139 research outputs found
Stringency of the 2-His–1-Asp Active-Site Motif in Prolyl 4-Hydroxylase
The non-heme iron(II) dioxygenase family of enzymes contain a common 2-His–1-carboxylate iron-binding motif. These enzymes catalyze a wide variety of oxidative reactions, such as the hydroxylation of aliphatic C–H bonds. Prolyl 4-hydroxylase (P4H) is an α-ketoglutarate-dependent iron(II) dioxygenase that catalyzes the post-translational hydroxylation of proline residues in protocollagen strands, stabilizing the ensuing triple helix. Human P4H residues His412, Asp414, and His483 have been identified as an iron-coordinating 2-His–1-carboxylate motif. Enzymes that catalyze oxidative halogenation do so by a mechanism similar to that of P4H. These halogenases retain the active-site histidine residues, but the carboxylate ligand is replaced with a halide ion. We replaced Asp414 of P4H with alanine (to mimic the active site of a halogenase) and with glycine. These substitutions do not, however, convert P4H into a halogenase. Moreover, the hydroxylase activity of D414A P4H cannot be rescued with small molecules. In addition, rearranging the two His and one Asp residues in the active site eliminates hydroxylase activity. Our results demonstrate a high stringency for the iron-binding residues in the P4H active site. We conclude that P4H, which catalyzes an especially demanding chemical transformation, is recalcitrant to change
Effects of isoflavones (soy phyto-estrogens) on serum lipids: a meta-analysis of randomized controlled trials
OBJECTIVES: To determine the effects of isoflavones (soy phyto-estrogens) on serum total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL) and triglyceride (TG). METHODS: We searched electronic databases and included randomized trials with isoflavones interventions in the forms of tablets, isolated soy protein or soy diets. Review Manager 4.2 was used to calculate the pooled risk differences with fixed effects model. RESULTS: Seventeen studies (21 comparisons) with 853 subjects were included in this meta-analysis. Isoflavones tablets had insignificant effects on serum TC, 0.01 mmol/L (95% CI: -0.17 to 0.18, heterogeneity p = 1.0); LDL, 0.00 mmol/L (95% CI: -0.14 to 0.15, heterogeneity p = 0.9); HDL, 0.01 mmol/L (95% CI: -0.05 to 0.06, heterogeneity p = 1.0); and triglyceride, 0.03 mmol/L (95% CI: -0.06 to 0.12, heterogeneity p = 0.9). Isoflavones interventions in the forms of isolated soy protein (ISP), soy diets or soy protein capsule were heterogeneous to combine. CONCLUSIONS: Isoflavones tablets, isolated or mixtures with up to 150 mg per day, seemed to have no overall statistical and clinical benefits on serum lipids. Isoflavones interventions in the forms of soy proteins may need further investigations to resolve whether synergistic effects are necessary with other soy components
The Effect of Carbon Credits on Savanna Land Management and Priorities for Biodiversity Conservation
Carbon finance offers the potential to change land management and conservation planning priorities. We develop a novel approach to planning for improved land management to conserve biodiversity while utilizing potential revenue from carbon biosequestration. We apply our approach in northern Australia's tropical savanna, a region of global significance for biodiversity and carbon storage, both of which are threatened by current fire and grazing regimes. Our approach aims to identify priority locations for protecting species and vegetation communities by retaining existing vegetation and managing fire and grazing regimes at a minimum cost. We explore the impact of accounting for potential carbon revenue (using a carbon price of US5 per hectare per year in carbon revenue and prevent the release of 1–2 billion tonnes of carbon dioxide