bluuebunny/crossref_metadata_2025 huggingface dataset:
TH‐D‐L100J‐02: Exact Image Reconstruction in Reverse Helical Cone‐Beam CT for Radiation Therapy
Authors: Cho S , Xia D , Pelizzari C , Pan X
Published: July 2007

Purpose: To propose an exact image reconstruction algorithm based on Pack‐Noo formula for a reverse helical cone‐beam CT (CBCT) which is potentially a useful scanning geometry for image‐acquisition in image‐guided radiation therapy. Method and Materials: Last year, we proposed a novel scanning geometry named reverse helical trajectory for a CBCT imager mounted on a linear accelerator (LINAC) treatment system, and applied a chord‐based backprojection filtration (BPF) algorithm for exact image reconstruction. It was shown that there is a middle gap in the reconstructed image which is due to lack of chords passing through the gap. The gap was removed when we used an additional long line segment connecting the end points of the revere helices. However, larger patient dose and longer scan time due to additional line scan were pointed out as drawbacks of the proposed method. In this work, we applied Pack‐Noo formula, which does not depend on the existence of chords for reconstructing the exact image, to propose an exact image reconstruction algorithm for a reverse helical trajectory. Cone‐beam data requirement for the proposed algorithm was exploited to address the concept of reduced cone‐beam scan. A numerical study using 3D Shepp‐Logan phantom was performed. Results: We showed the proposed algorithm can reconstruct the image without any gap in the middle from the cone‐beam data acquired by a reverse helical scan. Additional line scan, which is necessary for chord‐based BPF algorithms to remove the middle gap, is not needed for exact image reconstruction with the proposed algorithm. Conclusion: A new algorithm based on Pack‐Noo formula for exact image reconstruction in reverse helical cone‐beam CT was proposed. Without any additional line scan which is necessary for chord‐based BPF algorithms to reconstruct the complete image, the proposed algorithm successfully reconstructed the image.
TH‐D‐L100J‐03: An Investigation of the Spatial Resolution Properties of MiniCAT: Flat‐Panel‐Based Volume CT System for Head and Neck Imaging
Authors: Stayman J , Wang E
Published: July 2007

Purpose: Volume computed tomography (VCT) using flat panel detectors has the capability to provide isotropic high spatial resolution, whereas traditional multislice scanners often exhibit decreased spatial resolution in the axial direction. In many clinical applications including temporal bone imaging, reformatted images reviewed for diagnostic purposes and anisotropic resolution can reduce the clinical utility of such views. We present a spatial resolution investigation of the MiniCAT system, a commercially available flat‐panel‐based VCT system made by Xoran Technologies, Inc. and compare spatial resolution with a traditional multislice CT (MSCT) system (Siemens Sensation 16) using standard acquisition protocols. Method and Materials: We investigate the spatial resolution properties of the flat‐panel‐based VCT and traditional MSCT using line pair phantoms and a comparison of scanned human temporal bones. Graded line pair phantoms are scanned in three orientations to provide resolution measures along each axis (X,Y, and Z). The modulation transfer function (MTF) of the MiniCAT system is computed using conventional techniques. Human temporal bone scans are analyzed qualitatively and clarity of various fine detail features is assessed. Results: We find the spatial resolution of the MiniCAT system to be highly isotropic with an MTF that yields 10% contrast at 17 lp/cm. In the qualitative image quality study we find that fine feature details in the temporal bone like the bone overlying the tympanic section of the facial nerve canal are better resolved using the flat‐panel‐based VCT system than in the traditional MSCT. Conclusion: Flat‐panel‐based VCT can provide finer isotropic resolution than traditional MSCT which may give it an advantage in clinical diagnosis — particularly when looking at small details in oblique views as is common in the diagnosis of otologic pathology. Conflict of Interest: Research sponsored by Xoran Technologies, Inc.
TH‐D‐L100J‐05: Quality Assurance of Megavoltage Cone‐Beam CT
Authors: Morin O , Aubin M , Aubry J , Chen J , Descovich M , Pouliot J
Published: July 2007

Purpose: Megavoltage Cone‐Beam CT (MVCBCT) is now widely used in radiation therapy. The objective of this work was to evaluate the stability of MVCBCT and define a quality assurance protocol. Methods and Materials: Two MVCBCT systems were followed for a period of 4 months. The systems were fully calibrated (geometry, CT♯ scaling factor and flat panel corrections) and analyzed daily on the first week, weekly for a month and monthly thereafter. Images of a gold seed placed at the machine isocenter were used to track the positional accuracy and stability of the system. An image quality phantom was used to monitor the stability with respect to CT♯, contrast‐to‐noise ratio (CNR), spatial resolution, noise and uniformity. A graphical user interface was developed with Matlab to automatically analyze the image quality. For each day of analysis, images were reconstructed using the calibrations obtained that day and the oldest calibrations available to investigate how frequently calibration is needed. Results: The stability of all measurements over the 4‐month period was excellent. The reconstructed gold seed position relative to isocenter was better than 1 mm for a period of 4 months. Small variations in image quality were observed between the two systems. The inserts mean CNR were 12.4±0.7 and 12.2±0.7 for the two systems. Using the initial calibrations resulted in slightly more variability in the measurements. Based on the measurements and our experience of the last 5 years, we generated a practical list of possible artifacts occurring with MVCBCT. Conclusion: Monthly calibration of the MVCBCT system is largely sufficient. Imaging a small fiducial on a daily or weekly basis may also be warranted to detect geometric misalignments caused by sudden mechanical failures. Based on the measurements, a system performance baseline for MVCBCT has been defined. Conflict of Interest: Research sponsored by Siemens OCS.
TH‐D‐M100F‐07: Topology Preserving Diffusion Registration Incorporating with Gradient Orientation Information
Authors: Gao S , Wang H , Zhang L , Mohan R , Dong L
Published: July 2007

