CyberKnife(® )radiosurgery in the treatment of complex skull base tumors: analysis of treatment planning parameters

BACKGROUND: Tumors of the skull base pose unique challenges to radiosurgical treatment because of their irregular shapes, proximity to critical structures and variable tumor volumes. In this study, we investigate whether acceptable treatment plans with excellent conformity and homogeneity can be generated for complex skull base tumors using the Cyberknife(® )radiosurgical system. METHODS: At Georgetown University Hospital from March 2002 through May 2005, the CyberKnife(® )was used to treat 80 patients with 82 base of skull lesions. Tumors were classified as simple or complex based on their proximity to adjacent critical structures. All planning and treatments were performed by the same radiosurgery team with the goal of minimizing dosage to adjacent critical structures and maximizing target coverage. Treatments were fractionated to allow for safer delivery of radiation to both large tumors and tumors in close proximity to critical structures. RESULTS: The CyberKnife(® )treatment planning system was capable of generating highly conformal and homogeneous plans for complex skull base tumors. The treatment planning parameters did not significantly vary between spherical and non-spherical target volumes. The treatment parameters obtained from the plans of the complex base of skull group, including new conformity index, homogeneity index and percentage tumor coverage, were not significantly different from those of the simple group. CONCLUSION: Our data indicate that CyberKnife(® )treatment plans with excellent homogeneity, conformity and percent target coverage can be obtained for complex skull base tumors. Longer follow-up will be required to determine the safety and efficacy of fractionated treatment of these lesions with this radiosurgical system

Treatment of malignant tumors of the skull base with multi-session radiosurgery

<p>Abstract</p> <p>Objective</p> <p>Malignant tumors that involve the skull base pose significant challenges to the clinician because of the proximity of critical neurovascular structures and limited effectiveness of surgical resection without major morbidity. The purpose of this study was to evaluate the efficacy and safety of multi-session radiosurgery in patients with malignancies of the skull base.</p> <p>Methods</p> <p>Clinical and radiographic data for 37 patients treated with image-guided, multi-session radiosurgery between January 2002 and December 2007 were reviewed retrospectively. Lesions were classified according to involvement with the bones of the base of the skull and proximity to the cranial nerves.</p> <p>Results</p> <p>Our cohort consisted of 37 patients. Six patients with follow-up periods less than four weeks were eliminated from statistical consideration, thus leaving the data from 31 patients to be analyzed. The median follow-up was 37 weeks. Ten patients (32%) were alive at the end of the follow-up period. At last follow-up, or the time of death from systemic disease, tumor regression or stable local disease was observed in 23 lesions, representing an overall tumor control rate of 74%. For the remainder of lesions, the median time to progression was 24 weeks. The median progression-free survival was 230 weeks. The median overall survival was 39 weeks. In the absence of tumor progression, there were no cranial nerve, brainstem or vascular complications referable specifically to CyberKnife^®radiosurgery.</p> <p>Conclusion</p> <p>Our experience suggests that multi-session radiosurgery for the treatment of malignant skull base tumors is comparable to other radiosurgical techniques in progression-free survival, local tumor control, and adverse effects.</p

Erythromycin improves gastric emptying half-time in adult cystic fibrosis patients with gastroparesis

AbstractBackgroundGastrointestinal manifestations are frequently encountered in cystic fibrosis patients. Gastroparesis evidenced by a variety of diagnostic methods has been described in patients with cystic fibrosis, predominantly in children and in individuals with advanced lung disease. The presence of gastroparesis in adult patients with different degrees of lung involvement and its response to the acute and chronic administration of macrolides have not been reported.MethodsUsing the University of Florida Cystic Fibrosis database we identified symptomatic patients who had gastroparesis confirmed by a prolonged half-time during gastric emptying scintigraphy.ResultsOf 86 cystic fibrosis patients, periodically followed in our institution, we found five who had classical symptoms and prolonged gastric emptying half-time. Age 25.2±8 years, 80% females, BMI 22±9 kg/m2, HbA1c 5.8±0.6 g/dl, FEV1 53.2±15% of predicted. Gastric emptying half-time was 191.4±91.4 min (range 100–300 min) and decreased to 12.2±6 min (range 5–20 min) after IV administration of erythromycin (p=0.043). Patients were followed up for 3±2.1 years. All patients but one, who was taking opiods, had good clinical response to PO macrolides.ConclusionsGastroparesis occurs in patients with cystic fibrosis, even in patients with relatively preserved lung function and in those without cystic-fibrosis related diabetes. Macrolides may be an effective therapy in cystic fibrosis patients with gastroparesis when administered acutely or chronically

Industrial constructions of publics and public knowledge: a qualitative investigation of practice in the UK chemicals industry

This is a post print version of the article. The official published version can be obtained from the link below - © 2007 by SAGE PublicationsWhile the rhetoric of public engagement is increasingly commonplace within industry, there has been little research that examines how lay knowledge is conceptualized and whether it is really used within companies. Using the chemicals sector as an example, this paper explores how companies conceive of publics and "public knowledge," and how this relates to modes of engagement/communication with them. Drawing on qualitative empirical research in four companies, we demonstrate that the public for industry are primarily conceived as "consumers" and "neighbours," having concerns that should be allayed rather than as groups with knowledge meriting engagement. We conclude by highlighting the dissonance between current advocacy of engagement and the discourses and practices prevalent within industry, and highlight the need for more realistic strategies for industry/public engagement.Funding was received from the ESRC Science in Society Programme

