bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adrenaline (epinephrine) microcrystal sublingual tablet formulation: enhanced absorption in a preclinical model
Authors: Rawas-Qalaji Mutasem , Rachid Ousama , Mendez Belacryst A , Losada Annette , Simons F Estelle R , Simons Keith J 
Published: September 2014

Abstract

Objectives
For anaphylaxis treatment in community settings, adrenaline (epinephrine) administration using an auto-injector in the thigh is universally recommended. Despite this, many people at risk of anaphylaxis in community settings do not carry their prescribed auto-injectors consistently and hesitate to use them when anaphylaxis occurs.The objective of this research was to study the effect of a substantial reduction in adrenaline (Epi) particle size to a few micrometres (Epi microcrystals (Epi-MC)) on enhancing adrenaline dissolution and increasing the rate and extent of sublingual absorption from a previously developed rapidly disintegrating sublingual tablet (RDST) formulation in a validated preclinical model.

Methods
The in-vivo absorption of Epi-MC 20 mg RDSTs and Epi 40 mg RDSTs was evaluated in rabbits. Epi 0.3 mg intramuscular (IM) injection in the thigh and placebo RDSTs were used as positive and negative controls, respectively.

Key findings
Epimean(standard deviation) area under the plasma concentration vs time curves up to 60 min and Cmax from Epi-MC 20 mg and Epi 40 mg RDSTs did not differ significantly (P &gt; 0.05) from Epi 0.3 mg IM injection. After adrenaline, regardless of route of administration, pharmacokinetic parameters were significantly higher (P &lt; 0.05) than after placebo RDSTs administration (reflecting endogenous adrenaline levels).

Conclusion
Epi-MC RDSTs facilitated a twofold increase in Epi absorption and a 50% reduction in the sublingual dose. This novel sublingual tablet formulation is potentially useful for the first-aid treatment of anaphylaxis in community settings.
Identification of disulfide bond isomerase substrates reveals bacterial virulence factors
Authors: Ren Guoping , Champion Matthew M. , Huntley Jason F. 
Published: September 2014

SummaryBacterial pathogens are exposed to toxic molecules inside the host and require efficient systems to form and maintain correct disulfide bonds for protein stability and function. The intracellular pathogen Francisella tularensis encodes a disulfide bond formation protein ortholog, DsbA, which previously was reported to be required for infection of macrophages and mice. However, the molecular mechanisms by which F. tularensis DsbA contributes to virulence are unknown. Here, we demonstrate that F. tularensis DsbA is a bifunctional protein that oxidizes and, more importantly, isomerizes complex disulfide connectivity in substrates. A single amino acid in the conserved cis‐proline loop of the DsbA thioredoxin domain was shown to modulate both isomerase activity and F. tularensis virulence. Trapping experiments in F. tularensis identified over 50 F. tularensis DsbA substrates, including outer membrane proteins, virulence factors, and many hypothetical proteins. Six of these hypothetical proteins were randomly selected and deleted, revealing two novel proteins, FTL_1548 and FTL_1709, which are required for F. tularensis virulence. We propose that the extreme virulence of F. tularensis is partially due to the bifunctional nature of DsbA, that many of the newly identified substrates are required for virulence, and that the development of future DsbA inhibitors could have broad anti‐bacterial implications.
International survey of knowledge of food‐induced anaphylaxis
Authors: Wang Julie , Young Michael C. , Nowak‐Węgrzyn Anna 
Published: September 2014

AbstractBackgroundStudies show that anaphylaxis is under‐recognized and epinephrine (adrenaline) is under‐used by medical personnel as well as patients and their families. This study assesses the knowledge of food‐induced anaphylaxis diagnosis and management across different populations of providers and caregivers and other interested respondents.MethodsAn online survey embedded in a case discussion of food‐induced anaphylaxis was distributed by Medscape to registered members.ResultsA total of 7822 responders who started the activity chose to answer at least some of the questions presented (response rate 39.5%). Over 80% of responders in all groups correctly identified the case of anaphylaxis with prominent skin and respiratory symptoms; however, only 55% correctly recognized the case without skin symptoms as anaphylaxis. Only 23% of responders correctly selected risk factors for anaphylaxis, with physicians significantly more likely to choose the correct answers as compared to allied health, other health professionals, and medical students (p < 0.001). Ninety‐five percent selected epinephrine (adrenaline) as the most appropriate treatment for anaphylaxis, and 81% correctly indicated that there are no absolute contraindications for epinephrine (adrenaline) in the setting of anaphylaxis. When presented a case of a child with no documented history of allergies who has symptoms of anaphylaxis, more physicians than any other group chose to administer stock epinephrine (adrenaline) (73% vs. 60%, p < 0.001).ConclusionSpecific knowledge deficits for food‐induced anaphylaxis persist across all groups. Further educational efforts should be aimed not only at the medical community but also for the entire caregiver community and general public, to optimize care for food allergic individuals.
Highly Efficient Photodegradation of Organic Pollutants Assisted by Sonoluminescence
Authors: Volkova Anna V. , Nemeth Silke , Skorb Ekaterina V. , Andreeva Daria V. 
Published: September 2014

