Erythropoeitin dose variation in different facilities in different countries and its relationship to drug resistance Management of comorbidities in kidney disease in the 21st century: Anemia and bone disease

Erythropoeitin dose variation in different facilities in different countries and its relationship to drug resistance.BackgroundThe correction of anemia using erythropoeitin (EPO) is accorded high priority in the management of patients undergoing hemodialysis (HD). Target hemoglobin (Hb) levels have been established in many countries. Following an observation that the mean facility EPO dose in a chain of facilities in the United States varied by more than two-fold, an examination of the practice of anemia correction in other settings was carried out.MethodsWe reviewed demographic and laboratory parameters in prevalent HD patients in 50 United States facilities and in a single HD facility in Vicenza, Italy. The mean EPO dose profile of the United States facilities was compared with the profiles in 10 facilities in the eastern United Kingdom (UKER) and in 20 facilities reporting to the United Kingdom Renal Registry (UKRR). Analysis of the factors that correlate with EPO resistance was carried out using the United States and Italian data.ResultsThe average EPO doses, by facility, in the 51 United States, the 10 UKER, and the 19 UKRR facilities were 19,569, 8,416, and 7,992 international units per week (IU/wk), respectively. While examination of the UKRR revealed a similar degree of inter-facility variation (2.6-fold), much larger doses of EPO were being administered in the United States patients, particularly in the low Hb group. Multivariate analysis of the United States data suggested that factors related to inflammation, including low albumin, the use of tunneled catheters for vascular access, and low protein catabolic rate (enPCR) correlated with low Hb and relative EPO resistance.ConclusionDespite similar guidelines for anemia management, significant differences in practice are observed. While there seems to be a reluctance to administer large EPO doses to individual patients in Europe, this does not seem to apply in the United States, where more EPO is given. EPO resistance seems relative rather than absolute in many patients, allowing some to respond to the higher doses

The quantification of physical performance and internal training load in youth male soccer players during preseason

Purpose: The monitoring of training loads and quantification of physical performance are common practices in youth soccer academies to support coaches in prescribing and programming training for individuals. The interaction between training load and physical performance is unknown during a preseason period in youth soccer players. The current study assessed changes in training load and physical assessments across a 4-week preseason period. The relationship between physical performance and match playing time in youth male soccer players was also investigated. Methods: The training loads of 25 professional youth academy male soccer players were monitored throughout a 4-week preseason period. Assessments of power, agility, speed, and aerobic capacity were undertaken in the first training session. Session ratings of perceived exertion (sRPE) and well-being questionnaires were collected during all training sessions and preseason matches. Playing time during subsequent competitive matches was recorded. Results: T test and 30-m-sprint assessments, conducted on the first day of preseason, were predictors of sRPE throughout preseason (t test χ2/df = 2.895, poor adjustment; 30-m sprint χ2/df = 1.608, good adjustment). YoYo Test performance was related with changes in perceived fatigue (χ2/df = 0.534, very good adjustment). Faster players reported higher values of sRPE, and players with higher aerobic capacity reported higher levels of fatigue across preseason. Well-being, perceived fatigue and soreness, and sRPE decreased across preseason. Greater match durations were related to higher levels of fatigue during preseason (P < .05). Conclusion: The current study highlights the relationship between training load, physical assessments, and playing time. Coaches and practitioners can use physical test data at the start of preseason as an indication of players that report higher sRPE, perceived fatigue, and reduced well-being across preseason, supporting decisions around individualized training prescriptions

52 Genetic Loci Influencing Myocardial Mass.

BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Toward the Supramolecular Cyclodextrin Dimers Using Nucleobase Pairs

International audienceThe synthesis of eleven new cyclodextrin derivatives having nucleobase moiety - thymin-1-yl, adenin-9-yl, and guanin-9-yl - is described. These two moieties are linked by different spacers, such as aminoethyl and 1,2,3-triazolyl group. Direct nucleophilic substitution and 1,3-dipolar cycloaddition were performed in good yields (13-73%) for some of the synthesized compounds