equivalent over approximately 90 years. This revenue could be used to reduce the costs of improved land management by three quarters or double the number of biodiversity targets achieved and meet carbon storage targets for the same cost. These results are based on generalised cost and carbon data; more comprehensive applications will rely on fine scale, site-specific data and a supportive policy environment. Our research illustrates that the duel objective of conserving biodiversity and reducing the release of greenhouse gases offers important opportunities for cost-effective land management investments
Synthesis of 5-Hydroxyectoine from Ectoine: Crystal Structure of the Non-Heme Iron(II) and 2-Oxoglutarate-Dependent Dioxygenase EctD
As a response to high osmolality, many microorganisms synthesize various types of compatible solutes. These organic osmolytes aid in offsetting the detrimental effects of low water activity on cell physiology. One of these compatible solutes is ectoine. A sub-group of the ectoine producer's enzymatically convert this tetrahydropyrimidine into a hydroxylated derivative, 5-hydroxyectoine. This compound also functions as an effective osmostress protectant and compatible solute but it possesses properties that differ in several aspects from those of ectoine. The enzyme responsible for ectoine hydroxylation (EctD) is a member of the non-heme iron(II)-containing and 2-oxoglutarate-dependent dioxygenases (EC 1.14.11). These enzymes couple the decarboxylation of 2-oxoglutarate with the formation of a high-energy ferryl-oxo intermediate to catalyze the oxidation of the bound organic substrate. We report here the crystal structure of the ectoine hydroxylase EctD from the moderate halophile Virgibacillus salexigens in complex with Fe3+ at a resolution of 1.85 Å. Like other non-heme iron(II) and 2-oxoglutarate dependent dioxygenases, the core of the EctD structure consists of a double-stranded β-helix forming the main portion of the active-site of the enzyme. The positioning of the iron ligand in the active-site of EctD is mediated by an evolutionarily conserved 2-His-1-carboxylate iron-binding motif. The side chains of the three residues forming this iron-binding site protrude into a deep cavity in the EctD structure that also harbours the 2-oxoglutarate co-substrate-binding site. Database searches revealed a widespread occurrence of EctD-type proteins in members of the Bacteria but only in a single representative of the Archaea, the marine crenarchaeon Nitrosopumilus maritimus. The EctD crystal structure reported here can serve as a template to guide further biochemical and structural studies of this biotechnologically interesting enzyme family
Sex Differences in the Brain: A Whole Body Perspective
Most writing on sexual differentiation of the mammalian brain (including our own) considers just two organs: the gonads and the brain. This perspective, which leaves out all other body parts, misleads us in several ways. First, there is accumulating evidence that all organs are sexually differentiated, and that sex differences in peripheral organs affect the brain. We demonstrate this by reviewing examples involving sex differences in muscles, adipose tissue, the liver, immune system, gut, kidneys, bladder, and placenta that affect the nervous system and behavior. The second consequence of ignoring other organs when considering neural sex differences is that we are likely to miss the fact that some brain sex differences develop to compensate for differences in the internal environment (i.e., because male and female brains operate in different bodies, sex differences are required to make output/function more similar in the two sexes). We also consider evidence that sex differences in sensory systems cause male and female brains to perceive different information about the world; the two sexes are also perceived by the world differently and therefore exposed to differences in experience via treatment by others. Although the topic of sex differences in the brain is often seen as much more emotionally charged than studies of sex differences in other organs, the dichotomy is largely false. By putting the brain firmly back in the body, sex differences in the brain are predictable and can be more completely understood
