Fine-mapping identifies multiple prostate cancer risk loci on 5p15 some associating with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.

Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010 : a systematic analysis for the Global Burden of Disease Study 2010

Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient −0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. Funding Bill & Melinda Gates Foundation.

The probability archive : from essence to uncertainty in the mediation of knowledge

This volume puts together the works of a group of distinguished scholars and active researchers in the field of media and communication studies to reflect upon the past, present, and future of new media research. The chapters examine the implications of new media technologies on everyday life, existing social institutions, and the society at large at various levels of analysis. Macro-level analyses of changing techno-social formation – such as discussions of the rise of surveillance society and the "fifth estate" – are combined with studies on concrete and specific new media phenomena, such as the rise of Pro-Am collaboration and "fan labor" online. In the process, prominent concepts in the field of new media studies, such as social capital, displacement, and convergence, are critically examined, while new theoretical perspectives are proposed and explicated. Reflecting the inter-disciplinary nature of the field of new media studies and communication research in general, the chapters interrogate into the problematic through a range of theoretical and methodological approaches. The book should offer students and researchers who are interested in the social impact of new media both critical reviews of the existing literature and inspirations for developing new research questions.

How to stop binge drinking and speeding motorists : effects of relational-interdependent self-construal and self-referencing on attitudes toward social marketing

How can marketers stop speeding motorists and binge drinking? Two experiments show that the beliefs consumers have about the degree to which they define themselves in terms of their close relationships (i.e., relational-interdependent self-construal (RISC)) offer useful insights into the effectiveness of communications for two key social marketing issues—road safety (Study 1, New Zealand sample) and alcohol consumption (Study 2, English sample). Further, self-referencing is a mechanism for these effects. Specifically, people who define themselves in terms of their close relationships (high-RISCs) respond most favorably to advertisements featuring a dyadic relationship (two people), and this favorable response is mediated by self-referencing. In contrast, people who do not include close relationships in their sense of self (low-RISCs) respond most favorably to self-reference advertisements featuring solitary models.

Californian 'John Schools' and the social construction of prostitution

Within political and social arenas, prostitution continues to be a highly contested and debated issue. Generally conceptualised as a ‘problem’ in need of eradication, prostitution is strongly linked to immorality and deviance. The methods of addressing this phenomenon have experienced a shift from focusing predominantly on the sex worker, to directly targeting the clients of commercial sex. Such practices have resulted in the creation of policy initiatives such as ‘John Schools’—diversionary programs for clients, or ‘Johns’ who have been arrested for prostitution offences. The programs aim to educate participants on the various harms and risks associated with such behaviour and claim to offer a means to reduce prostitution by targeting the demand for sexual services. It is evident however, that these programs perpetuate traditional social constructions of prostitution, characterising the act, and the actors, as sexually deviant. This paper examines the curriculum of these programs in order to identify how prostitution is constructed—firstly through the depiction of the victims in the program and secondly through the characterisation of prostitution offenders—and argues that such initiatives merely extend the charge of sexual deviance from the sellers of sex to the buyers,whilst failing to acknowledge autonomy and choice for sex workers and clients.

Integrated genomic characterization of endometrial carcinoma

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

The economics of awards, status and performance: the John Bates Clark Medal and the Fellowship of the Econometric Society

This thesis investigates whether receiving an important award in academia raises recipients’ subsequent research productivity and status compared to a synthetic control group of non-recipient scholars with similar previous research performance. It examines the case of being awarded the John Bates Clark Medal and becoming a Fellow of the Econometric Society finding evidence of positive incentive and status effects that raise both productivity and citation levels.

