White Dwarf Mergers on Adaptive Meshes I. Methodology and Code Verification

The Type Ia supernova progenitor problem is one of the most perplexing and exciting problems in astrophysics, requiring detailed numerical modeling to complement observations of these explosions. One possible progenitor that has merited recent theoretical attention is the white dwarf merger scenario, which has the potential to naturally explain many of the observed characteristics of Type Ia supernovae. To date there have been relatively few self-consistent simulations of merging white dwarf systems using mesh-based hydrodynamics. This is the first paper in a series describing simulations of these systems using a hydrodynamics code with adaptive mesh refinement. In this paper we describe our numerical methodology and discuss our implementation in the compressible hydrodynamics code CASTRO, which solves the Euler equations, and the Poisson equation for self-gravity, and couples the gravitational and rotation forces to the hydrodynamics. Standard techniques for coupling gravitation and rotation forces to the hydrodynamics do not adequately conserve the total energy of the system for our problem, but recent advances in the literature allow progress and we discuss our implementation here. We present a set of test problems demonstrating the extent to which our software sufficiently models a system where large amounts of mass are advected on the computational domain over long timescales. Future papers in this series will describe our treatment of the initial conditions of these systems and will examine the early phases of the merger to determine its viability for triggering a thermonuclear detonation.Comment: Accepted for publication in the Astrophysical Journa

Effects of Exenatide vs. Metformin on endothelial function in obese patients with pre-diabetes: a randomized trial

BACKGROUND: Glucagon like peptide-1 (GLP-1) receptor agonist treatment may improve endothelial function via direct and indirect mechanisms. We compared the acute and chronic effects of the GLP-1 receptor agonist exenatide vs. metformin on endothelial function in patients with obesity and pre-diabetes. METHODS: We performed a randomized, open-label, clinical trial in 50 non-diabetic individuals (mean age 58.5 ± 10.0; 38 females) with abdominal obesity and either impaired fasting glucose, elevated HbA1c, or impaired glucose tolerance (IGT) who were randomized to receive 3-months of exenatide or metformin. Microvascular endothelial function, assessed by digital reactive hyperemia (reactive hyperemic index: RHI), C-reactive protein (CRP), circulating oxidized LDL (oxLDL), and vascular cell adhesion molecule-1 (VCAM-1) were measured at baseline and 3-months. Seven subjects with IGT participated in a sub-study comparing the effects of pre-administration of exenatide and metformin on postprandial endothelial function. RESULTS: There were no differences for the change in RHI (Δ exenatide: 0.01 ± 0.68 vs. Δ metformin: -0.17 ± 0.72, P = 0.348), CRP, oxLDL, or VCAM-1 between exenatide and metformin treatment. Triglycerides were reduced more with exenatide compared to metformin (Δ exenatide: -25.5 ± 45.7 mg/dL vs. Δ metformin: -2.9 ± 22.8 mg/dL, P = 0.032). In the sub-study, there was no difference in postprandial RHI between exenatide and metformin. CONCLUSIONS: Three months of exenatide therapy had similar effects on microvascular endothelial function, markers of inflammation, oxidative stress, and vascular activation, as metformin, in patients with obesity and pre-diabetes. CLINICAL TRIALS REGISTRATION: This study is registered on http://www.clinicaltrials.gov/: NCT0054672

Increasing Adipocyte Lipoprotein Lipase Improves Glucose Metabolism in High Fat Diet-Induced Obesity

