bluuebunny/crossref_metadata_2025_split huggingface dataset:
TH‐C‐BRC‐09: Tracking Moving Tumors with a Scanned Carbon Beam: Robustness to Changing Target Motion Characteristics and Tracking Uncertainties
Authors: Eley J , Lüchtenborg R , Richter D , Durante M , Bert C 
Published: November 2011

Purpose: Beam tracking of moving tumors with scanned carbon ion radiotherapy achieves uniform target dose by adapting carbon pencil beams to follow moving tissues using real‐time lateral magnetic deflection and range modulation. The purpose of the current study was to establish the robustness of target dose coverage that can be achieved in the presence of changing target motion characteristics and uncertainties in the motion tracking system. Methods: A 4D research treatment planning system code for ion therapy was extended to compute the resulting target dose coverage when various random and systematic uncertainties were introduced to ideal tracking dose simulations. Treatment plans were prepared using the in‐ house code for a hypothetical sphere target volume with sinusoidal motion in a water phantom. Uncertainties were simulated by shifting pencil beam coordinates and modifying target motion signals. To simulate imperfect tracking, we considered variations to the following: (1) respiratory period, (2) starting respiratory phase, (3) target position drift, (4) random tracking offsets, (5) range tracking wedge acceleration, and (6) external respiratory motion signal phase delay. We also considered imperfect tracking with combinations of varying target motion characteristics and tracking uncertainties. A total of 13713 dose distributions were computed. For all cases, mean, standard deviation, minimum, and maximum of target dose were analyzed. Results: For perfect tracking of the moving sphere, mean and standard deviation of target dose were 98.2 and 0.8 % of the prescription dose, respectively. Of the variations considered, systematic drifts of target position of up to 5 mm had the most significant effect on target coverage ((6.6 ± 20.3) % decrease), and range tracking wedge accelerations above 1.0 g had the least effect on target dose ((0.0 ±1.1) %). Conclusions: The results provide insight into beam tracking precision requirements and the need to monitor and mitigate changes in patient motion.Work supported by research grant from the Deutscher Akademischer Austausch Dienst, Bonn, Germany.
TH‐C‐214‐02: MRI for Radiation Treatment Planning
Authors: Cao Y 
Published: November 2011

The advantages of MRI for radiation treatment planning, such as soft tissue discrimination and multi‐contrast capability, are well recognized. It is routine practice to use MRI for tumor target definition of brain tumors, with or without a corresponding CT scan. Superior soft tissue visualization has led to the emergence of MRI‐guided brachytherapy for cervical and prostate cancers. In addition, functional and physiological MR imaging can aid assessment of tumor and normal tissue response for adaptive RT as well as pre‐treatment boost target definition. Several past limitations of MRI have hindered its wide application in radiation therapy, including concerns about geometric accuracy, high resolution volumetric acquisition, acquisition speed, motion‐sensitivity, small bore size, and lack of definition of bony structures and electron density. Many of these shortcomings have been overcome or will be overcome by new MRI technologies.This lecture will provide an overview on new MRI technologies and their application for radiation treatment planning. The limitations of these techniques will also be discussed.Learning objectives:1. Understand new MRI technologies that are relevant to radiation treatment planning;2. Understand the influence of imaging parameters on image quality and contrast.3. Understand clinical applications and limitations.
TH‐C‐214‐04: This House Believes That the Use of Functional Imaging for Treatment Planning of Head and Neck Tumors Needs to Be Carefully Considered
Authors: Gregoire V , Geets X , Lee J 
Published: November 2011

