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BACKGROUND: The prevalence of cardiometabolic disease (CMD) is rising globally, with environmentally induced epigenetic changes suggested to play a role. Few studies have investigated epigenetic associations with CMD risk factors in children from low- and middle-income countries. We sought to identify associations between DNA methylation (DNAm) and CMD risk factors in children from India and The Gambia. RESULTS: Using the Illumina Infinium HumanMethylation 850 K Beadchip array, we interrogated DNAm in 293 Gambian (7-9 years) and 698 Indian (5-7 years) children. We identified differentially methylated CpGs (dmCpGs) associated with systolic blood pressure, fasting insulin, triglycerides and LDL-Cholesterol in the Gambian children; and with insulin sensitivity, insulinogenic index and HDL-Cholesterol in the Indian children. There was no overlap of the dmCpGs between the cohorts. Meta-analysis identified dmCpGs associated with insulin secretion and pulse pressure that were different from cohort-specific dmCpGs. Several differentially methylated regions were associated with diastolic blood pressure, insulin sensitivity and fasting glucose, but these did not overlap with the dmCpGs. We identified significant cis-methQTLs at three LDL-Cholesterol-associated dmCpGs in Gambians; however, methylation did not mediate genotype effects on the CMD outcomes. CONCLUSION: This study identified cardiometabolic biomarkers associated with differential DNAm in Indian and Gambian children. Most associations were cohort specific, potentially reflecting environmental and ethnic differences.

We report on the growth of zinc oxide/polyaniline (ZnO/PANI) nanocomposites deposited on platinum (Pt)–coated glass substrate via chemical bath deposition and dip–casting technique is reported. Scanning electron micrographs of the nanocomposites revealed that etching of ZnO nanorods takes place during growth which turn into plate–like and distorted nanostructures. We found out that increasing the concentration of NH4OH triggered increase in nanostructure diameter. The surface morphology of nanocomposites significantly changed as the molar concentration of NH4OH precursor varies. Fast fourier transform infrared spectroscopy results showed the interaction of ZnO and PANI by observing the shift of peaks to the higher wavenumbers. The measured optical band gap of the nanocomposites are in good aggreement with the reported values. This result indicates that the grown ZnO/PANI nanocomposites is a good material for solar cell device.

This deliverable addresses EOSC-Life WP1's objectives related to publication of data and data resources in cloud repositories by making available resources in EOSC-Life's registries; the implementation of FAIR services and standards, by development of FAIR registries in collaboration with WP6; and evolution of repository infrastructure by making available registry entries deriving from WP3 demonstrators. Use cases for EOSC-Life registries have been defined for general and clinical research data use and the 'EOSC-Life' collection in FAIRsharing has been populated and released comprising more than 100 data resources and standards. A clinical MetaData Repository has also been developed to address challenges of clinical data sharing in Europe. We have engaged with EOSC, sister projects such as FAIRsFAIR and ENVRI to consider the features of registries, cross registry interoperability and use cases which link EOSC projects. We will continue to update the registries as the project progresses and as new dataset and resources are made available and will engage with pan-EOSC registry planning based on our work to date.

