bluuebunny/crossref_metadata_2025 huggingface dataset:
Upregulation of T‐cell factor‐4 isoform‐responsive target genes in hepatocellular carcinoma
Authors: Tomimaru Yoshito , Koga Hironori , Yano Hirohisa , de la Monte Suzanne , Wands Jack R. , Kim Miran
Published: April 2013

Background

The Wnt/β‐catenin signalling pathway regulates genes involved in cell proliferation, survival, migration and invasion through regulation by T‐cell factor (TCF)‐4 transcription factor proteins. However, the role ofTCF‐4 isoforms generated by alternative splicing events in hepatocellular carcinoma (HCC) is unknown.

Aim

Here, we investigatedTCF‐4 isoforms (TCF‐4J and K)‐responsive target genes that are important in hepatic oncogenesis and tumour development.

Methods

Gene expression microarray was performed onHCCcells overexpressingTCF‐4J and K isoforms. Expression level of selected target genes was evaluated and correlations were made between their expression level and that ofTCF‐4 isoform in 47 pairs of humanHCCtumours.

Results

Comparison by gene expression microarray revealed that 447 genes were upregulated and 343 downregulated more than 2.0‐fold inTCF‐4J compared withTCF‐4K expressing cells. We validated expression of 18 selected target genes involved in Wnt/β‐catenin, insulin/IGF‐1/IRS1 and Notch signalling pathways in 47 pairs of humanHCCs and adjacent uninvolved liver tissues. It was observed that 13 genes (CLDN2,STK17B,SPP1,AXIN2,WISP2,MMP7,IRS1,ANXA1,CAMK2N1,ASPH,GPR56,CD24 andJAG1) activated byTCF‐4J isoform inHCCcells, were also upregulated inHCCtumours compared with adjacent peritumour tissue; more importantly, 10 genes exhibited a significant correlation with theTCF‐4J expression level in tumour.

Conclusion

TCF‐4 isoforms (TCF‐4J and K) activated different downstream target genes inHCC. The biological consequence ofTCF‐4J isoform expression was upregulation of genes associated with tripartite Wnt/β‐catenin, insulin/IGF‐1/IRS1 and Notch signal transduction pathway activation, which contribute to the pathogenesis ofHCC.
Oxidative stress and antibody levels to periodontal bacteria in adults: the Nagasaki Islands study
Authors: Tamaki N , Hayashida H , Fukui M , Kitamura M , Kawasaki K , Nakazato M , Maeda T , Saito T , Ito H‐O
Published: April 2013

Objective

Periodontitis is a chronic inflammatory disease of the tissues supporting the teeth and is caused by subgingival plaque. Systemic increases in reactive oxygen species are involved in pathogenesis of periodontitis. This study addressed the relationship between levels of serum oxidative stress and antibodies against putative periodontopathic bacteria and their association with periodontal conditions, in a community‐based study.

Subjects and Methods

Serum samples were measured for reactive oxygen metabolite (ROM) levels and anti‐oxidant capacity. The serum levels of immunoglobulin G (IgG) antibodies to Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Aggregatibacter actinomycetemcomitans (Aa), and Eikenella corrodens (Ec) were determined by ELISA.

Results

The participants with greater clinical attachment loss had higher serum ROM levels and IgG antibody titers to Pg. Serum ROM levels were positively correlated with antibody titers to Pg, Pi, and Ec. When the participants with greater probing pocket depth and clinical attachment loss were used as the dependent variables, high ROM levels showed a statistically significant associations in multivariate logistic analyses; the adjusted odds ratios were 2.9 (95% confidence interval = 1.0–8.5) and 6.0 (95% confidence interval = 2.0–17.6), respectively.

Conclusions

It was concluded that an increased oxidative stress may be detrimental to periodontitis in Japanese community‐dwelling adults.
Pre‐processing, registration and selection of adaptive optics corrected retinal images
Authors: Ramaswamy Gomathy , Devaney Nicholas
Published: April 2013

Purpose

In this paper, the aim is to demonstrate enhanced processing of sequences of fundus images obtained using a commercial AO flood illumination system. The purpose of the work is to (1) correct for uneven illumination at the retina (2) automatically select the best quality images and (3) precisely register the best images.

Methods

Adaptive optics corrected retinal images are pre‐processed to correct uneven illumination using different methods; subtracting or dividing by the average filtered image, homomorphic filtering and a wavelet based approach. These images are evaluated to measure the image quality using various parameters, including sharpness, variance, power spectrum kurtosis and contrast. We have carried out the registration in two stages; a coarse stage using cross‐correlation followed by fine registration using two approaches; parabolic interpolation on the peak of the cross‐correlation and maximum‐likelihood estimation. The angle of rotation of the images is measured using a combination of peak tracking and Procrustes transformation.

Results

We have found that a wavelet approach (Daubechies 4 wavelet at 6th level decomposition) provides good illumination correction with clear improvement in image sharpness and contrast. The assessment of image quality using a ‘Designer metric’ works well when compared to visual evaluation, although it is highly correlated with other metrics. In image registration, sub‐pixel translation measured using parabolic interpolation on the peak of the cross‐correlation function and maximum‐likelihood estimation are found to give very similar results (RMS difference 0.047 pixels). We have confirmed that correcting rotation of the images provides a significant improvement, especially at the edges of the image. We observed that selecting the better quality frames (e.g. best 75% images) for image registration gives improved resolution, at the expense of poorer signal‐to‐noise. The sharpness map of the registered and de‐rotated images shows increased sharpness over most of the field of view.