Biological image‐guided radiotherapy aims at specifically irradiating biologically relevant sub‐volumes within the tumor, as determined for instance by PET imaging. This approach requires that PET imaging be sensitive and specific enough to image various biological pathways of interest, e.g. tumor metabolism, proliferation and hypoxia. In this framework, the use of PET imaging for adaptive radiotherapy needs to be evaluated in term of accuracy and added value in comparison with standard procedures.It first requires the optimization of the PET image quality during the acquisition and the reconstruction, to try to improve the spatial resolution, the level of noise and the contrast, that are typical features of PET imaging. Thereafter, it requires robust and validated tools for accurate segmentation of the regions of interest. The blur effect related to the poor spatial resolution of the camera and the high level of noise severely corrupt the images, and consequently interfere with the tumor segmentation. The use of “image restoration tools” for deblurring and denoising PET images before any segmentation represents an elegant way to improve image quality. Associated with a gradient‐based segmentation technique, this approach has been shown to outperform the conventional threshold‐based methods. However, even when using optimal procedures for image acquisition, reconstruction and segmentation, one has to keep in mind that there will always exist some discrepancies between the information from a PET image and the underlying microscopic reality. Such differences may be of critical importance when considering giving boost doses to small and highly active PET regions. This issue should be carefully looked at before applying on a clinical routine basis sub‐volume segmentation with some form of dose‐ painting. Last outcome studies should be ideally performed as an ultimate endpoint to ascertain the clinical benefit of the use of functional imaging in routine practice.
TH‐C‐110‐01: Current and Future Clinical Applications of Quantitative CT
Authors: Boone J 
Published: November 2011

Computed tomography (CT) is the only current clinical modality which is fundamentally quantitative. While other modalities can in many cases be calibrated to deliver a linear response, the normalization with respect to water of the Hounsfield Unit is the standard in clinical CT imaging. Furthermore, gray scale in CT is linearly related to the concentration of injected iodine contrast agent, which is useful for CT‐based organ function assessment. In addition to a quantitative gray scale, CT is a robust quantitative tool in regards to distances in three dimensions. Because of the straight‐line assumption used in x‐ray imaging including CT, in the absence of patient motion, distances, areas, and volumes can in principle be measured with accuracy. Modern multi‐slice CT scanners allow thin section imaging, and thus the volume data sets produce near‐isotropic spatial resolution. These properties of CT have led to a number of quantitative applications: CT has been used to quantify bone mineral density for almost 30 years, and this tool has proven useful in quantitative risk assessment in patients with osteoporosis. Researchers in pulmonary function have used CT to measure changes in the lung parenchyma over time. Organ perfusion measurements are commonly performed in the head for the evaluation in patients suspected of stroke or vasospasm, and abdominal organ perfusion measurements have also been studied in cancer patients. Computed tomography remains a primary tool for the assessment of tumor size, in monitoring the response to chemotherapy in cancer patients. While linear dimension assessment is a RECIST criterion, there has been a recent move towards tumor volume assessment to better capture tumor response. After a brief review of the fundamental properties of CT pertinent to its quantitative performance, a number of clinically used quantitative CT applications will be discussed. Issues of accuracy and precision will also be addressed. A discussion of the expansion of CT as a quantitative tool in other clinical applications will conclude this presentation.Learning Objectives:1. The physical basis for quantitative CT will be described2. Current applications of quantitative CT will be outlined3. The precision and accuracy of volume and HU metrics will be described4. A list of potential future applications in quantitative CT will be presented.
TH‐C‐301‐05: Practical Medical Physics Session
Authors: Lewis D 
Published: November 2011

Among dosimetry tools radiographic films have the unique advantage of providing the capability for dose measurements at very high spatial resolution; and between dosimetry films, radiochromic films are particularly advantageous for their versatility. Thus radiochromic films can be handled in light, easily cut to any size and shape, bent to conform to curved surfaces and immersed in water. All these attributes are embodied in the GAFCHROMIC® family of dosimetry films as used in a broad spectrum of medical applications including external beam therapy, brachytherapy, machine quality assurance and radiology.Current trends in external beam therapy are towards ever more precise treatment protocols with less dose fractionation. Both these factors increase the importance of pre‐treatment validation of treatment plans and place a high and increasing value on those measurement techniques that are able to deliver the ability for excellent resolution in the spatial frequency and dose domains.The talk will show, by example, the range of medical applications covered by radiochromic dosimetry films. It will demonstrate how the attributes of these films are being used to advantage in a full spectrum of radiotherapy applications. The presentation will finish by introducing another advantage of radiochromic film and showing the benefit of multi‐channel film dosimetry as a means for improving the integrity of dose measurements by separating dose‐independent artifacts and removing them from the response measurement.
Downregulation of Mitogen-Activated Protein Kinase 1 of Leishmania donovani Field Isolates Is Associated with Antimony Resistance
Authors: Ashutosh  , Garg Mansi , Sundar Shyam , Duncan Robert , Nakhasi Hira L. , Goyal Neena 
Published: November 2011