The purpose of the article is to determine the factors influencing the mental specificity formation of theLuhanskpopulation and determining its place in the social and cultural space.The implementation of the research goal is subject to the methodological framework, which consists of Primaryresearch methods (information gathering, studying information sources, observation), and Secondary methods, which areused in processing and analysis (quantitative and qualitative). The empirical analysis and synthesis allowed studying thevarious social and cultural qualities of separate groups of the Luganskpopulation and the conditions that unite them.The method of generalization allowed deeper defining the essence of the social and cultural phenomenon of Luganskregion people.In the article the author characterizes the population of Luhansk as a specific community of people, which was formed by migration, reveals the historical basis of population formation processes, specifies the ethnic structure of thenewly formed community, presents a chronological sequence of the different cultures andsocialgroups’representatives’inclusion to the general social order within a certain settlement. Features of the Luhansk museumsnetwork, which were created in a specific cultural and aesthetic environment, are considered on this background.In this article the chronological process of the formation of the population of Lugansk covers the period from thebeginning of the XVIII century to the first quarter of the XIX century. The main emphasis in this issue is on the event, whichbegan the active settlement of the area, where today there is a city of Lugansk. It is about building a Lugansk steelworkswhich became a city-forming enterprise, as well as the opening of minerals around, the organization of coal mining,ironstone, and others. Also, it is described the historical necessity of building the Lugansk steelworks and its role in nationalhistorical processes.The article presents specific individuals who have made a significant contribution to the economic development ofLuhansk and its national status.Features of Lugansk development are considered. The author gives some statistical data concerning population andits resettlement. The author of the article emphasizes the need to highlight the research of the theory and practice of themuseum movement in Lugansk region. Today museum collections of the existing museums of Lugansk are valuable collections. Among them there are many rarities of world importance. Under the occupation of Lugansk there is a realthreat of the loss of these collections. The publication of the structure of the Luhansk museum collections, the ways of theirformation and place in the cultural heritage of Ukraine become more relevant than ever.

Background: Mounting evidence suggests that nutritional exposures during pregnancy influence the fetal epigenome, and that these epigenetic changes can persist postnatally, with implications for disease risk across the life course. Methods: We review human intergenerational studies using a three-part search strategy. Search 1 investigates associations between preconceptional or pregnancy nutritional exposures, focusing on one-carbon metabolism, and offspring DNA methylation. Search 2 considers associations between offspring DNA methylation at genes found in the first search and growth-related, cardiometabolic and cognitive outcomes. Search 3 isolates those studies explicitly linking maternal nutritional exposure to offspring phenotype via DNA methylation. Finally, we compile all candidate genes and regions of interest identified in the searches and describe their genomic locations, annotations and coverage on the Illumina Infinium Methylation beadchip arrays. Results: We summarize findings from the 34 studies found in the first search, the 31 studies found in the second search and the eight studies found in the third search. We provide details of all regions of interest within 45 genes captured by this review. Conclusions: Many studies have investigated imprinted genes as priority loci, but with the adoption of microarray-based platforms other candidate genes and gene classes are now emerging. Despite a wealth of information, the current literature is characterized by heterogeneous exposures and outcomes, and mostly comprise observational associations that are frequently underpowered. The synthesis of current knowledge provided by this review identifies research needs on the pathway to developing possible early life interventions to optimize lifelong health.

Introduction: Docetaxel and erlotinib are registered second line treatments for wild-type EGFR NSCLC. Previous studies suggested a predictive value of the VeriStrat test in second line therapy of NSCLC, classifying patients as either VeriStrat good or VeriStrat poor. EMPHASIS-lung aimed at exploring this predictive effect in patients with squamous cell NSCLC. The trial closed prematurely because of low accrual and results from other trials. Our analysis includes an exploratory combined analysis with results from the PROSE trial.Methods: EMPHASIS-lung was a randomized phase III multicenter trial exploring the differential effect of second line erlotinib versus docetaxel on progression-free survival (PFS) in VeriStrat good versus VeriStrat poor patients with squamous cell NSCLC.Results: A total of 80 patients were randomized, with 72.5% categorized as VeriStrat good. Patient characteristics were balanced between VeriStrat status and treatment groups. The median PFS times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 4.1 and 1.6 months, respectively, versus 1.9 and 2.1 months, respectively, in the VeriStrat poor cohort. The median overall survival (OS) times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 7.8 and 8.4 months, respectively, and 4.4 and 5.2 months, respectively, in the VeriStrat poor cohort. An additional exploratory analysis was performed; in it, 47 patients from the squamous cell subgroup of PROSE were included in a combined analysis, contributing with 45 PFS and 41 OS events.Conclusions: The final analysis of EMPHASIS-lung did not show a differential effect on PFS for erlotinib versus docetaxel stratified by VeriStrat status. Similarly, in the combined analysis, no significant treatment by VeriStrat status interaction was observed (interaction p=0.24 for PFS and 0.45 for OS, stratified by study). (C) 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Thirteen biomedical research infrastructures (BMS RIs) have been prioritised by the European Strategy Forum on Research Infrastructures as ESFRI Projects or ESFRI Landmarks. This working paper describes a core set of eight principles on quality management recognised by all BMS RIs.