Sensitivity of the T2K accelerator-based neutrino experiment with an Extended run to POT
18 pages, 4 figures18 pages, 4 figures18 pages, 4 figures18 pages, 4 figures18 pages, 4 figuresRecent measurements at the T2K experiment indicate that CP violation in neutrino mixing may be observed in the future by long-baseline neutrino oscillation experiments. We explore the physics program of an extension to the currently approved T2K running of protons-on-target to protons-on-target,aiming at initial observation of CP violation with 3 or higher significance for the case of maximum CP violation. With accelerator and beam line upgrades, as well as analysis improvements, this program would occur before the next generation of long-baseline neutrino oscillation experiments that are expected to start operation in 2026.We acknowledge the support of MEXT, Japan; NSERC (Grant No. SAPPJ-2014-00031), NRC and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SERI, Switzerland; STFC, UK; and DOE, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, and GridPP in the United Kingdom. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), H2020 Grant No. RISE-GA644294-JENNIFER, EU; JSPS, Japan; Royal Society, UK; and the DOE Early Career program, USA. CNRS/IN2P3: Centre National de la Recherche ScientifiqueInstitut National de Physique Nucleaire et de Physique des Particules RSF: Russian Science Foundation MES: Ministry of Education and Science, Russia ERDF: European Regional Development Fund SNSF: Swiss National Science Foundation SER (should be SERI): State Secretariat for Education, Research and Innovatio
T2K neutrino flux prediction
cited By 15 art_number: 012001 affiliation: Centre for Particle Physics, Department of Physics, University of Alberta, Edmonton, AB, Canada; Albert Einstein Center for Fundamental Physics, Laboratory for High Energy Physics (LHEP), University of Bern, Bern, Switzerland; Department of Physics, Boston University, Boston, MA, United States; Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada; Department of Physics and Astronomy, University of California Irvine, Irvine, CA, United States; IRFU, CEA Saclay, Gif-sur-Yvette, France; Institute for Universe and Elementary Particles, Chonnam National University, Gwangju, South Korea; Department of Physics, University of Colorado at Boulder, Boulder, CO, United States; Department of Physics, Colorado State University, Fort Collins, CO, United States; Department of Physics, Dongshin University, Naju, South Korea; Department of Physics, Duke University, Durham, NC, United States; IN2P3-CNRS, Laboratoire Leprince-Ringuet, Ecole Polytechnique, Palaiseau, France; Institute for Particle Physics, ETH Zurich, Zurich, Switzerland; Section de Physique, DPNC, University of Geneva, Geneva, Switzerland; H. Niewodniczanski Institute of Nuclear Physics PAN, Cracow, Poland; High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki, Japan; Institut de Fisica d’Altes Energies (IFAE), Bellaterra (Barcelona), Spain; IFIC (CSIC and University of Valencia), Valencia, Spain; Department of Physics, Imperial College London, London, United Kingdom; INFN Sezione di Bari, Dipartimento Interuniversitario di Fisica, Università e Politecnico di Bari, Bari, Italy; INFN Sezione di Napoli and Dipartimento di Fisica, Università