The principle underlying antiaromaticity

Aromaticity is one of the most widely used chemical concepts. Current definitions are purely phenomenological and relate symmetry, reactive stability and the occurence of molecular diamagnetic response currents. The antithetical concept of antiaromaticity provides a connection between the contrary properties of structural instability or distortion out of higher symmetry, a small HOMO-LUMO gap, and paramagnetic response currents. We reveal the principle that is underlying antiaromaticity in showing an intimate and strict symmetry induced relation between these properties. This principle can be proven and is formulated like: First order (and related) Jahn-Teller distorted molecules out of non-isometric point groups are prone to paramagnetic current susceptibility parallel to the main axis of symmetry. We show by the exemplary cases of cyclobutadiene, cylcooctatetraene, pentalene and manganese trifluoride how this principle works and discuss this new perspective on antiaromaticity

Effects of endotoxin on lactate metabolism in humans.

ABSTRACT: INTRODUCTION: Hyperlactatemia represents one prominent component of the metabolic response to sepsis. In critically ill patients, hyperlactatemia is related to the severity of the underlying condition. Both an increased production and a decreased utilization and clearance might be involved in this process, but their relative contribution remains unknown. The present study aimed at assessing systemic and muscle lactate production and systemic lactate clearance in healthy human volunteers, using intravenous endotoxin (LPS) challenge. METHODS: Fourteen healthy male volunteers were enrolled in 2 consecutive studies (n = 6 in trial 1 and n = 8 in trial 2). Each subject took part in one of two investigation days (LPS-day with endotoxin injection and placebo-day with saline injection) separated by one week at least and in a random order. In trial 1, their muscle lactate metabolism was monitored using microdialysis. In trial 2, their systemic lactate metabolism was monitored by means of a constant infusion of exogenous lactate. Energy metabolism was monitored by indirect calorimetry and glucose kinetics was measured with 6,6-H2 glucose. RESULTS: In both trials, LPS increased energy expenditure (p = 0.011), lipid oxidation (p<0.0001), and plasma lactate concentration (p = 0.016). In trial 1, lactate concentration in the muscle microdialysate was higher than in blood, indicating lactate production by muscles. This was, however, similar with and without LPS. In trial 2, calculated systemic lactate production increased after LPS (p = 0.031), while lactate clearance remained unchanged. CONCLUSIONS: LPS administration increases lactatemia by increasing lactate production rather than by decreasing lactate clearance. Muscle is, however, unlikely to be a major contributor to this increase in lactate production. TRIAL REGISTRATION: ClinicalTrials.gov NCT01647997

Impact of medical practice guidelines on the assessment of patients with acute coronary syndrome without persistent ST segment elevation

Objective. To assess the impact of introducing clinical practice guidelines on acute coronary syndrome without persistent ST segment elevation (ACS) on patient initial assessment. Design. Prospective before-after evaluation over a 3-month period. Setting. The emergency ward of a tertiary teaching hospital. Patients. All consecutive patients with ACS evaluated in the emergency ward over the two 3-month periods. Intervention. Implementation of the practice guidelines, and the addition of a cardiology consultant to the emergency team. Main outcome measures. Diagnosis, electrocardiogram interpretation, and risk stratification after the initial evaluation. Results. The clinical characteristics of the 328 and 364 patients evaluated in the emergency ward for suspicion of ACS before and after guideline implementation were similar. Significantly more patients were classified as suffering from atypical chest pain (39.6% versus 47.0%; P = 0.006) after guideline implementation. Guidelines availability was associated with significantly more formal diagnoses (79.9% versus 92.9%; P < 0.0001) and risk stratification (53.7% versus 65.4%, P < 0.0001) at the end of initial assessment. Conclusion. Guidelines implementation, along with availability of a cardiology consultant in the emergency room had a positive impact on initial assessment of patients evaluated for suspicion of ACS. It led to increased confidence in diagnosis and stratification by risk, which are the first steps in initiating effective treatment for this common conditio

