Relationship of national institutes of health stroke scale to 30-day mortality in medicare beneficiaries with acute ischemic stroke.

BackgroundThe National Institutes of Health Stroke Scale (NIHSS), a well-validated tool for assessing initial stroke severity, has previously been shown to be associated with mortality in acute ischemic stroke. However, the relationship, optimal categorization, and risk discrimination with the NIHSS for predicting 30-day mortality among Medicare beneficiaries with acute ischemic stroke has not been well studied.Methods and resultsWe analyzed data from 33102 fee-for-service Medicare beneficiaries treated at 404 Get With The Guidelines-Stroke hospitals between April 2003 and December 2006 with NIHSS documented. The 30-day mortality rate by NIHSS as a continuous variable and by risk-tree determined or prespecified categories were analyzed, with discrimination of risk quantified by the c-statistic. In this cohort, mean age was 79.0 years and 58% were female. The median NIHSS score was 5 (25th to 75th percentile 2 to 12). There were 4496 deaths in the first 30 days (13.6%). There was a strong graded relation between increasing NIHSS score and higher 30-day mortality. The 30-day mortality rates for acute ischemic stroke by NIHSS categories were as follows: 0 to 7, 4.2%; 8 to 13, 13.9%; 14 to 21, 31.6%; 22 to 42, 53.5%. A model with NIHSS alone provided excellent discrimination whether included as a continuous variable (c-statistic 0.82 [0.81 to 0.83]), 4 categories (c-statistic 0.80 [0.79 to 0.80]), or 3 categories (c-statistic 0.79 [0.78 to 0.79]).ConclusionsThe NIHSS provides substantial prognostic information regarding 30-day mortality risk in Medicare beneficiaries with acute ischemic stroke. This index of stroke severity is a very strong discriminator of mortality risk, even in the absence of other clinical information, whether used as a continuous or categorical risk determinant. (J Am Heart Assoc. 2012;1:42-50.)

Holographic three-point functions for short operators

We consider holographic three-point functions for operators dual to short string states at strong coupling in N=4 super Yang-Mills. We treat the states as point-like as they come in from the boundary but as strings in the interaction region in the bulk. The interaction position is determined by saddle point, which is equivalent to conservation of the canonical momentum for the interacting particles, and leads to conservation of their conformal charges. We further show that for large dimensions the rms size of the interaction region is small compared to the radius of curvature of the AdS space, but still large compared to the string Compton wave-length. Hence, one can approximate the string vertex operators as flat-space vertex operators with a definite momentum, which depends on the conformal and R-charges of the operator. We then argue that the string vertex operator dual to a primary operator is chosen by satisfying a twisted version of Q^L=Q^R, up to spurious terms. This leads to a unique choice for a scalar vertex operator with the appropriate charges at the first massive level. We then comment on some features of the corresponding three-point functions, including the application of these results to Konishi operators.Comment: 24 pages; v2: References added, typos fixed, minor change

On the Stratospheric Aerosol and Gas Experiment III on the International Space Station

The Stratospheric Aerosol and Gas Experiment III on International Space Station (SAGE3/ISS) is anticipated to be delivered to Cape Canaveral in the spring of 2015. This is the fourth generation, fifth instrument, of visible/near-IR solar occultation instruments operated by the National Aeronautics and Space Agency (NASA) to investigate the Earth's upper atmosphere. The instrument is a moderate resolution spectrometer covering wavelengths from 290 nm to 1550 nm. The nominal science products include vertical profiles of trace gases, such as ozone, nitrogen dioxide and water vapor, along with multi-wavelength aerosol extinction. The SAGE3/ISS validation program will be based upon internal consistency of the measurements, detailed analysis of the retrieval algorithm, and comparisons with independent correlative measurements. The Instrument Payload (IP), mission architecture, and major challenges are also discussed

World-sheet scattering in AdS_5 x S^5 at two loops

We study the AdS_5 x S^5 sigma-model truncated to the near-flat-space limit to two-loops in perturbation theory. In addition to extending previously known one-loop results to the full SU(2|2)^2 S-matrix we calculate the two-loop correction to the dispersion relation and then compute the complete two-loop S-matrix. The result of the perturbative calculation can be compared with the appropriate limit of the conjectured S-matrix for the full theory and complete agreement is found.Comment: 26pages, 3 figure

Infinite spin limit of semiclassical string states

Motivated by recent works of Hofman and Maldacena and Dorey we consider a special infinite spin limit of semiclassical spinning string states in AdS5 x S5. We discuss examples of known folded and circular 2-spin string solutions and demonstrate explicitly that the 1-loop superstring correction to the classical expression for the energy vanishes in the limit when one of the spins is much larger that the other. We also give a general discussion of this limit at the level of integral equations describing finite gap solutions of the string sigma model and argue that the corresponding asymptotic form of the string and gauge Bethe equations is the same.Comment: 38 pages, 3 figures; v2: comments on derivation of bound states of magnons from discrete Bethe equations added in section 4 and appendix C, references added, Imperial-TP-AT-6-4, HUTP-06/A002

Associations Between Methylation of Paternally Expressed Gene 3 (PEG3), Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer.