Zinc oxide (ZnO) on silica modified polyaniline (SM-PANI) was prepared via chemical bath deposition and in situ polymerization. The optical characteristics of the nanocomposites were investigated using ultraviolet-visible (UV-Vis) spectroscopy. The bands showed higher absorbance in the visible region. Fourier transform infrared (FTIR) spectroscopy revealed that there is an interaction between SM-PANI and ZnO.

Objectives: The study sought to investigate the safety and efficacy of eplerenone in patients at high risk for hyperkalemia or worsening renal function (WRF) in EMPHASIS-HF, a trial that enrolled p...

Introduction Docetaxel and erlotinib are registered second-line treatments for wild-type EGFR NSCLC. Previous studies suggested a predictive value of the VeriStrat test in second-line therapy of NSCLC, classifying patients as either VeriStrat good or VeriStrat poor. EMPHASIS-lung aimed at exploring this predictive effect in patients with squamous cell NSCLC. The trial closed prematurely because of low accrual and results from other trials. Our analysis includes an exploratory combined analysis with results from the PROSE trial. Methods EMPHASIS-lung was a randomized phase III multicenter trial exploring the differential effect of second-line erlotinib versus docetaxel on progression-free survival (PFS) in VeriStrat good versus VeriStrat poor patients with squamous cell NSCLC. Results A total of 80 patients were randomized, with 72.5% categorized as VeriStrat good. Patient characteristics were balanced between VeriStrat status and treatment groups. The median PFS times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 4.1 and 1.6 months, respectively, versus 1.9 and 2.1 months, respectively, in the VeriStrat poor cohort. The median overall survival (OS) times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 7.8 and 8.4 months, respectively, and 4.4 and 5.2 months, respectively, in the VeriStrat poor cohort. An additional exploratory analysis was performed; in it, 47 patients from the squamous cell subgroup of PROSE were included in a combined analysis, contributing with 45 PFS and 41 OS events. Conclusions The final analysis of EMPHASIS-lung did not show a differential effect on PFS for erlotinib versus docetaxel stratified by VeriStrat status. Similarly, in the combined analysis, no significant treatment by VeriStrat status interaction was observed (interaction p = 0.24 for PFS and 0.45 for OS, stratified by study). © 2017 International Association for the Study of Lung Cancer

BACKGROUND: Animal studies have shown that nutritional exposures during pregnancy can modify epigenetic marks regulating fetal development and susceptibility to later disease, providing a plausible mechanism to explain the developmental origins of health and disease. Human observational studies have shown that maternal peri-conceptional diet predicts DNA methylation in offspring. However, a causal pathway from maternal diet, through changes in DNA methylation, to later health outcomes has yet to be established. The EMPHASIS study (Epigenetic Mechanisms linking Pre-conceptional nutrition and Health Assessed in India and Sub-Saharan Africa, ISRCTN14266771) will investigate epigenetically mediated links between peri-conceptional nutrition and health-related outcomes in children whose mothers participated in two randomized controlled trials of micronutrient supplementation before and during pregnancy. METHODS: The original trials were the Mumbai Maternal Nutrition Project (MMNP, ISRCTN62811278) in which Indian women were offered a daily snack made from micronutrient-rich foods or low-micronutrient foods (controls), and the Peri-conceptional Multiple Micronutrient Supplementation Trial (PMMST, ISRCTN13687662) in rural Gambia, in which women were offered a daily multiple micronutrient (UNIMMAP) tablet or placebo. In the EMPHASIS study, DNA methylation will be analysed in the children of these women (~1100 children aged 5–7 y in MMNP and 298 children aged 7–9 y in PMMST). Cohort-specific and cross-cohort effects will be explored. Differences in DNA methylation between allocation groups will be identified using the Illumina Infinium MethylationEPIC array, and by pyrosequencing top hits and selected candidate loci. Associations will be analysed between DNA methylation and health-related phenotypic outcomes, including size at birth, and children’s post-natal growth, body composition, skeletal development, cardio-metabolic risk markers (blood pressure, serum lipids, plasma glucose and insulin) and cognitive function. Pathways analysis will be used to test for enrichment of nutrition-sensitive loci in biological pathways. Causal mechanisms for nutrition-methylation-phenotype associations will be explored using Mendelian Randomization. Associations between methylation unrelated to supplementation and phenotypes will also be analysed. CONCLUSION: The study will increase understanding of the epigenetic mechanisms underpinning the long-term impact of maternal nutrition on offspring health. It will potentially lead to better nutritional interventions for mothers preparing for pregnancy, and to identification of early life biomarkers of later disease risk.

