Analytic Evidence for Continuous Self Similarity of the Critical Merger Solution

The double cone, a cone over a product of a pair of spheres, is known to play a role in the black-hole black-string phase diagram, and like all cones it is continuously self similar (CSS). Its zero modes spectrum (in a certain sector) is determined in detail, and it implies that the double cone is a co-dimension 1 attractor in the space of those perturbations which are smooth at the tip. This is interpreted as strong evidence for the double cone being the critical merger solution. For the non-symmetry-breaking perturbations we proceed to perform a fully non-linear analysis of the dynamical system. The scaling symmetry is used to reduce the dynamical system from a 3d phase space to 2d, and obtain the qualitative form of the phase space, including a non-perturbative confirmation of the existence of the "smoothed cone".Comment: 25 pages, 4 figure

Classical Effective Field Theory and Caged Black Holes

Matched asymptotic expansion is a useful technique in General Relativity and other fields whenever interaction takes place between physics at two different length scales. Here matched asymptotic expansion is argued to be equivalent quite generally to Classical Effective Field Theory (CLEFT) where one (or more) of the zones is replaced by an effective theory whose terms are organized in order of increasing irrelevancy, as demonstrated by Goldberger and Rothstein in a certain gravitational context. The CLEFT perspective has advantages as the procedure is clearer, it allows a representation via Feynman diagrams, and divergences can be regularized and renormalized in standard field theoretic methods. As a side product we obtain a wide class of classical examples of regularization and renormalization, concepts which are usually associated with Quantum Field Theories. We demonstrate these ideas through the thermodynamics of caged black holes, both simplifying the non-rotating case, and computing the rotating case. In particular we are able to replace the computation of six two-loop diagrams by a single factorizable two-loop diagram, as well as compute certain new three-loop diagrams. The results generalize to arbitrary compactification manifolds. For caged rotating black holes we obtain the leading correction for all thermodynamic quantities. The angular momentum is found to non-renormalize at leading order.Comment: 33 pages 11 figures. v2: Relatively minor changes, detailed at end of introductio

On rolling, tunneling and decaying in some large N vector models

Various aspects of time-dependent processes are studied within the large N approximation of O(N) vector models in three dimensions. These include the rolling of fields, the tunneling and decay of vacua. We present an exact solution for the quantum conformal case and find a solution for more general potentials when the total change of the value of the field is small. Characteristic times are found to be shorter when the time dependence of the field is taken into account in constructing the exact large N effective potentials. We show that the different approximations yield the same answers in the regions of the overlap of the validity. A numerical solution of this potential reveals a tunneling in which the bubble that separates the true vacuum from the false one is thick

Durable Near-Complete Response to Anti-PD-1 Checkpoint Immunotherapy in a Refractory Malignant Solitary Fibrous Tumor of the Pleura

Solitary fibrous tumor of the pleura is a rare and usually benign primary neoplasm arising from mesenchymal cells of the submesothelial tissue. We present here the case of a patient diagnosed with CD34-positive advanced malignant solitary fibrous tumor of the pleura whose disease failed to respond to combination cytotoxic chemotherapy agents, but demonstrated a prompt near-complete response to checkpoint blockade treatment using the anti-programmed death (PD)-1 monoclonal antibody pembrolizumab, based on tumor molecular profiling revealing tumoral expression positivity for both programmed death-ligand 1 (PD-L1) and PD-1. The patient experienced minimal adverse effects from the treatment with durable favorable response lasting up to cycle 26

Dynamic changes in cellular infiltrates with repeated cutaneous vaccination: a histologic and immunophenotypic analysis

