Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease: Design and baseline characteristics of SOUL, a randomized trial

Aim: To describe the design of the SOUL trial (Semaglutide cardiOvascular oUtcomes triaL) and the baseline clinical data of its participants. Materials and methods: In SOUL, the effects of oral semaglutide, the first oral glucagon-like peptide-1 receptor agonist, on the risk of cardiovascular (CV) events in individuals with type 2 diabetes and established atherosclerotic CV disease (ASCVD) and/or chronic kidney disease (CKD) will be assessed. SOUL is a randomized, double-blind, parallel-group, placebo-controlled CV outcomes trial comparing oral semaglutide (14 mg once daily) with placebo, both in addition to standard of care, in individuals aged ≥50 years with type 2 diabetes and evidence of ASCVD (coronary artery disease [CAD], cerebrovascular disease, symptomatic peripheral arterial disease [PAD]) and/or CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2). The primary outcome is time from randomization to first occurrence of a major adverse CV event (MACE; a composite of CV death, nonfatal myocardial infarction or nonfatal stroke). This event-driven trial will continue until 1225 first adjudication-confirmed MACEs have occurred. Enrolment has been completed. Results: Overall, 9650 participants were enrolled between June 17, 2019 and March 24, 2021 (men 71.1%, White ethnicity 68.9%, mean age 66.1 years, diabetes duration 15.4 years, body mass index 31.1 kg/m2, glycated haemoglobin 63.5 mmol/mol [8.0%]). The most frequently used antihyperglycaemic medications at baseline were metformin (75.7%), insulin and insulin analogues (50.5%), sulphonylureas (29.1%), sodium-glucose cotransporter-2 inhibitors (26.7%) and dipeptidyl peptidase-4 inhibitors (23.0%). At randomization, 70.7% of participants had CAD, 42.3% had CKD, 21.1% had cerebrovascular disease and 15.7% had symptomatic PAD (categories not mutually exclusive). Prevalent heart failure was reported in 23.0% of participants. Conclusion: SOUL will provide evidence regarding the CV effects of oral semaglutide in individuals with type 2 diabetes and established ASCVD and/or CKD

Coordinated optimization of visual cortical maps (I) Symmetry-based analysis

In the primary visual cortex of primates and carnivores, functional architecture can be characterized by maps of various stimulus features such as orientation preference (OP), ocular dominance (OD), and spatial frequency. It is a long-standing question in theoretical neuroscience whether the observed maps should be interpreted as optima of a specific energy functional that summarizes the design principles of cortical functional architecture. A rigorous evaluation of this optimization hypothesis is particularly demanded by recent evidence that the functional architecture of OP columns precisely follows species invariant quantitative laws. Because it would be desirable to infer the form of such an optimization principle from the biological data, the optimization approach to explain cortical functional architecture raises the following questions: i) What are the genuine ground states of candidate energy functionals and how can they be calculated with precision and rigor? ii) How do differences in candidate optimization principles impact on the predicted map structure and conversely what can be learned about an hypothetical underlying optimization principle from observations on map structure? iii) Is there a way to analyze the coordinated organization of cortical maps predicted by optimization principles in general? To answer these questions we developed a general dynamical systems approach to the combined optimization of visual cortical maps of OP and another scalar feature such as OD or spatial frequency preference.Comment: 90 pages, 16 figure

Coordinated optimization of visual cortical maps (II) Numerical studies

It is an attractive hypothesis that the spatial structure of visual cortical architecture can be explained by the coordinated optimization of multiple visual cortical maps representing orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we defined a class of analytically tractable coordinated optimization models and solved representative examples in which a spatially complex organization of the orientation preference map is induced by inter-map interactions. We found that attractor solutions near symmetry breaking threshold predict a highly ordered map layout and require a substantial OD bias for OP pinwheel stabilization. Here we examine in numerical simulations whether such models exhibit biologically more realistic spatially irregular solutions at a finite distance from threshold and when transients towards attractor states are considered. We also examine whether model behavior qualitatively changes when the spatial periodicities of the two maps are detuned and when considering more than 2 feature dimensions. Our numerical results support the view that neither minimal energy states nor intermediate transient states of our coordinated optimization models successfully explain the spatially irregular architecture of the visual cortex. We discuss several alternative scenarios and additional factors that may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with arXiv:1102.335

Active Electric Imaging: Body-Object Interplay and Object's “Electric Texture”