From 2002 to 2007, 1,590 individuals were enrolled in an active surveillance program conducted in Metro Cebu, Philippines, where the anti-HCV-positive rate was significantly and constantly high among injecting drug users (83%, 793/960; 71-88%), especially among those living in downtown (89%, 683/770; 87-100%), despite the extremely low percentage of anti-HIV-positives (0.34%, 3/874). Sampling areas were then enlarged nationwide and the number of samples increased to 2,645 at the end of 2007. A total of 444 samples were positive for HCV RNA. Phylogenetic analysis based on NS5B and E1-E2 regions revealed that the most dominant HCV subtype was 1a, and followed by 2b, 2a, and 1b, and that the HCV strains had the largest variety in Metro Manila and its vicinity (P < 0.01). Interestingly, subtype 1b was detected solely in Metro Manila, and four HCV strains collected in this area showed higher homology to specific foreign strains retrieved from the Genbank/EMBL/DDBJ database with bootstrap values of 68-95% comparing with other strains analyzed in this nationwide study. These data suggest that HCV strains may be introduced occasionally into the Philippines possibly through Metro Manila as a main entry point. Considering the fact that an HIV epidemic started primarily via contaminated needle sharing in Asia, the constantly high rate of HCV infections and the newly introduced foreign HCV strains in the absence of HIV epidemic warrant further investigation on HCV entry and spread for early detection of an HIV epidemic in the Philippines.

The results described in this thesis provide a rather complex picture of climatic, environmental and biotic changes preceding and arising from the onset of Antarctic glaciation. This period is commonly known as the greenhouse to icehouse transition across the Eocene-Oligocene Transition (EOT, 34-33 million years ago). The studies, based on fossil remains of algae and micro-organisms, do now for the first time constrain the timing and magnitude of cooling and ice-growth across the EOT. Environmental change occurred in two steps with the first, the EOT-1 shift (33.9 million years ago), representing cooling, bottom water production and ephemeral ice sheet-development, to be followed ~300.000 year later by abrupt ice sheet expansion towards a continent-scale size at the Oi-1 shift. Seen in the light of the reconstructed late Eocene evolution of the Southern Ocean, it is proposed that a series of intimately coupled positive feedbacks became active before glacial expansion across the Oi-1 shift. Enhanced west-ward circum-Antarctic circulation acted to support cooling of Antarctica, through 'thermal isolation', leading to increased latitudinal temperature gradients. The enhanced gradients enhanced polar wind-fields that spurred the westward circulation. Associated with this circulation-regime, bottom water was produced and enhanced vertical mixing supported biological productivity, which eventually may have acted to sequester CO2 from the atmosphere. This all may have resulted in the accelerated cooling during the initial phases of the EOT. With orbital preconditioning, the Antarctic ice-sheets could expand rapidly to eventually reach a continent-scale across the Oi-1 shift. Consequences of the Oi-1 glaciation were profound. Low-latitude shelf biota are notably affected by cooling and sea-level change during the initial phases of the EOT. The most profound reorganization is recorded in the Southern Ocean, where the onset of modern plankton ecosystems responds to the inception of seasonal sea-ice conditions along Antarctica's margins during the Oi-1. In contrary to what was intuitively assumed, sea-level variations act strongly non-linear. Close to Antarctica, the sea-level increased by ~100 m. This provides a containing feedback for the newly established ice-sheets. The origin of the present-day Antarctic ice-sheets provides an example of a strongly non-linear process, with a series of positive feedbacks leading to relatively rapid and abrupt glacial expansion. Once established, stabilizing feedbacks (e.g., albedo, circum-Antarctic sea-level change) prevent a return to the initial ice-free state. The evaluation of these processes using numerical climate models will yield crucial insight in the role of the climate-ocean-atmosphere systems with regard to ice-sheet stability. This is important because ice-sheets are already affected at observable rate by anthropogenic carbon dioxide emissions and elevated earth surface temperatures