ABSTRACT

Emergence of resistance to pentavalent antimonials has become a severe obstacle in the treatment of visceral leishmaniasis (VL) on the Indian subcontinent. The mechanisms operating in laboratory-generated strains are somewhat known, but the determinants of clinical antimony resistance are not well understood. By utilizing a DNA microarray expression profiling approach, we identified a gene encoding mitogen-activated protein kinase 1 (MAPK1) for the kinetoplast protozoan
Leishmania donovani
(LdMAPK1) that was consistently downregulated in antimony-resistant field isolates. The expression level of the gene was validated by real-time PCR. Furthermore, decreased expression of LdMAPK1 was also confirmed at the protein level in resistant isolates. Primary structure analysis of LdMAPK1 revealed the presence of all of the characteristic features of MAPK1. When expressed in
Escherichia coli
, the recombinant enzyme showed kinase activity with myelin basic protein as the substrate and was inhibited by staurosporine. Interestingly, overexpression of this gene in a drug-sensitive laboratory strain and a resistant field isolate resulted in increased the sensitivity of the transfectants to potassium antimony tartrate, suggesting that it has a role in antimony resistance. Our results demonstrate that downregulation of LdMAPK1 may be in part correlated with antimony drug resistance in Indian VL isolates.
Low Prevalence of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Isolates among Connecticut Veterans
Authors: Fink Susan L. , Martinello Richard A. , Campbell Sheldon M. , Murray Thomas S. 
Published: November 2011

ABSTRACT

The Etest glycopeptide resistance detection identified two potential heterogeneous vancomycin-intermediate
Staphylococcus aureus
(hVISA) isolates from a screen of 288 methicillin-resistant
Staphylococcus aureus
(MRSA) isolates from patients at a Connecticut Veterans Hospital. However, the two isolates did not meet the criteria for hVISA by the population analysis profile-area under the curve analysis, arguing against routine screening for hVISA in this low prevalence population.
Simulated Antibiotic Exposures in an
In Vitro
Hollow-Fiber Infection Model Influence Toxin Gene Expression and Production in Community-Associated Methicillin-Resistant Staphylococcus aureus Strain MW2
Authors: Pichereau Solen , Pantrangi Madhulatha , Couet William , Badiou Cedric , Lina Gerard , Shukla Sanjay K. , Rose Warren E. 
Published: November 2011

ABSTRACT

Community-associated methicillin-resistant
Staphylococcus aureus
(CA-MRSA) strain MW2 harbors a plethora of toxins to mediate its virulence. However, toxin expression and regulation with simulated clinical antimicrobial exposures are unclear. This study evaluated these relationships using an
in vitro
pharmacodynamic hollow-fiber infection model. Clinical doses of clindamycin, linezolid, minocycline, trimethoprim-sulfamethoxazole (SXT), and vancomycin were simulated over 72 h against MW2 in the hollow fiber model. Expression levels of
lukSF-PV
and enterotoxin genes
sec4
,
sek
,
seq
, and
sel2
were quantified by real-time PCR. Panton-Valentine leukocidin (PVL) was quantified by enzyme-linked immunosorbent assay (ELISA), and cytotoxicity was determined on polymorphonuclear cells (PMNs). Vancomycin produced the maximum MW2 killing (2.53 log
10
CFU/ml) after the first dose, but the greatest sustained killing over 72 h occurred with linezolid and clindamycin. Vancomycin and minocycline induced gene upregulation from 0 to 8 h, followed by downregulation for the remaining simulation period. Clindamycin decreased gene expression in the first 24 h, followed by moderate increases (2.5-fold) thereafter. Linezolid increased gene expression 11.4- to 200.4-fold but inhibited PVL production (0.6 ± 0.3 versus 5.9 ± 0.2 μg/ml, linezolid versus control at 72 h;
P
< 0.05). Similar effects on PVL production occurred with clindamycin and minocycline. SXT increased PVL production at 48 h (2.8-fold) and 72 h (4.9-fold) of treatment (
P
< 0.05), resulting in increased PVL cytotoxicity on PMNs. Linezolid, clindamycin, and minocycline were the most effective agents on decreasing the virulence potential in CA-MRSA, notably after 8 h of treatment. SXT had minimal effects on toxin gene regulation, but it increased production and cytotoxicity of PVL toxin in the model and may enhance virulence when it is used to treat severe infections.
Distribution of Spontaneous
gyrA
Mutations in 97 Fluoroquinolone-Resistant Helicobacter pylori Isolates Collected in France
Authors: Garcia Magali , Raymond Josette , Garnier Martine , Cremniter Julie , Burucoa Christophe 
Published: November 2011

