bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectroscopic Observation of Chemical Species From High-Temperature Air Pulverized Coal Combustion
Authors: Desmira Nelfa , Nagasaka Takuya , Narukawa Kimihito , Ishikawa Akira , Kitagawa Kuniyuki , Gupta Ashwani K.
Published: April 2013

In situ monitoring of chemical species from the combustion pulverized coal in high-temperature air is examined using several different spectroscopic diagnostic at different equivalence ratios. Two-dimensional (2D) distributions of flame temperature were obtained using a thermal video camera. The experimental results showed the temperatures to range from low to 1400 °C under various conditions of fuel-lean, stoichiometric, and fuel-rich. The highest temperature and flame stability were obtained under fuel-lean combustion condition. The chemical species generated from within the combustion zone were analyzed from the spontaneous emission spectra of the flame in the Ultraviolet–visible (UV-Vis) range. The spatial distribution of NO, OH, and CN were identified from the spectra. The 2D distribution of emission intensity visualized and recorded for NO, OH, and CN revealed high-temperatures close to the root of the flame that rapidly dispersed radially outward to provide very high temperatures over a much larger volume at further downstream locations of the flame.
Po‐Poster ‐ 06: Beam spot motion of medical linear accelerators
Authors: Yeboah C , Challacombe J , Pang G , O'Brien P
Published: April 2013

Megavoltage cone‐beam computed tomography (MV‐CBCT) is a volumetric imaging method that can improve patient setup verification techniques. MV‐CBCT utilizes the treatment beam to obtain projections at every 1–2° around the patient. For this to be clinically acceptable, total dose received by the patient from all imaging sessions must be kept to a minimum and typically should be ⩽5% of the prescribed dose. This necessitates the use of extremely low doses (<<1MU) in the acquisition of each projection. At such low dose levels beam spot instability is known to exist and can compromise image quality. The purpose of this work is to quantify the beam spot motion of Siemen's accelerator for a conventional 6 MV beam and 5.4 MV “imaging beam” generated with a beryllium target. This was accomplished by using an a‐Si flat panel detector to image a cone‐beam geometric calibration phantom and using a calibration algorithm to derive the spot motion in reference frames fixed in space and/or attached to the gantry. Motion of the beam spot was observed immediately after beam startup primarily in the gun‐target direction. The maximum fixed motion of the 6MV beam spot was 1.1±0.3 mm and is similar to that observed for the low Z beam (1.2±0.1 mm). However, the beam spot position of the latter stabilized at about 0.5 MU compared to 6 MU for the 6 MV beam and had much less fluctuations once stabilized. The beam spot position of the conventional beam was much less reproducible than the low Z beam.
Po‐Poster ‐ 10: Influence of varying SSD on the penumbra and the mean square scattering angle for electron beams
Authors: Hodefi D
Published: April 2013

The objective of this study was to quantify how varying source to surface distance (SSD) for electron beam therapy affects the width of the penumbra at the surface of the patient and to determine the influence of the SSD on the mean square scattering angle at the base of the electron applicator, 〈θ2〉(0), for use in electron beam treatment planning. Penumbra values were extracted from profiles measured at the surface of a water phantom for SSDs spanning 103–116 cm for numerous combinations of beam energy and electron applicator. 〈θ2〉(0) was derived from the measured penumbra values. The width of the penumbra was shown to climb in a linear fashion with increasing SSD over the range of values investigated. It was also observed that the size of the electron cone exerted considerably more influence on the penumbra for a given SSD for lower beam energies than for higher beam energies. In the case of lower beam energies, the penumbra width for a given SSD rose in a very significant way with increasing applicator size. 〈θ2〉(0) demonstrated a decreasing trend as SSD was increased. This decline was more drastic for lower beam energies. For higher beam energies, 〈θ2〉(0) values tended to be quite similar, despite varying SSD.
Po‐Poster ‐ 17: GE Lightspeed‐RT WideView image reconstructions: Are they suitable for radiation therapy treatment planning?
Authors: Chow T , Hayward J , Shim M
Published: April 2013

GE Lightspeed‐RT CT scanner was introduced to address Radiation Therapy limitations by increasing the bore of conventional CT scanners from 70cm to 85cm, and increasing the reconstruction field of view (FOV) from 50cm to 65cm. However, the gantry detectors were not increased and still only covers a 50cm circle in the bore. The additional 7.5cm FOV is created by a WideView reconstruction algorithm that uses some basic assumptions to estimate the missing data. The resulting images have associated artifacts with the sparse data reconstruction. We investigate these artifacts and their effect on treatment planning for radiation therapy.
Po‐Poster ‐ 35: The BioMedical Imaging and Therapy Beamline at the Canadian Light Source Inc.
Authors: Christensen C , Chapman D , Sidhu N
Published: April 2013

The BioMedical Imaging and Therapy (BMIT) Beamline is a multidisciplinary, multiuse facility that is being constructed at the Canadian Light Source, Canada's National Synchrotron Facility. The BMIT Beamline will have two specific research uses, non‐destructive imaging of tissues and radiation therapy in living organisms. The total cost of this project will be approximately $17M. Funding for this project has been obtained from the Canadian Foundation for Innovation, the provincial governments and charitable foundations. The BMIT Beamline is projected to be ready for operations in 2007.
Sci‐AM Fri ‐ 01: Effects of low‐dose gamma‐radiation on micronucleus formation in non‐mammalian fish cell lines
Authors: Cassidy C , Lemon J , Boreham D
Published: April 2013