The ECORBIO project in a nutshell and its major achievements

ECORBIO is the acronym for Evaluation of CORrosion issues in advanced BIOrefineries. Advanced biorefining according to IEA task 42 corresponds to sustainable transformation of biomass into a marketable portfolio of products comprising food, feed, biomolecules, biomaterials and energy vectors (see fig.1) . To our knowledge, the ECORBIO project is the first initiative undertaken at EU level focusing on potential corrosion problems inside these new and versatile production systems. The 3 years long research project has been financially supported by CR Picardie (now integrated in the new Region Nord-Pas-de-Calais-Picardie, according to recently redefined French administrative Regions) from 2012 to 2015 as a winning proposal submitted by INERIS (acting as coordinator) and 5 key regional partners (UTC-TIMR/ESCOM, UPJV (through GEC FRE CNRS3580 Unit, LEREM, CETIM and MAGUIN SAS) grouping 2 academic laboratories, 3 technical centres and one industrial partner involved in biorefining as equipment and biorefinery process units supplier. The consortium has developed a multidirectional approach entailing analytical and experimental works, bibliographical review, database setting, exchanges with stakeholders. Key objectives of the project was to identify whether or not corrosion was a issue in modern biorefining, analyze past and current research contributing to put corrosion under control and success obtained so far in the matter, and bring proper contribution to advance new knowledge. As a general introduction to the CORABIO workshop, the purpose of this communication is to remind the delegates of some key contextual facts about corrosion concerns, to provide a first overview of workplan and findings of the project, including a first overview of major learning regarding the various tasks undertaken, lessons from bibliometric indicators, major feedback from incidents, potential corrosive environments induced by key materials like carboxylic acids and ionic liquids, evaluation of the corrosion protocol “C1” recently supporting according to GHS (Global Harmonised System) the classification of substances that must be labelled as “corrosive to metal” substances or mixtures and other experimental developments. Major findings are subject to dedicated talks or posters which are included as specific items in the ECORBIO project

Exponential growth combined with exponential decline explains lifetime performance evolution in individual and human species

International audienceThe physiological parameters characterizing human capacities (the ability to move, reproduce or perform tasks) evolve with ageing: performance is limited at birth, increases to a maximum and then decreases back to zero at the day of death. Physical and intellectual skills follow such a pattern. Here, we investigate the development of sport and chess performances during the lifetime at two different scales: the individual athletes' careers and the world record by age class in 25 Olympic sports events and in grandmaster chess players. For all data sets, a biphasic development of growth and decline is described by a simple model that accounts for 91.7% of the variance at the individual level and 98.5% of the variance at the species one. The age of performance peak is computed at 26.1 years old for the events studied (26.0 years old for track and field, 21.0 years old for swimming and 31.4 years old for chess). The two processes (growth and decline) are exponential and start at age zero. Both were previously demonstrated to happen in other human and non-human biological functions that evolve with age. They occur at the individual and species levels with a similar pattern, suggesting a scale invariance property

Corrosive properties of liquid fractions issued from lignocellulosic biomass pretreatment with ionic liquids

