Oncolog, Volume 37, Issue 04, October-December 1992

Universal access to health care requires insurance reform, says AMA\u27s Painter Tissue conservation techniques for patients with vulvar cancerhttps://openworks.mdanderson.org/oncolog/1040/thumbnail.jp

Minimal breast milk transfer of rituximab, a monoclonal antibody used in neurological conditions.

ObjectiveTo determine the transfer of rituximab, an anti-CD20 monoclonal antibody widely used for neurologic conditions, into mature breast milk.MethodsBreast milk samples were collected from 9 women with MS who received rituximab 500 or 1,000 mg intravenous once or twice while breastfeeding from November 2017 to April 2019. Serial breast milk samples were collected before infusion and at 8 hours, 24 hours, 7 days, and 18-21 days after rituximab infusion in 4 patients. Five additional patients provided 1-2 samples at various times after rituximab infusion.ResultsThe median average rituximab concentration in mature breast milk was low at 0.063 μg/mL (range 0.046-0.097) in the 4 patients with serial breast milk collection, with an estimated median absolute infant dose of 0.0094 mg/kg/d and a relative infant dose (RID) of 0.08% (range 0.06%-0.10%). Most patients had a maximum concentration at 1-7 days after infusion. The maximum concentration occurred in a woman with a single breast milk sample and was 0.29 μg/mL at 11 days postinfusion, which corresponds with an estimated RID of 0.33%. Rituximab concentration in milk was virtually undetectable by 90 days postinfusion.ConclusionsWe determined minimal transfer of rituximab into mature breast milk. The RID for rituximab was less than 0.4% and well below theoretically acceptable levels of less than 10%. Low oral bioavailability would probably also limit the absorption of rituximab by the newborn. In women with serious autoimmune neurologic conditions, monoclonal antibody therapy may afford an acceptable benefit to risk ratio, supporting both maternal treatment and breastfeeding

Atmospheric extinction coefficients in the Ic\mathrm{I_c} band for several major international observatories: Results from the BiSON telescopes, 1984 to 2016

Over 30 years of solar data have been acquired by the Birmingham Solar Oscillations Network (BiSON), an international network of telescopes used to study oscillations of the Sun. Five of the six BiSON telescopes are located at major observatories. The observational sites are, in order of increasing longitude: Mount Wilson (Hale) Observatory (MWO), California, USA; Las Campanas Observatory (LCO), Chile; Observatorio del Teide, Iza\~{n}a, Tenerife, Canary Islands; the South African Astronomical Observatory (SAAO), Sutherland, South Africa; Carnarvon, Western Australia; and the Paul Wild Observatory, Narrabri, New South Wales, Australia. The BiSON data may be used to measure atmospheric extinction coefficients in the $\mathrm{I_c}$ band (approximately 700-900 nm), and presented here are the derived atmospheric extinction coefficients from each site over the years 1984 to 2016.Comment: 15 pages, 10 figures, 4 tables. Accepted by Astronomical Journal: 2017 July 2

Proximate and fatty acid composition of 40 southeastern U.S. finfish species

This report describes the proximate compositions (protein, moisture, fat, and ash) and major fatty acid profiles for raw and cooked samples of 40 southeastern finfish species. All samples (fillets) were cooked by a standard procedure in laminated plastic bags to an internal temperature of 70'C (lS8'F). Both summarized compositional data, with means and ranges for each species, and individual sample data including harvest dates and average lengths and weights are presented. When compared with raw samples, cooked samples exhibited an increase in protein content with an accompanying decrease in moisture content. Fat content either remained approximately the same or increased due to moisture loss during cooking. Our results are discussed in reference to compositional data previously published by others on some of the same species. Although additional data are needed to adequately describe the seasonal and geographic variations in the chemical compositions of many of these fish species, the results presented here should be useful to nutritionists, seafood marketers, and consumers.(PDF file contains 28 pages.

On the Mechanism of Time--Delayed Feedback Control

The Pyragas method for controlling chaos is investigated in detail from the experimental as well as theoretical point of view. We show by an analytical stability analysis that the revolution around an unstable periodic orbit governs the success of the control scheme. Our predictions concerning the transient behaviour of the control signal are confirmed by numerical simulations and an electronic circuit experiment.Comment: 4 pages, REVTeX, 4 eps-figures included Phys. Rev. Lett., in press also available at http://athene.fkp.physik.th-darmstadt.de/public/wolfram.htm