Conclusion

Adaptive optics assisted images of the cone photoreceptors can be better pre‐processed using a wavelet approach. These images can be assessed for image quality using a ‘Designer Metric’. Two‐stage image registration including correcting for rotation significantly improves the final image contrast and sharpness.
Pediatric Pyoderma Gangrenosum with Splenic and Pulmonary Involvement
Authors: Allen Caroline P. , Hull Jeremy , Wilkison Nick , Burge Susan M.
Published: April 2013

An 8‐year‐old boy presented with ulcers on the lip and limbs, scattered pustules, fever, and general malaise. Further investigation revealed splenic and pulmonary lesions. A diagnosis of pyoderma gangrenosum with splenic and pulmonary involvement was made. The authors have not found a previous report of pediatric pyoderma with splenic involvement in the literature.
Pathologic Features of Pediatric Head and Neck Melanoma
Authors: Tcheung Win Janet , Nelson Kelly , Aldabagh Bishr , Puja Puri
Published: April 2013

Although malignant melanoma is rare in children, its incidence is steadily increasing, and it is potentially lethal. Few studies have examined head and neck melanoma in children, and even fewer have focused on the histopathologic features of melanoma within this anatomic region. To further the understanding of this entity, we examined pathology specimens from nine subjects age 18 years and younger with an original diagnosis of head or neck melanoma. The anatomic locations of these primary melanomas were the face and nose (n = 4), scalp and neck (n = 4), and ear (n = 1). The cases included seven superficial spreading melanomas, one unclassified (possible nodular) melanoma, and one melanoma in situ. No melanomas demonstrating desmoplastic or spindle cell morphologies were noted upon review. Breslow depth ranged from 0 to 2.9 mm (mean 1.3 mm, median 0.6 mm), with Clark level ranging from I to V. Pagetoid scatter was found in eight cases. Other notable features included regression (n = 5), ulceration (n = 1), and associated melanocytic nevus (n = 4). We did not observe any small cell variants; all nine cases had an epithelioid appearance. Nor was any melanoma‐associated mortality observed at last follow‐up (mean 60.4 mos, median 48 mos, range 2–174 mos). These histopathologic features were consistent with adult‐type melanoma, which is in agreement with other histopathologic studies of melanoma in children.
Factors Related to Sexual Practices and Successful Sexually Transmitted Infection/HIV Intervention Programs for Latino Adolescents
Authors: Lee Young‐Me , Dancy Barbara , Florez Elizabeth , Holm Karyn
Published: April 2013

Objective

The purpose of this integrative literature review was to explore factors that are related to sexual practices among Latino adolescents and identify which of those factors are common across successful sexually transmitted infection (STI)/HIV intervention programs for Latino adolescents.

Design

An integrative literature review was conducted. Search terms included Latino, Hispanic, education, intervention/prevention programs, sex, sexuality, reproductive health, health risk behaviors, multiple sex partners, contraception, STI/HIV/AIDS, sexually transmitted diseases, delay in initiation of sexual intercourse, consistent use of birth control, avoidance of STI/HIV infections, unintended pregnancy, cultural factors, and gender roles.

Results

Findings revealed from the review of 17 articles addressing factors related to sexual practices among Latino adolescents included familialism, religion, gender roles, level of knowledge/information, and privacy/confidentiality. Five successful STI/HIV intervention programs, that incorporated those factors to effectively reduce risky sexual behaviors were identified. STI/HIV knowledge and gender roles were recognized as common factors integrated into and across successful intervention programs for this population.

Conclusion

Only STI/HIV knowledge and gender roles were found as common factors across the five successful STI/HIV intervention programs and should be incorporated into future intervention programs that are culturally and gender specific. Therefore, health care providers need to understand culturally related gender roles and their impact on sexual practices to provide culturally sensitive and appropriate sex education about STIs and HIV for Latino adolescents to increase the program potential for reducing STI/HIV.
Severe vitamin D deficiency is associated with non‐tuberculous mycobacterial lung disease: A case‐control study
Authors: Jeon Kyeongman , Kim Su‐Young , Jeong Byeong‐Ho , Chang Boksoon , Shin Sung Jae , Koh Won‐Jung
Published: April 2013

Background and objective

Previous studies have found evidence of an association between tuberculosis and vitamin D deficiency (VDD). However, the association between VDD and infection caused by non‐tuberculous mycobacteria (NTM) has never been studied. This study evaluated the prevalence and severity of VDD in NTM lung disease and attempted to identify predictive factors.

Methods

Age‐ and sex‐matched case‐control study was conducted to assess the prevalence and severity of VDD in patients with NTM lung disease.

Results

After adjusting for potential confounding factors, the adjusted mean serum level of 25‐hydroxyvitamin D (25(OH)D) levels was lower in 104 patients with NTM lung disease (10.7 ng/mL, 95% confidence interval (CI) 4.5–16.8 ng/mL) than that of 312 controls (13.7 ng/mL, 95% CI 7.4–19.5 ng/mL) (P = 0.012). Although the prevalence of VDD defined as serum 25(OH)D level <20 ng/mL was not different, severe VDD defined as serum 25(OH)D level <10 ng/mL was more prevalent in patients (P < 0.001). In multivariate analysis, severe (but not mild) VDD was independently associated with NTM lung disease (adjusted odds ratio 3.9, 95% CI 1.9–8.5, P < 0.001).