Environmental concerns of potential contamination of ecosystems with radionuclides from nuclear power plants are becoming increasingly important. This concern makes it important to study the effects that radiation may be having on chromosomal damage in non‐human biota. This can lead to a better understanding of the potential effects of radiation on aquatic organisms (i.e. radiation sensitivity), and by extension, the impact on ecosystems. A common technique for determining chromosomal aberrations is the cytokinesis‐block micronucleus (MN) assay. This assay blocks cell division prior to cytokinesis, allowing detection of DNA damage or improper chromosome segregation. This DNA damage then results in the formation of micronuclei. Micronuclei are similar to the cell's main nucleus but are smaller and may contain either whole chromosome pieces or fragments of a chromosome. We hypothesize that the frequency of micronuclei in fish will be proportional to the exposed dose. Studies have also shown that some cells are capable of an adaptive response when exposed to a low priming dose prior to a large challenge dose of ionizing radiation. It is believed that the priming dose stimulates various cellular systems including DNA repair processes, making the cells more resistant to the larger dose of ionizing radiation. There is little data concerning the adaptive response in fish cells. Our preliminary experiments have determined that Chinook Salmon are significantly more radiation resistant than mammalian cells. Adaptive response experiments are in progress. We will also report on the sensitivity of low dose ionizing radiation in other fish species.
Sci‐AM Fri ‐ 03: Radio‐electro therapy of murine fibrosarcoma: In vivo study
Authors: Vidyasagar P , Shil P , Mishra K
Published: April 2013

Radiation therapy and chemotherapy are important modalities of cancer treatment. However, there are several limitations due to the development of radio‐resistance and chemoresistance of cancer cells. This requires the development of new protocols for improved cancer therapy. The present study is an attempt to modify radiation damage by using the electric pulses (electroporation) using murine fibrosarcoma as a model system. Electroporation is a membrane phenomenon that involves the enhanced permeability of the cell membrane by application of the electric pulses of high voltage and short duration. In the present study the fibrosarcoma tumors have been treated with gamma radiation and/or electroporation (both monophasic and biphasic pulses separately). The tumor growth kinetics shows considerable growth delays in case of tumors treated with combination modality. On 7th day of treatment the average tumor volume of the treatment groups Electroporation (monophasic), Radiation, and combination of both were 85%, 80% and 51% of that of control respectively. Similarly, the treatments with Electroporation with biphasic pulses in combination with radiation also resulted in considerable tumor growth delay as compared to the control. The study reveals that the combination of radiation with electroporation has produced enhanced cytotoxicity in tumor cells and that the monophasic pulses were more effective than the biphasic pulses in modulating the radiation‐induced toxicity.
Sci‐AM Fri ‐ 05: Shielding design for a PET‐CT simulator in a radiotherapy department
Authors: Breen S , Tourneur F
Published: April 2013

Purpose: To design the shielding for a PET‐CT simulator in a radiation therapy department, and to verify the adequacy of shielding during acceptance testing. Method and Materials: A Discovery ST (GE Healthcare, Milwaukee, USA) PET‐CT scanner replaced a CT‐Simulator in our centre. Existing space was reconfigured to include a patient rest area for FDG uptake and a hot lab. Adjacent areas included a simulator control room, patient waiting rooms, and corridors; floors above and below contained offices and linac bunkers and control rooms. Patients were modeled as point sources; attenuation by concrete walls and lead shielding explicitly included build‐up. Design limits were set to 1 mSv per year for nuclear energy workers (NEWs), and 0.05 mSv per year for non‐NEWs. A linear 1.5‐GBq source of in scattering material was used to verify the adequacy of the shielding. Results: The control room was shielded with 6.35 mm of Pb. Two sheets of lead glass (48% Pb by weight) totaling 14 mm provided sufficient attenuation for a window. The patient uptake area and the scanner room were shielded with 4.7 mm of Pb on walls adjacent to corridors. No shielding was required on the floor and ceiling. Measurement showed that design goals were met. Conclusion: Strategic location of patients, NEWs, and low‐occupancy areas simplified design to these stringent limits. Careful consideration of workloads and occupancy factors are needed to meet the design criteria, particularly when older facilities are being redesigned. Design to such low limits unnecessarily increases construction cost.
Sci‐YIS Fri ‐ 04: Clinical impact of seed density and prostate elemental composition on permanent seed implant dosimetry
Authors: Carrier J , Therriault‐Proulx F , Roy R , Beaulieu L
Published: April 2013

The purpose is to evaluate the impact of inter‐seed attenuation and prostate elemental composition in clinical prostate treatment plans with 6711 125I permanent seed implants using the Monte Carlo (MC) method. The effect of seed density (number of seeds per prostate unit volume) is specifically investigated. The MC toolkit Geant4 is used to perform the simulations. The study focuses on treatment plans that were generated for clinical cases. For each plan, four different dose calculation techniques are compared: TG43‐based calculation, superposition MC (SMC), full MC with water prostate (MCW), and full MC with realistic prostate tissue (MCP). The SMC method is a technique for which a shifted one‐source MC distribution is added to the total dose distribution for each source position. It was found that seed density has a definite influence on inter‐seed attenuation. A typical low seed density (42 0.6 mCi seeds in a 26 cc prostate) yields a 0.7% drop in the CTV D90 value when comparing SMC to MCW while a drop of 2.5% is calculated for a higher seed density (75 0.3 mCi seeds, same prostate). The influence of the prostate composition is similar for all plans. When comparing MCW to MCP, the difference in total dose deposited in the CTV is 2.9 +/− 0.2%, while it is 3.6 +/− 0.3% for the D90 parameter. Overall, the effect on D90 is ranging from 4.3% to 9.3% when comparing TG43 to MCP. This effect is clinically significant.
Sci‐YIS Fri ‐ 05: Design and testing of a new sealed water calorimeter for electron beams
Authors: Stewart K , Klassen N , Ross C , Seuntjens J
Published: April 2013

