Abstract
Background
Global cardiovascular risk scores frequently underestimate risk in persons with underlying asymptomatic cardiac lesions who eventually experience cardiovascular events. The ...Get-With-The-Guidelines Initiative analysis revealed that over 70% of patients with a first cardiac event were well within guideline targets for lipid values. Most artery flow-disrupting events occur at locations with less than 50% lumen narrowing. From clinical studies published in the late 1990s using IVUS (in-the-artery-ultrasound) to visualize disease status, the typical heart attack occurs at locations with about 20% stenosis (narrowing), prior to sudden lumen closure and resulting ACS. This sudden lumen closure is caused by rupture of an unstable cardiac lesion causing a blood clot and occlusion in up to 75% of heart attacks. The role of multi-biomarker algorithms to identify vulnerable patients with these lesions at risk of short-term ACS events is of great interest.
Methods
We studied 725 adults (≥18 yrs) from Cardiology practices who received a 5-year modified Framingham Risk Score (mFRS), and a coronary artery disease predictive algorithm (CADPA) multi-biomarker score. CADPA incorporates 9 biomarkers (CTACK, Eotaxin, Fas Ligand, HGF, IL-16, MCP-3, sFas, HDL, and HbA1c) with age, sex, diabetes, and family history of myocardial infarction, previously shown to more accurately reclassify risk of cardiovascular events (cNRI=43%). Patients were classified into low (<3.5%), intermediate (3.5% - <7.5%), and high (≥7.5%) 5-year risk categories with both mFRS and CADPA. Patients low or intermediate risk by mFRS, but reclassified high by CADPA are reported and compared.
Results
Persons at low, intermediate, and high global risk categories were successively more likely to demonstrate high-risk scores with CADPA (Figure). However, 349 (65%) in the low mFRS risk group were reclassified into higher CADPA risk groups and 104 (70%) intermediate risk patients were reclassified into the high-risk group (p<0.0001 for CADPA vs. mFRS). Analysis demonstrated that 89% (309) of the low or intermediate mFRS 125 females (99%); 184 males (83%); p<0.0001 and, 86 below 65 years (93%) and 223 above 65 years (88%); p=0.26) were classified as high-risk by CADPA, indicating that many persons who may be at high risk are not identified as such by global risk assessment.
CADPA Risk Reclassification
Conclusions
We conclude that this novel multi-biomarker panel (CADPA) identifies many persons at increased risk of cardiac events due to asymptomatic cardiac lesions missed by traditional global risk methods. Further investigation of the value of such a test for prediction of near-term CVD events is required.
LUX-ZEPLIN (LZ) is a second-generation direct dark matter experiment with spin-independent WIMP-nucleon scattering sensitivity above
1.4
×
10
-
48
cm
2
for a WIMP mass of
40
GeV
/
c
2
and a
1000
days
...exposure. LZ achieves this sensitivity through a combination of a large
5.6
t
fiducial volume, active inner and outer veto systems, and radio-pure construction using materials with inherently low radioactivity content. The LZ collaboration performed an extensive radioassay campaign over a period of six years to inform material selection for construction and provide an input to the experimental background model against which any possible signal excess may be evaluated. The campaign and its results are described in this paper. We present assays of dust and radon daughters depositing on the surface of components as well as cleanliness controls necessary to maintain background expectations through detector construction and assembly. Finally, examples from the campaign to highlight fixed contaminant radioassays for the LZ photomultiplier tubes, quality control and quality assurance procedures through fabrication, radon emanation measurements of major sub-systems, and bespoke detector systems to assay scintillator are presented.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction Document Development Process Writing Committee Organization The writing committee was selected to represent the American College of Cardiology (ACC) and included a cardiovascular ...training program director, several active cardiovascular scientists and research methodology experts, early-career cardiologists, highly experienced research experts representing both academic and community-based practice settings, the chair of the ACC's Academic Cardiology Section Leadership Council, and a physician experienced in defining and applying training standards according to the 6 general competency domains promulgated by the Accreditation Council for Graduate Medical Education (ACGME) and American Board of Medical Specialties (ABMS) and endorsed by the American Board of Internal Medicine (ABIM). Name Employment Representation Consultant Speakers Bureau Ownership/Partnership/Principal Personal Research Institutional/Organizational or Other Financial Benefit Expert Witness Richard Kovacs Krannert Institute of Cardiology--Professor, Clinical Medicine Official Reviewer, ACC Board of Trustees None None None None None None Dhanunjaya Lakkireddy Kansas University Cardiovascular Research Institute Official Reviewer, ACC Board of Governors None None None None None None Howard Weitz Thomas Jefferson University Hospital--Director, Division of Cardiology; Sidney Kimmel Medical College at Thomas Jefferson University--Professor of Medicine Official Reviewer, Competency Management Committee Lead Reviewer None None None None None None Alex Auseon The Ohio State University Wexner Medical Center Content Reviewer, Academic Cardiology Section Leadership Council None None None None None None John Canty University at Buffalo Clinical and Translational Research Center--Albert and Elizabeth Rekate Professor and Chief Content Reviewer, Academic Cardiology Section Leadership Council None None None None None None Larry Jacobs Lehigh Valley Health Network, Division of Cardiology; University of South Florida--Professor, Cardiology Content Reviewer, Cardiology Training and Workforce Committee None None None None None None Andrew Kates Washington University School of Medicine Content Reviewer, Academic Cardiology Section Leadership Council None None None None None None Kiran Musunuru Brigham and Women's Hospital, Harvard University Organizational Reviewer, AHA None None None None None None Table 1 Core Competency Components and Curricular Milestones for Training in Cardiovascular Research and Scholarly Activity Add = additional months beyond the 3-year cardiovascular fellowship; DNA = deoxyribonucleic acid; RNA = ribonucleic acid.