Lipid accumulation in liver and skeletal muscle contributes to co-morbidities associated with diabetes and obesity. We made a transgenic mouse in which the adiponectin (Adipoq) promoter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissue lipid storage. These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well as increased energy expenditure when challenged with a high fat diet (HFD). To identify the mechanism(s) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to reduce peripheral lipotoxicity, but we found no evidence for this. Instead, characterization of the adipose tissue of the male mice after HFD challenge revealed that the mRNA levels of peroxisome proliferator-activated receptor-γ (PPARγ) and a number of PPARγ-regulated genes were higher in the epididymal fat pads of Adipoq-LPL mice than control mice. This included adiponectin, whose mRNA levels were increased, leading to increased adiponectin serum levels in the Adipoq-LPL mice. In many respects, the adipose phenotype of these animals resembles thiazolidinedione treatment except for one important difference, the Adipoq-LPL mice did not gain more fat mass on HFD than control mice and did not have increased expression of genes in adipose such as glycerol kinase, which are induced by high affinity PPAR agonists. Rather, there was selective induction of PPARγ-regulated genes such as adiponectin in the adipose of the Adipoq-LPL mice, suggesting that increasing adipose tissue LPL improves glucose metabolism in diet-induced obesity by improving the adipose tissue phenotype. Adipoq-LPL mice also have increased energy expenditure

Hypofractionated Stereotactic Radiotherapy for Non-breast or Prostate Cancer Oligometastases: A Tail of Survival Beyond 10 Years

Purpose and Objective(s): We sought to analyze the long-term follow-up of patients treated with hypofractionated, stereotactic radiotherapy (HSRT) for oligometastases from malignancies other than breast or prostate cancer.Materials and Methods: From 2001 to 2006, 82 cancer patients with 1–5 radiographically apparent metastatic lesions (in 1–3 organs) from primary sites other than breast or prostate cancer, were enrolled on a prospective study of HSRT. Freedom from widespread metastasis (FFWM) was defined from date of enrollment until death, an event (i.e., widespread distant metastasis not amenable to local therapy), or last radiographic study. Local recurrence was scored as an event if pathologically confirmed or if a treated lesion increased by ≥20% using RECIST criteria. Prognostic variables were assessed using Cox regression analysis.Results: The mean age was 61 ± 11 years, with a male to female ratio of 46:36. The most common metastatic sites were liver (50%), lung (48%), thoracic lymph nodes (18%), and bone (5%). Sixty-one patients (74%) had 1 involved organ and 18 (22%) had 1 lesion treated. The preferred dose-fractionation scheduled was 50 Gy in 10 fractions (52 patients). The median follow-up was 1.7 years. Eleven patients lived >5 years, and 6 lived >10 years. The 5-year OS, PFS, FFWM, and LC rates were 13.4, 7.3, 18.3, and 63.4%, and the 10-years OS, PFS, FFWM, and patient LC rates were 7.3, 6.1, 13.4, and 62.2%, respectively. A greater net gross tumor volume (GTV) was significantly adverse for OS (p < 0.01) and LC (p < 0.01). For FFWM, net GTV was not a significant factor (p = 0.14). Four patients remain alive at >13 years from enrollment and treatment, without evidence of active disease.Conclusion: A small subset of select non-breast, non-prostate cancer patients with limited metastasis treated with HSRT are long-term survivors. Net GTV is a significant factor for tumor control and survival. Further research is needed to help better select patients most likely to benefit from local therapy for metastatic disease

Quasi-Periodic Occultation by a Precessing Accretion Disk and Other Variabilities of SMC X-1

We have investigated the variability of the binary X-ray pulsar, SMC X-1, in data from several X-ray observatories. We confirm the ~60-day cyclic variation of the X-ray flux in the long-term monitoring data from the RXTE and CGRO observatories. X-ray light curves and spectra from the ROSAT, Ginga, and ASCA observatories show that the uneclipsed flux varies by as much as a factor of twenty between a high-flux state when 0.71 second pulses are present and a low-flux state when pulses are absent. In contrast, during eclipses when the X-rays consist of radiation scattered from circumsource matter, the fluxes and spectra in the high and low states are approximately the same. These observations prove that the low state of SMC X-1 is not caused by a reduction in the intrinsic luminosity of the source, or a spectral redistribution thereof, but rather by a quasi-periodic blockage of the line of sight, most likely by a precessing tilted accretion disk. In each of two observations in the midst of low states a brief increase in the X-ray flux and reappearance of 0.71 second pulses occurred near orbital phase 0.2. These brief increases result from an opening of the line of sight to the pulsar that may be caused by wobble in the precessing accretion disk. The records of spin up of the neutron star and decay of the binary orbit are extended during 1991-1996 by pulse-timing analysis of ROSAT, ASCA, and RXTE PCA data. The pulse profiles in various energy ranges from 0.1 to >21 keV are well represented as a combination of a pencil beam and a fan beam. Finally, there is a marked difference between the power spectra of random fluctuations in the high-state data from the RXTE PCA below and above 3.4 keV. Deviation from the fitted power law around 0.06 Hz may be QPO.Comment: Accepted to ApJ. 33 pages including 11 figure