Conclusions

Patients with NTM lung disease have a high prevalence of severe VDD and VDD was independently associated with NTM lung disease. Further studies are needed to examine causality.
Epicene Agreement and Inflected Infinitives When the Data Is “Under Control”: A Reply to Modesto ()
Authors: Rodrigues Cilene , Hornstein Norbert
Published: April 2013

Two empirical domains in Brazilian Portuguese have recently been claimed by Modesto (2010) to be problematic for the movement theory of control. We employ experimental‐syntax methods and find that more rigorous methodology reveals a more robust set of results that undermines both lines of argumentation. The first argument concerns agreement with epicene nouns in Romance that can be used as a diagnostic for the underlying presence of a moved element and, in particular, whether embedded null subjects are the result of finite control (as movement). The evidence confirms that embedded null subjects in finiteCPs pattern together with obligatory control in Brazilian Portuguese, but not in Italian, and that the methodology is sensitive enough to distinguish these two language types. The second set of experimental‐syntax results concern the interpretation of inflected infinitives in Portuguese and demonstrate that null subjects of inflected infinitives do not favor partial‐control readings, instead patterning together with nonobligatory control. As such, although they raise interesting questions about the status ofproin partialpro‐drop grammars, inflected infinitives are orthogonal to the predictions of the movement theory of control.
Apelin acts in the subfornical organ to influence neuronal excitability and cardiovascular function
Authors: Dai Li , Smith Pauline M. , Kuksis Markus , Ferguson Alastair V.
Published: April 2013

Key points

Apelin receptor mRNA is expressed in the subfornical organ.

Apelin influences the excitability of the majority of subfornical organ neurons, with similar proportion showing depolarizing and hyperpolarizing effects.

Hyperpolarizations appear to result from the activation of a sustained voltage‐activated potassium conductance, while depolarizations may result from modulation of a non‐selective cationic conductance.

In vivo microinjection of apelin into the subfornical organ results in decreases in blood pressure.

Abstract  Apelin is an adipocyte‐derived hormone involved in the regulation of water balance, food intake and the cardiovascular system partially through actions in the CNS. The subfornical organ (SFO) is a circumventricular organ with identified roles in body fluid homeostasis, cardiovascular control and energy balance. The SFO lacks a normal blood–brain barrier, and is thus able to detect circulating signalling molecules such as angiotensin II and leptin. In this study, we investigated actions of apelin‐13, the predominant apelin isoform in brain and circulatory system, on the excitability of dissociated SFO neurons using electrophysiological approaches, and determined the cardiovascular consequences of direct administration into the SFO of anaesthetized rats. Whole cell current clamp recording revealed that bath‐applied 100 nm apelin‐13 directly influences the excitability of the majority of SFO neurons by eliciting either depolarizing (31.8%, mean 7.0 ± 0.8 mV) or hyperpolarizing (28.6%, mean −10.4 ± 1.8 mV) responses. Using voltage‐clamp techniques, we also identified modulatory actions of apelin‐13 on specific ion channels, demonstrating that apelin‐13 activates a non‐selective cationic conductance to depolarize SFO neurons while activation of the delayed rectifier potassium conductance underlies hyperpolarizing effects. In anaesthetized rats, microinjection of apelin into SFO decreased both blood pressure (BP) (mean area under the curve −1492.3 ± 357.1 mmHg.s, n= 5) and heart rate (HR) (−32.4 ± 10.39 beats, n= 5). Our data suggest that circulating apelin can directly affect BP and HR as a consequence of the ability of this peptide to modulate the excitability of SFO neurons.
Optical Analysis of a Heliostat Array With Linked Tracking
Authors: Dunham M. T. , Kasetty R. , Mathur A. , Lipiński W.
Published: April 2013

The optical performance of a novel solar concentrator consisting of a 400 spherical heliostat array and a linked two-axis tracking system is analyzed using the Monte Carlo ray-tracing technique. The optical efficiency and concentration ratio are compared for four different heliostat linkage configurations, including linkages of 1 × 1, 1 × 2, 2 × 2, 4 × 4, and 5 × 5 heliostats for 7-hour operation and the selected months of June and December. The optical performance of the concentrator decreases with the increasing number of heliostats in the individual groups due to increasing optical inaccuracies. In June, the best-performing linked configuration, in which 1 heliostat in the east-west direction and 2 heliostats in the north-south direction are linked, provides a monthly-averaged 7-hour optical efficiency and average concentration ratio of 79% and 511 suns, respectively. In December, the optical efficiency and the average concentration ratio decreases to 61% and 315 suns, respectively.
Experimental and Numerical Investigation of Torsion Fatigue of Bearing Steel
Authors: Bomidi John A. R. , Weinzapfel Nick , Slack Trevor , Mobasher Moghaddam Sina , Sadeghi Farshid , Liebel Alexander , Weber Joerg , Kreis Thomas
Published: April 2013

