Radar detection of a localized 1.4 Hz pulsation in auroral plasma, simultaneous with pulsating optical emissions, during a substorm

Many pulsating phenomena are associated with the auroral substorm. It has been considered that some of these phenomena involve kilometer-scale Alfvén waves coupling the magnetosphere and ionosphere. Electric field oscillations at the altitude of the ionosphere are a signature of such wave activity that could distinguish it from other sources of auroral particle precipitation, which may be simply tracers of magnetospheric activity. Therefore, a ground based diagnostic of kilometer-scale oscillating electric fields would be a valuable tool in the study of pulsations and the auroral substorm. In this study we attempt to develop such a tool in the Poker Flat incoherent scatter radar (PFISR). The central result is a statistically significant detection of a 1.4 Hz electric field oscillation associated with a similar oscillating optical emission, during the recovery phase of a substorm. The optical emissions also contain a bright, lower frequency (0.2 Hz) pulsation that does not show up in the radar backscatter. The fact that higher frequency oscillations are detected by the radar, whereas the bright, lower frequency optical pulsation is not detected by the radar, serves to strengthen a theoretical argument that the radar is sensitive to oscillating electric fields, but not to oscillating particle precipitation. Although it is difficult to make conclusions as to the physical mechanism, we do not find evidence for a plane-wave-like Alfvén wave; the detected structure is evident in only two of five adjacent beams. We emphasize that this is a new application for ISR, and that corroborating results are needed

A Comparison of DSM-IV and DSM-5 Panel Members' Financial Associations with Industry: A Pernicious Problem Persists

Lisa Cosgrove and Sheldon Krimsky examine the new competing interest disclosure policy of the American Psychiatric Association (APA) and report that DSM panel members still have considerable financial conflicts of interest

Killing tensors in pp-wave spacetimes

The formal solution of the second order Killing tensor equations for the general pp-wave spacetime is given. The Killing tensor equations are integrated fully for some specific pp-wave spacetimes. In particular, the complete solution is given for the conformally flat plane wave spacetimes and we find that irreducible Killing tensors arise for specific classes. The maximum number of independent irreducible Killing tensors admitted by a conformally flat plane wave spacetime is shown to be six. It is shown that every pp-wave spacetime that admits an homothety will admit a Killing tensor of Koutras type and, with the exception of the singular scale-invariant plane wave spacetimes, this Killing tensor is irreducible.Comment: 18 page

Investigation of a lattice Boltzmann model with a variable speed of sound

A lattice Boltzmann model is considered in which the speed of sound can be varied independently of the other parameters. The range over which the speed of sound can be varied is investigated and good agreement is found between simulations and theory. The onset of nonlinear effects due to variations in the speed of sound is also investigated and good agreement is again found with theory. It is also shown that the fluid viscosity is not altered by changing the speed of sound

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Canonical Quantization of the Gowdy Model

The family of Gowdy universes with the spatial topology of a three-torus is studied both classically and quantum mechanically. Starting with the Ashtekar formulation of Lorentzian general relativity, we introduce a gauge fixing procedure to remove almost all of the non-physical degrees of freedom. In this way, we arrive at a reduced model that is subject only to one homogeneous constraint. The phase space of this model is described by means of a canonical set of elementary variables. These are two real, homogeneous variables and the Fourier coefficients for four real fields that are periodic in the angular coordinate which does not correspond to a Killing field of the Gowdy spacetimes. We also obtain the explicit expressions for the line element and reduced Hamiltonian. We then proceed to quantize the system by representing the elementary variables as linear operators acting on a vector space of analytic functionals. The inner product on that space is selected by imposing Lorentzian reality conditions. We find the quantum states annihilated by the operator that represents the homogeneous constraint of the model and construct with them the Hilbert space of physical states. Finally, we derive the general form of the quantum observables of the model.Comment: 13 pages, Revte

Epigenome-wide SRC-1 mediated gene silencing represses cellular differentiation in advanced breast cancer

Abstract Purpose: Despite the clinical utility of endocrine therapies for estrogen receptor–positive (ER) breast cancer, up to 40% of patients eventually develop resistance, leading to disease progression. The molecular determinants that drive this adaptation to treatment remain poorly understood. Methylome aberrations drive cancer growth yet the functional role and mechanism of these epimutations in drug resistance are poorly elucidated. Experimental Design: Genome-wide multi-omics sequencing approach identified a differentially methylated hub of prodifferentiation genes in endocrine resistant breast cancer patients and cell models. Clinical relevance of the functionally validated methyl-targets was assessed in a cohort of endocrine-treated human breast cancers and patient-derived ex vivo metastatic tumors. Results: Enhanced global hypermethylation was observed in endocrine treatment resistant cells and patient metastasis relative to sensitive parent cells and matched primary breast tumor, respectively. Using paired methylation and transcriptional profiles, we found that SRC-1–dependent alterations in endocrine resistance lead to aberrant hypermethylation that resulted in reduced expression of a set of differentiation genes. Analysis of ER-positive endocrine-treated human breast tumors (n = 669) demonstrated that low expression of this prodifferentiation gene set significantly associated with poor clinical outcome (P = 0.00009). We demonstrate that the reactivation of these genes in vitro and ex vivo reverses the aggressive phenotype. Conclusions: Our work demonstrates that SRC-1-dependent epigenetic remodeling is a ’high level’ regulator of the poorly differentiated state in ER-positive breast cancer. Collectively these data revealed an epigenetic reprograming pathway, whereby concerted differential DNA methylation is potentiated by SRC-1 in the endocrine resistant setting. Clin Cancer Res; 24(15); 3692–703. ©2018 AACR.</jats:p

Analytic and Asymptotic Methods for Nonlinear Singularity Analysis: a Review and Extensions of Tests for the Painlev\'e Property

The integrability (solvability via an associated single-valued linear problem) of a differential equation is closely related to the singularity structure of its solutions. In particular, there is strong evidence that all integrable equations have the Painlev\'e property, that is, all solutions are single-valued around all movable singularities. In this expository article, we review methods for analysing such singularity structure. In particular, we describe well known techniques of nonlinear regular-singular-type analysis, i.e. the Painlev\'e tests for ordinary and partial differential equations. Then we discuss methods of obtaining sufficiency conditions for the Painlev\'e property. Recently, extensions of \textit{irregular} singularity analysis to nonlinear equations have been achieved. Also, new asymptotic limits of differential equations preserving the Painlev\'e property have been found. We discuss these also.Comment: 40 pages in LaTeX2e. To appear in the Proceedings of the CIMPA Summer School on "Nonlinear Systems," Pondicherry, India, January 1996, (eds) B. Grammaticos and K. Tamizhman