Interpreting ambiguous ‘trace’ results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard

Background The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results. Methodology/Principle findings We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population. Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries. Conclusions Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence

Sensitivity and Specificity of Multiple Kato-Katz Thick Smears and a Circulating Cathodic Antigen Test for Schistosoma mansoni Diagnosis Pre- and Post-repeated-Praziquantel Treatment

Two Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This ‘gold standard’ has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings

The Ursinus Weekly, March 6, 1969

Officers inducted; Emig emphasizes new responsibility • American dream, brotherhood highlight Festival of the Arts • USGA officers interviewed; Communication gap stressed • Placement interviews scheduled • 200 attend Lorelei; Fischer crowned king • Semi-formal ball highlights junior-senior weekend • Editorial: Potpourri - Or, Could this ever happen here? • State set to punish protestors; Laws threaten civil liberties • Letters to the editor • Remark • Lantern literary lapse termed titanic bomb • Staying out of uniform: A practical guide for the Ursinus male, part I • Whose risk? • Columnist proposes solution to UC\u27s dearth of black students • Albright draws Fifth Dimension • Racism symposium set for March 20 with Lincoln Univ. • Dorm lounges opened; Slacks rule slackened • Rice discusses status for Phi Beta Kappa • Ursinus grapplers rally to win over Drexel, 22-13 • New gym complex to include pool • Carson paces Bearettes over Gettysburg • Badminton team wins six in row • Trackmen run at Swarthmore and Delaware • Gillespie hits 37 points to lead Bears over Swarthmore in finale • Girl swimmers win over Penn and Elizabethtown • Junior varsity hoopmen finish with 11-6 record • Dickinson frat system defended • UC celebrates centennial with unique innovation • Forum features Howellhttps://digitalcommons.ursinus.edu/weekly/1171/thumbnail.jp

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response

Comparison of quality of life after stereotactic body radiotherapy and surgery for early-stage prostate cancer

Background: As the long-term efficacy of stereotactic body radiation therapy (SBRT) becomes established and other prostate cancer treatment approaches are refined and improved, examination of quality of life (QOL) following prostate cancer treatment is critical in driving both patient and clinical treatment decisions. We present the first study to compare QOL after SBRT and radical prostatectomy, with QOL assessed at approximately the same times pre- and post-treatment and using the same validated QOL instrument. Methods: Patients with clinically localized prostate cancer were treated with either radical prostatectomy (n = 123 Spanish patients) or SBRT (n = 216 American patients). QOL was assessed using the Expanded Prostate Cancer Index Composite (EPIC) grouped into urinary, sexual, and bowel domains. For comparison purposes, SBRT EPIC data at baseline, 3 weeks, 5, 11, 24, and 36 months were compared to surgery data at baseline, 1, 6, 12, 24,and 36 months. Differences in patient characteristics between the two groups were assessed using Chi-squared tests for categorical variables and t-tests for continuous variables. Generalized estimating equation (GEE) models were constructed for each EPIC scale to account for correlation among repeated measures and used to assess the effect of treatment on QOL. Results: The largest differences in QOL occurred in the first 1-6 months after treatment, with larger declines following surgery in urinary and sexual QOL as compared to SBRT, and a larger decline in bowel QOL following SBRT as compared to surgery. Long-term urinary and sexual QOL declines remained clinically significantly lower for surgery patients but not for SBRT patients. Conclusions: Overall, these results may have implications for patient and physician clinical decision making which are often influenced by QOL. These differences in sexual, urinary and bowel QOL should be closely considered in selecting the right treatment, especially in evaluating the value of non-invasive treatments, such as SBRT