bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation and validation of an ultrasonic tissue characterization technique for quantitative assessment of normal‐tissue toxicity in radiation therapy
Authors: Zhou Jun , Zhang PengPeng , Osterman K. Sunshine , Woodhouse Shermian A. , Schiff Peter B. , Yoshida Emi J. , Lu Zheng Feng , Pile‐Spellman Eliza R. , Kutcher Gerald J. , Liu Tian
Published: April 2009

The goal of this study was to implement and validate a noninvasive, quantitative ultrasonic technique for accurate and reproducible measurement of normal‐tissue toxicity in radiation therapy. The authors adapted an existing ultrasonic tissue characterization (UTC) technique that used a calibrated 1D spectrum based on region‐of‐interest analysis. They modified the calibration procedure by using a reference phantom instead of a planar reflector. This UTC method utilized ultrasonic radio‐frequency echo signals to generate spectral parameters related to the physical properties (e.g., size, shape, and relative acoustic impedance) of tissue microstructures. Three spectral parameters were investigated for quantification of normal‐tissue injury: Spectral slope, intercept, and midband fit. They conducted a tissue‐mimicking phantom study to verify the reproducibility of UTC measurements and initiated a clinical study of radiation‐induced breast‐tissue toxicity. Spectral parameter values from measurements on two phantoms were reproducible within 1% of each other. Eleven postradiation breast‐cancer patients were studied and significant differences between the irradiated and untreated (contralateral) breasts were observed for spectral intercept and midband fit but not for slope . In comparison to the untreated breast, the average difference in the spectral intercept was and the average difference in the midband fit was . The preliminary clinical study demonstrated the feasibility of using the quantitative ultrasonic method to evaluate normal‐tissue toxicity in radiation therapy.
A method to dynamically balance intensity modulated radiotherapy dose between organs‐at‐risk
Authors: Das Shiva K.
Published: April 2009

The IMRT treatment planning process typically follows a path that is based on the manner in which the planner interactively adjusts the target and organ‐at‐risk (OAR) constraints and priorities. The time‐intensive nature of this process restricts the planner from fully understanding the dose trade‐off between structures, making it unlikely that the resulting plan fully exploits the extent to which dose can be redistributed between anatomical structures. Multiobjective Pareto optimization has been used in the past to enable the planner to more thoroughly explore alternatives in dose trade‐off by combining pre‐generated Pareto optimal solutions in real time, thereby potentially tailoring a plan more exactly to requirements. However, generating the Pareto optimal solutions can be nonintuitive and computationally time intensive. The author presents an intuitive and fast non‐Pareto approach for generating optimization sequences (prior to planning), which can then be rapidly combined by the planner in real time to yield a satisfactory plan. Each optimization sequence incrementally reduces dose to one OAR at a time, starting from the optimization solution where dose to all OARs are reduced with equal priority, until user‐specified target coverage limits are violated. The sequences are computationally efficient to generate, since the optimization at each position along a sequence is initiated from the end result of the previous position in the sequence. The pre‐generated optimization sequences require no user interaction. In real time, a planner can more or less instantaneously visualize a treatment plan by combining the dose distributions corresponding to user‐selected positions along each of the optimization sequences (target coverage is intrinsically maintained in the combination). Interactively varying the selected positions along each of the sequences enables the planner to rapidly understand the nature of dose trade‐off between structures and, thereby, arrive at a suitable plan in a short time. This methodology is demonstrated on a prostate cancer case and olfactory neuroblastoma case.
Focused RF hyperthermia using magnetic fluids
Authors: Tasci T. Onur , Vargel Ibrahim , Arat Anil , Guzel Elif , Korkusuz Petek , Atalar Ergin
Published: April 2009

Heat therapies such as hyperthermia and thermoablation are very promising approaches in the treatment of cancer. Compared with available hyperthermia modalities, magnetic fluid hyperthermia (MFH) yields better results in uniform heating of the deeply situated tumors. In this approach, fluid consisting of superparamagnetic particles (magnetic fluid) is delivered to the tumor. An alternating (ac) magnetic field is then used to heat the particles and the corresponding tumor, thereby ablating it. However, one of the most serious shortcomings of this technique is the unwanted heating of the healthy tissues. This results from the magnetic fluid diffusion from the tumor to the surrounding tissues or from incorrect localization of the fluids in the target tumor area. In this study, the authors demonstrated that by depositing appropriate static (dc) magnetic field gradients on the alternating (ac) magnetic fields, focused heating of the magnetic particles can be achieved. A focused hyperthermia system was implemented by using two types of coils: dc and ac coils. The ac coil generated the alternating magnetic field responsible for the heating of the magnetic particles; the dc coil was used to superimpose a static magnetic field gradient on the alternating magnetic field. In this way, focused heating of the particles was obtained in the regions where the static field was dominated by the alternating magnetic field. In vitro experiments showed that as the magnitude of the dc solenoid currents was increased from 0 to 1.8 A, the specific absorption rate (SAR) of the superparamagnetic particles 2 cm apart from the ac solenoid center decreased by a factor of 4.5, while the SAR of the particles at the center was unchanged. This demonstrates that the hyperthermia system is capable of precisely focusing the heat at the center. Additionally, with this approach, shifting of the heat focus can be achieved by applying different amounts of currents to individual dc solenoids. In vivo experiments were performed with adult rats, where magnetic fluids were injected percutaneously into the tails (with homogeneous fluid distribution inside the tails). Histological examination showed that, as we increased the dc solenoid current from 0.5 to 1.8 A, the total burned volume decreased from 1.6 to verifying the focusing capability of the system. The authors believe that the studies conducted in this work show that MFH can be a much more effective method with better heat localization and focusing abilities.
Liquid scintillator for 2D dosimetry for high‐energy photon beams
Authors: Pönisch Falk , Archambault Louis , Briere Tina Marie , Sahoo Narayan , Mohan Radhe , Beddar Sam , Gillin Michael T.
Published: April 2009