Purpose: The goal of this study was to develop an image intensity‐based diffusion registration algorithm that can be used for reliable automatic delineation of anatomical structures on daily CT images. The constraint of the topology preservation method used in this algorithm ensures that the transformations are reliable and accurate. Method and Materials: To achieve accurate deformable image registration using a diffusion‐based method, we proposed to incorporate the gradient orientation information into the driving force in diffusion registration. This is similar to the symmetric force in the demons algorithm. We also introduced to use the positive Jacobian constraint, which is the fundamental requirement for topology preservation, as a guideline to determine the smoothing parameter in the diffusion algorithm to ensure that a realistic registration can be achieved. The planning contours were mapped onto the daily CT image using the displacement field after the deformable image registration. The contour mapping serves as a validation of the algorithm proposed in this study. The performance of the proposed algorithm for register 3D CT images of prostate and head and neck cancer patients were evaluated by visually assessing the agreement of the anatomical structures with deformed contours in target image. Results: The contours deformed with the topology preservation method are more accurate segmentation of the anatomical structures, compared to a similar method without this constraint. The positivity of Jacobian provided a way to evaluate the performance of the registration and to serve as guidance for selecting smoothing parameters. Conclusion: We proposed a diffusion registration algorithm incorporated with the intensity gradient information and the positive Jacobian constraint that ensures the transformations to topologically preservation of anatomical structures. Compared to demons algorithm, the proposed algorithm is more computational efficient and accurate, especially for prostate CT images registration.

The research is in part sponsored by Varian.
TH‐D‐M100F‐09: Ultrasound‐Guided Prostate IMRT Planning: An Ultrasound‐CT Application
Authors: Li X , Ding C , Yang Y , Smith R , Deustch M , Beriwal S , Heron D , Huq M
Published: July 2007

Purpose: The prostate contours drawn by physicians on CT images tend to overestimate the real volume due to the poor contrast between the prostate and the surrounding soft tissues. The aim of this study was to utilize ultrasound (US)‐CT to guide a more accurate prostate segmentation for prostate IMRT planning. Method and Materials: In US‐CT modality, the ultrasound system (Restitu™, Resonant Medical System, Montreal, Canada) was integrated with CT‐Sim through an optic camera system, which was calibrated to the intersection point of wall lasers of CT‐Sim and was able to trace the position of ultrasound probe in real‐time. Thus, for each patient, the CT scan and ultrasound scan can take place at the same position and almost the same time. After compensating for the mechanical inaccuracy of CT‐sim and the image distortion of 3‐D US images due to inconsistent ultrasound wave propagation speed in different tissue types, 3‐D CT and 3‐D US images can be superimposed together naturally, since they share the same spatial coordinate system. Thus, the prostate contour drawn on 3‐D Ultrasound images can be transferred into CT images for IMRT planning. Results: Five patients underwent 3‐D US‐CT scan in this study. First, a physician contoured the target volumes and surrounding critical organs on CT images. Then the prostate was contoured on US images for comparison. The fused US‐CT images revealed that the discrepancy between the prostate volume drawn on CT images and ultrasound images takes place mostly at the lateral surface of prostate and the interface between prostate and rectum. The volume of the prostate drawn on US images is 30%∼50% less than that obtained from CT. Conclusion: Ultrasound‐CT, a new multi‐modality imaging system, has a potential to provide a more accurate prostate anatomy definition for prostate IMRT planning thereby reducing radiation dose to surrounding critical structures.
TH‐D‐AUD‐03: Accuracy Assessment of An Optic‐Guided Target Localization System for Non‐Invasive Intra‐Cranial SRS Using CBCT‐Based 3D/3D Match
Authors: Yang Y , Fu W , Li F , Li X , Heron D , Huq M
Published: July 2007

Purpose: To assess the total accuracy of an optic‐guided target localization system for non‐invasive stereotactic radiosurgery(SRS) of intra‐cranial lesions using a 3D/3D match based on an on‐board imager(OBI) CBCT. Methods and Materials: A head phantom with 5 gold markers and data from 32 SRS/IMRS patients with intracranial lesions were used to validate the localization accuracy of Varian Trilogy frameless SRS system. For all the cases, a Varian stereotactic mask system was used for immobilization and planning CT was acquired with a slice thickness of 1.25mm. The target was first localized under the guidance of the optical positioning system through monitoring the reference fiducials on the phantom or on a custom biteblock fixed on the maxillary dentition for real patients. kV‐OBI images and CBCT with a slice thickness of 1.0mm were then acquired. 2D/2D registration between kV‐OBI images and DRRs and 3D/3D registration between CBCT and planning CT were performed. For real treatments, the online setup was adjusted based on the 3D/3D registration. Offline analysis of the total accuracy of optic‐guided positioning system and kV image‐based 2D/2D match was evaluated with the CBCT‐based 3D/3D match as benchmark. Results: The optical positioning system provided a target localization accuracy of 0.9±0.4mm for the phantom study and 1.3±0.4mm for the clinical investigation. The errors encountered mainly consist of the camera calibration inaccuracy, the biteblock repositioning reproducibility and the fiducial registration inaccuracy. With the aid of the kV image‐based 2D/2D match, the target localization accuracy improved to 0.5±0.3mm for clinical cases. Conclusions: The non‐invasive frameless SRS can provide a target localization accuracy of about 1.3mm with the aid of optical positioning system. If combined with kV images or CBCT, the system has the capability of delivering similar accuracy as that of a frame‐based invasive system(∼0.5mm), providing an excellent tool for fractionated treatment without patients' discomfort.
SHARED RISK RESOURCE GROUP COMPLEXITY AND APPROXIMABILITY ISSUES
Authors: COUDERT D. , DATTA P. , PERENNES S. , RIVANO H. , VOGE M.-E.
Published: July 2007