<p>Abstract</p> <p>Background</p> <p>Melanoma vaccines have not been optimized. Adjuvants are added to activate dendritic cells (DCs) and to induce a favourable immunologic milieu, however, little is known about their cellular and molecular effects in human skin. We hypothesized that a vaccine in incomplete Freund's adjuvant (IFA) would increase dermal Th1 and Tc1-lymphocytes and mature DCs, but that repeated vaccination may increase regulatory cells.</p> <p>Methods</p> <p>During and after 6 weekly immunizations with a multipeptide vaccine, immunization sites were biopsied at weeks 0, 1, 3, 7, or 12. In 36 participants, we enumerated DCs and lymphocyte subsets by immunohistochemistry and characterized their location within skin compartments.</p> <p>Results</p> <p>Mature DCs aggregated with lymphocytes around superficial vessels, however, immature DCs were randomly distributed. Over time, there was no change in mature DCs. Increases in T and B-cells were noted. Th2 cells outnumbered Th1 lymphocytes after 1 vaccine 6.6:1. Eosinophils and FoxP3⁺cells accumulated, especially after 3 vaccinations, the former cell population most abundantly in deeper layers.</p> <p>Conclusions</p> <p>A multipeptide/IFA vaccine may induce a Th2-dominant microenvironment, which is reversed with repeat vaccination. However, repeat vaccination may increase FoxP3⁺T-cells and eosinophils. These data suggest multiple opportunities to optimize vaccine regimens and potential endpoints for monitoring the effects of new adjuvants.</p> <p>Trail Registration</p> <p>ClinicalTrials.gov Identifier: NCT00705640</p

Non-Relativistic Gravitation: From Newton to Einstein and Back

We present an improvement to the Classical Effective Theory approach to the non-relativistic or Post-Newtonian approximation of General Relativity. The "potential metric field" is decomposed through a temporal Kaluza-Klein ansatz into three NRG-fields: a scalar identified with the Newtonian potential, a 3-vector corresponding to the gravito-magnetic vector potential and a 3-tensor. The derivation of the Einstein-Infeld-Hoffmann Lagrangian simplifies such that each term corresponds to a single Feynman diagram providing a clear physical interpretation. Spin interactions are dominated by the exchange of the gravito-magnetic field. Leading correction diagrams corresponding to the 3PN correction to the spin-spin interaction and the 2.5PN correction to the spin-orbit interaction are presented.Comment: 10 pages, 3 figures. v2: published version. v3: Added a computation of Einstein-Infeld-Hoffmann in higher dimensions within our improved ClEFT which partially confirms and partially corrects a previous computation. See notes added at end of introductio

On the dynamical generation of the Maxwell term and scale invariance

Gauge theories with no Maxwell term are investigated in various setups. The dynamical generation of the Maxwell term is correlated to the scale invariance properties of the system. This is discussed mainly in the cases where the gauge coupling carries dimensions. The term is generated when the theory contains a scale explicitly, when it is asymptotically free and in particular also when the scale invariance is spontaneously broken. The terms are not generated when the scale invariance is maintained. Examples studied include the large $N$ limit of the $CP^{N-1}$ model in $(2+\epsilon)$ dimensions, a 3D gauged $\phi^6$ vector model and its supersymmetric extension. In the latter case the generation of the Maxwell term at a fixed point is explored. The phase structure of the $d=3$ case is investigated in the presence of a Chern-Simons term as well. In the supersymmetric $\phi^6$ model the emergence of the Maxwell term is accompanied by the dynamical generation of the Chern-Simons term and its multiplet and dynamical breaking of the parity symmetry. In some of the phases long range forces emerge which may result in logarithmic confinement. These include a dilaton exchange which plays a role also in the case when the theory has no gauge symmetry. Gauged Lagrangian realizations of the 2D coset models do not lead to emergent Maxwell terms. We discuss a case where the gauge symmetry is anomalous.Comment: 38 pages, 4 figures; v2 slightly improved, typos fixed, references added, published versio

A numerical approach to finding general stationary vacuum black holes

The Harmonic Einstein equation is the vacuum Einstein equation supplemented by a gauge fixing term which we take to be that of DeTurck. For static black holes analytically continued to Riemannian manifolds without boundary at the horizon this equation has previously been shown to be elliptic, and Ricci flow and Newton's method provide good numerical algorithms to solve it. Here we extend these techniques to the arbitrary cohomogeneity stationary case which must be treated in Lorentzian signature. For stationary spacetimes with globally timelike Killing vector the Harmonic Einstein equation is elliptic. In the presence of horizons and ergo-regions it is less obviously so. Motivated by the Rigidity theorem we study a class of stationary black hole spacetimes, considered previously by Harmark, general enough to include the asymptotically flat case in higher dimensions. We argue the Harmonic Einstein equation consistently truncates to this class of spacetimes giving an elliptic problem. The Killing horizons and axes of rotational symmetry are boundaries for this problem and we determine boundary conditions there. As a simple example we numerically construct 4D rotating black holes in a cavity using Anderson's boundary conditions. We demonstrate both Newton's method and Ricci flow to find these Lorentzian solutions.Comment: 43 pages, 7 figure