Complex radiation therapy techniques require dosimetric verification of treatment planning and delivery. The authors investigated a liquid scintillator (LS) system for application for real‐time high‐energy photon beam dosimetry. The system was comprised of a transparent acrylic tank filled with liquid scintillating material, an opaque outer tank, and a CCD camera. A series of images was acquired when the tank with liquid scintillator was irradiated with a 6 MV photon beam, and the light data measured with the CCD camera were filtered to correct for scattering of the optical light inside the liquid scintillator. Depth‐dose and lateral profiles as well as two‐dimensional (2D) dose distributions were found to agree with results from the treatment planning system. Further, the corrected light output was found to be linear with dose, dose rate independent, and is robust for single or multiple acquisitions. The short time needed for image acquisition and processing could make this system ideal for fast verification of the beam characteristics of the treatment machine. This new detector system shows a potential usefulness of the LS for 2D QA.
Pseudomonoenergetic x‐ray diffraction measurements using balanced filters for coherent‐scatter computed tomography
Authors: Beath S. R. , Cunningham I. A.
Published: April 2009

Coherent‐scatter computed tomography (CSCT) is a method of “composition” imaging based on measurements of diffraction patterns from tissues. Use of an x‐ray tube degrades scatter pattern angular resolution due to the x‐ray spectral width, making it difficult to uniquely identify some materials. The use of two transmission filters with similar atomic numbers (balanced “Ross filters”) to generate pseudomonoenergetic scatter patterns is described as it applies to CSCT. An analysis of angular‐blur mechanisms reveals that focal spot size and beam width are the most important factors determining Bragg‐peak width when Er–Tm filters are used. A relative RMS spectral width of 1% can be achieved in the difference spectrum and a Bragg‐peak RMS angular width of approximately 0.14° (relative width of 3% at 5° scatter angle) can be achieved with an effective energy of 58 keV.
A new automated method for the segmentation and characterization of breast masses on ultrasound images
Authors: Cui Jing , Sahiner Berkman , Chan Heang‐Ping , Nees Alexis , Paramagul Chintana , Hadjiiski Lubomir M. , Zhou Chuan , Shi Jiazheng
Published: April 2009

Segmentation is one of the first steps in most computer‐aided diagnosis systems for characterization of masses as malignant or benign. In this study, the authors designed an automated method for segmentation of breast masses on ultrasound (US) images. The method automatically estimated an initial contour based on a manually identified point approximately at the mass center. A two‐stage active contour method iteratively refined the initial contour and performed self‐examination and correction on the segmentation result. To evaluate the method, the authors compared it with manual segmentation by two experienced radiologists (R1 and R2) on a data set of 488 US images from 250 biopsy‐proven masses (100 malignant and 150 benign). Two area overlap ratios ( and ) and an area error measure were used as performance measures to evaluate the segmentation accuracy. Values for , defined as the ratio of the intersection of the computer and the reference segmented areas to the reference segmented area, were and , respectively, when manually segmented mass regions by R1 and R2 were used as the reference. Although this indicated a high agreement between the computer and manual segmentations, the two radiologists’ manual segmentation results were significantly more consistent, with and , respectively, when the segmented regions by R1 and R2 were used as the reference. To evaluate the segmentation method in terms of lesion classification accuracy, feature spaces were formed by extracting texture, width‐to‐height, and posterior shadowing features based on either automated computer segmentation or the radiologists’ manual segmentation. A linear discriminant analysis classifier was designed using stepwise feature selection and two‐fold cross validation to characterize the mass as malignant or benign. For features extracted from computer segmentation, the case‐based test values ranged from to , indicating a comparable performance to those extracted from manual segmentation by radiologists ( value range: to ).
Impact of motion velocity on four‐dimensional target volumes: A phantom study
Authors: Nakamura Mitsuhiro , Narita Yuichiro , Sawada Akira , Matsugi Kiyotomo , Nakata Manabu , Matsuo Yukinori , Mizowaki Takashi , Hiraoka Masahiro
Published: April 2009

