Relationship between radiation dose reduction and image quality change in photostimulable phosphor luminescence X-ray imaging systems.

PubMed

Sakurai, T; Kawamata, R; Kozai, Y; Kaku, Y; Nakamura, K; Saito, M; Wakao, H; Kashima, I

2010-05-01

The aim of the study was to clarify the change in image quality upon X-ray dose reduction and to re-analyse the possibility of X-ray dose reduction in photostimulable phosphor luminescence (PSPL) X-ray imaging systems. In addition, the study attempted to verify the usefulness of multiobjective frequency processing (MFP) and flexible noise control (FNC) for X-ray dose reduction. Three PSPL X-ray imaging systems were used in this study. Modulation transfer function (MTF), noise equivalent number of quanta (NEQ) and detective quantum efficiency (DQE) were evaluated to compare the basic physical performance of each system. Subjective visual evaluation of diagnostic ability for normal anatomical structures was performed. The NEQ, DQE and diagnostic ability were evaluated at base X-ray dose, and 1/3, 1/10 and 1/20 of the base X-ray dose. The MTF of the systems did not differ significantly. The NEQ and DQE did not necessarily depend on the pixel size of the system. The images from all three systems had a higher diagnostic utility compared with conventional film images at the base and 1/3 X-ray doses. The subjective image quality was better at the base X-ray dose than at 1/3 of the base dose in all systems. The MFP and FNC-processed images had a higher diagnostic utility than the images without MFP and FNC. The use of PSPL imaging systems may allow a reduction in the X-ray dose to one-third of that required for conventional film. It is suggested that MFP and FNC are useful for radiation dose reduction.

Charging for hospital pharmaceutical services: flat free based on the medication record.

PubMed

Wyatt, B K

1979-03-01

A 200-bed hospital's change in pricing drug products from a cost-plus-fee system to a flat fee per dose based on the medication administration record (MAR) is described. With the flat-fee system, drug charges are not recorded when the drug is dispensed by the pharmacy; data for charging doses are obtained directly from the MAR forms generated by the nursing staff. Charges are 55 cents per oral or suppository dose and $3.00 per injection dose. Drugs administered intravenously, topical drugs, injections costing more than $10.00 per dose, and miscellaneous nondrug items are still charged on a cost-plus-fee basis. Man-hours are saved in the pharmacy department because of the elimination of the pricing function and maintenance of price lists. The need for nursing staff to charge for any doses administered from emergency or Schedule II floor-stock supplies is eliminated. The workload for business office personnel is reduced because the number of individual charges is less than with the cost-plus charging system. The system is accepted by patients and third-party payers and has made a complete unit dose drug distribution system possible at lower cost.

The utility of rat jejunal permeability for biopharmaceutics classification system.

PubMed

Zakeri-Milani, Parvin; Valizadeh, Hadi; Tajerzadeh, Hosnieh; Islambulchilar, Ziba

2009-12-01

The biopharmaceutical classification system has been developed to provide a scientific approach for classifying drug compounds based on their dose/solubility ratio and human intestinal permeability. Therefore in this study a new classification is presented, which is based on a correlation between rat and human intestinal permeability values. In situ technique in rat jejunum was used to determine the effective intestinal permeability of tested drugs. Then three dimensionless parameters--dose number, absorption number, and dissolution number (D(o), A(n), and D(n))--were calculated for each drug. Four classes of drugs were defined, that is, class I, D(0) < 0.5, P(eff(rat)) > 5.09 x 10(-5) cm/s; class II, D(o) > 1, P(eff(rat)) > 5.09 x 10( -5) cm/s; class III, D(0) < 0.5, P(eff(rat)) < 4.2 x 10(-5) cm/s; and class IV, D(o) > 1, P(eff(rat)) < 4.2 x 10(-5) cm/s. A region of borderline drugs (0.5 < D(o) < 1, 4.2 x 10(-5) < P(eff(rat)) < 5.09 x 10(-5) cm/s) was also defined. According to obtained results and proposed classification for drugs, it is concluded that drugs could be categorized correctly based on dose number and their intestinal permeability values in rat model using single-pass intestinal perfusion technique. This classification enables us to remark defined characteristics for intestinal absorption of all four classes using suitable cutoff points for both dose number and rat effective intestinal permeability values.

MO-G-18A-01: Radiation Dose Reducing Strategies in CT, Fluoroscopy and Radiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahesh, M; Gingold, E; Jones, A

2014-06-15

Advances in medical x-ray imaging have provided significant benefits to patient care. According to NCRP 160, there are more than 400 million x-ray procedures performed annually in the United States alone that contributes to nearly half of all the radiation exposure to the US population. Similar growth trends in medical x-ray imaging are observed worldwide. Apparent increase in number of medical x-ray imaging procedures, new protocols and the associated radiation dose and risk has drawn considerable attention. This has led to a number of technological innovations such as tube current modulation, iterative reconstruction algorithms, dose alerts, dose displays, flat panelmore » digital detectors, high efficient digital detectors, storage phosphor radiography, variable filters, etc. that are enabling users to acquire medical x-ray images at a much lower radiation dose. Along with these, there are number of radiation dose optimization strategies that users can adapt to effectively lower radiation dose in medical x-ray procedures. The main objectives of this SAM course are to provide information and how to implement the various radiation dose optimization strategies in CT, Fluoroscopy and Radiography. Learning Objectives: To update impact of technological advances on dose optimization in medical imaging. To identify radiation optimization strategies in computed tomography. To describe strategies for configuring fluoroscopic equipment that yields optimal images at reasonable radiation dose. To assess ways to configure digital radiography systems and recommend ways to improve image quality at optimal dose.« less

Risk equivalent of exposure versus dose of radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bond, V.P.

This report describes a risk analysis study of low-dose irradiation and the resulting biological effects on a cell. The author describes fundamental differences between the effects of high-level exposure (HLE) and low-level exposure (LLE). He stresses that the concept of absorbed dose to an organ is not a dose but a level of effect produced by a particular number of particles. He discusses the confusion between a linear-proportional representation of dose limits and a threshold-curvilinear representation, suggesting that a LLE is a composite of both systems. (TEM)

Conformity of commercial oral single solid unit dose packages in hospital pharmacy practice.

PubMed

Thibault, Maxime; Prot-Labarthe, Sonia; Bussières, Jean-François; Lebel, Denis

2008-06-01

There are limited published data on the labelling of single unit dose packages in hospitals. The study was conducted in three large hospitals (two adult and one paediatric) in the metropolitan Montreal area, Quebec, Canada. The objective is to evaluate the labelling of commercial oral single solid unit dose packages available in Canadian urban hospital pharmacy practice. The study endpoint was the labelling conformity of each unit dose package for each criterion and overall for each manufacturer. Complete labelling of unit dose packages should include the following information: (1) brand name, (2) international non-proprietary name or generic name, (3) dosage, (4) pharmaceutical form, (5) manufacturer's name, (6) expiry date, (7) batch number and (8) drug identification number. We also evaluated the ease with which a single unit dose package is detached from a multiple unit dose package for quick, easy and safe use by pharmacy staff. Conformity levels were compared between brand-name and generic packages. A total of 124 different unit dose packages were evaluated. The level of conformity of each criterion varied between 19 and 50%. Only 43% of unit dose packages provided an easy-to-detach system for single doses. Among the 14 manufacturers with three or more unit dose packages evaluated, eight (57%) had a conformity level less than 50%. This study describes the conformity of commercial oral single solid unit dose packages in hospital pharmacy practice in Quebec. A large proportion of unit dose packages do not conform to a set of nine criteria set out in the guidelines of the American Society of Health-System Pharmacists and the Canadian Society of Hospital Pharmacists.

Real-time colour pictorial radiation monitoring during coronary angiography: effect on patient peak skin and total dose during coronary angiography.

PubMed

Wilson, Sharon M; Prasan, Ananth M; Virdi, Amy; Lassere, Marissa; Ison, Glenn; Ramsay, David R; Weaver, James C

2016-10-10

The aim of this study was to evaluate whether a real-time (RT) colour pictorial radiation dose monitoring system reduces patient skin and total radiation dose during coronary angiography and intervention. Patient demographics, procedural variables and radiation parameters were recorded before and after institution of the RT skin dose recording system. Peak skin dose as well as traditionally available measures of procedural radiation dose were compared. A total of 1,077 consecutive patients underwent coronary angiography, of whom 460 also had PCI. Institution of the RT skin dose recording system resulted in a 22% reduction in peak skin dose after accounting for confounding variables. Radiation dose reduction was most pronounced in those having PCI but was also seen over a range of subgroups including those with prior coronary artery bypass surgery, high BMI, and with radial arterial access. This was associated with a significant reduction in the number of patients placed at risk of skin damage. Similar reductions in parameters reflective of total radiation dose were also demonstrated after institution of RT radiation monitoring. Institution of an RT skin dose recording reduced patient peak skin and total radiation dose during coronary angiography and intervention. Consideration should be given to widespread adoption of this technology.

SU-F-T-648: Sharpening Dose Fall-Off Via Beam Number Enhancements For Stereotactic Brain Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiu, J; Braunstein, S; McDermott, M

Purpose: Sharp dose fall-off is the hallmark of brain radiosurgery to deliver a high dose of radiation to the target while minimizing dose to normal brain tissue. In this study, we developed a technique for the purpose of enhancing the peripheral dose gradient by magnifying the total number of beams focused toward each isocenter via patient head tilt and simultaneous beam intensity modulations. Methods: Computer scripting for the proposed beam number enhancement (BNE) technique was developed. The technique was tested and then implemented on a clinical treatment planning system for a dedicated brain radiosurgical system (GK Perfexion, Elekta Oncology). Tomore » study technical feasibility and dosimetric advantages of the technique, we compared treatment planning quality and delivery efficiency for 20 radiosurgical cases previously treated at our institution. These cases included relatively complex treatments such as acoustic schwannoma, meningioma, brain metastasis and mesial temporal lobe epilepsy. Results: The BNE treatment plans were found to produce nearly identical target volume coverage (absolute value < 0.5%, P > 0.2) and dose conformity (BNE CI= 1.41±0.15 versus 1.41±0.20, P>0.9) as the original treatment plans. The total beam-on time for theBNE treatment plans were comparable (within 1.0 min or 1.8%) with those of the original treatment plans for all the cases. However, BNE treatment plans significantly improved the mean gradient index (BNE GI = 2.9±0.3 versus original GI =3.0±0.3 p<0.0001) and low-level isodose volumes, e.g. 20-50% prescribed isodose volumes, by 2.0% to 5.0% (p<0.02). Furthermore, with 4 to 5-fold increase in the total number of beams, the GI decreased by as much as 20% or 0.5 in absolute values. Conclusion: BNE via head tilt and simultaneous beam intensity modulation is an effective and efficient technique that physically sharpens the peripheral dose gradient for brain radiosurgery.« less

Safety assessment of Hibiscus sabdariffa after maternal exposure on male reproductive parameters in rats.

PubMed

de Arruda, Aline; Cardoso, Claudia Andrea L; Vieira, Maria do Carmo; Arena, Arielle Cristina

2016-01-01

Hibiscus sabdariffa L. (Malvaceae) is a species widely used in folk medicine for the treatment of some disorders. This study evaluated the effects of H. sabdariffa (HS) on the development of the male reproductive tract in rats following in utero exposure. Pregnant rats received 250 or 500 mg/kg of HS extract or vehicle from gestational day 12 until day 21 of lactation. Both doses of HS increased the body weight of male offspring at weaning, without compromising the puberty onset parameters. At puberty, there was a significant increase in the vas deferens absolute weight and a significant reduction in the relative weight of kidney at higher dose. These animals also presented a significant reduction in the sperm number in the caput/corpus of epididymis after exposure to both doses and a reduction in the sperm number in the cauda epididymis for the lower dose. At adulthood, the highest dose significantly reduced the sperm production in relation to controls and both doses provoked a reduction in the relative sperm number in the epididymis without affecting the sperm morphology. These findings demonstrated that maternal exposure to H. sabdariffa can adversely influence the male reproductive system in rats.

Study on the Dose Uncertainties in the Lung during Passive Proton Irradiation with a Proton Beam Range Compensator

NASA Astrophysics Data System (ADS)

Yoo, Seung Hoon; Son, Jae Man; Yoon, Myonggeun; Park, Sung Yong; Shin, Dongho; Min, Byung Jun

2018-06-01

A moving phantom is manufactured for mimicking lung model to study the dose uncertainty from CT number-stopping power conversion and dose calculation in the soft tissue, light lung tissue and bone regions during passive proton irradiation with compensator smearing value. The phantom is scanned with a CT system, and a proton beam irradiation plan is carried out with the use of a treatment planning system (Eclipse). In the case of the moving phantom, a RPM system is used for respiratory gating. The uncertainties in the dose distribution between the measured data and the planned data are investigated by a gamma analysis with 3%-3 mm acceptance criteria. To investigate smearing effect, three smearing values (0.3 cm, 0.7 cm, 1.2 cm) are used to for fixed and moving phantom system. For both fixed and moving phantom, uncertainties in the light lung tissue are severe than those in soft tissue region in which the dose uncertainties are within clinically tolerable ranges. As the smearing value increases, the uncertainty in the proton dose distribution decreases.

Controlled release systems containing solid dispersions: strategies and mechanisms.

PubMed

Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Park, Jun Bom; Lee, Beom-Jin

2011-10-01

In addition to a number of highly soluble drugs, most new chemical entities under development are poorly water-soluble drugs generally characterized by an insufficient dissolution rate and a small absorption window, leading to the low bioavailability. Controlled-release (CR) formulations have several potential advantages over conventional dosage forms, such as providing a uniform and prolonged therapeutic effect to improve patient compliance, reducing the frequency of dosing, minimizing the number of side effects, and reducing the strength of the required dose while increasing the effectiveness of the drug. Solid dispersions (SD) can be used to enhance the dissolution rate of poorly water-soluble drugs and to sustain the drug release by choosing an appropriate carrier. Thus, a CR-SD comprises both functions of SD and CR for poorly water-soluble drugs. Such CR dosage forms containing SD provide an immediately available dose for an immediate action followed by a gradual and continuous release of subsequent doses to maintain the plasma concentration of poorly water-soluble drugs over an extended period of time. This review aims to summarize all currently known aspects of controlled release systems containing solid dispersions, focusing on the preparation methods, mechanisms of action and characterization of physicochemical properties of the system.

MO-FG-202-05: Identifying Treatment Planning System Errors in IROC-H Phantom Irradiations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kerns, J; Followill, D; Howell, R

Purpose: Treatment Planning System (TPS) errors can affect large numbers of cancer patients receiving radiation therapy. Using an independent recalculation system, the Imaging and Radiation Oncology Core-Houston (IROC-H) can identify institutions that have not sufficiently modelled their linear accelerators in their TPS model. Methods: Linear accelerator point measurement data from IROC-H’s site visits was aggregated and analyzed from over 30 linear accelerator models. Dosimetrically similar models were combined to create “classes”. The class data was used to construct customized beam models in an independent treatment dose verification system (TVS). Approximately 200 head and neck phantom plans from 2012 to 2015more » were recalculated using this TVS. Comparison of plan accuracy was evaluated by comparing the measured dose to the institution’s TPS dose as well as the TVS dose. In cases where the TVS was more accurate than the institution by an average of >2%, the institution was identified as having a non-negligible TPS error. Results: Of the ∼200 recalculated plans, the average improvement using the TVS was ∼0.1%; i.e. the recalculation, on average, slightly outperformed the institution’s TPS. Of all the recalculated phantoms, 20% were identified as having a non-negligible TPS error. Fourteen plans failed current IROC-H criteria; the average TVS improvement of the failing plans was ∼3% and 57% were found to have non-negligible TPS errors. Conclusion: IROC-H has developed an independent recalculation system to identify institutions that have considerable TPS errors. A large number of institutions were found to have non-negligible TPS errors. Even institutions that passed IROC-H criteria could be identified as having a TPS error. Resolution of such errors would improve dose delivery for a large number of IROC-H phantoms and ultimately, patients.« less

SU-F-T-26: A Study of the Consistency of Brachytherapy Treatments for Vaginal Cuff

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shojaei, M; Pella, S; Dumitru, N

2016-06-15

Purpose: To evaluate to treatment consistency over the total number of fractions when treatment what HDR brachytherapy using the ML cylinders. At the same time the dosimetric impact on the critical organs is monitored over the total number of fractions. Methods: A retrospective analysis of 10 patients treated with Cylinder applicators, from 2015–2016 were considered for this study. The CT scans of these patients, taken before each treatment were separately imported in to the treatment planning system and paired with the initial CT scan after completing the contouring. Two sets of CT images were fused together with respective to themore » applicator, using landmark registration. The doses of each plan were imported as well and a cumulative dosimetric analysis was made for bladder, bowels, and rectum and PTV. Results: No contour of any of the OAR was exactly similar when CT images were fused on each other. The PTV volumes vary from fraction to fraction. There was always a difference between the doses received by the OARs between treatments. The maximum dose varied between 5% and 30% in rectum and bladder. The minimum dose varied between 5% and 8% in rectum and bladder. The average dose varied between 15% and 20% in rectum and bladder. Deviation in placement were noticed between fractions. Conclusion: The variation in volumes of OARs and isodoses near the OARs, indicate that the estimated doses to OARs on the planning system may not be the same dose delivered to the patient in all the fractions. There are no major differences between the prescribed dose and the delivered dose over the total number of fractions. In some cases the critical organs will benefit if the consecutive plans will made after the CT scans will be registered with the initial scan and then planned.« less

Intraoperative radiation exposure in spinal scoliosis surgery for pediatric patients using the O-arm® imaging system.

PubMed

Kobayashi, Kazuyoshi; Ando, Kei; Ito, Kenyu; Tsushima, Mikito; Morozumi, Masayoshi; Tanaka, Satoshi; Machino, Masaaki; Ota, Kyotaro; Ishiguro, Naoki; Imagama, Shiro

2018-05-01

The O-arm ® navigation system allows intraoperative CT imaging that can facilitate highly accurate instrumentation surgery, but radiation exposure is higher than with X-ray radiography. This is a particular concern in pediatric surgery. The purpose of this study is to examine intraoperative radiation exposure in pediatric spinal scoliosis surgery using O-arm. The subjects were 38 consecutive patients (mean age 12.9 years, range 10-17) with scoliosis who underwent spinal surgery with posterior instrumentation using O-arm. The mean number of fused vertebral levels was 11.0 (6-15). O-arm was performed before and after screw insertion, using an original protocol for the cervical, thoracic, and lumbar spine doses. The average scanning range was 6.9 (5-9) intervertebral levels per scan, with 2-7 scans per patient (mean 4.0 scans). Using O-arm, the dose per scan was 92.5 (44-130) mGy, and the mean total dose was 401 (170-826) mGy. This dose was 80.2% of the mean preoperative CT dose of 460 (231-736) mGy (P = 0.11). The total exposure dose and number of scans using intraoperative O-arm correlated strongly and significantly with the number of fused levels; however, there was no correlation with the patient's height. As the fused range became wider, several scans were required for O-arm, and the total radiation exposure became roughly the same as that in preoperative CT. Use of O-arm in our original protocol can contribute to reduction in radiation exposure.

SU-E-T-268: Differences in Treatment Plan Quality and Delivery Between Two Commercial Treatment Planning Systems for Volumetric Arc-Based Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, S; Zhang, H; Zhang, B

2015-06-15

Purpose: To clinically evaluate the differences in volumetric modulated arc therapy (VMAT) treatment plan and delivery between two commercial treatment planning systems. Methods: Two commercial VMAT treatment planning systems with different VMAT optimization algorithms and delivery approaches were evaluated. This study included 16 clinical VMAT plans performed with the first system: 2 spine, 4 head and neck (HN), 2 brain, 4 pancreas, and 4 pelvis plans. These 16 plans were then re-optimized with the same number of arcs using the second treatment planning system. Planning goals were invariant between the two systems. Gantry speed, dose rate modulation, MLC modulation, planmore » quality, number of monitor units (MUs), VMAT quality assurance (QA) results, and treatment delivery time were compared between the 2 systems. VMAT QA results were performed using Mapcheck2 and analyzed with gamma analysis (3mm/3% and 2mm/2%). Results: Similar plan quality was achieved with each VMAT optimization algorithm, and the difference in delivery time was minimal. Algorithm 1 achieved planning goals by highly modulating the MLC (total distance traveled by leaves (TL) = 193 cm average over control points per plan), while maintaining a relatively constant dose rate (dose-rate change <100 MU/min). Algorithm 2 involved less MLC modulation (TL = 143 cm per plan), but greater dose-rate modulation (range = 0-600 MU/min). The average number of MUs was 20% less for algorithm 2 (ratio of MUs for algorithms 2 and 1 ranged from 0.5-1). VMAT QA results were similar for all disease sites except HN plans. For HN plans, the average gamma passing rates were 88.5% (2mm/2%) and 96.9% (3mm/3%) for algorithm 1 and 97.9% (2mm/2%) and 99.6% (3mm/3%) for algorithm 2. Conclusion: Both VMAT optimization algorithms achieved comparable plan quality; however, fewer MUs were needed and QA results were more robust for Algorithm 2, which more highly modulated dose rate.« less

Differential pencil beam dose computation model for photons.

PubMed

Mohan, R; Chui, C; Lidofsky, L

1986-01-01

Differential pencil beam (DPB) is defined as the dose distribution relative to the position of the first collision, per unit collision density, for a monoenergetic pencil beam of photons in an infinite homogeneous medium of unit density. We have generated DPB dose distribution tables for a number of photon energies in water using the Monte Carlo method. The three-dimensional (3D) nature of the transport of photons and electrons is automatically incorporated in DPB dose distributions. Dose is computed by evaluating 3D integrals of DPB dose. The DPB dose computation model has been applied to calculate dose distributions for 60Co and accelerator beams. Calculations for the latter are performed using energy spectra generated with the Monte Carlo program. To predict dose distributions near the beam boundaries defined by the collimation system as well as blocks, we utilize the angular distribution of incident photons. Inhomogeneities are taken into account by attenuating the primary photon fluence exponentially utilizing the average total linear attenuation coefficient of intervening tissue, by multiplying photon fluence by the linear attenuation coefficient to yield the number of collisions in the scattering volume, and by scaling the path between the scattering volume element and the computation point by an effective density.

Out-of-field doses from pediatric craniospinal irradiations using 3D-CRT, IMRT, helical tomotherapy and electron-based therapy

NASA Astrophysics Data System (ADS)

De Saint-Hubert, Marijke; Verellen, Dirk; Poels, Kenneth; Crijns, Wouter; Magliona, Federica; Depuydt, Tom; Vanhavere, Filip; Struelens, Lara

2017-07-01

Medulloblastoma treatment involves irradiation of the entire central nervous system, i.e. craniospinal irradiation (CSI). This is associated with the significant exposure of large volumes of healthy tissue and there is growing concern regarding treatment-associated side effects. The current study compares out-of-field organ doses in children receiving CSI through 3D-conformal radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT), helical tomotherapy (HT) and an electron-based technique, and includes radiation doses resulting from imaging performed during treatment. An extensive phantom study is performed, using an anthropomorphic phantom corresponding to a five year old child, in which organ absorbed doses are measured using thermoluminescent detectors. Additionally, the study evaluates and explores tools for calculating out-of-field patient doses using the treatment planning system (TPS) and analytical models. In our study, 3D-CRT resulted in very high doses to a limited number of organs, while it was able to spare organs such as the lungs and breast when compared to IMRT and HT. Both IMRT and HT spread the dose over more organs and were able to spare the heart, thyroid, bladder, uterus and testes when compared to 3D-CRT. The electron-based technique considerably decreased the out-of-field doses in deep-seated organs but could not avoid nearby out-of-field organs such as the lungs, ribs, adrenals, kidneys and uterus. The daily imaging dose is small compared to the treatment dose burden. The TPS error for out-of-field doses was most pronounced for organs further away from the target; nevertheless, no systematic underestimation was observed for any of the studied TPS systems. Finally, analytical modeling was most optimal for 3D-CRT although the number of organs that could be modeled was limited. To conclude, none of the techniques studied was capable of sparing all organs from out-of-field doses. Nevertheless, the electron-based technique showed the most promise for out-of-field organ dose reduction during CSI when compared to photon techniques.

Dose measurement based on threshold shift in MOSFET arrays in commercial SRAMS

NASA Technical Reports Server (NTRS)

Scheick, L. Z.; Swift, G.

2002-01-01

A new method using an array of MOS transistors isdescribed for measuring dose absorbed from ionizingradiation. Using the array of MOSFETs in a SRAM, a direct measurement of the number of MOS cells which change as a function of applied bias on the SRAM. Since the input and output of a SRAM used as a dosimeter is completely digital, the measurement of dose is easily accessible by a remote processing system.

Potential drug related problems detected by electronic expert support system in patients with multi-dose drug dispensing.

PubMed

Tora, Hammar; Bo, Hovstadius; Bodil, Lidström; Göran, Petersson; Birgit, Eiermann

2014-10-01

Background Drug related problems (DRPs) are frequent and cause suffering for patients and substantial costs for society. Multi-dose drug dispensing (MDDD) is a service by which patients receive their medication packed in bags with one unit for each dose occasion. The clinical decision support system (CDSS) electronic expert support (EES) analyses patients' prescriptions in the Swedish national e-prescription repository and provides alerts if potential DRPs are detected, i.e. drug-drug interactions, duplicate therapy, drug-disease contraindications, high dose, gender warnings, geriatric, and paediatric alerts. Objective To analyse potential DRPs in patients with MDDD, detected by means of EES. Setting A register study of all electronically stored prescriptions for patients with MDDD in Sweden (n = 180,059) March 5-June 5, 2013. Method Drug use and potential DRPs detected in the study population during the 3 month study period by EES were analysed. The potential DRPs were analysed in relation to patients' age, gender, number of drugs, and type of medication. Main outcome measure Prevalence of potential DRPs measured as EES alerts. Results The study population was on average 75.8 years of age (± 17.5, range 1-110) and had 10.0 different medications (± 4.7, range 1-53). EES alerted for potential DRPs in 76 % of the population with a mean of 2.2 alerts per patient (± 2.4, range 0-27). The older patients received a lower number of alerts compared to younger patients despite having a higher number of drugs. The most frequent alert categories were drug-drug interactions (37 % of all alerts), duplicate therapy (30 %), and geriatric warnings for high dose or inappropriate drugs (23 %). Psycholeptics, psychoanaleptics, antithrombotic agents, anti-epileptics, renin-angiotensin system agents, and analgesics represented 71 % of all drugs involved in alerts. Conclusions EES detected potential DRPs in the majority of patients with MDDD. The number of potential DRPs was associated with the number of drugs, age, gender, and type of medication. A CDSS such as EES might be a useful tool for physicians and pharmacists to assist in the important task of monitoring patients with MDDD for potential DRPs.

Radiation dose and image quality of X-ray volume imaging systems: cone-beam computed tomography, digital subtraction angiography and digital fluoroscopy.

PubMed

Paul, Jijo; Jacobi, Volkmar; Farhang, Mohammad; Bazrafshan, Babak; Vogl, Thomas J; Mbalisike, Emmanuel C

2013-06-01

Radiation dose and image quality estimation of three X-ray volume imaging (XVI) systems. A total of 126 patients were examined using three XVI systems (groups 1-3) and their data were retrospectively analysed from 2007 to 2012. Each group consisted of 42 patients and each patient was examined using cone-beam computed tomography (CBCT), digital subtraction angiography (DSA) and digital fluoroscopy (DF). Dose parameters such as dose-area product (DAP), skin entry dose (SED) and image quality parameters such as Hounsfield unit (HU), noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were estimated and compared using appropriate statistical tests. Mean DAP and SED were lower in recent XVI than its previous counterparts in CBCT, DSA and DF. HU of all measured locations was non-significant between the groups except the hepatic artery. Noise showed significant difference among groups (P < 0.05). Regarding CNR and SNR, the recent XVI showed a higher and significant difference compared to its previous versions. Qualitatively, CBCT showed significance between versions unlike the DSA and DF which showed non-significance. A reduction of radiation dose was obtained for the recent-generation XVI system in CBCT, DSA and DF. Image noise was significantly lower; SNR and CNR were higher than in previous versions. The technological advancements and the reduction in the number of frames led to a significant dose reduction and improved image quality with the recent-generation XVI system. • X-ray volume imaging (XVI) systems are increasingly used for interventional radiological procedures. • More modern XVI systems use lower radiation doses compared with earlier counterparts. • Furthermore more modern XVI systems provide higher image quality. • Technological advances reduce radiation dose and improve image quality.

SU-F-J-193: Efficient Dose Extinction Method for Water Equivalent Path Length (WEPL) of Real Tissue Samples for Validation of CT HU to Stopping Power Conversion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, R; Baer, E; Jee, K

Purpose: For proton therapy, an accurate model of CT HU to relative stopping power (RSP) conversion is essential. In current practice, validation of these models relies solely on measurements of tissue substitutes with standard compositions. Validation based on real tissue samples would be much more direct and can address variations between patients. This study intends to develop an efficient and accurate system based on the concept of dose extinction to measure WEPL and retrieve RSP in biological tissue in large number of types. Methods: A broad AP proton beam delivering a spread out Bragg peak (SOBP) is used to irradiatemore » the samples with a Matrixx detector positioned immediately below. A water tank was placed on top of the samples, with the water level controllable in sub-millimeter by a remotely controlled dosing pump. While gradually lowering the water level with beam on, the transmission dose was recorded at 1 frame/sec. The WEPL were determined as the difference between the known beam range of the delivered SOBP (80%) and the water level corresponding to 80% of measured dose profiles in time. A Gammex 467 phantom was used to test the system and various types of biological tissue was measured. Results: RSP for all Gammex inserts, expect the one made with lung-450 material (<2% error), were determined within ±0.5% error. Depends on the WEPL of investigated phantom, a measurement takes around 10 min, which can be accelerated by a faster pump. Conclusion: Based on the concept of dose extinction, a system was explored to measure WEPL efficiently and accurately for a large number of samples. This allows the validation of CT HU to stopping power conversions based on large number of samples and real tissues. It also allows the assessment of beam uncertainties due to variations over patients, which issue has never been sufficiently studied before.« less

ISDD: A computational model of particle sedimentation, diffusion and target cell dosimetry for in vitro toxicity studies

PubMed Central

2010-01-01

Background The difficulty of directly measuring cellular dose is a significant obstacle to application of target tissue dosimetry for nanoparticle and microparticle toxicity assessment, particularly for in vitro systems. As a consequence, the target tissue paradigm for dosimetry and hazard assessment of nanoparticles has largely been ignored in favor of using metrics of exposure (e.g. μg particle/mL culture medium, particle surface area/mL, particle number/mL). We have developed a computational model of solution particokinetics (sedimentation, diffusion) and dosimetry for non-interacting spherical particles and their agglomerates in monolayer cell culture systems. Particle transport to cells is calculated by simultaneous solution of Stokes Law (sedimentation) and the Stokes-Einstein equation (diffusion). Results The In vitro Sedimentation, Diffusion and Dosimetry model (ISDD) was tested against measured transport rates or cellular doses for multiple sizes of polystyrene spheres (20-1100 nm), 35 nm amorphous silica, and large agglomerates of 30 nm iron oxide particles. Overall, without adjusting any parameters, model predicted cellular doses were in close agreement with the experimental data, differing from as little as 5% to as much as three-fold, but in most cases approximately two-fold, within the limits of the accuracy of the measurement systems. Applying the model, we generalize the effects of particle size, particle density, agglomeration state and agglomerate characteristics on target cell dosimetry in vitro. Conclusions Our results confirm our hypothesis that for liquid-based in vitro systems, the dose-rates and target cell doses for all particles are not equal; they can vary significantly, in direct contrast to the assumption of dose-equivalency implicit in the use of mass-based media concentrations as metrics of exposure for dose-response assessment. The difference between equivalent nominal media concentration exposures on a μg/mL basis and target cell doses on a particle surface area or number basis can be as high as three to six orders of magnitude. As a consequence, in vitro hazard assessments utilizing mass-based exposure metrics have inherently high errors where particle number or surface areas target cells doses are believed to drive response. The gold standard for particle dosimetry for in vitro nanotoxicology studies should be direct experimental measurement of the cellular content of the studied particle. However, where such measurements are impractical, unfeasible, and before such measurements become common, particle dosimetry models such as ISDD provide a valuable, immediately useful alternative, and eventually, an adjunct to such measurements. PMID:21118529

Dosimetric comparison of helical tomotherapy treatment plans for total marrow irradiation created using GPU and CPU dose calculation engines.