CyberKnife® enhanced conventionally fractionated chemoradiation for high grade glioma in close proximity to critical structures

<p>Abstract</p> <p>Introduction</p> <p>With conventional radiation technique alone, it is difficult to deliver radical treatment (≥ 60 Gy) to gliomas that are close to critical structures without incurring the risk of late radiation induced complications. Temozolomide-related improvements in high-grade glioma survival have placed a higher premium on optimal radiation therapy delivery. We investigated the safety and efficacy of utilizing highly conformal and precise CyberKnife radiotherapy to enhance conventional radiotherapy in the treatment of high grade glioma.</p> <p>Methods</p> <p>Between January 2002 and January 2009, 24 patients with good performance status and high-grade gliomas in close proximity to critical structures (i.e. eyes, optic nerves, optic chiasm and brainstem) were treated with the CyberKnife. All patients received conventional radiation therapy following tumor resection, with a median dose of 50 Gy (range: 40 - 50.4 Gy). Subsequently, an additional dose of 10 Gy was delivered in 5 successive 2 Gy daily fractions utilizing the CyberKnife^®image-guided radiosurgical system. The majority of patients (88%) received concurrent and/or adjuvant Temozolmide.</p> <p>Results</p> <p>During CyberKnife treatments, the mean number of radiation beams utilized was 173 and the mean number of verification images was 58. Among the 24 patients, the mean clinical treatment volume was 174 cc, the mean prescription isodose line was 73% and the mean percent target coverage was 94%. At a median follow-up of 23 months for the glioblastoma multiforme cohort, the median survival was 18 months and the two-year survival rate was 37%. At a median follow-up of 63 months for the anaplastic glioma cohort, the median survival has not been reached and the 4-year survival rate was 71%. There have been no severe late complications referable to this radiation regimen in these patients.</p> <p>Conclusion</p> <p>We utilized fractionated CyberKnife radiotherapy as an adjunct to conventional radiation to improve the targeting accuracy of high-grade glioma radiation treatment. This technique was safe, effective and allowed for optimal dose-delivery in our patients. The value of image-guided radiation therapy for the treatment of high-grade gliomas deserves further study.</p

Exploring the Partonic Structure of Hadrons through the Drell-Yan Process

The Drell-Yan process is a standard tool for probing the partonic structure of hadrons. Since the process proceeds through a quark-antiquark annihilation, Drell-Yan scattering possesses a unique ability to selectively probe sea distributions. This review examines the application of Drell-Yan scattering to elucidating the flavor asymmetry of the nucleon's sea and nuclear modifications to the sea quark distributions in unpolarized scattering. Polarized beams and targets add an exciting new dimension to Drell-Yan scattering. In particular, the two initial-state hadrons give Drell-Yan sensitivity to chirally-odd transversity distributions.Comment: 23 pages, 9 figures, to appear in J. Phys. G, resubmission corrects typographical error

Human PrimPol is a highly error-prone polymerase regulated by single-stranded DNA binding proteins

PrimPol is a recently identified polymerase involved in eukaryotic DNA damage tolerance, employed in both re-priming and translesion synthesis mechanisms to bypass nuclear and mitochondrial DNA lesions. In this report, we investigate how the enzymatic activities of human PrimPol are regulated. We show that, unlike other TLS polymerases, PrimPol is not stimulated by PCNA and does not interact with it in vivo. We identify that PrimPol interacts with both of the major single-strand binding proteins, RPA and mtSSB in vivo. Using NMR spectroscopy, we characterize the domains responsible for the PrimPol-RPA interaction, revealing that PrimPol binds directly to the N-terminal domain of RPA70. In contrast to the established role of SSBs in stimulating replicative polymerases, we find that SSBs significantly limit the primase and polymerase activities of PrimPol. To identify the requirement for this regulation, we employed two forward mutation assays to characterize PrimPol's replication fidelity. We find that PrimPol is a mutagenic polymerase, with a unique error specificity that is highly biased towards insertion-deletion errors. Given the error-prone disposition of PrimPol, we propose a mechanism whereby SSBs greatly restrict the contribution of this enzyme to DNA replication at stalled forks, thus reducing the mutagenic potential of PrimPol during genome replication

Restricting quark matter models by gravitational wave observation

We consider the possibilities for obtaining information about the equation of state for quark matter by using future direct observational data on gravitational waves. We study the nonradial oscillations of both fluid and spacetime modes of pure quark stars. If we observe the $f$ and the lowest $w_{\rm II}$ modes from quark stars, by using the simultaneously obtained radiation radius we can constrain the bag constant $B$ with reasonable accuracy, independently of the $s$ quark mass.Comment: To appear in Phys. Rev.

Two lectures on color superconductivity

The first lecture provides an introduction to the physics of color superconductivity in cold dense quark matter. The main color superconducting phases are briefly described and their properties are listed. The second lecture covers recent developments in studies of color superconducting phases in neutral and beta-equilibrated matter. The properties of gapless color superconducting phases are discussed.Comment: 56 pages, 9 figures. Minor corrections and references added. Lectures delivered at the IARD 2004 conference, Saas Fee, Switzerland, June 12 - 19, 2004, and at the Helmholtz International Summer School and Workshop on Hot points in Astrophysics and Cosmology, JINR, Dubna, Russia, August 2 - 13, 200