The Electron Sealed Water (ESW) calorimeter is a new device designed for measurements in clinical electron beams. This work presents the calorimeter design, preliminary measurements and evaluation of correction factors. The calorimeter contains a 30×30×20 cm3 water phantom surrounded by a cooling system to allow for operation at 4°C. Two thermistor probes measure temperature change inside a glass vessel filled with high‐purity nitrogen‐saturated water. Correction factors for glass perturbation were calculated using Monte Carlo simulations. Corrections for thermal conduction were simulated using Femlab software. Resistance of the thermistor probes was measured using a lock‐in amplifier and an AC bridge circuit. Measurements were done for 6, 9, 12, 16 and 20 MeV electron beams from a Varian Clinac 21EX. Irradiations of 667 MU were done at 1000 MU/min for an irradiation time of 40 s. Measurements were also taken with a PTW Roos ion chamber inside the calorimeter phantom. For 30 runs, the standard error on the mean temperature change was less than 0.2% for all energies. When normalized to the 12 MeV measurements, values of k′R‐50 for the Roos chamber calculated from calorimeter measurements for the 9, 16 and 20 MeV beams agreed with TG‐51 values within 0.7 %. Water calorimetry in electron beams has previously been regarded as unfeasible as high dose gradients were thought to provoke unmanageable temperature gradients. Using the ESW calorimeter, we have shown for the first time that reproducible measurements can be performed in electron beams with energies as low as 6 MeV.
Sci‐YIS Fri ‐ 07: Fitting the linear‐quadratic model to detailed data set for different dose ranges
Authors: Garcia L , Leblanc J , Wilkins D , Raaphorst G
Published: April 2013

Survival curve behaviour and degree of correspondence between Linear Quadratic model1 (LQ) and experimental data in an extensive dose range for high dose rate was analyzed. Detailed clonogenic assays with irradiation given in 0.5Gy increments and a total dose range varying from 10.5 and 16Gy were performed. The cell lines investigated were: CHOAA8, hamster fibroblast cells; U373MG, human glioblastoma cells; and human prostate carcinoma cell lines CP‐3, and DU‐145. The analyses were based on χ2 statistic and Monte Carlo simulation of the experiment. A decline of fit quality at very low doses (<2Gy) is observed. This result can be explained by the hypersensitive effect observed in CHOAA8 and U373MG data and an adaptive type response in CP3 cell line. A clear improvement is discerned at slightly higher doses. This could be a result of the linearity existent in the trend of survival curve at low doses, that will affect the total fit in a range from 0Gy to final dose in linear quadratic region. The impact of including low dose data is shown through α/β ratios showing relative differences of 42, 40 and 23% for CHOAA8, CP3 and U373MG. LQ model cannot explain survival at high doses. This is shown as a deterioration of goodness of fit for high doses. A comparison of Linear Quadratic Linear model2 (LQL) with the LQ in fitting the experimental data at high doses was also performed.
Sci‐YIS Fri ‐ 08: Regional change in brain perfusion after fractionated stereotactic radiotherapy (FSRT) at 4 months and 3 years follow‐up
Authors: Igna C , Spencer D , Kay I , Chan A , Kiss Z , Frayne R
Published: April 2013

Purpose: The change in hemodynamic parameters, such as mean transit time and cerebral blood volume, reflect the damage to vasculature. A relationship between the change in hemodynamic parameters and radiation dose delivered would help predict the degree and nature of damage, and would be most beneficial for patients with a long life‐expectancy who are at risk of long‐term radiation‐induced injury. Method and Materials: We applied the relative perfusion weighted MRI technique, currently used in stroke imaging, to calculate the relative regional mean transit time (rrMTT) and relative regional cerebral blood volume (rrCBV). We acquired data for one patient. We used a 3.0 T magnet at the Seaman Family MRI Centre in Calgary and a single‐shot echo‐planar imaging (EPI) sequence following the injection of a paramagnetic contrast agent (Gd‐DTPA‐Magnevist; Berlex, Wayne, NJ). These images have been processed to yield rrMTT and rrCBV. The patient had previously been treated with surgery, but had received no chemotherapy. The percentage change in rrMTT and rrCBV was correlated to the spatial distribution of radiation dose delivered using the Pinnacle® radiation treatment planning system. Results: Our preliminary results show that with a follow‐up time of 4 months and 3 years after receiving approximately 5000 cGy/25 fractions, rrMTT and rrCBV change significantly in normal tissue and tumour. The most important normal tissue changes occur in the near‐target area. Conclusion: The change in rrMTT and rrCBV indicates response to treatment. Perfusion weighted MRI can be used to assess the change in hemodynamic measures after radiotherapy.
Sci‐PM Fri ‐ 07: The development and testing of an all‐glass vessel for absorbed dose to water
Authors: Ross C , Klassen N , McEwen M
Published: April 2013

