Relationship between genome and epigenome - challenges and requirements for future research

Understanding the links between genetic, epigenetic and non-genetic factors throughout the lifespan and across generations and their role in disease susceptibility and disease progression offer entirely new avenues and solutions to major problems in our society. To overcome the numerous challenges, we have come up with nine major conclusions to set the vision for future policies and research agendas at the European level.

The relationship between BMI and the prescription of anti-obesity medication according to social factors: a population cross sectional study

Background: Obesity is a global public health problem. There are a range of treatments available with varying short and long term success rates. One option is the use of anti-obesity medication the prescription of which has increased dramatically in recent years. Despite this, little is known about the individual and GP practice factors that influence the prescription of anti-obesity medication. Methods: Multi-level logistic regression analysis was used to investigate factors associated with the prescription of anti-obesity medication in Northern Ireland using a population primary care prescribing database (~1.5 million people aged 16+ years) during 2009/10. Results: While 25.0% of people are obese, only 1.3% (2.1% of females, 0.6% of males) received anti-obesity medication. The relationship between medication rates and age differed by gender (P < 0.001) with prescriptions higher in younger females and older males. Prescribing of anti-obesity medication reflected obesity prevalence across urban/rural areas and deprivation. There was an unexplained two-fold difference, between the 25th and 75th percentile, in the GP practice prescription of anti-obesity medication. Conclusions: There is evidence of relative under-prescribing in males compared to females despite a similar prevalence of obesity. While the prevalence (and presumably the health consequences) of obesity worsens with age, younger females are more likely to be prescribed anti-obesity medication. This suggests an element of patient demand. Educational material to improve the understanding of the role of anti-obesity medication, for patients and practitioners, is recommended. But further study is needed to understand the factors responsible for the variation in prescribing between GP practices.

The enemy of my enemy is my friend: intraguild predation between invaders and natives facilitates coexistence with shared invasive prey

Understanding and predicting the outcomes of biological invasions is challenging where multiple invader and native species interact. We hypothesize that antagonistic interactions between invaders and natives could divert their impact on subsequent invasive species, thus facilitating coexistence. From field data, we found that, when existing together in freshwater sites, the native amphipod Gammarus duebeni celticus and a previous invader G. pulex appear to facilitate the establishment of a second invader, their shared prey Crangonyx pseudogracilis. Indeed, the latter species was rarely found at sites where each Gammarus species was present on its own. Experiments indicated that this may be the result of G. d. celticus and G. pulex engaging in more intraguild predation (IGP) than cannibalism; when the ‘enemy’ of either Gammarus species was present, that is, the other Gammarus species, C. pseudogracilis significantly more often escaped predation. Thus, the presence of mutual enemies and the stronger inter- than intraspecific interactions they engage in can facilitate other invaders. With some invasive species such as C. pseudogracilis having no known detrimental effects on native species, and indeed having some positive ecological effects, we also conclude that some invasions could promote biodiversity and ecosystem functioning.

Survival for haematological malignancies in Europe between 1997 and 2008 by region and age: results of EUROCARE-5, a population-based study

Background: More effective treatments have become available for haematological malignancies from the early 2000s, but few large-scale population-based studies have investigated their effect on survival. Using EUROCARE data, and HAEMACARE morphological groupings, we aimed to estimate time trends in population-based survival for 11 lymphoid and myeloid malignancies in 20 European countries, by region and age. Methods: In this retrospective observational study, we included patients (aged 15 years and older) diagnosed with haematological malignancies, diagnosed up to Dec 31, 2007, and followed up to Dec 31, 2008. We used data from the 30 cancer registries (across 20 countries) that provided continuous incidence and good quality data from 1992 to 2007. We used a hybrid approach to estimate age-standardised and age-specific 5-year relative survival, for each malignancy, overall and for five regions (UK, and northern, central, southern, and eastern Europe), and four 3-year periods (1997–99, 2000–02, 2003–05, 2006–08). For each malignancy, we also estimated the relative excess risk of death during the 5 years after diagnosis, by period, age, and region. Findings: We analysed 560 444 cases. From 1997–99 to 2006–08 survival increased for most malignancies: the largest increases were for diffuse large B-cell lymphoma (42·0% [95% CI 40·7–43·4] to 55·4% [54·6–56·2], p<0·0001), follicular lymphoma (58·9% [57·3–60·6] to 74·3% [72·9–75·5], p<0·0001), chronic myeloid leukaemia (32·3% [30·6–33·9] to 54·4% [52·5–56·2], p<0·0001), and acute promyelocytic leukaemia (50·1% [43·7–56·2] to 61·9% [57·0–66·4], p=0·0038, estimate not age-standardised). Other survival increases were seen for Hodgkin's lymphoma (75·1% [74·1–76·0] to 79·3% [78·4–80·1], p<0·0001), chronic lymphocytic leukaemia/small lymphocytic lymphoma (66·1% [65·1–67·1] to 69·0% [68·1–69·8], p<0·0001), multiple myeloma/plasmacytoma (29·8% [29·0–30·6] to 39·6% [38·8–40·3], p<0·0001), precursor lymphoblastic leukaemia/lymphoma (29·8% [27·7–32·0] to 41·1% [39·0–43·1], p<0·0001), acute myeloid leukaemia (excluding acute promyelocytic leukaemia, 12·6% [11·9–13·3] to 14·8% [14·2–15·4], p<0·0001), and other myeloproliferative neoplasms (excluding chronic myeloid leukaemia, 70·3% [68·7–71·8] to 74·9% [73·8–75·9], p<0·0001). Survival increased slightly in southern Europe, more in the UK, and conspicuously in northern, central, and eastern Europe. However, eastern European survival was lower than that for other regions. Survival decreased with advancing age, and increased with time only slightly in patients aged 75 years or older, although a 10% increase in survival occurred in elderly patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic myeloid leukaemia. Interpretation: These trends are encouraging. Widespread use of new and more effective treatment probably explains much of the increased survival. However, the persistent differences in survival across Europe suggest variations in the quality of care and availability of the new treatments. High-resolution studies that collect data about stage at diagnosis and treatments for representative samples of cases could provide further evidence of treatment effectiveness and explain geographic variations in survival.

