Antiplatelet Therapy in Patients With Abdominal Aortic Aneurysm Without Symptomatic Atherosclerotic Disease

IMPORTANCE: Patients with abdominal aortic aneurysm have a high risk of ischemic events associated with concomitant atherosclerotic cardiovascular disease, and current clinical practice guidelines recommend antiplatelet therapy to mitigate this risk. However, in patients with aneurysms without symptomatic atherosclerosis, the benefit of antiplatelet therapy has been sparsely investigated.OBJECTIVE: To estimate the effect of antiplatelets on the risk of ischemic events and bleeding in individuals with abdominal aneurysms with no symptomatic atherosclerotic vascular disease.DESIGN, SETTING, AND PARTICIPANTS: A comparative effectiveness research study using a target trial emulation framework was performed. Population-based, cross-linked observational data from Danish national health registries containing comprehensive, individual-level information on all Danish citizens were used to evaluate patients who were antiplatelet-naive and diagnosed with abdominal aortic aneurysms, with no record of symptomatic atherosclerotic vascular disease, from January 1, 2010, through August 21, 2021.EXPOSURE: Prescription filled for aspirin or clopidogrel.MAIN OUTCOMES AND MEASURES: Risk of ischemic events (myocardial infarction and/or ischemic stroke) and risk of major bleeding. For target trial emulation, trials were emulated as sequential, contingent on patient eligibility at the time of inclusion, and were evaluated by means of pooled logistic regression models to estimate the intention-to-treat and as-treated effects, expressed as hazard ratio (HR) and event-free survival.RESULTS: A total of 6344 patients (65.2% men; age, 72 [IQR, 64-78] years) provided 131 047 trial cases; 3363 of these cases involved initiation of antiplatelet therapy and 127 684 did not. A total of 182 ischemic events occurred among initiators and 5602 ischemic events occurred among noninitiators, corresponding to an intention-to-treat HR of 0.91 (95% CI, 0.73-1.17) and an estimated absolute event-free survival difference of -0.6% (95% CI, -1.7% to 0.5%). After censoring nonadherent person-time, the treatment HR was 0.90 (95% CI, 0.68-1.20), with similar risk difference. For bleeding, the intention-to-treat HR was 1.26 (95% CI, 0.97-1.58) and the event-free survival difference was 1.0%. The treatment HR was 1.21 (95% CI, 0.82-1.72); the risk difference was similar.CONCLUSIONS AND RELEVANCE: In this study, no evidence of effectiveness of antiplatelet therapy to lower the risk of ischemic events and a trend toward higher bleeding risk was noted. The observed differences between the treatment groups were minimal, suggesting limited clinical relevance of antiplatelet treatment.</p

Strong Attraction between Charged Spheres due to Metastable Ionized States

We report a mechanism which can lead to long range attractions between like-charged spherical macroions, stemming from the existence of metastable ionized states. We show that the ground state of a single highly charged colloid plus a few excess counterions is overcharged. For the case of two highly charged macroions in their neutralizing divalent counterion solution we demonstrate that, in the regime of strong Coulomb coupling, the counterion clouds are very likely to be unevenly distributed, leading to one overcharged and one undercharged macroion. This long-living metastable configuration in turn leads to a long range Coulomb attraction.Comment: REVTEX-published versio

Site-specific incorporation of phosphotyrosine using an expanded genetic code.

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination

Spiral spin-liquid and the emergence of a vortex-like state in MnSc2_2S4_4

Spirals and helices are common motifs of long-range order in magnetic solids, and they may also be organized into more complex emergent structures such as magnetic skyrmions and vortices. A new type of spiral state, the spiral spin-liquid, in which spins fluctuate collectively as spirals, has recently been predicted to exist. Here, using neutron scattering techniques, we experimentally prove the existence of a spiral spin-liquid in MnSc$_2$S$_4$ by directly observing the 'spiral surface' - a continuous surface of spiral propagation vectors in reciprocal space. We elucidate the multi-step ordering behavior of the spiral spin-liquid, and discover a vortex-like triple-q phase on application of a magnetic field. Our results prove the effectiveness of the $J_1$-$J_2$ Hamiltonian on the diamond lattice as a model for the spiral spin-liquid state in MnSc$_2$S$_4$, and also demonstrate a new way to realize a magnetic vortex lattice.Comment: 10 pages, 11 figure