PubMed

Nalichowski, Adrian; Burmeister, Jay

2013-07-01

To compare optimization characteristics, plan quality, and treatment delivery efficiency between total marrow irradiation (TMI) plans using the new TomoTherapy graphic processing unit (GPU) based dose engine and CPU/cluster based dose engine. Five TMI plans created on an anthropomorphic phantom were optimized and calculated with both dose engines. The planning treatment volume (PTV) included all the bones from head to mid femur except for upper extremities. Evaluated organs at risk (OAR) consisted of lung, liver, heart, kidneys, and brain. The following treatment parameters were used to generate the TMI plans: field widths of 2.5 and 5 cm, modulation factors of 2 and 2.5, and pitch of either 0.287 or 0.43. The optimization parameters were chosen based on the PTV and OAR priorities and the plans were optimized with a fixed number of iterations. The PTV constraint was selected to ensure that at least 95% of the PTV received the prescription dose. The plans were evaluated based on D80 and D50 (dose to 80% and 50% of the OAR volume, respectively) and hotspot volumes within the PTVs. Gamma indices (Γ) were also used to compare planar dose distributions between the two modalities. The optimization and dose calculation times were compared between the two systems. The treatment delivery times were also evaluated. The results showed very good dosimetric agreement between the GPU and CPU calculated plans for any of the evaluated planning parameters indicating that both systems converge on nearly identical plans. All D80 and D50 parameters varied by less than 3% of the prescription dose with an average difference of 0.8%. A gamma analysis Γ(3%, 3 mm) < 1 of the GPU plan resulted in over 90% of calculated voxels satisfying Γ < 1 criterion as compared to baseline CPU plan. The average number of voxels meeting the Γ < 1 criterion for all the plans was 97%. In terms of dose optimization/calculation efficiency, there was a 20-fold reduction in planning time with the new GPU system. The average optimization/dose calculation time utilizing the traditional CPU/cluster based system was 579 vs 26.8 min for the GPU based system. There was no difference in the calculated treatment delivery time per fraction. Beam-on time varied based on field width and pitch and ranged between 15 and 28 min. The TomoTherapy GPU based dose engine is capable of calculating TMI treatment plans with plan quality nearly identical to plans calculated using the traditional CPU/cluster based system, while significantly reducing the time required for optimization and dose calculation.

Improved-resolution real-time skin-dose mapping for interventional fluoroscopic procedures

NASA Astrophysics Data System (ADS)

Rana, Vijay K.; Rudin, Stephen; Bednarek, Daniel R.

2014-03-01

We have developed a dose-tracking system (DTS) that provides a real-time display of the skin-dose distribution on a 3D patient graphic during fluoroscopic procedures. Radiation dose to individual points on the skin is calculated using exposure and geometry parameters from the digital bus on a Toshiba C-arm unit. To accurately define the distribution of dose, it is necessary to use a high-resolution patient graphic consisting of a large number of elements. In the original DTS version, the patient graphics were obtained from a library of population body scans which consisted of larger-sized triangular elements resulting in poor congruence between the graphic points and the x-ray beam boundary. To improve the resolution without impacting real-time performance, the number of calculations must be reduced and so we created software-designed human models and modified the DTS to read the graphic as a list of vertices of the triangular elements such that common vertices of adjacent triangles are listed once. Dose is calculated for each vertex point once instead of the number of times that a given vertex appears in multiple triangles. By reformatting the graphic file, we were able to subdivide the triangular elements by a factor of 64 times with an increase in the file size of only 1.3 times. This allows a much greater number of smaller triangular elements and improves resolution of the patient graphic without compromising the real-time performance of the DTS and also gives a smoother graphic display for better visualization of the dose distribution.

Provider risk factors for medication administration error alerts: analyses of a large-scale closed-loop medication administration system using RFID and barcode.

PubMed

Hwang, Yeonsoo; Yoon, Dukyong; Ahn, Eun Kyoung; Hwang, Hee; Park, Rae Woong

2016-12-01

To determine the risk factors and rate of medication administration error (MAE) alerts by analyzing large-scale medication administration data and related error logs automatically recorded in a closed-loop medication administration system using radio-frequency identification and barcodes. The subject hospital adopted a closed-loop medication administration system. All medication administrations in the general wards were automatically recorded in real-time using radio-frequency identification, barcodes, and hand-held point-of-care devices. MAE alert logs recorded during a full 1 year of 2012. We evaluated risk factors for MAE alerts including administration time, order type, medication route, the number of medication doses administered, and factors associated with nurse practices by logistic regression analysis. A total of 2 874 539 medication dose records from 30 232 patients (882.6 patient-years) were included in 2012. We identified 35 082 MAE alerts (1.22% of total medication doses). The MAE alerts were significantly related to administration at non-standard time [odds ratio (OR) 1.559, 95% confidence interval (CI) 1.515-1.604], emergency order (OR 1.527, 95%CI 1.464-1.594), and the number of medication doses administered (OR 0.993, 95%CI 0.992-0.993). Medication route, nurse's employment duration, and working schedule were also significantly related. The MAE alert rate was 1.22% over the 1-year observation period in the hospital examined in this study. The MAE alerts were significantly related to administration time, order type, medication route, the number of medication doses administered, nurse's employment duration, and working schedule. The real-time closed-loop medication administration system contributed to improving patient safety by preventing potential MAEs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Asynchronous data acquisition and on-the-fly analysis of dose fractionated cryoEM images by UCSFImage

PubMed Central

Li, Xueming; Zheng, Shawn; Agard, David A.; Cheng, Yifan

2015-01-01

Newly developed direct electron detection cameras have a high image output frame rate that enables recording dose fractionated image stacks of frozen hydrated biological samples by electron cryomicroscopy (cryoEM). Such novel image acquisition schemes provide opportunities to analyze cryoEM data in ways that were previously impossible. The file size of a dose fractionated image stack is 20 ~ 60 times larger than that of a single image. Thus, efficient data acquisition and on-the-fly analysis of a large number of dose-fractionated image stacks become a serious challenge to any cryoEM data acquisition system. We have developed a computer-assisted system, named UCSFImage4, for semi-automated cryo-EM image acquisition that implements an asynchronous data acquisition scheme. This facilitates efficient acquisition, on-the-fly motion correction, and CTF analysis of dose fractionated image stacks with a total time of ~60 seconds/exposure. Here we report the technical details and configuration of this system. PMID:26370395

Radiation leakage dose from Elekta electron collimation system

PubMed Central

Hogstrom, Kenneth R.; Carver, Robert L.

2016-01-01

This study provided baseline data required for a greater project, whose objective was to design a new Elekta electron collimation system having significantly lighter electron applicators with equally low out‐of field leakage dose. Specifically, off‐axis dose profiles for the electron collimation system of our uniquely configured Elekta Infinity accelerator with the MLCi2 treatment head were measured and calculated for two primary purposes: 1) to evaluate and document the out‐of‐field leakage dose in the patient plane and 2) to validate the dose distributions calculated using a BEAMnrc Monte Carlo (MC) model for out‐of‐field dose profiles. Off‐axis dose profiles were measured in a water phantom at 100 cm SSD for 1 and 2 cm depths along the in‐plane, cross‐plane, and both diagonal axes using a cylindrical ionization chamber with the 10×10 and 20×20 cm2 applicators and 7, 13, and 20 MeV beams. Dose distributions were calculated using a previously developed BEAMnrc MC model of the Elekta Infinity accelerator for the same beam energies and applicator sizes and compared with measurements. Measured results showed that the in‐field beam flatness met our acceptance criteria (±3% on major and ±4% on diagonal axes) and that out‐of‐field mean and maximum percent leakage doses in the patient plane met acceptance criteria as specified by the International Electrotechnical Commission (IEC). Cross‐plane out‐of‐field dose profiles showed greater leakage dose than in‐plane profiles, attributed to the curved edges of the upper X‐ray jaws and multileaf collimator. Mean leakage doses increased with beam energy, being 0.93% and 0.85% of maximum central axis dose for the 10×10 and 20×20 cm2 applicators, respectively, at 20 MeV. MC calculations predicted the measured dose to within 0.1% in most profiles outside the radiation field; however, excluding modeling of nontrimmer applicator components led to calculations exceeding measured data by as much as 0.2% for some regions along the in‐plane axis. Using EGSnrc LATCH bit filtering to separately calculate out‐of‐field leakage dose components (photon dose, primary electron dose, and electron dose arising from interactions in various collimating components), MC calculations revealed that the primary electron dose in the out‐of‐field leakage region was small and decreased as beam energy increased. Also, both the photon dose component and electron dose component resulting from collimator scatter dominated the leakage dose, increasing with increasing beam energy. We concluded that our custom Elekta Infinity with the MLCi2 treatment head met IEC leakage dose criteria in the patient plane. Also, accuracy of our MC model should be sufficient for our use in the design of a new, improved electron collimation system. PACS number(s): 87.56.nk, 87.10.Rt, 87.56.J PMID:27685101

Two‐year experience with the commercial Gamma Knife Check software

PubMed Central

Bhatnagar, Jagdish; Bednarz, Greg; Novotny, Josef; Flickinger, John; Lunsford, L. Dade; Huq, M. Saiful

2016-01-01

The Gamma Knife Check software is an FDA approved second check system for dose calculations in Gamma Knife radiosurgery. The purpose of this study was to evaluate the accuracy and the stability of the commercial software package as a tool for independent dose verification. The Gamma Knife Check software version 8.4 was commissioned for a Leksell Gamma Knife Perfexion and a 4C unit at the University of Pittsburgh Medical Center in May 2012. Independent dose verifications were performed using this software for 319 radiosurgery cases on the Perfexion and 283 radiosurgery cases on the 4C units. The cases on each machine were divided into groups according to their diagnoses, and an averaged absolute percent dose difference for each group was calculated. The percentage dose difference for each treatment target was obtained as the relative difference between the Gamma Knife Check dose and the dose from the tissue maximum ratio algorithm (TMR 10) from the GammaPlan software version 10 at the reference point. For treatment plans with imaging skull definition, results obtained from the Gamma Knife Check software using the measurement‐based skull definition method are used for comparison. The collected dose difference data were also analyzed in terms of the distance from the treatment target to the skull, the number of treatment shots used for the target, and the gamma angles of the treatment shots. The averaged percent dose differences between the Gamma Knife Check software and the GammaPlan treatment planning system are 0.3%, 0.89%, 1.24%, 1.09%, 0.83%, 0.55%, 0.33%, and 1.49% for the trigeminal neuralgia, acoustic neuroma, arteriovenous malformation (AVM), meningioma, pituitary adenoma, glioma, functional disorders, and metastasis cases on the Perfexion unit. The corresponding averaged percent dose differences for the 4C unit are 0.33%, 1.2%, 2.78% 1.99%, 1.4%, 1.92%, 0.62%, and 1.51%, respectively. The dose difference is, in general, larger for treatment targets in the peripheral regions of the skull owing to the difference in the numerical methods used for skull shape simulation in the GammaPlan and the Gamma Knife Check software. Larger than 5% dose differences were observed on both machines for certain targets close to patient skull surface and for certain targets in the lower half of the brain on the Perfexion, especially when shots with 70 and/or 110 gamma angles are used. Out of the 1065 treatment targets studied, a 5% cutoff criterion cannot always be met for the dose differences between the studied versions of the Gamma Knife Check software and the planning system for 40 treatment targets. PACS number(s): 87.55.Qr, 87.56.Fc PMID:27455470

ALARA database value in future outage work planning and dose management

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, D.W.; Green, W.H.

1995-03-01

ALARA database encompassing job-specific duration and man-rem plant specific information over three refueling outages represents an invaluable tool for the outage work planner and ALARA engineer. This paper describes dose-management trends emerging based on analysis of three refueling outages at Clinton Power Station. Conclusions reached based on hard data available from a relational database dose-tracking system is a valuable tool for planning of future outage work. The system`s ability to identify key problem areas during a refueling outage is improving as more outage comparative data becomes available. Trends over a three outage period are identified in this paper in themore » categories of number and type of radiation work permits implemented, duration of jobs, projected vs. actual dose rates in work areas, and accuracy of outage person-rem projection. The value of the database in projecting 1 and 5 year station person-rem estimates is discussed.« less

Dosing antibiotics in neonates: review of the pharmacokinetic data.

PubMed

Rivera-Chaparro, Nazario D; Cohen-Wolkowiez, Michael; Greenberg, Rachel G

2017-09-01

Antibiotics are often used in neonates despite the absence of relevant dosing information in drug labels. For neonatal dosing, clinicians must extrapolate data from studies for adults and older children, who have strikingly different physiologies. As a result, dosing extrapolation can lead to increased toxicity or efficacy failures in neonates. Driven by these differences and recent legislation mandating the study of drugs in children and neonates, an increasing number of pharmacokinetic studies of antibiotics are being performed in neonates. These studies have led to new dosing recommendations with particular consideration for neonate body size and maturation. Herein, we highlight the available pharmacokinetic data for commonly used systemic antibiotics in neonates.

A new method for designing dual foil electron beam forming systems. II. Feasibility of practical implementation of the method

NASA Astrophysics Data System (ADS)

Adrich, Przemysław

2016-05-01

In Part I of this work a new method for designing dual foil electron beam forming systems was introduced. In this method, an optimal configuration of the dual foil system is found by means of a systematic, automatized scan of system performance in function of its parameters. At each point of the scan, Monte Carlo method is used to calculate the off-axis dose profile in water taking into account detailed and complete geometry of the system. The new method, while being computationally intensive, minimizes the involvement of the designer. In this Part II paper, feasibility of practical implementation of the new method is demonstrated. For this, a prototype software tools were developed and applied to solve a real life design problem. It is demonstrated that system optimization can be completed within few hours time using rather moderate computing resources. It is also demonstrated that, perhaps for the first time, the designer can gain deep insight into system behavior, such that the construction can be simultaneously optimized in respect to a number of functional characteristics besides the flatness of the off-axis dose profile. In the presented example, the system is optimized in respect to both, flatness of the off-axis dose profile and the beam transmission. A number of practical issues related to application of the new method as well as its possible extensions are discussed.

Calculation of Organ Doses for a Large Number of Patients Undergoing CT Examinations.

PubMed

Bahadori, Amir; Miglioretti, Diana; Kruger, Randell; Flynn, Michael; Weinmann, Sheila; Smith-Bindman, Rebecca; Lee, Choonsik

2015-10-01

The objective of our study was to develop an automated calculation method to provide organ dose assessment for a large cohort of pediatric and adult patients undergoing CT examinations. We adopted two dose libraries that were previously published: the volume CT dose index-normalized organ dose library and the tube current-exposure time product (100 mAs)-normalized weighted CT dose index library. We developed an algorithm to calculate organ doses using the two dose libraries and the CT parameters available from DICOM data. We calculated organ doses for pediatric (n = 2499) and adult (n = 2043) CT examinations randomly selected from four health care systems in the United States and compared the adult organ doses with the values calculated from the ImPACT calculator. The median brain dose was 20 mGy (pediatric) and 24 mGy (adult), and the brain dose was greater than 40 mGy for 11% (pediatric) and 18% (adult) of the head CT studies. Both the National Cancer Institute (NCI) and ImPACT methods provided similar organ doses (median discrepancy < 20%) for all organs except the organs located close to the scanning boundaries. The visual comparisons of scanning coverage and phantom anatomies revealed that the NCI method, which is based on realistic computational phantoms, provides more accurate organ doses than the ImPACT method. The automated organ dose calculation method developed in this study reduces the time needed to calculate doses for a large number of patients. We have successfully used this method for a variety of CT-related studies including retrospective epidemiologic studies and CT dose trend analysis studies.

Sharpening peripheral dose gradient via beam number enhancement from patient head tilt for stereotactic brain radiosurgery

NASA Astrophysics Data System (ADS)

Chiu, Joshua; Pierce, Marlon; Braunstein, Steve E.; Theodosopoulos, Philip V.; McDermott, Michael W.; Sneed, Penny K.; Ma, Lijun

2016-10-01

Sharp dose fall-off is the hallmark of brain radiosurgery for the purpose of delivering high dose radiation to the target while minimizing peripheral dose to regional normal brain tissue. In this study, a technique was developed to enhance the peripheral dose gradient by magnifying the total number of beams focused toward each isocenter through pre-programmed patient head tilting. This technique was tested in clinical settings on a dedicated brain radiosurgical system (GKPFX, Gamma Knife Perfexion, Elekta Oncology) by comparing dosimetry as well as delivery efficiency for 20 radiosurgical cases previously treated with the system. The 3-fold beam number enhancement (BNE) treatment plans were found to produce nearly identical target volume coverage (absolute value  <  0.5%, P  >  0.2) and dose conformity (BNE CI  =  1.41  ±  0.22 versus 1.41  ±  0.11, P  >  0.99) as the original treatment plans. The total beam-on time for the 3-fold BNE treatment plans were also found to be comparable (<0.5 min or 2%) with those of the original treatment plans for all the cases. However, BNE treatment plans significantly improved the mean gradient index (BNE GI  =  2.94  ±  0.27 versus original GI  =  2.98  ±  0.28 P  <  0.0001) and low-level isodose volumes, e.g. 20-50% prescribed isodose volumes, by 1.7%-3.9% (P  <  0.03). With further 4-5-fold increase in the total number of beams, the absolute gradient index can decrease by as much as  -0.5 in absolute value or  -20% for a treatment. In conclusion, BNE via patient head tilt has been demonstrated to be a clinically suitable and efficient technique for physically sharpening the peripheral dose gradient for brain radiosurgery. This work was presented in part at the 2015 ISRS Congress in Yokohama Japan.

The effect of hydroxychloroquine on lupus erythematosus-like skin lesions in MRL/lpr mice.

PubMed

Shimomatsu, Tatsuya; Kanazawa, Nobuo; Mikita, Naoya; Nakatani, Yumi; Li, Hong-Jin; Inaba, Yutaka; Ikeda, Takaharu; Kondo, Toshikazu; Furukawa, Fukumi

2016-09-01

To evaluate the effect and safety of hydroxychloroquine (HCQ) on lupus erythematosus (LE)-like skin lesions in the MRL/lpr mouse, a model for systemic LE (SLE). We divided the MRL/lpr mice into three groups that were given: (1) drinking water, (2) HCQ at a dose of 4 mg/kg/d, or (3) HCQ at a dose of 40 mg/kg/d. The HCQ was administered to examine the effect and safety of HCQ on skin lesions and the number of infiltrating cells including mast cells in the dermis. Six of 13 mice in the group given drinking water, 3 of 11 mice in the group administered low-dose HCQ (4 mg/kg/d), and 1 of 10 mice in the group administered high-dose HCQ (40 mg/kg/d) presented the skin lesions. The average number of mast cells was 81, 50, and 12 (magnification, ×100), the mortality rate was 24%, 8%, and 9% and the mean body weight gain was 4.6 g, 8.0 g and 5.1 g, respectively. HCQ was demonstrated to decrease the appearance of LE-like lesions and the number of mast cells in the dermis. Furthermore, there were no obvious systemic adverse effects. This study provides evidence that suggests benefits in human patients.

An assessment of mumps vaccine effectiveness by dose during an outbreak in Canada

PubMed Central

Deeks, Shelley L.; Lim, Gillian H.; Simpson, Mary Anne; Gagné, Louise; Gubbay, Jonathan; Kristjanson, Erik; Fung, Cecilia; Crowcroft, Natasha S.

2011-01-01

Background This investigation was done to assess vaccine effectiveness of one and two doses of the measles, mumps and rubella (MMR) vaccine during an outbreak of mumps in Ontario. The level of coverage required to reach herd immunity and interrupt community transmission of mumps was also estimated. Methods Information on confirmed cases of mumps was retrieved from Ontario’s integrated Public Health Information System. Cases that occurred between Sept. 1, 2009, and June 10, 2010, were included. Selected health units supplied coverage data from the Ontario Immunization Record Information System. Vaccine effectiveness by dose was calculated using the screening method. The basic reproductive number (R0) represents the average number of new infections per case in a fully susceptile population, and R0 values of between 4 and 10 were considered for varying levels of vaccine effectiveness. Results A total of 134 confirmed cases of mumps were identified. Information on receipt of MMR vaccine was available for 114 (85.1%) cases, of whom 63 (55.3%) reported having received only one dose of vaccine; 32 (28.1%) reported having received two doses. Vaccine effectiveness of one dose of the MMR vaccine ranged from 49.2% to 81.6%, whereas vaccine effectiveness of two doses ranged from 66.3% to 88.0%. If we assume vaccine effectiveness of 85% for two doses of the vaccine, vaccine coverage of 88.2% and 98.0% would be needed to interrupt community transmission of mumps if the corresponding reproductive values were four and six. Interpretation Our estimates of vaccine effectiveness of one and two doses of mumps-containing vaccine were consistent with the estimates that have been reported in other outbreaks. Outbreaks occurring in Ontario and elsewhere serve as a warning against complacency over vaccination programs. PMID:21576295

An assessment of mumps vaccine effectiveness by dose during an outbreak in Canada.

PubMed

Deeks, Shelley L; Lim, Gillian H; Simpson, Mary Anne; Gagné, Louise; Gubbay, Jonathan; Kristjanson, Erik; Fung, Cecilia; Crowcroft, Natasha S

2011-06-14

This investigation was done to assess vaccine effectiveness of one and two doses of the measles, mumps and rubella (MMR) vaccine during an outbreak of mumps in Ontario. The level of coverage required to reach herd immunity and interrupt community transmission of mumps was also estimated. Information on confirmed cases of mumps was retrieved from Ontario's integrated Public Health Information System. Cases that occurred between Sept. 1, 2009, and June 10, 2010, were included. Selected health units supplied coverage data from the Ontario Immunization Record Information System. Vaccine effectiveness by dose was calculated using the screening method. The basic reproductive number (R(0)) represents the average number of new infections per case in a fully susceptible population, and R(0) values of between 4 and 10 were considered for varying levels of vaccine effectiveness. A total of 134 confirmed cases of mumps were identified. Information on receipt of MMR vaccine was available for 114 (85.1%) cases, of whom 63 (55.3%) reported having received only one dose of vaccine; 32 (28.1%) reported having received two doses. Vaccine effectiveness of one dose of the MMR vaccine ranged from 49.2% to 81.6%, whereas vaccine effectiveness of two doses ranged from 66.3% to 88.0%. If we assume vaccine effectiveness of 85% for two doses of the vaccine, vaccine coverage of 88.2% and 98.0% would be needed to interrupt community transmission of mumps if the corresponding reproductive values were four and six. Our estimates of vaccine effectiveness of one and two doses of mumps-containing vaccine were consistent with the estimates that have been reported in other outbreaks. Outbreaks occurring in Ontario and elsewhere serve as a warning against complacency over vaccination programs.

Accurate heterogeneous dose calculation for lung cancer patients without high‐resolution CT densities

PubMed Central

Li, Jonathan G.; Liu, Chihray; Olivier, Kenneth R.; Dempsey, James F.

2009-01-01

The aim of this study was to investigate the relative accuracy of megavoltage photon‐beam dose calculations employing either five bulk densities or independent voxel densities determined by calibration of the CT Houndsfield number. Full‐resolution CT and bulk density treatment plans were generated for 70 lung or esophageal cancer tumors (66 cases) using a commercial treatment planning system with an adaptive convolution dose calculation algorithm (Pinnacle3, Philips Medicals Systems). Bulk densities were applied to segmented regions. Individual and population average densities were compared to the full‐resolution plan for each case. Monitor units were kept constant and no normalizations were employed. Dose volume histograms (DVH) and dose difference distributions were examined for all cases. The average densities of the segmented air, lung, fat, soft tissue, and bone for the entire set were found to be 0.14, 0.26, 0.89, 1.02, and 1.12 g/cm3, respectively. In all cases, the normal tissue DVH agreed to better than 2% in dose. In 62 of 70 DVHs of the planning target volume (PTV), agreement to better than 3% in dose was observed. Six cases demonstrated emphysema, one with bullous formations and one with a hiatus hernia having a large volume of gas. These required the additional assignment of density to the emphysemic lung and inflammatory changes to the lung, the regions of collapsed lung, the bullous formations, and the hernia gas. Bulk tissue density dose calculation provides an accurate method of heterogeneous dose calculation. However, patients with advanced emphysema may require high‐resolution CT studies for accurate treatment planning. PACS number: 87.53.Tf

Gafchromic EBT‐XD film: Dosimetry characterization in high‐dose, volumetric‐modulated arc therapy

PubMed Central

Ozawa, Shuichi; Hosono, Fumika; Sumida, Naoki; Okazue, Toshiya; Yamada, Kiyoshi; Nagata, Yasushi

2016-01-01

Radiochromic films are important tools for assessing complex dose distributions. Gafchromic EBT‐XD films have been designed for optimal performance in the 40–4,000 cGy dose range. We investigated the dosimetric characteristics of these films, including their dose‐response, postexposure density growth, and dependence on scanner orientation, beam energy, and dose rate with applications to high‐dose volumetric‐modulated arc therapy (VMAT) verification. A 10 MV beam from a TrueBeam STx linear accelerator was used to irradiate the films with doses in the 0–4,000 cGy range. Postexposure coloration was analyzed at postirradiation times ranging from several minutes to 48 h. The films were also irradiated with 6 MV (dose rate (DR): 600 MU/min), 6 MV flattening filter‐free (FFF) (DR: 1,400 MU/ min), and 10 MV FFF (DR: 2,400 MU/min) beams to determine the energy and dose‐rate dependence. For clinical examinations, we compared the dose distribution measured with EBT‐XD films and calculated by the planning system for four VMAT cases. The red channel of the EBT‐XD film exhibited a wider dynamic range than the green and blue channels. Scanner orientation yielded a variation of ∼3% in the net optical density (OD). The difference between the film front and back scan orientations was negligible, with variation of ∼1.3% in the net OD. The net OD increased sharply within the first 6 hrs after irradiation and gradually afterwards. No significant difference was observed for the beam energy and dose rate, with a variation of ∼1.5% in the net OD. The gamma passing rates (at 3%, 3 mm) between the film‐ measured and treatment planning system (TPS)‐calculated dose distributions under a high dose VMAT plan in the absolute dose mode were more than 98.9%. PACS number(s): 87.56 Fc PMID:27929504

Intraoral radiology in general dental practices - a comparison of digital and film-based X-ray systems with regard to radiation protection and dose reduction.

PubMed

Anissi, H D; Geibel, M A

2014-08-01

The purpose of this study was to gain insight into the distribution and application of digital intraoral radiographic techniques within general dental practices and to compare these with film-based systems in terms of patient dose reduction. 1100 questionnaires were handed out to general dental practitioners. Data was analyzed with respect to the type of system by using descriptive statistics and nonparametric tests, i.e. Kruskal-Wallis, Mann-Whitney and chi-square test (SPSS 20). 64% of the questioned dentists still use film-based radiology, 23% utilize storage phosphor plate (SPP) systems and 13% use a charge-coupled device (CCD). A strong correlation between the number of dentists working in a practice and the use of digital dental imaging was observed. Almost 3/4 of the film users work with E- or F-speed film. 45% of them refuse to change to a digital system. The use of lead aprons was popular, while only a minority preferred thyroid shields and rectangular collimators. A fourfold reduction of exposure time from D-speed film to CCD systems was observed. Due to detector size and positioning errors, users of CCD systems take significantly more single-tooth radiographs in total. Considering the number of radiographs per patient, there is only a slight tendency towards more X-rays with CCD systems. Up to image generation, digital systems seem to be as or even more difficult to handle than film-based systems, while their handling was favored after radiographic exposure. Despite a slight increase of radiographs taken with CCD systems, there is a significant dosage reduction. Corresponding to the decrease in exposure time, the patient dose for SPP systems is reduced to one half compared to film. The main issues in CCD technology are positioning errors and the size of the X-ray detectors which are difficult to eliminate. The usage of radiation protection measures still needs to be improved. ► Responsible use of digital intraoral radiology results in a significant dose reduction in everyday practice. ► The ALARA principle is only achieved by strict implementation of dose-reducing methods. ► The efforts to use dose-reducing devices must be increased. © Georg Thieme Verlag KG Stuttgart · New York.

Dynamically accumulated dose and 4D accumulated dose for moving tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Heng; Li Yupeng; Zhang Xiaodong

2012-12-15

Purpose: The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion. Methods: The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove themore » principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a 'pulsed beam'; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a 'continuous beam.' A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam. Results: The numerical simulations confirmed that the number of deliveries for each phase converges to K/N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and/or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation. Conclusions: Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose difference between the dynamic dose and 4D dose as a function of number of deliveries and/or total deliver time was also established.« less

SU-F-T-403: Impact of Dose Reduction for Simulation CT On Radiation Therapy Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, Q; Shah, P; Li, S

Purpose: To investigate the feasibility of applying ALARA principles to current treatment planning CT scans. The study aims to quantitatively verify lower dose scans does not alter treatment planning. Method: Gammex 467 tissue characterization phantom with inserts of 14 different materials was scanned at seven different mA levels (30∼300 mA). CT numbers of different inserts were measured. Auto contouring for bone and lung in treatment planning system (Pinnacle) was used to evaluate the effect of CT number accuracy from treatment planning aspect, on the 30 and 300 mA-scanned images. A head CT scan intended for a 3D whole brain radiationmore » treatment was evaluated. Dose calculations were performed on normal scanned images using clinical protocol (120 kVP, Smart mA, maximum 291 mA), and the images with added simulating noise mimicking a 70 mA scan. Plan parameters including isocenter, beam arrangements, block shapes, dose grid size and resolution, and prescriptions were kept the same for these two plans. The calculated monitor units (MUs) for these two plans were compared. Results: No significant degradation of CT number accuracy was found at lower dose levels from both the phantom scans, and the patient images with added noise. The CT numbers kept consistent when mA is higher than 60 mA. The auto contoured volumes for lung and cortical bone show 0.3% and 0.12% of differences between 30 mA and 300 mA respectively. The two forward plans created on regular and low dose images gave the same calculated MU, and 98.3% of points having <1% of dose difference. Conclusion: Both phantom and patient studies quantitatively verified low dose CT provides similar quality for treatment planning at 20–25% of regular scan dose. Therefore, there is the potential to optimize simulation CT scan protocol to fulfil the ALARA principle and limit unnecessary radiation exposure to non-targeted tissues.« less

A novel radiation detector for removing scattered radiation in chest radiography: Monte Carlo simulation-based performance evaluation

NASA Astrophysics Data System (ADS)

Roh, Y. H.; Yoon, Y.; Kim, K.; Kim, J.; Kim, J.; Morishita, J.

2016-10-01

Scattered radiation is the main reason for the degradation of image quality and the increased patient exposure dose in diagnostic radiology. In an effort to reduce scattered radiation, a novel structure of an indirect flat panel detector has been proposed. In this study, a performance evaluation of the novel system in terms of image contrast as well as an estimation of the number of photons incident on the detector and the grid exposure factor were conducted using Monte Carlo simulations. The image contrast of the proposed system was superior to that of the no-grid system but slightly inferior to that of the parallel-grid system. The number of photons incident on the detector and the grid exposure factor of the novel system were higher than those of the parallel-grid system but lower than those of the no-grid system. The proposed system exhibited the potential for reduced exposure dose without image quality degradation; additionally, can be further improved by a structural optimization considering the manufacturer's specifications of its lead contents.

European Scientific Notes. Volume 35, Number 2,

DTIC Science & Technology

1981-02-28

The risk is as- however, that he did not move forward sociated with the absorbed radiation dose in a straight line from his earliest to the ... dose in latter hdbefomdoiialtoa target region rk per iici-h in a source study the fallout from atomic bombs. However as medical aspects increased in ...enables supported from the Unix systems. The the users to manipulate

Biplane interventional pediatric system with cone‐beam CT: dose and image quality characterization for the default protocols

PubMed Central

Vañó, Eliseo; Alejo, Luis; Ubeda, Carlos; Gutiérrez‐Larraya, Federico; Garayoa, Julia

2016-01-01

The aim of this study was to assess image quality and radiation dose of a biplane angiographic system with cone‐beam CT (CBCT) capability tuned for pediatric cardiac procedures. The results of this study can be used to explore dose reduction techniques. For pulsed fluoroscopy and cine modes, polymethyl methacrylate phantoms of various thicknesses and a Leeds TOR 18‐FG test object were employed. Various fields of view (FOV) were selected. For CBCT, the study employed head and body dose phantoms, Catphan 504, and an anthropomorphic cardiology phantom. The study also compared two 3D rotational angiography protocols. The entrance surface air kerma per frame increases by a factor of 3–12 when comparing cine and fluoroscopy frames. The biggest difference in the signal‐to‐noise ratio between fluoroscopy and cine modes occurs at FOV 32 cm because fluoroscopy is acquired at a 1440×1440 pixel matrix size and in unbinned mode, whereas cine is acquired at 720×720 pixels and in binned mode. The high‐contrast spatial resolution of cine is better than that of fluoroscopy, except for FOV 32 cm, because fluoroscopy mode with 32 cm FOV is unbinned. Acquiring CBCT series with a 16 cm head phantom using the standard dose protocol results in a threefold dose increase compared with the low‐dose protocol. Although the amount of noise present in the images acquired with the low‐dose protocol is much higher than that obtained with the standard mode, the images present better spatial resolution. A 1 mm diameter rod with 250 Hounsfield units can be distinguished in reconstructed images with an 8 mm slice width. Pediatric‐specific protocols provide lower doses while maintaining sufficient image quality. The system offers a novel 3D imaging mode. The acquisition of CBCT images results in increased doses administered to the patients, but also provides further diagnostic information contained in the volumetric images. The assessed CBCT protocols provide images that are noisy, but with very good spatial resolution. PACS number(s): 87.59.‐e, 87.59.‐C, 87.59.‐cf, 87.59.Dj, 87.57. uq PMID:27455474

Minimizing human error in radiopharmaceutical preparation and administration via a bar code-enhanced nuclear pharmacy management system.