The use of Ionic Liquids (ILs) in the lignocellulosic biomass pretreatment necessary to 2nd generation bioethanol production has gained considerable attention in recent years [1]. Owing to an imminent scale-up phase, the study of corrosive properties of ILs is necessary to anticipate future problems, which could be encountered at industrial scale, especially considering that annual direct cost worldwide for corrosion is over 3% of the world's Gross Domestic Product [2]. Thus prevention and reduction of corrosion in lignocellulose pretreatment, as more globally in major processes of advanced biorefining [3] is of great scientific, technological and economical interest. Consequently the purpose of the present work was to study the corrosive properties of liquid fractions issued from pretreatment of various lignocellulosic biomasses: model cellulose, oak sawdust or spruce sawdust. Liquid fractions were collected at two steps: 1) after lignocellulosic biomass pretreatment with 2 ILs: 1-ethyl-3- methylimidazolium acetate or 1-ethyl-3-methylimidazolium methylphosphonate, and 2) precipitation using water or ethanol as an anti-solvent. The corrosive behavior of the fractions collected was determined by mass loss of S235 carbon steel and corrosion pit observation of 316L stainless steel, with a rectangular form (1 x 4 x 0.1 cm) during 7 days at 100°C. The morphology and the elemental composition of the corroded metal surfaces resulting of exposition to the pretraitment liquid fractions, were analyzed by scanning electron microscopy (SEM) with energy dispersive X-ray spectrometry (EDX). Our results showed that corrosion rates for S235 carbon steel varied from fairly low to 400 μm/year depending on the nature of the liquid fraction, whereas corrosion pit was not observed in 316L stainless steel, regardless of the liquid fraction used. Micrographies of S235 carbon steel specimens, revealed the formation of a passivation layer when [Emim]+[Methylphosphonate]- is used for pretreatment contrary to the used of [Emim]+[Acetate]-. In addition, biomass nature (cellulose, oak sawdust or spruce sawdust) and anti-solvent (water or ethanol) used for regeneration step (precipitation) influenced the morphology and the elemental composition at the surface of metal specimens with both [Emim]+[Acetate]- and [Emim]+[Methylphosphonate]- ILs. We are grateful to the European Union/FEDER and Conseil Regional de Picardie (CRP) for funding this project (ECORBIO). Europe is engaged in Picardy with the European Fund of Regional Development (FEDER)

Learning on potential corrosive environments in advanced biorefineries

Advanced biorefining is a versatile concept that promotes the sustainable production of a portfolio of biobased products including biomolecules, biomaterials, bioenergy and energy vectors from various biomass resources and residues. Early development of so-called 1G (first generation) biorefineries that were essentially concentrating on mass production of biodiesel or bioethanol has shown a number of limitations in the related value chains in terms of sustainability issues. Among those issues, a number of corrosion problems have been reported and identified, at least partially understood and sometimes solved. We can quote for example the corrosion of some metallic components of engines due to heat driven conversion of ethanol into acidic species before combustion, the high temperature corrosion in biomass burning furnaces due to the presence of alcali salts as well as stress corrosion cracking in ethanol carbon steel tanks and in pipelines. However no global assessment of corrosion issues in the biorefineries of the future has been performed so far, hence leaving significant interrogation where research efforts have to be deployed to accompany their sustainable implementation. This paper first offers a first overview of the topic from results obtained from the ECORBIO project (for Evaluation of CORrosion in BIOrefineries of the future), the main aim of which is to cover this gap by delivering useful information to process managers, engineering companies and investors for evaluation of corrosion in bioprocesses. The project (Oct 2012 to March 2016) lies on a diversity of scientific approaches comprising: a) literature review b) analysis of accident statistics, exchanges with stakeholders c) testing with existing and purpose developed procedures with a focus on 'biocorrosion', organic acids and ionic liquids, d) learning on a case study in relation with 2G ethanol one pot process . Preliminary results exposed in this paper comprise: a) the analysis of the corrosive environment potentially developed by key microbial products such as organic acids (lactic acid, acetic acid, succinic acid, citric acid....) with sulphuric and distilled water as reference substances for three different grades of steels ; b) corrosive potencies of some imidazolium and phosphonium based ionic liquids that may play a role e.g. in lignocellulosic biomass defragmentation and/or in cellulose dissolution c) first lessons from experience in biorefining and from more general statistics d) first learnings on the pertinence of the C1 test protocol that is used to state whether or not a given substance (e.g. a process juice) is 'corrosive to metals' as an identified dangerous physico-chemical intrinsic property, according to the recently implemented CLP Regulation in the EU (also included in the Globally Harmonised System at UN level)