Polypharmacy, functional outcome, and treatment effect of intravenous alteplase for acute ischemic stroke

Background: Polypharmacy is an important challenge in clinical practice. We aimed at determining the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischemic stroke. Methods: Post‐hoc analysis of the randomized, placebo‐controlled WAKE‐UP trial of MRI‐guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as intake of ≥5 medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favorable outcome defined by a score of 0‐1 on the modified Rankin Scale at 90 days. We used logistic regression analysis to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis. Results: Polypharmacy was present in 133/503 (26%) patients. Patients with polypharmacy were older (mean age 70 vs 64 years; P&lt;0.0001) and had a higher score on the National Institutes of Health Stroke Scale at baseline (median 7 vs 5; P=0.0007). A comorbidity load defined by a CCI score ≥2 was more frequent in patients with polypharmacy (48% vs 8%; P&lt;0.001). Polypharmacy was associated with lower odds of favorable outcome (adjusted odds ratio 0.50, 95% CI, 0.30‐0.85; P=0.0099), while the CCI score was not. Treatment with alteplase was associated with higher odds of favorable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, P=0.29). Conclusion: In stroke patients, polypharmacy is associated with worse functional outcome after intravenous thrombolysis independent of comorbidities. However, polypharmacy does not interact with the beneficial effect of alteplase

Scintillation Observations and Response of The Ionosphere to Electrodynamics (SORTIE) Mission First Light

At low and middle latitudes, wave-like plasma perturbations are thought to provide the seeds for larger perturbations that may evolve non-linearly to produce irregularities, which in turn have deleterious effects on HF communications and global positioning systems. Unfortunately, there is currently no comprehensive atlas of measurements describing the global spatial or temporal distribution of wave-like perturbations in the ionosphere. The SORTIE mission, a CubeSat experiment with team members from ASTRA, AFRL, UTD, and Boston College, was designed to help map and further understand the wave-like plasma perturbation distributions throughout the ionosphere. The SORTIE 6U CubeSat sensor package measures key in-situ plasma parameters, and includes an ion velocity meter and a planar Langmuir probe. SORTIE will provide (1) the initial spectrum of wave perturbations which are the starting point for plasma instabilities; (2) measured electric fields which determine the magnitude of the instability growth rate near the region where plasma bubbles are generated; (3) initial observations of irregularities in plasma density which result from plasma instability growth. The SORTIE spacecraft was deployed from the ISS in February 2020 and began data collections shortly after orbit insertion. The measurements are expected to continue for at least a year. In this presentation we present the first light results of the SORTIE mission, as well as reviewing the science objectives and providing an overview of the spacecraft and instruments

A histomorphometric meta-analysis of sinus elevation with various grafting materials

Several grafting materials have been used in sinus augmentation procedures including autogenous bone, demineralized freeze-dried bone (DFDBA), hydroxyapatite, β-tricalcium phosphate (β-TCP), anorganic deproteinized bovine bone and combination of these and others. Up to now a subject of controversy in maxillofacial surgery and dentistry is, what is the most appropriate graft material for sinus floor augmentation

Circulating Glucagon 1-61 Regulates Blood Glucose by Increasing Insulin Secretion and Hepatic Glucose Production

Glucagon is secreted from pancreatic a cells, and hypersecretion (hyperglucagonemia) contributes to diabetic hyperglycemia. Molecular heterogeneity in hyperglucagonemia is poorly investigated. By screening human plasma using high-resolution-proteomics, we identified several glucagon variants, among which proglucagon 1-61 (PG 1-61) appears to be the most abundant form. PG 1-61 is secreted in subjects with obesity, both before and after gastric bypass surgery, with protein and fat as the main drivers for secretion before surgery, but glucose after. Studies in hepatocytes and in b cells demonstrated that PG 1-61 dose-dependently increases levels of cAMP, through the glucagon receptor, and increases insulin secretion and protein levels of enzymes regulating glycogenolysis and gluconeogenesis. In rats, PG 1-61 increases blood glucose and plasma insulin and decreases plasma levels of amino acids in vivo. We conclude that glucagon variants, such as PG 1-61, may contribute to glucose regulation by stimulating hepatic glucose production and insulin secretion

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits