Testing "microscopic" theories of glass-forming liquids

We assess the validity of "microscopic" approaches of glass-forming liquids based on the sole k nowledge of the static pair density correlations. To do so we apply them to a benchmark provided by two liquid models that share very similar static pair density correlation functions while disp laying distinct temperature evolutions of their relaxation times. We find that the approaches are unsuccessful in describing the difference in the dynamical behavior of the two models. Our study is not exhausti ve, and we have not tested the effect of adding corrections by including for instance three-body density correlations. Yet, our results appear strong enough to challenge the claim that the slowd own of relaxation in glass-forming liquids, for which it is well established that the changes of the static structure factor with temperature are small, can be explained by "microscopic" appr oaches only requiring the static pair density correlations as nontrivial input.Comment: 10 pages, 7 figs; Accepted to EPJE Special Issue on The Physics of Glasses. Arxiv version contains an addendum to the appendix which does not appear in published versio

Dynamics of fluctuations in a fluid below the onset of Rayleigh-B\'enard convection

We present experimental data and their theoretical interpretation for the decay rates of temperature fluctuations in a thin layer of a fluid heated from below and confined between parallel horizontal plates. The measurements were made with the mean temperature of the layer corresponding to the critical isochore of sulfur hexafluoride above but near the critical point where fluctuations are exceptionally strong. They cover a wide range of temperature gradients below the onset of Rayleigh-B\'enard convection, and span wave numbers on both sides of the critical value for this onset. The decay rates were determined from experimental shadowgraph images of the fluctuations at several camera exposure times. We present a theoretical expression for an exposure-time-dependent structure factor which is needed for the data analysis. As the onset of convection is approached, the data reveal the critical slowing-down associated with the bifurcation. Theoretical predictions for the decay rates as a function of the wave number and temperature gradient are presented and compared with the experimental data. Quantitative agreement is obtained if allowance is made for some uncertainty in the small spacing between the plates, and when an empirical estimate is employed for the influence of symmetric deviations from the Oberbeck-Boussinesq approximation which are to be expected in a fluid with its density at the mean temperature located on the critical isochore.Comment: 13 pages, 10 figures, 52 reference

Cost-effectiveness of Evolocumab therapy for reducing cardiovascular events in patients with atherosclerotic cardiovascular disease

Importance: The proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab has been demonstrated to reduce the composite of myocardial infarction, stroke, or cardiovascular death in patients with established atherosclerotic cardiovascular disease. To our knowledge, long-term cost-effectiveness of this therapy has not been evaluated using clinical trial efficacy data. Objective: To evaluate the cost-effectiveness of evolocumab in patients with atherosclerotic cardiovascular disease when added to standard background therapy. Design, Setting, and Participants: A Markov cohort state-transition model was used, integrating US population-specific demographics, risk factors, background therapy, and event rates along with trial-based event risk reduction. Costs, including price of drug, utilities, and transitional probabilities, were included from published sources. Exposures: Addition of evolocumab to standard background therapy including statins. Main Outcomes and Measures: Cardiovascular events including myocardial infarction, ischemic stroke and cardiovascular death, quality-adjusted life-year (QALY), incremental cost-effectiveness ratio (ICER), and net value-based price. Results: In the base case, using US clinical practice patients with atherosclerotic cardiovascular disease with low-density lipoprotein cholesterol levels of at least 70 mg/dL (to convert to millimoles per liter, multiply by 0.0259) and an annual events rate of 6.4 per 100 patient-years, evolocumab was associated with increased cost and improved QALY: incremental cost, $105 398; incremental QALY, 0.39, with an ICER of$268 637 per QALY gained ($165 689 with discounted price of$10 311 based on mean rebate of 29% for branded pharmaceuticals). Sensitivity and scenario analyses demonstrated ICERs ranging from $100 193 to$488 642 per QALY, with ICER of $413 579 per QALY for trial patient characteristics and event rate of 4.2 per 100 patient-years ($270 192 with discounted price of $10 311) and$483 800 if no cardiovascular mortality reduction emerges. Evolocumab treatment exceeded $150 000 per QALY in most scenarios but would meet this threshold at an annual net price of$9669 ($6780 for the trial participants) or with the discounted net price of$10 311 in patients with low-density lipoprotein cholesterol levels of at least 80 mg/dL. Conclusions and Relevance: At its current list price of $14 523, the addition of evolocumab to standard background therapy in patients with atherosclerotic cardiovascular disease exceeds generally accepted cost-effectiveness thresholds. To achieve an ICER of$150 000 per QALY, the annual net price would need to be substantially lower ($9669 for US clinical practice and$6780 for trial participants), or a higher-risk population would need to be treated

Anthropogenic Space Weather

Anthropogenic effects on the space environment started in the late 19th century and reached their peak in the 1960s when high-altitude nuclear explosions were carried out by the USA and the Soviet Union. These explosions created artificial radiation belts near Earth that resulted in major damages to several satellites. Another, unexpected impact of the high-altitude nuclear tests was the electromagnetic pulse (EMP) that can have devastating effects over a large geographic area (as large as the continental United States). Other anthropogenic impacts on the space environment include chemical release ex- periments, high-frequency wave heating of the ionosphere and the interaction of VLF waves with the radiation belts. This paper reviews the fundamental physical process behind these phenomena and discusses the observations of their impacts.Comment: 71 pages, 35 figure

Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology

Publisher Copyright: © 2022, The Author(s).Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (ORIDD = 0.92, P = 1.6 × 10−39; ORdorsalgia = 0.92, P = 7.2 × 10−15) is with a 3’UTR variant (rs1871452-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 − 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 × 10−11); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory processes.Peer reviewe

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

Measurement of the branching ratio Γ(Λb⁰ → ψ(2S)Λ0)/Γ(Λb⁰ → J/ψΛ0) with the ATLAS detector

An observation of the $\Lambda_b^0 \rightarrow \psi(2S) \Lambda^0$ decay and a comparison of its branching fraction with that of the $\Lambda_b^0 \rightarrow J/\psi \Lambda^0$ decay has been made with the ATLAS detector in proton--proton collisions at $\sqrt{s}=8\,$TeV at the LHC using an integrated luminosity of $20.6\,$fb$^{-1}$. The $J/\psi$ and $\psi(2S)$ mesons are reconstructed in their decays to a muon pair, while the $\Lambda^0\rightarrow p\pi^-$ decay is exploited for the $\Lambda^0$ baryon reconstruction. The $\Lambda_b^0$ baryons are reconstructed with transverse momentum $p_{\rm T}>10\,$GeV and pseudorapidity $|\eta|<2.1$. The measured branching ratio of the $\Lambda_b^0 \rightarrow \psi(2S) \Lambda^0$ and $\Lambda_b^0 \rightarrow J/\psi \Lambda^0$ decays is $\Gamma(\Lambda_b^0 \rightarrow \psi(2S)\Lambda^0)/\Gamma(\Lambda_b^0 \rightarrow J/\psi\Lambda^0) = 0.501\pm 0.033 ({\rm stat})\pm 0.019({\rm syst})$, lower than the expectation from the covariant quark model.Comment: 12 pages plus author list (28 pages total), 5 figures, 1 table, published on Physics Letters B 751 (2015) 63-80. All figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/BPHY-2013-08

Measurement of the View the tt production cross-section using eμ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper describes a measurement of the inclusive top quark pair production cross-section (σtt¯) with a data sample of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of √s = 13 TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron–muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously σtt¯ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be: σtt¯ = 818 ± 8 (stat) ± 27 (syst) ± 19 (lumi) ± 12 (beam) pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented