DED or alive: assembly and regulation of the death effector domain complexes.

Death effector domains (DEDs) are protein-protein interaction domains initially identified in proteins such as FADD, FLIP and caspase-8 involved in regulating apoptosis. Subsequently, these proteins have been shown to have important roles in regulating other forms of cell death, including necroptosis, and in regulating other important cellular processes, including autophagy and inflammation. Moreover, these proteins also have prominent roles in innate and adaptive immunity and during embryonic development. In this article, we review the various roles of DED-containing proteins and discuss recent developments in our understanding of DED complex formation and regulation. We also briefly discuss opportunities to therapeutically target DED complex formation in diseases such as cancer.

Survival of patients with skin melanoma in Europe increases further: Results of the EUROCARE-5 study

Background In Europe skin melanoma (SM) survival has increased over time. The aims were to evaluate recent trends and differences between countries and regions of Europe.

Methods Relative survival (RS) estimates and geographical comparisons were based on 241,485 patients aged 15 years and over with a diagnosis of invasive SM in Europe (2000-2007). Survival time trends during 1999-2007 were estimated using the period approach, for 213,101 patients. Age, gender, sub-sites and morphology subgroups were considered. 

Results In European patients, estimated 5-year RS was 83% (95% confidence interval, CI 83-84%). The highest values were found for patients resident in Northern (88%; 87-88%) and Central (88%; 87-88%) Europe, followed by Ireland and United Kingdom (UK) (86%; 85-86%) and Southern Europe (83%; 82-83%). The lowest survival was in Eastern Europe (74%; 74-75%). Within regions the intercountry absolute difference in percentage points of RS varied from 4% (North) to 34% (East). RS decreased markedly with patients' age and was higher in women than men. Differences according to SM morphology and skin sub-sites also emerged. Survival has slightly increased from 1999 to 2007, with a small improvement in Northern and the most pronounced improvement in Eastern Europe. 

Discussion SM survival is high and still increasing in European patients. The gap between Northern and Southern and especially Eastern European countries, although still present, diminished over time. Differences in stage distribution at diagnosis may explain most of the geographical differences. However, part of the improvement in survival may be attributed to overdiagnosis from early diagnosis practices.

ANRIL Variants and Aggressive Periodontitis in European and African Populations

Introduction: The chromosome 9p21 locus has been identified as a marker of coronary artery disease. In this locus studies have focused on variations in the ANRIL gene that has also been identified as a strong candidate for association with aggressive periodontitis (AgP).
Objective: To investigate possible associations between gene variants of ANRIL and AgP in European and African populations.
Methods: European AgP cases (n= 213) and age-matched periodontally healthy controls (n= 81) were recruited from centres in the United Kingdom (Belfast, Glasgow, Newcastle and London). African AgP cases (n= 95) and controls (n= 105) were recruited in Khartoum, Sudan. Five single nucleotide polymorphisms (SNPs) in ANRIL were genotyped using Sequenom and analysed using Haploview with permutation testing to correct for multiple candidates. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated.
Results: In the European subjects there was a significant association between rs518394 (p=0.0013; OR = 1.81, 95%CI 1.26-2.61) and rs1333049 (p=0.0028; OR = 1.75, 95%CI 1.21-2.52) and AgP. These associations remained significant after permutation testing. In addition there was an association between rs 1360590 (p=0.035) and AgP in females. In the African subjects there was a significant association between only one SNP rs1537415 and AgP (p=0.036; OR = 1.59, 95%CI 1.04-2.43), however, this was not significant following permutation testing. There were no significant associations with rs3217992 in either population.
Conclusions: SNP variants in the ANRIL locus were shown to be significantly associated with AgP in a European population and for the first time in an African population confirming this as the best replicated locus for aggressive periodontitis.

Willingness to pay for cataract surgery in rural Southern China.

