Oral fumaric acid esters for psoriasis: abridged Cochrane systematic review including GRADE assessments

Fumaric acid esters (FAE) are licensed for the treatment of moderate to severe psoriasis in Germany but are also used off-label in many other countries. We conducted this systematic review to synthesize the highest quality evidence for the benefits and risks of FAE for psoriasis. Our primary outcomes were change in PASI score and drop-out rates due to adverse effects. Randomised controlled trials (RCTs) of FAE or dimethyl fumarate were included, with no restriction on age or psoriasis subtype. We searched The Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library, MEDLINE, EMBASE, LILACS, five trials registers and handsearched six conference proceedings. Six RCTs with 544 participants were included, four of which were published only as abstracts or brief reports, limiting study reporting. Five RCTs compared FAE with placebo and all demonstrated benefit in favour of FAE but meta-analysis was only possible for PASI 50 after 12-16 weeks, which was achieved by 64% of participants on FAE compared to 14% on placebo (risk ratio (RR) 4.55; 95% CI 2.80 to 7.40; 2 studies; 247 participants; low quality evidence). There was no difference in drop-out rates due to adverse effects (RR 5.36, 95% CI 0.28 to 102.12; 1 study; 27 participants; very low-quality evidence and wide confidence interval). More participants experienced nuisance adverse effects with FAE (76%) compared to placebo (16%) (RR 4.72, 95% CI 2.45 to 9.08; 1 study; 99 participants; moderate-quality evidence), mainly abdominal pain, diarrhoea and flushing. One head-to-head study of very low quality evidence comparing FAE with methotrexate reported comparable efficacy and drop-out rates, although FAE caused more flushing. The evidence in this review was limited and must be interpreted with caution; better designed and reported studies are needed

A New and Elementary CP^n Dyonic Magnon

We show that the dressing transformation method produces a new type of dyonic CP^n magnon in terms of which all the other known solutions are either composites or arise as special limits. In particular, this includes the embedding of Dorey's dyonic magnon via an RP^3 subspace of CP^n. We also show how to generate Dorey's dyonic magnon directly in the S^n sigma model via the dressing method without resorting to the isomorphism with the SU(2) principle chiral model when n=3. The new dyon is shown to be either a charged dyon or topological kink of the related symmetric-space sine-Gordon theories associated to CP^n and in this sense is a direct generalization of the soliton of the complex sine-Gordon theory.Comment: 21 pages, JHEP3, typos correcte

Anti-CRISPR-mediated control of gene editing and synthetic circuits in eukaryotic cells.

Repurposed CRISPR-Cas molecules provide a useful tool set for broad applications of genomic editing and regulation of gene expression in prokaryotes and eukaryotes. Recent discovery of phage-derived proteins, anti-CRISPRs, which serve to abrogate natural CRISPR anti-phage activity, potentially expands the ability to build synthetic CRISPR-mediated circuits. Here, we characterize a panel of anti-CRISPR molecules for expanded applications to counteract CRISPR-mediated gene activation and repression of reporter and endogenous genes in various cell types. We demonstrate that cells pre-engineered with anti-CRISPR molecules become resistant to gene editing, thus providing a means to generate "write-protected" cells that prevent future gene editing. We further show that anti-CRISPRs can be used to control CRISPR-based gene regulation circuits, including implementation of a pulse generator circuit in mammalian cells. Our work suggests that anti-CRISPR proteins should serve as widely applicable tools for synthetic systems regulating the behavior of eukaryotic cells

ArborZ: Photometric Redshifts Using Boosted Decision Trees

Precision photometric redshifts will be essential for extracting cosmological parameters from the next generation of wide-area imaging surveys. In this paper we introduce a photometric redshift algorithm, ArborZ, based on the machine-learning technique of Boosted Decision Trees. We study the algorithm using galaxies from the Sloan Digital Sky Survey and from mock catalogs intended to simulate both the SDSS and the upcoming Dark Energy Survey. We show that it improves upon the performance of existing algorithms. Moreover, the method naturally leads to the reconstruction of a full probability density function (PDF) for the photometric redshift of each galaxy, not merely a single "best estimate" and error, and also provides a photo-z quality figure-of-merit for each galaxy that can be used to reject outliers. We show that the stacked PDFs yield a more accurate reconstruction of the redshift distribution N(z). We discuss limitations of the current algorithm and ideas for future work.Comment: 10 pages, 13 figures, submitted to Ap