Calorimetry is widely used for establishing primary standards for absorbed dose. The advantage of using water as a calorimetric material is that it gives directly the absorbed dose to water, which is the quantity of interest for radiation therapy. Unfortunately, radiation‐induced chemical reactions in the water (sometimes with impurities) may be exothermic or endothermic, thus contributing to an unknown “heat defect”. Calculations and measurements show that there are a few aqueous systems for which the heat defect can be established with small uncertainty. In particular, the heat defect of pure water saturated with an inert gas or with hydrogen gas is expected to be zero after an accumulated dose of a few gray. The need for maintaining high purity water systems and techniques for cleaning, filling and sealing vessels contributes significantly to the complexity associated with water calorimetry. In an effort to overcome this limitation, we have developed a vessel in which only glass comes in contact with the water and which is flame‐sealed after being filled and saturated with an appropriate gas. We have measured the response of one such vessel over several years and found it to be stable and consistent with expected results. We believe these all‐glass vessels will ease the effort of maintaining water calorimeters as absorbed dose standards and may be used for direct comparisons among laboratories with similar devices.
Sci‐PM Fri ‐ 08: Accurate surface dose measurements in CT exam using isotropic high sensitivity MOSFET dosimeters calibrated by Monte Carlo simulations
Authors: Lemire M , Hegyi G , Seuntjens J , Verhaegen F
Published: April 2013

Purpose: To measure surface dose in CT exam using isotropic high sensitivity MOSFET dosimeters calibrated by Monte Carlo (MC) simulations. Method and Materials: The EGSnrc MC code was used to model the x‐ray source of a Phillips PQ5000 CT simulator for energies ranging from 80 – 140 kVp. Half‐value layers and profiles measured in air were used as a means of validation for the CT x‐ray source model. A model of the MOSFET was build which allowed us to simulate their energy response. The MOSFET dosimeters (Thomson and Nielsen) were calibrated on the surface of a CTDI head phantom by comparing the measured dose (mV) to the calculated dose (mGy) in a voxel at the surface. Surface dose measurements were carried out on the CTDI phantom and compared with dose calculations. Results: The agreement between the simulated and measured HVL is within 2.2% over the whole kVp and filtration range. The measured and simulated profiles are within 3% up to 14 cm off‐axis and within 7.2 % over the full fan beam width considered in this study. Simulated and measured MOSFET energy response in‐air are within 5.4 % over 80–140 kVp range. The MOSFET exhibit an over‐response of about 10 % at 80 kVp compared to 140 kVp. Discrepancies between measured and calculated surface dose on the CTDI phantom increase as we move away from the point of dose normalization. Conclusion: MOSFET dosimeters offer a fast and easy means of accurately measuring surface dose in CT examinations.
β-Arrestin–Dependent Activation of the Cofilin Pathway Is Required for the Scavenging Activity of the Atypical Chemokine Receptor D6
Authors: Borroni Elena M. , Cancellieri Cinzia , Vacchini Alessandro , Benureau Yann , Lagane Bernard , Bachelerie Françoise , Arenzana-Seisdedos Fernando , Mizuno Kensaku , Mantovani Alberto , Bonecchi Raffaella , Locati Massimo
Published: April 2013

Far from being silent, the atypical chemokine receptor D6 depends on β-arrestin signaling to perform its scavenging function to degrade chemokines.
Where Parkin Parks
Authors: Ray L. Bryan
Published: April 2013

The Parkinson’s disease factors PINK1 and Parkin interact with mitofusin 2 on damaged mitochondria.
Tracking Secreted Proteins
Authors: Ray L. Bryan
Published: April 2013

A mass spectrometry–based method detects picogram quantities of proteins secreted by macrophages.
Daylight Determines Dopamine
Authors: Stern Peter R.
Published: April 2013

Switching rats from long days to short days causes neurons to change their neurotransmitters, and this changes behavior.
Translating Memories
Authors: Gough Nancy R.
Published: April 2013

Memory involves degradation of an inhibitor of translation.
Novel
erm
(T)-Carrying Multiresistance Plasmids from Porcine and Human Isolates of Methicillin-Resistant Staphylococcus aureus ST398 That Also Harbor Cadmium and Copper Resistance Determinants
Authors: Gómez-Sanz Elena , Kadlec Kristina , Feßler Andrea T. , Zarazaga Myriam , Torres Carmen , Schwarz Stefan
Published: April 2013

This study describes three novel
erm
(T)-carrying multiresistance plasmids that also harbor cadmium and copper resistance determinants. The plasmids, designated pUR1902, pUR2940, and pUR2941, were obtained from porcine and human methicillin-resistant
Staphylococcus aureus
(MRSA) of the clonal lineage ST398. In addition to the macrolide-lincosamide-streptogramin B (MLS
B
) resistance gene
erm
(T), all three plasmids also carry the tetracycline resistance gene
tet
(L). Furthermore, plasmid pUR2940 harbors the trimethoprim resistance gene
dfrK
and the MLS
B
resistance gene
erm
(C), while plasmids pUR1902 and pUR2941 possess the kanamycin/neomycin resistance gene
aadD
. Sequence analysis of approximately 18.1 kb of the
erm
(T)-flanking region from pUR1902, 20.0 kb from pUR2940, and 20.8 kb from pUR2941 revealed the presence of several copies of the recently described insertion sequence IS
Sau10
, which is probably involved in the evolution of the respective plasmids. All plasmids carried a functional cadmium resistance operon with the genes
cadD
and
cadX
, in addition to the multicopper oxidase gene
mco
and the ATPase copper transport gene
copA
, which are involved in copper resistance. The comparative analysis of
S. aureus
RN4220 and the three
S. aureus
RN4220 transformants carrying plasmid pUR1902, pUR2940, or pUR2941 revealed an 8-fold increase in CdSO
4
and a 2-fold increase in CuSO
4
MICs. The emergence of multidrug resistance plasmids that also carry heavy metal resistance genes is alarming and requires further surveillance. The colocalization of antimicrobial resistance genes and genes that confer resistance to heavy metals may facilitate their persistence, coselection, and dissemination.
The Staphylococcus aureus Thiol/Oxidative Stress Global Regulator Spx Controls
trfA
, a Gene Implicated in Cell Wall Antibiotic Resistance
Authors: Jousselin Ambre , Kelley William L. , Barras Christine , Lew Daniel P. , Renzoni Adriana
Published: April 2013

