Induction chemotherapy in the treatment of nasopharyngeal carcinoma: Clinical outcomes and patterns of care

Abstract The role of induction chemotherapy in nasopharyngeal carcinoma (NPC) remains controversial. The primary aim of this study was to use the National Cancer Database to evaluate the patterns of care of induction chemotherapy in NPC and its impact on overall survival (OS). Patients with NPC from 2004 to 2014 were obtained from the NCDB. Patients were considered to have received induction chemotherapy if it was started ≥43 days before the start of RT and concurrent CRT if chemotherapy started within 21 days after the start of RT. Propensity score matching was used to control for selection bias. Cox proportional hazards model was used to determine significant predictors of OS. Logistic regression model was used to determine predictors of the use of induction chemotherapy. Significance was defined as a P value <.05. A total of 4857 patients were identified: 4041 patients (87.2%) received concurrent CRT and 816 patients (16.8%) received induction chemotherapy. The use of induction therapy remained stable between 2004 and 2014. Younger patients and those with higher T‐ and N‐stage had a higher likelihood of being treated with induction chemotherapy. The 5‐year OS in patients treated with induction chemotherapy and CRT was 66.3% vs 69.1%, respectively (P = .25). There was no difference in OS when these two groups were analyzed after propensity score matching. No differences in OS existed between these treatment groups in patients with T3‐T4N1 or TanyN2‐3 disease (P = .76). Propensity score matching also did not reveal any difference in OS in patients with T3‐T4N1 or TanyN2‐3 disease. The use of induction chemotherapy has remained stable in the last decade. In this study of patients with NPC, induction chemotherapy was not associated with improved OS compared to CRT alone

The Spectral Types of White Dwarfs in Messier 4

We present the spectra of 24 white dwarfs in the direction of the globular cluster Messier 4 obtained with the Keck/LRIS and Gemini/GMOS spectrographs. Determining the spectral types of the stars in this sample, we find 24 type DA and 0 type DB (i.e., atmospheres dominated by hydrogen and helium respectively). Assuming the ratio of DA/DB observed in the field with effective temperature between 15,000 - 25,000 K, i.e., 4.2:1, holds for the cluster environment, the chance of finding no DBs in our sample due simply to statistical fluctuations is only 6 X 10^(-3). The spectral types of the ~100 white dwarfs previously identified in open clusters indicate that DB formation is strongly suppressed in that environment. Furthermore, all the ~10 white dwarfs previously identified in other globular clusters are exclusively type DA. In the context of these two facts, this finding suggests that DB formation is suppressed in the cluster environment in general. Though no satisfactory explanation for this phenomenon exists, we discuss several possibilities.Comment: Accepted for Publication in Astrophys. J. 11 pages including 4 figures and 2 tables (journal format

Deep ACS Imaging in the Globular Cluster NGC6397: Dynamical Models

We present N-body models to complement deep imaging of the metal-poor core-collapsed cluster NGC6397 obtained with the Hubble Space Telescope. All simulations include stellar and binary evolution in-step with the stellar dynamics and account for the tidal field of the Galaxy. We focus on the results of a simulation that began with 100000 objects (stars and binaries), 5% primordial binaries and Population II metallicity. After 16 Gyr of evolution the model cluster has about 20% of the stars remaining and has reached core-collapse. We compare the color-magnitude diagrams of the model at this age for the central region and an outer region corresponding to the observed field of NGC6397 (about 2-3 half-light radii from the cluster centre). This demonstrates that the white dwarf population in the outer region has suffered little modification from dynamical processes - contamination of the luminosity function by binaries and white dwarfs with non-standard evolution histories is minimal and should not significantly affect measurement of the cluster age. We also show that the binary fraction of main-sequence stars observed in the NGC6397 field can be taken as representative of the primordial binary fraction of the cluster. For the mass function of the main-sequence stars we find that although this has been altered significantly by dynamics over the cluster lifetime, especially in the central and outer regions, that the position of the observed field is close to optimal for recovering the initial mass function of the cluster stars (below the current turn-off mass). More generally we look at how the mass function changes with radius in a dynamically evolved stellar cluster and suggest where the best radial position to observe the initial mass function is for clusters of any age.Comment: 34 pages, 11 figures, submitted to AJ, companion paper to 0708.403

The Masses of Population II White Dwarfs

Globular star clusters are among the first stellar populations to have formed in the Milky Way, and thus only a small sliver of their initial spectrum of stellar types are still burning hydrogen on the main-sequence today. Almost all of the stars born with more mass than 0.8 M_sun have evolved to form the white dwarf cooling sequence of these systems, and the distribution and properties of these remnants uniquely holds clues related to the nature of the now evolved progenitor stars. With ultra-deep HST imaging observations, rich white dwarf populations of four nearby Milky Way globular clusters have recently been uncovered, and are found to extend an impressive 5 - 8 magnitudes in the faint-blue region of the H-R diagram. In this paper, we characterize the properties of these population II remnants by presenting the first direct mass measurements of individual white dwarfs near the tip of the cooling sequence in the nearest of the Milky Way globulars, M4. Based on Gemini/GMOS and Keck/LRIS multiobject spectroscopic observations, our results indicate that 0.8 M_sun population II main-sequence stars evolving today form 0.53 +/- 0.01 M_sun white dwarfs. We discuss the implications of this result as it relates to our understanding of stellar structure and evolution of population II stars and for the age of the Galactic halo, as measured with white dwarf cooling theory.Comment: Accepted for Publication in Astrophys. J. on Aug. 05th, 2009. 19 pages including 9 figures and 2 tables (journal format

Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans

Dissection of a Complex Disease Susceptibility Region Using a Bayesian Stochastic Search Approach to Fine Mapping.

Identification of candidate causal variants in regions associated with risk of common diseases is complicated by linkage disequilibrium (LD) and multiple association signals. Nonetheless, accurate maps of these variants are needed, both to fully exploit detailed cell specific chromatin annotation data to highlight disease causal mechanisms and cells, and for design of the functional studies that will ultimately be required to confirm causal mechanisms. We adapted a Bayesian evolutionary stochastic search algorithm to the fine mapping problem, and demonstrated its improved performance over conventional stepwise and regularised regression through simulation studies. We then applied it to fine map the established multiple sclerosis (MS) and type 1 diabetes (T1D) associations in the IL-2RA (CD25) gene region. For T1D, both stepwise and stochastic search approaches identified four T1D association signals, with the major effect tagged by the single nucleotide polymorphism, rs12722496. In contrast, for MS, the stochastic search found two distinct competing models: a single candidate causal variant, tagged by rs2104286 and reported previously using stepwise analysis; and a more complex model with two association signals, one of which was tagged by the major T1D associated rs12722496 and the other by rs56382813. There is low to moderate LD between rs2104286 and both rs12722496 and rs56382813 (r2 ≃ 0:3) and our two SNP model could not be recovered through a forward stepwise search after conditioning on rs2104286. Both signals in the two variant model for MS affect CD25 expression on distinct subpopulations of CD4+ T cells, which are key cells in the autoimmune process. The results support a shared causal variant for T1D and MS. Our study illustrates the benefit of using a purposely designed model search strategy for fine mapping and the advantage of combining disease and protein expression data.We acknowledge use of DNA from The UK Blood Services collection of Common Controls (UKBS-CC collection), which is funded by the Wellcome Trust grant 076113/C/04/Z and by the USA National Institute for Health Research program grant to the National Health Service Blood and Transplant (RP-PG-0310-1002). We acknowledge the use of DNA from the British 1958 Birth Cohort collection, which is funded by the UK Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. This research utilized resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the National Human Genome Research Institute, the National Institute of Child Health and Human Development and the JDRF and is supported by the USA National Institutes of Health grant U01-DK062418. The JDRF/Wellcome Trust Diabetes and Inflammation Laboratory is funded by the JDRF (9-2011-253), the Wellcome Trust (091157) and the National Institute for Health Research Cambridge Biomedical Centre. The research leading to these results has received funding from the European Union's 7th Framework Programme (FP7/2007-2013) under grant agreement no.241447 (NAIMIT). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140). CW is supported by the Wellcome Trust (089989). We acknowledge the National Institute for Health Research Cambridge Biomedical Research Centre for funding.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pgen.100527

Publisher Correction: Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

The original version of this article contained an error in the name of the author Ramachandran S. Vasan, which was incorrectly given as Vasan S. Ramachandran. This has now been corrected in both the PDF and HTML versions of the article

Magnetorheology in an aging, yield stress matrix fluid

Field-induced static and dynamic yield stresses are explored for magnetorheological (MR) suspensions in an aging, yield stress matrix fluid composed of an aqueous dispersion of Laponite® clay. Using a custom-built magnetorheometry fixture, the MR response is studied for magnetic field strengths up to 1 T and magnetic particle concentrations up to 30 v%. The yield stress of the matrix fluid, which serves to inhibit sedimentation of dispersed carbonyl iron magnetic microparticles, is found to have a negligible effect on the field-induced static yield stress for sufficient applied fields, and good agreement is observed between field-induced static and dynamic yield stresses for all but the lowest field strengths and particle concentrations. These results, which generally imply a dominance of inter-particle dipolar interactions over the matrix fluid yield stress, are analyzed by considering a dimensionless magnetic yield parameter that quantifies the balance of stresses on particles. By characterizing the applied magnetic field in terms of the average particle magnetization, a rheological master curve is generated for the field-induced static yield stress that indicates a concentration–magnetization superposition. The results presented herein will provide guidance to formulators of MR fluids and designers of MR devices who require a field-induced static yield stress and a dispersion that is essentially indefinitely stable to sedimentation.Petroleum Research Fund (ACS-PRF Grant No. 49956-ND9)American Chemical Society (ACS-PRF Grant No. 49956-ND9