Cytology-based screening for invasive cervical cancer (ICC) lacks sensitivity and specificity to discriminate between cervical intraepithelial neoplasia (CIN) likely to persist or progress from cases likely to resolve. Genome-wide approaches have been used to identify DNA methylation marks associated with CIN persistence or progression. However, associations between DNA methylation marks and CIN or ICC remain weak and inconsistent. Between 2008-2009, we conducted a hospital-based, case-control study among 213 Tanzania women with CIN 1/2/3 or ICC. We collected questionnaire data, biopsies, peripheral blood, cervical scrapes, Human papillomavirus (HPV) and HIV-1 infection status. We assessed PEG3 methylation status by bisulfite pyrosequencing. Multinomial logistic regression was used to estimate odds ratios (OR) and confidence intervals (CI 95%) for associations between PEG3 methylation status and CIN or ICC. After adjusting for age, gravidity, hormonal contraceptive use and HPV infection, a 5% increase in PEG3 DNA methylation was associated with increased risk for ICC (OR = 1.6; 95% CI 1.2-2.1). HPV infection was associated with a higher risk of CIN1-3 (OR = 15.7; 95% CI 5.7-48.6) and ICC (OR = 29.5, 95% CI 6.3-38.4). Infection with high risk HPV was correlated with mean PEG3 differentially methylated regions (DMRs) methylation (r = 0.34 p<0.0001), while the correlation with low risk HPV infection was weaker (r = 0.16 p = 0.047). Although small sample size limits inference, these data support that PEG3 methylation status has potential as a molecular target for inclusion in CIN screening to improve prediction of progression. Impact statement: We present the first evidence that aberrant methylation of the PEG3 DMR is an important co-factor in the development of Invasive cervical carcinoma (ICC), especially among women infected with high risk HPV. Our results show that a five percent increase in DNA methylation of PEG3 is associated with a 1.6-fold increase ICC risk. Suggesting PEG3 methylation status may be useful as a molecular marker for CIN screening to improve prediction of cases likely to progress

A phase II study of glembatumumab vedotin for metastatic uveal melanoma

Glembatumumab vedotin (CDX-011, GV) is a fully human Immunoglobulin G2 monoclonal antibody directed against glycoprotein NMB coupled via a peptide linker to monomethyl auristatin E (MMAE), a potent cytotoxic microtubule inhibitor. This phase II study evaluated the overall response rate and safety of GV, glycoprotein NMB (GPNMB) expression, and survival in patients with metastatic uveal melanoma. Eligible patients with metastatic uveal melanoma who had not previously been treated with chemotherapy received GV 1.9 mg/kg every three weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included GPNMB expression, progression-free survival (PFS), overall survival (OS), and toxicity analysis. GPNMB expression was assessed pre- and post-treatment via immunohistochemistry for patients with available tumor tissue. Out of 35 patients who received treatment, two patients had confirmed partial responses (PRs; 6%), and 18 patients had a stable disease (SD; 51%) as the best objective response. 38% of the patients had stable disease \u3e100 days. The grade 3 or 4 toxicities that occurred in two or more patients were neutropenia, rash, hyponatremia, and vomiting. The median progression-free survival was 3.1 months (95% CI: 1.5-5.6), and the median overall survival was 11.9 months (95% CI 9.0-16.9) in the evaluable study population. GV is well-tolerated in metastatic uveal melanoma. The disease control rate was 57% despite a low objective response rate. Exploratory immune correlation studies are underway to provide insight into target saturation, combination strategies, and antigen release

Normal breast tissue of obese women is enriched for macrophage markers and macrophage-associated gene expression

Activation of inflammatory pathways is one plausible mechanism underlying the association between obesity and increased breast cancer risk. However, macrophage infiltration and local biomarkers of inflammation in breast adipose tissue have seldom been studied in association with obesity

Multiplicative slices, relativistic Toda and shifted quantum affine algebras

We introduce the shifted quantum affine algebras. They map homomorphically into the quantized $K$-theoretic Coulomb branches of $3d\ {\mathcal N}=4$ SUSY quiver gauge theories. In type $A$, they are endowed with a coproduct, and they act on the equivariant $K$-theory of parabolic Laumon spaces. In type $A_1$, they are closely related to the open relativistic quantum Toda lattice of type $A$.Comment: 125 pages. v2: references updated; in section 11 the third local Lax matrix is introduced. v3: references updated. v4=v5: 131 pages, minor corrections, table of contents added, Conjecture 10.25 is now replaced by Theorem 10.25 (whose proof is based on the shuffle approach and is presented in a new Appendix). v6: Final version as published, references updated, footnote 4 adde

High-content siRNA screening of the kinome identifies kinases involved in Alzheimer's disease-related tau hyperphosphorylation

<p>Abstract</p> <p>Background</p> <p>Neurofibrillary tangles (NFT), a cardinal neuropathological feature of Alzheimer's disease (AD) that is highly correlated with synaptic loss and dementia severity, appear to be partly attributable to increased phosphorylation of the microtubule stabilizing protein tau at certain AD-related residues. Identifying the kinases involved in the pathologic phosphorylation of tau may provide targets at which to aim new AD-modifying treatments.</p> <p>Results</p> <p>We report results from a screen of 572 kinases in the human genome for effects on tau hyperphosphorylation using a loss of function, high-throughput RNAi approach. We confirm effects of three kinases from this screen, the eukaryotic translation initiation factor 2 α kinase 2 (EIF2AK2), the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A), and the A-kinase anchor protein 13 (AKAP13) on tau phosphorylation at the 12E8 epitope (serine 262/serine 356). We provide evidence that EIF2AK2 effects may result from effects on tau protein expression, whereas DYRK1A and AKAP13 are likely more specifically involved in tau phosphorylation pathways.</p> <p>Conclusions</p> <p>These findings identify novel kinases that phosphorylate tau protein and provide a valuable reference data set describing the kinases involved in phosphorylating tau at an AD-relevant epitope.</p