Large-scale association analysis identifies new risk loci for coronary artery disease

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2)

De bankencrisis van de jaren twintig

Lessen uit een lang vergeten crisis voor hedendaagse beleidsmakers en banken.

Reconstructing apology: David Cameron's Bloody Sunday apology in the press

While there is an acknowledgement in apology research that political apologies are highly mediated, the process of mediation itself has lacked scrutiny. This article suggests that the idea of reconstruction helps to understand how apologies are mediated and evaluated. David Cameron's apology for Bloody Sunday is examined to see how he constructs four aspects of apology: social actors, consequences, categorization, and reasons. The reconstruction of those aspects by British, Unionist, and Nationalist press along with reconstructions made by soldiers in an online forum are considered. Data analysis was informed by thematic analysis and discourse analysis which helped to explore key aspects of reconstruction and how elements of Cameron's apology are altered in subsequent mediated forms of the apology. These mediated reconstructions of the apology allowed their authors to evaluate the apology in different ways. Thus, in this article, it is suggested that the evaluation of the apology by different groups is preceded by a reconstruction of it in accordance with rhetorical goals. This illuminates the process of mediation and helps to understand divergent responses to political apologies.

ARTD1/PARP1 Negatively Regulates Glycolysis by Inhibiting Hexokinase 1 Independent of NAD(+) Depletion

ARTD1 (PARP1) is a key enzyme involved in DNA repair through the synthesis of poly(ADP-ribose) (PAR) in response to strand breaks, and it plays an important role in cell death following excessive DNA damage. ARTD1-induced cell death is associated with NAD(+) depletion and ATP loss; however, the molecular mechanism of ARTD1-mediated energy collapse remains elusive. Using real-time metabolic measurements, we compared the effects of ARTD1 activation and direct NAD(+) depletion. We found that ARTD1-mediated PAR synthesis, but not direct NAD(+) depletion, resulted in a block to glycolysis and ATP loss. We then established a proteomics-based PAR interactome after DNA damage and identified hexokinase 1 (HK1) as a PAR binding protein. HK1 activity is suppressed following nuclear ARTD1 activation and binding by PAR. These findings help explain how prolonged activation of ARTD1 triggers energy collapse and cell death, revealing insight into the importance of nucleus-to-mitochondria communication via ARTD1 activation.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

The Politics of Observation:Radical Psychiatry and Social Documentary

How did the counter-cultural aims of Radical Psychiatry coincide with those of documentary filmmaking in the 1960s? Where the forms and structures of new approaches to the documentary necessarily complicit in promoting the clinical and anti-clinical practices, and wider political agenda, of Radical Psychiatry? How did the documentary deal with the ethical, aesthetic, and audience-related issues associated with filming personalities and environments associated with Radical Psychiatry? How did Radical Psychiatry and the documentary shape postwar discourses on trauma, especially within conflict and post-conflict (PTSD) contexts? What is the legacy of Radical Pschiatry today, and how has it been explored by contemporary documentray film?

This article addresses these question by examining a range of documentaries dealing with the radical and 'anti-psychiatric' ideas and methods of figures such as R.D.Laing, David Cooper, Jan Bastiaans, Timothy Leary, and Franco Basaglia. Films analysed include Peter Robinson's Asylum (1972) and Psychiatry and Violence (1973); Ah, Sunflower (Klinkert and Sinclair, 1967); Anatomy of Violence (Davis, 1967); Turn On, Tune In, Drop Out (Robin Clarke, 1967), W. R. - Mysteries of the Organism (Makavejev, 1971); Raymond Depardon's San Clemente (1980) and Urgences (1988); and Louis van Gasteren's trilogy Now Do You Get it Why I am Crying (1969), The Price of Survival (2003), and There is No Plane to Zagreb (2012). 
The article concludes with a discussion of Nicolas Philibert's Every Little Thing (1997) within the context of the French documentary tradition and the film's more immediate subject - the famous clinic at La Borde established by Jean Oury, and associated with the methods and theories of figures such as Jacques
 Lacan, Francesc Tosquelles, Franz Fanon, and Félix Guattari.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Study on risk assessment and management and prevention of conflicts of interest in the prevention and fight against betting-related match fixing in the EU 28: Final Report

This report concerns the provisions and practices on betting-related match fixing in sports
within the 28 Member States. Carried out in late 2013/early 2014, respondents in each Member
State reported on that state’s gambling-related provisions in respect of football and tennis and
(in each country) a third sport determined on the basis of either its popularity (in terms of
participation or television viewing) or the existence of betting-related “scandals” in that sport
within that particular jurisdiction. Those reports helped the authors to compare the Member
States’ regulatory and self-regulatory frameworks relating to risk assessment and conflict of
interest management, with a view to indicating areas of best practice, identifying particularly
good legislative frameworks and highlighting areas where change was either desirable or
necessary. While some individual Member States have legislation which might provide
templates that others could adapt for their own use, the authors were not convinced that “more
law”, whether at the national or European level, was desirable. Rather, more effective
cooperation among the stakeholders was identified as being more likely to provide tangible
benefits than would new legal frameworks.

Single vocal cord irradiation:a competitive treatment strategy in early glottic cancer

INTRODUCTION: The treatment of choice for early glottic cancer is still being debated; ultimately it relies on the functional outcome. This paper reports on a novel sparing 4D conformal technique for single vocal cord irradiation (SVCI).

MATERIAL AND METHODS: The records of 164 T1a patients with SCC of the vocal cord, irradiated in the Erasmus MC between 2000 and 2008, were analyzed for local control and overall survival. The quality of life was determined by EORTC H&N35 questionnaires. Also the VHI (voice handicap index), and the TSH (thyroid stimulating hormone) blood levels, were established. On-line image guided SVCI, using cone beam CT or stereotactic radiation therapy (SRT) techniques, were developed.

RESULTS: A LC rate at five-years of 93% and a VHI of 12.7 (0-63) was determined. It appeared feasible to irradiate one vocal cord within 1-2mm accuracy. This way sparing of the contralateral (CL) vocal cord and CL normal tissues, could be achieved.

CONCLUSIONS: Given the accuracy (1-2mm) and small volume disease (CTV limited to one vocal cord), for the use of stereotactic RT techniques SVCI with large fraction sizes is currently being investigated in clinic. It is argued that hypofractionated SVCI can be a competitive alternative to laser surgery.

Milling plant and soil material in plastic tubes over-estimates carbon and under-estimates nitrogen concentrations

Milling of plant and soil material in plastic tubes, such as microcentrifuge tubes, over-estimates carbon (C) and under-estimates nitrogen (N) concentrations due to the introduction of polypropylene into milled samples, as identified using Fourier-transform infra-red spectroscopy.

This study compares C and N concentrations of roots and soil milled in microcentrifuge tubes versus stainless steel containers, demonstrating that a longer milling time, greater milling intensity, smaller sample size and inclusion of abrasive sample material all increase polypropylene contamination from plastic tubes leading to overestimation of C concentrations by up to 8 % (0.08 g g(-1)).

Erroneous estimations of C and N, and other analytes, must be assumed after milling in plastic tubes and milling methods should be adapted to minimise such error.

Book Review - An Architecture of Parts: Architects, Building Workers and Industrialisation in Britain 1940–1970 by Christine Wall and Architecture and the Welfare State, edited by Mark Swenarton, Tom Avermaete and Dirk van den Heuvel.

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.

METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.

RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)).

CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.