Tuning Locked Inflation: Supergravity versus Phenomenology

We analyze the cosmological consequences of locked inflation, a model recently proposed by Dvali and Kachru that can produce significant amounts of inflation without requiring slow-roll. We pay particular attention to the end of inflation in this model, showing that a secondary phase of saddle inflation can follow the locked inflationary era. However, this subsequent period of inflation results in a strongly scale dependent spectrum that can lead to massive black hole formation in the primordial universe. Avoiding this disastrous outcome puts strong constraints on the parameter space open to models of locked inflation.Comment: 7 pages, 2 figure

Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

Importance: The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ( guided therapy ) with inconsistent results. Objective: To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). Design, Settings, and Participants: The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. Interventions: Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. Main Outcomes and Measures: The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. Results: The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI; 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. Conclusions and Relevance: In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT01685840

Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure.

OBJECTIVES: The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study is designed to determine the safety, efficacy, and cost-effectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of BACKGROUND: Elevations in natriuretic peptide (NP) levels provide key prognostic information in patients with HF. Therapies proven to improve outcomes in patients with HF are generally associated with decreasing levels of NPs, and observational data show that decreases in NP levels over time are associated with favorable outcomes. Results from smaller prospective, randomized studies of this strategy thus far have been mixed, and current guidelines do not recommend serial measurement of NP levels to guide therapy in patients with HF. METHODS: GUIDE-IT is a prospective, randomized, controlled, unblinded, multicenter clinical trial designed to randomize approximately 1,100 high-risk subjects with systolic HF (left ventricular ejection fraction ≤40%) to either usual care (optimized guideline-recommended therapy) or a strategy of adjusting therapy with the goal of achieving and maintaining a target NT-proBNP level of CONCLUSIONS: The GUIDE-IT study is designed to definitively assess the effects of an NP-guided strategy in high-risk patients with systolic HF on clinically relevant endpoints of mortality, hospitalization, quality of life, and medical resource use. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840)

Rapidly-Varying Speed of Sound, Scale Invariance and Non-Gaussian Signatures

We show that curvature perturbations acquire a scale invariant spectrum for any constant equation of state, provided the fluid has a suitably time-dependent sound speed. In order for modes to exit the physical horizon, and in order to solve the usual problems of standard big bang cosmology, we argue that the only allowed possibilities are inflationary (albeit not necessarily slow-roll) expansion or ekpyrotic contraction. Non-Gaussianities offer many distinguish features. As usual with a small sound speed, non-Gaussianity can be relatively large, around current sensitivity levels. For DBI-like lagrangians, the amplitude is negative in the inflationary branch, and can be either negative or positive in the ekpyrotic branch. Unlike the power spectrum, the three-point amplitude displays a large tilt that, in the expanding case, peaks on smallest scales. While the shape is predominantly of the equilateral type in the inflationary branch, as in DBI inflation, it is of the local form in the ekpyrotic branch. The tensor spectrum is also generically far from scale invariant. In the contracting case, for instance, tensors are strongly blue tilted, resulting in an unmeasurably small gravity wave amplitude on cosmic microwave background scales.Comment: 41 pages, 12 figures. v4: Few typos in equations (7.39) correcte

Closed String Tachyon Condensation on Twisted Circles

We study IIA/B string theory compactified on twisted circles. These models possess closed string tachyons and reduce to type 0B/A theory in a special limit. Using methods of gauged linear sigma models and mirror symmetry we construct a conformal field theory which interpolates between these models and flat space via an auxiliary Liouville direction. Interpreting motion in the Liouville direction as renormalization group flow, we argue that the end point of tachyon condensation in all these models (including 0B/A theory) is supersymmetric type II theory. We also find a zero-slope limit of these models which is best described in a T-dual picture as a type II NS-NS fluxbrane. In this limit tachyon condensation is an interesting and well posed problem in supergravity. We explicitly determine the tachyon as a fluctuation of supergravity fields, and perform a rudimentary numerical analysis of the relevant flows.Comment: 21 pages plus appendices (12 pages), harvmac, 1 fig, v2: minor changes and references added, v3: minor changes version published in JHE

Design of a Novel Multifunction Decision Support Display for Anesthesia Care: AlertWatch® OR