This study aims to assess the impact of motion velocity that may cause motion artifacts on target volumes (TVs) using a one‐dimensional moving phantom. A 20 mm diameter spherical object embedded in a QUASAR™ phantom sinusoidally moved with approximately 5.0 or 10.0 mm amplitude along the longitudinal axis of the computed tomography (CT) couch. The motion period was manually set in the range of 2.0–10.0 s at approximately 2.0 s interval. Four‐dimensional (4D) CT images were acquired by a four‐slice CT scanner (LightSpeed RT; General Electric Medical Systems, Waukesha, WI) with a slice thickness of 1.25 mm in axial cine mode. The minimum gantry rotation of 1.0 s was employed to achieve the maximum in‐slice temporal resolution. Projection data over a full gantry rotation (1.0 s) were used for image reconstruction. Reflective marker position was recorded by the real‐time positioning management system (Varian Medical Systems, Palo Alto, CA). ADVANTAGE 4D software exported ten respiratory phase volumes and the maximum intensity volume generated from all reconstructed data (MIV). The threshold to obtain static object volume (, 4.19 ml) was used to automatically segment TVs on CT images, and then the union of TVs on 4D CT images was constructed. TVs on MIV were also segmented by the threshold that can determine the area occupied within the central slice of . The maximum motion velocity for each phase bin was calculated using the actual averaged motion period displayed on ADVANTAGE 4D software , the range of phases used to construct the target phase bin (phase range), and a mathematical model of sinusoidal function. Each volume size and the motion range of TV in the cranial‐caudal (CC) direction were measured. Subsequently, cross‐correlation coefficients between TV size and motion velocity as well as phase range were calculated. Both misalignment and motion‐blurring artifacts were caused by high motion velocity. Less than 6% phase range was needed to construct the 4D CT data set, except for of 2.0 s. While the positional differences between the TV and ideal centroid in the CC direction were within the voxel size for , the differences were up to 2.43 and 4.15 mm for and (10.0 mm, 2.0 s), respectively. The maximum volumetric deviations between TV sizes and were 43.68% and 91.41% for of 5.0 and 10.0 mm, respectively. sizes were slightly larger than sizes. Volumetric deviation between TV size and had a stronger correlation with motion velocity rather than phase range. This phantom study demonstrated that motion artifacts were substantially reduced when the phantom moved longitudinally at low motion velocity during 4D CT image acquisition; therefore, geometrical uncertainties due to motion artifacts should be recognized when determining TVs, especially with a fast period.
Comparison of low‐pitch and respiratory‐averaged CT protocols for attenuation correction of cardiac PET studies
Authors: Nye Jonathon A. , Hamill James , Tudorascu Dana , Carew John , Esteves Fabio , Votaw John R.
Published: April 2009

PET/CT perfusion studies suffer from artifacts caused by misalignment of transmission and emission data due to contractile cardiac and respiratory motion. This study investigates whether substantial differences exist between two respiration‐averaging approaches for attenuation correction (AC): low‐pitch helical (HCT) and time‐averaged CT (ACT). Fifty‐four consecutive patients received paired HCT (0.45 pitch, 120 kVp, 76 mA, collimated slice width, 1 s gantry rotation time, 4.93 mGy CTDI) and ACT (sequence mode: 6.1 s acq./bed, 80 kVp, 13 mA, collimated slice width, 5.53 mGy CTDI) AC scans under free‐breathing prior to Rb‐82 rest/adenosine stress. Mismatch between the emission and paired transmission data was compared by calculating the volume of myocardial uptake overlying the left CT lung field. Data were then reconstructed with the CT AC scans and normalized to injected dose and bodyweight. Paired rest and paired stress PET images were reoriented identically along the short axis and sampled into a 17‐segment polar map for comparison. The ratio of HCT‐PET and ACT‐PET polar maps at rest and stress was calculated and grouped by segment for all patients. 95% confidence intervals were calculated to compare changes in the polar map ratios between the two AC methods. No significant difference was observed between the HCT and ACT overlying volume in the rest or stress emission data. 68% of the patients presented visual respiratory artifacts in the HCT images compared to 32% in the ACT. That 23% of the ACT images presented with photon starvation artifacts and increasing BMI was a significant indicator for the occurrence of photon starvation in the ACT AC scans . The ratio of the reconstructed PET polar segment data showed good agreement between AC methods with 95% confidence intervals ranging from 0.92 to 1.07 in the rest data and 0.93 to 1.07 in the stress data segments. Bias, calculated by averaging the polar segment ratios, showed 1% higher values in the ACT‐PET rest reconstructions compared to the HCT‐PET rest reconstructions and no measurable bias in the stress reconstructions. This study shows good agreement and negligible bias between low‐pitch HCT and ACT protocols for attenuation correction of cardiac PET data.
Optimal number of respiratory gates in positron emission tomography: A cardiac patient study
Authors: Dawood Mohammad , Büther Florian , Stegger Lars , Jiang Xiaoyi , Schober Otmar , Schäfers Michael , Schäfers Klaus P.
Published: April 2009

Respiratory gating is the method of dividing the data from a tomographic scan with respect to the respiratory phase of the patient. It enables more accurate images by reducing the effects of motion blur and attenuation artifacts due to motion. However, it induces image degradation due to higher noise levels as the number of events per gate is reduced. Due to lack of systematic studies in this regard, different numbers of gates are being used in the scientific and clinical practice. The present study aims at examining the relationship between the respiratory signal, the number of gates required for accurate motion detection, and the level of noise with two different methods of gating: (1) Amplitude‐based gating and (2) time‐based gating. Patient data with a wide range of motion are used for the study. The results show that time‐based gating underestimates the real respiratory displacement by up to 50%. The optimal number of gates is 8 for amplitude‐ and 6 for time‐based gatings. The noise properties remain the same with either method but noise increases with increasing number of gates.
Virtual tagging for laxative‐free CT colonography: Pilot evaluation
Authors: Näppi Janne , Yoshida Hiroyuki
Published: April 2009