Visualizing Spacetime Curvature via Gradient Flows I: Introduction

Traditional approaches to the study of the dynamics of spacetime curvature in a very real sense hide the intricacies of the nonlinear regime. Whether it be huge formulae, or mountains of numerical data, standard methods of presentation make little use of our remarkable skill, as humans, at pattern recognition. Here we introduce a new approach to the visualization of spacetime curvature. We examine the flows associated with the gradient fields of invariants derived from the spacetime. These flows reveal a remarkably rich structure, and offer fresh insights even for well known analytical solutions to Einstein's equations. This paper serves as an overview and as an introduction to this approach.Comment: 10 pages twocolumn revtex 4-1 two figures. Final form to appear in Phys Rev

A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial of Tafenoquine for Weekly Prophylaxis against \u3ci\u3ePlasmodium falciparum\u3c/i\u3e

Tafenoquine is a promising new 8-aminoquinoline drug that may be useful for malaria prophylaxis in nonpregnant persons with normal glucose-6-phosphate dehydrogenase (G6PD) function. A randomized, doubleblind, placebo-controlled chemoprophylaxis trial was conducted with adult residents of northern Ghana to determine the minimum effective weekly dose of tafenoquine for the prevention of infection by Plasmodium falciparum. The primary end point was a positive malaria blood smear result during the 13 weeks of study drug coverage. Relative to the placebo, all 4 tafenoquine dosages demonstrated significant protection against P. falciparum infection: for 25 mg/week, protective efficacy was 32% (95% confidence interval [CI], 20%–43%); for 50 mg/week, 84% (95% CI, 75%–91%); for 100 mg/week, 87% (95% CI, 78%–93%); and for 200 mg/week, 86% (95% CI, 76%–92%). The mefloquine dosage of 250 mg/week also demonstrated significant protection against P. falciparum infection (protective efficacy, 86%; 95% CI, 72%–93%). There was little difference between study groups in the adverse events reported, and there was no evidence of a relationship between tafenoquine dosage and reports of physical complaints or the occurrence of abnormal laboratory parameters. Tafenoquine dosages of 50, 100, and 200 mg/week were safe, well tolerated, and effective against P. falciparum infection in this study population

1962: Abilene Christian College Bible Lectures - Full Text

THE RESTORATION PRINCIPLE” Being the Abilene Christian College Annual Bible Lectures 1962 Price: $3.95 Published by ABILENE CHRISTIAN COLLEGE STUDENTS EXCHANGE ACC Station Abilene, Texa

Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G

Background: The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised. Methodology/Principal Findings: We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy. Conclusions/Significance: We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality

The TYK2-P1104A Autoimmune Protective Variant Limits Coordinate Signals Required to Generate Specialized T Cell Subsets

TYK2 is a JAK family member that functions downstream of multiple cytokine receptors. Genome wide association studies have linked a SNP (rs34536443) within TYK2 encoding a Proline to Alanine substitution at amino acid 1104, to protection from multiple autoimmune diseases including systemic lupus erythematosus (SLE) and multiple sclerosis (MS). The protective role of this SNP in autoimmune pathogenesis, however, remains incompletely understood. Here we found that T follicular helper (Tfh) cells, switched memory B cells, and IFNAR signaling were decreased in healthy individuals that expressed the protective variant TYK2A1104 (TYK2P). To study this variant in vivo, we developed a knock-in murine model of this allele. Murine Tyk2P expressing T cells homozygous for the protective allele, but not cells heterozygous for this change, manifest decreased IL-12 receptor signaling, important for Tfh lineage commitment. Further, homozygous Tyk2P T cells exhibited diminished in vitro Th1 skewing. Surprisingly, despite these signaling changes, in vivo formation of Tfh and GC B cells was unaffected in two models of T cell dependent immune responses and in two alternative SLE models. TYK2 is also activated downstream of IL-23 receptor engagement. Here, we found that Tyk2P expressing T cells had reduced IL-23 dependent signaling as well as a diminished ability to skew toward Th17 in vitro. Consistent with these findings, homozygous, but not heterozygous, Tyk2P mice were fully protected in a murine model of MS. Homozygous Tyk2P mice had fewer infiltrating CD4+ T cells within the CNS. Most strikingly, homozygous mice had a decreased proportion of IL-17+/IFNγ+, double positive, pathogenic CD4+ T cells in both the draining lymph nodes (LN) and CNS. Thus, in an autoimmune model, such as EAE, impacted by both altered Th1 and Th17 signaling, the Tyk2P allele can effectively shield animals from disease. Taken together, our findings suggest that TYK2P diminishes IL-12, IL-23, and IFN I signaling and that its protective effect is most likely manifest in the setting of autoimmune triggers that concurrently dysregulate at least two of these important signaling cascades