AbstractThe mechanism of the photodegradation of azo dyes via ultrasonication is studied using a combination of the high‐performance liquid chromatography and UV–vis spectroscopy with detailed analysis of the kinetics. Based on the kinetics studies of the sonodegradation, it was proposed that the degradation of azo dyes was a multistage process that involved: (1) the direct attack of azo bonds and phenyl rings of dyes by the sonochemically formed reactive oxygen species; (2) the activation of semiconductor particles by the light emitted during cavitation and the triggering of the photocatalytic pathways of dye degradation and (3) increase of the adsorption capacity of the semiconductor particles due to the sonomechanically induced interparticle collisions. The detailed kinetics study can help in following an effective process up‐scaling. It was demonstrated that extremely short pulses of light flashes in a cavitated mixture activated the surface of photocatalysts and significantly enhanced dye degradation processes.
Hyperhemolysis syndrome in a patient without a hemoglobinopathy, unresponsive to treatment with eculizumab
Authors: Gupta Shruti , Fenves Andrew , Nance Sandra Taddie , Sykes David B. , Dzik Walter “Sunny” 
Published: September 2014

BackgroundHyperhemolysis is a serious transfusion reaction, most often described in patients with hemoglobinopathies. Hyperhemolysis is characterized by the destruction of host red blood cells (RBCs), in addition to donorRBCs, via an unknown mechanism.Study Design and MethodsWe present the case of a 58‐year‐old woman with treated human immunodeficiency virus and a normal hemoglobin (Hb) electrophoresis who developed hyperhemolysis in the setting of a delayed hemolytic transfusion reaction (DHTR).ResultsThe patient wasABOgroupBand had a previously identified anti‐Fyballoantibody. After transfusion ofFyb–RBCs, she developed aDHTRand was found to have anti‐E, anti‐Cw, anti‐s, and an additional antibody to an unrecognized high‐frequencyRBCalloantigen. Subsequent transfusion ofABO‐compatibleRBCsthat were negative forFyb,E,Cw, and s antigens resulted in immediate intravascular hemolysis. In the absence of bleeding, her hematocrit (Hct) decreased to 10.2%. An extensive serologic evaluation failed to identify the specificity of the high‐frequency antibody. Severe hemolytic reactions also occurred despite pretransfusion conditioning with eculizumab. TheHctand clinical symptoms slowly improved after the cessation of transfusions and treatment with erythropoietin and steroids. This case demonstrates several noteworthy features including hyperhemolysis in a patient without aHbdisorder, the development of an antibody to an unknownRBCantigen, and the failure of eculizumab to prevent intravascular hemolysis after transfusion.ConclusionHyperhemolysis is not restricted to patients with hemoglobinopathies. Whether eculizumab offers any benefit in the hyperhemolysis syndrome or in the prevention of intravascular hemolysis due toRBCalloantibodies remains uncertain.
Poster — Thur Eve — 23: Dose and Position Quality Assurance using the RADPOS System for 4D Radiotherapy with CyberKnife
Authors: Marants R , Vandervoort E , Cygler J E 
Published: September 2014