Laxative‐free computed tomographic colonography (lf CTC) could significantly improve patient adherence to colorectal screening. However, the interpretation of lf CTC data is complicated by the presence of poorly tagged feces and partial‐volume artifacts that imitate colorectal lesions. The authors developed a method for virtual tagging of such artifacts. A probabilistic model of colonic wall was developed, and virtual tagging was performed on artifacts that were identified by the model. The method was evaluated with 46 clinical lf CTC cases that were prepared with dietary fecal tagging only. Visual examples show that the method can label partial‐volume artifacts, poorly tagged feces, nonadhering completely untagged feces, and artifacts such as rectal tubes. The effect of virtual tagging was evaluated by comparing the detection accuracy of a fully automated polyp detection scheme without and with the method. With virtual tagging, the per‐lesion detection sensitivity was 100% for lesions with 3.8 false positives per patient (per two CT scan volumes) and 90% for lesions with 5.4 false positives per patient on average. The improvement in detection performance by virtual tagging was statistically significant (; JAFROC and JAFROC‐1).
An MRI‐compatible system for focused ultrasound experiments in small animal models
Authors: Chopra Rajiv , Curiel Laura , Staruch Robert , Morrison Laetitia , Hynynen Kullervo
Published: April 2009

The development of novel MRI‐guided therapeutic ultrasound methods including potentiated drug delivery and targeted thermal ablation requires extensive testing in small animals such as rats and mice due to the widespread use of these species as models of disease. An MRI‐compatible, computer‐controlled three‐axis positioning system was constructed to deliver focused ultrasound exposures precisely to a target anatomy in small animals for high‐throughput preclinical drug delivery studies. Each axis was constructed from custom‐made nonmagnetic linear ball stages driven by piezoelectric actuators and optical encoders. A range of motion of was achieved, and initial bench top characterization demonstrated the ability to deliver ultrasound to the brain with a spatial accuracy of 0.3 mm. Operation of the positioning system within the bore of a clinical 3 T MR imager was feasible, and simultaneous motion and MR imaging did not result in any mutual interference. The system was evaluated in its ability to deliver precise sonications within the mouse brain, linear scanned exposures in a rat brain for blood barrier disruption, and circular scans for controlled heating under MR temperature feedback. Initial results suggest that this is a robust and precise apparatus for use in the investigation of novel ultrasound‐based therapeutic strategies in small animal preclinical models.
Dosimetric verification of a commercial Monte Carlo treatment planning system (VMC++) for a 9 MeV electron beam
Authors: Schiapparelli P. , Zefiro D. , Taccini G.
Published: April 2009

The aim of this work was to evaluate the performance of the voxel‐based Monte Carlo algorithm implemented in the commercial treatment planning system ONCENTRA MASTERPLAN for a 9 MeV electron beam produced by a linear accelerator Varian Clinac 2100 C/D. In order to realize an experimental verification of the computed data, three different groups of tests were planned. The first set was performed in a water phantom to investigate standard fields, custom inserts, and extended treatment distances. The second one concerned standard field, irregular entrance surface, and oblique incidence in a homogeneous PMMA phantom. The last group involved the introduction of inhomogeneities in a PMMA phantom to simulate high and low density materials such as bone and lung. Measurements in water were performed by means of cylindrical and plane‐parallel ionization chambers, whereas measurements in PMMA were carried out by the use of radiochromic films. Point dose values were compared in terms of percentage difference, whereas the gamma index tool was used to perform the comparison between computed and measured dose profiles, considering different tolerances according to the test complexity. In the case of transverse scans, the agreement was searched in the plane formed by the intersection of beam axis and the profile (2D analysis), while for percentage depth dose curves, only the beam axis was explored (1D analysis). An excellent agreement was found for point dose evaluation in water (discrepancies smaller than 2%). Also the comparison between planned and measured dose profiles in homogeneous water and PMMA phantoms showed good results (agreement within 2%‐2 mm). Profile evaluation in phantoms with internal inhomogeneities showed a good agreement in the case of “lung” insert, while in tests concerning a small “bone” inhomogeneity, a discrepancy was particularly evidenced in dose values on the beam axis. This is due to the inaccurate geometrical description of the phantom that is linked to the calculation voxel size, a feature over which the user has no control.
Systematic uncertainties in the Monte Carlo calculation of ion chamber replacement correction factors
Authors: Wang L. L. W. , La Russa D. J. , Rogers D. W. O.
Published: April 2009