This article investigates complexity and approximability properties of combinatorial optimization problems yielded by the notion of Shared Risk Resource Group (SRRG). SRRG has been introduced in order to capture network survivability issues where a failure may break a whole set of resources, and has been formalized as colored graphs, where a set of resources is represented by a set of edges with same color. We consider here the analogous of classical problems such as determining paths or cuts with the minimum numbers of colors or color disjoint paths. These optimization problems are much more difficult than their counterparts in classical graph theory. In particular standard relationship such as the Max Flow - Min Cut equality do not hold any longer. In this article we identify cases where these problems are polynomial, for example when the edges of a given color form a connected subgraph, and otherwise give hardness and non approximability results for these problems.
RELATION BETWEEN LEPTON FLAVOR VIOLATING PROCESSES
Authors: KOVALENKO SERGEY , SCHMIDT IVAN
Published: July 2007

We demonstrate the existence of model-independent one-to-one correspondence relations between different lepton flavor violating processes (LFV). Applying the criterion of naturalness, based on the idea of "custodial symmetry", we show that all the LFV processes, independently of specific mechanisms behind them, but with the same external leptons, have a priori comparable amplitudes modulo their kinematics and involved hadronic form factors.
SPLIT SUPERSYMMETRY AND THE ROLE OF A LIGHT FERMION IN A SUPERGRAVITY-BASED SCENARIO
Authors: MUKHOPADHYAYA BISWARUP , SENGUPTA SOUMITRA
Published: July 2007

We investigate split supersymmetry (SUSY) within a supergravity framework, where local SUSY is broken by the F-term of a hidden sector chiral superfield X. With reasonably general assumptions, we show that the fermionic component of X will always have mass within a TeV. Though its coupling to the observable sector superfields is highly suppressed in TeV scale SUSY, we show that it can be enhanced by many orders in split SUSY, leading to its likely participation in accelerator phenomenology. We conclude with a specific example of such a scenario in a string based supergravity model.
The Spin-Dependent Gluon Distribution in a Proton
Authors: Morii Toshiyuki , Tanaka Shun-ichi , Yamanishi Teruya
Published: July 2007

By using the positivity condition of distribution functions together with the unpolarized and polarized experimental data, we restrict the x dependence of the polarized gluon distribution. If we take the form of the spin-dependent gluon distribution as δG(x)=Bxγ(1−x)p as a typical form, the γ and p are restricted as γ≲ −0.3 and p≳10.
Dynamics of a Supercooled Lennard-Jones System: Qualitative and Quantitative Tests of Mode-Coupling Theory
Authors: Kob Walter , Nauroth Markus , Andersen Hans C.
Published: July 2007

Using molecular dynamics computer simulations, we investigate the dynamics of a binary Lennard-Jones system at low temperatures. We show that this dynamics can be described well by mode-coupling theory. By solving numerically the mode-coupling equations for this system, we demonstrate that the theory is not only able to correctly predict the universal properties of this dynamics but also the nonuniversal properties.
Transcriptional Functionality of Germ Line p53 Mutants Influences Cancer Phenotype
Authors: Monti Paola , Ciribilli Yari , Jordan Jennifer , Menichini Paola , Umbach David M. , Resnick Michael A. , Luzzatto Lucio , Inga Alberto , Fronza Gilberto
Published: July 2007

Purpose: The TP53 tumor suppressor gene encodes a sequence-specific transcription factor that is able to transactivate several sets of genes, the promoters of which include appropriate response elements. Although human cancers frequently contain mutated p53, the alleles as well as the clinical expression are often heterogeneous. Germ line mutations of TP53 result in cancer proneness syndromes known as Li-Fraumeni, Li-Fraumeni–like, and nonsyndromic predisposition with or without family history. p53 mutants can be classified as partial deficiency alleles or severe deficiency alleles depending on their ability to transactivate a set of human target sequences, as measured using a standardized yeast-based assay (see http://www.umd.be:2072/index.html). We have investigated the extent to which the functional features of p53 mutant alleles determine clinical features in patients who have inherited these alleles and have developed cancer.

Experimental Design: We retrieved clinical data from the IARC database (see http://www.p53.iarc.fr/Germline.html) for all cancer patients with germ line p53 mutations and applied stringent statistical evaluations to compare the functional classification of p53 alleles with clinical phenotypes.

Results: Our analyses reveal that partial deficiency alleles are associated with a milder family history (P = 0.007), a lower numbers of tumors (P = 0.007), and a delayed disease onset (median, 31 versus 15 years; P = 0.007) which could be related to distinct tumor spectra.