Global warming is continuing without delay and this is caused by the accumulation of greenhouse gases in the atmosphere. Methane is a strong greenhouse gas, 25 times stronger compared to CO2. The increase in methane concentrations in the atmosphere is largely the result of human influences, but there are also natural sources of methane, as for instance peat bogs. Peat bogs store an enormous amount of carbon, three times as much as tropical rain forests, yet are also responsible for about 10% of the methane flux to the atmosphere. This methane flux is substantial, however, it is already strongly reduced by methane-oxidizing bacteria (methanotrophs), which live in symbiosis with peat moss (Sphagnum). This thesis comprises the investigation of Sphagnum-associated methanotrophy on a global scale and down to a molecular level, aiming to further the understanding of the interactions between the methane cycle and a changing climate. The work described in this thesis demonstrates that Sphagnum-associated methane oxidation occurs ubiquitously across the globe. Labelling experiments showed that methane-derived carbon is transferred, via methane-oxidizing bacteria, into plant material in different Sphagnum mosses. This way, carbon is efficiently recycled. Climate change projections indicate that areas at mid- to high latitude, where peat bogs are situated, will become increasingly wetter and warmer. It was shown in this theses that, with increasing temperature and increasing humidity, methane oxidation rates rise. At the same time, the balance between methane oxidation and methane production becomes more critical, as methanotrophs cannot compensate for the increase in methane production that occurs concurrently. Methanotrophs act as an efficient filter for the escape of methane, reducing diffusive methane emissions up to 98%. The efficiency of this filter, however, strongly declines at increasing temperatures, from 98% at 5ºC to only 50% at 25ºC. Even though methane consumption increased with increasing temperature, methanotrophs were not able to compensate for the increase in methane production, at least on the time scale of the experiment. Therefore, global warming may be enhanced by increased methane release from peat bogs. Biomarkers can be used to assess the long term influence of environmental change on peat bogs. The stable carbon isotopic composition of hopenes and the BHPs aminobacteriohopanetetrol and aminobacteriohopanepentol have been shown to be the most suitable biomarkers to assess methanotrophy in peat bogs. Methanotrophic biomarkers in a peat record from Misten Bog indicated that methanotrophic activity is strongly influenced by humidity, being higher during cold, wet periods compared warm and dry episodes over the past 1200 years. Since methane emissions increase with increasing water level, this implies that peat bogs probably generated highest methane emissions during cold periods, providing a negative feedback for the prevailing colder conditions. What the future will bring thus critically depends on the extent of the increase in temperature and precipitation. It is, however, clear that methanotrophs play a vital role in reducing methane emissions from peat bogs worldwide and this role may become increasingly important when the climate changes in the near future.