Introduction:RADPOS 4D dosimetry system consists of a microMOSFET dosimeter combined with an electromagnetic positioning sensor, which allows for performing real‐time dose and position measurements simultaneously. In this report the use of RADPOS as an independent quality assurance (QA) tool during CyberKnife 4D radiotherapy treatment is described. In addition to RADPOS, GAFCHROMIC® films were used for simultaneous dose measurement.Methods:RADPOS and films were calibrated in a Solid Water® phantom at 1.5 cm depth, SAD= 80 cm, using 60 mm cone. CT based treatment plan was created for a Solid Water® breast phantom containing metal fiducials and RADPOS probe. Dose calculations were performed using iPlan pencil beam algorithm. Before the treatment delivery, GAFCHROMIC® film was inserted inside the breast phantom, next to the RADPOS probe. Then the phantom was positioned on the chest platform of the QUASAR, to which Synchrony LED optical markers were also attached. Position logging began for RADPOS and the Synchrony tracking system, the QUASAR motion was initiated and the treatment was delivered.Results:RADPOS position measurements very closely matched the LED marker positions recorded by the Synchrony camera tracking system. The RADPOS measured dose was 2.5% higher than the average film measured dose, which is within the experimental uncertainties. Treatment plan calculated dose was 4.1 and 1.6% lower than measured by RADPOS and film, respectively. This is most likely due to the inferior nature of the dose calculation algorithm.Conclusions:Our study demonstrates that RADPOS system is a useful tool for independent QA of CyberKnife treatments.
Poster — Thur Eve — 27: Flattening Filter Free VMAT Quality Assurance: Dose Rate Considerations for Detector Response
Authors: Viel Francis , Duzenli Cheryl , Camborde Marie‐Laure , Strgar Vincent , Horwood Ron , Atwal Parmveer , Gete Ermias , Karan Tania 
Published: September 2014

Introduction:Radiation detector responses can be affected by dose rate. Due to higher dose per pulse and wider range of mu rates in FFF beams, detector responses should be characterized prior to implementation of QA protocols for FFF beams. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. This study looks at the dose per pulse variation throughout a 3D volume for typical VMAT plans and the response characteristics for a variety of detectors, and makes recommendations on the design of QA protocols for FFF VMAT QA.Materials and Methods:Linac log file data and a simplified dose calculation algorithm are used to calculate dose per pulse for a variety of clinical VMAT plans, on a voxel by voxel basis, as a function of time in a cylindrical phantom. Diode and ion chamber array responses are characterized over the relevant range of dose per pulse and dose rate.Results:Dose per pulse ranges from <0.1 mGy/pulse to 1.5 mGy/pulse in a typical VMAT treatment delivery using the 10XFFF beam. Diode detector arrays demonstrate increased sensitivity to dose (+./− 3%) with increasing dose per pulse over this range. Ion chamber arrays demonstrate decreased sensitivity to dose (+/− 1%) with increasing dose rate over this range.Conclusions:QA protocols should be designed taking into consideration inherent changes in detector sensitivity with dose rate. Neglecting to account for changes in detector response with dose per pulse can lead to skewed QA results.
Poster — Thur Eve — 36: Implementation of constant dose rate and gantry speed arc therapy(CDR‐CAS‐IMAT) for thoracic esophageal carcinoma on Varian 23EX
Authors: Zhang Ruohui , Fan Xiaomei , Bai Wenwen , Han Chun 
Published: September 2014

Objective:The purpose of this study is to propose an alternative planning approach for VMAT using constant dose rate and gantry speed arc therapy(CDR‐CAS‐IMAT) implementation on conventional Linac Varian 23EX and used IMRT as a benchmark to evaluate the performance.Methods and materials:Eighteen patients with thoracic esophageal carcinoma who were previously treated with IMRT on Varian 23EX were retrospectively planned for CDR‐CAS‐IMAT plans. Dose prescription was set to 60 Gy to PTVs in 30 fractions. The planning objectives for PTVs and OAR were corresponding with the IMRT plans. Dose to the PTVs and OAR were compared to IMRT with respect to plan quality, MU, treatment time and delivery accuracy.Results:CDR‐CAS‐IMAT plans led to equivalent or superior plan quality as compared to IMRT, PTV's CI relative increased 16.2%, while small deviations were observed on minimum dose for PTV. Volumes in the cord receiving 40Gy were increased from 3.6% with IMRT to 7.0%. Treatment times were reduced significantly with CDR‐CAS‐IMAT(mean 85.7s vs. 232.1s, p < .05), however, MU increased by a factor of 1.3 and lung V10/5/3.5/aver were relative increase 6.7%,12%,17.9%,4.2%, respectively. And increased the E‐P low dose area volume decreased the hight dose area. There were no significant difference in Delta4 measurements results between both planning techniques.Conclusion:CDR‐CAS‐IMAT plans can be implemented smoothly and quickly into a busy cancer center, which improved PTV CI and reduces treatment time but increased the MU and low dose irradiated area. An evaluation of weight loss must be performed during treatment for CDR‐CAS‐IMAT patients.
Sci—Thur AM: YIS ‐ 04: Gold Nanoparticle Enhanced Arc Radiotherapy: A Monte Carlo Feasibility Study
Authors: Koger B , Kirkby C 
Published: September 2014