PubMed

Hakala, John L; Hung, Joseph C; Mosman, Elton A

2012-09-01

The objective of this project was to ensure correct radiopharmaceutical administration through the use of a bar code system that links patient and drug profiles with on-site information management systems. This new combined system would minimize the amount of manual human manipulation, which has proven to be a primary source of error. The most common reason for dosing errors is improper patient identification when a dose is obtained from the nuclear pharmacy or when a dose is administered. A standardized electronic transfer of information from radiopharmaceutical preparation to injection will further reduce the risk of misadministration. Value stream maps showing the flow of the patient dose information, as well as potential points of human error, were developed. Next, a future-state map was created that included proposed corrections for the most common critical sites of error. Transitioning the current process to the future state will require solutions that address these sites. To optimize the future-state process, a bar code system that links the on-site radiology management system with the nuclear pharmacy management system was proposed. A bar-coded wristband connects the patient directly to the electronic information systems. The bar code-enhanced process linking the patient dose with the electronic information reduces the number of crucial points for human error and provides a framework to ensure that the prepared dose reaches the correct patient. Although the proposed flowchart is designed for a site with an in-house central nuclear pharmacy, much of the framework could be applied by nuclear medicine facilities using unit doses. An electronic connection between information management systems to allow the tracking of a radiopharmaceutical from preparation to administration can be a useful tool in preventing the mistakes that are an unfortunate reality for any facility.

Impact of a phenytoin loading dose program in the emergency department.

PubMed

Brancaccio, Adam; Giuliano, Christopher; McNorton, Kelly; Delgado, George

2014-11-01

The use of a combined physician-and pharmacist-directed phenytoin loading dose program in an emergency department (ED) was evaluated. This single-center, observational, preimplementation-postimplementation study evaluated adult patients who received a phenytoin loading dose in the ED. The primary outcome compared the proportion of optimal phenytoin loading doses in the preimplementation and postimplementation groups. The postimplementation group was further stratified into pharmacist- and prescriber-dosing groups. Other outcomes evaluated included the numbers of appropriate serum phenytoin concentrations measured, adverse drug reactions (ADRs), and recurrence of seizures within 24 hours of loading dose administration in the preimplementation and postimplementation groups. There was no difference in the proportion of optimal phenytoin loading doses between the preimplementation and postimplementation groups (50% versus 62%, respectively; p=0.19). When stratified by individual groups, the rate of optimal phenytoin loading doses increased by 64% in the postimplementation pharmacist group (50% versus 82%, p=0.007), while the rate in the prescriber-dosing group remained relatively unchanged (50% versus 49%, p=0.91). The number of appropriate serum phenytoin concentrations significantly improved in the postimplementation versus preimplementation group (65% versus 40%, p=0.025). Rates of ADRs and recurrence of seizures did not differ across the study groups. No change in the percentage of optimal phenytoin loading doses in the ED was observed after implementation of a combined pharmacist- and physician- dosing program. When stratified into pharmacist or prescriber dosing, the pharmacist-led dosing program significantly improved the proportion of patients who received optimal phenytoin loading doses. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Patient handling system for carbon ion beam scanning therapy

PubMed Central

Shirai, Toshiyuki; Takei, Yuka; Furukawa, Takuji; Inaniwa, Taku; Matsuzaki, Yuka; Kumagai, Motoki; Murakami, Takeshi; Noda, Koji

2012-01-01

Our institution established a new treatment facility for carbon ion beam scanning therapy in 2010. The major advantages of scanning beam treatment compared to the passive beam treatment are the following: high dose conformation with less excessive dose to the normal tissues, no bolus compensator and patient collimator/ multi‐leaf collimator, better dose efficiency by reducing the number of scatters. The new facility was designed to solve several problems encountered in the existing facility, at which several thousand patients were treated over more than 15 years. Here, we introduce the patient handling system in the new treatment facility. The new facility incorporates three main systems, a scanning irradiation system (S‐IR), treatment planning system (TPS), and patient handling system (PTH). The PTH covers a wide range of functions including imaging, geometrical/position accuracy including motion management (immobilization, robotic arm treatment bed), layout of the treatment room, treatment workflow, software, and others. The first clinical trials without respiratory gating have been successfully started. The PTH allows a reduction in patient stay in the treatment room to as few as 7 min. The PTH plays an important role in carbon ion beam scanning therapy at the new institution, particularly in the management of patient handling, application of image‐guided therapy, and improvement of treatment workflow, and thereby allows substantially better treatment at minimum cost. PACS numbers: 87.56.‐v; 87.57.‐s; 87.55.‐x PMID:23149784

Comprehensive clinical commissioning and validation of the RayStation treatment planning system for proton therapy with active scanning and passive treatment techniques.

PubMed

Bäumer, C; Geismar, D; Koska, B; Kramer, P H; Lambert, J; Lemke, M; Plaude, S; Pschichholz, L; Qamhiyeh, S; Schiemann, A; Timmermann, B; Vermeren, X

2017-11-01

To commission the treatment planning system (TPS) RayStation for proton therapy including beam models for spot scanning and for uniform scanning. Tests consist of procedures from ESTRO booklet number 7, the German DIN for constancy checks of TPSs, and extra tests checking the dose perturbation function. The dose distributions within patients were verified in silico by a comparison of 65 clinical treatment plans with the TPS XiO. Dose-volume parameters, dose differences, and three-dimensional gamma-indices serve as measures of similarity. The monthly constancy checks of Raystation have been automatized with a script. The basic functionality of the software complies with ESTRO booklet number 7. For a few features minor enhancements are suggested. The dose distribution in RayStation agrees with the calculation in XiO. This is supported by a gamma-index (3mm/3%) pass rate of >98.9% (median over 59 plans) for the volume within the 20% isodose line and a difference of <0.3% of V 95 of the PTV (median over 59 plans). If spot scanning is used together with a range shifter, the dose level calculated by RayStation can be off by a few percent. RayStation can be used for the creation of clinical proton treatment plans. Compared to XiO RayStation has an improved modelling of the lateral dose fall-off in passively delivered fields. For spot scanning fields with range shifter blocks an empirical adjustment of monitor units is required. The computation of perturbed doses also allows the evaluation of the robustness of a treatment plan. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

SU-F-J-45: Sparing Normal Tissue with Ultra-High Dose Rate in Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Y

Purpose: To spare normal tissue by reducing the location uncertainty of a moving target, we proposed an ultra-high dose rate system and evaluated. Methods: High energy electrons generated with a linear accelerator were injected into a storage ring to be accumulated. The number of the electrons in the ring was determined based on the prescribed radiation dose. The dose was delivered within a millisecond, when an online imaging system found that the target was in the position that was consistent with that in a treatment plan. In such a short time period, the displacement of the target was negligible. Themore » margin added to the clinical target volume (CTV) could be reduced that was evaluated by comparing of volumes between CTV and ITV in 14 cases of lung stereotactic body radiation therapy (SBRT) treatments. A design of the ultra-high dose rate system was evaluated based clinical needs and the recent developments of low energy (a few MeV) electron storage ring. Results: This design of ultra-high dose rate system was feasible based on the techniques currently available. The reduction of a target volume was significant by reducing the margin that accounted the motion of the target. ∼50% volume reduction of the internal target volume (ITV) could be achieved in lung SBRT treatments. Conclusion: With this innovation of ultra-high dose rate system, the margin of target is able to be significantly reduced. It will reduce treatment time of gating and allow precisely specified gating window to improve the accuracy of dose delivering.« less

Implementation of the systems approach to improve a pharmacist-managed vancomycin dosing service.

PubMed

Gagnon, David J; Roberts, Russel; Sylvia, Lynne

2014-12-01

Quality improvements achieved by applying the systems approach to assess the clinical effectiveness, operational efficiency, and financial feasibility of a pharmacist-managed vancomycin dosing service are described. Faced with increased patient volumes and resource demands, the pharmacy department at Tufts Medical Center conducted an evaluation of its adult inpatient vancomycin dosing service using the systems approach, which emphasizes multidisciplinary assessment of system inputs, processes, and outcomes and consensus-building methods to identify needed changes and recommended action steps. A multidisciplinary committee composed of representatives of the medical center's pharmacy, internal medicine, infectious diseases, nursing, phlebotomy, and clinical laboratory services was assembled; in a series of three moderated monthly sessions, committee members deliberated and ultimately reached consensus on a list of action items. Relative to a concurrent intradepartmental assessment of the vancomycin dosing service based solely on pharmacist feedback, the systems approach identified a greater number and wider array of needed improvements in key program areas. Quality improvements implemented as a direct result of the systems-based analysis included a policy change authorizing pharmacists to order serum vancomycin determinations without physician cosignature and inclusion of a vancomycin dosing algorithm in the institutional antibiotic dosing guide. Future changes based on deliverable action items will result in a structured process to help direct program resources toward the patients most in need of pharmacist-managed vancomycin dosing services. The systems approach allowed for a comprehensive multidisciplinary evaluation of the service, as indicated by the identification of process improvements not identified by the department of pharmacy alone. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

A Web-Based System for Bayesian Benchmark Dose Estimation.

PubMed

Shao, Kan; Shapiro, Andrew J

2018-01-11

Benchmark dose (BMD) modeling is an important step in human health risk assessment and is used as the default approach to identify the point of departure for risk assessment. A probabilistic framework for dose-response assessment has been proposed and advocated by various institutions and organizations; therefore, a reliable tool is needed to provide distributional estimates for BMD and other important quantities in dose-response assessment. We developed an online system for Bayesian BMD (BBMD) estimation and compared results from this software with U.S. Environmental Protection Agency's (EPA's) Benchmark Dose Software (BMDS). The system is built on a Bayesian framework featuring the application of Markov chain Monte Carlo (MCMC) sampling for model parameter estimation and BMD calculation, which makes the BBMD system fundamentally different from the currently prevailing BMD software packages. In addition to estimating the traditional BMDs for dichotomous and continuous data, the developed system is also capable of computing model-averaged BMD estimates. A total of 518 dichotomous and 108 continuous data sets extracted from the U.S. EPA's Integrated Risk Information System (IRIS) database (and similar databases) were used as testing data to compare the estimates from the BBMD and BMDS programs. The results suggest that the BBMD system may outperform the BMDS program in a number of aspects, including fewer failed BMD and BMDL calculations and estimates. The BBMD system is a useful alternative tool for estimating BMD with additional functionalities for BMD analysis based on most recent research. Most importantly, the BBMD has the potential to incorporate prior information to make dose-response modeling more reliable and can provide distributional estimates for important quantities in dose-response assessment, which greatly facilitates the current trend for probabilistic risk assessment. https://doi.org/10.1289/EHP1289.

Ir-192 HDR transit dose and radial dose function determination using alanine/EPR dosimetry

NASA Astrophysics Data System (ADS)

Guzmán Calcina, Carmen S.; de Almeida, Adelaide; Oliveira Rocha, José R.; Abrego, Felipe Chen; Baffa, Oswaldo

2005-03-01

Source positioning close to the tumour in high dose rate (HDR) brachytherapy is not instantaneous. An increment of dose will be delivered during the movement of the source in the trajectory to its static position. This increment is the transit dose, often not taken into account in brachytherapeutic treatment planning. The transit dose depends on the prescribed dose, number of treatment fractions, velocity and activity of the source. Combining all these factors, the transit dose can be 5% higher than the prescribed absorbed dose value (Sang-Hyun and Muller-Runkel, 1994 Phys. Med. Biol. 39 1181 8, Nath et al 1995 Med. Phys. 22 209 34). However, it cannot exceed this percentage (Nath et al 1995). In this work, we use the alanine-EPR (electron paramagnetic resonance) dosimetric system using analysis of the first derivative of the signal. The transit dose was evaluated for an HDR system and is consistent with that already presented for TLD dosimeters (Bastin et al 1993 Int. J. Radiat. Oncol. Biol. Phys. 26 695 702). Also using the same dosimetric system, the radial dose function, used to evaluate the geometric dose degradation around the source, was determined and its behaviour agrees better with those obtained by Monte Carlo simulations (Nath et al 1995, Williamson and Nath 1991 Med. Phys. 18 434 48, Ballester et al 1997 Med. Phys. 24 1221 8, Ballester et al 2001 Phys. Med. Biol. 46 N79 90) than with TLD measurements (Nath et al 1990 Med. Phys. 17 1032 40).

Ir-192 HDR transit dose and radial dose function determination using alanine/EPR dosimetry.

PubMed

Calcina, Carmen S Guzmán; de Almeida, Adelaide; Rocha, José R Oliveira; Abrego, Felipe Chen; Baffa, Oswaldo

2005-03-21

Source positioning close to the tumour in high dose rate (HDR) brachytherapy is not instantaneous. An increment of dose will be delivered during the movement of the source in the trajectory to its static position. This increment is the transit dose, often not taken into account in brachytherapeutic treatment planning. The transit dose depends on the prescribed dose, number of treatment fractions, velocity and activity of the source. Combining all these factors, the transit dose can be 5% higher than the prescribed absorbed dose value (Sang-Hyun and Muller-Runkel, 1994 Phys. Med. Biol. 39 1181-8, Nath et al 1995 Med. Phys. 22 209-34). However, it cannot exceed this percentage (Nath et al 1995). In this work, we use the alanine-EPR (electron paramagnetic resonance) dosimetric system using analysis of the first derivative of the signal. The transit dose was evaluated for an HDR system and is consistent with that already presented for TLD dosimeters (Bastin et al 1993 Int. J. Radiat. Oncol. Biol. Phys. 26 695-702). Also using the same dosimetric system, the radial dose function, used to evaluate the geometric dose degradation around the source, was determined and its behaviour agrees better with those obtained by Monte Carlo simulations (Nath et al 1995, Williamson and Nath 1991 Med. Phys. 18 434-48, Ballester et al 1997 Med. Phys. 24 1221-8, Ballester et al 2001 Phys. Med. Biol. 46 N79-90) than with TLD measurements (Nath et al 1990 Med. Phys. 17 1032-40).

SU-F-J-194: Development of Dose-Based Image Guided Proton Therapy Workflow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pham, R; Sun, B; Zhao, T

Purpose: To implement image-guided proton therapy (IGPT) based on daily proton dose distribution. Methods: Unlike x-ray therapy, simple alignment based on anatomy cannot ensure proper dose coverage in proton therapy. Anatomy changes along the beam path may lead to underdosing the target, or overdosing the organ-at-risk (OAR). With an in-room mobile computed tomography (CT) system, we are developing a dose-based IGPT software tool that allows patient positioning and treatment adaption based on daily dose distributions. During an IGPT treatment, daily CT images are acquired in treatment position. After initial positioning based on rigid image registration, proton dose distribution is calculatedmore » on daily CT images. The target and OARs are automatically delineated via deformable image registration. Dose distributions are evaluated to decide if repositioning or plan adaptation is necessary in order to achieve proper coverage of the target and sparing of OARs. Besides online dose-based image guidance, the software tool can also map daily treatment doses to the treatment planning CT images for offline adaptive treatment. Results: An in-room helical CT system is commissioned for IGPT purposes. It produces accurate CT numbers that allow proton dose calculation. GPU-based deformable image registration algorithms are developed and evaluated for automatic ROI-delineation and dose mapping. The online and offline IGPT functionalities are evaluated with daily CT images of the proton patients. Conclusion: The online and offline IGPT software tool may improve the safety and quality of proton treatment by allowing dose-based IGPT and adaptive proton treatments. Research is partially supported by Mevion Medical Systems.« less

Methodology for the in vitro evaluation of the delivery efficiency from valved holding chambers with facemasks.

PubMed

Xu, Zhen; Hsu, Wenchi; von Hollen, Dirk; Viswanath, Ashwin; Nikander, Kurt; Dalby, Richard

2014-08-01

In vitro performance studies of valved holding chamber (VHC)-facemask systems are a cost-effective means of circumventing potentially confounding clinical variables. This article reports results of an in vitro investigation into VHC-facemask performance, using three age-specific soft anatomical model (SAM) faces, under clinically relevant conditions. A potentially standardized method was developed to assess VHC-facemask seal leakage, and evaluate the in vitro delivery efficiency of conventional and antistatic VHC-facemask systems. A custom-built test rig and VHC cradles were used to position the VHC-facemask systems against the SAM faces, with a constant, reproducible force. A standardized simulated pediatric breathing pattern (tidal volume = 155 mL; inhalation:exhalation ratio = 40:60; 25 breaths/min) was utilized. Percent facemask seal leakage, percent delivered dose, and the effect of different numbers of simulated breaths (2 to 8) were investigated. Of the VHC-facemask systems tested, the OptiChamber Diamond VHC with LiteTouch facemask (Diamond) system had the lowest percent seal leakage with each SAM face. Percent seal leakage from the other VHC-facemask systems was similar with SAM0 and SAM2 faces; the AeroChamber Plus Z-Stat VHC with ComfortSeal facemask (AC Z-Stat) system had a substantially greater percent seal leakage with the SAM1 face. Regardless of the number of simulated breaths, the Diamond system delivered the greatest mean percent delivered dose, with the lowest coefficient of variation, with each SAM face. Percent delivered dose did not correlate well with seal leakage, particularly for VHC-facemask systems with high seal leakage. The electrostatic properties of the VHCs appeared to influence drug delivery. This study describes a potentially standardized method for the evaluation of VHC-facemask systems. Use of this method enabled a comprehensive investigation into the influence of clinically relevant variables, including age-specific facial anatomy, number of simulated breaths, and seal leakage, on the delivery efficiency of several commercially available VHC-facemask systems.

A preliminary study of in-house Monte Carlo simulations: an integrated Monte Carlo verification system.

PubMed

Mukumoto, Nobutaka; Tsujii, Katsutomo; Saito, Susumu; Yasunaga, Masayoshi; Takegawa, Hideki; Yamamoto, Tokihiro; Numasaki, Hodaka; Teshima, Teruki

2009-10-01

To develop an infrastructure for the integrated Monte Carlo verification system (MCVS) to verify the accuracy of conventional dose calculations, which often fail to accurately predict dose distributions, mainly due to inhomogeneities in the patient's anatomy, for example, in lung and bone. The MCVS consists of the graphical user interface (GUI) based on a computational environment for radiotherapy research (CERR) with MATLAB language. The MCVS GUI acts as an interface between the MCVS and a commercial treatment planning system to import the treatment plan, create MC input files, and analyze MC output dose files. The MCVS consists of the EGSnrc MC codes, which include EGSnrc/BEAMnrc to simulate the treatment head and EGSnrc/DOSXYZnrc to calculate the dose distributions in the patient/phantom. In order to improve computation time without approximations, an in-house cluster system was constructed. The phase-space data of a 6-MV photon beam from a Varian Clinac unit was developed and used to establish several benchmarks under homogeneous conditions. The MC results agreed with the ionization chamber measurements to within 1%. The MCVS GUI could import and display the radiotherapy treatment plan created by the MC method and various treatment planning systems, such as RTOG and DICOM-RT formats. Dose distributions could be analyzed by using dose profiles and dose volume histograms and compared on the same platform. With the cluster system, calculation time was improved in line with the increase in the number of central processing units (CPUs) at a computation efficiency of more than 98%. Development of the MCVS was successful for performing MC simulations and analyzing dose distributions.

Practical dose point-based methods to characterize dose distribution in a stationary elliptical body phantom for a cone-beam C-arm CT system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Jang-Hwan, E-mail: jhchoi21@stanford.edu; Constantin, Dragos; Ganguly, Arundhuti

2015-08-15

Purpose: To propose new dose point measurement-based metrics to characterize the dose distributions and the mean dose from a single partial rotation of an automatic exposure control-enabled, C-arm-based, wide cone angle computed tomography system over a stationary, large, body-shaped phantom. Methods: A small 0.6 cm{sup 3} ion chamber (IC) was used to measure the radiation dose in an elliptical body-shaped phantom made of tissue-equivalent material. The IC was placed at 23 well-distributed holes in the central and peripheral regions of the phantom and dose was recorded for six acquisition protocols with different combinations of minimum kVp (109 and 125 kVp)more » and z-collimator aperture (full: 22.2 cm; medium: 14.0 cm; small: 8.4 cm). Monte Carlo (MC) simulations were carried out to generate complete 2D dose distributions in the central plane (z = 0). The MC model was validated at the 23 dose points against IC experimental data. The planar dose distributions were then estimated using subsets of the point dose measurements using two proposed methods: (1) the proximity-based weighting method (method 1) and (2) the dose point surface fitting method (method 2). Twenty-eight different dose point distributions with six different point number cases (4, 5, 6, 7, 14, and 23 dose points) were evaluated to determine the optimal number of dose points and their placement in the phantom. The performances of the methods were determined by comparing their results with those of the validated MC simulations. The performances of the methods in the presence of measurement uncertainties were evaluated. Results: The 5-, 6-, and 7-point cases had differences below 2%, ranging from 1.0% to 1.7% for both methods, which is a performance comparable to that of the methods with a relatively large number of points, i.e., the 14- and 23-point cases. However, with the 4-point case, the performances of the two methods decreased sharply. Among the 4-, 5-, 6-, and 7-point cases, the 7-point case (1.0% [±0.6%] difference) and the 6-point case (0.7% [±0.6%] difference) performed best for method 1 and method 2, respectively. Moreover, method 2 demonstrated high-fidelity surface reconstruction with as few as 5 points, showing pixelwise absolute differences of 3.80 mGy (±0.32 mGy). Although the performance was shown to be sensitive to the phantom displacement from the isocenter, the performance changed by less than 2% for shifts up to 2 cm in the x- and y-axes in the central phantom plane. Conclusions: With as few as five points, method 1 and method 2 were able to compute the mean dose with reasonable accuracy, demonstrating differences of 1.7% (±1.2%) and 1.3% (±1.0%), respectively. A larger number of points do not necessarily guarantee better performance of the methods; optimal choice of point placement is necessary. The performance of the methods is sensitive to the alignment of the center of the body phantom relative to the isocenter. In body applications where dose distributions are important, method 2 is a better choice than method 1, as it reconstructs the dose surface with high fidelity, using as few as five points.« less

A comprehensive study on decreasing the kilovoltage cone-beam CT dose by reducing the projection number.

PubMed

Lu, Bo; Lu, Haibin; Palta, Jatinder

2010-05-12

The objective of this study was to evaluate the effect of kilovoltage cone-beam computed tomography (CBCT) on registration accuracy and image qualities with a reduced number of planar projections used in volumetric imaging reconstruction. The ultimate goal is to evaluate the possibility of reducing the patient dose while maintaining registration accuracy under different projection-number schemes for various clinical sites. An Elekta Synergy Linear accelerator with an onboard CBCT system was used in this study. The quality of the Elekta XVI cone-beam three-dimensional volumetric images reconstructed with a decreasing number of projections was quantitatively evaluated by a Catphan phantom. Subsequently, we tested the registration accuracy of imaging data sets on three rigid anthropomorphic phantoms and three real patient sites under the reduced projection-number (as low as 1/6th) reconstruction of CBCT data with different rectilinear shifts and rota-tions. CBCT scan results of the Catphan phantom indicated the CBCT images got noisier when the number of projections was reduced, but their spatial resolution and uniformity were hardly affected. The maximum registration errors under the small amount transformation of the reference CT images were found to be within 0.7 mm translation and 0.3 masculine rotation. However, when the projection number was lower than one-fourth of the full set with a large amount of transformation of reference CT images, the registration could easily be trapped into local minima solutions for a nonrigid anatomy. We concluded, by using projection-number reduction strategy under conscientious care, imaging-guided localization procedure could achieve a lower patient dose without losing the registration accuracy for various clinical sites and situations. A faster scanning time is the main advantage compared to the mA decrease-based, dose-reduction method.

The effects of repetitious topical use of mitomycin C on antrostomy patency in maxillary antrostomy created rabbit model.

PubMed

Kavuzlu, Ali; Arslan, Necmi; Tastan, Eren; Islam, Ahmet; Ustun, Huseyin; Aydogan, Filiz

2011-11-01

The aim of our study was to investigate the effect of the topical use of mitomycin C (MMC) intraoperatively in single dose and intra-postoperatively in two doses on the narrowing of antrostomy in maxillary rabbit sinus antrostomies created experimentally. And also to determine the local and systemic side effects of topical MMC. With this objective, 0.6 mg/ml MMC was used to the first group at single dose and to the second group intraoperatively and on third day postoperatively in two doses topically for 5 min. After 8 weeks, although the mean area of antrostomy was larger than that in the control side in the first group, which received single dose MMC, the difference was not statistically significant (p = 0.287). The second group received two doses, and the antrostomy areas were found to be significantly larger than the controls (p = 0.05). Overall, the sides that received MMC were significantly larger (p = 0.029). From the point of histopathological examination of the tissue, it was seen that two-dose MMC increased the edema indicating inflammation and antrostomy resolved with normal respiratory tract epithelium. It was shown by measuring the blood values that nephrotoxic and myelosupressant effect of MMC occurring in systemic use did not occur with single or double dose topical use. Our results demonstrate that even if the number of cases was low, two doses of topical MMC usage prevent the narrowing of antrostomy while single dose MMC does not. And two-dose topical MMC usage does not have local and systemic side effects.

Radiation dose equivalent to stowaways in vehicles.

PubMed

Khan, Siraj M; Nicholas, Paul E; Terpilak, Michael S

2004-05-01

The U.S. Bureau of Customs and Border Protection has deployed a large number of non-intrusive inspection (NII) systems at land border crossings and seaports throughout the United States to inspect cars, trucks, and sea containers. These NII systems use x rays and gamma rays for the detection of contraband. Unfortunately, undocumented aliens infrequently stow away in these same conveyances to illegally enter the United States. It is extremely important that the radiation dose equivalent imparted to these stowaways be within acceptable limits. This paper discusses the issues involved and describes a protocol the U.S. Bureau of Customs and Border Protection has used in a study to measure and document these levels. The results of this study show that the radiation dose equivalent to the stowaways from the deployed NII systems is negligibly small and does not pose a health hazard.

Feasibility and robustness of dose painting by numbers in proton therapy with contour-driven plan optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barragán, A. M., E-mail: ana.barragan@uclouvain.be; Differding, S.; Lee, J. A.

Purpose: To prove the ability of protons to reproduce a dose gradient that matches a dose painting by numbers (DPBN) prescription in the presence of setup and range errors, by using contours and structure-based optimization in a commercial treatment planning system. Methods: For two patients with head and neck cancer, voxel-by-voxel prescription to the target volume (GTV{sub PET}) was calculated from {sup 18}FDG-PET images and approximated with several discrete prescription subcontours. Treatments were planned with proton pencil beam scanning. In order to determine the optimal plan parameters to approach the DPBN prescription, the effects of the scanning pattern, number ofmore » fields, number of subcontours, and use of range shifter were separately tested on each patient. Different constant scanning grids (i.e., spot spacing = Δx = Δy = 3.5, 4, and 5 mm) and uniform energy layer separation [4 and 5 mm WED (water equivalent distance)] were analyzed versus a dynamic and automatic selection of the spots grid. The number of subcontours was increased from 3 to 11 while the number of beams was set to 3, 5, or 7. Conventional PTV-based and robust clinical target volumes (CTV)-based optimization strategies were considered and their robustness against range and setup errors assessed. Because of the nonuniform prescription, ensuring robustness for coverage of GTV{sub PET} inevitably leads to overdosing, which was compared for both optimization schemes. Results: The optimal number of subcontours ranged from 5 to 7 for both patients. All considered scanning grids achieved accurate dose painting (1% average difference between the prescribed and planned doses). PTV-based plans led to nonrobust target coverage while robust-optimized plans improved it considerably (differences between worst-case CTV dose and the clinical constraint was up to 3 Gy for PTV-based plans and did not exceed 1 Gy for robust CTV-based plans). Also, only 15% of the points in the GTV{sub PET} (worst case) were above 5% of DPBN prescription for robust-optimized plans, while they were more than 50% for PTV plans. Low dose to organs at risk (OARs) could be achieved for both PTV and robust-optimized plans. Conclusions: DPBN in proton therapy is feasible with the use of a sufficient number subcontours, automatically generated scanning patterns, and no more than three beams are needed. Robust optimization ensured the required target coverage and minimal overdosing, while PTV-approach led to nonrobust plans with excessive overdose. Low dose to OARs can be achieved even in the presence of a high-dose escalation as in DPBN.« less

Use of convolution/superposition-based treatment planning system for dose calculations in the kilovoltage energy range

NASA Astrophysics Data System (ADS)

Alaei, Parham

2000-11-01

A number of procedures in diagnostic radiology and cardiology make use of long exposures to x rays from fluoroscopy units. Adverse effects of these long exposure times on the patients' skin have been documented in recent years. These include epilation, erythema, and, in severe cases, moist desquamation and tissue necrosis. Potential biological effects from these exposures to other organs include radiation-induced cataracts and pneumonitis. Although there have been numerous studies to measure or calculate the dose to skin from these procedures, there have only been a handful of studies to determine the dose to other organs. Therefore, there is a need for accurate methods to measure the dose in tissues and organs other than the skin. This research was concentrated in devising a method to determine accurately the radiation dose to these tissues and organs. The work was performed in several stages: First, a three dimensional (3D) treatment planning system used in radiation oncology was modified and complemented to make it usable with the low energies of x rays used in diagnostic radiology. Using the system for low energies required generation of energy deposition kernels using Monte Carlo methods. These kernels were generated using the EGS4 Monte Carlo system of codes and added to the treatment planning system. Following modification, the treatment planning system was evaluated for its accuracy of calculations in low energies within homogeneous and heterogeneous media. A study of the effects of lungs and bones on the dose distribution was also performed. The next step was the calculation of dose distributions in humanoid phantoms using this modified system. The system was used to calculate organ doses in these phantoms and the results were compared to those obtained from other methods. These dose distributions can subsequently be used to create dose-volume histograms (DVHs) for internal organs irradiated by these beams. Using this data and the concept of normal tissue complication probability (NTCP) developed for radiation oncology, the risk of future complications in a particular organ can be estimated.

Ophthalmologist-patient communication, self-efficacy, and glaucoma medication adherence

PubMed Central

Sleath, Betsy; Blalock, Susan J.; Carpenter, Delesha M.; Sayner, Robyn; Muir, Kelly W.; Slota, Catherine; Lawrence, Scott D.; Giangiacomo, Annette L.; Hartnett, Mary Elizabeth; Tudor, Gail; Goldsmith, Jason A.; Robin, Alan L.

2015-01-01

Objective The objective of the study was to examine the association between provider-patient communication, glaucoma medication adherence self-efficacy, outcome expectations, and glaucoma medication adherence. Design Prospective observational cohort study. Participants 279 patients with glaucoma who were newly prescribed or on glaucoma medications were recruited at six ophthalmology clinics. Methods Patients’ visits were video-tape recorded and communication variables were coded using a detailed coding tool developed by the authors. Adherence was measured using Medication Event Monitoring Systems for 60 days after their visits. Main outcome measures The following adherence variables were measured for the 60 day period after their visits: whether the patient took 80% or more of the prescribed doses, percent correct number of prescribed doses taken each day, and percent prescribed doses taken on time. Results Higher glaucoma medication adherence self-efficacy was positively associated with better adherence with all three measures. African American race was negatively associated with percent correct number of doses taken each day (beta= −0.16, p<0.05) and whether the patient took 80% or more of the prescribed doses (odds ratio=0.37, 95% confidence interval 0.16, 0.86). Physician education about how to administer drops was positively associated with percent correct number of doses taken each day (beta= 0.18, p<0.01) and percent prescribed doses taken on time (beta=0.15, p<0.05). Conclusions These findings indicate that provider education about how to administer glaucoma drops and patient glaucoma medication adherence self-efficacy are positively associated with adherence. PMID:25542521

Systemic fluoroquinolone prescriptions for hospitalized children in Belgium, results of a multicenter retrospective drug utilization study.

PubMed

Meesters, Kevin; Mauel, Reiner; Dhont, Evelyn; Walle, Johan Vande; De Bruyne, Pauline

2018-02-23

Fluoroquinolones (FQ) are increasingly prescribed for children, despite being labeled for only a limited number of labeled pediatric indications. In this multicenter retrospective drug utilization study, we analyzed indications for systemic FQ prescriptions in hospitalized children and the appropriateness of the prescribed dose. Using data obtained from electronic medical files, the study included all children who received a systemic FQ prescription in two Belgian university children's hospitals between 2010 and 2013. Two authors reviewed prescribed daily doses. Univariate and multivariate logistic regression models were used to analyze risk factors for inadequately dosing. Results262 FQ prescriptions for individual patients were included for analysis. 16.8% of these prescriptions were for labeled indications, and 35.1% were guided by bacteriological findings. Prescribed daily dose was considered to be inappropriate in 79 prescriptions (30.2%). Other FQ than ciprofloxacin accounted for 9 prescriptions (3.4%), of which 8 were correctly dosed. Underdosing represented 45 (56.9%) dosing errors. Infants and preschool children were at particular risk for dosing errors, with associated adjusted OR of 0.263 (0.097-0.701) and 0.254 (0.106-0.588) respectively. FQ were often prescribed off-label and not guided by bacteriological findings in our study population. Dosing errors were common, particularly in infants and preschool children. FQ prescriptions for children should be improved by specific pediatric antimicrobial stewardship teams. Furthermore, pharmacokinetic studies should optimise dosing recommendations for children.

