the extent to which deficits in classroom climate limit educational attainment and equality of educational opportunity in English schools. The findings question the suggestion that behaviour is satisfactory or better in 99.7% of English schools and the concluding section suggests ways in which deficits in classroom climate might be addressed. Although the study is limited to classrooms in England, OECD studies suggest that deficits in the working atmosphere in classrooms occur in many countries. The study therefore has potential relevance for education systems in other countries

Voicing passion: The emotional economy of songwriting

This article examines articulations of the role of passion in accounts of the life and work of the songwriter. It draws upon a range of interviews with successful artists captured in the Sodajerker On Songwriting podcast. It is suggested that these interviews capture the ‘voicing’ of the conventions of creativity in popular music, exploring a context in which passionate motivation, expression and understanding of the (potentially) affective responses to songs are paramount to the labour of the songwriter. The article explores how the core of this labour deals in emotion, attempting to articulate feelings in recognisable, tradable form. This is a process that is both instrumentally rationalised but often felt to be a deeply authentic process, understood (and believed) to spring from the individual’s emotional experience, so conferring identity in a generic field. In light of current debates about the nature of creative work and emotional labour, the accounts drawn upon here can be seen to epitomise many of the qualities of what constitutes ‘good work’ through a mode of self-actualisation

Cholesteatoma of the external ear canal: etiological factors, symptoms and clinical findings in a series of 48 cases

BACKGROUND: To evaluate symptoms, clinical findings, and etiological factors in external ear canal cholesteatoma (EECC). METHOD: Retrospective evaluation of clinical records of all consecutive patients with EECC in the period 1979 to 2005 in a tertiary referral centre. Main outcome measures were incidence rates, classification according to causes, symptoms, extensions in the ear canal including adjacent structures, and possible etiological factors. RESULTS: Forty-five patients were identified with 48 EECC. Overall incidence rate was 0.30 cases per year per 100,000 inhabitants. Twenty-five cases were primary, while 23 cases were secondary: postoperative (n = 9), postinflammatory (n = 5), postirradiatory (n = 7), and posttraumatic (n = 2). Primary EECC showed a right/left ratio of 12/13 and presented with otalgia (n = 15), itching (n = 5), occlusion (n = 4), hearing loss (n = 3), fullness (n = 2), and otorrhea (n = 1). Similar symptoms were found in secondary EECC, but less pronounced. In total the temporomandibular joint was exposed in 11 cases, while the mastoid and middle ear was invaded in six and three cases, respectively. In one primary case the facial nerve was exposed and in a posttraumatic case the atticus and antrum were invaded. In primary EECC 48% of cases reported mechanical trauma. CONCLUSION: EECC is a rare condition with inconsistent and silent symptoms, whereas the extent of destruction may be pronounced. Otalgia was the predominant symptom and often related to extension into nearby structures. Whereas the aetiology of secondary EECC can be explained, the origin of primary EECC remains uncertain; smoking and minor trauma of the ear canal may predispose

Distinguishing Financialization from Neoliberalism

This article contends that neoliberalism and financialization, although sharing much in common, are not synonymous developments. Not only do strongly financialized nations display structural, economic differences, they are also directed by alternative economic epistemologies, cultures and practices. The argument is made by examining the financialization of the UK economy since the mid-1970s. This shift was not simply part of a broad transition away from Keynesianism and towards free market fundamentalism. It was also one very much guided by the particular economic paradigm, discursive practices and devices of the City of London as financial elites took up influential positions in the Thatcher government. The discussion and case example highlight five epistemological elements specific to finance: the creation of money in financial markets, the transactional focus of finance, the centrality of financial markets to economic management, the orthodoxy of shareholder value, and the intense microeconomic approach to financial calculation. Such elements, in conjuction with neoliberalism’s reliance upon finance-blind neoclassical economics, lies at the cultural and epistemological distinction between fiancialization and neoliberalism. Identifying such distinctions opens up new possibilities for understanding financialization, elites, and the neoliberal condition that brought about the financial crash of 2007-08, as well as the political and economic crises that have followed

Data & Agency

This introduction to the special issue on data and agency argues that datafication should not only be understood as the process of collecting and analysing data about Internet users, but also as feeding such data back to users, enabling them to orient themselves in the world. It is important that debates about data power recognise that data is also generated, collected and analysed by alternative actors, enhancing rather than undermining the agency of the public. Developing this argument, we first make clear why and how the question of agency should be central to our engagement with data. Subsequently, we discuss how this question has been operationalized in the five contributions to this special issue, which empirically open up the study of alternative forms of datafication. Building on these contributions, we conclude that as data acquire new power, it is vital to explore the space for citizen agency in relation to data structures and to examine the practices of data work, as well as the people involved in these practices