This paper presents the results of torsion fatigue of widely used bearing steels (through hardening with bainite, martensite heat treatments, and case hardened). An MTS torsion fatigue test rig (TFTR) was modified with custom mechanical grips and used to evaluate torsional fatigue life and failure mechanism of bearing steel specimen. Tests were conducted on the TFTR to determine the ultimate strength in shear (Sus) and stress cycle (S-N) results. Evaluation of the fatigue specimens in the high cycle regime indicates shear driven crack initiation followed by normal stress driven propagation, resulting in a helical crack pattern. A 3D finite element model was then developed to investigate fatigue damage in torsion specimen and replicate the observed fatigue failure mechanism for crack initiation and propagation. In the numerical model, continuum damage mechanics (CDM) were employed in a randomly generated 3D Voronoi tessellated mesh of the specimen to provide unstructured, nonplanar, interelement, and inter/transgranular paths for fatigue damage accumulation and crack evolution as observed in micrographs of specimen. Additionally, a new damage evolution procedure was implemented to capture the change in fatigue failure mechanism from shear to normal stress assisted crack growth. The progression of fatigue failure and the stress-life results obtained from the fatigue damage model are in good agreement with the experimental results. The fatigue damage model was also used to assess the influence of topological microstructure randomness accompanied by material inhomogeneity and defects on fatigue life dispersion.
Intersection-Free and Topologically Faithful Slicing of Implicit Solid
Authors: Huang Pu , Wang Charlie C. L. , Chen Yong
Published: April 2013

We present a robust and efficient approach to directly slicing implicit solids. Different from prior slicing techniques that reconstruct contours on the slicing plane by tracing the topology of intersected line segments, which is actually not robust, we generate contours by a topology guaranteed contour extraction on binary images sampled from given solids and a subsequent contour simplification algorithm which has the topology preserved and the geometric error controlled. The resultant contours are free of self-intersection, topologically faithful to the given r-regular solids and with shape error bounded. Therefore, correct objects can be fabricated from them by rapid prototyping. Moreover, since we do not need to generate the tessellated B-rep of given solids, the memory cost our approach is low—only the binary image and the finest contours on one particular slicing plane need to be stored in-core. Our method is general and can be applied to any implicit representations of solids.
Po‐Poster ‐ 08: Comparison of two methods for commissioning BEAMnrc Elekta SL25 accelerator model
Authors: Richard C A‐ , Munger P
Published: April 2013

Incident electron beam parameters of Monte Carlo linear accelerator model are typically determined by comparing computed profiles and depth‐dose curves with measurements. Several variations have been suggested in literature: Sheikh 2002 used kerma equivalent off‐axis factors while van der Zee 1999 used cross profiles in large water phantom. In this study, we compared both methods. The BEAMnrc and DOSXYZnrc codes are used to simulate 6MV and 25MV photon beam from medical linear accelerator Elekta SL25. The mean energy and radial width of the incident electron beam intensity distributions (assumed Gaussian and cylindrically symmetric) are derived by both in air and in water technique. Excluding region of electronic disequilibrium (build‐up and penumbra) local dose difference between simulated and measured curves must be under 2% to found agreement. The statistical uncertainties on calculated dose at each point is about 0.7% (or better) at 1 sigma level. We show that off‐axis curves are more sensitive to mean energy of electron beam than depth‐dose curves. The matching mean energy and radial parameters of the incident electrons beam (6MV & 25MV) for both in air and in water technique converge within 6%. Particular attention is also devoted to measurement in air and their consequences on matching parameters.
Po‐Poster ‐ 09: Depth dose gradients: A new approach to bremsstrahlung spectrum reconstruction
Authors: Paniak L , Charland P
Published: April 2013

A new approach to significantly improve the accuracy of bremsstrahlung spectra reconstructed from central axis depth dose data is introduced. While typical methods directly use the measured depth dose data, we show the advantages of using the gradient of this data for reconstruction. The inverse problem in terms of gradients is shown to be markedly less ill‐conditioned than the depth dose based inverse problem. We regularize the ill‐conditioning by truncating a diagonalization of the inverse problem to alleviate the effects of noise due to measurement and computational errors. The error in taking derivatives of depth dose data is demonstrated to be sufficiently controllable in an explicit Monte Carlo generated 15 MV spectrum example as not to overtake the improvements in the conditioning of the inverse problem.
Po‐Poster ‐ 11: Interface dosimetry around air cavities for cobalt‐60, 6MV and 15MV beams using EGSnrc/DOSXYZnrc Monte‐Carlo simulation
Authors: Joshi C , Darko J , Vidyasagar P , Schreiner J
Published: April 2013

Underdosing of the treatment target in radiation therapy can occur when tumors are situated near natural air cavities due to charged particle disequilibrium around air‐tissue interfaces. These effects increase with energy and decrease with radiation field size. Significant underdosing may occur with small field sizes, which may be critical for IMRT and tomotherapy techniques, which employ radiation beamlets of varying intensities to deliver conformal radiation therapy. Cobalt‐60 based tomotherapy has been suggested as a clinically and commercially viable alternative to 6MV linac based approaches. The work presented here is undertaken to explore potential reduction in interface underdosing with Co‐60 based tomotherapy due to lower beam energy. The Monte‐Carlo simulations using EGSnrc/DOSXYZnrc code were performed for single, parallel opposed and four beams of Co‐60 γ‐rays, and 6MV and 15MV x‐rays. The radiation fields were varied in size from small beamlets of 2×2cm2 to large fields up to 9×9cm2. The doses were scored near the air‐water interfaces for the air cavity of sizes 1×1×1cm3, 3×3×3cm3 and 5×5×5cm3 centered within a 20×20×20cm3 water phantom in 2×2×2mm3 voxels and compared with doses in homogeneous water phantom. In all situations, no significant interface underdosing is observed for 1×1×1cm3 cavity or where radiation beam is comparable or larger than the cavity size. The interface underdosing decreases with an increase in the numbers and size of the radiation beams, and increases with energy. Significant interface underdosing is observed for small beams. Co‐60 simulations show significantly less underdosing near the interfaces than that with 6MV and 15MV beams.
Po‐Poster ‐ 20: Octree based compression method of DICOM images for voxel number reduction and faster Monte Carlo simulations
Authors: Hubert‐Tremblay V , Archambault L , Beaulieu L , Roy R
Published: April 2013