Conclusions: These findings establish for the first time significant correlations between the residual transactivation function of individual TP53 alleles and clinical variables in patients with inherited p53 mutations who develop cancer.
Correlation between Development of Rash and Efficacy in Patients Treated with the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib in Two Large Phase III Studies
Authors: Wacker Bret , Nagrani Tina , Weinberg Jacqueline , Witt Karsten , Clark Gary , Cagnoni Pablo J.
Published: July 2007

Purpose: Data from two large phase III studies were analyzed to characterize the correlation between the occurrence of rash during treatment with the epidermal growth factor receptor inhibitor erlotinib and improved clinical outcomes.

Experimental Design: Overall survival, progression-free survival (PFS), and tumor response were compared between patients in a rash-evaluable subset who did or did not develop rash in National Cancer Institute of Canada Clinical Trials Group Studies BR.21 (single agent in non–small-cell lung cancer, n = 444 in erlotinib group and n = 229 in placebo group) and PA.3 (combination with gemcitabine in pancreatic cancer, n = 254 in erlotinib plus gemcitabine group and n = 245 in placebo plus gemcitabine group).

Results: Presence of rash strongly correlated with overall survival in both studies. In Study BR.21, these correlations increased with rash severity grade: grade 1 versus no rash [hazard ratio (HR), 0.41, P < 0.001] and grade ≥2 versus no rash (HR, 0.29, P < 0.001). Similar results were observed for PFS. Disease control (complete response + partial response + stable disease) seemed to increase with the presence and severity of rash. In Study PA.3, grade ≥2 rash (but not grade 1) strongly correlated with overall survival improvement: grade ≥2 versus no rash (HR, 0.47, P < 0.001). Similarly, grade ≥2 rash was strongly correlated with improvements in PFS and disease control.

Conclusions: Physicians and patients should view rash development as a positive event indicative of greater likelihood of clinical benefit. Further studies are required to identify patients most likely to develop rash and to determine if dose escalation to induce rash can improve efficacy.
Prognostic Significance of the Immunohistochemical Staining of Cleaved Caspase-3, an Activated Form of Caspase-3, in Gliomas
Authors: Kobayashi Tatsuya , Masumoto Junya , Tada Tsuyoshi , Nomiyama Tetsuo , Hongo Kazuhiro , Nakayama Jun
Published: July 2007

Purpose: Gliomas are common tumors of the central nervous system, and the majority of patients with gliomas have a poor prognosis. The prediction of prognosis is very important in selecting treatment. In the present study, we retrospectively examined the immunohistochemical staining of cleaved caspase-3 (CC3), an activated form of caspase-3 that acts as a lethal protease at the most distal stage of the apoptosis pathway, in gliomas, and the correlation between the prognosis of patients and caspase-3 activation to find useful prognostic indicators.

Experimental Design: Immunohistochemical staining of CC3 was done in 65 patients with gliomas. The percentage of CC3 staining-positive cells was defined as the CC3 immunoreactivity score (IRS). Survival analysis between CC3 IRS of glioma patients and survival time was carried out using the Kaplan-Meier method with the log-rank test and the Cox proportional hazards regression model.

Results: CC3 IRS was statistically analyzed to designate the best provisional cutoff point, and when detected in >10% of glioma cells, it was considered positive. The Kaplan-Meier method with the log-rank test revealed that patients with CC3 IRS-positive tumors had significantly greater survival than those with CC3 IRS-negative tumors among three grades, 2, 3, and 4 (P = 0.0061), and within grade 3 of anaplastic astrocytoma (P = 0.0458). After adjustment for known clinical prognostic factors, such as age, WHO grade, and performance status, the hazard ratio for CC3 IRS-positive was 0.39 with 95% confidence interval between 0.19 and 0.85 (P = 0.0187). Within high grades, including grades 3 and 4, the hazard ratio was 0.40 with 95% confidence interval between 0.20 and 0.86 (P = 0.0192).

Conclusions: CC3 IRS could be useful as a good prognostic indicator for glioma patients.
Granulocyte Macrophage Colony-Stimulating Factor–Secreting Allogeneic Cellular Immunotherapy for Hormone-Refractory Prostate Cancer
Authors: Small Eric J. , Sacks Natalie , Nemunaitis John , Urba Walter J. , Dula Eugene , Centeno Arthur S. , Nelson William G. , Ando Dale , Howard Catherine , Borellini Flavia , Nguyen Minh , Hege Kristen , Simons Jonathan W.
Published: July 2007

Purpose: This trial evaluated the safety, clinical activity, and immunogenicity of an allogeneic cellular immunotherapy in 55 chemotherapy-naïve patients with hormone-refractory prostate cancer (HRPC). The immunotherapy, based on the GVAX platform, is a combination of two prostate carcinoma cell lines modified with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene.

Experimental Design: HRPC patients with radiologic metastases (n = 34) or rising prostate-specific antigen (PSA) only (n = 21) received a prime dose of 500 million cells and 12 boost doses of either 100 million cells (low dose) or 300 million cells (high dose) biweekly for 6 months. End points were changes in PSA, time to progression, and survival.