Abstract Background This paper describes the design of a multifunction alerting display for intraoperative anesthetic care. The design was inspired by the multifunction primary flight display used in modern aviation. Results The display retrieves live data from multiple sources; the physiologic monitors, the anesthesia information management system, the laboratory values and comorbidities from patient’s problem summary list, medical history or history & physical. This information is integrated into a display composed of readily identifiable icons of organ systems, which are color coded to signify normal range, marginal range, abnormal range (by green, yellow, red respectively) and orange outlines for comorbidities/risk factors. There are dozens of text alerts, which can be presented as black text (informational), red text (important information) and red scrolling text (highest importance information). The alerts are derived from current standards in the literature and some involve complex calculations being conducted in the background. Conclusions The goal of such a system is to improve the quality and safety of anesthetic care by providing enhanced situational awareness in a fashion analogous to the “glass cockpit” and its primary flight display which has improved aviation safety.https://deepblue.lib.umich.edu/bitstream/2027.42/142347/1/12871_2018_Article_478.pd

The Pseudo-Conformal Universe: Scale Invariance from Spontaneous Breaking of Conformal Symmetry

We present a novel theory of the very early universe which addresses the traditional horizon and flatness problems of big bang cosmology and predicts a scale invariant spectrum of perturbations. Unlike inflation, this scenario requires no exponential accelerated expansion of space-time. Instead, the early universe is described by a conformal field theory minimally coupled to gravity. The conformal fields develop a time-dependent expectation value which breaks the flat space so(4,2) conformal symmetry down to so(4,1), the symmetries of de Sitter, giving perturbations a scale invariant spectrum. The solution is an attractor, at least in the case of a single time-dependent field. Meanwhile, the metric background remains approximately flat but slowly contracts, which makes the universe increasingly flat, homogeneous and isotropic, akin to the smoothing mechanism of ekpyrotic cosmology. Our scenario is very general, requiring only a conformal field theory capable of developing the appropriate time-dependent expectation values, and encompasses existing incarnations of this idea, specifically the U(1) model of Rubakov and the Galileon Genesis scenario. Its essential features depend only on the symmetry breaking pattern and not on the details of the underlying lagrangian. It makes generic observational predictions that make it potentially distinguishable from standard inflation, in particular significant non-gaussianities and the absence of primordial gravitational waves.Comment: 51 pages, 3 figures. v2 discussion and refs added, minus sign in transformation laws fixed. Version appearing in JCA

Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis

Malaria is caused by eukaryotic Plasmodium spp. parasites that classically infect red blood cells. These are difficult organisms to investigate genetically because of their AT-rich genomes. Zhang et al. have exploited this peculiarity by using piggyBac transposon insertion sites to achieve saturation-level mutagenesis for identifying and ranking essential genes and drug targets (see the Perspective by White and Rathod). Genes that are current candidates for drug targets were identified as essential, in contrast to many vaccine target genes. Notably, the proteasome degradation pathway was confirmed as a target for developing therapeutic interventions because of the several essential genes involved and the link to the mechanism of action of the current frontline drug, artemisinin

Two flavor chiral phase transition from nonperturbative flow equations

We employ nonperturbative flow equations to compute the equation of state for two flavor QCD within an effective quark meson model. This yields the temperature and quark mass dependence of quantities like the chiral condensate or the pion mass. A precision estimate of the universal critical equation of state for the three-dimensional O(4) Heisenberg model is presented. We explicitly connect the O(4) universal behavior near the critical temperature and zero quark mass with the physics at zero temperature and a realistic pion mass. For realistic quark masses the pion correlation length near T_c turns out to be smaller than its zero temperature value.Comment: 49 pages including 15 figures, LaTeX, uses epsf.sty and rotate.st

The Worldvolume Action of Kink Solitons in AdS Spacetime

A formalism is presented for computing the higher-order corrections to the worldvolume action of co-dimension one solitons. By modifying its potential, an explicit "kink" solution of a real scalar field in AdS spacetime is found. The formalism is then applied to explicitly compute the kink worldvolume action to quadratic order in two expansion parameters--associated with the hypersurface fluctuation length and the radius of AdS spacetime respectively. Two alternative methods are given for doing this. The results are expressed in terms of the trace of the extrinsic curvature and the intrinsic scalar curvature. In addition to conformal Galileon interactions, we find a non-Galileon term which is never sub-dominant. This method can be extended to any conformally flat bulk spacetime.Comment: 32 pages, 3 figures, typos corrected and additional comments adde