Purpose: Diminish the number of voxels created from a set of DICOM images while keeping critical information at tissue interfaces needed in a Monte Carlo simulation without compromising the physical quality of the voxelized image. An algorithm was developed to apply an octree compression to DICOM images. The algorithm works as follows: the whole set of DICOM image is assumed as a cube. It is then split in eight equal smaller cubes. Each of the cubes is checked for density homogeneity. If a high density gradient is encountered in a cube, it is also split in eight equal parts. This process goes on until the minimum specified voxel size is reach. The resulting image is composed of various voxels size. To verify precision, Monte Carlo simulation with GEANT4 using a narrow beam passing through several high density gradients was done. The resulting number of voxels range from 5 to 20% of the original size depending on configuration. The voxel area on a typical slice is 1 square voxel (i.e. no compression) at high density gradient to 64 square voxel for homogeneous sections. Mean volume was about 5.43 voxels for the phantom used. Monte Carlo simulation shows less then 1% difference in dose at the high gradient interface. The octree compression is an excellent method to compress DICOM information for Monte Carlo treatment planning without losing precision at the interfaces in homogeneous regions. Given good parameters the algorithm also has the ability to smooth digital noise in the homogenous area.
Po‐Poster ‐ 22: Patient specific quality assurance for helical tomotherapy
Authors: Thomas S , MacKenzie M , Field G , Syme A , Fallone B
Published: April 2013

Helical tomotherapy is a highly integrated platform for delivering image guided and inverse planned IMRT. The TomoTherapy system combines highly conformal external beam IMRT with on board megavoltage CT, as well as integrated image fusion, moveable lasers, and a highly accurate couch. Patient specific QA, using film and ion chamber, helps ensure that the dose distributions that are delivered as planned. The patient specific QA employs several software tools, some provided by TomoTherapy Inc., and some developed in house. The QA process hinges on the integrated system ability to export patient delivery sinograms for calculation in a phantom. Analysis tools for comparing calculation and measured results are also present. Results from the film dosimetry system, ion chamber point measurements, as well as the use of the gamma function to assess the resulting measured vs. calculated distribution are presented. An in house computer code is employed which allows the gamma analysis to be constrained to region of interest. Results for ten recent of patients on in house research protocols are presented, showing that average point dose measurement are within 1.06% of the planning system. The gamma value from film is better for more recent patients; differences found in earlier patients are shown to result from the inherent difficulties in using film as a dosimeter (processing, need for care and refinement in calibration technique).
Po‐Poster ‐ 27: An anthropomorphic study in evaluating scattered radiation at pediatric CT
Authors: Wu H , Gallet J
Published: April 2013

Purpose: The object of this study was to evaluate the dose contribution resulting from scattered radiation in CT head scans for pediatric patients using a one‐year‐old anthropomorphic tissue equivalent phantom. The dose due to scattered radiation was calculated, and the distribution of scattered radiation was analyzed. Methods and Materials: The direct exposure values were measured from specifically tagged organs by wedging TLD chips into tissue equivalent plugs. The absorbed doses were calculated with the roentgen‐rad conversion factors for tissues of one year olds. Additionally, absorbed doses were measured for nearly all the radiosensitive organs and tissues, inside and outside the scanned volume. The attribution of the scattered radiation was analyzed. Results: Two scan techniques were selected: 12mm and 20mm collimation head scans, both imaged at 120 kV. Scattered radiation contributed nearly 15 % to the total effective dose for both scanning techniques. The absorbed organ doses due to scattered radiation decreased exponentially as a function of the distance from the scanned volume. Conclusions: Scattered radiation had an appreciable contribution to the total effective dose. Pediatric radio‐sensitive organs close to the scanned volume could potentially receive relatively high absorbed doses, as determined from our study. It was also shown that absorbed doses due to scattered radiation fell exponentially, the further the organs from the irradiated volume. Further studies are required to understand the dependence of scatter on pediatric age, and CT technique factors.
Sci‐AM Fri ‐ 02: Probing radiation induced cell damage with 31P NMR spectroscopy
Authors: Rapley P , Shewchuk C , Richard C
Published: April 2013

Nuclear magnetic resonance has the ability to detect changes in tumour, and cell metabolism induced by radiation therapy. This study examined the feasibility of using NMR spectroscopy to quantify metabolic change in response to radiation dose. The metabolites of MCF‐7 cancer cells were extracted using a freeze‐thaw procedure developed for this study, and analyzed by NMR spectroscopy. A reproducibility study was performed consisting of 28 non‐irradiated samples processed from 10 different batch experiments. Peak height ratios relative to inorganic phosphate (Pi) were determined for all phosphorous metabolites present. The intra‐batch standard deviation in peak height ratios was determined to be 1.8%, 7.47%, 3.42%, 2.40%, 2.74%, and 3.21% for phosphoethanolamine, phosphocholine, glycerophosphoethanolamine, glycerophosphocholine, and two unidentified groups of peaks in the high‐energy phosphate range, respectively. In addition, the spectral position (ppm) of Pi was investigated, and found to have intra‐batch standard deviation of 0.014 ppm. The biological response delay time of 48 hrs was determined to yield the greatest metabolic change. Three batch experiments with cells in growth medium where irradiated to 6 Gy, 12 Gy and 0 Gy (control) with a 6 MeV electron linear accelerator beam. Although the sensitivity varied between batches, quantitative analysis of the change (relative to the control) in peak height ratios of the metabolites and Pi spectral shift suggests a significant correlation between dose and metabolic response.
Sci‐AM Fri ‐ 04: Radiation induced apoptosis and chromosomal aberrations in human lymphocytes: Estimating the risks associated with radiation exposures
Authors: Ryan L , Lavoie J , Schnarr K , Almardini M , Ho A , Boreham D
Published: April 2013