ABSTRACT

We determined the prevalence of
gyrA
mutations conferring fluoroquinolone resistance in 97
Helicobacter pylori
isolates collected in France from 2007 to 2010. Ninety-four harbored one or two mutations already found in the quinolone resistance determining region (QRDR) of
gyrA
(for T87I,
n
= 23; for N87K,
n
= 32; for D91N,
n
= 30; for D91G,
n
= 7; for D91Y,
n
= 6), 2 harbored a mutation never previously described (D91H and A88P), and one strain was resistant (ciprofloxacin MIC of 8 mg/liter) without a detected mutation conferring this resistance in
gyrA
or
gyrB
genes.
Zinc Acetate/Carrageenan Gels Exhibit Potent Activity
In Vivo
against High-Dose Herpes Simplex Virus 2 Vaginal and Rectal Challenge
Authors: Fernández-Romero José A. , Abraham Ciby J. , Rodriguez Aixa , Kizima Larisa , Jean-Pierre Ninochka , Menon Radhika , Begay Othell , Seidor Samantha , Ford Brian E. , Gil Pedro I. , Peters Jennifer , Katz David , Robbiani Melissa , Zydowsky Thomas M. 
Published: November 2011

ABSTRACT

Topical microbicides that block the sexual transmission of HIV and herpes simplex virus 2 (HSV-2) are desperately needed to reduce the incidence of HIV infections worldwide. Previously we completed phase 3 testing of the carrageenan-based gel Carraguard. Although the trial did not show that Carraguard is effective in preventing HIV transmission during vaginal sex, it did show that Carraguard is safe when used weekly for up to 2 years. Moreover, Carraguard has
in vitro
activity against human papillomavirus (HPV) and HSV-2 and favorable physical and rheological properties, which makes it a useful vehicle to deliver antiviral agents such as zinc acetate. To that end, we previously reported that a prototype zinc acetate carrageenan gel protects macaques against vaginal challenge with combined simian-human immunodeficiency virus reverse transcriptase (SHIV-RT). Herein, we report the safety and efficacy of a series of zinc acetate and/or carrageenan gels. The gels protected mice (75 to 85% survival;
P
< 0.001) against high-dose (10
6
-PFU) HSV-2 vaginal or rectal challenge. In contrast, zinc acetate formulated in HEC (hydroxyethylcellulose; or the Universal Placebo) failed to protect mice against the high-dose vaginal HSV-2 challenge (similar to aqueous zinc acetate solution and the placebo controls). The gels were found to be effective spreading gels, exhibited limited toxicity
in vitro
, caused minimal damage to the architecture of the cervicovaginal and rectal mucosae
in vivo
, and induced no increased susceptibility to HSV-2 infection in a mouse model. Our results provide a strong rationale to further optimize and evaluate the zinc acetate/carrageenan gels for their ability to block the sexual transmission of HIV and HSV-2.
Combined Roles of Human IgG Subclass, Alternative Complement Pathway Activation, and Epitope Density in the Bactericidal Activity of Antibodies to Meningococcal Factor H Binding Protein
Authors: Giuntini Serena , Reason Donald C. , Granoff Dan M. 
Published: November 2011