Results: Median survival was 26.2 months (95% confidence interval, 17, 36) in the radiologic group: 34.9 months (8, 57) after treatment with the high dose (n = 10) of immunotherapy and 24.0 months (11, 35) with the low dose (n = 24). The median time to bone scan progression in the radiologic group was 5.0 months (2.6, 11.6) with the high dose and 2.8 months (2.8, 5.7) with the low dose. In the rising-PSA group (n = 21) receiving the low dose, the median time to bone scan progression was 5.9 months (5.6, not reached), and median survival was 37.5 months (29, 56). No dose-limiting or autoimmune toxicities were seen; the most common adverse events were injection site reaction and fatigue.

Conclusions: These results suggest that this GM-CSF–secreting, allogeneic cellular immunotherapy is well tolerated and may have clinical activity in patients with metastatic HRPC. Phase 3 trials to confirm these results are under way.
Age-Related DNA Methylation Changes in Normal Human Prostate Tissues
Authors: Kwabi-Addo Bernard , Chung Woonbok , Shen Lanlan , Ittmann Michael , Wheeler Thomas , Jelinek Jaroslav , Issa Jean-Pierre J.
Published: July 2007

Purpose: Prostate cancer is a leading cause of cancer death among the aging male population but the mechanism underlying this association is unclear. Aberrant methylation of promoter CpG islands is associated with silencing of genes and age-dependent methylation of several genes has been proposed as a risk factor for sporadic cancer. We examined the extent of gene methylation in pathologically normal human prostate as a function of age.

Experimental Design: We used pyrosequencing to quantitatively analyze the methylation status of nine CpG islands in normal prostate tissue DNA from 45 organ donors and 45 patients who had undergone cystoprostatectomy for bladder cancer. We also analyzed 12 pairs of matched benign and prostate cancer tissue DNA from patients with prostate cancer.

Results: Linear regression analysis revealed a significant increase in promoter methylation levels correlating with age for CpG islands at RARβ2 (r = 0.4; P < 0.0001), RASSF1A (r = 0.27; P = 0.01), GSTP1 (r = 0.59; P < 0.0001), NKX2-5 (r = 0.27; P = 0.008), and ESR1 (r = 0.244; P = 0.023) in the normal prostate tissue samples studied. A calculated average methylation (z score) at all nine CpG loci analyzed in the normal prostate tissues showed a strong correlation with age (r = 0.6; P < 0.001). Comparison of the methylation level for the matched benign and prostate cancer tissues from individual patients with prostate cancer showed significantly higher methylation in the prostate cancer tissue samples for RARβ2 (P < 0.001), RASSF1A (P = 0.005), GSTP1 (P < 0.001), NKX2-5 (P = 0.003), ESR1 (P = 0.016), and CLSTN1 (P = 0.01).

Conclusions: Our findings show aberrant hypermethylation as a function of age in the normal prostate tissues. Such age-related methylation may precede and predispose to full-blown malignancy.
Long-Term Protective Effect of Mature DC-LAMP+ Dendritic Cell Accumulation in Sentinel Lymph Nodes Containing Micrometastatic Melanoma
Authors: Elliott Bruce , Scolyer Richard A. , Suciu Stefan , Lebecque Serge , Rimoldi Donata , Gugerli Oliver , Musat Elena , Sharma Raghwa N. , Lienard Danielle , Keilholz Ulrich , Testori Alessandro , Eggermont Alexander , MacKie Rona , Robert Caroline , Cook Martin , Thompson John F. , Angevin Eric , Spatz Alain ,   on behalf of the European Organization for Research and Treatment of Cancer Melanoma Group
Published: July 2007

Purpose: In a previous immunohistochemical study of dendritic cells (DC) in sentinel lymph nodes (SLN) draining regressing melanomas, we found that the accumulation of mature DC-LAMP+ DCs in SLNs was associated with local expansion of antigen-specific memory effector CTLs and the absence of metastasis in downstream lymph nodes. The aim of this study was to investigate the prognostic importance of the maximal density of mature DCs in SLNs.

Experimental Design: A total of 458 consecutive patients with micrometastatic melanoma within SLNs were eligible for analysis. The maximal density of mature DC-LAMP+ DCs was evaluated by three independent observers and categorized into three classes (<100, 100 to <200, and ≥200/mm2).

Results: There was excellent interobserver reproducibility for maximum density of mature DC-LAMP+ DC scores (κ score = 0.82). There were differences in the maximal density scores and staining intensity according to the treating melanoma center (P < 0.001). The higher the mature DC density in the SLN is, the longer is the duration of survival [P = 0.047; hazard ratio, 0.70; 95% confidence interval, 0.50-1.00]. Adjusted by thickness and ulceration, the prognostic importance of DC density was lower (P = 0.36).

Conclusion: This study is the first to report the prognostic value of DC-LAMP+ DC counts in SLNs containing metastatic melanoma. Patients with a high density of mature DCs (≥200/mm2) have the lowest risk of death. It also provides evidence that a lack of maturation in the SLNs is important in biological facilitation of melanoma progression.
A Vascular Endothelial Growth Factor Receptor-2 Inhibitor Enhances Antitumor Immunity through an Immune-Based Mechanism
Authors: Manning Elizabeth A. , Ullman John G.M. , Leatherman James M. , Asquith Justin M. , Hansen Timothy R. , Armstrong Todd D. , Hicklin Daniel J. , Jaffee Elizabeth M. , Emens Leisha A.
Published: July 2007

Purpose: Given the complex tumor microenvironment, targeting multiple cellular components may be the most effective cancer treatment strategy. Therefore, we tested whether antiangiogenic and immune-based therapy might synergize by characterizing the activity of DC101, an antiangiogenic monoclonal antibody specific for vascular endothelial growth factor receptor-2 (VEGF-R2), alone and with HER-2/neu (neu)–targeted vaccination.