China’s new creative strategy : the utilization of cultural soft power and new markets

This book examines different aspects of Asian popular culture, including films, TV, music, comedy, folklore, cultural icons, the Internet and theme parks. It raises important questions such as – What are the implications of popularity of Asian popular culture for globalization? Do regional forces impede the globalizing of cultures? Or does the Asian popular culture flow act as a catalyst or conveying channel for cultural globalization? Does the globalization of culture pose a threat to local culture? It addresses two seemingly contradictory and yet parallel processes in the circulation of Asian popular culture: the interconnectedness between Asian popular culture and western culture in an era of cultural globalization that turns subjects such as Pokémon, Hip Hop or Cosmopolitan into truly global phenomena, and the local derivatives and versions of global culture that are necessarily disconnected from their origins in order to cater for the local market. It thereby presents a collective argument that, whilst local social formations, and patterns of consumption and participation in Asia are still very much dependent on global cultural developments and the phenomena of modernity, yet such dependence is often concretized, reshaped and distorted by the local media to cater for the local market. Contents: Introduction: Asian Popular Culture: The Global (Dis)continuity Anthony Y.H. Fung Part 1: The Dominance of Global Continuity: Cultural Localization and Adaptation 1. One Region, Two Modernities: Disneyland in Tokyo and Hong Kong Micky Lee and Anthony Y.H. Fung 2. Comic Travels: Disney Publishing in the People’s Republic of China Jennifer Altehenger 3. When Chinese Youth Meet Harry Potter: Translating Consumption and Middle Class Identification John Nguyet Erni 4.New Forms of Transborder Visuality in Urban China: Saving Face for Magazine Covers Eric Kit-Wai Ma 5. Cultural Consumption and Masculinity: A Case Study of GQ Magazine Covers in Taiwan Hong-Chi Shiau Part 2: Global Discontinuity: The Local Absorption of Global Culture 6. An Unlocalized and Unglobalized Subculture: English Language Independent Music in Singapore Kai Khiun Liew and Shzr Ee Tan 7. The Localized Production of Jamaican Music in Thailand Viriya Sawangchot 8. Consuming Online Games in Taiwan: Global Games and Local Market Lai-Chi Chen 9. The Rise of the Korean Cinema in Inbound and Outbound Globalization Shin Dong Kim Part 3: Cultural Domestication: A New Form of Global Continuity 10. Pocket Capitalism and Virtual Intimacy: Pokémon as a Symptom of Post-Industrial Youth Culture Anne Allison 11. Playing the Global Game: Japan Brand and Globalization Kukhee Choo Part 4: China as a Rising Market: Cultural Antagonism and Globalization 12. China’s New Creative Strategy: The Utilization of Cultural Soft Power and New Markets Michael Keane and Bonnie Liu 13. Renationalizing Hong Kong Cinema: The Gathering Force of the Mainland Market Michael Curtin

Directing democracy : competing interests and contested terrain in the John Lewis Partnership

The John Lewis Partnership is one of Europe’s largest models of employee ownership and has been operating a form of employee involvement and participation since its formation in 1929. It is frequently held up as a model of best practice (Cathcart, 2013) and has been described as a ‘workers’ paradise’ (Stummer and Lacey, 2001). At the beginning of 2012, the Deputy Prime Minister of the UK unveiled plans to create a ‘John Lewis Economy’ (Wintour, 2012). As John Lewis is being positioned at the heart of political and media discussions in the UK about alternatives to the corporate capitalist model of enterprise, it is vital that more is known about the experience of employee involvement and participation within the organisation. This article explores the ways in which the practice of employee involvement and participation has changed in John Lewis as a result of competing employee and managerial interests. Its contribution is a contemporary exploration of participation in the John Lewis Partnership and an examination of the ways in which management and employees contested the meaning and practice of employee involvement and participation as part of a ‘democracy project’, which culminated in significant changes and degeneration of the democratic structures.

The John Lewis model reveals the tensions and paradoxes at the heart of workplace democracy

Politicians of all parties have been keen to promote the ‘John Lewis model’ of industrial organisation, emphasising its features of employee ownership and workplace democracy. Dr Abby Cathcart’s research into the company shows that management and workers have different visions of what ‘partnership’ means, with ongoing struggle taking place via the organisation’s democratic structures. This, she argues, has stark implications for other organisations with partnership models that are less robust.