S. aureus
combats cell wall antibiotic stress by altered gene expression mediated by various environmental signal sensors. In this study, we examined the transcriptional regulation of
trfA
, a gene related to
mecA
of
Bacillus subtilis
encoding an adaptor protein implicated in multiple roles, notably, proteolysis and genetic competence. Despite strong sequence similarity to
B. subtilis
mecA
, the function of
S. aureus
trfA
remains largely unexplored; however, its deletion leads to almost complete loss of resistance to oxacillin and glycopeptide antibiotics in glycopeptide-intermediate
S. aureus
(GISA) derivatives of methicillin-susceptible or methicillin-resistant
S. aureus
(MRSA) clinical or laboratory isolates. Northern blot analysis and 5′ rapid amplification of cDNA ends (RACE) mapping revealed that
trfA
was expressed monocistronically by three promoters. Cell wall-active antibiotic exposure led to both increased
trfA
transcription and enhanced steady-state TrfA levels.
trfA
promoter regulation was not dependent upon the cell wall stress sentinel VraSR and other sensory stress systems, such as GraRS, WalkRK, Stk1/Stp1, and SigB. Notably, we discovered that the global oxidative-stress regulator Spx controlled
trfA
transcription. This finding was also confirmed using a strain with enhanced Spx levels resulting from a defect in
yjbH
, encoding a Spx-interacting protein governing Spx proteolytic degradation. A cohort of clinical GISA strains revealed significant steady-state upregulation of
trfA
compared to corresponding susceptible parental strains, further supporting a role for
trfA
in antibiotic resistance. These data provide strong evidence for a link between cell wall antibiotic stress and evoked responses mediated by an oxidative-stress sensor.
Potential Factors for Inadequate Voriconazole Plasma Concentrations in Intensive Care Unit Patients and Patients with Hematological Malignancies
Authors: Hoenigl Martin , Duettmann Wiebke , Raggam Reinhard B. , Seeber Katharina , Troppan Katharina , Fruhwald Sonja , Prueller Florian , Wagner Jasmin , Valentin Thomas , Zollner-Schwetz Ines , Wölfler Albert , Krause Robert
Published: April 2013

Voriconazole plasma concentrations (VPCs) vary widely, and concentrations outside the therapeutic range are associated with either worse outcome in invasive aspergillosis (IA) or increased toxicity. The primary goal of this cohort study conducted in a real-life setting was to identify potential factors associated with inadequate VPCs in ICU patients and patients with hematological malignancies. Within a period of 12 months, trough VPCs were obtained and analyzed with high-performance liquid chromatography, and the adequate range was defined as 1.5 to 5.5 mg/liter. VPCs of <1.5 mg/liter were defined as low, whereas VPCs of >5.5 mg/liter were defined as potentially toxic. A total of 221 trough VPCs were obtained in 61 patients receiving voriconazole, and 124/221 VPCs (56%) were found to be low. Multivariate analysis revealed that low VPCs were significantly associated with clinical failure of voriconazole, prophylactic use, younger age, underlying hematological malignancy, concomitant proton pump inhibitor (PPI) (pantoprazole was used in 88% of the patients), and absence of side effects. Low VPCs remained an independent predictor of clinical failure of voriconazole. The defined adequate range was reached in 79/221 (36%) VPCs. In 18 samples (8%), potentially toxic levels were measured. Multivariate analysis revealed higher body mass index (BMI), absence of hematological malignancy, therapeutic application, and diarrhea as factors associated with potentially toxic VPCs. Neurotoxic adverse events occurred in six patients and were mostly associated with VPCs in the upper quartile of our defined adequate range. In conclusion, potential factors like younger age, prophylaxis, underlying hematological malignancy, BMI, and concomitant PPI should be considered within the algorithm of voriconazole treatment.
Molecular Mechanisms of Drug Resistance in Clinical Candida Species Isolated from Tunisian Hospitals
Authors: Eddouzi Jamel , Parker Josie E. , Vale-Silva Luis A. , Coste Alix , Ischer Françoise , Kelly Steve , Manai Mohamed , Sanglard Dominique
Published: April 2013

Antifungal resistance ofCandidaspecies is a clinical problem in the management of diseases caused by these pathogens. In this study we identified from a collection of 423 clinical samples taken from Tunisian hospitals two clinicalCandidaspecies (Candida albicansJEY355 andCandida tropicalisJEY162) with decreased susceptibility to azoles and polyenes. For JEY355, the fluconazole (FLC) MIC was 8 μg/ml. Azole resistance inC. albicansJEY355 was mainly caused by overexpression of a multidrug efflux pump of the major facilitator superfamily, Mdr1. The regulator of Mdr1,MRR1, contained a yet-unknown gain-of-function mutation (V877F) causingMDR1overexpression. TheC. tropicalisJEY162 isolate demonstrated cross-resistance between FLC (MIC > 128 μg/ml), voriconazole (MIC > 16 μg/ml), and amphotericin B (MIC > 32 μg/ml). Sterol analysis using gas chromatography-mass spectrometry revealed that ergosterol was undetectable in JEY162 and that it accumulated 14α-methyl fecosterol, thus indicating a perturbation in the function of at least two main ergosterol biosynthesis proteins (Erg11 and Erg3). Sequence analyses ofC. tropicalis ERG11(CtERG11) andCtERG3from JEY162 revealed a deletion of 132 nucleotides and a single amino acid substitution (S258F), respectively. These two alleles were demonstrated to be nonfunctional and thus are consistent with previous studies showing thatERG11mutants can only survive in combination with otherERG3mutations.CtERG3andCtERG11wild-type alleles were replaced by the defective genes in a wild-typeC. tropicalisstrain, resulting in a drug resistance phenotype identical to that of JEY162. This genetic evidence demonstrated thatCtERG3andCtERG11mutations participated in drug resistance. During reconstitution of the drug resistance inC. tropicalis, a strain was obtained harboring only defectiveCterg11allele and containing as a major sterol the toxic metabolite 14α-methyl-ergosta-8,24(28)-dien-3α,6β-diol, suggesting thatERG3was still functional. This strain therefore challenged the current belief thatERG11mutations cannot be viable unless accompanied by compensatory mutations. In conclusion, this study, in addition to identifying a novelMRR1mutation inC. albicans, constitutes the first report on a clinicalC. tropicaliswith defective activity of sterol 14α-demethylase and sterol Δ5,6-desaturase leading to azole-polyene cross-resistance.
Development of a Population Pharmacokinetic Model To Describe Azithromycin Whole-Blood and Plasma Concentrations over Time in Healthy Subjects
Authors: Pene Dumitrescu T. , Anic-Milic T. , Oreskovic K. , Padovan J. , Brouwer K. L. R. , Zuo P. , Schmith V. D.
Published: April 2013