Experimental Design: Neu-expressing breast tumors were measured in treated nontolerant FVB mice and immune-tolerant neu transgenic (neu-N) mice. Neu-specific and tumor cell–specific immune responses were assessed by intracellular cytokine staining, ELISPOT, and CTL assays.

Results: DC101 decreased angiogenesis and increased tumor cell apoptosis. Although DC101 increased serum levels of the immunosuppressive cytokine VEGF, no evidence of systemic immune inhibition was detected. Moreover, DC101 did not impede the influx of tumor-infiltrating lymphocytes. In FVB mice, DC101 inhibited tumor growth in part through a T cell–dependent mechanism, resulting in both increased tumor-specific CD8+ T cells and tumor regression. Combining DC101 with neu-specific vaccination accelerated tumor regression, augmenting the lytic activity of CD8+ cytotoxic T cells. In tolerant neu-N mice, DC101 only delayed tumor growth without inducing frank tumor regression or antigen-specific T-cell activation. Notably, mitigating immune tolerance by inhibiting regulatory T cell activity with cyclophosphamide revealed DC101-mediated augmentation of antitumor responses in vaccinated neu-N mice.

Conclusions: This is the first report of DC101-induced antitumor immune responses. It establishes the induction of tumor-specific T-cell responses as one consequence of VEGF-R2 targeting with DC101. These data support the development of multitargeted cancer therapy combining immune-based and antiangiogenic agents for clinical translation.
Mechanism of Action and Preclinical Antitumor Activity of the Novel Hypoxia-Activated DNA Cross-Linking Agent PR-104
Authors: Patterson Adam V. , Ferry Dianne M. , Edmunds Shelley J. , Gu Yongchuan , Singleton Rachelle S. , Patel Kashyap , Pullen Susan M. , Hicks Kevin O. , Syddall Sophie P. , Atwell Graham J. , Yang Shangjin , Denny William A. , Wilson William R.
Published: July 2007

Purpose: Hypoxia is a characteristic of solid tumors and a potentially important therapeutic target. Here, we characterize the mechanism of action and preclinical antitumor activity of a novel hypoxia-activated prodrug, the 3,5-dinitrobenzamide nitrogen mustard PR-104, which has recently entered clinical trials.

Experimental Design: Cytotoxicity in vitro was evaluated using 10 human tumor cell lines. SiHa cells were used to characterize metabolism under hypoxia, by liquid chromatography-mass spectrometry, and DNA damage by comet assay and γH2AX formation. Antitumor activity was evaluated in multiple xenograft models (PR-104 ± radiation or chemotherapy) by clonogenic assay 18 h after treatment or by tumor growth delay.

Results: The phosphate ester “pre-prodrug” PR-104 was well tolerated in mice and converted rapidly to the corresponding prodrug PR-104A. The cytotoxicity of PR-104A was increased 10- to 100-fold by hypoxia in vitro. Reduction to the major intracellular metabolite, hydroxylamine PR-104H, resulted in DNA cross-linking selectively under hypoxia. Reaction of PR-104H with chloride ion gave lipophilic cytotoxic metabolites potentially able to provide bystander effects. In tumor excision assays, PR-104 provided greater killing of hypoxic (radioresistant) and aerobic cells in xenografts (HT29, SiHa, and H460) than tirapazamine or conventional mustards at equivalent host toxicity. PR-104 showed single-agent activity in six of eight xenograft models and greater than additive antitumor activity in combination with drugs likely to spare hypoxic cells (gemcitabine with Panc-01 pancreatic tumors and docetaxel with 22RV1 prostate tumors).

Conclusions: PR-104 is a novel hypoxia-activated DNA cross-linking agent with marked activity against human tumor xenografts, both as monotherapy and combined with radiotherapy and chemotherapy.
Description and Evaluation of the Characteristics of the NCAR High-Resolution Land Data Assimilation System
Authors: Chen Fei , Manning Kevin W. , LeMone Margaret A. , Trier Stanley B. , Alfieri Joseph G. , Roberts Rita , Tewari Mukul , Niyogi Dev , Horst Thomas W. , Oncley Steven P. , Basara Jeffrey B. , Blanken Peter D.
Published: July 2007

This paper describes important characteristics of an uncoupled high-resolution land data assimilation system (HRLDAS) and presents a systematic evaluation of 18-month-long HRLDAS numerical experiments, conducted in two nested domains (with 12- and 4-km grid spacing) for the period from 1 January 2001 to 30 June 2002, in the context of the International H2O Project (IHOP_2002). HRLDAS was developed at the National Center for Atmospheric Research (NCAR) to initialize land-state variables of the coupled Weather Research and Forecasting (WRF)–land surface model (LSM) for high-resolution applications. Both uncoupled HRDLAS and coupled WRF are executed on the same grid, sharing the same LSM, land use, soil texture, terrain height, time-varying vegetation fields, and LSM parameters to ensure the same soil moisture climatological description between the two modeling systems so that HRLDAS soil state variables can be used to initialize WRF–LSM without conversion and interpolation. If HRLDAS is initialized with soil conditions previously spun up from other models, it requires roughly 8–10 months for HRLDAS to reach quasi equilibrium and is highly dependent on soil texture. However, the HRLDAS surface heat fluxes can reach quasi-equilibrium state within 3 months for most soil texture categories. Atmospheric forcing conditions used to drive HRLDAS were evaluated against Oklahoma Mesonet data, and the response of HRLDAS to typical errors in each atmospheric forcing variable was examined. HRLDAS-simulated finescale (4 km) soil moisture, temperature, and surface heat fluxes agreed well with the Oklahoma Mesonet and IHOP_2002 field data. One case study shows high correlation between HRLDAS evaporation and the low-level water vapor field derived from radar analysis.
Single-Scattering Properties of Aggregates of Bullet Rosettes in Cirrus
Authors: Um Junshik , McFarquhar Greg M.
Published: July 2007

