Genome-wide and candidate gene approaches of clopidogrel efficacy using pharmacodynamic and clinical end points—Rationale and design of the International Clopidogrel Pharmacogenomics Consortium (ICPC)

Bergmeijer, Thomas O.,Reny, Jean-Luc,Pakyz, Ruth E.,Gong, Li,Lewis, Joshua P.,Kim, Eun-Young,Aradi, Daniel,Fernandez-Cadenas, Israel,Horenstein, Richard B.,Lee, Ming Ta Michael,Whaley, Ryan M.,Montane Elsevier 2018 American Heart Journal Vol.198 No.-

<P><B>Rationale</B></P> <P>The P2Y<SUB>12</SUB> receptor inhibitor clopidogrel is widely used in patients with acute coronary syndrome, percutaneous coronary intervention, or ischemic stroke. Platelet inhibition by clopidogrel shows wide interpatient variability, and high on-treatment platelet reactivity is a risk factor for atherothrombotic events, particularly in high-risk populations. <I>CYP2C19</I> polymorphism plays an important role in this variability, but heritability estimates suggest that additional genetic variants remain unidentified. The aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify genetic determinants of clopidogrel pharmacodynamics and clinical response.</P> <P><B>Study design</B></P> <P>Based on the data published on www.clinicaltrials.gov, clopidogrel intervention studies containing genetic and platelet function data were identified for participation. Lead investigators were invited to share DNA samples, platelet function test results, patient characteristics, and cardiovascular outcomes to perform candidate gene and genome-wide studies.</P> <P><B>Results</B></P> <P>In total, 17 study sites from 13 countries participate in the ICPC, contributing individual patient data from 8,829 patients. Available adenosine diphosphate–stimulated platelet function tests included vasodilator-stimulated phosphoprotein assay, light transmittance aggregometry, and the VerifyNow P2Y<SUB>12</SUB> assay. A proof-of-principle analysis based on genotype data provided by each group showed a strong and consistent association between <I>CYP2C19</I>*2 and platelet reactivity (<I>P</I> value=5.1 × 10<SUP>−40</SUP>).</P> <P><B>Conclusion</B></P> <P>The ICPC aims to identify new loci influencing clopidogrel efficacy by using state-of-the-art genetic approaches in a large cohort of clopidogrel-treated patients to better understand the genetic basis of on-treatment response variability.</P>

Report of the CCQM-K97: measurement of arsenobetaine standard solution and arsenobetaine content in fish tissue (tunafish)

Ma, L D,Wang, J,WEI, C,Kuroiwa, T,Narukawa, T,Ito, N,HIOKI, A,CHIBA, K,Yim, Y H,Lee, K S,Lim, Y R,Turk, G C,Davis, C W,Mester, Z,Yang, L,McCooeye, M,Maxwell, P,Cankur, O,Tokman, N,Coskun, F G BUREAU INTERNATIONAL DES POIDS ET MESURES 2017 METROLOGIA -BERLIN- Vol.54 No.-

<P></P> <P>The CCQM-K97 key comparison was organized by the inorganic analysis working group (IAWG) of CCQM as a follow-up to completed pilot study CCQM-P96 and P96.1 to test the abilities of the national metrology institutes to accurately quantitate the mass fraction of arsenobetaine (AsB) in standard solution and in fish tissue. A pilot study CCQM-P133 was parallelized with this key comparison. National Institute of Metrology (NIM), China and National Metrology Institute of Japan (NMIJ) acted as the coordinating laboratories.</P> <P>Six NMIs participated in CCQM-K97 and two institutes participated in CCQM-P133, and all of them submitted the results. Some NMIs submitted more than one results by different methods. The results were in excellent agreement with each other, and obviously better than those of previous P96 and P96.1. Therefore the calibrant which each NMI used was comparable. It shows that the capabilities of some of the participants have been improved after the previous pilot studies.</P> <H2>Main text</H2> <P> To reach the main text of this paper, click on <A HREF='http://www.bipm.org/utils/common/pdf/final_reports/QM/K97/CCQM-K97.pdf'>Final Report</A>. Note that this text is that which appears in Appendix B of the BIPM key comparison database <A HREF='http://kcdb.bipm.org/'>kcdb.bipm.org/</A>.</P> <P>The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).</P>