Objectives. This study sought to determine the frequency of thrombocytopenia and its relation with clinical outcomes in high risk patients undergoing percutaneous coronary revascularization who ...received either the platelet glycoprotein (GP) IIb/IIIa receptor antagonist abciximab (ReoPro, c7E3 Fab) or conventional therapy.
Background. The development of thrombocytopenia on exposure to GPIIb/IIIa antagonists threatens the utility and economic viability of this drug class for patients with vascular disease.
Methods. We analyzed data from the Evaluation of c7E3 for the Prevention of Ischemic Complications trial (EPIC), a 2,099-patient, randomized trial of placebo, abciximab bolus or abciximab bolus plus a 12-h infusion during high-risk coronary revascularization.
Results. Thrombocytopenia (nadir platelet count <100 × 109/liter) developed in 81 patients (3.9%) during their hospital stay, with 19 (0.9%) developing severe (<50 × 109/liter) thrombocytopenia. Both thrombocytopenia and severe thrombocytopenia were more frequent in the bolus-plus-infusion arm (5.2% and 1.6%, respectively) than in the bolus-only and placebo arms combined (p = 0.020 and p = 0.025, respectively). Acute profound thrombocytopenia developed in two patients in the bolus-plus-infusion arm. Patients with thrombocytopenia experienced more unfavorable clinical outcomes than those who did not develop thrombocytopenia, regardless of treatment assignment, but those with thrombocytopenia who received abciximab had fewer worse outcomes at 30 days. Multivariable logistic modeling revealed a lower baseline platelet count, older age and lighter weight to be important predictors of thrombocytopenia. In a logistic regression model, bolus-plus-infusion treatment was a significant predictor of thrombocytopenia (p = 0.016) and remained so after adjustment for procedures and baseline risk factors (p = 0.0077).
Conclusions. Thrombocytopenia was associated with adverse clinical outcomes and excessive bleeding, but patients receiving abciximab fared better than those receiving placebo.
The significance of thrombocytopenia in patients experiencing an acute coronary syndrome (ACS) has not been examined systematically. We evaluated this condition in a large non-ST-elevation ACS ...clinical trial, with particular interest paid to its correlation with clinical outcomes.
Patients presenting without persistent ST elevation during an ACS were randomized to receive a double-blind infusion of the platelet glycoprotein (GP) IIb/IIIa inhibitor eptifibatide or placebo in addition to other standard therapies including heparin and aspirin. The primary end point was death/nonfatal myocardial infarction (MI) at 30 days, whereas bleeding and stroke were the main safety outcomes. Thrombocytopenia (nadir platelet count <100x10(9)/L or <50% of baseline) occurred in 7.0% of enrolled patients. The time to onset was a median of 4 days in both treatment arms. Patients with thrombocytopenia were older, weighed less, were more likely nonwhite, and had more cardiac risk factors. These patients experienced significantly more bleeding events: they were more than twice as likely to experience moderate/severe bleeding after adjustment for confounders. Univariably, ischemic events (stroke, MI, and death) occurred significantly (P<0.001) more frequently in patients with thrombocytopenia; multivariable regression modeling preserved this association with death/nonfatal MI at 30 days. Neither the use of heparin or eptifibatide was found to independently increase thrombocytopenic risk.
Although causality between thrombocytopenia and adverse clinical events could not be established definitively, thrombocytopenia was highly correlated with both bleeding and ischemic events, and the presence of this condition identified a more-at-risk patient population.
Indistinguishability of particles is a fundamental principle of quantum mechanics
. For all elementary and quasiparticles observed to date-including fermions, bosons and Abelian anyons-this principle ...guarantees that the braiding of identical particles leaves the system unchanged
. However, in two spatial dimensions, an intriguing possibility exists: braiding of non-Abelian anyons causes rotations in a space of topologically degenerate wavefunctions
. Hence, it can change the observables of the system without violating the principle of indistinguishability. Despite the well-developed mathematical description of non-Abelian anyons and numerous theoretical proposals
, the experimental observation of their exchange statistics has remained elusive for decades. Controllable many-body quantum states generated on quantum processors offer another path for exploring these fundamental phenomena. Whereas efforts on conventional solid-state platforms typically involve Hamiltonian dynamics of quasiparticles, superconducting quantum processors allow for directly manipulating the many-body wavefunction by means of unitary gates. Building on predictions that stabilizer codes can host projective non-Abelian Ising anyons
, we implement a generalized stabilizer code and unitary protocol
to create and braid them. This allows us to experimentally verify the fusion rules of the anyons and braid them to realize their statistics. We then study the prospect of using the anyons for quantum computation and use braiding to create an entangled state of anyons encoding three logical qubits. Our work provides new insights about non-Abelian braiding and, through the future inclusion of error correction to achieve topological protection, could open a path towards fault-tolerant quantum computing.