Azithromycin (AZI), a broad-spectrum antibiotic, accumulates in polymorphonuclear cells and peripheral blood mononuclear cells. The distribution of AZI in proinflammatory cells may be important to the anti-inflammatory properties. Previous studies have described plasma AZI pharmacokinetics. The objective of this study was to describe the pharmacokinetics of AZI in whole blood (concentration in whole blood [

C
b

]) and plasma (concentration in plasma [

C
p

]) of healthy subjects. In this study, 12 subjects received AZI (500 mg once a day for 3 days). AZI

C
b

and

C
p

were quantified in serial samples collected up to 3 weeks after the last dose and analyzed using noncompartmental and compartmental methods. After the last dose,

C
b

was greater than

C
p

. Importantly,

C
b

, but not

C
p

, was quantifiable in all but one subject at 3 weeks. The blood area under the curve during a 24-h dosing interval (AUC
24
) was ∼2-fold greater than the plasma AUC
24
, but simulations suggested that

C
b

was not at steady state by day 3. Upon exploration of numerous models, an empirical 3-compartment model adequately described

C
p

and

C
b

, but

C
p

was somewhat underestimated. Intercompartmental clearance (CL; likely representing cells) was lower than apparent oral CL (18 versus 118 liters/h). Plasma, peripheral, and cell compartmental volumes were 439 liters, 2,980 liters, and 3,084 liters, respectively. Interindividual variability in CL was low (26.2%), while the volume of distribution variability was high (107%). This is the first report to describe AZI

C
b

in healthy subjects, the distribution parameters between

C
p

and

C
b

, and AZI retention in blood for up to 3 weeks following 3 daily doses. The model can be used to predict

C
b

from

C
p

for AZI under various dosing regimens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01026064.)
Regulation of Rab5 Function during Phagocytosis of Live Pseudomonas aeruginosa in Macrophages
Authors: Mustafi Sushmita , Rivero Nathalie , Olson Joan C. , Stahl Philip D. , Barbieri M. Alejandro
Published: April 2013

Pseudomonas aeruginosa
, a Gram-negative opportunistic human pathogen, is a frequent cause of severe hospital-acquired infections. Effectors produced by the type III secretion system disrupt mammalian cell membrane trafficking and signaling and are integral to the establishment of
P. aeruginosa
infection. One of these effectors, ExoS, ADP-ribosylates several host cell proteins, including Ras and Rab GTPases. In this study, we demonstrated that Rab5 plays a critical role during early stages of
P. aeruginosa
invasion of J774-Eclone macrophages. We showed that live, but not heat-inactivated,
P. aeruginosa
inhibited phagocytosis and that this occurred in conjunction with downregulation of Rab5 activity. Inactivation of Rab5 was dependent on ExoS ADP-ribosyltransferase activity, and in J744-Eclone cells, ExoS ADP-ribosyltransferase activity caused a more severe inhibition of phagocytosis than ExoS Rho GTPase activity. Furthermore, we found that expression of Rin1, a Rab5 guanine exchange factor, but not Rabex5 and Rap6, partially reversed the inactivation of Rab5 during invasion of live
P. aeruginosa
. These studies provide evidence that live
P. aeruginosa
cells are able to influence their rate of phagocytosis in macrophages by directly regulating activation of Rab5.
Anaesthesia management for acute appendicitis in cases with Sjögren's syndrome accompanying autoimmune hepatitis
Authors: Demirel Ismail , Ozer Ayse Belin , Bayar Mustafa K , Erhan Omer L
Published: April 2013

Characterised by lymphocytic infiltration of exocrine glands, Sjögren's syndrome (SS) is a chronic autoimmune disease. Symptoms belonging to the involved systems may occur owing to the fact that it affects multiple systems. While rheumatoid arthritis is observed concomitantly, its co-occurrence with autoimmune hepatitis is astonishingly common. Through this case report, we intended to review issues that should be attended to while administering anaesthesia to a patient with SS accompanying autoimmune hepatitis. In the light of literature, we aimed to discuss anaesthesia management to the patient with SS and issues stemming from the clinical features of SS. In SS, the expected issues are liver problems related autoimmune hepatitis and respiratory problems related pulmonary fibrosis.