During the March 2000 Cloud Intensive Operational Period, the University of North Dakota Citation executed spiral descents through midlatitude cirrus of a nonconvective origin over the Atmospheric Radiation Measurement Program’s Southern Great Plains site. Aggregates of bullet rosettes (ABRs) observed during the descents using a cloud particle imager are used to derive a relationship between the length L and width W of bullets that are the fundamental components of the ABRs, which is given by W = 7.14L0.455, where 100 μm ≤ L ≤ 600 μm. To derive a representation of an aggregate of bullet rosettes, six bullet rosettes, each of which is composed of six bullets of the same size but each of which has different-sized bullets from the other bullet rosettes, are attached together randomly without overlap. Using a geometric ray-tracing method, the phase function, asymmetry parameter g, and single-scattering albedo of the representation of ABR (rABR) and the component bullets and bullet rosettes are calculated at wavelengths λ of 0.55, 0.64, 1.38, 1.62, 2.11, and 3.78 μm. As the aspect ratio of the component bullets increases, the forward scattering increases by up to 1.3% and the lateral and backward scattering decrease by up to 8.9% and 10.2%, respectively, for a bullet rosette at a nonabsorbing λ (0.55 μm). For longer λ, light absorption decreases the rate at which these scatterings change with aspect ratio. The shape of the aggregates also affects the scattering properties. The rABR constructed here scatters up to 4.4% (7.0%; 20.4%) and 34.2% (11.1%; 32.7%) more light in the lateral and backward directions, respectively, and 1.2% (1.3%; 2.4%) less in the forward direction in comparison with the component bullets (component bullet rosettes; equivalent projected area bullet rosette), resulting in up to 2.5% (1.6%; 3.8%) decrease in g at 0.55 μm. In addition, as the aspect ratio and number of attached bullets in ABRs increase, g increases by up to 1.8% and decreases by up to 2.0% at 0.55 μm, increases by 2.0% and decreases by 0.3% at 2.11 μm, and increases by 1.1% and decreases by 0.5% at 3.78 μm, respectively. As an implication for remote sensing studies, the difference in the bidirectional reflectance distribution function calculated using the rABR and a bullet rosette is shown to vary by up to 107% at moderately absorbing (2.11 μm) wavelengths and by up to 35% and 28% at nonabsorbing (0.55 μm) and strongly absorbing (3.78 μm) wavelengths.
Estimation of Daylight Downward Longwave Atmospheric Irradiance under Clear-Sky and All-Sky Conditions
Authors: Bilbao Julia , de Miguel Argimiro H.
Published: July 2007

Daylight downward longwave irradiance data recorded over a flat place for the period between April 2001 and December 2004 in Valladolid, Spain, have been compared with estimates generated using four different schemes. The parameterization schemes of Brutsaert, Swinbank, Idso, and Brunt have been considered and calibrated for the comparison. Root-mean-square errors (rmse), mean bias errors, and linear regression correlations have been used to compare measured and estimated values. The results of this comparison show that, for clear-sky conditions, rmse values range between 19.57 and 8.85 W m−2 for calibrated schemes and between 39.78 and 11.13 W m−2 for original ones. The Idso and Brunt schemes give the best results with calibrated coefficients, and the Brunt scheme performs the best with original coefficients. A new scheme for estimating daylight downward longwave irradiance under “all-sky” conditions has been developed based on clear-sky schemes and solar global shortwave irradiance, and, after comparing measured and estimated values by calibrated schemes, it has been found that the Idso and Brunt schemes give the best results.
Penalized Maximal t Test for Detecting Undocumented Mean Change in Climate Data Series
Authors: Wang Xiaolan L. , Wen Qiuzi H. , Wu Yuehua
Published: July 2007

In this paper, a penalized maximal t test (PMT) is proposed for detecting undocumented mean shifts in climate data series. PMT takes the relative position of each candidate changepoint into account, to diminish the effect of unequal sample sizes on the power of detection. Monte Carlo simulation studies are conducted to evaluate the performance of PMT, in comparison with the most popularly used method, the standard normal homogeneity test (SNHT). An application of the two methods to atmospheric pressure series recorded at a Canadian site is also presented. It is shown that the false-alarm rate of PMT is very close to the specified level of significance and is evenly distributed across all candidate changepoints, whereas that of SNHT can be up to 10 times the specified level for points near the ends of series and much lower for the middle points. In comparison with SNHT, therefore, PMT has higher power for detecting all changepoints that are not too close to the ends of series and lower power for detecting changepoints that are near the ends of series. On average, however, PMT has significantly higher power of detection. The smaller the shift magnitude Δ is relative to the noise standard deviation σ, the greater is the improvement of PMT over SNHT. The improvement in hit rate can be as much as 14%–25% for detecting small shifts (Δ < σ) regardless of time series length and up to 5% for detecting medium shifts (Δ = σ–1.5σ) in time series of length N < 100. For all detectable shift sizes, the largest improvement is always obtained when N < 100, which is of great practical importance, because most annual climate data series are of length N < 100.
Error Propagation of Radar Rainfall Nowcasting Fields through a Fully Distributed Flood Forecasting Model
Authors: Vivoni Enrique R. , Entekhabi Dara , Hoffman Ross N.
Published: July 2007

