Suggested Improvements in the Law of Evidence

The Washington Committee on Judicial Administration assigned a section of its membership to study the law of evidence in the state of Washington in the light of the Reports of the Section of Judicial Administration of the American Bar Association, published in July, 1938. The observations and recommendations of the Washington Section on the Law of Evidence appear in the following report

Matching Three-Dimensional Objects Using a Relational Paradigm

A relational model for describing three-dimensional objects has been designed and implemented as part of a database system. The models which provide rough descriptions to be used at the top level of a hierarchy for describing objects, were designed for initial matching attempts on an unknown object. The descriptions are in terms of the set of simple parts of the objects. Simple parts can be sticks (long, thin parts), plates (flat, wide parts) , and blobs (parts that have three significant dimensions). The relations include an attribute-value table for global properties of the object, the properties of the simple parts, binary connection and support relationships, ternary connection relationships, parallel relationships, perpendicular relationships, and binary constraints. An important use of the system is to characterize the similarity and differences between three-dimensional objects. Toward this end, we have defined a measure of relational similarity between three-dimensional object models and a measure of feature similarity, based only on Euclidean distance between attribute-value tables. In a series of experiments, we compare the results of using the two different similarity measures and conclude that the relational similarity is much more powerful than the feature similarity and should be used when grouping the objects in the database for fast access

Planet Hunters. VI: An Independent Characterization of KOI-351 and Several Long Period Planet Candidates from the Kepler Archival Data

We report the discovery of 14 new transiting planet candidates in the Kepler field from the Planet Hunters citizen science program. None of these candidates overlapped with Kepler Objects of Interest (KOIs) at the time of submission. We report the discovery of one more addition to the six planet candidate system around KOI-351, making it the only seven planet candidate system from Kepler. Additionally, KOI-351 bears some resemblance to our own solar system, with the inner five planets ranging from Earth to mini-Neptune radii and the outer planets being gas giants; however, this system is very compact, with all seven planet candidates orbiting $\lesssim 1$ AU from their host star. A Hill stability test and an orbital integration of the system shows that the system is stable. Furthermore, we significantly add to the population of long period transiting planets; periods range from 124-904 days, eight of them more than one Earth year long. Seven of these 14 candidates reside in their host star's habitable zone.Comment: 27 pages, 6 figures, 5 tables, Accepted to AJ (in press) (updated title from original astro-ph submission

Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome

Background: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). Objectives: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). Methods: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. Results: Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081). Conclusions: Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)

Risk Categorization Using New American College of Cardiology/American Heart Association Guidelines for Cholesterol Management and Its Relation to Alirocumab Treatment Following Acute Coronary Syndromes

BACKGROUND: The 2018 US cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with lowdensity lipoprotein cholesterol ≥70 mg/dL or non−high-density lipoprotein cholesterol ≥100 mg/dL despite maximum tolerated statin therapy. Such patients are considered at very high risk (VHR) based on a history of >1 major atherosclerotic cardiovascular disease (ASCVD) event or a single ASCVD event and multiple high-risk conditions. We investigated the association of US guideline-defined risk categories with the occurrence of ischemic events after acute coronary syndrome and reduction of those events by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. METHODS: In the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), patients with recent acute coronary syndrome and residual dyslipidemia despite optimal statin therapy were randomly assigned to alirocumab or placebo. The primary trial outcome (major adverse cardiovascular events, ie, coronary heart disease death, nonfatal myocardial infarction, is

Phylogenomics Reveals Ancient Gene Tree Discordance in the Amphibian Tree of Life