In a previous study [Med. Phys. 35, 1747–1755 (2008)], the authors proposed two direct methods of calculating the replacement correction factors (or) for ion chambers by Monte Carlo calculation. By “direct” we meant the stopping‐power ratio evaluation is not necessary. The two methods were named as the high‐density air (HDA) and low‐density water (LDW) methods. Although the accuracy of these methods was briefly discussed, it turns out that the assumption made regarding the dose in an HDA slab as a function of slab thickness is not correct. This issue is reinvestigated in the current study, and the accuracy of the LDW method applied to ion chambers in aphoton beam is also studied. It is found that the two direct methods are in fact not completely independent of the stopping‐power ratio of the two materials involved. There is an implicit dependence of the calculatedvalues upon the stopping‐power ratio evaluation through the choice of an appropriate energy cutoff, which characterizes a cavity size in the Spencer‐Attix cavity theory. Since thevalue is not accurately defined in the theory, this dependence on the stopping‐power ratio results in a systematic uncertainty on the calculatedvalues. For phantom materials of similar effective atomic number to air, such as water and graphite, this systematic uncertainty is at most 0.2% for most commonly used chambers for either electron or photon beams. This uncertainty level is good enough for current ion chamber dosimetry, and the merits of the two direct methods of calculatingvalues are maintained, i.e., there is no need to do a separate stopping‐power ratio calculation. For high‐materials, the inherent uncertainty would make it practically impossible to calculate reliablevalues using the two direct methods.
Characterization of a water‐equivalent fiber‐optic coupled dosimeter for use in diagnostic radiology
Authors: Hyer Daniel E. , Fisher Ryan F. , Hintenlang David E.
Published: April 2009

This work reports on the characterization of a new fiber‐optic coupled (FOC) dosimeter for use in the diagnostic radiology energy range. The FOC dosimeter was constructed by coupling a small cylindrical plastic scintillator, in diameter and 2 mm in length, to a 2 m long optical fiber, which acts as a light guide to transmit scintillation photons from the sensitive element to a photomultiplier tube (PMT). A serial port interface on the PMT permits real‐time monitoring of light output from the dosimeter via a custom computer program. The FOC dosimeter offered excellent sensitivity and reproducibility, allowing doses as low as 0.16 mGy to be measured with a coefficient of variation of only 3.64%. Dose linearity was also excellent with a correlation coefficient of 1.000 over exposures ranging from 0.16 to 57.29 mGy. The FOC dosimeter exhibited little angular dependence from axial irradiation, varying by less than 5% over an entire revolution. A positive energy dependence was observed and measurements performed within a scatter medium yielded a 10% variation in sensitivity as beam quality changed due to hardening and scatter across a 16 cm depth range. The current dosimetry system features an array of five PMTs to allow multiple FOC dosimeters to be monitored simultaneously. Overall, the system allows for rapid and accurate dose measurements relevant to a range of diagnostic imaging applications.
Improved critical structure sparing with biologically based IMRT optimization
Authors: Qi X. Sharon , Semenenko Vladimir A. , Li X. Allen
Published: April 2009

The impact of using biological models in treatment planning on plan quality is studied by comparing IMRT plans generated using selected commercially available treatment planning systems (TPSs) employing biological models/quantities in IMRT optimization (bIMRT) and the conventional physically (dose‐volume) based optimization (pIMRT). A total of 25 IMRT plans, generated for five cases of different anatomic sites (brain, head and neck, lung, pancreas, and prostate) using five TPSs, two bIMRT (CMS Monaco and Phillips ) and three pIMRT (CMS Xio, Phillips , and Tomotherapy) systems, were compared. Dose‐volume histograms, maximum, minimum, and mean doses, target heterogeneity and conformity indices, equivalent uniform dose (EUD), and an overall plan‐ranking index (fEUD) were used in the comparison. It is clear from the comparison that the use of biological models in treatment planning optimization can generate IMRT plans with significantly improved normal tissue sparing with similar or slightly increased dose heterogeneity in the target, as compared to the conventional dose‐volume based optimization for the same beam arrangement. For example, the bIMRT plans lead to smaller EUDs in 32 out of 37 normal structures in all five cases combined, as compared to the pIMRT plans. Caution should be exercised in choosing appropriate models and/or model parameters and in evaluating the plan obtained when using the biologically based treatment planning system.
Molecular Imaging in Oncology.
Authors: Bourland Daniel
Published: April 2009

Molecular Imaging in Oncology. Pomper Martin G. and Gelovani Juri G. Informa Healthcare USA, Inc., 2008. Hardcover 744 pp. Price: $399.95. ISBN 9780849374173.
The Physics of Clinical MR Taught Through Images, Second Edition.
Authors: Clarke Geoffrey
Published: April 2009

The Physics of Clinical MR Taught Through Images, Second Edition. Runge Val M., Nitz Wolfgang R. and SchmeetsStuart H. Thieme Medical Publishers, Inc., New York, NY, 2009. Softcover 256 pp. Price: $59.95. ISBN: 9781604061611.
Laboratory services for thyroglobulin and implications for monitoring of differentiated thyroid cancer
Authors: Clark P M
Published: April 2009

Serum thyroglobulin is used as a marker for monitoring differentiated thyroid cancer. There are a number of analytical challenges: the need for stability of the assay over decades, differences in assay bias, and interference in immunoassays by endogenous thyroglobulin antibodies. Improved precision at low analyte concentrations is desirable. Approaches to identifying assay interference are discussed. No single approach is likely to be successful on all occasions. Decision limits should be assay-specific, and clinicians should be aware of the limitations of current immunoassays.
My approach to interstitial lung disease using clinical, radiological and histopathological patterns
Authors: Leslie K O
Published: April 2009

The complex world of interstitial lung disease presents nearly insurmountable challenges to the general surgical pathologist faced with a lung biopsy in this setting. The pathology is often inflammatory and always requires clinical and radiological context for a relevant and clinically useful histopathological diagnosis. A pattern-based histopathological approach to interstitial lung disease provides a “map” for the general pathologist to navigate this area successfully, especially so when used with aid of the clinical and radiological patterns of presentation.
Vascular endothelial growth factor activity after switching of bisphosphonate treatment for metastatic breast cancer
Authors: Amir E , Trinkaus M , Simmons C E , Dranitsaris G , Clemons M J
Published: April 2009

Background:

Recent data have shown a fall in vascular endothelial growth factor (VEGF) concentrations after bisphosphonate (BP) treatment in BP-naïve patients. It has therefore been proposed that BPs may have in vivo anti-VEGF effects.