This study presents a first attempt to address the propagation of radar rainfall nowcasting errors to flood forecasts in the context of distributed hydrological simulations over a range of catchment sizes or scales. Rainfall forecasts with high spatiotemporal resolution generated from observed radar fields are used as forcing to a fully distributed hydrologic model to issue flood forecasts in a set of nested subbasins. Radar nowcasting introduces errors into the rainfall field evolution that result from spatial and temporal changes of storm features that are not captured in the forecast algorithm. The accuracy of radar rainfall and flood forecasts relative to observed radar precipitation fields and calibrated flood simulations is assessed. The study quantifies how increases in nowcasting errors with lead time result in higher flood forecast errors at the basin outlet. For small, interior basins, rainfall forecast errors can be simultaneously amplified or dampened in different flood forecast locations depending on the forecast lead time and storm characteristics. Interior differences in error propagation are shown to be effectively averaged out for larger catchment scales.
Community-Based Collaboration: An Overarching Best Practice in Prevention
Authors: Bond Lynne A. , Carmola Hauf Amy M.
Published: July 2007

Several groups of prevention scholars and practitioners have recently worked independently and simultaneously to identify and disseminate guidelines for effective prevention and health promotion, reaching remarkably similar conclusions. The authors argue that community-based collaboration is an overarching best practice in prevention because it is crucial for achieving the characteristics identified as distinguishing effective prevention. This article reviews the elements that scholars have agreed are necessary for effective prevention and summarizes the ways in which community-based collaborations contribute to each.
Prevention Activities in Professional Psychology
Authors: Rivera-Mosquera Evelyn , Dowd E. Thomas , Mitchell-Blanks Marsha
Published: July 2007

In this reaction article, the authors provide a historical context for prevention activities and their place in psychological practice. They then discuss the prevention guidelines in the Major Contribution authored by S. M. Hage et al. (2007 [this issue]) and provide their critique. Finally, the authors offer ideas for the future specific applications of these general guidelines and illustrate with a case example.
Walking the Talk
Authors: Hage Sally M. , Romano John L. , Conyne Robert K. , Kenny Maureen , Schwartz Jonathan P. , Waldo Michael
Published: July 2007

The Major Contribution aimed at strengthening a prevention focus in psychology, so as to more effectively and equitably promote the well-being of all members of psychology communities. The 3 reactions (L. A. Bond & A. Carmola Hauf, 2007 [this issue]; L. Reese, 2007 [this issue]; E. Rivera-Mosquera, E. T. Dowd, & M. Mitchell-Blanks 2007 [this issue]) give strong support for the best practice prevention guidelines, while providing new insights for their implementation in the field of psychology. In this rejoinder, the authors make an effort to build upon their colleagues' ideas, by addressing the topics of community-based collaboration, prevention across the life span, and implementation of the best practice guidelines. The authors urge further interdisciplinary collaboration by members of the American Psychological Association, and others interested in prevention, and invite genuine action to expand prevention efforts.
Beyond Rhetoric
Authors: Reese Le'Roy E.
Published: July 2007

Many of the serious public health problems affecting U.S. citizens and the global community can be addressed by prevention science and practice. Instructive standards or guidance for prevention work have largely been missing from the professional literature. Despite empirical evidence that prevention works, the epidemiological literature continues to reflect significant disparities in the health status of ethnic minorities and the poor. The Major Contribution by Hage and colleagues addresses this gap in the literature by offering standards for conducting meaningful and effective prevention work. This response highlights the imperatives for prevention work and other themes that deserve attention if prevention's potential impact on health is to be realized. The author discusses the necessity for training in prevention, multidisciplinary collaboration, and understanding and changing the social determinants of health. Prevention scientists must disseminate effective prevention strategies, and prevention practitioners must work with prevention scientists to adapt these strategies to respond to the challenges of conducting prevention work across diverse settings.
Absolute Transmission Delay Guarantee in Optical Burst-Switched Networks: A Scheme and Performance Evaluation
Authors: Boudriga Noureddine , Lazzez Amor , Obaidat Mohammad S.
Published: July 2007

Among the promising solutions for next generation Internet backbone, one can consider optical burst switching (OBS) technology. This technology does not, however, provide suitable quality-of-service (QoS) support. Several schemes have been proposed to provide QoS differentiation in OBS networks. The majority of these schemes are based on a relative QoS model in which the performance of a given traffic class is defined in comparison with other classes. A set of mechanisms have been proposed to provide an absolute traffic loss guarantee, but no mechanism has been proposed to handle absolute transmission delay in OBS networks. The aim of this paper is to propose a solution to provide an absolute transmission delay guarantee over an OBS network and thus support emerging multimedia applications with delay and bandwidth constraints based on a network architecture that is suitable for OBS switching and QoS provisioning. We also develop an analytic model based on a queuing system of the proposed solution. Finally, simulation experiments are conducted to validate the proposed scheme and study its features.