Study of 5 and 10 mm thick CZT strip detectors

We report progress in the study of 5 and 10 mm thick CZT strip detectors featuring orthogonal coplanar anode contacts. This novel anode geometry combines the advantages of pixel detectors with those of double-sided strip detectors. Like pixel detectors, these are electron-only devices that perform well as hard x-ray and y-ray spectrometers and imagers even in the thicker configurations required for reasonable detection efficiency at 1 MeV. Like double-sided strip detectors in an N x N configuration, these detectors require only 2N readout channels to form N2 “pixels”. Unlike doublesided strip detectors, all signal contacts for spectroscopy and 3- d imaging are formed on one detector surface. Polymer flip chip bonding to a ceramic substrate is employed resulting in a rugged and compact detector assembly. Prototype detector modules 5 mm thick have been fabricated and tested. Prototype modules, 10 mm thick, are currently in procurement. Measurements confirm these devices are efficient detectors throughout their volume. Sub-millimeter position resolution and energy resolution (FWHM) better than 3% at 662 keV and 15% at 60 keV throughout the detector volume are demonstrated. Options for processing the signals from the non-collecting anode strip contacts are discussed. Results from tests of one prototype circuit are presented. We also report on detector simulation studies aimed at defining an optimum geometry for the anode contacts and at determining optimum operating conditions and the requirements of the signal processing electronics

A Comprehensive Spectroscopic Analysis of DB White Dwarfs

We present a detailed analysis of 108 helium-line (DB) white dwarfs based on model atmosphere fits to high signal-to-noise optical spectroscopy. We derive a mean mass of 0.67 Mo for our sample, with a dispersion of only 0.09 Mo. White dwarfs also showing hydrogen lines, the DBA stars, comprise 44% of our sample, and their mass distribution appears similar to that of DB stars. As in our previous investigation, we find no evidence for the existence of low-mass (M < 0.5 Mo) DB white dwarfs. We derive a luminosity function based on a subset of DB white dwarfs identified in the Palomar-Green survey. We show that 20% of all white dwarfs in the temperature range of interest are DB stars, although the fraction drops to half this value above Teff ~ 20,000 K. We also show that the persistence of DB stars with no hydrogen features at low temperatures is difficult to reconcile with a scenario involving accretion from the interstellar medium, often invoked to account for the observed hydrogen abundances in DBA stars. We present evidence for the existence of two different evolutionary channels that produce DB white dwarfs: the standard model where DA stars are transformed into DB stars through the convective dilution of a thin hydrogen layer, and a second channel where DB stars retain a helium-atmosphere throughout their evolution. We finally demonstrate that the instability strip of pulsating V777 Her white dwarfs contains no nonvariables, if the hydrogen content of these stars is properly accounted for.Comment: 74 pages including 30 figures, accepted for publication in the Astrophysical Journa

Energy and position resolution of a CdZnTe gamma-ray detector with orthogonal coplanar anodes

We report on the simulation, construction and performance of prototype CZT imaging detectors employing orthogonal coplanar anodes. These detectors employ a novel electrode geometry with non-collecting anode strips in 1D and collecting anode pixels, interconnected in rows, in the orthogonal dimensions. These detectors retain the spectroscopic and detection efficiency advantages of single carried charge sensing devices as well as the principal advantage of conventional strip detectors with orthogonal anode and cathode strips, i.e. an N X N array of imagin pixels are realized with only 2N electronic channels. Charge signals induced on the various electrodes of a prototype detector with 8 X 8 unit cells are in good agreement with the simulations. The position resolution is about 1 mm in the direction perpendicular to the pixel lines while it is of the order of 100 micrometers in the other direction. Energy resolutions of 0.9 percent at 662 keV, 2.6 percent at 122 keV and 5.7 percent at 60 keV have been obtained at room temperature

The Solar Neighborhood. XXXIX. Parallax Results from the CTIOPI and NOFS Programs: 50 New Members of the 25 Parsec White Dwarf Sample

We present 114 trigonometric parallaxes for 107 nearby white dwarf (WD) systems from both the Cerro Tololo Inter-American Observatory Parallax Investigation (CTIOPI) and the U. S. Naval Observatory Flagstaff Station (NOFS) parallax programs. Of these, 76 parallaxes for 69 systems were measured by the CTIOPI program and 38 parallaxes for as many systems were measured by the NOFS program. A total of 50 systems are confirmed to be within the 25 pc horizon of interest. Coupled with a spectroscopic confirmation of a common proper motion companion to a Hipparcos star within 25 pc as well as confirmation parallax determinations for two WD systems included in the recently released Tycho Gaia Astrometric Solution (TGAS) catalog, we add 53 new systems to the 25 pc WD sample $-$ a 42% increase. Our sample presented here includes four strong candidate halo systems, a new metal-rich DAZ WD, a confirmation of a recently discovered nearby short-period (P = 2.85 hr) double degenerate, a WD with a new astrometric pertubation (long period, unconstrained with our data), and a new triple system where the WD companion main-sequence star has an astrometric perturbation (P $\sim$ 1.6 yr).Comment: 32 pages, 12 figures. Figure 4 in the manuscript is a representative set of plots - plots for all WDs presented here are available (allfits_photo.pdf, allfits_photo_DQ.pdf, and allfits_photo_DZ.pdf). Accepted for publication in The Astronomical Journa