A careful preoperative evaluation, a comprehensive preparation against difficulty in intubation, a selective anaesthesia management in terms of autoimmune hepatitis and close monitoring of postoperative respiration may prevent or decrease possible complications.
Bilateral anterior shoulder dislocation
Authors: Nourredine Hussein , El Sayad Mohamed , Gull Syed , Davies Andrew P
Published: April 2013

We describe a case of simultaneous bilateral anterior shoulder dislocation in a 70-year-old gentleman post-trauma. There was no associated motor, sensory or vascular deficit. Patient underwent closed reduction for both his dislocated shoulder joints under general anaesthesia followed by immobilisation for 4 weeks, and subsequent follow-up showed good functional outcomes.
Poorly controlled type 2 diabetes complicated by an episode of severe hypertriglyceridaemia-induced pancreatitis
Authors: Denecker Nathalie , Decochez Katelijn
Published: April 2013

A 23-year-old woman with a history of type 2 diabetes and non-compliance presented to the emergency department with abdominal epigastric pain and nausea. Laboratory examination revealed a mild ketoacidosis while an abdominal CT scan performed the following day demonstrated a severe acute pancreatitis of the body and tail (Balthazar grade E) despite normal amylase serum levels on admission. The presence of a lactescent serum was the clue to an extremely high triglyceride level (>10 000 mg/dl) causing the pancreatitis. The hypertriglyceridaemia itself was attributed mainly to the diabetic ketoacidosis. There was no family history of hypertriglyceridaemia. The triad consisting of diabetic ketoacidosis, hypertriglyceridaemia and acute pancreatitis is an unusual presentation of poorly controlled diabetes which can occur in type 1 as well as type 2 diabetic adults and children. Treatment with intravenous insulin and hydration successfully resolved the ketoacidosis and hypertriglyceridaemia and reversed the episode of acute pancreatitis.
Polyglandular autoimmune syndrome disguised as mental illness
Authors: Wei Randy , Chang Allen , Rockoff Aaron
Published: April 2013

Our case acts to highlight the numerous presentations of polyglandular autoimmune syndromes. A 62-year-old Taiwanese woman with a history of schizophrenia presented to our emergency department with a brain tumour causing her headaches. She was admitted due to severe anaemia, and after further investigation, the patient was discovered to have pernicious anaemia and autoimmune thyroiditis—consistent with the diagnosis of  polyglandular autoimmune syndrome IIIb. Her underlying primary psychiatric diagnosis was then questioned. The diagnosis of her endocrinopathies were likely delayed for many years due to the psychiatric disorder which may have been due to her long-standing autoimmune hypothyroidism and/or vitamin B12deficiency. Initial treatment brought about major behavioural improvement, and encourages physicians to investigate secondary causes of psychosis and other coexisting autoimmune diseases when a patient presents with one endocrinopathy.
Just a sore throat? Uncommon causes of significant respiratory disease
Authors: Wahab Dalia , Bichard Julia , Shah Anand , Mann Bhupinder
Published: April 2013

We present two uncommon underlying causes of a sore throat which, if missed or delayed in diagnosis, can lead to disastrous consequences. Our first case is of Lemierre's syndrome diagnosed in a 21-year-old man presenting with a 5-day history of sore throat, fever, right-sided pleuritic chest pain and bilateral pulmonary nodules on CT imaging.Fusobacterium necrophorumcultured from peripheral blood and an occluded left internal jugular vein on ultrasound lead to an eventual diagnosis. Our second case presents a 29-year-old woman with a 5-day history of sore throat, fever and right-sided pleuritic chest pain. A left-sided quinsy was diagnosed and aspirated and the patient was discharged home. She represented shortly with worsening pleuritic pain and was found to have a right-sided pleural effusion with descending mediastinitis originating from the tonsillar abscess. Delayed diagnosis resulted in open thoracotomy, decortication and prolonged intravenous antibiotics.
Successful anticoagulation with fresh frozen plasma for cardiopulmonary bypass in a patient with heparin resistance: a cautionary tale
Authors: Badrin Omar , Kushairi Suana , Zakaria Zuhrah , Sachithanandan Anand
Published: April 2013

Heparin resistance (HR) is an increasingly common occurrence due to a greater awareness of the benefits of antithrombosis prophylaxis in hospitalised patients with low molecular weight and unfractionated heparin. Furthermore as more high-risk patients with prior heparin exposure undergo cardiac surgery we can expect to encounter more such cases. Adequate anticoagulation is essential for the safe conduct of any operation requiring cardiopulmonary bypass and is usually achieved with systemic heparinisation. We report a case of successful anticoagulation with the intraoperative administration of fresh frozen plasma in a high-risk coronary patient with HR and highlight the perils of unwitting overheparinisation in such cases. This case highlights the importance of clinical awareness of this phenomenon and the available alternative anticoagulants.
Curative surgical management of isolated adrenal recurrence of oesophageal adenocarcinoma
Authors: O'Sullivan K E , Moriarty A R , Larkin J O , Reynolds J V
Published: April 2013

Adrenal metastases of oesophageal adenocarcinoma are rarely detected in the clinical setting, more frequently being found as an incidental postmortem finding in the presence of widespread metastases. With improvements in the sensitivity of radiological diagnostic modalities, the incidence of adrenal tumour detection is on the rise. We report herein a particularly rare case of primary operative management by adrenalectomy for an isolated right-sided adrenal metastasis secondary to oesophageal adenocarcinoma, with a long-term survival.
Age-dependent climate–growth relationships and regeneration ofPicea abiesin a drought-prone mixed-coniferous forest in the Alps
Authors: Schuster Roman , Oberhuber Walter
Published: April 2013