The AdS(5)xS(5) Semi-Symmetric Space Sine-Gordon Theory

The generalized symmetric space sine-Gordon theories are a series of 1+1-integrable field theories that are classically equivalent to superstrings on symmetric space spacetimes F/G. They are formulated in terms of a semi-symmetric space as a gauged WZW model with fermions and a potential term to deform it away from the conformal fixed point. We consider in particular the case of PSU(2,2|4)/Sp(2,2)xSp(4) which corresponds to AdS(5)xS(5). We argue that the infinite tower of conserved charges of these theories includes an exotic N=(8,8) supersymmetry that is realized in a mildy non-local way at the Lagrangian level. The supersymmetry is associated to a double central extension of the superalgebra psu(2|2)+psu(2|2) and includes a non-trivial R symmetry algebra corresponding to global gauge transformations, as well as 2-dimensional spacetime translations. We then explicitly construct soliton solutions and show that they carry an internal moduli superspace CP(2|1)xCP(2|1) with both bosonic and Grassmann collective coordinates. We show how to semi-classical quantize the solitons by writing an effective quantum mechanical system on the moduli space which takes the form of a co-adjoint orbit of SU(2|2)xSU(2|2). The spectrum consists of a tower of massive states in the short, or atypical, symmetric representations, just as the giant magnon states of the string world sheet theory, although here the tower is truncated.Comment: 39 pages, references adde

The Relativistic Avatars of Giant Magnons and their S-Matrix

The motion of strings on symmetric space target spaces underlies the integrability of the AdS/CFT correspondence. Although these theories, whose excitations are giant magnons, are non-relativistic they are classically equivalent, via the Polhmeyer reduction, to a relativistic integrable field theory known as a symmetric space sine-Gordon theory. These theories can be formulated as integrable deformations of gauged WZW models. In this work we consider the class of symmetric spaces CP^{n+1} and solve the corresponding generalized sine-Gordon theories at the quantum level by finding the exact spectrum of topological solitons, or kinks, and their S-matrix. The latter involves a trignometric solution of the Yang-Baxer equation which exhibits a quantum group symmetry with a tower of states that is bounded, unlike for magnons, as a result of the quantum group deformation parameter q being a root of unity. We test the S-matrix by taking the semi-classical limit and comparing with the time delays for the scattering of classical solitons. We argue that the internal CP^{n-1} moduli space of collective coordinates of the solitons in the classical theory can be interpreted as a q-deformed fuzzy space in the quantum theory. We analyse the n=1 case separately and provide a further test of the S-matrix conjecture in this case by calculating the central charge of the UV CFT using the thermodynamic Bethe Ansatz.Comment: 33 pages, important correction to S-matrix to ensure crossing symmetr