Origin of double dinitrogen release feature during fast switching between lean and rich cycles for NOx storage reduction catalysts

The performance of NOx storage and reduction over 1.5 wt% Pt/20 wt% KNO3/K2Ti8O17 and 1.5 wt% Pt/K2Ti8O17 catalysts has been investigated using combined fast transient kinetic switching and isotopically labelled (NO)-N-15 at 350 degrees C. The evolution of product N-2 has revealed two significant peaks during 60 s lean/1.3 s rich switches. It also found that the presence of CO2 in the feed affects the release of N-2 in the second peak. Regardless of the presence/absence of water in the feed, only one peak of N-2 was observed in the absence of CO2. Gas-phase NH3 was not observed in any of the experiments. However, in the presence of CO2 the results obtained from in situ DRIFTS-MS analysis showed that isocyanate species are formed and stored during the rich cycles, probably from the reaction between NOx and CO, in which CO was formed via the reverse water-gas shift reaction. 

A Comparison of Support Needs Between Rural and Urban Family Caregivers Providing Palliative Care

The present study examined the support needs for urban and rural family caregivers of a palliative family member using a cross-sectional telephone survey in northeastern Ontario, Canada (n = 140; 70 urban, 70 rural). Support needs identified as most important by both the groups were informational. Rural caregivers reported greater unmet needs in tangible support (P =.01). No differences were observed between the groups for emotional or informational support needs (P =.25 and P =.35, respectively). Rural and urban caregivers perceived care for care recipients as accessible (mean accessibility score 1.9, standard deviation [SD] = 0.09 and 1.7, SD = 0.7, respectively, P =.20); the majority indicated that when needed, services were easily and quickly obtained. Although there are similarities in the formal care experiences, rural caregivers experience greater unmet needs in receiving support for instrumental activities. © The Author(s) 2013.

Article 23: Equality between women and men

This analysis of Article 23 CFREU (Charter of Fundamental Rights for the European Union) argues that this provision can promote a more progressive understanding of gender equality then promoted by the European Court of Justice, in that it requires actual change in gender relations. It also finds shortcomings in that the EU conceptualises gender equality by relating women to men, thus falling short of providing a basis for women's rights.

Genome-wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress

In response to genotoxic stress the TP53 tumour suppressor activates target gene expression to induce cell cycle arrest or apoptosis depending on the extent of DNA damage. These canonical activities can be repressed by TP63 in normal stratifying epithelia to maintain proliferative capacity or drive proliferation of squamous cell carcinomas, where TP63 is frequently overexpressed/amplified. Here we use ChIP-sequencing, integrated with microarray analysis, to define the genome-wide interplay between TP53 and TP63 in response to genotoxic stress in normal cells. We reveal that TP53 and TP63 bind to overlapping, but distinct cistromes of sites through utilization of distinctive consensus motifs and that TP53 is constitutively bound to a number of sites. We demonstrate that cisplatin and adriamycin elicit distinct effects on TP53 and TP63 binding events, through which TP53 can induce or repress transcription of an extensive network of genes by direct binding and/or modulation of TP63 activity. Collectively, this results in a global TP53-dependent repression of cell cycle progression, mitosis and DNA damage repair concomitant with activation of anti-proliferative and pro-apoptotic canonical target genes. Further analyses reveal that in the absence of genotoxic stress TP63 plays an important role in maintaining expression of DNA repair genes, loss of which results in defective repair.