SU-D-204-06: Dose and Image Quality Evaluation of a Low-Dose Slot-Scanning X-Ray System for Pediatric Orthopedic Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Z; Hoerner, M; Lamoureux, R

Purpose: Children in early teens with scoliosis require repeated radiographic exams over a number of years. The EOS (EOS imaging S.A., Paris, France) is a novel low-dose slot-scanning digital radiographic system designed to produce full-spine images of a free-standing patient. The radiation dose and image quality characteristics of the EOS were evaluated relative to those of a Computed Radiography (CR) system for scoliosis imaging. Methods: For dose evaluation, a full-torso anthropomorphic phantom was scanned five times using the default standard clinical protocols for both the EOS and a CR system, which include both posteroanterior and lateral full-spine views. Optically stimulatedmore » luminescent dosimeters (OSLDs), also known as nanoDots™ (Landauer, Inc., Glenwood, IL), were placed on the phantom’s surface to measure entrance skin dose. To assess image quality, MTF curves were generated from sampling the noise levels within the high-contrast regions of a line-pair phantom. Vertical and horizontal distortions were measured for the square line-pair phantom with the EOS system to evaluate the effects of geometric magnification and misalignment with the indicated imaging plane. Results: The entrance skin dose was measured to be 0.4 to 1.1 mGy for the EOS, and 0.7 to 3.6 mGy for the CR study. MTF comparison shows that CR greatly outperforms the EOS, despite both systems having a limiting resolution at 1.8 line-pairs per mm. Vertical distortion was unaffected by phantom positioning, because of the EOS slot-scanning geometry. Horizontal distortion increased linearly with miscentering distance. Conclusion: The EOS system resulted in approximately 70% lower radiation dose than CR for full-spine images. Image quality was found to be inferior to CR. Further investigation is required to see if EOS system is an acceptable modality for performing clinically diagnostic scoliosis examinations.« less

Systemic immune cell response in rats after pulmonary exposure to manganese-containing particles collected from welding aerosols.

PubMed

Antonini, James M; Zeidler-Erdely, Patti C; Young, Shih-Houng; Roberts, Jenny R; Erdely, Aaron

2012-01-01

Welding fume inhalation affects the immune system of exposed workers. Manganese (Mn) in welding fume may induce immunosuppressive effects. The goal was to determine if Mn in welding fume alters immunity by reducing the number of circulating total leukocytes and specific leukocyte sub-populations. Sprague-Dawley rats were treated by intratracheal instillation (ITI) with either a single dose (2.00 mg/rat) or repeated doses (0.125 or 2.00 mg/rat for 7 weeks) with welding fumes that contained different levels of Mn. Additional rats were treated by ITI once a week for 7 weeks with the two doses of manganese chloride (MnCl₂). Bronchoalveolar lavage was performed to assess lung inflammation. Also, whole blood was recovered, and the number of circulating total leukocytes, as well as specific lymphocyte subsets, was determined by flow cytometry. The welding fume highest in Mn content significantly increased lung inflammation, injury, and production of inflammatory cytokines and chemokines compared to all other treatment groups. In addition, the same group expressed significant decreases in the number of circulating CD4⁺ and CD8⁺ T-lymphocytes after a single exposure, and significant reductions in the number of circulating total lymphocytes, primarily CD4⁺ and CD8⁺ T-lymphocytes, after repeated exposures (compared to control values). Repeated MnCl₂ exposure led to a trend of a reduction (but not statistically significant) in circulating total lymphocytes, attributable to the changes in the CD4⁺ T-lymphocyte population levels. The welding fume with the lower concentration of Mn had no significant effect on the numbers of blood lymphocytes and lymphocyte subsets compared to control values. Evidence from this study indicates that pulmonary exposure to certain welding fumes cause decrements in systemic immune cell populations, specifically circulating T-lymphocytes, and these alterations in immune cell number are not dependent exclusively on Mn, but likely a combination of other metals present in welding fume.

Performance optimization of the Varian aS500 EPID system.

PubMed

Berger, Lucie; François, Pascal; Gaboriaud, Geneviève; Rosenwald, Jean-Claude

2006-01-01

Today, electronic portal imaging devices (EPIDs) are widely used as a replacement to portal films for patient position verification, but the image quality is not always optimal. The general aim of this study was to optimize the acquisition parameters of an amorphous silicon EPID commercially available for clinical use in radiation therapy with the view to avoid saturation of the system. Special attention was paid to selection of the parameter corresponding to the number of rows acquired between accelerator pulses (NRP) for various beam energies and dose rates. The image acquisition system (IAS2) has been studied, and portal image acquisition was found to be strongly dependent on the accelerator pulse frequency. This frequency is set for each "energy - dose rate" combination of the linear accelerator. For all combinations, the image acquisition parameters were systematically changed to determine their influence on the performances of the Varian aS500 EPID system. New parameters such as the maximum number of rows (MNR) and the number of pulses per frame (NPF) were introduced to explain portal image acquisition theory. Theoretical and experimental values of MNR and NPF were compared, and they were in good agreement. Other results showed that NRP had a major influence on detector saturation and dose per image. A rule of thumb was established to determine the optimum NRP value to be used. This practical application was illustrated by a clinical example in which the saturation of the aSi EPID was avoided by NRP optimization. Moreover, an additional study showed that image quality was relatively insensitive to this parameter.

Tier-2 studies on monocrotaline immunotoxicity in C57BL/6 mice.

PubMed

Deyo, J A; Kerkvliet, N I

1991-01-01

Monocrotaline (MCT) is a member of a class of naturally occurring phytotoxins known as pyrrolizidine alkaloids, and is a toxicological concern to both man and his livestock. The purpose of these studies was to evaluate the effect of a 14-day oral MCT (0-100 mg/kg per day) exposure on the functional integrity of various immunocyte effector systems in C57BL/6 mice, as well as to investigate potential mechanisms for its immunotoxicity. Decreases in lymphoid organ weights and cellularity, and resident peritoneal exudate cell (PEC) number were only observed after exposure to the highest dose of 100 mg/kg MCT. This dose also inhibited NK cell cytotoxicity, while the total number of NK lytic units per spleen was decreased (-53%) after exposure to 50 mg/kg MCT. Following i.p. injection of SRBC, the percentage of PEC macrophages containing engulfed SRBC was significantly increased in MCT-exposed mice, while the percentage of large vacuolated (activated) macrophages was decreased in a dose-dependent manner. Exposure to MCT significantly decreased the total number of Ig+ cells without altering the number of CD4+ and CD8+ cells. The antibody responses (PFC/10(6) spleen cells) to two T cell-independent antigens, TNP-LPS and DNP-Ficoll, were significantly decreased at all MCT doses, and the degree of suppression of both responses was identical at coincident doses. MCT exposure (25 mg/kg) significantly suppressed the blastogenic response to the T cell mitogen concanavalin A (-38%), and to the B cell mitogen lipopolysaccharide (-58%). These results indicate that exposure to MCT can alter the functional integrity of various immune effector responses in a dose-dependent manner, and suggest that the B cell may be a relatively more sensitive target of MCT immunotoxicity compared to T cells, macrophages and NK cells.

Experimental and Monte Carlo evaluation of Eclipse treatment planning system for effects on dose distribution of the hip prostheses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Çatlı, Serap, E-mail: serapcatli@hotmail.com; Tanır, Güneş

2013-10-01

The present study aimed to investigate the effects of titanium, titanium alloy, and stainless steel hip prostheses on dose distribution based on the Monte Carlo simulation method, as well as the accuracy of the Eclipse treatment planning system (TPS) at 6 and 18 MV photon energies. In the present study the pencil beam convolution (PBC) method implemented in the Eclipse TPS was compared to the Monte Carlo method and ionization chamber measurements. The present findings show that if high-Z material is used in prosthesis, large dose changes can occur due to scattering. The variance in dose observed in the presentmore » study was dependent on material type, density, and atomic number, as well as photon energy; as photon energy increased back scattering decreased. The dose perturbation effect of hip prostheses was significant and could not be predicted accurately by the PBC method for hip prostheses. The findings show that for accurate dose calculation the Monte Carlo-based TPS should be used in patients with hip prostheses.« less

Maximizing Tumor Immunity With Fractionated Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schaue, Doerthe, E-mail: dschaue@mednet.ucla.edu; Ratikan, Josephine A.; Iwamoto, Keisuke S.

Purpose: Technologic advances have led to increased clinical use of higher-sized fractions of radiation dose and higher total doses. How these modify the pathways involved in tumor cell death, normal tissue response, and signaling to the immune system has been inadequately explored. Here we ask how radiation dose and fraction size affect antitumor immunity, the suppression thereof, and how this might relate to tumor control. Methods and Materials: Mice bearing B16-OVA murine melanoma were treated with up to 15 Gy radiation given in various-size fractions, and tumor growth followed. The tumor-specific immune response in the spleen was assessed by interferon-{gamma}more » enzyme-linked immunospot (ELISPOT) assay with ovalbumin (OVA) as the surrogate tumor antigen and the contribution of regulatory T cells (Tregs) determined by the proportion of CD4{sup +}CD25{sup hi}Foxp3{sup +} T cells. Results: After single doses, tumor control increased with the size of radiation dose, as did the number of tumor-reactive T cells. This was offset at the highest dose by an increase in Treg representation. Fractionated treatment with medium-size radiation doses of 7.5 Gy/fraction gave the best tumor control and tumor immunity while maintaining low Treg numbers. Conclusions: Radiation can be an immune adjuvant, but the response varies with the size of dose per fraction. The ultimate challenge is to optimally integrate cancer immunotherapy into radiation therapy.« less

Technical Note: Out‐of‐field dose measurement at near surface with plastic scintillator detector

PubMed Central

Bourgouin, Alexandra; Varfalvy, Nicolas

2016-01-01

Out‐of‐field dose depends on multiple factors, making peripheral dosimetry complex. Only a few dosimeters have the required features for measuring peripheral dose. Plastic scintillator dosimeters (PSDs) offer numerous dosimetric advantages as required for out‐of‐field dosimetry. The purpose of this study is to determine the potential of using PSD as a surface peripheral dosimeter. Measurements were performed with a parallel‐plate ion chamber, a small volume ion chamber, and with a PSD. Lateral‐dose measurements (LDM) at 0.5 cm depth and depth‐dose curve (PDD) were made and compared to the dose calculation provided by a treatment planning system (TPS). This study shows that a PSD can measure a dose as low as 0.51±0.17cGy for photon beam and 0.58±0.20cGy for electron beam with a difference of 0.2 and 0.1 cGy compared to a parallel‐plate ion chamber. This study demonstrates the potential of using PSD as an out‐of‐field dosimeter since measurements with PSD avoid averaging over a too‐large depth, at 1 mm diameter, and can make precise measurement at very low dose. Also, electronic equilibrium is easier to reach with PSD due to its small sensitive volume and its water equivalence. PACS number(s): 87.55.N, 87.55.km PMID:27685131

Systematic evaluation of four-dimensional hybrid depth scanning for carbon-ion lung therapy.

PubMed

Mori, Shinichiro; Furukawa, Takuji; Inaniwa, Taku; Zenklusen, Silvan; Nakao, Minoru; Shirai, Toshiyuki; Noda, Koji

2013-03-01

Irradiation of a moving target with a scanning beam requires a comprehensive understanding of organ motion as well as a robust dose error mitigation technique. The authors studied the effects of intrafractional respiratory motion for carbon-ion pencil beam scanning with phase-controlled rescanning on dose distributions for lung tumors. To address density variations, they used 4DCT data. Dose distributions for various rescanning methods, such as simple layer rescanning (LR), volumetric rescanning, and phase-controlled rescanning (PCR), were calculated for a lung phantom and a lung patient studies. To ensure realism, they set the scanning parameters such as scanning velocity and energy variation time to be similar to those used at our institution. Evaluation metrics were determined with regard to clinical relevance, and consisted of (i) phase-controlled rescanning, (ii) sweep direction, (iii) target motion (direction and amplitude), (iv) respiratory cycle, and (v) prescribed dose. Spot weight maps were calculated by using a beam field-specific target volume, which takes account of range variations for respective respiratory phases. To emphasize the impact of intrafractional motion on the dose distribution, respiratory gating was not used. The accumulated dose was calculated by applying a B-spline-based deformable image registration, and the results for phase-controlled layered rescanning (PCRL) and phase-controlled volumetric rescanning (PCRV) were compared. For the phantom study, simple LR was unable to improve the dose distributions for an increased number of rescannings. The phase-controlled technique without rescanning (1×PCRL and 1×PCRV) degraded dose conformity significantly due to a reduced scan velocity. In contrast, 4×PCRL or more significantly and consistently improved dose distribution. PCRV showed interference effects, but in general also improved dose homogeneity with higher numbers of rescannings. Dose distributions with single PCRL∕PCRV with a sweep direction perpendicular to motion direction showed large hot∕cold spots; however, this effect vanished with higher numbers of rescannings for both methods. Similar observations were obtained for the other dose metrics, such as target motion (SI∕AP), amplitude (6-22 mm peak-to-peak) and respiratory period (3.0-5.0 s). For four or more rescannings, both methods showed significantly better results, albeit that volumetric PCR was more affected by interference effects, which lead to severe degradation of a few dose distributions. The clinical example showed the same tendencies as the phantom study. Dose assessment metrics (D95, Dmax∕Dmin, homogeneity index) were improved with an increasing number of PCRL∕PCRV, but with PCRL being more robust. PCRL requires a longer treatment time than PCRV for high numbers of rescannings in the NIRS scanning system but is more robust. Although four or more rescans provided good dose homogeneity and conformity, the authors prefer to use more rescannings for clinical cases to further minimize dose degradation effects due to organ motion.

Patient dosimetry audit for establishing local diagnostic reference levels for nuclear medicine CT.

PubMed

Gardner, Matthew; Katsidzira, Ngonidzashe M; Ross, Erin; Larkin, Elizabeth A

2017-03-01

To establish a system for patient dosimetry audit and setting of local diagnostic reference levels (LDRLs) for nuclear medicine (NM) CT. Computed radiological information system (CRIS) data were matched with NM paper records, which provided the body region and dose mode for NMCT carried out at a large UK hospital. It was necessary to divide data in terms of the NM examination type, body region and dose mode. The mean and standard deviation dose-length products (DLPs) for common NMCT examinations were then calculated and compared with the proposed National Diagnostic Reference Levels (NDRLs). Only procedures which have 10 or more patients will be used to suggest LDRLs. For most examinations, the mean DLPs do not exceed the proposed NDRLs. The bone single-photon emission CT/CT lumbar spine data clearly show the need to divide data according to the purpose of the scan (dose mode), with mean (±standard error) DLPs ranging from 51 ± 5 mGy cm (low dose) to 1086 ± 124 mGy cm (metal dose). A system for NMCT patient dose audit has been developed, but there are non-trivial challenges which make the process labour intensive. These include limited information provided by CRIS downloads, dependence on paper records and limited number of examinations available owing to the need to subdivide data. Advances in knowledge: This article demonstrates that a system can be developed for NMCT patient dose audit, but also highlights the challenges associated with such audit, which may not be encountered with more routine audit of radiology CT.

Reduction of radiation dose during facet joint injection using the new image guidance system SabreSource™: a prospective study in 60 patients

PubMed Central

Proschek, Dirk; Kafchitsas, K.; Rauschmann, M. A.; Kurth, A. A.; Vogl, T. J.

2008-01-01

Interventional procedures are associated with high radiation doses for both patients and surgeons. To reduce the risk from ionizing radiation, it is essential to minimize radiation dose. This prospective study was performed to evaluate the effectiveness in reducing radiation dose during facet joint injection in the lumbar spine and to evaluate the feasibility and possibilities of the new real time image guidance system SabreSource™. A total of 60 patients, treated with a standardized injection therapy of the facet joints L4–L5 or L5–S1, were included in this study. A total of 30 patients were treated by fluoroscopy guidance alone, the following 30 patients were treated using the new SabreSource™ system. Thus a total of 120 injections to the facet joints were performed. Pain, according to the visual analogue scale (VAS), was documented before and 6 h after the intervention. Radiation dose, time of radiation and the number of exposures needed to place the needle were recorded. No significant differences concerning age (mean age 60.5 years, range 51–69), body mass index (mean BMI 26.2, range 22.2–29.9) and preoperative pain (VAS 7.9, range 6–10) were found between the two groups. There was no difference in pain reduction between the two groups (60 vs. 61.5%; P = 0.001) but the radiation dose was significantly smaller with the new SabreSource™ system (reduction of radiation dose 32.7%, P = 0.01; reduction of mean entrance surface dose 32.3%, P = 0.01). The SabreSource™ System significantly reduced the radiation dose received during the injection therapy of the lumbar facet joints. With minimal effort for the setup at the beginning of a session, the system is easy to handle and can be helpful for other injection therapies (e.g. nerve root block therapies). PMID:19082641

Non-induction of radioadaptive response in zebrafish embryos by neutrons

PubMed Central

Ng, Candy Y.P.; Kong, Eva Y.; Kobayashi, Alisa; Suya, Noriyoshi; Uchihori, Yukio; Cheng, Shuk Han; Konishi, Teruaki; Yu, Kwan Ngok

2016-01-01

In vivo neutron-induced radioadaptive response (RAR) was studied using zebrafish (Danio rerio) embryos. The Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility at the National Institute of Radiological Sciences (NIRS), Japan, was employed to provide 2-MeV neutrons. Neutron doses of 0.6, 1, 25, 50 and 100 mGy were chosen as priming doses. An X-ray dose of 2 Gy was chosen as the challenging dose. Zebrafish embryos were dechorionated at 4 h post fertilization (hpf), irradiated with a chosen neutron dose at 5 hpf and the X-ray dose at 10 hpf. The responses of embryos were assessed at 25 hpf through the number of apoptotic signals. None of the neutron doses studied could induce RAR. Non-induction of RAR in embryos having received 0.6- and 1-mGy neutron doses was attributed to neutron-induced hormesis, which maintained the number of damaged cells at below the threshold for RAR induction. On the other hand, non-induction of RAR in embryos having received 25-, 50- and 100-mGy neutron doses was explained by gamma-ray hormesis, which mitigated neutron-induced damages through triggering high-fidelity DNA repair and removal of aberrant cells through apoptosis. Separate experimental results were obtained to verify that high-energy photons could disable RAR. Specifically, 5- or 10-mGy X-rays disabled the RAR induced by a priming dose of 0.88 mGy of alpha particles delivered to 5-hpf zebrafish embryos against a challenging dose of 2 Gy of X-rays delivered to the embryos at 10 hpf. PMID:26850927

AREA MONITORING OF AMBIENT DOSE RATES IN PARTS OF SOUTH-WESTERN NIGERIA USING A GPS-INTEGRATED RADIATION SURVEY METER.

PubMed

Okeyode, I C; Rabiu, J A; Alatise, O O; Makinde, V; Akinboro, F G; Al-Azmi, D; Mustapha, A O

2017-04-01

A radiation monitoring system comprising a Geiger-Muller counter connected to a smart phone via Bluetooth was used for a dose rate survey in some parts of south-western Nigeria. The smart phone has the Geographical Positioning System, which provides the navigation information and saves it along with the dose rate data. A large number of data points was obtained that shows the dose rate distribution within the region. The results show that the ambient dose rates in the region range from 60 to 520 nSv -1 and showed a bias that is attributable to the influence of geology on the ambient radiation dose in the region. The geology influence was demonstrated by superimposing the dose rate plot and the geological map of the area. The potential applications of the device in determining baseline information and in area monitoring, e.g. for lost or abandoned sources, radioactive materials stockpiles, etc., were discussed in the article, particularly against the background of Nigeria's plan to develop its nuclear power program. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Risk-based approach to developing a national residue sampling plan for testing under European Union regulation for veterinary medicinal products and coccidiostat feed additives in domestic animal production.

PubMed

Danaher, Martin; Shanahan, Conor; Butler, Francis; Evans, Rhodri; O'Sullivan, Dan; Glynn, Denise; Camon, Tim; Lawlor, Peadar; O'Keeffe, Michael

2016-07-01

A ranking system for veterinary medicinal products and coccidiostat feed additives has been developed as a tool to be applied in a risk-based approach to the residue testing programme for foods of animal origin in the Irish National Residue Control Plan (NRCP). Three characteristics of substances that may occur as residues in food are included in the developed risk ranking system: Potency, as measured by the acceptable daily intake assigned by the European Medicines Agency Committee for Medicinal Products for Veterinary Use, to each substance; Usage, as measured by the three factors of Number of Doses, use on Individual animals or for Group treatment, and Withdrawal Period; and Residue Occurrence, as measured by the number of Non-Compliant Samples in the NRCP. For both Number of Doses and Non-Compliant Samples, data for the 5-year period 2008-12 have been used. The risk ranking system for substances was developed for beef cattle, sheep and goats, pigs, chickens and dairy cattle using a scoring system applied to the various parameters described above to give an overall score based on the following equation: Potency × Usage (Number of Doses + Individual/Group Use + Withdrawal Period) × Residue Occurrence. Applying this risk ranking system, the following substances are ranked very highly: antimicrobials such as amoxicillin (for all species except pigs), marbofloxacillin (for beef cattle), oxytetracycline (for all species except chickens), sulfadiazine with trimethoprim (for pigs and chickens) and tilmicosin (for chickens); antiparasitic drugs, such as the benzimidazoles triclabendazole (for beef and dairy cattle), fenbendazole/oxfendazole (for sheep/goats and dairy cattle) and albendazole (for dairy cattle), the avermectin ivermectin (for beef cattle), and anti-fluke drugs closantel and rafoxanide (for sheep/goats); the anticoccidials monensin, narasin, nicarbazin and toltrazuril (for chickens). The risk ranking system described is a relatively simple system designed to provide a reliable basis for selecting the veterinary medicinal products and coccidiostat feed additives that might be prioritised for residue testing.

Technical Note: Construction of heterogeneous head phantom for quality control in stereotactic radiosurgery.

PubMed

Najafi, Mohsen; Teimouri, Javad; Shirazi, Alireza; Geraily, Ghazale; Esfahani, Mahbod; Shafaei, Mostafa

2017-10-01

Stereotactic radiosurgery is a high precision modality for conformally delivering high doses of radiation to the brain lesion with a large dose volume. Several studies for the quality control of this technique were performed to measure the dose delivered to the target with a homogenous head phantom and some dosimeters. Some studies were also performed with one or two instances of heterogeneity in the head phantom to measure the dose delivered to the target. But these studies assumed the head as a sphere and simple shape heterogeneity. The construction of an adult human head phantom with the same size, shape, and real inhomogeneity as an adult human head is needed. Only then is measuring the accurate dose delivered to the area of interest and comparison with the calculated dose possible. According to the ICRU Report 44, polytetrafluoroethylene (PTFE) and methyl methacrylate were selected as a bone and soft tissue, respectively. A set of computed tomography (CT) scans from a standard human head were taken, and simplification of the CT images was used to design the layers of the phantom. The parts of each slice were cut and attached together. Tests of density and CT number were done to compare the material of the phantom with tissues of the head. The dose delivered to the target was measured with an EBT3 film. The density of the PTFE and Plexiglas that were inserted in the phantom are in good agreement with bone and soft tissue. Also, the CT numbers of these materials have a low difference. The dose distribution from the EBT3 film and the treatment planning system is similar. The constructed phantom with a size and inhomogeneity like an adult human head is suitable to measure the dose delivered to the area of interest. It also helps make an accurate comparison with the calculated dose by the treatment planning system. By using this phantom, the actual dose delivered to the target was obtained. This anthropomorphic head phantom can be used in other modalities of radiosurgery as well. © 2017 American Association of Physicists in Medicine.

Automated segmentation and dose-volume analysis with DICOMautomaton

NASA Astrophysics Data System (ADS)

Clark, H.; Thomas, S.; Moiseenko, V.; Lee, R.; Gill, B.; Duzenli, C.; Wu, J.

2014-03-01

Purpose: Exploration of historical data for regional organ dose sensitivity is limited by the effort needed to (sub-)segment large numbers of contours. A system has been developed which can rapidly perform autonomous contour sub-segmentation and generic dose-volume computations, substantially reducing the effort required for exploratory analyses. Methods: A contour-centric approach is taken which enables lossless, reversible segmentation and dramatically reduces computation time compared with voxel-centric approaches. Segmentation can be specified on a per-contour, per-organ, or per-patient basis, and can be performed along either an embedded plane or in terms of the contour's bounds (e.g., split organ into fractional-volume/dose pieces along any 3D unit vector). More complex segmentation techniques are available. Anonymized data from 60 head-and-neck cancer patients were used to compare dose-volume computations with Varian's EclipseTM (Varian Medical Systems, Inc.). Results: Mean doses and Dose-volume-histograms computed agree strongly with Varian's EclipseTM. Contours which have been segmented can be injected back into patient data permanently and in a Digital Imaging and Communication in Medicine (DICOM)-conforming manner. Lossless segmentation persists across such injection, and remains fully reversible. Conclusions: DICOMautomaton allows researchers to rapidly, accurately, and autonomously segment large amounts of data into intricate structures suitable for analyses of regional organ dose sensitivity.

Understanding the cognitive impact of the contraceptive estrogen Ethinyl Estradiol: tonic and cyclic administration impairs memory, and performance correlates with basal forebrain cholinergic system integrity.

PubMed

Mennenga, Sarah E; Gerson, Julia E; Koebele, Stephanie V; Kingston, Melissa L; Tsang, Candy W S; Engler-Chiurazzi, Elizabeth B; Baxter, Leslie C; Bimonte-Nelson, Heather A

2015-04-01

Ethinyl Estradiol (EE), a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives, and is found in at least 30 different contraceptive formulations currently prescribed to women as well as hormone therapies prescribed to menopausal women. Thus, EE is prescribed clinically to women at ages ranging from puberty to reproductive senescence. Here, in two separate studies, the cognitive effects of cyclic or tonic EE administration following ovariectomy (Ovx) were evaluated in young female rats. Study I assessed the cognitive effects of low and high doses of EE, delivered tonically via a subcutaneous osmotic pump. Study II evaluated the cognitive effects of low, medium, and high doses of EE administered via a daily subcutaneous injection, modeling the daily rise and fall of serum EE levels with oral regimens. Study II also investigated the impact of low, medium and high doses of EE on the basal forebrain cholinergic system. The low and medium doses utilized here correspond to the range of doses currently used in clinical formulations, and the high dose corresponds to doses prescribed to a generation of women between 1960 and 1970, when oral contraceptives first became available. We evaluate cognition using a battery of maze tasks tapping several domains of spatial learning and memory as well as basal forebrain cholinergic integrity using immunohistochemistry and unbiased stereology to estimate the number of choline acetyltransferase (ChAT)-producing cells in the medial septum and vertical/diagonal bands. At the highest dose, EE treatment impaired multiple domains of spatial memory relative to vehicle treatment, regardless of administration method. When given cyclically at the low and medium doses, EE did not impact working memory, but transiently impaired reference memory during the learning phase of testing. Of the doses and regimens tested here, only EE at the highest dose impaired several domains of memory; tonic delivery of low EE, a dose that corresponds to the most popular doses used in the clinic today, did not impact cognition on any measure. Both medium and high injection doses of EE reduced the number of ChAt-immunoreactive cells in the basal forebrain, and cell population estimates in the vertical/diagonal bands negatively correlated with working memory errors. Copyright © 2015 Elsevier Ltd. All rights reserved.

SU-E-T-586: Optimal Determination of Tolerance Level for Radiation Dose Delivery Verification in An in Vivo Dosimetry System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Y; Souri, S; Gill, G

Purpose: To statistically determine the optimal tolerance level in the verification of delivery dose compared to the planned dose in an in vivo dosimetry system in radiotherapy. Methods: The LANDAUER MicroSTARii dosimetry system with screened nanoDots (optically stimulated luminescence dosimeters) was used for in vivo dose measurements. Ideally, the measured dose should match with the planned dose and falls within a normal distribution. Any deviation from the normal distribution may be redeemed as a mismatch, therefore a potential sign of the dose misadministration. Randomly mis-positioned nanoDots can yield a continuum background distribution. A percentage difference of the measured dose tomore » its corresponding planned dose (ΔD) can be used to analyze combined data sets for different patients. A model of a Gaussian plus a flat function was used to fit the ΔD distribution. Results: Total 434 nanoDot measurements for breast cancer patients were collected across a period of three months. The fit yields a Gaussian mean of 2.9% and a standard deviation (SD) of 5.3%. The observed shift of the mean from zero is attributed to the machine output bias and calibration of the dosimetry system. A pass interval of −2SD to +2SD was applied and a mismatch background was estimated to be 4.8%. With such a tolerance level, one can expect that 99.99% of patients should pass the verification and at most 0.011% might have a potential dose misadministration that may not be detected after 3 times of repeated measurements. After implementation, a number of new start breast cancer patients were monitored and the measured pass rate is consistent with the model prediction. Conclusion: It is feasible to implement an optimal tolerance level in order to maintain a low limit of potential dose misadministration while still to keep a relatively high pass rate in radiotherapy delivery verification.« less

A physical anthropomorphic phantom of a one year old child with real-time dosimetry

NASA Astrophysics Data System (ADS)

Bower, Mark William

A physical heterogeneous phantom has been created with epoxy resin based tissue substitutes. The phantom is based on the Cristy and Eckerman mathematical phantom which in turn is a modification of the Medical Internal Radiation Dose (MIRD) model of a one-year-old child as presented by the Society of Nuclear Medicine. The Cristy and Eckerman mathematical phantom, and the physical phantom, are comprised of three different tissue types: bone, lung tissue and soft tissue. The bone tissue substitute is a homogenous mixture of bone tissues: active marrow, inactive marrow, trabecular bone, and cortical bone. Soft tissue organs are represented by a homogeneous soft tissue substitute at a particular location. Point doses were measured within the phantom with a Metal Oxide Semiconductor Field Effect Transistor (MOSFET)- based Patient Dose Verification System modified from the original radiotherapy application. The system features multiple dosimeters that are used to monitor entrance or exit skin doses and intracavity doses in the phantom in real-time. Two different MOSFET devices were evaluated: the typical therapy MOSFET and a developmental MOSFET device that has an oxide layer twice as thick as the therapy MOSFET thus making it of higher sensitivity. The average sensitivity (free-in-air, including backscatter) of the 'high-sensitivity' MOSFET dosimeters ranged from 1.15×105 mV per C kg-1 (29.7 mV/R) to 1.38×105 mV per C kg-1 (35.7 mV/R) depending on the energy of the x-ray field. The integrated physical phantom was utilized to obtain point measurements of the absorbed dose from diagnostic x-ray examinations. Organ doses were calculated based on these point dose measurements. The phantom dosimetry system functioned well providing real-time measurement of the dose to particular organs. The system was less reliable at low doses where the main contribution to the dose was from scattered radiation. The system also was of limited utility for determining the absorbed dose in larger systems such as the skeleton. The point dose method of estimating the organ dose to large disperse organs such as this are of questionable accuracy since only a limited number of points are measured in a field with potentially large exposure variations. The MOSFET system was simple to use and considerably faster than traditional thermoluminescent dosimetry. The one-year-old simulated phantom with the real-time MOSFET dosimeters provides a method to easily evaluate the risk to a previously understudied population from diagnostic radiographic procedures.

Dosimetric comparison of IMRT rectal and anal canal plans generated using an anterior dose avoidance structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leicher, Brian, E-mail: bleicher@wpahs.org; Day, Ellen; Colonias, Athanasios

2014-10-01

To describe a dosimetric method using an anterior dose avoidance structure (ADAS) during the treatment planning process for intensity-modulated radiation therapy (IMRT) for patients with anal canal and rectal carcinomas. A total of 20 patients were planned on the Elekta/CMS XiO treatment planning system, version 4.5.1 (Maryland Heights MO) with a superposition algorithm. For each patient, 2 plans were created: one employing an ADAS (ADAS plan) and the other replanned without an ADAS (non-ADAS plan). The ADAS was defined to occupy the volume between the inguinal nodes and primary target providing a single organ at risk that is completely outsidemore » of the target volume. Each plan used the same beam parameters and was analyzed by comparing target coverage, overall plan dose conformity using a conformity number (CN) equation, bowel dose-volume histograms, and the number of segments, daily treatment duration, and global maximum dose. The ADAS and non-ADAS plans were equivalent in target coverage, mean global maximum dose, and sparing of small bowel in low-dose regions (5, 10, 15, and 20 Gy). The mean difference between the CN value for the non-ADAS plans and ADAS plans was 0.04 ± 0.03 (p < 0.001). The mean difference in the number of segments was 15.7 ± 12.7 (p < 0.001) in favor of ADAS plans. The ADAS plan delivery time was shorter by 2.0 ± 1.5 minutes (p < 0.001) than the non-ADAS one. The ADAS has proven to be a powerful tool when planning rectal and anal canal IMRT cases with critical structures partially contained inside the target volume.« less

Anatomical background and generalized detectability in tomosynthesis and cone-beam CT.