Clonal architecture of secondary acute myeloid leukemia

BACKGROUND: The myelodysplastic syndromes are a group of hematologic disorders that often evolve into secondary acute myeloid leukemia (AML). The genetic changes that underlie progression from the myelodysplastic syndromes to secondary AML are not well understood. METHODS: We performed whole-genome sequencing of seven paired samples of skin and bone marrow in seven subjects with secondary AML to identify somatic mutations specific to secondary AML. We then genotyped a bone marrow sample obtained during the antecedent myelodysplastic-syndrome stage from each subject to determine the presence or absence of the specific somatic mutations. We identified recurrent mutations in coding genes and defined the clonal architecture of each pair of samples from the myelodysplastic-syndrome stage and the secondary-AML stage, using the allele burden of hundreds of mutations. RESULTS: Approximately 85% of bone marrow cells were clonal in the myelodysplastic-syndrome and secondary-AML samples, regardless of the myeloblast count. The secondary-AML samples contained mutations in 11 recurrently mutated genes, including 4 genes that have not been previously implicated in the myelodysplastic syndromes or AML. In every case, progression to acute leukemia was defined by the persistence of an antecedent founding clone containing 182 to 660 somatic mutations and the outgrowth or emergence of at least one subclone, harboring dozens to hundreds of new mutations. All founding clones and subclones contained at least one mutation in a coding gene. CONCLUSIONS: Nearly all the bone marrow cells in patients with myelodysplastic syndromes and secondary AML are clonally derived. Genetic evolution of secondary AML is a dynamic process shaped by multiple cycles of mutation acquisition and clonal selection. Recurrent gene mutations are found in both founding clones and daughter subclones. (Funded by the National Institutes of Health and others.

SeaWIFS satellite ocean color data from the Southern Ocean

SeaWiFS estimates of surface chlorophyll concentrations are reported for the region of the U.S. JGOFS study in the Southern Ocean (∼ 170 °W, 60 °S). Elevated chlorophyll was observed at the Southern Ocean fronts, near the edge of the seasonal ice sheet, and above the Pacific ­Antarctic Ridge. The elevated chlorophyll levels associated with the Pacific-Antarctic Ridge are surprising since even the crest of the ridge is at depths > 2000 m. This elevated phytoplankton biomass is likely the result of mesoscale physical-biological interactions where the Antarctic Circumpolar Current (ACC) encounters the ridge. Four cruises surveyed this region between October 1997 and March 1998, as part of the U.S. JGOFS. Satellite-derived chlorophyll concentrations were compared with in situ extracted chlorophyll measurements from these cruises. There was good agreement (r² of 0.72, from a linear regression of shipboard vs. satellite chlorophyll), although Sea WiFS underestimated chlorophyll concentrations relative to the ship data

Multi-epoch Spectroscopy of IY UMa: Quiescence, Rise, Normal Outburst & Superoutburst

We exploit rare observations covering the time before and during a normal outburst in the deeply-eclipsing SU UMa system IY UMa to study the dramatic changes in the accretion flow and emission at the onset of outburst. Through Doppler tomography we study the emission distribution, revealing classic accretion flow behaviour in quiescence, with the stream-disc impact ionizing the nearby accretion disc. We observe a delay of hours to a couple of days between the rise in continuum and the rise in the emission lines at the onset of the outburst. From line profiles and Doppler maps during normal and superoutburst we conclude that reprocessing of boundary layer radiation is the dominant emission line mechanism in outburst, and that the normal outburst began in the outer disc. The stream-disc impact feature (the `orbital hump') in the H alpha line flux light curve disappears before the onset of the normal outburst, and may be an observable signal heralding an impending outburst.Comment: 14 pages, 12 figures. Accepted for publication in Monthly Notices of the Royal Astronomical Societ

The impact of transcranial direct current stimulation on inhibitory control in young adults

In recent years, many important discoveries have been made to challenge current policy, guidelines, and practice regarding how best to prevent stroke associated with atherosclerotic stenosis of the origin of the internal carotid artery. TheUnited States Center forMedicare andMedicaid Services (CMS), for instance, is calling for expert advice as to whether its current policies should be modified. Using a thorough review of literature, 41 leading academic stroke-prevention clinicians from the United States and other countries, have united to advise CMS not to extend current reimbursement indications for carotid angioplasty/stenting (CAS) to patients with asymptomatic carotid stenosis or to patients with symptomatic carotid stenosis considered to be at low or standard risk from carotid endarterectomy (CEA). It was concluded that such expansion of reimbursement indications would have disastrous health and economic consequences for the United States and any other country that may follow such inappropriate action. This was an international effort because the experts to best advise CMS are relatively few and scattered around the world. In addition, US health policy, practice, and research have tended to have strong influences on other countries. © 2012 The Authors. Published by Wiley Periodicals, Inc