Aims:

To explore whether VEGF concentrations change after administration of a more potent BP in patients receiving long-term BP treatment.

Methods:

31 patients with breast cancer who had progressive metastatic bone disease despite treatment with early-generation BPs were switched to zoledronic acid. Serum VEGF concentrations were measured at baseline, and weeks 1, 2, 3, 4, 8 and 12.

Results:

VEGF concentration per platelet count did not change significantly at any time during the 12 weeks after treatment with zoledronic acid.

Conclusions:

Switching to zoledronic acid did not suppress circulating serum VEGF concentrations in BP-pretreated patients. Novel approaches to assess the effect of BPs on the bone milieu may provide further insight into the possible antiangiogenic properties of BPs.
Synchronous lung tumours in a patient with metachronous colorectal carcinoma and a germline MSH2 mutation
Authors: Canney A , Sheahan K , Keegan D , Tolan M , Hyland J , Green A
Published: April 2009

Mutations of DNA mismatch repair genes are characterised by microsatellite instability and are implicated in carcinogenesis. This mutation susceptible phenotype has been extensively studied in patients with hereditary non-polyposis colon carcinoma, but little is known of the contribution of such mutations in other tumour types, particularly non-small-cell lung carcinoma. This report describes the occurrence of two synchronous lung tumours, one mimicking a metastatic colon carcinoma, in a male patient with a history of metachronous colonic carcinoma. Immunohistochemistry supported a pulmonary origin for both lesions. Mismatch repair protein immunohistochemistry showed loss of MSH2 and MSH6 expression in both colonic tumours and in one lung tumour showing enteric differentiation. Subsequent mutational analysis demonstrated a deleterious germline mutation of the MSH2 mismatch repair gene. The significance of these findings and the practical diagnostic difficulties encountered in this case are discussed.
GENETIC PROGRAMMING WITH LINEAR REPRESENTATION: A SURVEY
Authors: OLTEAN MIHAI , GROŞAN CRINA , DIOŞAN LAURA , MIHĂILĂ CRISTINA
Published: April 2009

Genetic Programming (GP) is an automated method for creating computer programs starting from a high-level description of the problem to be solved. Many variants of GP have been proposed in the recent years. In this paper we are reviewing the main GP variants with linear representation. Namely, Linear Genetic Programming, Gene Expression Programming, Multi Expression Programming, Grammatical Evolution, Cartesian Genetic Programming and Stack-Based Genetic Programming. A complete description is provided for each method. The set of applications where the methods have been applied and several Internet sites with more information about them are also given.
A CONCEPT VECTOR SPACE MODEL FOR SEMANTIC KERNELS
Authors: ASEERVATHAM SUJEEVAN
Published: April 2009

Kernels are widely used in Natural Language Processing as similarity measures within inner-product based learning methods like the Support Vector Machine. The Vector Space Model (VSM) is extensively used for the spatial representation of the documents. However, it is purely a statistical representation. In this paper, we present a Concept Vector Space Model (CVSM) representation which uses linguistic prior knowledge to capture the meanings of the documents. We also propose a linear kernel and a latent kernel for this space. The linear kernel takes advantage of the linguistic concepts whereas the latent kernel combines statistical and linguistic concepts. Indeed, the latter kernel uses latent concepts extracted by the Latent Semantic Analysis (LSA) in the CVSM. The kernels were evaluated on a text categorization task in the biomedical domain. The Ohsumed corpus, well known for being difficult to categorize, was used. The results have shown that the CVSM improves performance compared to the VSM.
COMBINING TEXT CLASSIFIERS AND HIDDEN MARKOV MODELS FOR INFORMATION EXTRACTION
Authors: BARROS FLÁVIA A. , SILVA EDUARDO F. A. , PRUDÊNCIO RICARDO B. C. , FILHO VALMIR M. , NASCIMENTO ANDRÉ C. A.
Published: April 2009

In this paper, we propose a hybrid machine learning approach to Information Extraction by combining conventional text classification techniques and Hidden Markov Models (HMM). A text classifier generates a (locally optimal) initial output, which is refined by an HMM, providing a globally optimal classification. The proposed approach was evaluated in two case studies and the experiments revealed a consistent gain in performance through the use of the HMM. In the first case study, the implemented prototype was used to extract information from bibliographic references, reaching a precision rate of 87.48% in a test set with 3000 references. In the second case study, the prototype extracted information from author affiliations, reaching a precision rate of 90.27% in a test set with 300 affiliations.
MODIFIED CHAPLYGIN TRAVERSABLE WORMHOLES
Authors: CHAKRABORTY SUBENOY , BANDYOPADHYAY TANWI
Published: April 2009