PubMed

Gang, G J; Tward, D J; Lee, J; Siewerdsen, J H

2010-05-01

Anatomical background presents a major impediment to detectability in 2D radiography as well as 3D tomosynthesis and cone-beam CT (CBCT). This article incorporates theoretical and experimental analysis of anatomical background "noise" in cascaded systems analysis of 2D and 3D imaging performance to yield "generalized" metrics of noise-equivalent quanta (NEQ) and detectability index as a function of the orbital extent of the (circular arc) source-detector orbit. A physical phantom was designed based on principles of fractal self-similarity to exhibit power-law spectral density (kappa/Fbeta) comparable to various anatomical sites (e.g., breast and lung). Background power spectra [S(B)(F)] were computed as a function of source-detector orbital extent, including tomosynthesis (approximately 10 degrees -180 degrees) and CBCT (180 degrees + fan to 360 degrees) under two acquisition schemes: (1) Constant angular separation between projections (variable dose) and (2) constant total number of projections (constant dose). The resulting S(B) was incorporated in the generalized NEQ, and detectability index was computed from 3D cascaded systems analysis for a variety of imaging tasks. The phantom yielded power-law spectra within the expected spatial frequency range, quantifying the dependence of clutter magnitude (kappa) and correlation (beta) with increasing tomosynthesis angle. Incorporation of S(B) in the 3D NEQ provided a useful framework for analyzing the tradeoffs among anatomical, quantum, and electronic noise with dose and orbital extent. Distinct implications are posed for breast and chest tomosynthesis imaging system design-applications varying significantly in kappa and beta, and imaging task and, therefore, in optimal selection of orbital extent, number of projections, and dose. For example, low-frequency tasks (e.g., soft-tissue masses or nodules) tend to benefit from larger orbital extent and more fully 3D tomographic imaging, whereas high-frequency tasks (e.g., microcalcifications) require careful, application-specific selection of orbital extent and number of projections to minimize negative effects of quantum and electronic noise. The complex tradeoffs among anatomical background, quantum noise, and electronic noise in projection imaging, tomosynthesis, and CBCT can be described by generalized cascaded systems analysis, providing a useful framework for system design and optimization.

Influence of multiple brain metastases’ size and number on the quality of SRS - VMAT dose delivery

NASA Astrophysics Data System (ADS)

Prentou, G.; Koutsouveli, E.; Pantelis, E.; Papagiannis, P.; Georgiou, E.; Karaiskos, P.

2017-11-01

Stereotactic radiosurgery with volumetric modulated arc therapy (SRS-VMAT) has recently been introduced for treatment of multiple brain metastases with a single isocenter. The technique’s high efficiency is nevertheless dependent of metastatic tumors’ characteristics such as size and number. In this work the impact of the metastases’ size and number on the plan quality indices clinically used for plan evaluation and acceptance is investigated. Fifteen targets with a diameter of 1 cm and average volume of 0.7 cm3 and ten targets with a diameter of 2 cm and average volume of 6.5 cm3 were contoured on an anonymized patient CT dataset, in Monaco (Elekta) treatment planning system. VMAT plans for different target volumes (1 and 2 cm in diameter) and various target numbers (1-15) were generated using four non-coplanar arcs and the Agility (Elekta) linear accelerator (5 mm MLC width) using a Monte Carlo dose calculation algorithm and 1mm dose calculation grid resolution. Conformity index (CI), gradient index (GI) and heterogeneity index (HI) were determined for each target. High quality plans were created for both 1 cm and 2 cm in diameter targets for limited (<6) number of targets per plan. For increased number of irradiated targets (>6) both CI and GI, clinically used for plan evaluation and acceptance, were found to deteriorate.

MO-F-CAMPUS-I-01: A System for Automatically Calculating Organ and Effective Dose for Fluoroscopically-Guided Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiong, Z; Vijayan, S; Rana, V

2015-06-15

Purpose: A system was developed that automatically calculates the organ and effective dose for individual fluoroscopically-guided procedures using a log of the clinical exposure parameters. Methods: We have previously developed a dose tracking system (DTS) to provide a real-time color-coded 3D- mapping of skin dose. This software produces a log file of all geometry and exposure parameters for every x-ray pulse during a procedure. The data in the log files is input into PCXMC, a Monte Carlo program that calculates organ and effective dose for projections and exposure parameters set by the user. We developed a MATLAB program to readmore » data from the log files produced by the DTS and to automatically generate the definition files in the format used by PCXMC. The processing is done at the end of a procedure after all exposures are completed. Since there are thousands of exposure pulses with various parameters for fluoroscopy, DA and DSA and at various projections, the data for exposures with similar parameters is grouped prior to entry into PCXMC to reduce the number of Monte Carlo calculations that need to be performed. Results: The software developed automatically transfers data from the DTS log file to PCXMC and runs the program for each grouping of exposure pulses. When the dose from all exposure events are calculated, the doses for each organ and all effective doses are summed to obtain procedure totals. For a complicated interventional procedure, the calculations can be completed on a PC without manual intervention in less than 30 minutes depending on the level of data grouping. Conclusion: This system allows organ dose to be calculated for individual procedures for every patient without tedious calculations or data entry so that estimates of stochastic risk can be obtained in addition to the deterministic risk estimate provided by the DTS. Partial support from NIH grant R01EB002873 and Toshiba Medical Systems Corp.« less

MO-F-16A-06: Implementation of a Radiation Exposure Monitoring System for Surveillance of Multi-Modality Radiation Dose Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stewart, B; Kanal, K; Dickinson, R

2014-06-15

Purpose: We have implemented a commercially available Radiation Exposure Monitoring System (REMS) to enhance the processes of radiation dose data collection, analysis and alerting developed over the past decade at our sites of practice. REMS allows for consolidation of multiple radiation dose information sources and quicker alerting than previously developed processes. Methods: Thirty-nine x-ray producing imaging modalities were interfaced with the REMS: thirteen computed tomography scanners, sixteen angiography/interventional systems, nine digital radiography systems and one mammography system. A number of methodologies were used to provide dose data to the REMS: Modality Performed Procedure Step (MPPS) messages, DICOM Radiation Dose Structuredmore » Reports (RDSR), and DICOM header information. Once interfaced, the dosimetry information from each device underwent validation (first 15–20 exams) before release for viewing by end-users: physicians, medical physicists, technologists and administrators. Results: Before REMS, our diagnostic physics group pulled dosimetry data from seven disparate databases throughout the radiology, radiation oncology, cardiology, electrophysiology, anesthesiology/pain management and vascular surgery departments at two major medical centers and four associated outpatient clinics. With the REMS implementation, we now have one authoritative source of dose information for alerting, longitudinal analysis, dashboard/graphics generation and benchmarking. REMS provides immediate automatic dose alerts utilizing thresholds calculated through daily statistical analysis. This has streamlined our Closing the Loop process for estimated skin exposures in excess of our institutional specific substantial radiation dose level which relied on technologist notification of the diagnostic physics group and daily report from the radiology information system (RIS). REMS also automatically calculates the CT size-specific dose estimate (SSDE) as well as provides two-dimensional angulation dose maps for angiography/interventional procedures. Conclusion: REMS implementation has streamlined and consolidated the dosimetry data collection and analysis process at our institutions while eliminating manual entry error and providing immediate alerting and access to dosimetry data to both physicists and physicians. Brent Stewart has funded research through GE Healthcare.« less

The effect of electronic medical record system use on communication between pharmacists and prescribers.

PubMed

Singer, Alexander; Duarte Fernandez, Roberto

2015-10-28

The Electronic Medical Record (EMR) is becoming increasingly common in health care settings. Research shows that EMRs have the potential to reduce instances of medication errors and improve communication between pharmacists and prescribers; however, more research is required to demonstrate whether this is true. This study aims to determine the effect of a newly implemented EMR system on communication between pharmacists and primary care clinicians. A retrospective chart analysis of primary care EMR data comparing faxed pharmacy communications captured before and after the implementation of an EMR system at an academic family medicine clinic. Communication requests were classified into the following various categories: refill accepted, refill denied, clarification, incorrect dose, interaction, drug insurance/coverage application, new prescription request, supplies request, continued care information, duplicate fax substitution, opioid early release request, confirmation by phone call, and other. The number and percentage of clarification requests, interaction notifications, and incorrect dose notifications were lower after the implementation of the EMR system. The number and percentage of refills accepted and new prescription requests increased after the implementation of the EMR system. The implementation of an EMR in an academic family medicine clinic had a significant effect on the volume of communication between pharmacists and prescribers. The amount of clarification requests and incorrect dosing communications decreased after EMR implementation. This suggests that EMRs improve prescribing safety. The increased amount of refills accepted and new prescription requests post EMR implementation suggests that the EMR is capable of changing prescription patterns.

Dosimetric validation and clinical implementation of two 3D dose verification systems for quality assurance in volumetric‐modulated arc therapy techniques

PubMed Central

Pérez‐Vara, Consuelo

2015-01-01

A pretreatment quality assurance program for volumetric techniques should include redundant calculations and measurement‐based verifications. The patient‐specific quality assurance process must be based in clinically relevant metrics. The aim of this study was to show the commission, clinical implementation, and comparison of two systems that allow performing a 3D redundant dose calculation. In addition, one of them is capable of reconstructing the dose on patient anatomy from measurements taken with a 2D ion chamber array. Both systems were compared in terms of reference calibration data (absolute dose, output factors, percentage depth‐dose curves, and profiles). Results were in good agreement for absolute dose values (discrepancies were below 0.5%) and output factors (mean differences were below 1%). Maximum mean discrepancies were located between 10 and 20 cm of depth for PDDs (‐2.7%) and in the penumbra region for profiles (mean DTA of 1.5 mm). Validation of the systems was performed by comparing point‐dose measurements with values obtained by the two systems for static, dynamic fields from AAPM TG‐119 report, and 12 real VMAT plans for different anatomical sites (differences better than 1.2%). Comparisons between measurements taken with a 2D ion chamber array and results obtained by both systems for real VMAT plans were also performed (mean global gamma passing rates better than 87.0% and 97.9% for the 2%/2 mm and 3%/3 mm criteria). Clinical implementation of the systems was evaluated by comparing dose‐volume parameters for all TG‐119 tests and real VMAT plans with TPS values (mean differences were below 1%). In addition, comparisons between dose distributions calculated by TPS and those extracted by the two systems for real VMAT plans were also performed (mean global gamma passing rates better than 86.0% and 93.0% for the 2%/2 mm and 3%/3 mm criteria). The clinical use of both systems was successfully evaluated. PACS numbers: 87.56.Fc, 87.56.‐v, 87.55.dk, 87.55.Qr, 87.55.‐x, 07.57.Kp, 85.25.Pb PMID:26103189

A framework for optimizing micro-CT in dual-modality micro-CT/XFCT small-animal imaging system

NASA Astrophysics Data System (ADS)

Vedantham, Srinivasan; Shrestha, Suman; Karellas, Andrew; Cho, Sang Hyun

2017-09-01

Dual-modality Computed Tomography (CT)/X-ray Fluorescence Computed Tomography (XFCT) can be a valuable tool for imaging and quantifying the organ and tissue distribution of small concentrations of high atomic number materials in small-animal system. In this work, the framework for optimizing the micro-CT imaging system component of the dual-modality system is described, either when the micro-CT images are concurrently acquired with XFCT and using the x-ray spectral conditions for XFCT, or when the micro-CT images are acquired sequentially and independently of XFCT. This framework utilizes the cascaded systems analysis for task-specific determination of the detectability index using numerical observer models at a given radiation dose, where the radiation dose is determined using Monte Carlo simulations.

Short and long effects of Citrullus colocynthis L. on reproductive system and fertility in female Spague-Dawley rats.

PubMed

Qazan, Walid Sh; Almasad, Motasem M; Daradka, Haytham

2007-08-15

Aim of this study is to investigate the toxic effects of Citrullus colocynthis L. (400 mg/kg/body wight) on the reproductive system after administration to female Sprague-Dawley rats weighting 250-300 g for two time periods 4 and 12 weeks. Twenty adult female rats were divided into two groups and Citrullus colocynthis L. were intraperitoneally injected to experimental animals in dose of 400 mg/kg/body wight. First group containing 10 rats received treatment for 4 weeks and a second group of 10 rats received the same dose of treatment for a period of 12 weeks and compared with twenty non-exposed female rats received vehicle treatment. Female rats were allowed mating with males after 10 days prior to the last administration dose. Animals were autopsied under light anesthesia after mating and several parameters were determined including: number of pregnant rats, body and reproductive organ weight, number of implantation sites, viable fetuses and resorption sites. Assessment of pregnancies in females was measured and the significance of these results was calculated using students t and Chi-square tests. The effect of Citrullus colocynthis L. exposure on fertility was assessed in terms of pregnant rats number, implantation sites, viable fetuses and resorption sites. Exposure to Citrullus colocynthis L. for 4 weeks did not have much effect on fertility. Significant decrease in the relative ovarian weights and embryo weights in rats exposed to Citrullus colocynthis L. were observed. Exposure to Citrullus colocynthis L. for a 12 weeks resulted in a reduction in the percentage of pregnancies and in the number of implantation sites when compared with controls in both treatment periods. Rats receiving 12 weeks treatment showed a decrease in ovarian weights and a decrease in viable fetus's number. These results indicate that long-term exposure of female rats to Citrullus colocynthis L. causes adverse effects on the reproductive system and fertility.

Irradiate-anneal screening of total dose effects in semiconductor devices. [radiation hardening of spacecraft components of Mariner spacecraft

NASA Technical Reports Server (NTRS)

Stanley, A. G.; Price, W. E.

1976-01-01

An extensive investigation of irradiate-anneal (IRAN) screening against total dose radiation effects was carried out as part of a program to harden the Mariner Jupiter/Saturn 1977 (MJS'77) spacecraft to survive the Jupiter radiation belts. The method consists of irradiating semiconductor devices with Cobalt-60 to a suitable total dose under representative bias conditions and of separating the parts in the undesired tail of the distribution from the bulk of the parts by means of a predetermined acceptance limit. The acceptable devices are then restored close to their preirradiation condition by annealing them at an elevated temperature. IRAN was used when lot screen methods were impracticable due to lack of time, and when members of a lot showed a diversity of radiation response. The feasibility of the technique was determined by testing of a number of types of linear bipolar integrated circuits, analog switches, n-channel JFETS and bipolar transistors. Based on the results of these experiments a number of device types were selected for IRAN of flight parts in the MJS'77 spacecraft systems. The part types, screening doses, acceptance criteria, number of parts tested and rejected as well as the program steps are detailed.

The Mayak Worker Dosimetry System (MWDS-2013): Implementation of the Dose Calculations.

PubMed

Zhdanov, А; Vostrotin, V; Efimov, А; Birchall, A; Puncher, M

2016-07-15

The calculation of internal doses for the Mayak Worker Dosimetry System (MWDS-2013) involved extensive computational resources due to the complexity and sheer number of calculations required. The required output consisted of a set of 1000 hyper-realizations: each hyper-realization consists of a set (1 for each worker) of probability distributions of organ doses. This report describes the hardware components and computational approaches required to make the calculation tractable. Together with the software, this system is referred to here as the 'PANDORA system'. It is based on a commercial SQL server database in a series of six work stations. A complete run of the entire Mayak worker cohort entailed a huge amount of calculations in PANDORA and due to the relatively slow speed of writing the data into the SQL server, each run took about 47 days. Quality control was monitored by comparing doses calculated in PANDORA with those in a specially modified version of the commercial software 'IMBA Professional Plus'. Suggestions are also made for increasing calculation and storage efficiency for future dosimetry calculations using PANDORA. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Non-induction of radioadaptive response in zebrafish embryos by neutrons.

PubMed

Ng, Candy Y P; Kong, Eva Y; Kobayashi, Alisa; Suya, Noriyoshi; Uchihori, Yukio; Cheng, Shuk Han; Konishi, Teruaki; Yu, Kwan Ngok

2016-06-01

In vivo neutron-induced radioadaptive response (RAR) was studied using zebrafish (Danio rerio) embryos. The Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility at the National Institute of Radiological Sciences (NIRS), Japan, was employed to provide 2-MeV neutrons. Neutron doses of 0.6, 1, 25, 50 and 100 mGy were chosen as priming doses. An X-ray dose of 2 Gy was chosen as the challenging dose. Zebrafish embryos were dechorionated at 4 h post fertilization (hpf), irradiated with a chosen neutron dose at 5 hpf and the X-ray dose at 10 hpf. The responses of embryos were assessed at 25 hpf through the number of apoptotic signals. None of the neutron doses studied could induce RAR. Non-induction of RAR in embryos having received 0.6- and 1-mGy neutron doses was attributed to neutron-induced hormesis, which maintained the number of damaged cells at below the threshold for RAR induction. On the other hand, non-induction of RAR in embryos having received 25-, 50- and 100-mGy neutron doses was explained by gamma-ray hormesis, which mitigated neutron-induced damages through triggering high-fidelity DNA repair and removal of aberrant cells through apoptosis. Separate experimental results were obtained to verify that high-energy photons could disable RAR. Specifically, 5- or 10-mGy X-rays disabled the RAR induced by a priming dose of 0.88 mGy of alpha particles delivered to 5-hpf zebrafish embryos against a challenging dose of 2 Gy of X-rays delivered to the embryos at 10 hpf. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Systematic evaluation of four-dimensional hybrid depth scanning for carbon-ion lung therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mori, Shinichiro; Furukawa, Takuji; Inaniwa, Taku

2013-03-15

Purpose: Irradiation of a moving target with a scanning beam requires a comprehensive understanding of organ motion as well as a robust dose error mitigation technique. The authors studied the effects of intrafractional respiratory motion for carbon-ion pencil beam scanning with phase-controlled rescanning on dose distributions for lung tumors. To address density variations, they used 4DCT data. Methods: Dose distributions for various rescanning methods, such as simple layer rescanning (LR), volumetric rescanning, and phase-controlled rescanning (PCR), were calculated for a lung phantom and a lung patient studies. To ensure realism, they set the scanning parameters such as scanning velocity andmore » energy variation time to be similar to those used at our institution. Evaluation metrics were determined with regard to clinical relevance, and consisted of (i) phase-controlled rescanning, (ii) sweep direction, (iii) target motion (direction and amplitude), (iv) respiratory cycle, and (v) prescribed dose. Spot weight maps were calculated by using a beam field-specific target volume, which takes account of range variations for respective respiratory phases. To emphasize the impact of intrafractional motion on the dose distribution, respiratory gating was not used. The accumulated dose was calculated by applying a B-spline-based deformable image registration, and the results for phase-controlled layered rescanning (PCR{sub L}) and phase-controlled volumetric rescanning (PCR{sub V}) were compared. Results: For the phantom study, simple LR was unable to improve the dose distributions for an increased number of rescannings. The phase-controlled technique without rescanning (1 Multiplication-Sign PCR{sub L} and 1 Multiplication-Sign PCR{sub V}) degraded dose conformity significantly due to a reduced scan velocity. In contrast, 4 Multiplication-Sign PCR{sub L} or more significantly and consistently improved dose distribution. PCR{sub V} showed interference effects, but in general also improved dose homogeneity with higher numbers of rescannings. Dose distributions with single PCR{sub L}/PCR{sub V} with a sweep direction perpendicular to motion direction showed large hot/cold spots; however, this effect vanished with higher numbers of rescannings for both methods. Similar observations were obtained for the other dose metrics, such as target motion (SI/AP), amplitude (6-22 mm peak-to-peak) and respiratory period (3.0-5.0 s). For four or more rescannings, both methods showed significantly better results, albeit that volumetric PCR was more affected by interference effects, which lead to severe degradation of a few dose distributions. The clinical example showed the same tendencies as the phantom study. Dose assessment metrics (D95, Dmax/Dmin, homogeneity index) were improved with an increasing number of PCR{sub L}/PCR{sub V}, but with PCR{sub L} being more robust. Conclusions: PCR{sub L} requires a longer treatment time than PCR{sub V} for high numbers of rescannings in the NIRS scanning system but is more robust. Although four or more rescans provided good dose homogeneity and conformity, the authors prefer to use more rescannings for clinical cases to further minimize dose degradation effects due to organ motion.« less

SU-C-201-03: Ionization Chamber Collection Efficiency in Pulsed Radiation Fields of High Pulse Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gotz, M; Karsch, L; Pawelke, J

Purpose: To investigate the reduction of collection efficiency of ionization chambers (IC) by volume recombination and its correction in pulsed fields of very high pulse dose. Methods: Measurements of the collection efficiency of a plane-parallel advanced Markus IC (PTW 34045, 1mm electrode spacing, 300V nominal voltage) were obtained for collection voltages of 100V and 300V by irradiation with a pulsed electron beam (20MeV) of varied pulse dose up to approximately 600mGy (0.8nC liberated charge). A reference measurement was performed with a Faraday cup behind the chamber. It was calibrated for the liberated charge in the IC by a linear fitmore » of IC measurement to reference measurement at low pulse doses. The results were compared to the commonly used two voltage approximation (TVA) and to established theories for volume recombination, with and without considering a fraction of free electrons. In addition, an equation system describing the charge transport and reactions in the chamber was solved numerically. Results: At 100V collection voltage and moderate pulse doses the established theories accurately predict the observed collection efficiency, but at extreme pulse doses a fraction of free electrons needs to be considered. At 300V the observed collection efficiency deviates distinctly from that predicted by any of the established theories, even at low pulse doses. However, the numeric solution of the equation system is able to reproduce the measured collection efficiency across the entire dose range of both voltages with a single set of parameters. Conclusion: At high electric fields (3000V/cm here) the existing theoretical descriptions of collection efficiency, including the TVA, are inadequate to predict pulse dose dependency. Even at low pulse doses they might underestimate collection efficiency. The presented, more accurate numeric solution, which considers additional effects like electric shielding by the charges, might provide a valuable tool for future investigations. This project was funded by the German ministry of research and education (BMBF) under grant number: 03Z1N511 and by the state of Saxony under grant number: B 209.« less

SU-F-BRB-12: A Novel Haar Wavelet Based Approach to Deliver Non-Coplanar Intensity Modulated Radiotherapy Using Sparse Orthogonal Collimators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, D; Ruan, D; Low, D

2015-06-15

Purpose: Existing efforts to replace complex multileaf collimator (MLC) by simple jaws for intensity modulated radiation therapy (IMRT) resulted in unacceptable compromise in plan quality and delivery efficiency. We introduce a novel fluence map segmentation method based on compressed sensing for plan delivery using a simplified sparse orthogonal collimator (SOC) on the 4π non-coplanar radiotherapy platform. Methods: 4π plans with varying prescription doses were first created by automatically selecting and optimizing 20 non-coplanar beams for 2 GBM, 2 head & neck, and 2 lung patients. To create deliverable 4π plans using SOC, which are two pairs of orthogonal collimators withmore » 1 to 4 leaves in each collimator bank, a Haar Fluence Optimization (HFO) method was used to regulate the number of Haar wavelet coefficients while maximizing the dose fidelity to the ideal prescription. The plans were directly stratified utilizing the optimized Haar wavelet rectangular basis. A matching number of deliverable segments were stratified for the MLC-based plans. Results: Compared to the MLC-based 4π plans, the SOC-based 4π plans increased the average PTV dose homogeneity from 0.811 to 0.913. PTV D98 and D99 were improved by 3.53% and 5.60% of the corresponding prescription doses. The average mean and maximal OAR doses slightly increased by 0.57% and 2.57% of the prescription doses. The average number of segments ranged between 5 and 30 per beam. The collimator travel time to create the segments decreased with increasing leaf numbers in the SOC. The two and four leaf designs were 1.71 and 1.93 times more efficient, on average, than the single leaf design. Conclusion: The innovative dose domain optimization based on compressed sensing enables uncompromised 4π non-coplanar IMRT dose delivery using simple rectangular segments that are deliverable using a sparse orthogonal collimator, which only requires 8 to 16 leaves yet is unlimited in modulation resolution. This work is supported in part by Varian Medical Systems, Inc. and NIH R43 CA18339.« less

Carbon Heavy-ion Radiation Induced Biological effects on Oryza sativa L.

NASA Astrophysics Data System (ADS)

Zhang, Meng; Sun, Yeqing; Li, Xishan; Gong, Ning; Meng, Qingmei; Liu, Jiawei; Wang, Ting

2016-07-01

Large number of researches on rice after spaceflights indicated that rice was a favorable model organism to study biological effects induced by space radiation. The stimulative effect could often be found on rice seedlings after irradiation by low-dose energetic heavy-ion radiation. Spaceflight also could induce stimulative effect on kinds of seeds. To further understand the mechanism of low-dose radiation biological effects and the dose range, the germinated rice seeds which were irradiated by different doses of carbon heavy-ion (0, 0.02, 0.1, 0.2, 1, 2, 5, 10, 15 and 20Gy, LET=27.3keV/µm) were used as materials to study. By investigating the variation of rice phenotype under different doses, we found that 2Gy radiation dose was a dividing point of the phenotypic variation. Transmission electron microscopy was used to observe the variation of mitochondria, chloroplast, endoplasmic reticulum, ribosome and nucleus in mesophyll cell of rice apical meristem at 24 hours after radiation with different doses. The cells were not apparently physiologically damaged when the dose of radiation was less than 2Gy. The number of chloroplast did not change significantly, but the number of mitochondria was significantly increased, and gathered around in the chloroplast and endoplasmic reticulum; the obvious lesion of chloroplast and mitochondria were found at the mesophyll cells when radiation dose was higher than 2Gy. The mitochondria were swelling and appearing blurred crest. The chloroplast and mitochondrial mutation rate increased significantly (p<0.01). These phenomena showed that cell biological changes may be the reasons of the stimulation and inhibition effects with the boundary of 2Gy. Since mitochondrial was an important organelle involved in the antioxidative systems, its dysfunction could result in the increase of reactive oxygen species and lipid peroxidation. We found that the growth stimulation induced by low-dose radiation mainly occurred at three-leaf stage along with the increasing activity of antioxidase system and damages of lipid peroxidation. We also found that the relative expression of genes sdhb and aox1a which encode the key proteins in mitochondria changed differently after exposed to different doses of radiation, and the lower dose of the radiation could cause longer effect. The chlorophyll was an important organ of photosynthesis, its dysfunction could result in the phenotypic variation. We found that the chlorophyll fluorescence parameter Fv/Fm, the content of chlorophyll (including chlorophyll a, chlorophyll b and total chlorophyll) and both the relative expression of CP24 and its encoding gene lhcb6 changed significantly in different doses. The changes of the relative expression of CP24 and its encoding gene lhcb6 were completely opposite at the lower dose and agreed at the higher dose. The possible mechanisms of growth stimulation and inhibition effects induced by low and high dose radiations were discussed on multiple levels. Moreover, our findings were important to understand the spaceflight induced growth stimulation and inhibition effects of plant. Keywords: Heavy-ion radiation; Low dose; Stimulation effect; Inhibition effect; Rice.

Evaluation of Dose Uncertainty to the Target Associated With Real-Time Tracking Intensity-Modulated Radiation Therapy Using the CyberKnife Synchrony System.

PubMed

Iwata, Hiromitsu; Inoue, Mitsuhiro; Shiomi, Hiroya; Murai, Taro; Tatewaki, Koshi; Ohta, Seiji; Okawa, Kohei; Yokota, Naoki; Shibamoto, Yuta

2016-02-01

We investigated the dose uncertainty caused by errors in real-time tracking intensity-modulated radiation therapy (IMRT) using the CyberKnife Synchrony Respiratory Tracking System (SRTS). Twenty lung tumors that had been treated with non-IMRT real-time tracking using CyberKnife SRTS were used for this study. After validating the tracking error in each case, we did 40 IMRT planning using 8 different collimator sizes for the 20 patients. The collimator size was determined for each planning target volume (PTV); smaller ones were one-half, and larger ones three-quarters, of the PTV diameter. The planned dose was 45 Gy in 4 fractions prescribed at 95% volume border of the PTV. Thereafter, the tracking error in each case was substituted into calculation software developed in house and randomly added in the setting of each beam. The IMRT planning incorporating tracking errors was simulated 1000 times, and various dose data on the clinical target volume (CTV) were compared with the original data. The same simulation was carried out by changing the fraction number from 1 to 6 in each IMRT plan. Finally, a total of 240 000 plans were analyzed. With 4 fractions, the change in the CTV maximum and minimum doses was within 3.0% (median) for each collimator. The change in D99 and D95 was within 2.0%. With decreases in the fraction number, the CTV coverage rate and the minimum dose decreased and varied greatly. The accuracy of real-time tracking IMRT delivered in 4 fractions using CyberKnife SRTS was considered to be clinically acceptable. © The Author(s) 2014.

Dose-Dependent Effects of Theta Burst rTMS on Cortical Excitability and Resting-State Connectivity of the Human Motor System

PubMed Central

Nettekoven, Charlotte; Volz, Lukas J.; Kutscha, Martha; Pool, Eva-Maria; Rehme, Anne K.; Eickhoff, Simon B.; Fink, Gereon R.

2014-01-01

Theta burst stimulation (TBS), a specific protocol of repetitive transcranial magnetic stimulation (rTMS), induces changes in cortical excitability that last beyond stimulation. TBS-induced aftereffects, however, vary between subjects, and the mechanisms underlying these aftereffects to date remain poorly understood. Therefore, the purpose of this study was to investigate whether increasing the number of pulses of intermittent TBS (iTBS) (1) increases cortical excitability as measured by motor-evoked potentials (MEPs) and (2) alters functional connectivity measured using resting-state fMRI, in a dose-dependent manner. Sixteen healthy, human subjects received three serially applied iTBS blocks of 600 pulses over the primary motor cortex (M1 stimulation) and the parieto-occipital vertex (sham stimulation) to test for dose-dependent iTBS effects on cortical excitability and functional connectivity (four sessions in total). iTBS over M1 increased MEP amplitudes compared with sham stimulation after each stimulation block. Although the increase in MEP amplitudes did not differ between the first and second block of M1 stimulation, we observed a significant increase after three blocks (1800 pulses). Furthermore, iTBS enhanced resting-state functional connectivity between the stimulated M1 and premotor regions in both hemispheres. Functional connectivity between M1 and ipsilateral dorsal premotor cortex further increased dose-dependently after 1800 pulses of iTBS over M1. However, no correlation between changes in MEP amplitudes and functional connectivity was detected. In summary, our data show that increasing the number of iTBS stimulation blocks results in dose-dependent effects at the local level (cortical excitability) as well as at a systems level (functional connectivity) with a dose-dependent enhancement of dorsal premotor cortex-M1 connectivity. PMID:24828639

Evaluation of the uncertainty in an EBT3 film dosimetry system utilizing net optical density

PubMed Central

Marroquin, Elsa Y. León; Herrera González, José A.; Camacho López, Miguel A.; Barajas, José E. Villarreal

2016-01-01

Radiochromic film has become an important tool to verify dose distributions for intensity‐modulated radiotherapy (IMRT) and quality assurance (QA) procedures. A new radiochromic film model, EBT3, has recently become available, whose composition and thickness of the sensitive layer are the same as those of previous EBT2 films. However, a matte polyester layer was added to EBT3 to prevent the formation of Newton's rings. Furthermore, the symmetrical design of EBT3 allows the user to eliminate side‐orientation dependence. This film and the flatbed scanner, Epson Perfection V750, form a dosimetry system whose intrinsic characteristics were studied in this work. In addition, uncertainties associated with these intrinsic characteristics and the total uncertainty of the dosimetry system were determined. The analysis of the response of the radiochromic film (net optical density) and the fitting of the experimental data to a potential function yielded an uncertainty of 2.6%, 4.3%, and 4.1% for the red, green, and blue channels, respectively. In this work, the dosimetry system presents an uncertainty in resolving the dose of 1.8% for doses greater than 0.8 Gy and less than 6 Gy for red channel. The films irradiated between 0 and 120 Gy show differences in the response when scanned in portrait or landscape mode; less uncertainty was found when using the portrait mode. The response of the film depended on the position on the bed of the scanner, contributing an uncertainty of 2% for the red, 3% for the green, and 4.5% for the blue when placing the film around the center of the bed of scanner. Furthermore, the uniformity and reproducibility radiochromic film and reproducibility of the response of the scanner contribute less than 1% to the overall uncertainty in dose. Finally, the total dose uncertainty was 3.2%, 4.9%, and 5.2% for red, green, and blue channels, respectively. The above uncertainty values were obtained by minimizing the contribution to the total dose uncertainty of the film orientation and film homogeneity. PACS number(s): 87.53.Bn PMID:27685125

Air contamination measurements for the evaluation of internal dose to workers in nuclear medicine departments

NASA Astrophysics Data System (ADS)

De Massimi, B.; Bianchini, D.; Sarnelli, A.; D'Errico, V.; Marcocci, F.; Mezzenga, E.; Mostacci, D.

2017-11-01

Radionuclides handled in nuclear medicine departments are often characterized by high volatility and short half-life. It is generally difficult to monitor directly the intake of these short-lived radionuclides in hospital staff: this makes measuring air contamination of utmost interest. The aim of the present work is to provide a method for the evaluation of internal doses to workers in nuclear medicine, by means of an air activity sampling detector, to ensure that the limits prescribed by the relevant legislation are respected. A continuous air sampling system measures isotope concentration with a Nal(TI) detector. Energy efficiency of the system was assessed with GEANT4 and with known activities of 18F. Air is sampled in a number of areas of the nuclear medicine department of the IRST-IRCCS hospital (Meldola- Italy). To evaluate committed doses to hospital staff involved (doctors, technicians, nurses) different exposure situations (rooms, times, radionuclides etc) were considered. After estimating the intake, the committed effective dose has been evaluated, for the different radionuclides, using the dose coefficients mandated by the Italian legislation. Error propagation for the estimated intake and personal dose has been evaluated, starting from measurement statistics.