ABSTRACTMeningococcal vaccines containing factor H binding protein (fHbp) are in clinical development. fHbp binds human fH, which enables the meningococcus to resist complement-mediated bacteriolysis. Previously, we found that chimeric human IgG1 mouse anti-fHbp monoclonal antibodies (MAbs) had human complement-mediated bactericidal activity only if the MAb inhibited fH binding. Since IgG subclasses differ in their ability to activate complement, we investigated the role of human IgG subclasses on antibody functional activity. We constructed chimeric MAbs in which three different murine fHbp-specific binding domains were each paired with human IgG1, IgG2, or IgG3. Against a wild-type group B isolate, all three IgG3 MAbs, irrespective of their ability to inhibit fH binding, had bactericidal activity that was >5-fold higher than the respective IgG1 MAbs, while the IgG2 MAbs had the least activity. Against a mutant with increased fHbp expression, the anti-fHbp MAbs elicited greater C4b deposition (classical pathway) and greater bactericidal activity than against the wild-type strain, and the IgG1 MAbs had similar or greater activity than the respective IgG3 MAbs. The bactericidal activity against both wild-type and mutant strains also was dependent, in part, on activation of the alternative complement pathway. Thus, at lower epitope density in the wild-type strain, the IgG3 anti-fHbp MAbs had the greatest bactericidal activity. At a higher epitope density in the mutant, the IgG1 MAbs had similar or greater bactericidal activity than the IgG3 MAbs, and the activity was less dependent on the inhibition of fH binding than at a lower epitope density.
Ecology and productivity of Cantharellus cibarius var. roseocanus in two eastern Canadian jack pine stands
Authors: Rochon Caroline , Paré David , Pélardy Nellia , Khasa Damase P. , Fortin J. André 
Published: November 2011

Despite the economic importance of chanterelles, much remains to be known about their habitat requirements. Cantharellus cibarius var. roseocanus Redhead, Norvell & Danell sporocarp productivity was measured during three growing seasons in two Pinus banksiana Lamb. stands of boreal forest. The objective was to determine how the variability in stand, plant association, edaphic, and meteorological conditions was related to sporocarp productivity. DNA of this species was detected in organic and mineral soil horizons. Sporocarp productivity was similar for both stands, but the absence of colonies on trails at one of the sites likely reflects microenvironmental conditions that are unsuitable for chanterelle growth. Under the prevailing site conditions, preferred microhabitats were characterized by high stand density, high C:N ratio, and frequent moss presence. The Solidago puberula Nutt. – Comptonia peregrina (L.) Coulter – Pinus banksiana association, lichen presence, and as much clay and silt content as can possibly be found on this moderately acidic sandy soil favoured the productivity of this chanterelle, whereas ericaceous species presence was negatively correlated with chanterelle productivity. Positive correlations were found between total rainfall 1 week prior to fructification, air temperature 2 weeks prior to fructification, and sporocarp productivity. Results highlight the specific conditions favourable to Cantharellus cibarius var. roseocanus fructifications within these stands.
The association between Northern Hemisphere climate patterns and interannual variability in Canadian wildfire activity
Authors: Beverly J.L. , Flannigan M.D. , Stocks B.J. , Bothwell P. 
Published: November 2011

Wildfire impacts on ecological and socioeconomic systems are regulated, in part, by climate. Association between hemispheric-scale climate patterns and annual wildfire activity can be obscured by local factors that also control the initiation and spread of fires. Vegetation, topography, and fire suppression can be expected to influence conventional measures of annual wildfire activity such as area burned, effectively concealing evidence of broad-scale climate influences. This study investigates alternatives to area-burned statistics for quantifying annual wildfire activity in Canada in relation to Northern Hemisphere climate variability represented by the Atlantic Multidecadal Oscillation (AMO). We depart from conventional approaches by including socioeconomic measures of wildfire activity and by assessing spatially referenced wildfire data over units of observation chosen explicitly to diminish variability caused by factors unrelated to broad-scale climate. Our data-centred approach, combined with linear regression modelling, revealed that the AMO was positively correlated with national time series of very large fires (≥10 000 ha), wildfire-related evacuations, and fire suppression expenditures over the period 1975–2007. The AMO and wildfire activity were most closely coupled during a period of predominantly positive-phase Arctic Oscillation (AO) and Pacific Decadal Oscillation (PDO) between 1989 and 2001. Positive correlation between maximum evacuation wind speed and the AMO suggests that wind may be a causal factor in the AMO–wildfire relationship.