Introduction:The use of gold nanoparticles (GNPs) in radiotherapy has shown promise for therapeutic enhancement. In this study, we explore the feasibility of enhancing radiotherapy with GNPs in an arc‐therapy context. We use Monte Carlo simulations to quantify the macroscopic dose‐enhancement ratio (DER) and tumour to normal tissue ratio (TNTR) as functions of photon energy over various tumour and body geometries.Methods:GNP‐enhanced arc radiotherapy (GEART) was simulated using the PENELOPE Monte Carlo code and penEasy main program. We simulated 360° arc‐therapy with monoenergetic photon energies 50 – 1000 keV and several clinical spectra used to treat a spherical tumour containing uniformly distributed GNPs in a cylindrical tissue phantom. Various geometries were used to simulate different tumour sizes and depths. Voxel dose was used to calculate DERs and TNTRs. Inhomogeneity effects were examined through skull dose in brain tumour treatment simulations.Results:Below 100 keV, DERs greater than 2.0 were observed. Compared to 6 MV, tumour dose at low energies was more conformai, with lower normal tissue dose and higher TNTRs. Both the DER and TNTR increased with increasing cylinder radius and decreasing tumour radius. The inclusion of bone showed excellent tumour conformality at low energies, though with an increase in skull dose (40% of tumour dose with 100 keV compared to 25% with 6 MV).Conclusions:Even in the presence of inhomogeneities, our results show promise for the treatment of deep‐seated tumours with low‐energy GEART, with greater tumour dose conformality and lower normal tissue dose than 6 MV.
Poster — Thur Eve — 38: Feasibility of a Table‐Top Total Body Irradiation Technique using Robotic Couch Motion
Authors: Chin Erika , Otto Karl , Hoppe Richard , Hsu Annie , Loo Billy , Million Lynn , Xing Lei , Fahimian Benjamin 
Published: September 2014

Purpose:To develop and test the feasibility of a table‐top implementation for total body irradiation (TBI) via robotic couch motion and coordinated monitor unit modulation on a standard C‐arm linac geometry.Methods:To allow for collision free delivery and to maximize the effective field size, the couch was rotated to 270° IEC and dropped to 150 cm from the vertical radiation source. The robotic delivery was programmed using the TrueBeam STx Developer Mode using custom XML scripting. To assess the dosimetry of a sliding 30×20 cm2 field, irradiation on a solid water phantom of varying thickness was analyzed using EDR2 radiographic film and OSLDs. Beam modulation was achieved by dividing the couch path into multiple segments of varying dose rates and couch speeds in order to deliver 120 cGy to the midline.Results:The programmed irradiation in conjunction with coordinated couch motion was successfully delivered on a TrueBeam linac. When no beam modulation was employed, the dose difference between two different phantom sections was 17.0%. With simple beam modulation via changing dose rates and couch speeds, the desired prescription dose can be achieved at the centre of each phantom section within 1.9%. However, dose deviation at the junction was 9.2% due to the nonphysical change in the phantom thickness.Conclusions:The feasibility of robotic table‐top TBI on a C‐arm linac geometry was experimentally demonstrated. To achieve a more uniform dose distribution, inverse‐planning allowing for a combination of dose rate modulation, jaw tracking and MLC motion is under investigation.
Sci—Thur AM: YIS ‐ 05: 10X‐FFF VMAT for Lung SABR: an Investigation of Peripheral Dose
Authors: Mader J , Mestrovic A 
Published: September 2014