Comparison of radiation dose, workflow, patient comfort and financial break-even of standard digital radiography and a novel biplanar low-dose X-ray system for upright full-length lower limb and whole spine radiography.

PubMed

Dietrich, Tobias J; Pfirrmann, Christian W A; Schwab, Alexander; Pankalla, Katja; Buck, Florian M

2013-07-01

To compare the radiation dose, workflow, patient comfort, and financial break-even of a standard digital radiography and a biplanar low-dose X-ray system. A standard digital radiography system (Ysio, Siemens Healthcare, Erlangen, Germany) was compared with a biplanar X-ray unit (EOS, EOS imaging, Paris, France) consisting of two X-ray tubes and slot-scanning detectors, arranged at an angle of 90° allowing simultaneous vertical biplanar linear scanning in the upright patient position. We compared data of standing full-length lower limb radiographs and whole spine radiographs of both X-ray systems. Dose-area product was significantly lower for radiographs of the biplanar X-ray system than for the standard digital radiography system (e.g. whole spine radiographs; standard digital radiography system: 392.2 ± 231.7 cGy*cm(2) versus biplanar X-ray system: 158.4 ± 103.8 cGy*cm(2)). The mean examination time was significantly shorter for biplanar radiographs compared with standard digital radiographs (e.g. whole spine radiographs: 449 s vs 248 s). Patients' comfort regarding noise was significantly higher for the standard digital radiography system. The financial break-even point was 2,602 radiographs/year for the standard digital radiography system compared with 4,077 radiographs/year for the biplanar X-ray unit. The biplanar X-ray unit reduces radiation exposure and increases subjective noise exposure to patients. The biplanar X-ray unit demands a higher number of examinations per year for the financial break-even point, despite the lower labour cost per examination due to the shorter examination time.

Challenges in validating the sterilisation dose for processed human amniotic membranes

NASA Astrophysics Data System (ADS)

Yusof, Norimah; Hassan, Asnah; Firdaus Abd Rahman, M. N.; Hamid, Suzina A.

2007-11-01

Most of the tissue banks in the Asia Pacific region have been using ionising radiation at 25 kGy to sterilise human tissues for save clinical usage. Under tissue banking quality system, any dose employed for sterilisation has to be validated and the validation exercise has to be a part of quality document. Tissue grafts, unlike medical items, are not produced in large number per each processing batch and tissues relatively have a different microbial population. A Code of Practice established by the International Atomic Energy Agency (IAEA) in 2004 offers several validation methods using smaller number of samples compared to ISO 11137 (1995), which is meant for medical products. The methods emphasise on bioburden determination, followed by sterility test on samples after they were exposed to verification dose for attaining of sterility assurance level (SAL) of 10 -1. This paper describes our experience in using the IAEA Code of Practice in conducting the validation exercise for substantiating 25 kGy as sterilisation dose for both air-dried amnion and those preserved in 99% glycerol.

Quality of Intensity Modulated Radiation Therapy Treatment Plans Using a ⁶⁰Co Magnetic Resonance Image Guidance Radiation Therapy System.

PubMed

Wooten, H Omar; Green, Olga; Yang, Min; DeWees, Todd; Kashani, Rojano; Olsen, Jeff; Michalski, Jeff; Yang, Deshan; Tanderup, Kari; Hu, Yanle; Li, H Harold; Mutic, Sasa

2015-07-15

This work describes a commercial treatment planning system, its technical features, and its capabilities for creating (60)Co intensity modulated radiation therapy (IMRT) treatment plans for a magnetic resonance image guidance radiation therapy (MR-IGRT) system. The ViewRay treatment planning system (Oakwood Village, OH) was used to create (60)Co IMRT treatment plans for 33 cancer patients with disease in the abdominal, pelvic, thorax, and head and neck regions using physician-specified patient-specific target coverage and organ at risk (OAR) objectives. Backup plans using a third-party linear accelerator (linac)-based planning system were also created. Plans were evaluated by attending physicians and approved for treatment. The (60)Co and linac plans were compared by evaluating conformity numbers (CN) with 100% and 95% of prescription reference doses and heterogeneity indices (HI) for planning target volumes (PTVs) and maximum, mean, and dose-volume histogram (DVH) values for OARs. All (60)Co IMRT plans achieved PTV coverage and OAR sparing that were similar to linac plans. PTV conformity for (60)Co was within <1% and 3% of linac plans for 100% and 95% prescription reference isodoses, respectively, and heterogeneity was on average 4% greater. Comparisons of OAR mean dose showed generally better sparing with linac plans in the low-dose range <20 Gy, but comparable sparing for organs with mean doses >20 Gy. The mean doses for all (60)Co plan OARs were within clinical tolerances. A commercial (60)Co MR-IGRT device can produce highly conformal IMRT treatment plans similar in quality to linac IMRT for a variety of disease sites. Additional work is in progress to evaluate the clinical benefit of other novel features of this MR-IGRT system. Copyright © 2015 Elsevier Inc. All rights reserved.

Dosimetric impact of a CT metal artefact suppression algorithm for proton, electron and photon therapies

NASA Astrophysics Data System (ADS)

Wei, Jikun; Sandison, George A.; Hsi, Wen-Chien; Ringor, Michael; Lu, Xiaoyi

2006-10-01

Accurate dose calculation is essential to precision radiation treatment planning and this accuracy depends upon anatomic and tissue electron density information. Modern treatment planning inhomogeneity corrections use x-ray CT images and calibrated scales of tissue CT number to electron density to provide this information. The presence of metal in the volume scanned by an x-ray CT scanner causes metal induced image artefacts that influence CT numbers and thereby introduce errors in the radiation dose distribution calculated. This paper investigates the dosimetric improvement achieved by a previously proposed x-ray CT metal artefact suppression technique when the suppressed images of a patient with bilateral hip prostheses are used in commercial treatment planning systems for proton, electron or photon therapies. For all these beam types, this clinical image and treatment planning study reveals that the target may be severely underdosed if a metal artefact-contaminated image is used for dose calculations instead of the artefact suppressed one. Of the three beam types studied, the metal artefact suppression is most important for proton therapy dose calculations, intermediate for electron therapy and least important for x-ray therapy but still significant. The study of a water phantom having a metal rod simulating a hip prosthesis indicates that CT numbers generated after image processing for metal artefact suppression are accurate and thus dose calculations based on the metal artefact suppressed images will be of high fidelity.

Gold-implanted shallow conducting layers in polymethylmethacrylate

NASA Astrophysics Data System (ADS)

Teixeira, F. S.; Salvadori, M. C.; Cattani, M.; Brown, I. G.

2009-03-01

PMMA (polymethylmethacrylate) was ion implanted with gold at very low energy and over a range of different doses using a filtered cathodic arc metal plasma system. A nanometer scale conducting layer was formed, fully buried below the polymer surface at low implantation dose, and evolving to include a gold surface layer as the dose was increased. Depth profiles of the implanted material were calculated using the Dynamic TRIM computer simulation program. The electrical conductivity of the gold-implanted PMMA was measured in situ as a function of dose. Samples formed at a number of different doses were subsequently characterized by Rutherford backscattering spectrometry, and test patterns were formed on the polymer by electron beam lithography. Lithographic patterns were imaged by atomic force microscopy and demonstrated that the contrast properties of the lithography were well maintained in the surface-modified PMMA.

SU-F-BRD-05: Robustness of Dose Painting by Numbers in Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montero, A Barragan; Sterpin, E; Lee, J

Purpose: Proton range uncertainties may cause important dose perturbations within the target volume, especially when steep dose gradients are present as in dose painting. The aim of this study is to assess the robustness against setup and range errors for high heterogeneous dose prescriptions (i.e., dose painting by numbers), delivered by proton pencil beam scanning. Methods: An automatic workflow, based on MATLAB functions, was implemented through scripting in RayStation (RaySearch Laboratories). It performs a gradient-based segmentation of the dose painting volume from 18FDG-PET images (GTVPET), and calculates the dose prescription as a linear function of the FDG-uptake value on eachmore » voxel. The workflow was applied to two patients with head and neck cancer. Robustness against setup and range errors of the conventional PTV margin strategy (prescription dilated by 2.5 mm) versus CTV-based (minimax) robust optimization (2.5 mm setup, 3% range error) was assessed by comparing the prescription with the planned dose for a set of error scenarios. Results: In order to ensure dose coverage above 95% of the prescribed dose in more than 95% of the GTVPET voxels while compensating for the uncertainties, the plans with a PTV generated a high overdose. For the nominal case, up to 35% of the GTVPET received doses 5% beyond prescription. For the worst of the evaluated error scenarios, the volume with 5% overdose increased to 50%. In contrast, for CTV-based plans this 5% overdose was present only in a small fraction of the GTVPET, which ranged from 7% in the nominal case to 15% in the worst of the evaluated scenarios. Conclusion: The use of a PTV leads to non-robust dose distributions with excessive overdose in the painted volume. In contrast, robust optimization yields robust dose distributions with limited overdose. RaySearch Laboratories is sincerely acknowledged for providing us with RayStation treatment planning system and for the support provided.« less

Transferring mixtures of chemicals from sediment to a bioassay using silicone-based passive sampling and dosing.

PubMed

Mustajärvi, Lukas; Eriksson-Wiklund, Ann-Kristin; Gorokhova, Elena; Jahnke, Annika; Sobek, Anna

2017-11-15

Environmental mixtures of chemicals consist of a countless number of compounds with unknown identity and quantity. Yet, chemical regulation is mainly built around the assessment of single chemicals. Existing frameworks for assessing the toxicity of mixtures require that both the chemical composition and quantity are known. Quantitative analyses of the chemical composition of environmental mixtures are however extremely challenging and resource-demanding. Bioassays may therefore serve as a useful approach for investigating the combined toxicity of environmental mixtures of chemicals in a cost-efficient and holistic manner. In this study, an unknown environmental mixture of bioavailable semi-hydrophobic to hydrophobic chemicals was sampled from a contaminated sediment in a coastal Baltic Sea area using silicone polydimethylsiloxane (PDMS) as an equilibrium passive sampler. The chemical mixture was transferred to a PDMS-based passive dosing system, and its applicability was demonstrated using green algae Tetraselmis suecica in a cell viability assay. The proportion of dead cells increased significantly with increasing exposure level and in a dose-response manner. At an ambient concentration, the proportion of dead cells in the population was nearly doubled compared to the control; however, the difference was non-significant due to high inter-replicate variability and a low number of replicates. The validation of the test system regarding equilibrium sampling, loading efficiency into the passive dosing polymer, stability of the mixture composition, and low algal mortality in control treatments demonstrates that combining equilibrium passive sampling and passive dosing is a promising tool for investigating the toxicity of bioavailable semi-hydrophobic and hydrophobic chemicals in complex environmental mixtures.

Image guided IMRT dosimetry using anatomy specific MOSFET configurations

PubMed Central

Norrlinger, Bern; Heaton, Robert; Islam, Mohammad

2008-01-01

We have investigated the feasibility of using a set of multiple MOSFETs in conjunction with the mobileMOSFET wireless dosimetry system, to perform a comprehensive and efficient quality assurance (QA) of IMRT plans. Anatomy specific MOSFET configurations incorporating 5 MOSFETs have been developed for a specially designed IMRT dosimetry phantom. Kilovoltage cone beam computed tomography (kV CBCT) imaging was used to increase the positional precision and accuracy of the detectors and phantom, and so minimize dosimetric uncertainties in high dose gradient regions. The effectiveness of the MOSFET based dose measurements was evaluated by comparing the corresponding doses measured by an ion chamber. For 20 head and neck IMRT plans the agreement between the MOSFET and ionization chamber dose measurements was found to be within −0.26±0.88% and 0.06±1.94% (1σ) for measurement points in the high dose and low dose respectively. A precision of 1 mm in detector positioning was achieved by using the X‐Ray Volume Imaging (XVI) kV CBCT system available with the Elekta Synergy Linear Accelerator. Using the anatomy specific MOSFET configurations, simultaneous measurements were made at five strategically located points covering high dose and low dose regions. The agreement between measurements and calculated doses by the treatment planning system for head and neck and prostate IMRT plans was found to be within 0.47±2.45%. The results indicate that a cylindrical phantom incorporating multiple MOSFET detectors arranged in an anatomy specific configuration, in conjunction with image guidance, can be utilized to perform a comprehensive and efficient quality assurance of IMRT plans. PACS number: 87.55.Qr

[The 308 nm Excimer laser for the treatment of psoriasis and inflammatory skin diseases].

PubMed

Fritz, K; Salavastru, C

2018-01-01

Overall, the 308 nm Excimer laser enables not only a more effective and safer UVB therapy than classical UV phototherapy, but also targeted irradiation in higher doses with a lower cumulative load, which results in faster healing of mainly circumscribed skin changes. This also applies to therapy-resistant residual lesions which, despite systemic therapy, did not diminish. Combination therapies usually improve the result and enable the dose of UVB and systemic medication to be reduced. Excimer laser therapy can be used for an increasing number of skin diseases, especially those that respond to phototherapy or photochemotherapy.

Postconditioning hormesis put in perspective: an overview of experimental and clinical studies.

PubMed

Wiegant, F A C; Prins, H A B; Van Wijk, R

2011-01-01

A beneficial effect of applying mild stress to cells or organisms, that were initially exposed to a high dose of stress, has been referred to as 'postconditioning hormesis'. The initial high dose of stress activates intrinsic self-recovery mechanisms. Modulation of these endogenous adaptation strategies by administration of a subsequent low dose of stress can confer effects that are beneficial to the biological system. Owing to its potentially therapeutic applications, postconditioning hormesis is subject to research in various scientific disciplines. This paper presents an overview of the dynamics of postconditioning hormesis and illustrates this phenomenon with a number of examples in experimental and clinical research.

Contrast-enhanced dual-energy digital subtraction mammography: optimization of the beam energy

NASA Astrophysics Data System (ADS)

Kwan, Alexander L. C.; Boone, John M.; Le-Petross, Huong; Lindfors, Karen K.; Seibert, J. A.; Lewin, John M.

2005-04-01

The implementation of contrast-enhanced dual-energy digital subtraction mammography may lead to better identification of breast tumors, and thus provide a lower cost and more widely available alternative to breast MRI. This technique involves the acquisition of low- and high-energy images after the IV administration of iodinated contrast agent. In this study, the effect of the beam energy (kVp) was examined using the CNR2/dose metric, where CNR is the contrast-to-noise ratio and dose implies the mean glandular dose. The mean glandular dose was calculated using parameterized normalized glandular dose coefficients (DgN), which allowed the computation of the mean glandular dose for the modeled spectra considered in this study, coupled with incident kerma measurements. Optimization studies were performed using a dedicated cone-beam breast CT scanner designed and fabricated in our laboratory, with the system operating in stationary imaging mode. A flat tissue-equivalent phantom (7.5 cm in thickness) was placed at the isocenter of the scanner, and an air gap of 34.5 cm was used in lieu of a grid. Dilute iodine-based contrast agent was introduced into the phantoms using plastic vials. Data were acquired from 40 to 90 kVp at 10 kVp intervals. Due to the low mA available on the breast CT system, a large number of images (1000) were acquired in fluoroscopic mode, which allowed us to match the dose and noise properties for each kVp combinations by changing the number of images used for averaging. Preliminary results demonstrate that the best CNR2/dose is achieved with a 50 kVp low-energy image and a 90 kVp high-energy image. Consequently, radiation doses for contrast-enhanced mammography should be far lower than regular mammography. Since the spatial resolution requirements should also be lower than regular mammography, dual-energy contrast-enhanced mammography, when performed using the optimal technique factor, may indeed provide very similar diagnostic information as breast MRI but at significantly reduced costs.

Dose Calculation on KV Cone Beam CT Images: An Investigation of the Hu-Density Conversion Stability and Dose Accuracy Using the Site-Specific Calibration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rong Yi, E-mail: rong@humonc.wisc.ed; Smilowitz, Jennifer; Tewatia, Dinesh

2010-10-01

Precise calibration of Hounsfield units (HU) to electron density (HU-density) is essential to dose calculation. On-board kV cone beam computed tomography (CBCT) imaging is used predominantly for patients' positioning, but will potentially be used for dose calculation. The impacts of varying 3 imaging parameters (mAs, source-imager distance [SID], and cone angle) and phantom size on the HU number accuracy and HU-density calibrations for CBCT imaging were studied. We proposed a site-specific calibration method to achieve higher accuracy in CBCT image-based dose calculation. Three configurations of the Computerized Imaging Reference Systems (CIRS) water equivalent electron density phantom were used to simulatemore » sites including head, lungs, and lower body (abdomen/pelvis). The planning computed tomography (CT) scan was used as the baseline for comparisons. CBCT scans of these phantom configurations were performed using Varian Trilogy{sup TM} system in a precalibrated mode with fixed tube voltage (125 kVp), but varied mAs, SID, and cone angle. An HU-density curve was generated and evaluated for each set of scan parameters. Three HU-density tables generated using different phantom configurations with the same imaging parameter settings were selected for dose calculation on CBCT images for an accuracy comparison. Changing mAs or SID had small impact on HU numbers. For adipose tissue, the HU discrepancy from the baseline was 20 HU in a small phantom, but 5 times lager in a large phantom. Yet, reducing the cone angle significantly decreases the HU discrepancy. The HU-density table was also affected accordingly. By performing dose comparison between CT and CBCT image-based plans, results showed that using the site-specific HU-density tables to calibrate CBCT images of different sites improves the dose accuracy to {approx}2%. Our phantom study showed that CBCT imaging can be a feasible option for dose computation in adaptive radiotherapy approach if the site-specific calibration is applied.« less

Iterative methods for dose reduction and image enhancement in tomography

DOEpatents

Miao, Jianwei; Fahimian, Benjamin Pooya

2012-09-18

A system and method for creating a three dimensional cross sectional image of an object by the reconstruction of its projections that have been iteratively refined through modification in object space and Fourier space is disclosed. The invention provides systems and methods for use with any tomographic imaging system that reconstructs an object from its projections. In one embodiment, the invention presents a method to eliminate interpolations present in conventional tomography. The method has been experimentally shown to provide higher resolution and improved image quality parameters over existing approaches. A primary benefit of the method is radiation dose reduction since the invention can produce an image of a desired quality with a fewer number projections than seen with conventional methods.

Seasonal regulation of condensed tannin consumption by free-ranging goats in a semi-arid savanna

PubMed Central

Heitkӧnig, Ignas M. A.; Scogings, Peter F.; Hattas, Dawood; Dziba, Luthando E.; Prins, Herbert H. T.; de Boer, Willem F.

2018-01-01

Although condensed tannins (CTs) are known to reduce forage intake by mammalian herbivores in controlled experiments, few studies have tested these effects in the field. Thus the role of CTs on foraging ecology of free-ranging herbivores is inadequately understood. To investigate the effects of CTs under natural savanna conditions, we pre-dosed groups of goats with polyethylene glycol (PEG, a CT-neutralising chemical), CT powder or water before observing their foraging behaviour. While accounting for the effects of season and time of the day, we tested the hypothesis that herbivores forage in ways that reduce the intake rate (g DM per minute) of CTs. We expected pre-dosing goats with CTs to reduce CT intake rates by (1) consuming diets low in CTs, (2) reducing bite rates, (3) increasing the number of foraging bouts, or (4) reducing the length of foraging bouts. Lastly, (5) expected CT to have no influence the number of dietary forage species. In both wet and dry seasons, pre-dosing goats with CTs resulted in lower CT consumption rates compared to PEG goats which seemed relieved from the stress associated with CT consumption. During dry season, the number of dietary forage species was similar across treatments, although goats that were dosed with PEG significantly increased this number in the wet season. Dosing goats with PEG increased the number and length of browsing bouts compared to goats from the other treatments. Pre-loading goats with PEG also tended to increase bite rates on browse forages, which contributed to increased consumption rates of CTs. Based on the behavioural adjustments made by goats in this study and within the constraints imposed by chemical complexity in savanna systems, we concluded that herbivores under natural conditions foraged in ways that minimised CTs consumption. More research should further elucidate the mechanism through which CTs regulated feeding behaviour. PMID:29293513

A GPU-accelerated and Monte Carlo-based intensity modulated proton therapy optimization system.

PubMed

Ma, Jiasen; Beltran, Chris; Seum Wan Chan Tseung, Hok; Herman, Michael G

2014-12-01

Conventional spot scanning intensity modulated proton therapy (IMPT) treatment planning systems (TPSs) optimize proton spot weights based on analytical dose calculations. These analytical dose calculations have been shown to have severe limitations in heterogeneous materials. Monte Carlo (MC) methods do not have these limitations; however, MC-based systems have been of limited clinical use due to the large number of beam spots in IMPT and the extremely long calculation time of traditional MC techniques. In this work, the authors present a clinically applicable IMPT TPS that utilizes a very fast MC calculation. An in-house graphics processing unit (GPU)-based MC dose calculation engine was employed to generate the dose influence map for each proton spot. With the MC generated influence map, a modified least-squares optimization method was used to achieve the desired dose volume histograms (DVHs). The intrinsic CT image resolution was adopted for voxelization in simulation and optimization to preserve spatial resolution. The optimizations were computed on a multi-GPU framework to mitigate the memory limitation issues for the large dose influence maps that resulted from maintaining the intrinsic CT resolution. The effects of tail cutoff and starting condition were studied and minimized in this work. For relatively large and complex three-field head and neck cases, i.e., >100,000 spots with a target volume of ∼ 1000 cm(3) and multiple surrounding critical structures, the optimization together with the initial MC dose influence map calculation was done in a clinically viable time frame (less than 30 min) on a GPU cluster consisting of 24 Nvidia GeForce GTX Titan cards. The in-house MC TPS plans were comparable to a commercial TPS plans based on DVH comparisons. A MC-based treatment planning system was developed. The treatment planning can be performed in a clinically viable time frame on a hardware system costing around 45,000 dollars. The fast calculation and optimization make the system easily expandable to robust and multicriteria optimization.

Optimization-based image reconstruction from sparse-view data in offset-detector CBCT

NASA Astrophysics Data System (ADS)

Bian, Junguo; Wang, Jiong; Han, Xiao; Sidky, Emil Y.; Shao, Lingxiong; Pan, Xiaochuan

2013-01-01

The field of view (FOV) of a cone-beam computed tomography (CBCT) unit in a single-photon emission computed tomography (SPECT)/CBCT system can be increased by offsetting the CBCT detector. Analytic-based algorithms have been developed for image reconstruction from data collected at a large number of densely sampled views in offset-detector CBCT. However, the radiation dose involved in a large number of projections can be of a health concern to the imaged subject. CBCT-imaging dose can be reduced by lowering the number of projections. As analytic-based algorithms are unlikely to reconstruct accurate images from sparse-view data, we investigate and characterize in the work optimization-based algorithms, including an adaptive steepest descent-weighted projection onto convex sets (ASD-WPOCS) algorithms, for image reconstruction from sparse-view data collected in offset-detector CBCT. Using simulated data and real data collected from a physical pelvis phantom and patient, we verify and characterize properties of the algorithms under study. Results of our study suggest that optimization-based algorithms such as ASD-WPOCS may be developed for yielding images of potential utility from a number of projections substantially smaller than those used currently in clinical SPECT/CBCT imaging, thus leading to a dose reduction in CBCT imaging.

SU-E-T-495: Neutron Induced Electronics Failure Rate Analysis for a Single Room Proton Accelerator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knutson, N; DeWees, T; Klein, E

2014-06-01

Purpose: To determine the failure rate as a function of neutron dose of the range modulator's servo motor controller system (SMCS) while shielded with Borated Polyethylene (BPE) and unshielded in a single room proton accelerator. Methods: Two experimental setups were constructed using two servo motor controllers and two motors. Each SMCS was then placed 30 cm from the end of the plugged proton accelerator applicator. The motor was then turned on and observed from outside of the vault while being irradiated to known neutron doses determined from bubble detector measurements. Anytime the motor deviated from the programmed motion a failuremore » was recorded along with the delivered dose. The experiment was repeated using 9 cm of BPE shielding surrounding the SMCS. Results: Ten SMCS failures were recorded in each experiment. The dose per monitor unit for the unshielded SMCS was 0.0211 mSv/MU and 0.0144 mSv/MU for the shielded SMCS. The mean dose to produce a failure for the unshielded SMCS was 63.5 ± 58.3 mSv versus 17.0 ±12.2 mSv for the shielded. The mean number of MUs between failures were 2297 ± 1891 MU for the unshielded SMCS and 2122 ± 1523 MU for the shielded. A Wilcoxon Signed Ranked test showed the dose between failures were significantly different (P value = 0.044) while the number of MUs between failures were not (P value = 1.000). Statistical analysis determined a SMCS neutron dose of 5.3 mSv produces a 5% chance of failure. Depending on the workload and location of the SMCS, this failure rate could impede clinical workflow. Conclusion: BPE shielding was shown to not reduce the average failure of the SMCS and relocation of the system outside of the accelerator vault was required to lower the failure rate enough to avoid impeding clinical work flow.« less

Triple dose of gadolinium-DTPA and delayed MRI in patients with benign multiple sclerosis.

PubMed Central

Filippi, M; Capra, R; Campi, A; Colombo, B; Prandini, F; Marcianò, N; Gasparotti, R; Comi, G

1996-01-01

OBJECTIVES--To evaluate whether a triple dose of gadolinium-DTPA (Gd-DTPA) or delayed MRI increase the number, size, and conspicuousness of enhancing lesions in patients with benign multiple sclerosis. METHODS--T1 weighted brain MRI was carried out on 20 patients with benign multiple sclerosis (expanded disability status scale < 3 with a disease duration > 10 years) in two sessions. In the first session, one scan was obtained before and two scans five to seven minutes and 20-30 minutes after the injection of 0.1 mmol/kg Gd-DTPA (standard dose). In the second session, six to 24 hours later, the same procedure was repeated with 0.3 mmol/kg Gd-DTPA (triple dose). RESULTS--Nine enhancing lesions were found in seven patients (35%) using the standard dose of Gd-DTPA. The numbers of enhancing lesions increased to 13 (P = 0.03) and the number of patients with such lesions to eight (40%) on the delayed standard dose scans. On the early triple dose scans, we found 19 enhancing lesions in 10 patients (50%). The number of enhancing lesions was significantly higher (P = 0.01) than that obtained with the early standard dose. The number of enhancing lesions was 18 and the number of "active" patients 11 (55%) on the delayed triple dose scans. The enhancing areas increased progressively from the early standard dose scans to the delayed triple dose scans. The contrast ratios of the lesions detected in early standard dose scans was lower than those of lesions present in the early (P = 0.01) and delayed (P = 0.04) triple dose scans. CONCLUSIONS--More enhancing lesions were detected in patients with benign multiple sclerosis with both delay of MRI and the use of triple dose of Gd-DTPA suggesting that the amount of inflammation in the lesions of such patients is mild and heterogeneous. Images PMID:8778257

Fipronil promotes motor and behavioral changes in honey bees (Apis mellifera) and affects the development of colonies exposed to sublethal doses.

PubMed

Zaluski, Rodrigo; Kadri, Samir Moura; Alonso, Diego Peres; Martins Ribolla, Paulo Eduardo; de Oliveira Orsi, Ricardo

2015-05-01

Bees play a crucial role in pollination and generate honey and other hive products; therefore, their worldwide decline is cause for concern. New broad-spectrum systemic insecticides such as fipronil can harm bees and their use has been discussed as a potential threat to bees' survival. In the present study, the authors evaluate the in vitro toxicity of fipronil and note behavioral and motor activity changes in Africanized adult Apis mellifera that ingest or come into contact with lethal or sublethal doses of fipronil. The effects of sublethal doses on brood viability, population growth, behavior, and the expression of the defensin 1 gene in adult bees were studied in colonies fed with contaminated sugar syrup (8 µg fipronil L(-1) ). Fipronil is highly toxic to bees triggering agitation, seizures, tremors, and paralysis. Bees that are exposed to a lethal or sublethal doses showed reduced motor activity. The number of eggs that hatched, the area occupied by worker eggs, and the number of larvae and pupae that developed were reduced, adult bees showed lethargy, and colonies were abandoned when they were exposed to sublethal doses of fipronil. No change was seen in the bees' expression of defensin 1. The authors conclude that fipronil is highly toxic to honey bees and even sublethal doses may negatively affect the development and maintenance of colonies. © 2015 SETAC.

Commissioning and quality assurance for the treatment delivery components of the AccuBoost system

PubMed Central

Talmadge, Mike; Ladd, Ron; Halvorsen, Per

2015-01-01

The objective for this work was to develop a commissioning methodology for the treatment delivery components of the AccuBoost system, as well as to establish a routine quality assurance program and appropriate guidance for clinical use based on the commissioning results. Various tests were developed: 1) assessment of the accuracy of the displayed separation value; 2) validation of the dwell positions within each applicator; 3) assessment of the accuracy and precision of the applicator localization system; 4) assessment of the combined dose profile of two opposed applicators to confirm that they are coaxial; 5) measurement of the absolute dose delivered with each applicator to confirm acceptable agreement with dose based on Monte Carlo modeling; 6) measurements of the skin‐to‐center dose ratio using optically stimulated luminescence dosimeters; and 7) assessment of the mammopad cushion's effect on the center dose. We found that the difference between the measured and the actual paddle separation is <0.1 cm for the separation range of 3 cm to 7.5 cm. Radiochromic film measurements demonstrated that the number of dwell positions inside the applicators agree with the values from the vendor, for each applicator type and size. The shift needed for a good applicator‐grid alignment was within 0.2 cm. The dry‐run test using film demonstrated that the shift of the dosimetric center is within 0.15 cm. Dose measurements in water converted to polystyrene agreed within 5.0% with the Monte Carlo data in polystyrene for the same applicator type, size, and depth. A solid water‐to‐water (phantom) factor was obtained for each applicator, and all future annual quality assurance tests will be performed in solid water using an average value of 1.07 for the solid water‐to‐water factor. The skin‐to‐center dose ratio measurements support the Monte Carlo‐based values within 5.0% agreement. For the treatment separation range of 4 cm to 8 cm, the change in center dose would be <1.0% for all applicators when using a compressed pad of 0.2 cm to 0.3 cm. The tests performed ensured that all treatment components of the AccuBoost system are functional and that a treatment plan can be delivered with acceptable accuracy. Based on the commissioning results, a quality assurance manual and guidance documents for clinical use were developed. PACS numbers: 87.55.Qr, 87.56.Da, 87.90.+y PMID:26103184

Characterization of an in vivo diode dosimetry system for clinical use

PubMed Central

Huang, Kai; Bice, William S.; Hidalgo‐Salvatierra, Oscar

2003-01-01

An in vivo dosimetry system that uses p‐type semiconductor diodes with buildup caps was characterized for clinical use on accelerators ranging in energy from 4 to 18 MV. The dose per pulse dependence was investigated. This was done by altering the source‐surface distance, field size, and wedge for photons. The off‐axis correction and effect of changing repetition rate were also investigated. A model was developed to fit the measured two‐dimensional diode correction factors. PACS number(s): 87.66.–a, 87.52.–g PMID:12777148

Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

PubMed

Jackson, Daniel J; Bacharier, Leonard B; Mauger, David T; Boehmer, Susan; Beigelman, Avraham; Chmiel, James F; Fitzpatrick, Anne M; Gaffin, Jonathan M; Morgan, Wayne J; Peters, Stephen P; Phipatanakul, Wanda; Sheehan, William J; Cabana, Michael D; Holguin, Fernando; Martinez, Fernando D; Pongracic, Jacqueline A; Baxi, Sachin N; Benson, Mindy; Blake, Kathryn; Covar, Ronina; Gentile, Deborah A; Israel, Elliot; Krishnan, Jerry A; Kumar, Harsha V; Lang, Jason E; Lazarus, Stephen C; Lima, John J; Long, Dayna; Ly, Ngoc; Marbin, Jyothi; Moy, James N; Myers, Ross E; Olin, J Tod; Raissy, Hengameh H; Robison, Rachel G; Ross, Kristie; Sorkness, Christine A; Lemanske, Robert F

2018-03-08

Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06). In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129 .).