Research conducted at McMaster University has shown a relative biological effect (RBE) of unity, between 280keV neutrons and gamma radiation, for the induction of apoptosis in human lymphocytes. Similar results have also been seen by Vral et al. (1998) and Warenius and Down (1995) for the induction of apoptosis in human lymphocytes and mouse thymocytes respectively. It has previously been reported that neutrons of energies 36keV to 14.6Mev have an RBE ranging from 67.1±28.9 to 16±6.8 for induction of dicentrics in human lymphocytes respectively (Schmid et al., 2003, 2002, and 2000). This discrepancy between RBEs suggests that further work is needed to understand why human lymphocytes have such varying response to different radiations. Radiation‐induced apoptosis and chromosomal aberrations are being measured in parallel. In this study, it was found that 280keV neutron induce chromosome breaks with an RBE of 6.4 (for the induction of 1 break/cell). An experiment was established to study the types of chromosomal aberrations which exist in the lymphocytes which have not committed apoptosis 48 hours after radiation. Isolated lymphocytes were incubated for 48 hours in complete media before PHA stimulation. This allowed the analysis of the chromosomal damage present in cells that do not commit apoptosis immediately. It is possible that the cells which have not committed apoptosis at 48 hours are those which have been less severely damaged and may be viewed by the organism as being repairable.
Sci‐YIS Fri ‐ 02: Calculated Pwall values in clinical photon beams
Authors: Buckley L , Rogers D
Published: April 2013

Dosimetry of high‐energy photon beams is based upon absorbed dose to water standards and requires the use of ionization chambers with several correction factors. This study investigates the wall correction factor, Pwall, in high‐energy photon beams for both cylindrical and parallel‐plate chambers using Monte Carlo calculations. For cylindrical chambers, dosimetry protocols use an empirical formula to determine Pwall despite high quality experimental evidence that there are problems with this formula. Wall corrections are not provided for parallel‐plate chambers in photon beams due to a lack of information available regarding the correction factors for these chambers. Monte Carlo calculations are carried out using the EGSnrc user‐code CSnrc to calculate the wall correction factor for a series of ion chambers using a correlated sampling variance reduction technique. Calculations of the wall correction are performed for a variety of chambers at the reference depth in photon beams, using realistic beam spectra from clinical accelerators, ranging in nominal energy from to 24 MV. For cylindrical chambers, Pwall values differ by as much as 0.8% from the predicted values. This discrepancy is used to resolve previous experimental results that pointed to problems with the Pwall formalism. Pwall values are also shown for parallel‐plate chambers in high‐energy photon beams and have corrections up to 2%. These data should allow parallel‐plate chambers to be used in photon as well as in electron beams.
Sci‐YIS Fri ‐ 09: Small volume dosimetry with multiple scintillation probes
Authors: Archambault L , Gingras L , Beddar A , Roy R , Beaulieu L
Published: April 2013

We present a novel matrix dosimeter with high sensitivity, good precision and reproducibility based on plastic scintillation dosimetry. This dosimeter possesses excellent water equivalence and linearity to dose, dose rate and energy. It was built by coupling scintillating fibers, chosen for their high collection efficiency, to clear optical fiber. Light measurements were performed with a color CCD camera in order to compare two techniques to remove the stem effect: background subtraction and chromatic filtering. Chromatic filtering uses light at two different wavelengths (green and blue channels of the CCD) to remove the undesired Cerenkov radiation. Irradiations were performed at 6 MV for various doses and field sizes. Stem effect caused by Cerenkov radiation ranged from 5 % (5×5 field) to 35 % (30×30 field) of the total signal. Chromatic filtering and background subtraction both allow to extract from the signal the stem effect with a similar precision. Linearity of the system was validated down to 2.5 cGy (1.31 % standard deviation) with 0.0055 cm2 probes. At 10 cGy the standard deviation dropped below 0.6 %. Depth dose curves were also measured with a precision below 1 % compared to ionization chamber measurements. Chromatic filtering removes the necessity of a second optical fiber for background subtraction, therefore increasing the spatial resolution while maintaining a precision below 1 % for most of the dose range. The CCD camera allows more than 150 detectors in its field of view, which can be used in water, in phantom or in vivo.
Sci‐YIS Fri ‐ 10: Tomographic composition analysis of intact urinary calculi by x‐ray coherent scatter
Authors: Davidson M , Batchelar D , Velupillai S , Denstedt J , Cunningham I
Published: April 2013