Modified Chaplygin gas (MCG) is a strong candidate for the unified model of dark matter and dark energy. The equation of state of this modified model is valid from the radiation era to the ΛCDM model. In the early epoch (when ρ was large), dark matter had the dominant role, while at later stages (when ρ is small), the MCG model behaves as dark energy. In this work, we have found an exact solution to static, spherically symmetric Einstein equations describing a wormhole for an inhomogeneous distribution of MCG. For the existence of a wormhole solution, there are some restrictions concerning the parameters in the equation of state for MCG and the throat radius of the wormhole. Physical properties and characteristics of such modified Chaplygin wormholes are analyzed in detail.
ASYMPTOTIC BEHAVIOR OF THE PROPER LENGTH AND VOLUME OF THE SCHWARZSCHILD SINGULARITY
Authors: QADIR ASGHAR , SIDDIQUI AZAD A.
Published: April 2009

Though popular presentations give the Schwarzschild singularity as a point, it is known that it is spacelike and not timelike. Thus, it has a "length" and is not a "point." In fact, its length is necessarily infinite. It has been proven that the proper length of the Qadir–Wheeler suture model goes to infinity,1 while its proper volume shrinks to zero, and the asymptotic behavior of the length and volume has been calculated. That model consists of two Friedmann sections connected by a Schwarzschild "suture." The question arises whether a similar analysis could provide the asymptotic behavior of the Schwarzschild black hole near the singularity. It is proven here that, unlike the behavior for the suture model, for the Schwarzschild essential singularity Δs ~ K1/3 ln K and V ~ K-1 ln K, where K is the mean extrinsic curvature, or the York time.
FITTING THE LUMINOSITY DATA FROM TYPE Ia SUPERNOVAE IN THE FRAME OF THE COSMIC DEFECT THEORY
Authors: TARTAGLIA A. , CAPONE M. , CARDONE V. , RADICELLA N.
Published: April 2009

The cosmic defect (CD) theory is reviewed and used to fit the data for the accelerated expansion of the universe, obtained from the apparent luminosity of 192 SnIa 's. The fit from the CD theory is compared with the one obtained by means of ΛCDM. The results from the two theories are in good agreement and the fits are satisfactory. The correspondence between the two approaches is discussed and interpreted.
NEUTRINO MASS SPECTRUM FROM NEUTRINO SPIN-FLIP-DRIVEN GRAVITATIONAL WAVES
Authors: CUESTA HERMAN J. MOSQUERA , LAMBIASE GAETANO
Published: April 2009

Neutrino (ν) oscillations during the core collapse and bounce of a supernova (SN) are shown to generate the most powerful detectable gravitational wave (GW) bursts. The SN neutronization phase produces mainly electron (νe) neutrinos, the oscillations of which must take place within a few mean-free paths of their resonance surface located near their neutrinosphere. Here we characterize the GW signals produced by spin-flip oscillations inside the fast-rotating protoneutron star in the SN core. In this novel mechanism, the release of both the oscillation-produced νμ's, ντ's and the spin-flip-driven GW pulse provides a unique emission offset [Formula: see text] for measuring the ν travel time to Earth. As massive ν's get noticeably delayed on its journey to Earth with respect to the GW, they generate over the oscillation transient, the accurate measurement of this time-of-flight delay by SNEWS + LIGO, VIRGO, BBO, DECIGO, etc. can assess the absolute ν mass spectrum straightforwardly.
MODELING THE DRUG THERAPY FOR HIV INFECTION
Authors: SRIVASTAVA P. K. , BANERJEE M. , CHANDRA PEEYUSH
Published: April 2009

A mathematical model for the effect of Reverse Transcriptase (RT) Inhibitor on the dynamics of HIV is proposed and analyzed. Further, with help of numerical simulations, the relation between efficacy of administered drug, the total number of virus particles emitted from the infected cell and the transition period is also discussed.
OPTIMAL CONTROL OF STOCHASTIC FLUCTUATIONS IN BIOCHEMICAL REACTIONS
Authors: GUO XIANPING , LIU QIULI , ZHOU TIANSHOU
Published: April 2009

Different experimental conditions can give rise to changes in rate constants of biochemical reactions, thus resulting in different stochastic fluctuations in the numbers of chemical species molecules. A naturally arising question is how to choose a set of reaction rate constants such that experiment-depending stochastic fluctuations can be optimally controlled. In this paper, we determine the optimal rate constants by optimally controlling stochastic fluctuations in the numbers of chemical species molecules based on the theory of continuous-time Markov decision processes. Specifically, we first propose a stochastic model for a coupled set of biochemical reactions, then solve an optimality problem for rate constants with the mean-maximal numbers of chemical species molecules, and finally find, using a policy iteration algorithm of the continuous-time Markov decision processes, optimal rate constants with the variance-minimal molecule numbers over all possible sets of the rate constants with the maximal-mean molecule numbers obtained.
ENDOGENOUS VERSUS EXOGENOUS ORIGINS OF DISEASES
Authors: SORNETTE D. , YUKALOV V. I. , YUKALOVA E. P. , HENRY J.-Y. , SCHWAB D. , COBB J. P.
Published: April 2009