Review : "Ghosts...of the Civil Dead" -- John Hillcoat

Synopsis and review of the Australian prison film Ghosts...of the Civil Dead (John Hillcoat, 1988). Drawing heavily from the book In the Belly of the Beast by American author and long-term prisoner Jack Henry Abbott, as well as from the historical and philosophical work of Michel Foucault (the credits include ‘Foucault Authority – Simon During’), Ghosts… Of the Civil Dead is a searing critique of the so-called ‘new generation’ prison system developed in the United States and recently introduced in Australia. Director John Hillcoat and producer Evan English conducted extensive research for the film, including spending time at the National Institute of Corrections, a think tank in Colorado, and visiting numerous institutions like the ‘new Alcatraz’ at Marion Illinois and other maximum security prisons across the United States. Using a mix of professionals and non-actors, including former prisoners and prison guards, the ‘story’ was workshopped during a lengthy rehearsal period with many actual events and experiences of participants incorporated into the film. The end result deliberately blurs the line between American and Australian prison experience to make the political point that what had happened in the US – from where many events and characters, and much of the architecture and design of the prison are drawn – was beginning to happen in Australia. The film emphasises the vicious cycle of institutionalisation, and highlights the role state authorities play in manufacturing, provoking and manipulating violence and fear both in prisons and in wider society as a means to augment policing and surveillance of the population, to oppress the working classes, and to maintain the political status quo...

Increased risk of hospitalization for acute lower respiratory tract infection among Australian Indigenous infants 5-23 months of age following pneumococcal vaccination : a cohort study

Background Australian Indigenous children are the only population worldwide to receive the 7-valent pneumococcal conjugate vaccine (7vPCV) at 2, 4, and 6 months of age and the 23-valent pneumococcal polysaccharide vaccine (23vPPV) at 18 months of age. We evaluated this program's effectiveness in reducing the risk of hospitalization for acute lower respiratory tract infection (ALRI) in Northern Territory (NT) Indigenous children aged 5-23 months. Methods We conducted a retrospective cohort study involving all NT Indigenous children born from 1 April 2000 through 31 October 2004. Person-time at-risk after 0, 1, 2, and 3 doses of 7vPCV and after 0 and 1 dose of 23vPPV and the number of ALRI following each dose were used to calculate dose-specific rates of ALRI for children 5-23 months of age. Rates were compared using Cox proportional hazards models, with the number of doses of each vaccine serving as time-dependent covariates. Results There were 5482 children and 8315 child-years at risk, with 2174 episodes of ALRI requiring hospitalization (overall incidence, 261 episodes per 1000 child-years at risk). Elevated risk of ALRI requiring hospitalization was observed after each dose of the 7vPCV vaccine, compared with that for children who received no doses, and an even greater elevation in risk was observed after each dose of the 23vPPV ( adjusted hazard ratio [HR] vs no dose, 1.39; 95% confidence interval [CI], 1.12-1.71;). Risk was highest among children Pp. 002 vaccinated with the 23vPPV who had received < 3 doses of the 7vPCV (adjusted HR, 1.81; 95% CI, 1.32-2.48). Conclusions Our results suggest an increased risk of ALRI requiring hospitalization after pneumococcal vaccination, particularly after receipt of the 23vPPV booster. The use of the 23vPPV booster should be reevaluated.

Punk’s fairy godfather : Go-Between John Willsteed on Lou Reed

Obituary on the death of Lou Reed, member of The Velvet Underground and acclaimed solo artist.

Monitoring the price and affordability of foods and diets globally

Food prices and food affordability are important determinants of food choices, obesity and non-communicable diseases. As governments around the world consider policies to promote the consumption of healthier foods, data on the relative price and affordability of foods, with a particular focus on the difference between ‘less healthy’ and ‘healthy’ foods and diets, are urgently needed. This paper briefly reviews past and current approaches to monitoring food prices, and identifies key issues affecting the development of practical tools and methods for food price data collection, analysis and reporting. A step-wise monitoring framework, including measurement indicators, is proposed. ‘Minimal’ data collection will assess the differential price of ‘healthy’ and ‘less healthy’ foods; ‘expanded’ monitoring will assess the differential price of ‘healthy’ and ‘less healthy’ diets; and the ‘optimal’ approach will also monitor food affordability, by taking into account household income. The monitoring of the price and affordability of ‘healthy’ and ‘less healthy’ foods and diets globally will provide robust data and benchmarks to inform economic and fiscal policy responses. Given the range of methodological, cultural and logistical challenges in this area, it is imperative that all aspects of the proposed monitoring framework are tested rigorously before implementation.