Human immunodeficiency virus (HIV) sentinel surveillance program for injecting drug users has been conducted in Metro Cebu, the Philippines. A low prevalence (0–0.52%) of anti-HIV-positivity had been detected in this population from 2002 to 2007. However, a 10-fold increase in HIV prevalence was detected in the 2009 national HIV sentinel surveillance program. It prompted an additional outreach program to be conducted in Metro Cebu in January 2010, which recorded the highest HIV prevalence rate ever documented in the Philippines (75%, 44/59). HIV genes from fourteen 2009 to 2010 Metro Cebu strains were clustered closely in the phylogenetic tree, but no other strain collected outside Metro Cebu and none stored in the International Nucleotide Sequence Database was allocated to the same phylogenetic cluster. All these HIV infections have emerged in the anti-hepatitis C virus (HCV)-positive population (100%, 62/62) in Metro Cebu from 2009 to 2010. The five HCV strains from the individuals harboring the closely related HIV strains were categorized into different subtypes. These results strongly suggest that HIV infections occurred recently and spread rapidly among injecting drug users, while HCV had been circulating previously among them. Considering the fact that injecting drug use was the first mode of HIV transmission in Asia, extensive monitoring of injecting drug users and associated bridging populations is necessary. Therefore, HCV-guided characterization of the spread of HIV to populations that are vulnerable to blood-borne infections could play an important role in alerting health authorities to the early phase of an HIV epidemic. J. Med. Virol. 83:941–947, 2011. © 2011 Wiley-Liss, Inc.

ZnO nanostructures grown on glass (SiO2) substrates have been successfully fabricated for ethanol gas sensor. These ZnOnanostructures were prepared by chemical bath deposition with various ammonium hydroxide concentrations. The response of ZnO- based ethanol gas sensor exhibited higher response at lower NH4OH concentration; this might be attributed to the uniform morphology of the ZnOnanostructures which facilitates easier interaction with the ethanol gas. On the other hand, at higher NH4OH concentration showed drastic decrease in sensor response. This might be due to the growth of broken nanorods. Scanning electron microscope (SEM) images confirmed the formation of uniform and vertically grown nanostructures with lower concentration of NH4OH. On the other hand, at higher NH4OH concentration, broken nanorodsand agglomerations were present as revealed in the SEM micrographs. Energy dispersive x-ray spectroscopy (EDS) measurements suggested that the grown nanostructures were most likely composed of ZnO. The calculated energy band gap from the UV-Vis spectra confirmed that the grown Zn Onanostructures.

International audience; The present study compared multiplex PCR (mPCR) and Whole Genome Sequencing (WGS) using the SCCmecFinder database to identify the Staphylococcal Cassette Chromosome (SCC) mec in five Staphylococcus aureus (SA) and nine non-aureus staphylococci (NAS) isolated from dairy cattle. mPCR identified an SCCmecIV in four SA and one NAS, but could not differentiate between SCCmecII and IV in the fifth SA, that all harbored the mecA gene and were phenotypically resistant to cefoxitin. SCCmecFinder confirmed the presence of an SCCmecIVc(2B) in four SA and of the SCCmecIVa(2B) in the fifth SA and the one NAS. Both methods also detected one untypeable SCCmec in another cefoxitin-resistant NAS harboring the mecA gene and a pseudo SCCmec in one cefoxitin-sensitive NAS harboring one mecC-related gene. No SCCmec elements were identified either in one cefoxitin-sensitive NAS harboring the mecA2 gene, or in five NAS (one resistant and four sensitive to cefoxitin) harboring the mecA1 gene. SCCmecFinder could even not identify the presence of any mecA1 gene in these five NAS, whose presence was nevertheless confirmed by ResFinder. The conclusions of this study are: (i) mPCR and WGS sequencing using SCCmecFinder are complementary methodologies to identify SCCmec; (ii) SCCmecFinder and ResFinder to a lesser extent cannot identify all mec gene allotypes; (iii) a specific classification of the SCCmec in NAS would be epidemiologically helpful; (iv) presence of a mecA gene and a complete SCCmec is linked to cefoxitin resistance, whereas presence of other mec genes and of pseudo or no SCCmec is not.

International audience; Making data compliant with the FAIR Data principles (Findable, Accessible, Interoperable, Reusable) is still a challenge for many researchers, who are not sure which criteria should be met first and how. Illustrated from experimental data tables associated with a Design of Experiments, we propose an approach that can serve as a model for a research data management that allows researchers to disseminate their data by satisfying the main FAIR criteria without insurmountable efforts. More importantly, this approach aims to facilitate the FAIRification process by providing researchers with tools to improve their data management practices.