PURPOSE: To study willingness to pay for cataract surgery, and its associations, in Southern China. DESIGN: Cross-sectional willingness-to-pay interview incorporating elements of the open-ended and bidding formats. PARTICIPANTS: Three-hundred thirty-nine persons presenting for cataract screening in Yangjiang, China, with presenting visual acuity (VA) < or = 6/60 in either eye due to cataract. METHODS: Subjects underwent measurement of their VA and a willingness-to-pay interview. Age, gender, literacy, education, and annual income also were recorded. MAIN OUTCOME MEASURES: Maximum amount that the subjects would be willing to pay for cataract surgery. RESULTS: Among 325 (95.9%) subjects completing the interview, 169 (52.0%) were 70 years or older, 213 (65.5%) were women, and 217 (66.8%) had an annual income of <5000 renminbi (5000 = US 625 dollars). Eighty percent (n = 257) of participants were willing to pay something for surgery (mean, 442+/-444 renminbi [US 55 dollars+/-55]). In regression models, older subjects were willing to pay less (8 renminbi [US 1 dollar] per year of age; P = 0.01). Blind subjects were significantly more likely (odds ratio, 5.7; 95% confidence interval, 1.7-19.3) to pay anything for surgery, but would pay on average 255 renminbi (US 32 dollars) less (P = 0.004). Persons at the highest annual income level (>10,000 renminbi [US 1250 dollars]) would pay 50 dollars more for surgery than those at the lowest level (<5000 renminbi) (P = 0.0003). The current cost of surgery in this program is 500 renminbi (US 63 dollars). CONCLUSIONS: Sustainable programs will need to attract younger, more well-to-do persons with better vision, while still providing access to the neediest patients.

DocLite: A Docker-Based Lightweight Cloud Benchmarking Tool

Existing benchmarking methods are time consuming processes as they typically benchmark the entire Virtual Machine (VM) in order to generate accurate performance data, making them less suitable for real-time analytics. The research in this paper is aimed to surmount the above challenge by presenting DocLite - Docker Container-based Lightweight benchmarking tool. DocLite explores lightweight cloud benchmarking methods for rapidly executing benchmarks in near real-time. DocLite is built on the Docker container technology, which allows a user-defined memory size and number of CPU cores of the VM to be benchmarked. The tool incorporates two benchmarking methods - the first referred to as the native method employs containers to benchmark a small portion of the VM and generate performance ranks, and the second uses historic benchmark data along with the native method as a hybrid to generate VM ranks. The proposed methods are evaluated on three use-cases and are observed to be up to 91 times faster than benchmarking the entire VM. In both methods, small containers provide the same quality of rankings as a large container. The native method generates ranks with over 90% and 86% accuracy for sequential and parallel execution of an application compared against benchmarking the whole VM. The hybrid method did not improve the quality of the rankings significantly.

Measuring the shape of degree distributions

Degree distribution is a fundamental property of networks. While mean degree provides a standard measure of scale, there are several commonly used shape measures. Widespread use of a single shape measure would enable comparisons between networks and facilitate investigations about the relationship between degree distribution properties and other network features. This paper describes five candidate measures of heterogeneity and recommends the Gini coefficient. It has theoretical advantages over many of the previously proposed measures, is meaningful for the broad range of distribution shapes seen in different types of networks, and has several accessible interpretations. While this paper focusses on degree, the distribution of other node based network properties could also be described with Gini coefficients.

The Extra-territorial Obligations of European States regarding Human Rights in the Context of Terrorism

This chapter focuses on the growing tendency of international human rights law to require states to protect the rights of non-nationals who are in the state unlawfully and of nationals and non-nationals who are outside the state, especially when any of these people are involved in terrorist or counter-terrorist activity. It reviews these additional obligations within a European context, focusing on EU law and the law of the European Convention on Human Rights and drawing on the case law of UK courts. Part 1 considers when a European state must grant asylum to alleged terrorists on the basis that otherwise they would suffer human rights abuses in the state from which they are fleeing. Part 2 examines whether, outside of asylum claims, a European state must not deport or extradite an alleged terrorist because he or she might suffer an abuse of human rights in the receiving state. Part 3 looks at whether a European state whose security forces are engaged in counter-terrorism activities abroad is obliged to protect the human rights of the individuals serving in those forces and/or the human rights of the alleged terrorists they are confronting. While welcoming the extension of state responsibility, the chapter notes that it is occurring in a way which introduces three aspects of relativity into the protection of human rights. First, European law protects only some human rights extra-territorially. Second, it protects those rights only when there is ‘a real risk’ of their being violated. Third, sometimes it protects those rights only when there is a real risk of their being violated ‘flagrantly’.