A methodology for on‐board CBCT imaging dose using optically stimulated luminescence detectors

PubMed Central

Yusuf, Muhammad; Alothmany, Nazeeh; Kinsara, A. Abdulrahman; Abdulkhaliq, Fahad; Ghamdi, Suliman M.; Saoudi, Abdelhamid

2016-01-01

Cone‐beam computed tomography CBCT systems are used in radiation therapy for patient alignment and positioning. The CBCT imaging procedure for patient setup adds substantial radiation dose to patient's normal tissue. This study presents a complete procedure for the CBCT dosimetry using the InLight optically‐stimulated‐luminescence (OSL) nanoDots. We report five dose parameters: the mean slice dose (DMSD); the cone beam dose index (CBDIW); the mean volume dose (DMVD); point‐dose profile, D(FOV); and the off‐field Dose. In addition, CBCT skin doses for seven pelvic tumor patients are reported. CBCT‐dose measurement was performed on a custom‐made cylindrical acrylic body phantom (50 cm length, 32 cm diameter). We machined 25 circular disks (2 cm thick) with grooves and holes to hold OSL‐nanoDots. OSLs that showed similar sensitivities were selected and calibrated against a Farmer‐type ionization‐chamber (0.6 CT) before being inserted into the grooves and holes. For the phantom scan, a standard CBCT‐imaging protocol (pelvic sites: 125 kVp, 80 mA and 25 ms) was used. Five dose parameters were quantified: DMSD, CBDIW, DMVD, D(FOV), and the off‐field dose. The DMSD for the central slice was 31.1±0.85 mGy, and CBDIW was 34.5±0.6 mGy at 16 cm FOV. The DMVD was 25.6±1.1 mGy. The off‐field dose was 10.5 mGy. For patients, the anterior and lateral skin doses attributable to CBCT imaging were 39.04±4.4 and 27.1±1.3 mGy, respectively. OSL nanoDots were convenient to use in measuring CBCT dose. The method of selecting the nanoDots greatly reduced uncertainty in the OSL measurements. Our detailed calibration procedure and CBCT dose measurements and calculations could prove useful in developing OSL routines for CBCT quality assessment, which in turn gives them the property of high spatial resolution, meaning that they have the potential for measurement of dose in regions of severe dose‐gradients. PACS number(s): 87.57.‐s, 87.57.Q, 87.57.uq PMID:27685143

Dose measurements in intraoral radiography using thermoluminescent dosimeters

NASA Astrophysics Data System (ADS)

Azorín, C.; Azorín, J.; Aguirre, F.; Rivera, T.

2015-01-01

The use of X-ray in medicine demands to expose the patient and the professional to the lowest radiation doses available in agreement with ALARA philosophy. The reference level for intraoral dental radiography is 7 mGy and, in Mexico, a number of examinations of this type are performed annually. It is considered that approximately 25% of all the X-rays examinations carried out in our country correspond to intraoral radiographies. In other hand, most of the intraoral X-ray equipment correspond to conventional radiological systems using film, which are developed as much manual as automatically. In this work the results of determining the doses received by the patients in intraoral radiological examinations made with different radiological systems using LiF:Mg,Cu,P+PTFE thermoluminescent dosimeters are presented. In some conventional radiological systems using film, when films are developed manual or automatically, incident kerma up to 10.61 ± 0.74 mGv were determined. These values exceed that reference level suggested by the IAEA and in the Mexican standards for intraoral examinations.

Multiscale benchmarking of drug delivery vectors.

PubMed

Summers, Huw D; Ware, Matthew J; Majithia, Ravish; Meissner, Kenith E; Godin, Biana; Rees, Paul

2016-10-01

Cross-system comparisons of drug delivery vectors are essential to ensure optimal design. An in-vitro experimental protocol is presented that separates the role of the delivery vector from that of its cargo in determining the cell response, thus allowing quantitative comparison of different systems. The technique is validated through benchmarking of the dose-response of human fibroblast cells exposed to the cationic molecule, polyethylene imine (PEI); delivered as a free molecule and as a cargo on the surface of CdSe nanoparticles and Silica microparticles. The exposure metrics are converted to a delivered dose with the transport properties of the different scale systems characterized by a delivery time, τ. The benchmarking highlights an agglomeration of the free PEI molecules into micron sized clusters and identifies the metric determining cell death as the total number of PEI molecules presented to cells, determined by the delivery vector dose and the surface density of the cargo. Copyright © 2016 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fox, Donald A., E-mail: dafox@uh.edu; Department of Biology and Biochemistry, University of Houston, Houston, TX; Department of Pharmacology and Pharmaceutical Sciences, University of Houston, Houston, TX

Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was {<=} 1,more » {<=} 10, {approx} 25 and {approx} 40 {mu}g/dL, respectively, on PN10 and by PN30 all were {<=} 1 {mu}g/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity. -- Highlights: Black-Right-Pointing-Pointer Peak [BPb] in control, low-, moderate- and high-dose newborn mice with gestational lead exposure: {<=} 1, {<=} 10, 25 and 40 {mu}g/dL Black-Right-Pointing-Pointer Gestational lead exposure dose-dependently decreased the number of TH-immunoreactive dopaminergic amacrine cells Black-Right-Pointing-Pointer Gestational lead exposure selectively decreased dopaminergic, but not GABAergic, glycinergic or cholinergic, amacrine cells Black-Right-Pointing-Pointer Gestational lead exposure dose-dependently decreased retinal dopamine content, its metabolites and dopamine utilization Black-Right-Pointing-Pointer A decrease in dopamine can alter ERG amplitudes, circadian rhythms, dark/light adaptation and spatial contrast sensitivity.« less

The effect of high concentrations of glufosinate ammonium on the yield components of transgenic spring wheat (Triticum aestivum L.) constitutively expressing the bar gene.

PubMed

Áy, Zoltán; Mihály, Róbert; Cserháti, Mátyás; Kótai, Éva; Pauk, János

2012-01-01

We present an experiment done on a bar(+) wheat line treated with 14 different concentrations of glufosinate ammonium-an effective component of nonselective herbicides-during seed germination in a closed experimental system. Yield components as number of spikes per plant, number of grains per spike, thousand kernel weight, and yield per plant were thoroughly analysed and statistically evaluated after harvesting. We found that a concentration of glufosinate ammonium 5000 times the lethal dose was not enough to inhibit the germination of transgenic plants expressing the bar gene. Extremely high concentrations of glufosinate ammonium caused a bushy phenotype, significantly lower numbers of grains per spike, and thousand kernel weights. Concerning the productivity, we observed that concentrations of glufosinate ammonium 64 times the lethal dose did not lead to yield depression. Our results draw attention to the possibilities implied in the transgenic approaches.

Skin dose mapping for fluoroscopically guided interventions.

PubMed

Johnson, Perry B; Borrego, David; Balter, Stephen; Johnson, Kevin; Siragusa, Daniel; Bolch, Wesley E

2011-10-01

To introduce a new skin dose mapping software system for interventional fluoroscopy dose assessment and to analyze the benefits and limitations of patient-phantom matching. In this study, a new software system was developed for visualizing patient skin dose during interventional fluoroscopy procedures. The system works by translating the reference point air kerma to the location of the patient's skin, which is represented by a computational model. In order to orient the model with the x-ray source, geometric parameters found within the radiation dose structured report (RDSR) are used along with a limited number of in-clinic measurements. The output of the system is a visual indication of skin dose mapped onto an anthropomorphic model at a resolution of 5 mm. In order to determine if patient-dependent and patient-sculpted models increase accuracy, peak skin dose was calculated for each of 26 patient-specific models and compared with doses calculated using an elliptical stylized model, a reference hybrid model, a matched patient-dependent model and one patient-sculpted model. Results were analyzed in terms of a percent difference using the doses calculated using the patient-specific model as the true standard. Anthropometric matching, including the use of both patient-dependent and patient-sculpted phantoms, was shown most beneficial for left lateral and anterior-posterior projections. In these cases, the percent difference using a reference model was between 8 and 20%, using a patient-dependent model between 7 and 15%, and using a patient-sculpted model between 3 and 7%. Under the table tube configurations produced errors less than 5% in most situations due to the flattening affects of the table and pad, and the fact that table height is the main determination of source-to-skin distance for these configurations. In addition to these results, several skin dose maps were produced and a prototype display system was placed on the in-clinic monitor of an interventional fluoroscopy system. The skin dose mapping program developed in this work represents a new tool that, as the RDSR becomes available through automated export or real-time streaming, can provide the interventional physician information needed to modify behavior when clinically appropriate. The program is nonproprietary and transferable, and also functions independent to the software systems already installed on the control room workstation. The next step will be clinical implementation where the workflow will be optimized along with further analysis of real-time capabilities.

A general model for stray dose calculation of static and intensity-modulated photon radiation.

PubMed

Hauri, Pascal; Hälg, Roger A; Besserer, Jürgen; Schneider, Uwe

2016-04-01

There is an increasing number of cancer survivors who are at risk of developing late effects caused by ionizing radiation such as induction of second tumors. Hence, the determination of out-of-field dose for a particular treatment plan in the patient's anatomy is of great importance. The purpose of this study was to analytically model the stray dose according to its three major components. For patient scatter, a mechanistic model was developed. For collimator scatter and head leakage, an empirical approach was used. The models utilize a nominal beam energy of 6 MeV to describe two linear accelerator types of a single vendor. The parameters of the models were adjusted using ionization chamber measurements registering total absorbed dose in simple geometries. Whole-body dose measurements using thermoluminescent dosimeters in an anthropomorphic phantom for static and intensity-modulated treatment plans were compared to the 3D out-of-field dose distributions calculated by a combined model. The absolute mean difference between the whole-body predicted and the measured out-of-field dose of four different plans was 11% with a maximum difference below 44%. Computation time of 36 000 dose points for one field was around 30 s. By combining the model-calculated stray dose with the treatment planning system dose, the whole-body dose distribution can be viewed in the treatment planning system. The results suggest that the model is accurate, fast and can be used for a wide range of treatment modalities to calculate the whole-body dose distribution for clinical analysis. For similar energy spectra, the mechanistic patient scatter model can be used independently of treatment machine or beam orientation.

Aluminum/vacuum multilayer configuration for spatial high-energy electron shielding via electron return effects induced by magnetic field.

PubMed

Chen, Tuo; Tang, Xiaobin; Chen, Feida; Ni, Minxuan; Huang, Hai; Zhang, Yun; Chen, Da

2017-06-26

Radiation shielding of high-energy electrons is critical for successful space missions. However, conventional passive shielding systems exhibit several limitations, such as heavy configuration, poor shielding ability, and strong secondary bremsstrahlung radiation. In this work, an aluminum/vacuum multilayer structure was proposed based on the electron return effects induced by magnetic field. The shielding property of several configurations was evaluated by using the Monte Carlo method. Results showed that multilayer systems presented improved shielding ability to electrons, and less secondary x-ray transmissions than those of conventional systems. Moreover, the influences of magnetic flux density and number of layers on the shielding property of multilayer systems were investigated using a female Chinese hybrid reference phantom based on cumulative dose. In the case of two aluminum layers, the cumulative dose in a phantom gradually decreased with increasing magnetic flux density. The maximum decline rate was found within 0.4-1 Tesla. With increasing layers of configuration, the cumulative dose decreased and the shielding ability improved. This research provides effective shielding measures for future space radiation protection in high-energy electron environments.

SU-D-BRC-03: Development and Validation of an Online 2D Dose Verification System for Daily Patient Plan Delivery Accuracy Check

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, J; Hu, W; Xing, Y

Purpose: All plan verification systems for particle therapy are designed to do plan verification before treatment. However, the actual dose distributions during patient treatment are not known. This study develops an online 2D dose verification tool to check the daily dose delivery accuracy. Methods: A Siemens particle treatment system with a modulated scanning spot beam is used in our center. In order to do online dose verification, we made a program to reconstruct the delivered 2D dose distributions based on the daily treatment log files and depth dose distributions. In the log files we can get the focus size, positionmore » and particle number for each spot. A gamma analysis is used to compare the reconstructed dose distributions with the dose distributions from the TPS to assess the daily dose delivery accuracy. To verify the dose reconstruction algorithm, we compared the reconstructed dose distributions to dose distributions measured using PTW 729XDR ion chamber matrix for 13 real patient plans. Then we analyzed 100 treatment beams (58 carbon and 42 proton) for prostate, lung, ACC, NPC and chordoma patients. Results: For algorithm verification, the gamma passing rate was 97.95% for the 3%/3mm and 92.36% for the 2%/2mm criteria. For patient treatment analysis,the results were 97.7%±1.1% and 91.7%±2.5% for carbon and 89.9%±4.8% and 79.7%±7.7% for proton using 3%/3mm and 2%/2mm criteria, respectively. The reason for the lower passing rate for the proton beam is that the focus size deviations were larger than for the carbon beam. The average focus size deviations were −14.27% and −6.73% for proton and −5.26% and −0.93% for carbon in the x and y direction respectively. Conclusion: The verification software meets our requirements to check for daily dose delivery discrepancies. Such tools can enhance the current treatment plan and delivery verification processes and improve safety of clinical treatments.« less

Radiation exposure of the radiologist's eye lens during CT-guided interventions.

PubMed

Heusch, Philipp; Kröpil, Patric; Buchbender, Christian; Aissa, Joel; Lanzman, Rotem S; Heusner, Till A; Ewen, Klaus; Antoch, Gerald; Fürst, Günther

2014-02-01

In the past decade the number of computed tomography (CT)-guided procedures performed by interventional radiologists have increased, leading to a significantly higher radiation exposure of the interventionalist's eye lens. Because of growing concern that there is a stochastic effect for the development of lens opacification, eye lens dose reduction for operators and patients should be of maximal interest. To determine the interventionalist's equivalent eye lens dose during CT-guided interventions and to relate the results to the maximum of the recommended equivalent dose limit. During 89 CT-guided interventions (e.g. biopsies, drainage procedures, etc.) measurements of eye lens' radiation doses were obtained from a dedicated dosimeter system for scattered radiation. The sensor of the personal dosimeter system was clipped onto the side of the lead glasses which was located nearest to the CT gantry. After the procedure, radiation dose (µSv), dose rate (µSv/min) and the total exposure time (s) were recorded. For all 89 interventions, the median total exposure lens dose was 3.3 µSv (range, 0.03-218.9 µSv) for a median exposure time of 26.2 s (range, 1.1-94.0 s). The median dose rate was 13.9 µSv/min (range, 1.1-335.5 µSv/min). Estimating 50-200 CT-guided interventions per year performed by one interventionalist, the median dose of the eye lens of the interventional radiologist does not exceed the maximum of the ICRP-recommended equivalent eye lens dose limit of 20 mSv per year.

Effect of Edge-Preserving Adaptive Image Filter on Low-Contrast Detectability in CT Systems: Application of ROC Analysis

PubMed Central

Okumura, Miwa; Ota, Takamasa; Kainuma, Kazuhisa; Sayre, James W.; McNitt-Gray, Michael; Katada, Kazuhiro

2008-01-01

Objective. For the multislice CT (MSCT) systems with a larger number of detector rows, it is essential to employ dose-reduction techniques. As reported in previous studies, edge-preserving adaptive image filters, which selectively eliminate only the noise elements that are increased when the radiation dose is reduced without affecting the sharpness of images, have been developed. In the present study, we employed receiver operating characteristic (ROC) analysis to assess the effects of the quantum denoising system (QDS), which is an edge-preserving adaptive filter that we have developed, on low-contrast resolution, and to evaluate to what degree the radiation dose can be reduced while maintaining acceptable low-contrast resolution. Materials and Methods. The low-contrast phantoms (Catphan 412) were scanned at various tube current settings, and ROC analysis was then performed for the groups of images obtained with/without the use of QDS at each tube current to determine whether or not a target could be identified. The tube current settings for which the area under the ROC curve (Az value) was approximately 0.7 were determined for both groups of images with/without the use of QDS. Then, the radiation dose reduction ratio when QDS was used was calculated by converting the determined tube current to the radiation dose. Results. The use of the QDS edge-preserving adaptive image filter allowed the radiation dose to be reduced by up to 38%. Conclusion. The QDS was found to be useful for reducing the radiation dose without affecting the low-contrast resolution in MSCT studies. PMID:19043565

Helium trapping in aluminium near the critical dose on blister formation

NASA Astrophysics Data System (ADS)

Fukahori, T.; Kanda, Y.; Mori, K.; Tobimatsu, H.

1985-08-01

Blistering and flaking caused by energetic He ions emitted from the plasma in fusion reactors possibly contribute to first-wall erosion. In order to study their characteristics, the numbers of He atoms trapped in He-ion-irradiated Al samples have been measured by a He atom measurement system and every sample has been observed by a scanning electron microscope. The samples have been prepared from a polycrystalline plate and irradiated with 20 keV He ions at room temperature. The saw-tooth like variation of the trapped He atoms with the dose has three edges corresponding to the blistering, flaking and double flaking, respectively. The critical doses for the three events are found to be 4 × 10 21, 7 × 10 21, 12 × 10 21 He atoms m -2, respectively. The average number of He atoms included in an event is 5.4 × 10 10 He atoms in the case of the blistering and 2.1 × 10 11 He atoms in the case of flaking.

TU-AB-201-04: Optimizing the Number of Catheter Implants and Their Tracks for Prostate HDR Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riofrio, D; Luan, S; Zhou, J

Purpose: In prostate HDR brachytherapy, interstitial implants are placed manually on the fly. The aim for this research is to develop a computer algorithm to find optimal and reliable implant trajectories using minimal number of implants. Methods: Our new algorithm mainly uses these key ideas: (1) positive charged static particles are uniformly placed on the surface of prostate and critical structures such as urethra, bladder, and rectum. (2) Positive charged kinetic particles are placed at a cross-section of the prostate with an initial velocity parallel to the principal implant direction. (3) The kinetic particles move through the prostate, interacting withmore » each other, spreading out, while staying away from the prostate surface and critical structures. The initial velocity ensures that the trajectories observe the curvature constraints of typical implant procedures. (4) The finial trajectories of kinetic particles are smoothed using a third-degree polynomial regression, which become the implant trajectories. (5) The dwelling times and final dose distribution are calculated using least-distance programming. Results: (1) We experimented with previously treated cases. Our plan achieves all prescription goals while reducing the number of implants by 41%! Our plan also has less uniform target dose, which implies a higher dose is delivered to the prostate. (2) We expect future implant procedures will be performed under the guidance of such pre-calculated trajectories. To assess the applicability, we randomly perturb the tracks to mimic the manual implant errors. Our studies showed the impact of these perturbations are negligible, which is compensated by the least distance programming. Conclusions: We developed a new inverse planning system for prostate HDR therapy that can find optimal implant trajectories while minimizing the number of implants. For future work, we plan to integrate our new inverse planning system with an existing needle tracking system.« less

Effects of β-blockers and anxiety on complication rates after acute myocardial infarction.

PubMed

Abu Ruz, Mohannad E; Lennie, Terry A; Moser, Debra K

2011-01-01

Anxiety is common after acute myocardial infarction and increases the number of complications and the length of stay in the hospital. Anxiety-induced activation of the sympathetic nervous system is hypothesized to be an underlying cause of increased complication rates. Little is known about whether use of β-blockers eliminates the effects of anxiety on complication rate and length of stay. To compare number of complications and length of stay among nonanxious and anxious patients receiving β-blockers during hospitalization. A total of 322 patients with acute myocardial infarction participated in this study within 48 hours of hospital admission. Patients completed the Brief Symptom Inventory to assess anxiety level. After discharge, medical records were reviewed to determine use of β-blockers, type and number of complications, and length of stay. Most patients (96%) were treated with less than 200 mg daily of metoprolol. Anxious patients had more complications (mean [SD], 1.43 [0.15] vs 0.73 [.09], P ≤ .01) and longer stays (7.0 [0.49] vs 5.7 [0.36] days, P < .05) than did nonanxious patients. To test whether the dose of β-blocker made a difference, the interaction between daily dose and anxiety score was tested. No interaction was found between metoprolol dose and anxiety score, and no main effect was found for metoprolol dose. Anxious patients had more complications and longer stays than did nonanxious patients. The administration of metoprolol did not eliminate this relationship, perhaps because patients did not receive a sufficient dose of metoprolol to counter the effect of anxiety.

Monte Carlo based electron treatment planning and cutout output factor calculations

NASA Astrophysics Data System (ADS)

Mitrou, Ellis

Electron radiotherapy (RT) offers a number of advantages over photons. The high surface dose, combined with a rapid dose fall-off beyond the target volume presents a net increase in tumor control probability and decreases the normal tissue complication for superficial tumors. Electron treatments are normally delivered clinically without previously calculated dose distributions due to the complexity of the electron transport involved and greater error in planning accuracy. This research uses Monte Carlo (MC) methods to model clinical electron beams in order to accurately calculate electron beam dose distributions in patients as well as calculate cutout output factors, reducing the need for a clinical measurement. The present work is incorporated into a research MC calculation system: McGill Monte Carlo Treatment Planning (MMCTP) system. Measurements of PDDs, profiles and output factors in addition to 2D GAFCHROMICRTM EBT2 film measurements in heterogeneous phantoms were obtained to commission the electron beam model. The use of MC for electron TP will provide more accurate treatments and yield greater knowledge of the electron dose distribution within the patient. The calculation of output factors could invoke a clinical time saving of up to 1 hour per patient.

The Natural History of Neoplasia

PubMed Central

Pitot, Henry C.

1977-01-01

The stages of initiation and promotion in the natural history of epidermal carcinogenesis have been known for many years. Recently, experimental systems other than skin have been shown to exhibit similar, if not completely analogous, stages in the natural history of neoplasia. In particular, the demonstration by Peraino and his associates that phenobarbital may enhance the production of hepatomas by a relatively subcarcinogenic dose of acetylaminofluorene was one of the first demonstrations of stages occurring in an extraepidermal neoplasm. Studies reported in this paper have demonstrated that administration of phenobarbital (0.05% in the diet) for 6 months following a single dose of diethylnitrosamine (5 to 10 mg/kg) given within 24 hours after partial hepatectomy resulted in a marked increase in the number of enzyme-altered foci in the liver as well as in the production of hepatocellular carcinomas. This was compared to animals receiving only a single dose of diethylnitrosamine following partial hepatectomy with no further treatment, in which only a relatively small number of foci were evident in the absence of phenobarbital feeding. Using three different enzyme markers, a distinct degree of phenotypic heterogeneity of the enzyme-altered foci in liver was demonstrated. These studies have shown that liver carcinogensis can be readily divided into two stages: a) initiation by a single dose of diethylnitrosamine following partial hepatectomy and b) promotion by the continuous feeding of phenobarbital. Furthermore, the immediate progeny of the initiated cells, the enzyme-altered focus, may be recognized by suitable microscopic means prior to the formation of gross lesions as required in the skin system. These initiated cell populations exhibit a degree of biochemical heterogeneity which reflects that seen in fully developed hepatic neoplasms, suggesting that promotion and progression in this system does not significantly alter the basic biochemical characteristics of the initiated cell. PMID:21565

Low-dose megavoltage cone-beam computed tomography for lung tumors using a high-efficiency image receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sillanpaa, Jussi; Chang Jenghwa; Mageras, Gikas

2006-09-15

We report on the capabilities of a low-dose megavoltage cone-beam computed tomography (MV CBCT) system. The high-efficiency image receptor consists of a photodiode array coupled to a scintillator composed of individual CsI crystals. The CBCT system uses the 6 MV beam from a linear accelerator. A synchronization circuit allows us to limit the exposure to one beam pulse [0.028 monitor units (MU)] per projection image. 150-500 images (4.2-13.9 MU total) are collected during a one-minute scan and reconstructed using a filtered backprojection algorithm. Anthropomorphic and contrast phantoms are imaged and the contrast-to-noise ratio of the reconstruction is studied as amore » function of the number of projections and the error in the projection angles. The detector dose response is linear (R{sup 2} value 0.9989). A 2% electron density difference is discernible using 460 projection images and a total exposure of 13 MU (corresponding to a maximum absorbed dose of about 12 cGy in a patient). We present first patient images acquired with this system. Tumors in lung are clearly visible and skeletal anatomy is observed in sufficient detail to allow reproducible registration with the planning kV CT images. The MV CBCT system is shown to be capable of obtaining good quality three-dimensional reconstructions at relatively low dose and to be clinically usable for improving the accuracy of radiotherapy patient positioning.« less

Dosing study of massage for chronic neck pain: protocol for the dose response evaluation and analysis of massage [DREAM] trial

PubMed Central

2012-01-01

Background Despite the growing popularity of massage, its effectiveness for treating neck pain remains unclear, largely because of the poor quality of research. A major deficiency of previous studies has been their use of low “doses” of massage that massage therapists consider inadequate. Unfortunately, the number of minutes per massage session, sessions per week, or weeks of treatment necessary for massage to have beneficial or optimal effects are not known. This study is designed to address these gaps in our knowledge by determining, for persons with chronic neck pain: 1) the optimal combination of number of treatments per week and length of individual treatment session, and 2) the optimal number of weeks of treatment. Methods/design In this study, 228 persons with chronic non-specific neck pain will be recruited from primary health care clinics in a large health care system in the Seattle area. Participants will be randomized to a wait list control group or 4 weeks of treatment with one of 5 different dosing combinations (2 or 3 30-min treatments per week or 1, 2, or 3 60-min treatments per week). At the end of this 4-week primary treatment period, participants initially receiving each of the 5 dosing combinations will be randomized to a secondary treatment period of either no additional treatment or 6 weekly 60-min massages. The primary outcomes, neck-related dysfunction and pain, will be assessed by blinded telephone interviewers 5, 12, and 26 weeks post-randomization. To better characterize the trajectory of treatment effects, these interview data will be supplemented with outcomes data collected by internet questionnaire at 10, 16, 20 and 39 weeks. Comparisons of outcomes for the 6 groups during the primary treatment period will identify the optimal weekly dose, while comparisons of outcomes during the secondary treatment period will determine if 10 weeks of treatment is superior to 4 weeks. Discussion A broad dosing schedule was included in this trial. If adherence to any of these doses is poor, those doses will be discontinued. Trial registration This trial is registered in ClinicalTrials.gov, with the ID number of NCT01122836 PMID:22985134

Study of Dose Perturbation at Bone-Tissue Interfaces in Megavoltage Photon Beam Therapy.

NASA Astrophysics Data System (ADS)

Das, Indra Jeet

Dose perturbations during photon beam irradiation occur at interfaces between two dissimilar media due to the loss of electronic equilibrium. The human body contains many different types of interfaces between soft tissue and other media such as, air cavities, lungs, bones, and high atomic number (Z) materials. The dose to critical organs in the vicinity of high Z interfaces, is what leads to this project. This work describes the dose perturbation at high Z (from bone to lead) interfaces with soft tissue for clinically used megavoltage photon beams in the range of CO-60 gamma rays to 24 MV X-rays. It is divided into three main sections: (1) the dose outside the inhomogeneity in the direction of backscatter, (2) the dose inside the inhomogeneity, and (3) the dose on the photon transmission side of the inhomogeneity. Using different types of parallel plate ion chambers, TLD (powder and chip), and film as dosimeters, the dose perturbation is studied as a function of photon energy, thickness, width, and depth of inhomogeneity, distance from the interface and radiation field size. The concept of Bragg-Gray cavity theory is applied and verified for dose determination inside the inhomogeneity. A significant dose enhancement has been observed on the backscatter side for all photon energies. It is strongly dependent on the atomic number of the inhomogeneity and less dependent on the photon energy, thickness, depth, width, and field size. In the forward direction, a dose reduction occurs at the interface at beam energies lower than 10 MV, whereas a dose enhancement occurs for higher photon energies. The interface effect persists up to a few millimeters on the backscatter side but a distance equivalent to the secondary electron range for the particular photon beams in the forward direction. The dose perturbation is explained on the basis of production and transport of secondary electrons. Empirical functions are derived from the experimental data to predict the dose distribution in the vicinity of an inhomogeneity. These equations could form the basis of a treatment planning system that would accurately represent the dose both at the interface and surrounding tissue.

Dengue and chikungunya viruses in plasma are effectively inactivated after treatment with methylene blue and visible light.

PubMed

Fryk, Jesse J; Marks, Denese C; Hobson-Peters, Jody; Prow, Natalie A; Watterson, Daniel; Hall, Roy A; Young, Paul R; Reichenberg, Stefan; Sumian, Chryslain; Faddy, Helen M

2016-09-01

Arboviruses, such as dengue viruses (DENV) and chikungunya virus (CHIKV), pose a risk to the safe transfusion of blood components, including plasma. Pathogen inactivation is an approach to manage this transfusion transmission risk, with a number of techniques being used worldwide for the treatment of plasma. In this study, the efficacy of the THERAFLEX MB-Plasma system to inactivate all DENV serotypes (DENV-1, DENV-2, DENV-3, DENV-4) or CHIKV in plasma, using methylene blue and light illumination at 630 nm, was investigated. Pooled plasma units were spiked with DENV-1, DENV-2, DENV-3 DENV-4, or CHIKV and treated with the THERAFLEX MB-Plasma system at four light illumination doses: 20, 40, 60, and 120 (standard dose) J/cm(2) . Pre- and posttreatment samples were collected and viral infectivity was determined. The reduction in viral infectivity was calculated for each dose. Treatment of plasma with the THERAFLEX MB-Plasma system resulted in at least a 4.46-log reduction in all DENV serotypes and CHIKV infectious virus. The residual infectivity for each was at the detection limit of the assay used at 60 J/cm(2) , with dose dependency also observed. Our study demonstrated the THERAFLEX MB-Plasma system can reduce the infectivity of all DENV serotypes and CHIKV spiked into plasma to the detection limit of the assay used at half of the standard illumination dose. This suggests this system has the capacity to be an effective option for managing the risk of DENV or CHIKV transfusion transmission in plasma. © 2016 AABB.

Probability Estimates of Solar Proton Doses During Periods of Low Sunspot Number for Short Duration Missions

NASA Technical Reports Server (NTRS)

Atwell, William; Tylka, Allan J.; Dietrich, William F.; Rojdev, Kristina; Matzkind, Courtney

2016-01-01

In an earlier paper presented at ICES in 2015, we investigated solar particle event (SPE) radiation exposures (absorbed dose) to small, thinly-shielded spacecraft during a period when the monthly smoothed sunspot number (SSN) was less than 30. Although such months are generally considered "solar-quiet", SPEs observed during these months even include Ground Level Events, the most energetic type of SPE. In this paper, we add to previous study those SPEs that occurred in 1973-2015 when the SSN was greater than 30 but less than 50. Based on the observable energy range of the solar protons, we classify the event as GLEs, sub-GLEs, and sub-sub-GLEs, all of which are potential contributors to the radiation hazard. We use the spectra of these events to construct a probabilistic model of the absorbed dose due to solar protons when SSN < 50 at various confidence levels for various depths of shielding and for various mission durations. We provide plots and tables of solar proton-induced absorbed dose as functions of confidence level, shielding thickness, and mission-duration that will be useful to system designers.


Intrathecal analgesia by bupivacaine is not enhanced by coadministration of morphine in patients with severe cancer-related pain: a randomized double-blind cross-over study.