di Napoli, Napoli, Italy; INFN Sezione di Padova, Dipartimento di Fisica, Università di Padova, Padova, Italy; INFN Sezione di Roma, Università di Roma la Sapienza, Roma, Italy; Institute for Nuclear Research, Russian Academy of Sciences, Moscow, Russian Federation; Kobe University, Kobe, Japan; Department of Physics, Kyoto University, Kyoto, Japan; Physics Department, Lancaster University, Lancaster, United Kingdom; Department of Physics, University of Liverpool, Liverpool, United Kingdom; Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA, United States; Université de Lyon, Université Claude Bernard Lyon 1, IPN Lyon (IN2P3), Villeurbanne, France; Department of Physics, Miyagi University of Education, Sendai, Japan; National Centre for Nuclear Research, Warsaw, Poland; State University of New York at Stony Brook, Stony Brook, NY, United States; Department of Physics and Astronomy, Osaka City University, Department of Physics, Osaka, Japan; Department of Physics, Oxford University, Oxford, United Kingdom; UPMC, Université Paris Diderot, Laboratoire de Physique Nucléaire et de Hautes Energies (LPNHE), Paris, France; Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA, United States; School of Physics, Queen Mary University of London, London, United Kingdom; Department of Physics, University of Regina, Regina, SK, Canada; Department of Physics and Astronomy, University of Rochester, Rochester, NY, United States; III. Physikalisches Institut, RWTH Aachen University, Aachen, Germany; Department of Physics and Astronomy, Seoul National University, Seoul, South Korea; Department of Physics and Astronomy, University of Sheffield, Sheffield, United Kingdom; University of Silesia, Institute of Physics, Katowice, Poland; STFC, Rutherford Appleton Laboratory, Harwell Oxford, Warrington, United Kingdom; Department of Physics, University of Tokyo, Tokyo, Japan; Institute for Cosmic Ray Research, Kamioka Observatory, University of Tokyo, Kamioka, Japan; Institute for Cosmic Ray Research, Research Center for Cosmic Neutrinos, University of Tokyo, Kashiwa, Japan; Department of Physics, University of Toronto, Toronto, ON, Canada; TRIUMF, Vancouver, BC, Canada; Department of Physics and Astronomy, University of Victoria, Victoria, BC, Canada; Faculty of Physics, University of Warsaw, Warsaw, Poland; Institute of Radioelectronics, Warsaw University of Technology, Warsaw, Poland; Department of Physics, University of Warwick, Coventry, United Kingdom; Department of Physics, University of Washington, Seattle, WA, United States; Department of Physics, University of Winnipeg, Winnipeg, MB, Canada; Faculty of Physics and Astronomy, Wroclaw University, Wroclaw, Poland; Department of Physics and Astronomy, York University, Toronto, ON, Canada references: Astier, P., (2003) Nucl. Instrum. Methods Phys. Res., Sect. A, 515, p. 800. , (NOMAD Collaboration), NIMAER 0168-9002 10.1016/j.nima.2003.07.054; Ahn, M., (2006) Phys. Rev. D, 74, p. 072003. , (K2K Collaboration), PRVDAQ 1550-7998 10.1103/PhysRevD.74.072003; Adamson, P., (2008) Phys. Rev. D, 77, p. 072002. , (MINOS Collaboration), PRVDAQ 1550-7998 10.1103/PhysRevD.77.072002; Aguilar-Arevalo, A., (2009) Phys. Rev. D, 79, p. 072002. , (MiniBooNE Collaboration), PRVDAQ 1550-7998 10.1103/PhysRevD.79.072002; (2003) Letter of Intent: Neutrino Oscillation Experiment at JHF, , http://neutrino.kek.jp/jhfnu/loi/loi_JHFcor.pdf, T2K Collaboration; Abe, K., (2011) Nucl. Instrum. Methods Phys. Res., Sect. A, 659, p. 106. , (T2K Collaboration), NIMAER 0168-9002 10.1016/j.nima.2011.06.067; Abe, K., (2011) Phys. Rev. Lett., 107, p. 041801. , (T2K Collaboration), PRLTAO 0031-9007 10.1103/PhysRevLett.107.041801; Abe, K., (2012) Phys. Rev. D, 85, p. 031103. , (T2K Collaboration), PRVDAQ 1550-7998 