Molecular phylogenies have yielded strong support for many parts of the amphibian Tree of Life, but poor support for the resolution of deeper nodes, including relationships among families and orders. To clarify these relationships, we provide a phylogenomic perspective on amphibian relationships by developing a taxon-specific Anchored Hybrid Enrichment protocol targeting hundreds of conserved exons which are effective across the class. After obtaining data from 220 loci for 286 species (representing 94% of the families and 44% of the genera), we estimate a phylogeny for extant amphibians and identify gene tree–species tree conflict across the deepest branches of the amphibian phylogeny. We perform locus-by-locus genealogical interrogation of alternative topological hypotheses for amphibian monophyly, focusing on interordinal relationships. We find that phylogenetic signal deep in the amphibian phylogeny varies greatly across loci in a manner that is consistent with incomplete lineage sorting in the ancestral lineage of extant amphibians. Our results overwhelmingly support amphibian monophyly and a sister relationship between frogs and salamanders, consistent with the Batrachia hypothesis. Species tree analyses converge on a small set of topological hypotheses for the relationships among extant amphibian families. These results clarify several contentious portions of the amphibian Tree of Life, which in conjunction with a set of vetted fossil calibrations, support a surprisingly younger timescale for crown and ordinal amphibian diversification than previously reported. More broadly, our study provides insight into the sources, magnitudes, and heterogeneity of support across loci in phylogenomic data sets

Phylogenomics Reveals Ancient Gene Tree Discordance in the Amphibian Tree of Life

The Author(s) 2020. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. Molecular phylogenies have yielded strong support for many parts of the amphibian Tree of Life, but poor support for the resolution of deeper nodes, including relationships among families and orders. To clarify these relationships, we provide a phylogenomic perspective on amphibian relationships by developing a taxon-specific Anchored Hybrid Enrichment protocol targeting hundreds of conserved exons which are effective across the class. After obtaining data from 220 loci for 286 species (representing 94% of the families and 44% of the genera), we estimate a phylogeny for extant amphibians and identify gene tree-species tree conflict across the deepest branches of the amphibian phylogeny. We perform locus-by-locus genealogical interrogation of alternative topological hypotheses for amphibian monophyly, focusing on interordinal relationships. We find that phylogenetic signal deep in the amphibian phylogeny varies greatly across loci in a manner that is consistent with incomplete lineage sorting in the ancestral lineage of extant amphibians. Our results overwhelmingly support amphibian monophyly and a sister relationship between frogs and salamanders, consistent with the Batrachia hypothesis. Species tree analyses converge on a small set of topological hypotheses for the relationships among extant amphibian families. These results clarify several contentious portions of the amphibian Tree of Life, which in conjunction with a set of vetted fossil calibrations, support a surprisingly younger timescale for crown and ordinal amphibian diversification than previously reported. More broadly, our study provides insight into the sources, magnitudes, and heterogeneity of support across loci in phylogenomic data sets.[AIC; Amphibia; Batrachia; Phylogeny; gene tree-species tree discordance; genomics; information theory.].This work was supported by grants from a graduate student research award from the Society of Systematic Biologists and the University of Kentucky G.F. Ribble Endowment (to P.M.H.), by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/BEX 2806/09-6 to P.L.V.P.), and by the National Science Foundation (DEB-0949532 and DEB-1355000 to D.W.W., DEB-1120516 to E.M.L., IIP-1313554 to A.R.L. and E.M.L, DEB-1355071 to J.M.B., DEB-1441719 to R.A.P., DEB-1311442 to P.L.V.P., DEB-1354506 to R.C.T., DEB-1021247 to E.P. and C.J.R., DEB-1021299 to K.M. Kjer, and DEB-1257610, DEB-0641023, DEB-0423286, and DEB-9984496 to C.J.R.), and the Australian Research Council (DP120104146 to J.S.K. and S.C.D.). S.R.R. thanks SENESCYT (Arca de Noé Initiative; SRR and O. Torres-Carvajal principal investigators) for funding for tissue collection. J.L. was supported by the Systematics Association and the Linnean Society Systematics Research Fund. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program (DGE-3048109801 to P.M.H.) and by the National Science Foundation-supported National Center for Supercomputing Applications Blue Waters Graduate Research Fellowship Program (under Grant No. 0725070, subaward 15836, to P.M.H.). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation

Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome

Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081). Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402