Determination of Optimal Conditions of Pressure Toasting on Legume Seeds for Dairy Deed Industry : I. Effects of Pressure Toasting on Nutritive Values of Lupinus albus in Lactating Dairy Cows

Yu, P.,Goelema, J.O.,Tamminga, S. Asian Australasian Association of Animal Productio 1999 Animal Bioscience Vol.12 No.8

Whole lupinus albus seeds were pressure toasted at temperatures of 100, 118 and $136^{\circ}C$ for 3, 7, 15 and 30 min to study rumen degradation and post-rumen digestion and to determine optimal heating conditions for the Dutch dairy feed industry. In sacco nylon bag and mobile bag techniques were employed for rumen and intestine incubations to determine ruminal degradation characteristics and intestinal digestion of crude protein (CP) in 4 lactation rumen cannulated and 4 lactating intestinal cannulated Dutch dairy cows fed 47% hay and 53% concentrate according to Dutch dairy requirements. Measured rumen degradation characteristics were soluble fraction (S), undegradable fraction (U), potentially degradable fraction (D), lag time (T0) and rate of degradation (Kd) of insoluble but degradable fraction. Percentage bypass feed protein (BCP), ruminal microbial protein synthesized based on available nitrogen (N_MP) and that based on available energy (E_MP), true protein supplied to the small intestine (TPSI), truly absorbed BCP (ABCP), absorbed microbial protein (AVP) in the small intestine, endogenous protein losses in the digestion (ENDP), true digested protein in the small intestine (TAP or DVE in Dutch) and degraded protein balance (PDB or OEB in Dutch) were totally evaluated using the new Dutch DVE/OEB System. Pressure toasting decreased (p<0.001) rumen degradability of CP. It reduced S (p<0.05) and Kd (p=0.06), increased D (p<0.05) and U (p<0.01) but did not alter T0 (p>0.05), thus resulting in dramatically increased BCP (p<0.001) with increasing time and temperature from 73.7 (raw) up to 182.5 g/kg DM ($136^{\circ}C/15min$). Although rumen microbial protein synthesized based on available energy (E_MP) was reduced, true protein (microbial and bypass feed protein) supplied to the small intestine (TPSI) was increased (p<0.001) from 153.1 (raw) to 247.6 g/kg DM ($136^{\circ}C/15min$). Due to digestibility of BCP in the intestine not changing (p>0.05) average 87.8%, the absorbed BCP increased (p<0.001) from 62.3 (raw) to 153.7 g/kg DM ($136^{\circ}C/15min$). Therefore DVE value of true digested protein in the small intestine was significantly increased (p<0.001) from 118.9 (raw) to 197.0 g/kg DM ($136^{\circ}C/15min$) and OEB value of degraded protein balance was significantly reduced (p<0.001) from 147.2 (raw) to 63.1 g/kg DM ($136^{\circ}C/15min$). It was concluded that pressure toasting was effective in shifting degradation of CP of lupinus albus from the rumen to small intestine without changing intestinal digestion. Further studies are required on the degradation and digestion of individual amino acids and on the damaging effects of processing on amino acids, especially the first limiting amino acids.

Characteristics of greenhouse gas concentrations derived from ground-based FTS spectra at Anmyeondo, South Korea

Oh, Young-Suk,Kenea, S. Takele,Goo, Tae-Young,Chung, Kyu-Sun,Rhee, Jae-Sang,Ou, Mi-Lim,Byun, Young-Hwa,Wennberg, Paul O.,Kiel, Matthä,us,DiGangi, Joshua P.,Diskin, Glenn S.,Velazco, Voltaire A.,Gr Copernicus GmbH 2018 Atmospheric measurement techniques Vol.11 No.4