A genetic validation study reveals a role of vitamin D metabolism in the response to interferon-alfa-based therapy of chronic hepatitis C

Background: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C. Methodology/Principal Findings: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D3<20 ng/mL) during all seasons, but 25(OH)D3 serum levels were not associated with treatment outcome. Conclusions/Significance: Our study suggests a role of bioactive vitamin D (1,25[OH]2D3, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D3 is not a suitable predictor of treatment outcome

First semi-empirical test of the white dwarf mass-radius relationship using a single white dwarf via astrometric microlensing

Funding: Support for this research was provided by NASA through grants from STScI. HST data used in this paper are available from the Mikulski Archive for Space Telescopes at STScI (https://archive.stsci.edu/hst/search.php) under proposal IDs 15705, 15961 and 16251. PM acknowledges studentship funding support from the United Kingdom Science and Technology Facilities Council (STFC) and the Cambridge Centre for Doctoral Training in Data Intensive Science (CDT-DIS). MBN acknowledges support from the UK Space Agency. This research is based on observations made with the NASA/ESA Hubble Space Telescope obtained from the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5–26555. This work presents results from the European Space Agency (ESA) space mission Gaia. Gaia data are being processed by the Gaia Data Processing and Analysis Consortium (DPAC). Funding for the DPAC is provided by national institutions, in particular the institutions participating in the Gaia Multi-Lateral Agreement (MLA). The Gaia mission website is https://www.cosmos.esa.int/gaia. The Gaia Archive website is http://archives.esac.esa.int/gaia.In November 2019 the nearby single, isolated DQ-type white dwarf LAWD 37 (LP 145-141) aligned closely with a distant background source and caused an astrometric microlensing event. Leveraging astrometry from Gaia and followup data from the Hubble Space Telescope we measure the astrometric deflection of the background source and obtain a gravitational mass for LAWD 37. The main challenge of this analysis is in extracting the lensing signal of the faint background source whilst it is buried in the wings of LAWD 37's point spread function. Removal of LAWD 37's point spread function induces a significant amount of correlated noise which we find can mimic the astrometric lensing signal. We find a deflection model including correlated noise caused by the removal of LAWD 37's point spread function best explains the data and yields a mass for LAWD 37 of 0.56 ± 0.08 M ⊙. This mass is in agreement with the theoretical mass-radius relationship and cooling tracks expected for CO core white dwarfs. Furthermore, the mass is consistent with no or trace amounts of hydrogen that is expected for objects with helium-rich atmospheres like LAWD 37. We conclude that further astrometric followup data on the source is likely to improve the inference on LAWD 37's mass at the ≈3 percent level and definitively rule out purely correlated noise explanations of the data. This work provides the first semi-empirical test of the white dwarf mass-radius relationship using a single, isolated white dwarf and supports current model atmospheres of DQ white dwarfs and white dwarf evolutionary theory.PreprintPostprintPeer reviewe

Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study)

<p>Abstract</p> <p>Background</p> <p>Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neo)adjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC) has been designed to explore the efficacy of neoadjuvant chemotherapy.</p> <p>Methods/Design</p> <p>This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m²) for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m², oxaliplatin 100 mg/m²) followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked intraoperatively, and representative histological sections will be centrally reviewed by a dedicated pathologist.</p> <p>Discussion</p> <p>The NEOPAC study will determine the efficacy of neoadjuvant chemotherapy in pancreatic cancer for the first time and offers a unique potential for translational research. Furthermore, this trial will provide the unbiased overall survival of all patients undergoing surgery for resectable cancer of the pancreatic head.</p> <p>Trial registration</p> <p>clinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01314027">NCT01314027</a></p

CD133, CD15/SSEA-1, CD34 or side populations do not resume tumor-initiating properties of long-term cultured cancer stem cells from human malignant glio-neuronal tumors