Knowledge of urinary stone composition and structure provides important insights in guiding treatment and preventing recurrence. No present method can successfully provide information relating structure and composition of intact stones. We are developing a tomographic technique that uses measures of coherently scattered diagnostic x rays to yield stone composition and structure. Coherent‐scatter (CS) properties depend on molecular structure and are, therefore, sensitive to material composition. For powdered, amorphous or polycrystalline materials with no significant parallel crystal orientation, CS patterns are azimuthally symmetric. In materials with preferred crystallite orientation, such as urinary stones, bright spots appear in their CS patterns. This may compromise a composition analysis based on comparing CS measurements from urinary calculi to a library of CS signatures from powdered chemicals. We show that a tomographic reconstruction of CS measurements (CSCT) effectively eliminates bright spots and yields CS patterns equivalent to powders. This allows for direct comparison with a powdered chemical reference library and provides more accurate material identification. Validation was achieved using an aluminium rod phantom, which exhibits bright spots much like calculi. CSCT composition analysis was performed on intact stones deemed chemically pure by infrared spectroscopy. Computed tomographic reconstruction of CS signals allowed the generation of composition maps, showing the distribution of components. These images provide strong evidence that current laboratory techniques risk missing critical stone components in their analysis due to inadequate sampling. This supports the development of CS analysis as a stone analysis technique both in the laboratory and possibly in situ.
Sci‐PM Fri ‐ 01: Application of broadly tunable asymmetric multiple‐quantum‐well (AMQW) lasers to optical coherence tomography (OCT)
Authors: Wang J , Cassidy D
Published: April 2013

Optical coherence tomography (OCT) requires a broad‐band light source for time domain OCT or a broadly tunable light source for Fourier domain OCT. People use an LED or an SLD for time domain OCT and use a swept laser for Fourier domain OCT. Asymmetric multiple‐quantum‐well (AMQW) lasers have superiority in obtaining a broad and flat gain spectrum, thus it should be possible to achieve both broadband and high‐power operation with AMQW lasers. We show in this work that with a DOE applied short external cavity system, an AMQW laser could work as both a tunable laser for Fourier domain OCT and as a broad‐band light source for time domain OCT. The former application is straight‐forward. We put our new idea in the latter application. If one uses a Fourier domain approach and integrates in time the output of the detector while the wavelength of the source is tuned rapidly, the tunable light source will appear as an incoherent light source with a depth resolution that is inversely proportional to the spectral width that the laser is tuned over. Therefore the depth resolution can be increased by broader spectral width. With our AMQW laser, the maximum tuning range is as broad as 100 nm, with a corresponding depth resolution of 10.6 μm in air with center wavelength of 1.55 μm. The maximum depth that could be measured depends on the spacing of the longitudinal modes of the laser and is 550 μm for a laser with mode‐spacing of 1 nm.
Sci‐PM Fri ‐ 02: Determination of optical properties of tissue in situ using four different frequency domain models
Authors: Xu H , Patterson M , Farrell T
Published: April 2013

The following problem was investigated: implant an intensity modulated light source and two detectors in tissue. From a measurement of the ratio of fluences and relative phase at the two detectors, estimate the absorption (μa) and reduced scattering (μs′) coefficients of the tissue. An initial guess of these quantities is iteratively improved by comparison of forward calculations with measurements. The model used for forward calculation must be fast, yet accurate. Four models were compared on the basis of errors in recovered optical properties: standard diffusion approximation (SDA), single Monte Carlo (SMC), delta‐P1, and isotropic similarity model (ISM). For μs′/μa>10, SDA recovered both coefficients within 5–10%, but for lower μs′/μa the errors were as large as 25%. Although the delta‐P1 model has been found to perform better under some conditions, we found no significant advantage in this application. The ISM was equivalent to SDA for μs′/μa>10 and gave errors in μa less than 7% and μs′ less than 17% for low albedo. The SMC model was the best; both coefficients were recovered to within 10% regardless of the albedo. In order to apply the SMC model, a restricted optical coefficient space must be used in the inverse problem solution.
Sci‐AM1 Sat ‐ 01: A system for MRI‐guided thermal therapy of prostate disease with transurethral ultrasound heating applicators
Authors: Chopra R , Choy V , Baker S , Tang K , Boyes A , Bronskill M
Published: April 2013

An increasing number of prostate cancers are detected at an early stage when the tumour is localised within the gland. Image‐guided transurethral thermal therapy is a promising minimally‐invasive approach to treat targeted regions of the prostate gland while sparing surrounding tissue from unwanted damage. This work describes both a system developed to deliver MRI‐guided transurethral thermal therapy, and the characterisation of multi‐element ultrasound heating applicators. The delivery system includes five independent channels capable of producing up to 50W of RF power. Heating patterns produced by the device can be visualised during treatment using MRI thermometry and software developed to interface with the MR scanner. A fully MRI‐compatible motor has also been developed to rotate the heating applicator during treatment within the scanner. Evaluation of the capability to perform quantitative thermometry during heating with these heating applicators has been performed in a thermal gel material (TGM) developed in our lab with tissue‐mimicking ultrasound and thermal properties. This system has enabled us to validate MRI measurements of temperature distributions with the boundary of thermal coagulation in the TGM. In addition, verification of numerical simulations of heating has been accomplished and the feasibility of using this technology for conformal treatment of the prostate has been addressed.
Sci‐PM Sat ‐ 07: Optical readout of sucrose radiation dosimeter
Authors: Allanson S , Jordan K
Published: April 2013