Discovering multi–level structures in bio-molecular data through the Bernstein inequality

Background: The unsupervised discovery of structures (i.e. clusterings) underlying data is a central issue in several branches of bioinformatics. Methods based on the concept of stability have been recently proposed to assess the reliability of a clustering procedure and to estimate the ”optimal ” number of clusters in bio-molecular data. A major problem with stability-based methods is the detection of multi-level structures (e.g. hierarchical functional classes of genes), and the assessment of their statistical significance. In this context, a chi-square based statistical test of hypothesis has been proposed; however, to assure the correctness of this technique some assumptions about the distribution of the data are needed. Results: To assess the statistical significance and to discover multi-level structures in bio-molecular data, a new method based on Bernstein’s inequality is proposed. This approach makes no assumptions about the distribution of the data, thus assuring a reliable application to a large range of bioinformatics problems. Results with synthetic and DNA microarray data show the effectiveness of the proposed method. Conclusions: The Bernstein test, due to its loose assumptions, is more sensitive than the chi-square test to the detection of multiple structures simultaneously present in the data. Nevertheless it is less selective, that is subject to more false positives, but adding independence assumptions, a more selective variant of the Bernstein inequality-based test is also presented. The proposed methods can be applied to discover multiple structures and to assess their significance in different types of bio-molecular data

SCAMP:standardised, concentrated, additional macronutrients, parenteral nutrition in very preterm infants: a phase IV randomised, controlled exploratory study of macronutrient intake, growth and other aspects of neonatal care

<p>Abstract</p> <p>Background</p> <p>Infants born <29 weeks gestation are at high risk of neurocognitive disability. Early postnatal growth failure, particularly head growth, is an important and potentially reversible risk factor for impaired neurodevelopmental outcome. Inadequate nutrition is a major factor in this postnatal growth failure, optimal protein and calorie (macronutrient) intakes are rarely achieved, especially in the first week. Infants <29 weeks are dependent on parenteral nutrition for the bulk of their nutrient needs for the first 2-3 weeks of life to allow gut adaptation to milk digestion. The prescription, formulation and administration of neonatal parenteral nutrition is critical to achieving optimal protein and calorie intake but has received little scientific evaluation. Current neonatal parenteral nutrition regimens often rely on individualised prescription to manage the labile, unpredictable biochemical and metabolic control characteristic of the early neonatal period. Individualised prescription frequently fails to translate into optimal macronutrient delivery. We have previously shown that a standardised, concentrated neonatal parenteral nutrition regimen can optimise macronutrient intake.</p> <p>Methods</p> <p>We propose a single centre, randomised controlled exploratory trial of two standardised, concentrated neonatal parenteral nutrition regimens comparing a standard macronutrient content (maximum protein 2.8 g/kg/day; lipid 2.8 g/kg/day, dextrose 10%) with a higher macronutrient content (maximum protein 3.8 g/kg/day; lipid 3.8 g/kg/day, dextrose 12%) over the first 28 days of life. 150 infants 24-28 completed weeks gestation and birthweight <1200 g will be recruited. The primary outcome will be head growth velocity in the first 28 days of life. Secondary outcomes will include a) auxological data between birth and 36 weeks corrected gestational age b) actual macronutrient intake in first 28 days c) biomarkers of biochemical and metabolic tolerance d) infection biomarkers and other intravascular line complications e) incidence of major complications of prematurity including mortality f) neurodevelopmental outcome at 2 years corrected gestational age</p> <p>Trial registration</p> <p>Current controlled trials: <a href="http://www.controlled-trials.com/ISRCTN76597892">ISRCTN76597892</a>; EudraCT Number: 2008-008899-14</p