This article deals with the role of fish's body and object's geometry on determining the image spatial shape in pulse Gymnotiforms. This problem was explored by measuring local electric fields along a line on the skin in the presence and absence of objects. We depicted object's electric images at different regions of the electrosensory mosaic, paying particular attention to the perioral region where a fovea has been described. When sensory surface curvature increases relative to the object's curvature, the image details depending on object's shape are blurred and finally disappear. The remaining effect of the object on the stimulus profile depends on the strength of its global polarization. This depends on the length of the object's axis aligned with the field, in turn depending on fish body geometry. Thus, fish's body and self-generated electric field geometries are embodied in this “global effect” of the object. The presence of edges or local changes in impedance at the nearest surface of closely located objects adds peaks to the image profiles (“local effect” or “object's electric texture”). It is concluded that two cues for object recognition may be used by active electroreceptive animals: global effects (informing on object's dimension along the field lines, conductance, and position) and local effects (informing on object's surface). Since the field has fish's centered coordinates, and electrosensory fovea is used for exploration of surfaces, fish fine movements are essential to perform electric perception. We conclude that fish may explore adjacent objects combining active movements and electrogenesis to represent them using electrosensory information

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table

Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics

We present a quasi-model-independent search for the physics responsible for electroweak symmetry breaking. We define final states to be studied, and construct a rule that identifies a set of relevant variables for any particular final state. A new algorithm ("Sleuth") searches for regions of excess in those variables and quantifies the significance of any detected excess. After demonstrating the sensitivity of the method, we apply it to the semi-inclusive channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review

Search For Heavy Pointlike Dirac Monopoles

We have searched for central production of a pair of photons with high transverse energies in $p\bar p$ collisions at $\sqrt{s} = 1.8$ TeV using $70 pb^{-1}$ of data collected with the D\O detector at the Fermilab Tevatron in 1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could rescatter pairs of nearly real photons into this final state via a box diagram. We observe no excess of events above background, and set lower 95% C.L. limits of $610, 870, or 1580 GeV/c^2$ on the mass of a spin 0, 1/2, or 1 Dirac monopole.Comment: 12 pages, 4 figure

The Dijet Mass Spectrum and a Search for Quark Compositeness in bar{p}p Collisions at sqrt{s} = 1.8 TeV

Using the DZero detector at the 1.8 TeV pbarp Fermilab Tevatron collider, we have measured the inclusive dijet mass spectrum in the central pseudorapidity region |eta_jet| < 1.0 for dijet masses greater than 200 Gev/c^2. We have also measured the ratio of spectra sigma(|eta_jet| < 0.5)/sigma(0.5 < |eta_jet| < 1.0). The order alpha_s^3 QCD predictions are in good agreement with the data and we rule out models of quark compositeness with a contact interaction scale < 2.4 TeV at the 95% confidence level.Comment: 11 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let

Search for High Mass Photon Pairs in p-pbar --> gamma-gamma-jet-jet Events at sqrt(s)=1.8 TeV

A search has been carried out for events in the channel p-barp --> gamma gamma jet jet. Such a signature can characterize the production of a non-standard Higgs boson together with a W or Z boson. We refer to this non-standard Higgs, having standard model couplings to vector bosons but no coupling to fermions, as a "bosonic Higgs." With the requirement of two high transverse energy photons and two jets, the diphoton mass (m(gamma gamma)) distribution is consistent with expected background. A 90(95)% C.L. upper limit on the cross section as a function of mass is calculated, ranging from 0.60(0.80) pb for m(gamma gamma) = 65 GeV/c^2 to 0.26(0.34) pb for m(gamma gamma) = 150 GeV/c^2, corresponding to a 95% C.L. lower limit on the mass of a bosonic Higgs of 78.5 GeV/c^2.Comment: 9 pages, 3 figures. Replacement has new H->gamma gamma branching ratios and corresponding new mass limit

Ratio of the Isolated Photon Cross Sections at \sqrt{s} = 630 and 1800 GeV

The inclusive cross section for production of isolated photons has been measured in \pbarp collisions at $\sqrt{s} = 630$ GeV with the \D0 detector at the Fermilab Tevatron Collider. The photons span a transverse energy ($E_T$) range from 7-49 GeV and have pseudorapidity $|\eta| < 2.5$. This measurement is combined with to previous \D0 result at $\sqrt{s} = 1800$ GeV to form a ratio of the cross sections. Comparison of next-to-leading order QCD with the measured cross section at 630 GeV and ratio of cross sections show satisfactory agreement in most of the $E_T$ range.Comment: 7 pages. Published in Phys. Rev. Lett. 87, 251805, (2001