Ferrous ions and xylenol orange dissolved in sulfuric acid (FX) is a common radiochromic chemical dosimeter for water‐equivalent dosimetry. The versatility of this reaction is extended by using it to readout dose deposited in materials that are soluble in FX. Sucrose has been used as a tissue‐equivalent dosimeter with electron spin resonance readout. In this work, doses recorded in sucrose are measured by dissolving the sugar into FX and recording the change in transmission at 590 nm. Conventional transmission measurements with a UV‐VIS absorption spectrometer and 10 cm cuvettes, determined a dose response of approximately 0.02 cm−1 Gy−1 with 10% sucrose‐FX solutions. Fructose, propylene glycol and water had lower but measurable dose sensitivities. Long liquid waveguides were investigated as a means to increase the transmission measurement sensitivity. Hydrophobic Teflon® FEP tubing and hydrophilic thin‐walled glass capillary tubing were both investigated. The Teflon® tubing was unsuitable to due large changes in transmission with time. This phenomenon was attributed to a lack of surface wetting by the aqueous solutions. The glass capillary waveguide provided stable transmission measurements. A linear response was measured with 0.4 g sucrose samples from 0.5 to 3 Gy with a 60 cm long glass tube. Optimizing the measurement conditions will allow measurement of 0.1 g sucrose samples to a minimum dose of approximately 0.1 Gy. Sucrose with optical readout is a simple and inexpensive dosimetry system.
Histone Demethylases Set the Stage for Cancer Metastasis
Authors: Cao Jian , Yan Qin
Published: April 2013

By modulating metastatic gene expression, histone demethylases are potential targets for suppressing cancer metastasis.
Antimicrobial Susceptibility of Propionibacterium acnes Isolates from Shoulder Surgery
Authors: Crane John K. , Hohman Donald W. , Nodzo Scott R. , Duquin Thomas R.
Published: April 2013

Orthopedic surgeons at our institution have noticed an increase in the number of infections due to
Propionibacterium acnes
, especially following operations on the shoulder. We collected
P. acnes
isolates from our hospital microbiology laboratory for 1 year and performed antimicrobial susceptibility testing on 28 strains from the shoulder. Antibiotics with the lowest MIC values against
P. acnes
(MIC
50
and MIC
90
) included penicillin G (0.006, 0.125), cephalothin (0.047 and 0.094), and ceftriaxone (0.016, 0.045), while others also showed activity. Strains resistant to clindamycin were noted.
Pharmacokinetics-Pharmacodynamics of Tazobactam in Combination with Ceftolozane in an
In Vitro
Infection Model
Authors: VanScoy Brian , Mendes Rodrigo E. , Nicasio Anthony M. , Castanheira Mariana , Bulik Catharine C. , Okusanya Olanrewaju O. , Bhavnani Sujata M. , Forrest Alan , Jones Ronald N. , Friedrich Lawrence V. , Steenbergen Judith N. , Ambrose Paul G.
Published: April 2013

Despite β-lactamase inhibitors being available for clinical use for nearly 30 years, a paucity of data exists describing the pharmacokinetic-pharmacodynamic (PK-PD) determinants of efficacy for these agents. Herein, we describe dose fractionation studies designed to determine the exposure measure most predictive of tazobactam efficacy in combination with ceftolozane and the magnitude of this measure necessary for efficacy in a PK-PD
in vitro
infection model. The challenge organism panel was comprised of an isogenic CTX-M-15-producing
Escherichia coli
triplet set, genetically engineered to transcribe different levels of
bla
CTX-M-15
. These recombinant strains exhibited ceftolozane MIC values of 4, 16, and 64 μg/ml representing low, moderate, and high levels of CTX-M-15, respectively. Different
bla
CTX-M-15
transcription levels were confirmed by relative quantitative real-time PCR (qRT-PCR) and β-lactamase hydrolytic assays. The exposure measure associated with efficacy was the percentage of the dosing interval that tazobactam concentrations remained above a threshold (%Time>threshold), regardless of enzyme expression (
r
2
= 0.938). The threshold concentrations identified were 0.05 μg/ml for low and moderate and 0.25 μg/ml for the high-β-lactamase expression strain constructs. The magnitudes of %Time>threshold for tazobactam associated with net bacterial stasis and a 1- and 2-log
10
CFU reduction in bacteria at 24 h were approximately 35, 50, and 70%, respectively. These data provide an initial target tazobactam concentration-time profile and a paradigm to optimize tazobactam dosing when combined with ceftolozane.
Ergothioneine Is a Secreted Antioxidant in Mycobacterium smegmatis
Authors: Sao Emani Carine , Williams Monique J. , Wiid Ian J. , Hiten Nicholas F. , Viljoen Albertus J. , Pietersen Ray-Dean D. , van Helden Paul D. , Baker Bienyameen
Published: April 2013

Ergothioneine (ERG) and mycothiol (MSH) are two low-molecular-weight thiols synthesized by mycobacteria. The role of MSH has been extensively investigated in mycobacteria; however, little is known about the role of ERG in mycobacterial physiology. In this study, quantification of ERG at various points in the growth cycle of
Mycobacterium smegmatis
revealed that a significant portion of ERG is found in the culture media, suggesting that it is actively secreted. A mutant of
M. smegmatis
lacking
egtD
(
MSMEG_6247
) was unable to synthesize ERG, confirming its role in ERG biosynthesis. Deletion of
egtD
from wild-type
M. smegmatis
and an MSH-deficient mutant did not affect their susceptibility to antibiotics tested in this study. The ERG- and MSH-deficient double mutant was significantly more sensitive to peroxide than either of the single mutants lacking either ERG or MSH, suggesting that both thiols play a role in protecting
M. smegmatis
against oxidative stress and that ERG is able to partly compensate for the loss of MSH.