Genetic effects on liver chromatin accessibility identify disease regulatory variants

Identifying the molecular mechanisms by which genome-wide association study (GWAS) loci influence traits remains challenging. Chromatin accessibility quantitative trait loci (caQTLs) help identify GWAS loci that may alter GWAS traits by modulating chromatin structure, but caQTLs have been identified in a limited set of human tissues. Here we mapped caQTLs in human liver tissue in 20 liver samples and identified 3,123 caQTLs. The caQTL variants are enriched in liver tissue promoter and enhancer states and frequently disrupt binding motifs of transcription factors expressed in liver. We predicted target genes for 861 caQTL peaks using proximity, chromatin interactions, correlation with promoter accessibility or gene expression, and colocalization with expression QTLs. Using GWAS signals for 19 liver function and/or cardiometabolic traits, we identified 110 colocalized caQTLs and GWAS signals, 56 of which contained a predicted caPeak target gene. At the LITAF LDL-cholesterol GWAS locus, we validated that a caQTL variant showed allelic differences in protein binding and transcriptional activity. These caQTLs contribute to the epigenomic characterization of human liver and help identify molecular mechanisms and genes at GWAS loci

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

Water hammer with column separation: A historical review

Column separation refers to the breaking of liquid columns in fully filled pipelines. This may occur in a water-hammer event when the pressure in a pipeline drops to the vapor pressure at specific locations such as closed ends, high points or knees (changes in pipe slope). The liquid columns are separated by a vapor cavity that grows and diminishes according to the dynamics of the system. The collision of two liquid columns, or of one liquid column with a closed end, may cause a large and nearly instantaneous rise in pressure. This pressure rise travels through the entire pipeline and forms a severe load for hydraulic machinery, individual pipes and supporting structures. The situation is even worse: in one water-hammer event many repetitions of cavity formation and collapse may occur. This paper reviews water hammer with column separation from the discovery of the phenomenon in the late 19th century, the recognition of its danger in the 1930s, the development of numerical methods in the 1960s and 1970s, to the standard models used in commercial software packages in the late 20th century. A comprehensive survey of laboratory tests and field measurements is given. The review focuses on transient vaporous cavitation. Gaseous cavitation and steam condensation are beyond the scope of the paper. © 2005 Elsevier Ltd. All rights reserved.A. Bergant, A.R. Simpson, and A.S. Tijsselinghttp://www.elsevier.com/wps/find/journaldescription.cws_home/622877/description#descriptio

Global Retinoblastoma Presentation and Analysis by National Income Level

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4) were female. Most patients (n = 3685 84.7%) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 62.8%), followed by strabismus (n = 429 10.2%) and proptosis (n = 309 7.4%). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 95% CI, 12.94-24.80, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 95% CI, 4.30-7.68). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs. © 2020 American Medical Association. All rights reserved

Nutritional improvements of cereal straws

SIGLEAvailable from British Library Document Supply Centre- DSC:D60133 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Nutrient composition, digestion and rumen fermentation in sheep of wheat straw treated with calcium oxide, sodium hydroxide and alkaline hydrogen peroxide

This study tested the effect of calcium oxide (CaO), sodium hydroxide (NaOH) and NaOH plus hydrogen peroxide (H2O2; AHP) on cell wall composition, digestion and fermentation of wheat straw (straw) in sheep. Treated straws were prepared by mixing straw either with water followed by dusting with CaO at 160 g kg-1 DM or with a NaOH solution alone at 3 l kg-1 DM to supply 80 g NaOH kg-1 DM (Na) or pre-soaked with Na exactly as in the previous treatment for 27 h followed by mixing with 130 g H2O2 kg-1 DM (AHP) for 6 h. After 14 days of storage, the treated straws and an untreated straw (U) were fed automatically every 2 h to four individually housed sheep together with a supplement in a 4×4 latin square experiment. Each kilogram supplement DM contained 422 g CP and 10.8 MJ ME. NDF (

An open-circuit hood system for gaseous exchange measurements in small ruminants

The description of an open-circuit hood system to measure gaseous exchange in small ruminants is reported along with the equations and constants needed for automatic calculations on a computer. The performance of the system was evaluated by using a series of methanol combustion tests and respiration trials on sheep eating Rhodes grass (Chloris gayana) or Lucerne (Medicago sativa) chaffs. The total dead space was 82 1 including 72 1 of hood capacity which gave a lag-time for expired gas analyses of 50 s when the hood was ventilated at 100 1 min. The measured rate of oxygen consumption was 102±1.1% of the value as confirmed by the methanol combustion tests. Preliminary animal evaluation tests showed that the postprandial profiles of gaseous exchange in sheep could be readily measured by using the open-circuit hood system. Moreover, the pattern of gaseous exchange was dependent upon the type of forage being consumed by the sheep

Synthesis and characterizations of a fluoride-releasing dental restorative material

The aim was to develop an obturating material which has the tendency to release fluoride and minimize interfaces with tooth. Nano-fluorapatite (nFA) powder was synthesized by sol-gel. The composite based on polyurethane (PU) was obtained by chemically binding the nFA (10, 15, 20% wt/wt) to the diisocyanate component by utilizing in-situ polymerization. The procedure involved stepwise addition of monomeric units of PU, and optimizing the reagent concentrations to synthesize composite. The structural, phase and morphological analysis of nFA was evaluated. The structural, fluoride release and in-vitro adhesion analysis with tooth structure of PU/nFA was conducted. For fluoride release analysis the samples were stored in artificial saliva and deionized water for periodical time intervals. Bond strength of composites was analyzed by push-out test. Chemical linkage was achieved between PU and nFA without intermediate coupling agent. The insignificant difference of fluoride release pattern was observed in artificial saliva and (p ≥ 0.05) deionized water. The PU/nFA composite provided sustained release of fluoride over a long period of time. The composite showed more adhesion toward tooth structure with the increase in concentration of nFA. Bond strength of composite was in accordance with root canal filling material, hence, the material with anti-cariogenic properties can be used as an obturating material. © 2013 Elsevier B.V