546 research outputs found
Ribonucleotide Reductase Inhibitors: A New Look at an Old Target for Radiosensitization
Ribonucleotide reductase (RR), the rate limiting enzyme in the synthesis and repair of DNA, has been studied as a target for inhibition in the treatment of cancer for many years. While some researchers have focused on RR inhibitors as chemotherapeutic agents, particularly in hematologic malignancies, some of the most promising data has been generated in the field of radiosensitization. Early pre-clinical studies demonstrated that the addition of the first of these drugs, hydroxyurea, to ionizing radiation (IR) produced a synergistic effect in vitro, leading to a large number of clinical studies in the 1970â1980s. These studies, mainly in cervical cancer, initially produced a great deal of interest, leading to the incorporation of hydroxyurea in the treatment protocols of many institutions. However, over time, the conclusions from these studies have been called into question and hydroxyurea has been replaced in the standard of care of cervical cancer. Over the last 10âyears, a number of well-done pre-clinical studies have greatly advanced our understanding of RR as a target. Those advances include the elucidation of the role of p53R2 and our understanding of the temporal relationship between the delivery of IR and the response of RR. At the same time, new inhibitors with increased potency and improved binding characteristics have been discovered, and pre-clinical and early clinical data look promising. Here we present a comprehensive review of the pre-clinical and clinical data in the field to date and provide some discussion of future areas of research
Current thinking and new paradigm for COPD
AbstractDuring the 2015 European Respiratory Society Congress, a symposium was held on âCurrent thinking and new paradigm for COPDâ. Through a combination of plenary lectures and interactive panel discussions, experts discussed the recent evidence for chronic obstructive pulmonary disease (COPD) treatment and how this evidence can be applied in clinical practice
MRI radiomic features are independently associated with overall survival in soft tissue sarcoma
Purpose: Soft tissue sarcomas (STS) represent a heterogeneous group of diseases, and selection of individualized treatments remains a challenge. The goal of this study was to determine whether radiomic features extracted from magnetic resonance (MR) images are independently associated with overall survival (OS) in STS.
Methods and Materials: This study analyzed 2 independent cohorts of adult patients with stage II-III STS treated at center 1 (N = 165) and center 2 (N = 61). Thirty radiomic features were extracted from pretreatment T1-weighted contrast-enhanced MR images. Prognostic models for OS were derived on the center 1 cohort and validated on the center 2 cohort. Clinical-only (C), radiomics-only (R), and clinical and radiomics (C+R) penalized Cox models were constructed. Model performance was assessed using Harrell\u27s concordance index.
Results: In the R model, tumor volume (hazard ratio [HR], 1.5) and 4 texture features (HR, 1.1-1.5) were selected. In the C+R model, both age (HR, 1.4) and grade (HR, 1.7) were selected along with 5 radiomic features. The adjusted c-indices of the 3 models ranged from 0.68 (C) to 0.74 (C+R) in the derivation cohort and 0.68 (R) to 0.78 (C+R) in the validation cohort. The radiomic features were independently associated with OS in the validation cohort after accounting for age and grade (HR, 2.4;
Conclusions: This study found that radiomic features extracted from MR images are independently associated with OS when accounting for age and tumor grade. The overall predictive performance of 3-year OS using a model based on clinical and radiomic features was replicated in an independent cohort. Optimal models using clinical and radiomic features could improve personalized selection of therapy in patients with STS
X-ray Thomson scattering absolute intensity from the f-sum rule in the imaginary-time domain
We evaluate the f-sum rule on the dynamic structure factor in the
imaginary-time domain as a formally exact and simulation-free means of
normalizing X-Ray Thomson Scattering (XRTS) spectra. This circumvents
error-prone real-time deconvolution of the source function and facilitates
calculating the static structure factor from the properly normalized
imaginary-time correlation function. We apply our technique to two distinct
sets of experimental data, finding that it is effective for both narrow and
broad x-ray sources. This approach could be readily adapted to other scattering
spectroscopies
Electronic Density Response of Warm Dense Matter
Matter at extreme temperatures and pressures -- commonly known as warm dense
matter (WDM) in the literature -- is ubiquitous throughout our Universe and
occurs in a number of astrophysical objects such as giant planet interiors and
brown dwarfs. Moreover, WDM is very important for technological applications
such as inertial confinement fusion, and is realized in the laboratory using
different techniques. A particularly important property for the understanding
of WDM is given by its electronic density response to an external perturbation.
Such response properties are routinely probed in x-ray Thomson scattering
(XRTS) experiments, and, in addition, are central for the theoretical
description of WDM. In this work, we give an overview of a number of recent
developments in this field. To this end, we summarize the relevant theoretical
background, covering the regime of linear-response theory as well as nonlinear
effects, the fully dynamic response and its static, time-independent limit, and
the connection between density response properties and imaginary-time
correlation functions (ITCF). In addition, we introduce the most important
numerical simulation techniques including ab initio path integral Monte Carlo
(PIMC) simulations and different thermal density functional theory (DFT)
approaches. From a practical perspective, we present a variety of simulation
results for different density response properties, covering the archetypal
model of the uniform electron gas and realistic WDM systems such as hydrogen.
Moreover, we show how the concept of ITCFs can be used to infer the temperature
from XRTS measurements of arbitrarily complex systems without the need for any
models or approximations. Finally, we outline a strategy for future
developments based on the close interplay between simulations and experiments
High-resolution ab initio three-dimensional X-ray diffraction microscopy
Coherent X-ray diffraction microscopy is a method of imaging non-periodic
isolated objects at resolutions only limited, in principle, by the largest
scattering angles recorded. We demonstrate X-ray diffraction imaging with high
resolution in all three dimensions, as determined by a quantitative analysis of
the reconstructed volume images. These images are retrieved from the 3D
diffraction data using no a priori knowledge about the shape or composition of
the object, which has never before been demonstrated on a non-periodic object.
We also construct 2D images of thick objects with infinite depth of focus
(without loss of transverse spatial resolution). These methods can be used to
image biological and materials science samples at high resolution using X-ray
undulator radiation, and establishes the techniques to be used in
atomic-resolution ultrafast imaging at X-ray free-electron laser sources.Comment: 22 pages, 11 figures, submitte
Gravity-driven Lyman-alpha blobs from cold streams into galaxies
We use high-resolution cosmological hydrodynamical AMR simulations to predict
the characteristics of La emission from the cold gas streams that fed galaxies
in massive haloes at high redshift. The La luminosity in our simulations is
powered by the release of gravitational energy as gas flows from the
intergalactic medium into the halo potential wells. The UV background
contributes only <20% to the gas heating. The La emissivity is due primarily to
electron-impact excitation cooling radiation in gas ~2x10^4K. We calculate the
La emissivities assuming collisional ionisation equilibrium (CIE) at all gas
temperatures. The simulated streams are self-shielded against the UV
background, so photoionisation and recombination contribute negligibly to the
La line formation. We produce theoretical maps of the La surface brightnesses,
assuming that ~85% of the La photons are directly observable. We find that
typical haloes of mass Mv~10^12-13 Msun at z~3 emit as La blobs (LABs) with
luminosities 10^43-44 erg/s. Most of the La comes from the extended narrow,
partly clumpy, inflowing, cold streams that feed the growing galaxies. The
predicted LAB morphology is therefore irregular, with dense clumps and
elongated extensions. The linewidth is expected to range from 10^2 to more than
10^3 km/s with a large variance. The typical La surface brightness profile is
proportional to r^-1.2 where r is the distance from the halo centre. Our
simulated LABs are similar in luminosity, morphology and extent to the observed
LABs, with distinct kinematic features. The predicted La luminosity function is
consistent with observations, and the predicted areas and linewidths roughly
recover the observed scaling relations. This mechanism for producing LABs
appears inevitable in many high-z galaxies. Some of the LABs may thus be
regarded as direct detections of the cold streams that drove galaxy evolution
at high z.Comment: 21 pages, 20 figures, final version accepted for publication in MNRA
ACR Appropriateness CriteriaÂŽ Non-Spine Bone Metastases
Bone metastases are a common clinical problem, affecting many types of cancer patients. The presence of tumor in bone can cause significant morbidity including pain, neurological dysfunction, hypercalcemia, and pathological fracture leading to functional loss. The optimal treatment of a patient with bone metastases depends on many factors, including evaluation of the patient's goals of care, performance status, mechanical stability of the affected bone, life expectancy, and overall extent of disease. Treatment options may include radiotherapy, systemic therapies, surgical stabilization, medical pain management, and radiopharmaceuticals. Ideal management of bone metastases requires a coordinated multidisciplinary approach among diagnostic radiologists, radiation oncologists, medical oncologists, orthopedic surgeons, pain specialists, physiatrists, and palliative care specialists. The American College of Radiology Appropriateness Criteria? are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guidelines development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140118/1/jpm.2014.9395.pd
Studies of the dose-effect relation
Dose-effect relations and, specifically, cell survival curves are surveyed with emphasis on the interplay of the random factors â biological variability, stochastic reaction of the cell, and the statistics of energy deposition âthat co-determine their shape. The global parameters mean inactivation dose, , and coefficient of variance, V, represent this interplay better than conventional parameters. Mechanisms such as lesion interaction, misrepair, repair overload, or repair depletion have been invoked to explain sigmoid dose dependencies, but these notions are partly synonymous and are largely undistinguishable on the basis of observed dose dependencies. All dose dependencies reflect, to varying degree, the microdosimetric fluctuations of energy deposition, and these have certain implications, e.g. the linearity of the dose dependence at small doses, that apply regardless of unresolved molecular mechanisms of cellular radiation action
Standalone vertex ďŹnding in the ATLAS muon spectrometer
A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at âs = 7 TeV collected with the ATLAS detector at the LHC during 2011
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