Stereotactic Body Radiotherapy (SBRT) for Oligometastatic Lung Nodules: A Single Institution Series

Aim: Lung metastases from an extra-pulmonary origin occasionally present with a limited metastatic disease burden. In cases where metastatectomy is not feasible, stereotactic body radiation therapy (SBRT) represents a non-invasive, efficacious option. We report the outcomes of patients treated with lung SBRT in cases of limited metastatic disease.Methods: We retrospectively reviewed outcomes in 44 patients with 50 lung nodules from various extra-pulmonary malignancies treated with SBRT. Fifty percent of the patients were male and median age was 64. The median number of nodules was 1 and 90% of patients had oligometastatic disease. Thirty-four percent of patients had extra-thoracic disease.Results: Fifty lung nodules were treated with SBRT in 44 patients. Median dose was 48 Gy in 5 fractions with a median biological effective dose (BED) of 100 Gy10. Follow-up imaging was available for review in 96% of nodules. Median follow-up was 17.5 months. One year local control was 82%. BED >72 Gy10 predicted improved local control (90 vs. 57% at 1 year). One year overall survival following SBRT was 66%. There was no difference in overall survival if patients had extra-thoracic disease.Conclusion: Lung SBRT is a safe, effective tool for treatment of limited lung metastases. Dose selection remains important for local control

Continuous-variable quantum teleportation of entanglement

Entangled coherent states can be used to determine the entanglement fidelity for a device that is designed to teleport coherent states. This entanglement fidelity is universal, in that the calculation is independent of the use of entangled coherent states and applies generally to the teleportation of entanglement using coherent states. The average fidelity is shown to be a poor indicator of the capability of teleporting entanglement; i.e., very high average fidelity for the quantum teleportation apparatus can still result in low entanglement fidelity for one mode of the two-mode entangled coherent state.Comment: 5 pages, 1 figure, published versio

Optimum detection for extracting maximum information from symmetric qubit sets

We demonstrate a class of optimum detection strategies for extracting the maximum information from sets of equiprobable real symmetric qubit states of a single photon. These optimum strategies have been predicted by Sasaki et al. [Phys. Rev. A{\bf 59}, 3325 (1999)]. The peculiar aspect is that the detections with at least three outputs suffice for optimum extraction of information regardless of the number of signal elements. The cases of ternary (or trine), quinary, and septenary polarization signals are studied where a standard von Neumann detection (a projection onto a binary orthogonal basis) fails to access the maximum information. Our experiments demonstrate that it is possible with present technologies to attain about 96% of the theoretical limit.Comment: 10 pages, 11 figures, to be submitted to Phys. Rev. A Converted to REVTeX4 format, and a few other minor modifications according to the comments from PRA referre

The Great Slump : Mrk 926 reveals discrete and varying Balmer line satellite components during a drastic phase of decline

This work has been supported by the DFG grants KO857/35-1 and CH71/34-3. K. H. acknowledges support from STFC grant ST/M001296/1. D. C. acknowledges support from ISF grant 2398/19.Aims. Mrk 926 is known to be a highly variable active galactic nucleus. Furthermore, it is known to show very broad line profiles. We intended to study the continuum and line profile variations of this object with high temporal resolution in order to determine its broad-line region structure and to derive its black hole mass. Methods. We carried out a high-cadence spectroscopic variability campaign of Mrk 926 with the 10m HET telescope, aided by photometric V-band data taken with the C18 telescope at the Wise Observatory, over a period of about five months. We extracted spectroscopic continuum and line light curves, and computed cross-correlation functions (CCFs) as well as velocity-resolved CCFs with respect to the combined spectroscopic and photometric V-band light curve. Results. The continuum luminosity of Mrk 926 showed a drastic decrease during our campaign. The luminosity dropped to less than 50% of its original luminosity within only 2.5 months. Furthermore, the spectra of Mrk 926 show complex and very broad Balmer line profiles, including outer Balmer satellites ranging from ±5000 to ±13 000 km s−1. The integrated Hα, Hβ, and He Iλ5876 line light curves are delayed relative to the continuum light curve. The Hα and Hβ lines show two velocity-delay structures in the central part of their line profile (within ±5000 km s−1), at ∼10 and ∼57 light-days and at ∼5 and ∼48 light-days, respectively. These structures might be interpreted as the upper and lower halves of an ellipse in the velocity-delay plane, which might be the signature of a line-emitting ring, inclined by ∼50° to the line of sight and orbiting the black hole at radii, R, of 33.5 and 26.5 light-days. We determined continuum luminosities, log(λ Lλ/erg s−1), of 43.68–44.13, which are in good agreement with the established RBLR − LAGN relation. Adopting delays of 33.5 and 26.5 days for Hα and Hβ, respectively, we derive a black hole mass of (1.1 ± 0.2)×108 M⊙; this indicates a low Eddington ratio, which decreased from 8 to 3 percent during our campaign. The Balmer satellite components show a higher correlation coefficient with respect to the continuum than the central line profile, and their response to the continuum variations is on the order of only 3 − 5 days. We attribute this to the central line segment and the Balmer satellites having different, spatially distinct regions of origin.Publisher PDFPeer reviewe

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease

Design and Rationale of the Fontan Udenafil Exercise Longitudinal (FUEL) Trial

The Fontan operation creates a circulation characterized by elevated central venous pressure and low cardiac output. Over time, these characteristics result in a predictable and persistent decline in exercise performance that is associated with an increase in morbidity and mortality. A medical therapy that targets the abnormalities of the Fontan circulation might, therefore, be associated with improved outcomes. Udenafil, a phosphodiesterase type 5 inhibitor, has undergone phase I/II testing in adolescents who have had the Fontan operation and has been shown to be safe and well tolerated in the short-term. However, there are no data regarding the long-term efficacy of udenafil in this population. The Fontan Udenafil Exercise Longitudinal (FUEL) Trial is a randomized, double blind, placebo controlled phase III clinical trial being conducted by the Pediatric Heart Network in collaboration with Mezzion Pharma Co., Ltd. This trial is designed to test the hypothesis that treatment with udenafil will lead to an improvement in exercise capacity in adolescents who have undergone the Fontan operation. A safety extension trial, the FUEL Open-Label Extension Trial (FUEL OLE), offers the opportunity for all FUEL subjects to obtain open-label udenafil for an additional 12 months following completion of FUEL, and evaluates the long-term safety and tolerability of this medication. This manuscript describes the rationale and study design for FUEL and FUEL OLE. Together, these trials provide an opportunity to better understand the role of medical management in the care of those who have undergone the Fontan operation

Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrating Lymphocytes

The immune system can mount T cell responses against tumors; however, the antigen specificities of tumor-infiltrating lymphocytes (TILs) are not well understood. We used yeast-display libraries of peptide-human leukocyte antigen (pHLA) to screen for antigens of “orphan” T cell receptors (TCRs) expressed on TILs from human colorectal adenocarcinoma. Four TIL-derived TCRs exhibited strong selection for peptides presented in a highly diverse pHLA-A∗02:01 library. Three of the TIL TCRs were specific for non-mutated self-antigens, two of which were present in separate patient tumors, and shared specificity for a non-mutated self-antigen derived from U2AF2. These results show that the exposed recognition surface of MHC-bound peptides accessible to the TCR contains sufficient structural information to enable the reconstruction of sequences of peptide targets for pathogenic TCRs of unknown specificity. This finding underscores the surprising specificity of TCRs for their cognate antigens and enables the facile identification of tumor antigens through unbiased screening