<p>Abstract</p> <p>Background</p> <p>Tumor initiating cells (TICs) provide a new paradigm for developing original therapeutic strategies.</p> <p>Methods</p> <p>We screened for TICs in 47 human adult brain malignant tumors. Cells forming floating spheres in culture, and endowed with all of the features expected from tumor cells with stem-like properties were obtained from glioblastomas, medulloblastoma but not oligodendrogliomas.</p> <p>Results</p> <p>A long-term self-renewal capacity was particularly observed for cells of malignant glio-neuronal tumors (MGNTs). Cell sorting, karyotyping and proteomic analysis demonstrated cell stability throughout prolonged passages. Xenografts of fewer than 500 cells in Nude mouse brains induced a progressively growing tumor. CD133, CD15/LeX/Ssea-1, CD34 expressions, or exclusion of Hoechst dye occurred in subsets of cells forming spheres, but was not predictive of their capacity to form secondary spheres or tumors, or to resist high doses of temozolomide.</p> <p>Conclusions</p> <p>Our results further highlight the specificity of a subset of high-grade gliomas, MGNT. TICs derived from these tumors represent a new tool to screen for innovative therapies.</p

Integrin/Fak/Src-mediated regulation of cell survival and anoikis in human intestinal epithelial crypt cells: selective engagement and roles of PI3-K isoform complexes

In human intestinal epithelial crypt (HIEC) cells, the PI3-K/Akt-1 pathway is crucial for the promotion of cell survival and suppression of anoikis. Class I PI3-K consists of a complex formed by a catalytic (C) and regulatory (R) subunit. Three R (p85α, β, and p55γ) and four C (p110α, β, γ and δ) isoforms are known. Herein, we analyzed the expression of PI3-K isoforms in HIEC cells and determined their roles in cell survival, as well as in the β1 integrin/Fak/Src-mediated suppression of anoikis. We report that: (1) the predominant PI3-K complexes expressed by HIEC cells are p110α/p85β and p110α/p55γ; (2) the inhibition and/or siRNA-mediated expression silencing of p110α, but not that of p110β, γ or δ, results in Akt-1 down-activation and consequent apoptosis; (3) the expression silencing of p85β or p55γ, but not that of p85α, likewise induces Akt-1 down-activation and apoptosis; however, the impact of a loss of p55γ on both Akt-1 activation and cell survival is significantly greater than that from the loss of p85β; and (4) both the p110α/p85β and p110α/p55γ complexes are engaged by β1 integrin/Fak/Src signaling; however, the engagement of p110α/p85β is primarily Src-dependent, whereas that of p110α/p55γ is primarily Fak-dependent (but Src-independent). Hence, HIEC cells selectively express PI3-K isoform complexes, translating into distinct roles in Akt-1 activation and cell survival, as well as in a selective engagement by Fak and/or Src within the context of β1 integrin/Fak/Src-mediated suppression of anoikis

Diagnostic performance of FibroTest, SteatoTest and ActiTest in patients with NAFLD using the SAF score as histological reference

BACKGROUND: Blood tests of liver injury are less well validated in non‐alcoholic fatty liver disease (NAFLD) than in patients with chronic viral hepatitis. AIMS: To improve the validation of three blood tests used in NAFLD patients, FibroTest for fibrosis staging, SteatoTest for steatosis grading and ActiTest for inflammation activity grading. METHODS: We pre‐included new NAFLD patients with biopsy and blood tests from a single‐centre cohort (FibroFrance) and from the multicentre FLIP consortium. Contemporaneous biopsies were blindly assessed using the new steatosis, activity and fibrosis (SAF) score, which provides a reliable and reproducible diagnosis and grading/staging of the three elementary features of NAFLD (steatosis, inflammatory activity) and fibrosis with reduced interobserver variability. We used nonbinary‐ROC (NonBinAUROC) as the main endpoint to prevent spectrum effect and multiple testing. RESULTS: A total of 600 patients with reliable tests and biopsies were included. The mean NonBinAUROCs (95% CI) of tests were all significant (P < 0.0001): 0.878 (0.864–0.892) for FibroTest and fibrosis stages, 0.846 (0.830–0.862) for ActiTest and activity grades, and 0.822 (0.804–0.840) for SteatoTest and steatosis grades. FibroTest had a higher NonBinAUROC than BARD (0.836; 0.820–0.852; P = 0.0001), FIB4 (0.845; 0.829–0.861; P = 0.007) but not significantly different than the NAFLD score (0.866; 0.850–0.882; P = 0.26). FibroTest had a significant difference in median values between adjacent stage F2 and stage F1 contrarily to BARD, FIB4 and NAFLD scores (Bonferroni test P < 0.05). CONCLUSIONS: In patients with NAFLD, SteatoTest, ActiTest and FibroTest are non‐invasive tests that offer an alternative to biopsy, and they correlate with the simple grading/staging of the SAF scoring system across the three elementary features of NAFLD: steatosis, inflammatory activity and fibrosis