Transcutaneous aortic valve implantation using the carotid artery access: Feasibility and clinical outcomes

Background: Transcarotid access is an alternative route for transcutaneous aortic valve implantation (TAVI) in patients with impossible transfemoral access.Aims: We evaluated the safety, effectiveness and early and late clinical outcomes of CoreValve® implantation via the common carotid artery.Methods: Eighteen patients (10 men, 8 women; mean age 84 ± 5 years) at high surgical risk (mean EuroSCORE II 16 ± 13%) with significant peripheral artery disease underwent TAVI via common carotid artery access under general anaesthesia. Mean aortic valve area was 0.64 ± 0.13 cm2 (0.36 ± 0.07 cm2/m2).Results: At a mean follow-up of 605 ± 352 days, two patients (11%) had died in hospital, on days 6 and 20, as a result of sepsis with multiorgan failure (n = 1) or pneumonia (n = 1). There were no perioperative deaths, myocardial infarctions or strokes. Perioperative prosthesis embolization occurred in one patient (6%), requiring implantation of a second valve. In-hospital complications occurred in four patients (23%): blood transfusion for transient significant bleeding at the access site in one patient (6%); permanent pacemaker implantation in two patients (11%); and pericardial drainage in one patient (6%). The rate of event-free in-hospital stay was 66%. Post-procedural echocardiography showed very good haemodynamic performance, with a mean gradient of 8 ± 3 mmHg. Moderate paravalvular leak was present in one patient (6%). Mean intensive care unit stay was 48 ± 31 h; mean in- hospital stay was 7 ± 3 days.Conclusion: TAVI performed by transcarotid access in this small series of severely ill patients was associated with a low incidence of complications, which were associated with the procedure itself rather than the access route

Existential witness extraction in classical realizability and via a negative translation

We show how to extract existential witnesses from classical proofs using Krivine's classical realizability---where classical proofs are interpreted as lambda-terms with the call/cc control operator. We first recall the basic framework of classical realizability (in classical second-order arithmetic) and show how to extend it with primitive numerals for faster computations. Then we show how to perform witness extraction in this framework, by discussing several techniques depending on the shape of the existential formula. In particular, we show that in the Sigma01-case, Krivine's witness extraction method reduces to Friedman's through a well-suited negative translation to intuitionistic second-order arithmetic. Finally we discuss the advantages of using call/cc rather than a negative translation, especially from the point of view of an implementation.Comment: 52 pages. Accepted in Logical Methods for Computer Science (LMCS), 201

Scaling limit of the disordered generalized Poland--Scheraga model for DNA denaturation

The Poland--Scheraga model, introduced in the 1970's, is a reference model to describe the denaturation transition of DNA. More recently, it has been generalized in order to allow for asymmetry in the strands lengths and in the formation of loops: the mathematical representation is based on a bivariate renewal process, that describes the pairs of bases that bond together. In this paper, we consider a disordered version of the model, in which the two strands interact via a potential $\beta V(\hat\omega_i,\bar\omega_j)+h$ when the $i$-th monomer of the first strand and the $j$-th monomer of the second strand meet. Here, $h\in\mathbb R$ is a homogeneous pinning parameter, $(\hat\omega_i)_{i\geq 1}$ and $(\bar\omega_j)_{j\geq 1}$ are two sequences of i.i.d.~random variables attached to each DNA strand, $V(\cdot,\cdot)$ is an interaction function and $\beta>0$ is the disorder intensity. Our main result finds some condition on the underlying bivariate renewal so that, if one takes $\beta,h\downarrow0$ at some appropriate (explicit) rate as the length of the strands go to infinity, the partition function of the model admits a non-trivial, i.e. disordered, scaling limit. This is known as an \textit{intermediate disorder} regime and is linked to the question of disorder relevance for the denaturation transition. Interestingly and surprisingly, the rate at which one has to take $\beta\downarrow0$ depends on the interaction function $V(\cdot,\cdot)$ and on the distribution of $(\hat\omega_i)_{i\geq 1}$, $(\bar\omega_j)_{j\geq 1}$. On the other hand, the intermediate disorder limit of the partition function, when it exists, is universal: it is expressed as a chaos expansion of iterated integrals against a Gaussian process~$\mathcal{M}$, which arises as the scaling limit of the field $(e^{\beta V(\hat\omega_i,\bar\omega_j)})_{i,j\geq 0}$ and exhibits strong correlations on lines and columns.Comment: 60 pages, 7 figure

