PCSK9 Loss-of-Function Variants, Low-Density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke: Data from 9 Studies of Blacks and Whites

PCSK9 loss-of-function (LOF) variants allow for the examination of the effects of lifetime reduced low-density lipoprotein cholesterol (LDL-C) on cardiovascular events. We examined the association of PCSK9 LOF variants with LDL-C and incident coronary heart disease and stroke through a meta-analysis of data from 8 observational cohorts and 1 randomized trial of statin therapy. Methods and Results - These 9 studies together included 17 459 blacks with 403 (2.3%) having at least 1 Y142X or C679X variant and 31 306 whites with 955 (3.1%) having at least 1 R46L variant. Unadjusted odds ratios for associations between PCSK9 LOF variants and incident coronary heart disease (851 events in blacks and 2662 events in whites) and stroke (523 events in blacks and 1660 events in whites) were calculated using pooled Mantel-Haenszel estimates with continuity correction factors. Pooling results across studies using fixed-effects inverse-variance-weighted models, PCSK9 LOF variants were associated with 35 mg/dL (95% confidence interval [CI], 32-39) lower LDL-C in blacks and 13 mg/dL (95% CI, 11-16) lower LDL-C in whites. PCSK9 LOF variants were associated with a pooled odds ratio for coronary heart disease of 0.51 (95% CI, 0.28-0.92) in blacks and 0.82 (95% CI, 0.63-1.06) in whites. PCSK9 LOF variants were not associated with incident stroke (odds ratio, 0.84; 95% CI, 0.48-1.47 in blacks and odds ratio, 1.06; 95% CI, 0.80-1.41 in whites). Conclusions - PCSK9 LOF variants were associated with lower LDL-C and coronary heart disease incidence. PCSK9 LOF variants were not associated with stroke risk

Volume I. Introduction to DUNE

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE\u27s physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology

Deep Underground Neutrino Experiment (DUNE), far detector technical design report, volume III: DUNE far detector technical coordination

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. Volume III of this TDR describes how the activities required to design, construct, fabricate, install, and commission the DUNE far detector modules are organized and managed. This volume details the organizational structures that will carry out and/or oversee the planned far detector activities safely, successfully, on time, and on budget. It presents overviews of the facilities, supporting infrastructure, and detectors for context, and it outlines the project-related functions and methodologies used by the DUNE technical coordination organization, focusing on the areas of integration engineering, technical reviews, quality assurance and control, and safety oversight. Because of its more advanced stage of development, functional examples presented in this volume focus primarily on the single-phase (SP) detector module

Managed relocation: Integrating the scientific, regulatory, and ethical challenges

Managed relocation is defined as the movement of species, populations, or genotypes to places outside the areas of their historical distributions to maintain biological diversity or ecosystem functioning with changing climate. It has been claimed that a major extinction event is under way and that climate change is increasing its severity. Projections indicating that climate change may drive substantial losses of biodiversity have compelled some scientists to suggest that traditional management strategies are insufficient. The managed relocation of species is a controversial management response to climate change. The published literature has emphasized biological concerns over difficult ethical, legal, and policy issues. Furthermore, ongoing managed relocation actions lack scientific and societal engagement. Our interdisciplinary team considered ethics, law, policy, ecology, and natural resources management to identify the key issues of managed relocation relevant for developing sound policies that support decisions for resource management. We recommend that government agencies develop and adopt best practices for managed relocation

PCSK9 Loss-of-Function Variants, Low-Density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke Data From 9 Studies of Blacks and Whites

Pathophysiology, epidemiology and therapy of agein

Phanerogamic flora and phytogeography of the Cloud Dwarf Forests of Ibitipoca State Park, Minas Gerais, Brazil

Abstract: This study was developed in Ibitipoca State Park (ISP), a mountainous massif that stands out in the Serra da Mantiqueira, in the Southeastern Region of Brazil. The vegetation is represented by a phytophysiognomic mosaic where areas of campos rupestres interspersed with cloud dwarf forests predominate, at altitudes of 1100 to 1700 m.s.m. The cloud dwarf forests exist in narrow altitude belts on the mountain peaks, immersed in a layer of clouds. They form a peculiar landscape high in the mountains by the short stature of the arboreal elements and richness of lichens and bryophytes, which develop under constant condensation of humidity, low temperatures, and frequent winds. The objective of the present work was to determine the floristic composition and phytogeography of the cloud dwarf forests of ISP. Twelve monthly campaigns were conducted to collect botanical material during the years 2014 and 2015. The collected material was deposited in the collection of the CESJ Herbarium. A total of 372 species, 209 genera, and 73 families of phanerogams were found. The richest families were Orchidaceae (84 spp.), Asteraceae (39 spp.), and Melastomataceae (21 spp). The genera with the greatest wealth were Leandra (09 spp.), Epidendrum (09 spp.), Pleurothallis (09 spp.), Mikania (07 spp.), and Miconia (07 spp). The arboreal habit was predominant with 103 species (27.7%), followed by 83 shrubs (22.3%), 82 epiphytic herbs (22%), 80 terrestrial herbs (21.5%), and 23 lianas (6.5%). The floristic composition presents elements typical of altitude vegetation, including species of campos rupestres and high epiphytes richness, especially of the families Orchidaceae and Bromeliaceae. The genera with tropical distribution represent 86.5%, whereas the temperate elements represent 13.5% of the total. The cloud dwarf forests presented similarity, at the family and gender levels, with the upper montane forests of the Andes, besides phytogeographic characteristics that allow to associate them to a transition environment between the campos rupestres and the upper montane forests of the Southeast Region of Brazil