10.1103/PhysRevD.85.031103; Fukuda, Y., (2003) Nucl. Instrum. Methods Phys. Res., Sect. A, 501, p. 418. , NIMAER 0168-9002 10.1016/S0168-9002(03)00425-X; Beavis, D., Carroll, A., Chiang, I., (1995), Physics Design Report, BNL 52459Abgrall, N., (2011) Phys. Rev. C, 84, p. 034604. , (NA61/SHINE Collaboration), PRVCAN 0556-2813 10.1103/PhysRevC.84.034604; Abgrall, N., (2012) Phys. Rev. C, 85, p. 035210. , (NA61/SHINE Collaboration), PRVCAN 0556-2813 10.1103/PhysRevC.85.035210; Bhadra, S., (2013) Nucl. Instrum. Methods Phys. Res., Sect. A, 703, p. 45. , NIMAER 0168-9002 10.1016/j.nima.2012.11.044; Van Der Meer, S., Report No. CERN-61-07Palmer, R., Report No. CERN-65-32, 141Ichikawa, A., (2012) Nucl. Instrum. Methods Phys. Res., Sect. A, 690, p. 27. , NIMAER 0168-9002 10.1016/j.nima.2012.06.045; Matsuoka, K., (2010) Nucl. Instrum. Methods Phys. Res., Sect. A, 624, p. 591. , NIMAER 0168-9002 10.1016/j.nima.2010.09.074; Abe, K., (2012) Nucl. Instrum. Methods Phys. Res., Sect. A, 694, p. 211. , (T2K Collaboration), NIMAER 0168-9002 10.1016/j.nima.2012.03.023; Abgrall, N., (2011) Nucl. Instrum. Methods Phys. Res., Sect. A, 637, p. 25. , (T2K ND280 TPC Collaboration), NIMAER 0168-9002 10.1016/j.nima.2011.02. 036; Amaudruz, P.-A., (2012) Nucl. Instrum. Methods Phys. Res., Sect. A, 696, p. 1. , (T2K ND280 FGD Collaboration), NIMAER 0168-9002 10.1016/j.nima.2012.08. 020; Battistoni, G., Cerutti, F., Fasso, A., Ferrari, A., Muraro, S., Ranft, J., Roesler, S., Sala, P.R., (2007) AIP Conf. Proc., 896, p. 31. , APCPCS 0094-243X 10.1063/1.2720455; A. Ferrari, P. R. Sala, A. Fasso, and J. Ranft, Report No. CERN-2005-010A. Ferrari P. R. Sala A. Fasso J. Ranft Report No. SLAC-R-773A. Ferrari P. R. Sala A. Fasso J. Ranft Report No. INFN-TC-05-11R. Brun, F. Carminati, and S. Giani, Report No. CERN-W5013Zeitnitz, C., Gabriel, T.A., (1993) Proceedings of International Conference on Calorimetry in High Energy Physics, , in Elsevier Science B.V., Tallahassee, FL; Fasso, A., Ferrari, A., Ranft, J., Sala, P.R., Proceedings of the International Conference on Calorimetry in High Energy Physics, 1994, , in; Beringer, J., (2012) Phys. Rev. D, 86, p. 010001. , (Particle Data Group), PRVDAQ 1550-7998 10.1103/PhysRevD.86.010001; Eichten, T., (1972) Nucl. Phys. B, 44, p. 333. , NUPBBO 0550-3213 10.1016/0550-3213(72)90120-4; Allaby, J.V., Tech. Rep. 70-12 (CERN, 1970)Chemakin, I., (2008) Phys. Rev. C, 77, p. 015209. , PRVCAN 0556-2813 10.1103/PhysRevC.77.015209; Abrams, R.J., Cool, R., Giacomelli, G., Kycia, T., Leontic, B., Li, K., Michael, D., (1970) Phys. Rev. D, 1, p. 1917. , PRVDAQ 0556-2821 10.1103/PhysRevD.1.1917; Allaby, J.V., (1970) Yad. Fiz., 12, p. 538. , IDFZA7 0044-0027; Allaby, J.V., (1969) Phys. Lett. B, 30, p. 500. , PYLBAJ 0370-2693 10.1016/0370-2693(69)90184-1; Allardyce, B.W., (1973) Nucl. Phys. A, 209, p. 1. , NUPABL 0375-9474 10.1016/0375-9474(73)90049-3; Bellettini, G., Cocconi, G., Diddens, A.N., Lillethun, E., Matthiae, G., Scanlon, J.P., Wetherell, A.M., (1966) Nucl. Phys., 79, p. 609. , NUPHA7 0029-5582 10.1016/0029-5582(66)90267-7; Bobchenko, B.M., (1979) Sov. J. Nucl. Phys., 30, p. 805. , SJNCAS 0038-5506; Carroll, A.S., (1979) Phys. Lett. B, 80, p. 319. , PYLBAJ 0370-2693 10.1016/0370-2693(79)90226-0; Cronin, J.W., Cool, R., Abashian, A., (1957) Phys. Rev., 107, p. 1121. , PHRVAO 0031-899X 10.1103/PhysRev.107.1121; Chen, F.F., Leavitt, C., Shapiro, A., (1955) Phys. Rev., 99, p. 857. , PHRVAO 0031-899X 10.1103/PhysRev.99.857; Denisov, S.P., Donskov, S.V., Gorin, Yu.P., Krasnokutsky, R.N., Petrukhin, A.I., Prokoshkin, Yu.D., Stoyanova, D.A., (1973) Nucl. Phys. B, 61, p. 62. , NUPBBO 0550-3213 10.1016/0550-3213(73)90351-9; Longo, M.J., Moyer, B.J., (1962) Phys. Rev., 125, p. 701. , PHRVAO 0031-899X 10.1103/PhysRev.125.701; Vlasov, A.V., (1978) Sov. J. Nucl. Phys., 27, p. 