Flattening Filter Free (FFF) beams exhibit high dose rates, reduced head scatter, leaf transmission and leakage radiation. For VMAT lung SABR, treatment time can be significantly reduced using high dose rate FFF beams while maintaining plan quality and accuracy. Another possible advantage offered by FFF beams for VMAT lung SABR is the reduction in peripheral dose. The focus of this study was to investigate and quantify the reduction of peripheral dose offered by FFF beams for VMAT lung SABR.The peripheral doses delivered by VMAT Lung SABR treatments using FFF and flattened beams were investigated for the Varian Truebeam linac. This study was conducted in three stages, (1): ion chamber measurement of peripheral dose for various plans, (2): validation of AAA, Acuros XB and Monte Carlo for peripheral dose using measured data, and (3): using the validated Monte Carlo model to evaluate peripheral doses for 6 VMAT lung SABR treatments. Three energies, 6X, 10X, and 10X‐FFF were used for all stages.Measured data indicates that 10X‐FFF delivers the lowest peripheral dose of the three energies studied. AAA and Acuros XB dose calculation algorithms were identified as inadequate, and Monte Carlo was validated for accurate peripheral dose prediction. The Monte Carlo‐calculated VMAT lung SABR plans show a significant reduction in peripheral dose for 10X‐FFF plans compared to the standard 6X plans, while no significant reduction was showed when compared to 10X. This reduction combined with shorter treatment time makes 10X‐FFF beams the optimal choice for superior VMAT lung SABR treatments.
Sci—Thur AM: YIS ‐ 10: Use of the Microsoft Kinect for applications of patient surface data to radiotherapy
Authors: Guillet Dominique , Syme Alasdair , DeBlois François 
Published: September 2014

Current techniques to acquire patient surface data are often very expensive and lack flexibility. In this study, the use of the Microsoft Kinect to reliably acquire 3D scans of patient surface is investigated. A design is presented to make the system easily applicable to the clinic. Potential applications of the device to radiotherapy are also presented.Scan reproducibility was tested by repeatedly scanning an anthropomorphic phantom. Scan accuracy was tested by comparing Kinect scans to the surface extracted from a CT dataset of a Rando® anthropomorphic phantom, which was considered as the true reference surface. Average signed distances of 0.12 ± 2.34 mm and 0.13 ± 2.04 mm were obtained between the compared surfaces for reproducibility and accuracy respectively. This is conclusive, since it indicates that the variations observed come largely from noise distributed around an average distance close to 0 mm. Moreover, the range of the noise is small enough for the system to reliably capture a patient's surface. A system was also designed using two Kinects used together to acquire 3D surfaces in a quick and stable way that is applicable to the clinic. Finally, applications of the device to radiotherapy are demonstrated. Its use to detect local positioning errors is presented, where small local variations difficult to see with the naked eye are clearly visible. The system was also used to predict collisions using gantry and patient scans and thus ensure the safety of unconventional trajectories.
Sci—Thur PM: Imaging — 05: Calibration of a SPECT/CT camera for quantitative SPECT with 99mTc
Authors: Gaudin Émilie , Montégiani Jean‐François , Beauregard Jean‐Mathieu , Després Philippe 
Published: September 2014

While quantitation is the norm in PET, it is not widely available yet in SPECT. This work's aim was to calibrate a commercially available SPECT/CT system to perform quantitative SPECT. Counting sensitivity, dead‐time (DT) constant and partial volume effect (PVE) of the system were assessed.A dual‐head Siemens SymbiaT6 SPECT/CT camera equipped with low energy high‐resolution collimators was studied. 99mTc was the radioisotope of interest because of its wide usage in nuclear medicine. First, point source acquisitions were performed (activity: 30–990MBq). Further acquisitions were then performed with a uniform Jaszczak phantom filled with water at high activity (25–5000MBq). PVE was studied using 6 hot spheres (diameters: 9.9–31.2 mm) filled with 99mTc (2.8MBq/cc) in the Jaszczak phantom, which was: (1) empty, (2) water‐filled and (3) water‐filled with low activity (0.1MBq/cc). The data was reconstructed with the Siemens's Flash3D iterative algorithm with 4 subsets and 8 iterations, attenuation‐correction (AC) and scatter‐correction (SC). DT modelling was based on the total spectrum counting rate. Sensitivity was assessed using AC‐SC reconstructed SPECT data.Sensitivity and DT for the sources were 99.51±1.46cps/MBq and 0.60±0.04µs. For the phantom, sensitivity and DT were 109.9±2.3cps/MBq and 0.62±0.13µs. The recovery‐coefficient varied from 5% for the 9.9mm, to 80% for the 31.2mm spheres.With our calibration methods, both sensitivity and DT constant of the SPECT camera had little dependence on the object geometry and attenuation. For small objects of known size, recovery‐coefficient can be applied to correct PVE. Clinical quantitative SPECT appears to be possible and has many potential applications.