Many illnesses are associated with an alteration of the immune system homeostasis due to a combination of factors, including exogenous bacterial insult, endogenous breakdown (e.g. development of a disease that results in immuno suppression), or an exogenous hit like surgery that simultaneously alters immune responsiveness and provides access to bacteria, or genetic disorder. We conjecture that, as a consequence of the co-evolution of the human immune system with the ecology of pathogens, the homeostasis of the immune system requires the influx of pathogens. This allows the immune system to keep the ever-present pathogens under control and to react and adjust fast to bursts of infections. We construct the simplest and most general system of rate equations which describes the dynamics of five compartments: healthy cells, altered cells, adaptive immune cells, innate immune cells, and pathogens. We study four regimes obtained with or without auto-immune disorder and with or without spontaneous proliferation of infected cells. For each of the four regimes, the phase space is always characterized by four (but not necessary identical) coexisting stationary structurally stable states. Over all four regimes among the 4 × 4 possibilities, there are only seven different states that are naturally described by the model: (i) strong healthy immune system, (ii) healthy organism with evanescent immune cells, (iii) chronic infections, (iv) strong infections, (v) cancer, (vi) critically ill state, and (vii) death. Our description provides a natural framework for describing the relationships and transitions between these seven states. The analysis of stability conditions demonstrates that these seven states depend on the balance between the robustness of the immune system and the influx of pathogens. In particular, the healthy state A is found to exist only under the influence of a sufficiently large pathogen flux, which suggests that health is not the absence of pathogens, but rather a strong ability to find balance by counteracting any pathogen attack.
FORWARD START OPTIONS UNDER STOCHASTIC VOLATILITY AND STOCHASTIC INTEREST RATES
Authors: AHLIP REHEZ , RUTKOWSKI MAREK
Published: April 2009

Forward start options are examined in Heston's (Review of Financial Studies6 (1993) 327–343) stochastic volatility model with the CIR (Econometrica53 (1985) 385–408) stochastic interest rates. The instantaneous volatility and the instantaneous short rate are assumed to be correlated with the dynamics of stock return. The main result is an analytic formula for the price of a forward start European call option. It is derived using the probabilistic approach combined with the Fourier inversion technique, as developed in Carr and Madan (Journal of Computational Finance2 (1999) 61–73).
A TRACTABLE MULTIVARIATE DEFAULT MODEL BASED ON A STOCHASTIC TIME-CHANGE
Authors: MAI JAN-FREDERIK , SCHERER MATTHIAS
Published: April 2009

A stochastic time-change is applied to introduce dependence to a portfolio of credit-risky assets whose default times are modeled as random variables with arbitrary distribution. The dependence structure of the vector of default times is completely separated from its marginal default probabilities, making the model analytically tractable. This separation is achieved by restricting the time-change to suitable Lévy subordinators which preserve the marginal distributions. Jump times of the Lévy subordinator are interpreted as times of excess default clustering. Relevant for practical implementations is that the parameters of the time-change allow for an intuitive economical explanation and can be calibrated independently of the marginal default probabilities. On a theoretical level, a so-called time normalization allows to compute the resulting copula of the default times. Moreover, the exact portfolio-loss distribution and an approximation for large portfolios under a homogeneous portfolio assumption are derived. Given these results, the pricing of complex portfolio derivatives is possible in closed-form. Three different implementations of the model are proposed, including a compound Poisson subordinator, a Gamma subordinator, and an Inverse Gaussian subordinator. Using two parameters to adjust the dependence structure in each case, the model is capable of capturing the full range of dependence patterns from independence to complete comonotonicity. A simultaneous calibration to portfolio-CDS spreads and CDO tranche spreads is carried out to demonstrate the model's applicability.
Mammalian Response to Cenozoic Climatic Change
Authors: Blois Jessica L. , Hadly Elizabeth A.
Published: April 2009

Multiple episodes of rapid and gradual climatic changes influenced the evolution and ecology of mammalian species and communities throughout the Cenozoic. Climatic change influenced the abundance, genetic diversity, morphology, and geographic ranges of individual species. Within communities these responses interacted to catalyze immigration, speciation, and extinction. Combined they affected long-term patterns of community stability, functional turnover, biotic turnover, and diversity. Although the relative influence of climate on particular evolutionary processes is oft debated, an understanding of processes at the root of biotic change yields important insights into the complexity of mammalian response. Ultimately, all responses trace to events experienced by populations. However, many such processes emerge as patterns above the species level, where shared life history traits and evolutionary history allow us to generalize about mammalian response to climatic change. These generalizations provide the greatest power to understand and predict mammalian responses to current and future global change.
Shearing Melt Out of the Earth: An Experimentalist's Perspective on the Influence of Deformation on Melt Extraction
Authors: Kohlstedt David L. , Holtzman Benjamin K.
Published: April 2009

Melt extraction from the Earth's mantle requires some form of channelized flow to produce the observed disequilibrium between the crust-forming lavas and their mantle sources. In this review, we discuss the influence of deformation on melt-extraction processes, with an emphasis on the understanding gained from a wide range of laboratory experimental investigations. Rheological properties of partially molten rocks are very sensitive to melt distribution, and melt distribution is profoundly influenced by deviatoric stress in a viscously deforming partially molten rock, establishing a coupling between deformation and melt distribution. During deformation, this coupling can lead to organization of melt into melt-enriched shear zones at length scales longer than the grain size. We discuss the current state of understanding of this process, with some speculation on its role in the ensemble of processes that constitute melt extraction from the Earth.