Effect of bicarbonate and lactate buffer on glucose and lactate metabolism during hemodiafiltration in patients with multiple organ failure

Objective: To compare the effects of sodium bicarbonate and lactate for continuous veno-venous hemodiafiltration (CVVHDF) in critically ill patients. Design and settings: Prospective crossed-over controlled trial in the surgical and medical ICUs of a university hospital. Patients: Eight patients with multiple organ dysfunction syndrome (MODS) requiring CVVHDF. Intervention: Each patient received the two buffers in a randomized sequence over two consecutive days. Measurements and results: The following variables were determined: acid-base parameters, lactate production and utilization (13C lactate infusion), glucose turnover (6,62H2-glucose), gas exchange (indirect calorimetry). No side effect was observed during lactate administration. Baseline arterial acid-base variables were equal with the two buffers. Arterial lactate (2.9 versus 1.5mmol/l), glycemia (+18%) and glucose turnover (+23%) were higher in the lactate period. Bicarbonate and glucose losses in CVVHDF were substantial, but not lactate elimination. Infusing 13C lactate increased plasma lactate levels equally with the two buffers. Lactate clearance (7.8±0.8 vs 7.5±0.8ml/kg per min in the bicarbonate and lactate periods) and endogenous production rates (14.0±2.6 vs 13.6±2.6mmol/kg per min) were similar. 13C lactate was used as a metabolic substrate, as shown by 13CO2 excretion. Glycemia and metabolic rate increased significantly and similarly during the two periods during lactate infusion. Conclusion: Lactate was rapidly cleared from the blood of critically ill patients without acute liver failure requiring CVVHDF, being transformed into glucose or oxidized. Lactate did not exert undesirable effects, except moderate hyperglycemia, and achieved comparable effects on acid-base balance to bicarbonat

High and Low-Speed Streaks in Turbulent Wedge Spreading

Boundary-layer transition triggered by a roughness element generates a turbulent wedge that spreads laterally as the flow proceeds downstream. The spreading half angle is about $6^{\circ}$ in zero-pressure-gradient flows regardless of Reynolds number and roughness shape. Recent simulations and experiments have sought to explain the lateral-spreading mechanism and have observed high- and low-speed streaks along the flanks of the wedge that appear central to the spreading process. To better elucidate the role of streaks, a naphthalene flow-visualization survey and hotwire measurements are conducted over a wider range of Reynolds numbers and a longer streamwise domain than previous experiments. The results reconfirm the spreading half angle is insensitive to Reynolds numbers based on roughness location, $Re_{x,k}$, and roughness height, $Re_{kk}$. When made nondimensional by the unit Reynolds number, the distance from the roughness to the effective origin of the turbulent wedge and to the first high-speed flanking streaks depends on $Re_{kk}$ but not $Re_{x,k}$. The distance between the first and second high-speed streaks is also observed to depend on $Re_{kk}$. In spite of a long measurement domain, third streaks are not observed and it remains unknown whether subsequent streak-to-streak distances collapse to a universal value. The reason downstream streaks are not observed may be low-frequency meandering of streak structures. Hotwire measurements confirm breakdown to turbulence first occurs via a shear-layer instability above low-speed streaks. Farther downstream, high-intensity broadband fluctuations are observed in equivalent positions on secondary low-speed streaks

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using √s=8 TeV proton-proton collision data

A search for squarks and gluinos in final states containing high-p T jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in s√=8 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb−1. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A 0 = −2m 0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector