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Search Results: 1 - 10 of 169259 matches for " Laurence E. Court "
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A Hybrid Algorithm to Address Ambiguities in Deformable Image Registration for Radiation Therapy  [PDF]
Song Gao, Yongbin Zhang, Jinzhong Yang, Catherine H. Wang, Lifei Zhang, Laurence E. Court, Lei Dong
International Journal of Medical Physics,Clinical Engineering and Radiation Oncology (IJMPCERO) , 2012, DOI: 10.4236/ijmpcero.2012.12007
Abstract: We proposed the use of a hybrid deformable image registration approach that combines compact-support radial basis functions (CSRBF) spline registration with intensity-based image registration. The proposed method first uses the pre-viously developed image intensity-based method to achieve voxel-by-voxel correspondences over the entire image re-gion. Next, for those areas of inaccurate registration, a sparse set of landmark correspondences was defined for local deformable image registration using a multi-step CSRBF approach. This hybrid registration takes advantage of both intensity-based method for automatic processing of entire images and the CSRBF spline method for fine adjustment over specific regions. The goal of using this hybrid registration is to locally control the quality of registration results in specific regions of interest with minimal human intervention. The major applications of this approach in radiation ther-apy are for the corrections of registration failures caused by various imaging artifacts resulting in, low image contrast, and non-correspondence situations where an object may not be imaged in both target and source images. Both synthetic and real patient data have been used to evaluate this hybrid method. We used contours mapping to validate the accuracy of this method on real patient image. Our studies demonstrated that this hybrid method could improve overall registra-tion accuracy with moderate overhead. In addition, we have also shown that the multi-step CSRBF registration proved to be more effective in handling large deformations while maintaining the smoothness of the transformation than origi-nal CSRBF.
Motion of the Esophagus Due to Cardiac Motion
Jacob Palmer, Jinzhong Yang, Tinsu Pan, Laurence E. Court
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089126
Abstract: When imaging studies (e.g. CT) are used to quantify morphological changes in an anatomical structure, it is necessary to understand the extent and source of motion which can give imaging artifacts (e.g. blurring or local distortion). The objective of this study was to assess the magnitude of esophageal motion due to cardiac motion. We used retrospective electrocardiogram-gated contrast-enhanced computed tomography angiography images for this study. The anatomic region from the carina to the bottom of the heart was taken at deep-inspiration breath hold with the patients' arms raised above their shoulders, in a position similar to that used for radiation therapy. The esophagus was delineated on the diastolic phase of cardiac motion, and deformable registration was used to sequentially deform the images in nearest-neighbor phases among the 10 cardiac phases, starting from the diastolic phase. Using the 10 deformation fields generated from the deformable registration, the magnitude of the extreme displacements was then calculated for each voxel, and the mean and maximum displacement was calculated for each computed tomography slice for each patient. The average maximum esophageal displacement due to cardiac motion for all patients was 5.8 mm (standard deviation: 1.6 mm, maximum: 10.0 mm) in the transverse direction. For 21 of 26 patients, the largest esophageal motion was found in the inferior region of the heart; for the other patients, esophageal motion was approximately independent of superior-inferior position. The esophagus motion was larger at cardiac phases where the electrocardiogram R-wave occurs. In conclusion, the magnitude of esophageal motion near the heart due to cardiac motion is similar to that due to other sources of motion, including respiratory motion and intra-fraction motion. A larger cardiac motion will result into larger esophagus motion in a cardiac cycle.
Assessment of shoulder position variation and its impact on IMRT and VMAT doses for head and neck cancer
Emily Neubauer, Lei Dong, David S Followill, Adam S Garden, Laurence E Court, R Allen White, Stephen F Kry
Radiation Oncology , 2012, DOI: 10.1186/1748-717x-7-19
Abstract: The extent of shoulder displacements relative to isocenter was assessed for 10 patients in 5-point thermoplastic masks using image registration and daily CT-on-rails scans. Dosimetric effects on IMRT and VMAT plans were evaluated in Pinnacle based on simulation CTs modified to represent shoulder shifts between 3 and 15 mm in the superior-inferior, anterior-posterior, and right-left directions. The impact of clinically observed shoulder shifts on the low-neck dose distributions was examined.Shoulder motion was 2-5 mm in each direction on average but reached 20 mm. Superior shifts resulted in coverage loss, whereas inferior shifts increased the dose to the brachial plexus. These findings were generally consistent for both IMRT and VMAT plans. Over a course of observed shifts, the dose to 99% of the CTV decreased by up to 101 cGy, and the brachial plexus dose increased by up to 72 cGy.he position of the shoulder affects target coverage and critical structure dose, and may therefore be a concern during the setup of head and neck patients, particularly those with low neck primary disease.Patient positioning and immobilization are essential in radiation therapy. Although extensive effort is spent in positioning and immobilizing the patient, the focus is on target alignment; the position of the body away from isocenter is often ignored. Nevertheless, such distant body positions may affect the delivered dose distribution.For head and neck radiotherapy or other treatments involving the low neck, the position of the shoulders is of particular concern. In many cases, 5-point masks that cover the head and shoulders are used to immobilize the patient. Still, without any displacement of isocenter, the shoulders can be in a position different from the one in the treatment plan. Most IMRT treatments are delivered in a co-planar beam arrangement, so if the patient's shoulders move superior relative to the planning setup the shoulders could intercept the radiation beams and cause an
Evolution of a Major Drug Metabolizing Enzyme Defect in the Domestic Cat and Other Felidae: Phylogenetic Timing and the Role of Hypercarnivory
Binu Shrestha,J. Michael Reed,Philip T. Starks,Gretchen E. Kaufman,Jared V. Goldstone,Melody E. Roelke,Stephen J. O'Brien,Klaus-Peter Koepfli,Laurence G. Frank,Michael H. Court
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018046
Abstract: The domestic cat (Felis catus) shows remarkable sensitivity to the adverse effects of phenolic drugs, including acetaminophen and aspirin, as well as structurally-related toxicants found in the diet and environment. This idiosyncrasy results from pseudogenization of the gene encoding UDP-glucuronosyltransferase (UGT) 1A6, the major species-conserved phenol detoxification enzyme. Here, we established the phylogenetic timing of disruptive UGT1A6 mutations and explored the hypothesis that gene inactivation in cats was enabled by minimal exposure to plant-derived toxicants. Fixation of the UGT1A6 pseudogene was estimated to have occurred between 35 and 11 million years ago with all extant Felidae having dysfunctional UGT1A6. Out of 22 additional taxa sampled, representative of most Carnivora families, only brown hyena (Parahyaena brunnea) and northern elephant seal (Mirounga angustirostris) showed inactivating UGT1A6 mutations. A comprehensive literature review of the natural diet of the sampled taxa indicated that all species with defective UGT1A6 were hypercarnivores (>70% dietary animal matter). Furthermore those species with UGT1A6 defects showed evidence for reduced amino acid constraint (increased dN/dS ratios approaching the neutral selection value of 1.0) as compared with species with intact UGT1A6. In contrast, there was no evidence for reduced amino acid constraint for these same species within UGT1A1, the gene encoding the enzyme responsible for detoxification of endogenously generated bilirubin. Our results provide the first evidence suggesting that diet may have played a permissive role in the devolution of a mammalian drug metabolizing enzyme. Further work is needed to establish whether these preliminary findings can be generalized to all Carnivora.
Evaluation of Hyperpolarized [1-13C]-Pyruvate by Magnetic Resonance to Detect Ionizing Radiation Effects in Real Time
Vlad C. Sandulache, Yunyun Chen, Jaehyuk Lee, Ashley Rubinstein, Marc S. Ramirez, Heath D. Skinner, Christopher M. Walker, Michelle D. Williams, Ramesh Tailor, Laurence E. Court, James A. Bankson, Stephen Y. Lai
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0087031
Abstract: Ionizing radiation (IR) cytotoxicity is primarily mediated through reactive oxygen species (ROS). Since tumor cells neutralize ROS by utilizing reducing equivalents, we hypothesized that measurements of reducing potential using real-time hyperpolarized (HP) magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) can serve as a surrogate marker of IR induced ROS. This hypothesis was tested in a pre-clinical model of anaplastic thyroid carcinoma (ATC), an aggressive head and neck malignancy. Human ATC cell lines were utilized to test IR effects on ROS and reducing potential in vitro and [1-13C] pyruvate HP-MRS/MRSI imaging of ATC orthotopic xenografts was used to study in vivo effects of IR. IR increased ATC intra-cellular ROS levels resulting in a corresponding decrease in reducing equivalent levels. Exogenous manipulation of cellular ROS and reducing equivalent levels altered ATC radiosensitivity in a predictable manner. Irradiation of ATC xenografts resulted in an acute drop in reducing potential measured using HP-MRS, reflecting the shunting of reducing equivalents towards ROS neutralization. Residual tumor tissue post irradiation demonstrated heterogeneous viability. We have adapted HP-MRS/MRSI to non-invasively measure IR mediated changes in tumor reducing potential in real time. Continued development of this technology could facilitate the development of an adaptive clinical algorithm based on real-time adjustments in IR dose and dose mapping.