222. , SJNCAS 0038-5506; Feynman, R., (1969) Phys. Rev. Lett., 23, p. 1415. , PRLTAO 0031-9007 10.1103/PhysRevLett.23.1415; Bonesini, M., Marchionni, A., Pietropaolo, F., Tabarelli De Fatis, T., (2001) Eur. Phys. J. C, 20, p. 13. , EPCFFB 1434-6044 10.1007/s100520100656; Barton, D.S., (1983) Phys. Rev. D, 27, p. 2580. , PRVDAQ 0556-2821 10.1103/PhysRevD.27.2580; Skubic, P., (1978) Phys. Rev. D, 18, p. 3115. , PRVDAQ 0556-2821 10.1103/PhysRevD.18.3115; Feynman, R.P., (1972) Photon-Hadron Interactions, , Benjamin, New York; Bjorken, J.D., Paschos, E.A., (1969) Phys. Rev., 185, p. 1975. , PHRVAO 0031-899X 10.1103/PhysRev.185.1975; Taylor, F.E., Carey, D., Johnson, J., Kammerud, R., Ritchie, D., Roberts, A., Sauer, J., Walker, J., (1976) Phys. Rev. D, 14, p. 1217. , PRVDAQ 0556-2821 10.1103/PhysRevD.14.1217; Abgrall, N., (2013) Nucl. Instrum. Methods Phys. Res., Sect. A, 701, p. 99. , NIMAER 0168-9002 10.1016/j.nima.2012.10.079; Hayato, Y., (2002) Nucl. Phys. B, Proc. Suppl., 112, p. 171. , NPBSE7 0920-5632 10.1016/S0920-5632(02)01759-0 correspondence_address1: Abe, K.; Institute for Cosmic Ray Research, Kamioka Observatory, University of Tokyo, Kamioka, Japan coden: PRVDA abbrev_source_title: Phys Rev D Part Fields Gravit Cosmol document_type: Article source: Scopu
Proposal for an Extended Run of T2K to POT
68 pages, 31 figures68 pages, 31 figures68 pages, 31 figuresRecent measurements by the T2K neutrino oscillation experiment indicate that CP violation in neutrino mixing may be observed in the future by long-baseline neutrino oscillation experiments. We propose an extension to the currently approved T2K running from 7.8\times 10^{21}~\mbox{POT} to 20\times 10^{21}~\mbox{POT}, aiming at initial observation of CP violation with 3 or higher significance for the case of maximum CP violation. The program also contains a measurement of mixing parameters, and , with a precision of 1.7 or better and 1%, respectively. With accelerator and beamline upgrades, as well as analysis improvements, this program would occur before the next generation of long-baseline neutrino oscillation experiments that are expected to start operation in 2026
Varying constants, Gravitation and Cosmology
Fundamental constants are a cornerstone of our physical laws. Any constant
varying in space and/or time would reflect the existence of an almost massless
field that couples to matter. This will induce a violation of the universality
of free fall. It is thus of utmost importance for our understanding of gravity
and of the domain of validity of general relativity to test for their
constancy. We thus detail the relations between the constants, the tests of the
local position invariance and of the universality of free fall. We then review
the main experimental and observational constraints that have been obtained
from atomic clocks, the Oklo phenomenon, Solar system observations, meteorites
dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic
microwave background and big bang nucleosynthesis. At each step we describe the
basics of each system, its dependence with respect to the constants, the known
systematic effects and the most recent constraints that have been obtained. We
then describe the main theoretical frameworks in which the low-energy constants
may actually be varying and we focus on the unification mechanisms and the
relations between the variation of different constants. To finish, we discuss
the more speculative possibility of understanding their numerical values and
the apparent fine-tuning that they confront us with.Comment: 145 pages, 10 figures, Review for Living Reviews in Relativit
Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial
Aims The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p
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