<P><p><strong>Abstract.</strong> Since the late 1990s, the meteorological observatory established in Anmyeondo (36.5382°<span class='thinspace'></span>N, 126.3311°<span class='thinspace'></span>E, and 30<span class='thinspace'></span>m above mean sea level) has been monitoring several greenhouse gases such as CO₂, CH₄, N₂O, CFCs, and SF₆ as a part of the Global Atmosphere Watch (GAW) Program. A high resolution ground-based (g-b) Fourier transform spectrometer (FTS) was installed at this observation site in 2013 and has been operated within the frame work of the Total Carbon Column Observing Network (TCCON) since August 2014. The solar spectra recorded by the g-b FTS cover the spectral range 3800 to 16<span class='thinspace'></span>000<span class='thinspace'></span>cm⁻¹ at a resolution of 0.02<span class='thinspace'></span>cm⁻¹. In this work, the GGG2014 version of the TCCON standard retrieval algorithm was used to retrieve total column average CO₂ and CH₄ dry mole fractions (XCO₂, XCH₄) and from the FTS spectra. Spectral bands of CO₂ (at 6220.0 and 6339.5<span class='thinspace'></span>cm⁻¹ center wavenumbers, CH₄ at 6002<span class='thinspace'></span>cm⁻¹ wavenumber, and O₂ near 7880<span class='thinspace'></span>cm⁻¹ ) were used to derive the XCO₂ and XCH₄. In this paper, we provide comparisons of XCO₂ and XCH₄ between the aircraft observations and g-b FTS over Anmyeondo station. A comparison of 13 coincident observations of XCO₂ between g-b FTS and OCO-2 (Orbiting Carbon Observatory) satellite measurements are also presented for the measurement period between February 2014 and November 2017. OCO-2 observations are highly correlated with the g-b FTS measurements (<i>r</i>² = 0.884) and exhibited a small positive bias (0.189<span class='thinspace'></span>ppm). Both data set capture seasonal variations of the target species with maximum and minimum values in spring and late summer, respectively. In the future, it is planned to further utilize the FTS measurements for the evaluation of satellite observations such as Greenhouse Gases Observing Satellite (GOSAT, GOSAT-2). This is the first report of the g-b FTS observations of XCO₂ species over the Anmyeondo station.</p> </P>

Comparative study on nano-crystalline titanium dioxide catalyzed photocatalytic degradation of aromatic carboxylic acids in aqueous medium

P.A. Joshi,V.G. Gandhi,M.K. Mishra,M.S. Rao,A. Kumar,D.O. Shah 한국공업화학회 2011 Journal of Industrial and Engineering Chemistry Vol.17 No.2

The comparative study on titanium dioxide (TiO2) catalyzed photocatalytic degradation (PCD) of aqueous aromatic carboxylic acids (phthalic acid, o-nitrobenzoic acid, o-chlorobenzoic acid and benzoic acid) was carried out in the presence of UV radiation using air. The TiO2 catalyst, synthesized by sol–gel technique and calcined at 673 K, resulted ca. 100% anatase phase with 23 nm crystallite size and surface area of 37 m2/g. This catalyst was found to be efficient for PCD of phthalic acid, o-nitrobenzoic acid, ochlorobenzoic acid and benzoic acid in aqueous medium. However, the reactivity and degradation pathway of these carboxylic acids were observed to be greatly influenced by the substituent group present in the aromatic ring. The order of degradation of aromatic carboxylic acids was found to be phthalic acid > o-nitrobenzoic acid > o-chlorobenzoic acid > benzoic acid. The aromatic carboxylic acids having electron withdrawing groups such as –COOH, –NO2 and –Cl were comparatively more reactive for PCD than unsubstituted aromatic acid i.e., benzoic acid. The degradation of ortho substituted benzoic acids (having electron withdrawing groups) follows different mechanistic pathway than that of benzoic acid. Study of various operational parameters like effect of catalyst loading, initial concentration of phthalic acid and kinetics of phthalic acid PCD was also carried out in batch type photocatalytic reactor.

Impaired expression of Toll-like receptor 2 in nontuberculous mycobacterial lung disease.