Clinical review: Myocardial depression in sepsis and septic shock
Olivier Court, Aseem Kumar, Joseph E Parrillo, Anand Kumar
Critical Care , 2002, DOI: 10.1186/cc1822
Abstract: Sepsis and septic shock have been recognized as an increasingly serious clinical problem, accounting for substantial morbidity and mortality. The past four decades have seen the age-adjusted mortality of sepsis increase from 0.5 to 7 per 100,000 episodes despite major advances in the understanding of its pathophysiology [1]. The incidence of severe sepsis in the United States today is estimated at 750,000 cases per year, resulting in 215,000 deaths annually [2]. The majority of these sepsis patients die of refractory hypotension and of cardiovascular collapse.Sepsis has been defined as the systemic inflammatory response to infection [3]. An infectious stimulus (e.g. endo-toxin or another microbiologic element) induces the release of local and systemic inflammatory mediators, especially tumor necrosis factor alpha (TNF-α) and IL-1β, from monocytes/macrophages and other cells [4]. These cytokines stimulate polymorphonuclear leukocytes, macrophages and endothelial cells to release a number of downstream inflammatory mediators, including platelet activating factor and nitric oxide (NO), further amplifying the inflammatory response. Several anti-inflammatory mediators are also released as part of this amplification cascade; namely, IL-10, transforming growth factor beta and IL-1 receptor antagonist. The relative contribution of these cytokines will determine the severity of the septic episode. If the inflammatory reaction is particularly intense, homeostasis of the cardiovascular system will be disrupted, leading to septic shock. One of the manifestations of cardiovascular dysfunction in septic shock is myocardial depression.The present article reviews the clinical manifestations of cardiac dysfunction in sepsis, from the point of view of both the right and left ventricle, as well as cardiovascular prognostic factors in sepsis and septic shock. We will also review the potential pathophysiologic processes responsible for myocardial depression in sepsis, from the perspecti
Synaptic sampling: A connection between PSP variability and uncertainty explains neurophysiological observations
Laurence Aitchison,Peter E. Latham
Quantitative Biology , 2015,
Abstract: When an action potential is transmitted to a postsynaptic neuron, a small change in the postsynaptic neuron's membrane potential occurs. These small changes, known as a postsynaptic potentials (PSPs), are highly variable, and current models assume that this variability is corrupting noise. In contrast, we show that this variability could have an important computational role: representing a synapse's uncertainty about the optimal synaptic weight (i.e. the best possible setting for the synaptic weight). We show that this link between uncertainty and variability, that we call synaptic sampling, leads to more accurate estimates of the uncertainty in task relevant quantities, leading to more effective decision making. Synaptic sampling makes four predictions, all of which have some experimental support. First the more variable a synapse is, the more it should change during LTP protocols. Second, variability should increase as the presynpatic firing rate falls. Third, PSP variance should be proportional to PSP mean. Fourth, variability should increase with distance from the cell soma. We provide support for the first two predictions by reanalysing existing datasets, and we find preexisting data in support of the last two predictions.
Bayesian synaptic plasticity makes predictions about plasticity experiments in vivo
Laurence Aitchison,Peter E. Latham
Quantitative Biology , 2014,
Abstract: Humans and other animals learn by updating synaptic weights in the brain. Rapid learning allows animals to adapt quickly to changes in their environment, giving them a large selective advantage. As brains have been evolving for several hundred million years, we might expect biological learning rules to be close to optimal, by exploiting all locally available information in order to learn as rapidly as possible. However, no previously proposed learning rules are optimal in this sense. We therefore use Bayes theorem to derive optimal learning rules for supervised, unsupervised and reinforcement learning. As expected, these rules prove to be significantly more effective than the best classical learning rules. Our learning rules make two predictions about the results of plasticity experiments in active networks. First, we predict that learning rates should vary across time, increasing when fewer inputs are active. Second, we predict that learning rates should vary across synapses, being higher for synapses whose presynaptic cells have a lower average firing rate. Finally, our methods are extremely flexible, allowing the derivation of optimal learning rules based solely on the information that is assumed, or known, to be available to the synapse. This flexibility should allow for the derivation of optimal learning rules for progressively more complex and realistic synaptic and neural models --- allowing us to connect theory with complex biological reality.
Pointing and asking: A note on deixis in Mentu Land Dayak
Christopher Court
Bijdragen tot de Taal-, Land- en Volkenkunde , 1967,
The kinship terms of reference of the Mentu Land Dayaks, in phonemic notation
C. Court
Bijdragen tot de Taal-, Land- en Volkenkunde , 1970,
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