The aim of this meta-analysis was to compare the benefit of "early" vs. "delayed" P2Y12 inhibition in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation myocardial ...infarction (STEMI).
We conducted a meta-analysis including seven randomised controlled trials (RCTs) which compared early vs. delayed P2Y12inhibition in STEMI patients scheduled for PCI, providing data on major adverse cardiac events (MACE), all-cause death, and major bleeding. The primary endpoint was MACE. Secondary endpoints included stent thrombosis and the use of GP IIb/IIIa inhibitors (GPI). All endpoints were analysed at the shortest follow-up available. A total of 9,648 patients were included ("early"=4,792, "delayed"=4,856). "Early" P2Y12 inhibition was associated with a significant reduction in MACE rate (OR 0.73, 95% CI: 0.61-0.88, p=0.0008), myocardial infarction (OR 0.71, 95% CI: 0.57-0.90, p=0.004), bail-out GPI use (OR 0.87, 95% CI: 0.75-1.00, p=0.04) and improved coronary reperfusion before PCI (OR for Thrombolysis In Myocardial Infarction TIMI flow grade 2-3=1.12, 95% CI: 1.00-1.26, p=0.04). Major bleeding was not increased (OR 0.87, 95% CI: 0.62-1.21, p=0.41).
A strategy of early effective P2Y12 inhibition in PCI of STEMI appears to improve coronary reperfusion before PCI, and reduce MACE, MI and bail-out GPI use without increase of major bleeding.
Empagliflozin after Acute Myocardial Infarction Butler, Javed; Jones, W. Schuyler; Udell, Jacob A. ...
The New England journal of medicine,
04/2024, Letnik:
390, Številka:
16
Journal Article
Recenzirano
Among patients hospitalized for acute myocardial infarction and at risk for heart failure, empagliflozin did not lead to a significantly lower risk of a first heart-failure hospitalization or death ...from any cause than placebo.
Growth and mortality of coast Douglas-fir (
Pseudotsuga menziesii var.
menziesii) were studied for 25 years after planting seedlings at 1–6-m spacings on a site of moderate quality in the western ...Cascade Mountains of Washington. Responses were compared to those from two other studies representing high and low site qualities. Third-year height did not differ among spacings (
P
=
0.80), providing no evidence that close spacing stimulated early growth. Piecewise regression identified the onset of competition-induced mortality when stand density index (SDI Reineke, L.H. 1933. Perfecting a stand density index for even-aged forests. Journal of Agricultural Research 46, 627–638) exceeded 52% (S.E.
=
4.6) of the species’ maximum or when average crown ratio (CR) declined below 52% (S.E.
=
0.9). For a range of SDI values, CR averaged 2–7% points greater at the high-quality site than at the moderate-quality site. In a regression analysis of combined data from the moderate- and high-quality sites, relative values of average stem diameter and stand volume (% of maximum values observed per site) 23–25 years after planting increased and decreased with planting spacing, respectively (
R
2
=
0.97 and 0.91, respectively). Intersection of these relationships at 3-m spacing indicated a point of equivalent relative development of tree size and stand yield. For a range of site qualities, stands planted at 3-m spacing: (1) maintained tree vigor (CR
≥
50%) and stability (average height:dbh ratio <90), (2) experienced little or no competition-induced mortality through age 25 years, and (3) allocated 25-year growth equitably to development of tree size and stand yield, thereby providing a desirable starting point for subsequent management.
We examined 5-year basal area growth of nearly 2600 trees in stem-mapped plots at five locations differing in site characteristics, species composition, and management history on the Olympic ...Peninsula in Western Washington, USA. Our objectives were to determine if internal edges, the boundaries within the stand between components of the variable-density thinning, influenced individual tree growth, and whether incorporation of individual tree local competition indices in growth prediction models could account for treatment and edge effects. Treatment significantly affected tree growth at all sites, with trees in the thinned matrix displaying on average over 25% greater basal area growth than trees in unthinned patches. Proximity to canopy gaps created as part of the variable-density thinning increased basal area growth of trees in the thinned matrix by nearly 11%. In addition, growth of trees close to skid trails was 11% greater than trees located away from the trails. Past thinning history, and its effect on initial stocking rate, appeared to affect the magnitude of the edge effects. Blocks that had received earlier commercial thinnings, and thus had lower stocking at the onset of the study, displayed lower growth responses than previously unthinned blocks. Including local competition indices in the models generally reduced growth prediction error; however, the indices examined did not fully account for treatment or edge effects. Our results suggest that not accounting for internal edges in spatially complex stands could result in errors in projected growth of trees, although these edge effects are highly variable. Failure to account for the effects of internal edges could affect not just estimates of future stand yield, but also projections of future stand structure.
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