Ryu, Y J,Kim, E J,Lee, S-H,Kim, S Y,Suh, G Y,Chung, M P,Kim, H,Kwon, O J,Koh, W-J Published jointly by the Society and Munksgaard 2007 The European respiratory journal Vol.30 No.4

<P>The aims of the present study were to investigate the expression of Toll-like receptor (TLR)2 on the peripheral blood monocytes of patients with nontuberculous mycobacterial (NTM) lung disease and healthy controls, and to assess the responses of these monocytes to TLR2 agonists such as Mycobacterium avium and lipoteichoic acid (LTA). Reverse transcriptase-PCR was used to analyse TLR2 mRNA expression in peripheral blood monocytes from 17 NTM patients and 10 healthy controls. mRNA and protein secretion levels were also determined for the cytokines interleukin (IL)-12 p40 and tumour necrosis factor (TNF)-alpha. Expression of TLR2 mRNA by peripheral blood monocytes after stimulation with M. avium or LTA was lower in NTM patients than in healthy controls. IL-12 p40 and TNF-alpha mRNA and cytokine secretion levels were also lower in patients than in healthy controls. Treatment with anti-TLR antibody decreased M. avium- and LTA-induced IL-12 p40 and TNF-alpha production in healthy controls, but not in NTM patients. The present results suggest that the downregulation of Toll-like receptor 2 and the resulting decreased production of interleukin-12 p40 and tumour necrosis factor-alpha following Mycobacterium avium or lipoteichoic acid stimulation may contribute to host susceptibility to nontuberculous mycobacterial lung disease.</P>

All-sky search for periodic gravitational waves in the O1 LIGO data

Abbott, B. P.,Abbott, R.,Abbott, T. D.,Acernese, F.,Ackley, K.,Adams, C.,Adams, T.,Addesso, P.,Adhikari, R. X.,Adya, V. B.,Affeldt, C.,Afrough, M.,Agarwal, B.,Agatsuma, K.,Aggarwal, N.,Aguiar, O. D.,A American Physical Society 2017 Physical Review D Vol.96 No.6

<P>We report on an all-sky search for periodic gravitational waves in the frequency band 20-475 Hz and with a frequency time derivative in the range of [-1.0, +0.1] x 10(-8) Hz/s. Such a signal could be produced by a nearby spinning and slightly nonaxisymmetric isolated neutron star in our galaxy. This search uses the data from Advanced LIGO's first observational run, O1. No periodic gravitational wave signals were observed, and upper limits were placed on their strengths. The lowest upper limits on worst-case (linearly polarized) strain amplitude h(0) are similar to 4 x 10(-25) near 170 Hz. For a circularly polarized source (most favorable orientation), the smallest upper limits obtained are similar to 1.5 x 10(-25). These upper limits refer to all sky locations and the entire range of frequency derivative values. For a population-averaged ensemble of sky locations and stellar orientations, the lowest upper limits obtained for the strain amplitude are similar to 2.5 x 10(-25).</P>

Global emissions of HFC-143a (CH3CF3) and HFC-32 (CH2F2) from in situ and air archive atmospheric observations

O&,apos,Doherty, S.,Rigby, M.,Mü,hle, J.,Ivy, D. J.,Miller, B. R.,Young, D.,Simmonds, P. G.,Reimann, S.,Vollmer, M. K.,Krummel, P. B.,Fraser, P. J.,Steele, L. P.,Dunse, B.,Salameh, P. K.,Harth, Copernicus GmbH 2014 Atmospheric chemistry and physics Vol.14 No.17

<P>Abstract. High-frequency, in situ observations from the Advanced Global Atmospheric Gases Experiment (AGAGE), for the period 2003 to 2012, combined with archive flask measurements dating back to 1977, have been used to capture the rapid growth of HFC-143a (CH3CF3) and HFC-32 (CH2F2) mole fractions and emissions into the atmosphere. Here we report the first in situ global measurements of these two gases. HFC-143a and HFC-32 are the third and sixth most abundant hydrofluorocarbons (HFCs) respectively and they currently make an appreciable contribution to the HFCs in terms of atmospheric radiative forcing (1.7 ± 0.04 and 0.7 ± 0.02 mW m−2 in 2012 respectively). In 2012 the global average mole fraction of HFC-143a was 13.4 ± 0.3 ppt (1σ) in the lower troposphere and its growth rate was 1.4 ± 0.04 ppt yr−1; HFC-32 had a global mean mole fraction of 6.2 ± 0.2 ppt and a growth rate of 1.1 ± 0.04 ppt yr−1 in 2012. The extensive observations presented in this work have been combined with an atmospheric transport model to simulate global atmospheric abundances and derive global emission estimates. It is estimated that 23 ± 3 Gg yr−1 of HFC-143a and 21 ± 11 Gg yr−1 of HFC-32 were emitted globally in 2012, and the emission rates are estimated to be increasing by 7 ± 5% yr−1 for HFC-143a and 14 ± 11% yr−1 for HFC-32. </P>