Within dry inner Alpine environments, climate warming is expected to affect the development of forest ecosystems by changing species composition and inducing shifts in forest distribution. By applying dendroecological techniques we evaluated the climate sensitivity of radial growth and the establishment of Picea abies (L.) Karst. in a drought-prone mixed-coniferous forest in the Austrian Alps. Time series of annual increments were developed from >220 trees and assigned to four age classes. While radial growth of old P. abies trees (mean ages of 121 and 174 years) had highly significant responses to May–June precipitation, young trees (mean ages 28 and 53 years) were insensitive to precipitation in the current year. Because tree age was closely correlated to height and diameter (r2= 0.709 and 0.784, respectively), we relate our findings to the increase in tree size rather than age per se. The synchronicity found among trends in basal area increment and tree establishment suggests that canopy openings increased light and water availability, which favoured growth and establishment of moderately shade-tolerant P. abies. We conclude that, although P. abies is able to regenerate at this drought-prone site, increasing inter-tree competition for water in dense stands gradually lowers competitive strength and restricts scattered occurrence to dry–mesic sites.
BOLTZMANN–ARRHENIUS–ZHURKOV (BAZ) MODEL IN PHYSICS-OF-MATERIALS PROBLEMS
Authors: SUHIR E. , KANG S.-M.
Published: April 2013

Boltzmann–Arrhenius–Zhurkov (BAZ) model enables one to obtain a simple, easy-to-use and physically meaningful formula for the evaluation of the probability of failure (PoF) of a material after the given time in operation at the given temperature and under the given stress (not necessarily mechanical). It is shown that the material degradation (aging, damage accumulation, flaw propagation, etc.) can be viewed, when BAZ model is considered, as a Markovian process, and that the BAZ model can be obtained as the steady-state solution to the Fokker–Planck equation in the theory of Markovian processes. It is shown also that the BAZ model addresses the worst and a reasonably conservative situation, when the highest PoF is expected. It is suggested therefore that the transient period preceding the condition addressed by the steady-state BAZ model need not be accounted for in engineering evaluations. However, when there is an interest in understanding the physics of the transient degradation process, the obtained solution to the Fokker–Planck equation can be used for this purpose.
DECOUPLED AND UNIDIRECTIONAL ASYMPTOTIC MODELS FOR THE PROPAGATION OF INTERNAL WAVES
Authors: DUCHÊNE VINCENT
Published: April 2013

We study the relevance of various scalar equations, such as inviscid Burgers', Korteweg–de Vries (KdV), extended KdV, and higher order equations, as asymptotic models for the propagation of internal waves in a two-fluid system. These scalar evolution equations may be justified in two ways. The first method consists in approximating the flow by two uncoupled, counterpropagating waves, each one satisfying such an equation. One also recovers these equations when focusing on a given direction of propagation, and seeking unidirectional approximate solutions. This second justification is more restrictive as for the admissible initial data, but yields greater accuracy. Additionally, we present several new coupled asymptotic models: a Green–Naghdi type model, its simplified version in the so-called Camassa–Holm regime, and a weakly decoupled model. All of the models are rigorously justified in the sense of consistency.
RESTRUCTURING COUNTERPARTY CREDIT RISK
Authors: ALBANESE CLAUDIO , BRIGO DAMIANO , OERTEL FRANK
Published: April 2013

We introduce an innovative theoretical framework for the valuation and replication of derivative transactions between defaultable entities based on the principle of arbitrage freedom. Our framework extends the traditional formulations based on credit and debit valuation adjustments (CVA and DVA). Depending on how the default contingency is accounted for, we list a total of ten different structuring styles. These include bi-partite structures between a bank and a counterparty, tri-partite structures with one margin lender in addition, quadri-partite structures with two margin lenders and, most importantly, configurations where all derivative transactions are cleared through a central counterparty clearing house (CCP). We compare the various structuring styles under a number of criteria including consistency from an accounting standpoint, counterparty risk hedgeability, numerical complexity, transaction portability upon default, induced behavior and macro-economic impact of the implied wealth allocation.
DUALITY IN STRING THEORY
Authors: LOZANO YOLANDA
Published: April 2013

Duality symmetries have played a key role in the discovery that the five consistent superstring theories in 10 dimensions emerge as different corners of the moduli space of a single unifying theory, known as M-theory. Focusing on the target space, or T, duality symmetry, we show how it can be formulated in spacetimes with abelian and non-abelian isometries. Finally, we discuss some recent work that realizes non-abelian T-duality as a consistent truncation to seven-dimensional supergravity, thus generalizing to the non-abelian case the realization of abelian T-duality at the supergravity level.
PREPARATION AND CHARACTERIZATION OF IN-SUBSTITUTED BaSnO3 COMPOUNDS
Authors: WANG YANZHONG , CHESNAUD ANTHONY , BEVILLON EMILE , HUANG JIN , YANG JINLONG
Published: April 2013

In-substituted BaSnO 3 ( BaSn 1-x In x O 3-δ, x = 0.125, 0.25 and 0.50) compounds were prepared by a gel polymerization method. Their microstructure, hydration energy and electrical properties were investigated. Single phases were confirmed by X-ray diffraction analysis over the whole range of substitution, and were identified as cubic perovskite-like structure. The grain size and conductivities of samples measured under dry and wet atmospheres increase significantly with indium content as such, 1–2 μm for BaSn 0.875 In 0.125 O 3-δ(x = 0.125) and 20 μm for BaSn 0.50 In 0.50 O 3-δ(x = 0.50). The highest proton conductivity at 600°C, σ = 9.5 × 10-4 S⋅cm-1, is obtained for BaSn 0.5 In 0.5 O 2.75(x = 0.50).