Effect of Xylanase on Performance and Apparent Metabolisable Energy in Starter Broilers Fed Diets Containing One Maize Variety Harvested in Different Regions of China

O'Neill, H.V. Masey,Liu, N.,Wang, J.P.,Diallo, A.,Hill, S. Asian Australasian Association of Animal Productio 2012 Animal Bioscience Vol.25 No.4

The objective of this study was to investigate the variability in broiler performance, apparent metabolisable energy (AME) and ileal digestible energy (IDE) between five different maize samples fed with and without xylanase at 16,000 U/kg. Various in vitro characterisations were conducted to determine if any could predict performance or AME. Samples of the maize were harvested in five diverse regions and fed individually in a mash diet as follows (g/kg): test maize 608.3; soya bean meal (SBM) 324.1; poultry fat 25.2; salt 4.6; met 2.6; lys 1.6; thr 0.5; limestone 9.7, dical 18.4; vit/min 5.0; CP 210 and ME (kcal/kg) 3,085. The diets were fed to 720 broilers with 6 replicates, each containing 12 birds per treatment, from 0 to 18 d of age. Maize samples were analysed for starch, protein, crude fibre, fat, protein solubility index (PSI) and vitreousness using near infra red reflectance spectroscopy (NIR). They were also assayed using an in vitro starch digestibility method. The results showed that there was no effect of harvest region on the feed intake (FI), body weight gain (BWG) or feed conversion ratio (FCR) of the broilers over the 18 d period (p = 0.959, 0.926, 0.819 respectively). There was an improvement in all parameters with the addition of xylanase (FI p = 0.011; BWG and FCR p<0.001). There was a significant positive effect of xylanase on IDE, AME, IDE Intake (IDEI) and AME intake (AMEI) (p<0.0001 in all cases). Although there was no significant effect of maize source, there was a strong trend towards variability in IDE (p = 0.066) and AME (p = 0.058). There were no significant correlations (p<0.05) between any proximate or physiochemical values and any performance or AME values. This may suggest that none of those selected were suitable predictors for performance or AME. The broilers performed well according to the breed guidelines, with slightly increased FI, increased BWG and similar FCR prior to the addition of xylanase. When FCR and BWG were analysed with FI as a covariate, xylanase addition remained significant suggesting that the improvement in BWG and FCR was driven by an increase in digestibility and nutrient availability.

Effects of pre-sowing treatments on the germination and early growth performance of Pouteria campachiana

O. A. Amoakoh,D. D. N. Nortey,F. Sagoe,P. K. Amoako,C. K. Jallah 한국산림과학회 2017 Forest Science And Technology Vol.13 No.2

Pouteria campachiana is a multipurpose fruit tree with diverse economic and medicinal significance. However, seed dormancy and low germination are problems for its use in agro-forestry practices. Investigations were carried out on the effect of pre-treatment on the germination and early seedling growth of P. campachiana. Germination was observed in seeds pre-treated with soaking and mechanical scarification in the 5th week after sowing, while untreated seeds germinated in the 7th week. Comparison between mechanically scarified and unscarified P. campachiana seeds showed no significant difference (P > 0.05). The study showed that soaking P. campachina seeds in cold water was not good for its germination, with a significant difference between soaked seeds and non soaked seeds. Percentage germination of seeds not soaked was 62.2% compared to 26.7% and 24.4% recorded for seeds soaked for 24 h and 48 h, respectively. The application of different pre-treatments, however, had no significant (P > 0.05) influence on the mean shoot length, collar diameter, and the number of leaves of P. campachiana. The study concludes that mechanical scarification improves germination of P. campachiana while soaking with cold water has a negative influence on seed germination.