PubMed

Reif, Ingalill; Wincent, Anders; Stiller, Carl-Olav

2017-06-01

The objective of this randomized double blind cross-over trial was to determine if patients with severe cancer-related pain and inadequate response to systemic opioids prefer intrathecal (IT) pain relief with a combination of bupivacaine and morphine or bupivacaine only. Adult patients with cancer-related pain (n = 23) scheduled for IT analgesia at the Pain Center at the Karo-linska University Hospital Solna, Stockholm, Sweden, were included. The optimal individual flow rate of IT bupivacaine (2 mg/mL) in addition to bolus doses was titrated and maintained for 4 days. Morphine (1 mg/mL) was added to bupivacaine either on day 2 or 4 according to a randomization protocol. Expression of pain relief preference for morphine instead of control (bupivacaine only) was the primary outcome. Secondary outcomes were difference in pain intensity, pain relief, total use of bupivacaine per 24 hours and number of requested bolus doses. Eight patients dropped out during the 4-day study period for reasons not related to the trial. IT bupivacaine significantly decreased median (interquartile range) pain intensity from 5 (3 - 7) at baseline (before catheter insertion) to 1 (0 - 1) (p = 0.0001; Wilcoxon test). Only 1 patient of 15 with 4-day data expressed any preference for morphine. The addition of IT morphine did not result in any significant change of pain intensity, pain relief score, total use of bupivacaine per 24 hours, or number of requested bolus doses. These results suggest that patients with cancer-related pain treated with high doses of systemic opioids, may start IT treatment with an optimal dose of IT bupivacaine without morphine.
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SU-G-JeP3-06: Lower KV Image Dose Are Expected From a Limited-Angle Intra-Fractional Verification (LIVE) System for SBRT Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, G; Yin, F; Ren, L

Purpose: In order to track the tumor movement for patient positioning verification during arc treatment delivery or in between 3D/IMRT beams for stereotactic body radiation therapy (SBRT), the limited-angle kV projections acquisition simultaneously during arc treatment delivery or in-between static treatment beams as the gantry moves to the next beam angle was proposed. The purpose of this study is to estimate additional imaging dose resulting from multiple tomosynthesis acquisitions in-between static treatment beams and to compare with that of a conventional kV-CBCT acquisition. Methods: kV imaging system integrated into Varian TrueBeam accelerators was modeled using EGSnrc Monte Carlo user code,more » BEAMnrc and DOSXYZnrc code was used in dose calculations. The simulated realistic kV beams from the Varian TrueBeam OBI 1.5 system were used to calculate dose to patient based on CT images. Organ doses were analyzed using DVHs. The imaging dose to patient resulting from realistic multiple tomosynthesis acquisitions with each 25–30 degree kV source rotation between 6 treatment beam gantry angles was studied. Results: For a typical lung SBRT treatment delivery much lower (20–50%) kV imaging doses from the sum of realistic six tomosynthesis acquisitions with each 25–30 degree x-ray source rotation between six treatment beam gantry angles were observed compared to that from a single CBCT image acquisition. Conclusion: This work indicates that the kV imaging in this proposed Limited-angle Intra-fractional Verification (LIVE) System for SBRT Treatments has a negligible imaging dose increase. It is worth to note that the MV imaging dose caused by MV projection acquisition in-between static beams in LIVE can be minimized by restricting the imaging to the target region and reducing the number of projections acquired. For arc treatments, MV imaging acquisition in LIVE does not add additional imaging dose as the MV images are acquired from treatment beams directly during the treatment.« less

Technogenesis and the main levels of soil ecosystems' transformation in oil production areas

NASA Astrophysics Data System (ADS)

Buzmakov, Sergey

2017-04-01

The obtained experimental data, the results of field studies and the analysis of references make it possible to describe peculiarities of technogenic transformation of ecosystems. Experimental data allow to determine the main levels of oil pollution on the basis of changes in biotope properties and reaction of a biota. Background level. Pollution is absent. Biotope corresponds to natural zonal sequence. The content of oil products is up to 0,11 g/kg. First level: the dose of pollution is 0,8-1g of oil on 1 kg of soil. Conditions for plants' growth are optimum. Initially plants gain gross weight, and then lose it to the background level. The number of saprotrophes and oil oxidizing microorganisms rises. Second level: the pollution dose is up to 15 g per 1 kg of soil. The capillary moisture capacity increases reaching the maximum. The number of saprophytes and oil oxidizing microorganisms rises. Third level: the pollution dose is 15-21g per 1 kg of soil. Capillary capacity of soils decreases to background level. Time of filtration and absorption of moisture is increased. Fourth level: the pollution dose is 21-32g per 1 kg of soil. Anaerobic and hydrophobic conditions develop. The number of saprophytes and oil oxidizing microorganisms rises. Fifth level: the dose of pollution is 32 - 50g per 1 kg of soil. Formation of 3,4 benzpyrene increases sharply. The number of saprophytes and oil oxidizing microorganisms is at maximum level. Sixth level: the dose of pollution is 50 - 91g per 1 kg of soil. Formation of 3,4 benzpyrene is dangerous for biota. Time of absorption and filtration of water through the soil reaches its maximum. The number of saprophytes and oil oxidizing microorganisms decreases, but remains higher than at background level. Seventh level: the pollution dose is 91-150g per 1 kg of soil. The number of saprophytes and oil oxidizing microorganisms decreases to background level. Eighth level: the pollution dose is of 150-300 g per 1 kg of soil. The substratum becomes toxic. The number of saprophytes and oil oxidizing microorganisms is lower than at background level. Ninth level: the dose of pollution is 300 g per 1 kg of soil and above. Substratum is abiogenic. Field researches show that the influence of oil fields is manifested in the form of intake of emergency oil and emergency salty waters as well as ground water runoff and surface water containing salts and oil products from platforms of oil sites into surrounding land ecosystems, along with their atmospheric pollution. Degradation and recovery process is manifested in formation of a natural- technogenic ecosystem with azonal biotopes. Around powerful sources of pollution there should be created the manageable natural and technogenic ecosystems facilitating self-restoration of the environment. It is necessary to create a system of accumulating and transit ecosystems which would make it possible to carry out the degradation and dispersion of accumulated pollutants. Implementation of our proposals will result in stabilization of ecological situation.

Field-relevant doses of the systemic insecticide fipronil and fungicide pyraclostrobin impair mandibular and hypopharyngeal glands in nurse honeybees (Apis mellifera).

PubMed

Zaluski, Rodrigo; Justulin, Luis Antonio; Orsi, Ricardo de Oliveira

2017-11-09

Global decreases in bee populations emphasize the importance of assessing how environmental stressors affect colony maintenance, especially considering the extreme task specialization observed in honeybee societies. Royal jelly, a protein secretion essential to colony nutrition, is produced by nurse honeybees, and development of bee mandibular glands, which comprise a reservoir surrounded by secretory cells and hypopharyngeal glands that are shaped by acini, is directly associated with production of this secretion. Here, we examined individual and combined effects of the systemic fungicide pyraclostrobin and insecticide fipronil in field-relevant doses (850 and 2.5 ppb, respectively) on mandibular and hypopharyngeal glands in nurse honeybees. Six days of pesticide treatment decreased secretory cell height in mandibular glands. When pyraclostrobin and fipronil were combined, the reservoir volume in mandibular glands also decreased. The total number of acini in hypopharyngeal glands was not affected, but pesticide treatment reduced the number of larger acini while increasing smaller acini. These morphological impairments appeared to reduce royal jelly secretion by nurse honeybees and consequently hampered colony maintenance. Overall, pesticide exposure in doses close to those experienced by bees in the field impaired brood-food glands in nurse honeybees, a change that could negatively influence development, survival, and colony maintenance.

UV Disinfection System for Cabin Air

NASA Astrophysics Data System (ADS)

Lim, Soojung

Ultraviolet (UV) radiation is commonly used for disinfection of water. As a result of advancements made in the last 10-15 years, the analysis and design of UV disinfection systems for water is well developed. UV disinfection is also used for disinfection of air; however, despite the fact the UV-air systems have a longer record of application than UV-water systems, the methods used to analyze and design UV-air disinfection systems remain quite empirical. It is well-established that the effectiveness of UV-air systems is strongly affected by the type of microorganisms, the irradiation level/type (lamp power and wavelength), duration of irradiation (exposure time), air movement pattern (mixing degree), and relative humidity. This paper will describe ongoing efforts to evaluate, design and test a UV-air system based on first principles. Specific issues to be addressed in this work will include laboratory measurements of relevant kinetics (i.e., UV dose-response behavior) and numerical simulations designed to represent fluid mechanics and the radiation intensity field. UV dose-response behavior of test microorganism was measured using a laboratory (bench-scale) system. Target microorganisms (e.g., bacterial spores) were first applied to membrane filters at sub-monolayer coverage. The filters were then transferred to an environmental chamber at fixed relative humidity (RH) and allowed to equilibrate with their surroundings. Microorganisms were then subjected to UV exposure under a collimated beam. The experiment was repeated at RH values ranging from 20% to 100%. UV dose-response behavior was observed to vary with RH. For example, at 100% RH, a UV dose of 20 mJ/cm2 accomplished 90% (1 log10 units) of the B. subtilis spore inactivation, whereas 99 % (2 log10 units) inactivation was accomplished at this same UV dose under 20% RH conditions. However, at higher doses, the result was opposite of that in low dose. Reactor behavior is simulated using an integrated application of computational fluid dynamics (CFD) and radiation intensity field models. These simulations followed a Lagrangian approach, wherein the UV radiation intensity field was mapped onto simulated particle trajectories for prediction of the UV dose delivered to each particle. By repeating these calculations for a large number of simulated particle trajectories, an estimate of the UV dose distribution delivered by the reactor can be made. In turn, these dose distribution estimates are integrated with the UV dose-response behavior described above to yield an estimate of microbial inactivation accomplished by the reactor. This modeling approach has the advantage of allowing simulation of many reactor configurations in a relatively short period of time. Moreover, by following this approach of "numerical prototyping," it is possible to "build" and analyze several virtual reactors before the construction of a physical prototype. As such, this procedure allows effective development of efficient reactors.

ANALYSIS OF RESPIRATORY DEPOSITION OF INHALED PARTICLES FOR DIFFERENT DOSE METRICS: COMPARISON OF NUMBER, SURFACE AREA AND MASS DOSE OF TYPICAL AMBIENT BI-MODAL AEROSOLS

EPA Science Inventory

ANALYSIS OF RESPIRATORY DEPOSITION OF INHALED PARTICLES FOR DIFFERENT DOSE METRICS: COMPARISON OF NUMBER, SURFACE AREA AND MASS DOSE OF TYPICAL AMBIENT BI-MODAL AEROSOLS.
Chong S. Kim, SC. Hu*, PA Jaques*, US EPA, National Health and Environmental Effects Research Laboratory, ...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, Xiaodong, E-mail: lxdctopone@sina.com; Ni, Lingqin; Hu, Wei

The objective of this study was to evaluate the dose conformity and feasibility of whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in patients with 1 to 3 brain metastases. Forward intensity-modulated radiation therapy plans were generated for 10 patients with 1 to 3 brain metastases on Pinnacle 6.2 Treatment Planning System. The prescribed dose was 30 Gy to the whole brain (planning target volume [PTV]{sub wbrt}) and 40 Gy to individual brain metastases (PTV{sub boost}) simultaneously, and both doses were given in 10 fractions. The maximum diameters of individual brain metastases ranged from 1.6 tomore » 6 cm, and the summated PTVs per patient ranged from 1.62 to 69.81 cm{sup 3}. Conformity and feasibility were evaluated regarding conformation number and treatment delivery time. One hundred percent volume of the PTV{sub boost} received at least 95% of the prescribed dose in all cases. The maximum doses were less than 110% of the prescribed dose to the PTV{sub boost}, and all of the hot spots were within the PTV{sub boost}. The volume of the PTV{sub wbrt} that received at least 95% of the prescribed dose ranged from 99.2% to 100%. The mean values of conformation number were 0.682. The mean treatment delivery time was 2.79 minutes. Ten beams were used on an average in these plans. Whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in 1 to 3 brain metastases is feasible, and treatment delivery time is short.« less

VMAT testing for an Elekta accelerator

PubMed Central

Sweeney, Larry E.; Marshall, Edward I.; Mahendra, Saikanth

2012-01-01

Volumetric‐modulated arc therapy (VMAT) has been shown to be able to deliver plans equivalent to intensity‐modulated radiation therapy (IMRT) in a fraction of the treatment time. This improvement is important for patient immobilization/ localization compliance due to comfort and treatment duration, as well as patient throughput. Previous authors have suggested commissioning methods for this modality. Here, we extend the methods reported for the Varian RapidArc system (which tested individual system components) to the Elekta linear accelerator, using custom files built using the Elekta iComCAT software. We also extend the method reported for VMAT commissioning of the Elekta accelerator by verifying maximum values of parameters (gantry speed, multileaf collimator (MLC) speed, and backup jaw speed), investigating: 1) beam profiles as a function of dose rate during an arc, 2) over/under dosing due to MLC reversals, and 3) over/under dosing at changing dose rate junctions. Equations for construction of the iComCAT files are given. Results indicate that the beam profile for lower dose rates varies less than 3% from that of the maximum dose rate, with no difference during an arc. The gantry, MLC, and backup jaw maximum speed are internally consistent. The monitor unit chamber is stable over the MUs and gantry movement conditions expected. MLC movement and position during VMAT delivery are within IMRT tolerances. Dose rate, gantry speed, and MLC speed are accurately controlled. Over/under dosing at junctions of MLC reversals or dose rate changes are within clinical acceptability. PACS numbers: 87.55.de, 87.55.Qr, 87.56.bd PMID:22402389

Dose of Prophylactic Platelet Transfusions and Prevention of Hemorrhage

PubMed Central

Slichter, Sherrill J.; Kaufman, Richard M.; Assmann, Susan F.; McCullough, Jeffrey; Triulzi, Darrell J.; Strauss, Ronald G.; Gernsheimer, Terry B.; Ness, Paul M.; Brecher, Mark E.; Josephson, Cassandra D.; Konkle, Barbara A.; Woodson, Robert D.; Ortel, Thomas L.; Hillyer, Christopher D.; Skerrett, Donna L.; McCrae, Keith R.; Sloan, Steven R.; Uhl, Lynne; George, James N.; Aquino, Victor M.; Manno, Catherine S.; McFarland, Janice G.; Hess, John R.; Leissinger, Cindy; Granger, Suzanne

2010-01-01

BACKGROUND We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia. METHODS We randomly assigned hospitalized patients undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, a medium dose, or a high dose (1.1×1011, 2.2×1011, or 4.4×1011 platelets per square meter of body-surface area, respectively), when morning platelet counts were 10,000 per cubic millimeter or lower. Clinical signs of bleeding were assessed daily. The primary end point was bleeding of grade 2 or higher (as defined on the basis of World Health Organization criteria). RESULTS In the 1272 patients who received at least one platelet transfusion, the primary end point was observed in 71%, 69%, and 70% of the patients in the low-dose group, the medium-dose group, and the high-dose group, respectively (differences were not significant). The incidences of higher grades of bleeding, and other adverse events, were similar among the three groups. The median number of platelets transfused was significantly lower in the low-dose group (9.25×1011) than in the medium-dose group (11.25×1011) or the high-dose group (19.63×1011) (P = 0.002 for low vs. medium, P<0.001 for high vs. low and high vs. medium), but the median number of platelet transfusions given was significantly higher in the low-dose group (five, vs. three in the medium-dose and three in the high-dose group; P<0.001 for low vs. medium and low vs. high). Bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6000 to 80,000 per cubic millimeter (P<0.001). CONCLUSIONS Low doses of platelets administered as a prophylactic transfusion led to a decreased number of platelets transfused per patient but an increased number of transfusions given. At doses between 1.1×1011 and 4.4×1011 platelets per square meter, the number of platelets in the prophylactic transfusion had no effect on the incidence of bleeding. (ClinicalTrials.gov number, NCT00128713.) PMID:20164484

Evaluation of lens dose from anterior electron beams: comparison of Pinnacle and Gafchromic EBT3 film

PubMed Central

Wronski, Matt; Yeboah, Collins

2015-01-01

Lens dose is a concern during the treatment of facial lesions with anterior electron beams. Lead shielding is routinely employed to reduce lens dose and minimize late complications. The purpose of this work is twofold: 1) to measure dose profiles under large‐area lead shielding at the lens depth for clinical electron energies via film dosimetry; and 2) to assess the accuracy of the Pinnacle treatment planning system in calculating doses under lead shields. First, to simulate the clinical geometry, EBT3 film and 4 cm wide lead shields were incorporated into a Solid Water phantom. With the lead shield inside the phantom, the film was positioned at a depth of 0.7 cm below the lead, while a variable thickness of solid water, simulating bolus, was placed on top. This geometry was reproduced in Pinnacle to calculate dose profiles using the pencil beam electron algorithm. The measured and calculated dose profiles were normalized to the central‐axis dose maximum in a homogeneous phantom with no lead shielding. The resulting measured profiles, functions of bolus thickness and incident electron energy, can be used to estimate the lens dose under various clinical scenarios. These profiles showed a minimum lead margin of 0.5 cm beyond the lens boundary is required to shield the lens to ≤10% of the dose maximum. Comparisons with Pinnacle showed a consistent overestimation of dose under the lead shield with discrepancies of ∼25% occurring near the shield edge. This discrepancy was found to increase with electron energy and bolus thickness and decrease with distance from the lead edge. Thus, the Pinnacle electron algorithm is not recommended for estimating lens dose in this situation. The film measurements, however, allow for a reasonable estimate of lens dose from electron beams and for clinicians to assess the lead margin required to reduce the lens dose to an acceptable level. PACS number(s): 87.53.Bn, 87.53.Kn, 87.55.‐x, 87.55.D‐ PMID:27074448

In vivo verification of particle therapy: how Compton camera configurations affect 3D image quality

NASA Astrophysics Data System (ADS)

Mackin, D.; Draeger, E.; Peterson, S.; Polf, J.; Beddar, S.

2017-05-01

The steep dose gradients enabled by the Bragg peaks of particle therapy beams are a double edged sword. They enable highly conformal dose distributions, but even small deviations from the planned beam range can cause overdosing of healthy tissue or under-dosing of the tumour. To reduce this risk, particle therapy treatment plans include margins large enough to account for all the sources of range uncertainty, which include patient setup errors, patient anatomy changes, and CT number to stopping power ratios. Any system that could verify the beam range in vivo, would allow reduced margins and more conformal dose distributions. Toward our goal developing such a system based on Compton camera (CC) imaging, we studied how three configurations (single camera, parallel opposed, and orthogonal) affect the quality of the 3D images. We found that single CC and parallel opposed configurations produced superior images in 2D. The increase in parallax produced by an orthogonal CC configuration was shown to be beneficial in producing artefact free 3D images.

Pulmonary nodules: effect of adaptive statistical iterative reconstruction (ASIR) technique on performance of a computer-aided detection (CAD) system-comparison of performance between different-dose CT scans.

PubMed

Yanagawa, Masahiro; Honda, Osamu; Kikuyama, Ayano; Gyobu, Tomoko; Sumikawa, Hiromitsu; Koyama, Mitsuhiro; Tomiyama, Noriyuki

2012-10-01

To evaluate the effects of ASIR on CAD system of pulmonary nodules using clinical routine-dose CT and lower-dose CT. Thirty-five patients (body mass index, 22.17 ± 4.37 kg/m(2)) were scanned by multidetector-row CT with tube currents (clinical routine-dose CT, automatically adjusted mA; lower-dose CT, 10 mA) and X-ray voltage (120 kVp). Each 0.625-mm-thick image was reconstructed at 0%-, 50%-, and 100%-ASIR: 0%-ASIR is reconstructed using only the filtered back-projection algorithm (FBP), while 100%-ASIR is reconstructed using the maximum ASIR and 50%-ASIR implies a blending of 50% FBP and ASIR. CAD output was compared retrospectively with the results of the reference standard which was established using a consensus panel of three radiologists. Data were analyzed using Bonferroni/Dunn's method. Radiation dose was calculated by multiplying dose-length product by conversion coefficient of 0.021. The consensus panel found 265 non-calcified nodules ≤ 30 mm (ground-glass opacity [GGO], 103; part-solid, 34; and solid, 128). CAD sensitivity was significantly higher at 100%-ASIR [clinical routine-dose CT, 71% (overall), 49% (GGO); lower-dose CT, 52% (overall), 67% (solid)] than at 0%-ASIR [clinical routine-dose CT, 54% (overall), 25% (GGO); lower-dose CT, 36% (overall), 50% (solid)] (p<0.001). Mean number of false-positive findings per examination was significantly higher at 100%-ASIR (clinical routine-dose CT, 8.5; lower-dose CT, 6.2) than at 0%-ASIR (clinical routine-dose CT, 4.6; lower-dose CT, 3.5; p<0.001). Effective doses were 10.77 ± 3.41 mSv in clinical routine-dose CT and 2.67 ± 0.17 mSv in lower-dose CT. CAD sensitivity at 100%-ASIR on lower-dose CT is almost equal to that at 0%-ASIR on clinical routine-dose CT. ASIR can increase CAD sensitivity despite increased false-positive findings. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Computerized Dose Range Checking Using Hard and Soft Stop Alerts Reduces Prescribing Errors in a Pediatric Intensive Care Unit.

PubMed

Balasuriya, Lilanthi; Vyles, David; Bakerman, Paul; Holton, Vanessa; Vaidya, Vinay; Garcia-Filion, Pamela; Westdorp, Joan; Sanchez, Christine; Kurz, Rhonda

2017-09-01

An enhanced dose range checking (DRC) system was developed to evaluate prescription error rates in the pediatric intensive care unit and the pediatric cardiovascular intensive care unit. An enhanced DRC system incorporating "soft" and "hard" alerts was designed and implemented. Practitioner responses to alerts for patients admitted to the pediatric intensive care unit and the pediatric cardiovascular intensive care unit were retrospectively reviewed. Alert rates increased from 0.3% to 3.4% after "go-live" (P < 0.001). Before go-live, all alerts were soft alerts. In the period after go-live, 68% of alerts were soft alerts and 32% were hard alerts. Before go-live, providers reduced doses only 1 time for every 10 dose alerts. After implementation of the enhanced computerized physician order entry system, the practitioners responded to soft alerts by reducing doses to more appropriate levels in 24.7% of orders (70/283), compared with 10% (3/30) before go-live (P = 0.0701). The practitioners deleted orders in 9.5% of cases (27/283) after implementation of the enhanced DRC system, as compared with no cancelled orders before go-live (P = 0.0774). Medication orders that triggered a soft alert were submitted unmodified in 65.7% (186/283) as compared with 90% (27/30) of orders before go-live (P = 0.0067). After go-live, 28.7% of hard alerts resulted in a reduced dose, 64% resulted in a cancelled order, and 7.4% were submitted as written. Before go-live, alerts were often clinically irrelevant. After go-live, there was a statistically significant decrease in orders that were submitted unmodified and an increase in the number of orders that were reduced or cancelled.

Quality of Intensity Modulated Radiation Therapy Treatment Plans Using a {sup 60}Co Magnetic Resonance Image Guidance Radiation Therapy System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wooten, H. Omar, E-mail: hwooten@radonc.wustl.edu; Green, Olga; Yang, Min

2015-07-15

Purpose: This work describes a commercial treatment planning system, its technical features, and its capabilities for creating {sup 60}Co intensity modulated radiation therapy (IMRT) treatment plans for a magnetic resonance image guidance radiation therapy (MR-IGRT) system. Methods and Materials: The ViewRay treatment planning system (Oakwood Village, OH) was used to create {sup 60}Co IMRT treatment plans for 33 cancer patients with disease in the abdominal, pelvic, thorax, and head and neck regions using physician-specified patient-specific target coverage and organ at risk (OAR) objectives. Backup plans using a third-party linear accelerator (linac)-based planning system were also created. Plans were evaluated bymore » attending physicians and approved for treatment. The {sup 60}Co and linac plans were compared by evaluating conformity numbers (CN) with 100% and 95% of prescription reference doses and heterogeneity indices (HI) for planning target volumes (PTVs) and maximum, mean, and dose-volume histogram (DVH) values for OARs. Results: All {sup 60}Co IMRT plans achieved PTV coverage and OAR sparing that were similar to linac plans. PTV conformity for {sup 60}Co was within <1% and 3% of linac plans for 100% and 95% prescription reference isodoses, respectively, and heterogeneity was on average 4% greater. Comparisons of OAR mean dose showed generally better sparing with linac plans in the low-dose range <20 Gy, but comparable sparing for organs with mean doses >20 Gy. The mean doses for all {sup 60}Co plan OARs were within clinical tolerances. Conclusions: A commercial {sup 60}Co MR-IGRT device can produce highly conformal IMRT treatment plans similar in quality to linac IMRT for a variety of disease sites. Additional work is in progress to evaluate the clinical benefit of other novel features of this MR-IGRT system.« less

Dose-dependent effects of theta burst rTMS on cortical excitability and resting-state connectivity of the human motor system.

PubMed

Nettekoven, Charlotte; Volz, Lukas J; Kutscha, Martha; Pool, Eva-Maria; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

2014-05-14

Theta burst stimulation (TBS), a specific protocol of repetitive transcranial magnetic stimulation (rTMS), induces changes in cortical excitability that last beyond stimulation. TBS-induced aftereffects, however, vary between subjects, and the mechanisms underlying these aftereffects to date remain poorly understood. Therefore, the purpose of this study was to investigate whether increasing the number of pulses of intermittent TBS (iTBS) (1) increases cortical excitability as measured by motor-evoked potentials (MEPs) and (2) alters functional connectivity measured using resting-state fMRI, in a dose-dependent manner. Sixteen healthy, human subjects received three serially applied iTBS blocks of 600 pulses over the primary motor cortex (M1 stimulation) and the parieto-occipital vertex (sham stimulation) to test for dose-dependent iTBS effects on cortical excitability and functional connectivity (four sessions in total). iTBS over M1 increased MEP amplitudes compared with sham stimulation after each stimulation block. Although the increase in MEP amplitudes did not differ between the first and second block of M1 stimulation, we observed a significant increase after three blocks (1800 pulses). Furthermore, iTBS enhanced resting-state functional connectivity between the stimulated M1 and premotor regions in both hemispheres. Functional connectivity between M1 and ipsilateral dorsal premotor cortex further increased dose-dependently after 1800 pulses of iTBS over M1. However, no correlation between changes in MEP amplitudes and functional connectivity was detected. In summary, our data show that increasing the number of iTBS stimulation blocks results in dose-dependent effects at the local level (cortical excitability) as well as at a systems level (functional connectivity) with a dose-dependent enhancement of dorsal premotor cortex-M1 connectivity. Copyright © 2014 the authors 0270-6474/14/346849-11$15.00/0.

SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Hildebrand, K; Ahmad, S

Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targetsmore » were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery.« less

SU-E-T-593: Clinical Evaluation of Direct Aperture Optimization in Head/Neck and Prostate IMRT Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hosini, M; GALAL, M; Emam, I

2014-06-01

Purpose: To investigate the planning and dosimetric advantages of direct aperture optimization (DAO) over beam-let optimization in IMRT treatment of head and neck (H/N) and prostate cancers. Methods: Five Head and Neck as well as five prostate patients were planned using the beamlet optimizer in Elekta-Xio ver 4.6 IMRT treatment planning system. Based on our experience in beamlet IMRT optimization, PTVs in H/N plans were prescribed to 70 Gy delivered by 7 fields. While prostate PTVs were prescribed to 76 Gy with 9 fields. In all plans, fields were set to be equally spaced. All cases were re-planed using Directmore » Aperture optimizer in Prowess Panther ver 5.01 IMRT planning system at same configurations and dose constraints. Plans were evaluated according to ICRU criteria, number of segments, number of monitor units and planning time. Results: For H/N plans, the near maximum dose (D2) and the dose that covers 95% D95 of PTV has improved by 4% in DAO. For organs at risk (OAR), DAO reduced the volume covered by 30% (V30) in spinal cord, right parotid, and left parotid by 60%, 54%, and 53% respectively. This considerable dosimetric quality improvement achieved using 25% less planning time and lower number of segments and monitor units by 46% and 51% respectively. In DAO prostate plans, Both D2 and D95 for the PTV were improved by only 2%. The V30 of the right femur, left femur and bladder were improved by 35%, 15% and 3% respectively. On the contrary, the rectum V30 got even worse by 9%. However, number of monitor units, and number of segments decreased by 20% and 25% respectively. Moreover the planning time reduced significantly too. Conclusion: DAO introduces considerable advantages over the beamlet optimization in regards to organs at risk sparing. However, no significant improvement occurred in most studied PTVs.« less

SU-E-T-110: An Investigation On Monitor Unit Threshold and Effects On IMPT Delivery in Proton Pencil Beam Planning System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Syh, J; Ding, X; Syh, J

2015-06-15

Purpose: An approved proton pencil beam scanning (PBS) treatment plan might not be able to deliver because of existed extremely low monitor unit per beam spot. A dual hybrid plan with higher efficiency of higher spot monitor unit and the efficacy of less number of energy layers were searched and optimized. The range of monitor unit threshold setting was investigated and the plan quality was evaluated by target dose conformity. Methods: Certain limitations and requirements need to be checks and tested before a nominal proton PBS treatment plan can be delivered. The plan needs to be met the machine characterization,more » specification in record and verification to deliver the beams. Minimal threshold of monitor unit, e.g. 0.02, per spot was set to filter the low counts and plan was re-computed. Further MU threshold increment was tested in sequence without sacrificing the plan quality. The number of energy layer was also alternated due to elimination of low count layer(s). Results: Minimal MU/spot threshold, spot spacing in each energy layer and total number of energy layer and the MU weighting of beam spots of each beam were evaluated. Plan optimization between increases of the spot MU (efficiency) and less energy layers of delivery (efficacy) was adjusted. 5% weighting limit of total monitor unit per beam was feasible. Scarce spreading of beam spots was not discouraging as long as target dose conformity within 3% criteria. Conclusion: Each spot size is equivalent to the relative dose in the beam delivery system. The energy layer is associated with the depth of the targeting tumor. Our work is crucial to maintain the best possible quality plan. To keep integrity of all intrinsic elements such as spot size, spot number, layer number and the carried weighting of spots in each layer is important in this study.« less

SU-C-BRB-06: Utilizing 3D Scanner and Printer for Dummy Eye-Shield: Artifact-Free CT Images of Tungsten Eye-Shield for Accurate Dose Calculation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, J; Lee, J; Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul

Purpose: To evaluate the effect of a tungsten eye-shield on the dose distribution of a patient. Methods: A 3D scanner was used to extract the dimension and shape of a tungsten eye-shield in the STL format. Scanned data was transferred into a 3D printer. A dummy eye shield was then produced using bio-resin (3D systems, VisiJet M3 Proplast). For a patient with mucinous carcinoma, the planning CT was obtained with the dummy eye-shield placed on the patient’s right eye. Field shaping of 6 MeV was performed using a patient-specific cerrobend block on the 15 x 15 cm{sup 2} applicator. Themore » gantry angle was 330° to cover the planning target volume near by the lens. EGS4/BEAMnrc was commissioned from our measurement data from a Varian 21EX. For the CT-based dose calculation using EGS4/DOSXYZnrc, the CT images were converted to a phantom file through the ctcreate program. The phantom file had the same resolution as the planning CT images. By assigning the CT numbers of the dummy eye-shield region to 17000, the real dose distributions below the tungsten eye-shield were calculated in EGS4/DOSXYZnrc. In the TPS, the CT number of the dummy eye-shield region was assigned to the maximum allowable CT number (3000). Results: As compared to the maximum dose, the MC dose on the right lens or below the eye shield area was less than 2%, while the corresponding RTP calculated dose was an unrealistic value of approximately 50%. Conclusion: Utilizing a 3D scanner and a 3D printer, a dummy eye-shield for electron treatment can be easily produced. The artifact-free CT images were successfully incorporated into the CT-based Monte Carlo simulations. The developed method was useful in predicting the realistic dose distributions around the lens blocked with the tungsten shield.« less

Optimization of image quality and dose for Varian aS500 electronic portal imaging devices (EPIDs).

PubMed

McGarry, C K; Grattan, M W D; Cosgrove, V P

2007-12-07

This study was carried out to investigate whether the electronic portal imaging (EPI) acquisition process could be optimized, and as a result tolerance and action levels be set for the PIPSPro QC-3V phantom image quality assessment. The aim of the optimization process was to reduce the dose delivered to the patient while maintaining a clinically acceptable image quality. This is of interest when images are acquired in addition to the planned patient treatment, rather than images being acquired using the treatment field during a patient's treatment. A series of phantoms were used to assess image quality for different acquisition settings relative to the baseline values obtained following acceptance testing. Eight Varian aS500 EPID systems on four matched Varian 600C/D linacs and four matched Varian 2100C/D linacs were compared for consistency of performance and images were acquired at the four main orthogonal gantry angles. Images were acquired using a 6 MV beam operating at 100 MU min(-1) and the low-dose acquisition mode. Doses used in the comparison were measured using a Farmer ionization chamber placed at d(max) in solid water. The results demonstrated that the number of reset frames did not have any influence on the image contrast, but the number of frame averages did. The expected increase in noise with corresponding decrease in contrast was also observed when reducing the number of frame averages. The optimal settings for the low-dose acquisition mode with respect to image quality and dose were found to be one reset frame and three frame averages. All patients at the Northern Ireland Cancer Centre are now imaged using one reset frame and three frame averages in the 6 MV 100 MU min(-1) low-dose acquisition mode. Routine EPID QC contrast tolerance (+/-10) and action (+/-20) levels using the PIPSPro phantom based around expected values of 190 (Varian 600C/D) and 225 (Varian 2100C/D) have been introduced. The dose at dmax from electronic portal imaging has been reduced by approximately 28%, and while the image quality has been reduced, the images produced are still clinically acceptable.

A novel curvilinear approach for prostate seed implantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Podder, Tarun K.; Dicker, Adam P.; Hutapea, Parsaoran

Purpose: A new technique called ''curvilinear approach'' for prostate seed implantation has been proposed. The purpose of this study is to evaluate the dosimetric benefit of curvilinear distribution of seeds for low-dose-rate (LDR) prostate brachytherapy. Methods: Twenty LDR prostate brachytherapy cases planned intraoperatively with VariSeed planning system and I-125 seeds were randomly selected as reference rectilinear cases. All the cases were replanned by using curved-needle approach keeping the same individual source strength and the volume receiving 100% of prescribed dose 145 Gy (V{sub 100}). Parameters such as number of needles, seeds, and the dose coverage of the prostate (D{sub 90},more » V{sub 150}, V{sub 200}), urethra (D{sub 30}, D{sub 10}) and rectum (D{sub 5}, V{sub 100}) were compared for the rectilinear and the curvilinear methods. Statistical significance was assessed using two-tailed student's t-test. Results: Reduction of the required number of needles and seeds in curvilinear method were 30.5% (p < 0.001) and 11.8% (p < 0.49), respectively. Dose to the urethra was reduced significantly; D{sub 30} reduced by 10.1% (p < 0.01) and D{sub 10} reduced by 9.9% (p < 0.02). Reduction in rectum dose D{sub 5} was 18.5% (p < 0.03) and V{sub 100} was also reduced from 0.93 cc in rectilinear to 0.21 cc in curvilinear (p < 0.001). Also the V{sub 150} and V{sub 200} coverage of prostate reduced by 18.8% (p < 0.01) and 33.9% (p < 0.001), respectively. Conclusions: Significant improvement in the relevant dosimetric parameters was observed in curvilinear needle approach. Prostate dose homogeneity (V{sub 150}, V{sub 200}) improved while urethral dose was reduced, which might potentially result in better treatment outcome. Reduction in rectal dose could potentially reduce rectal toxicity and complications. Reduction in number of needles would minimize edema and thereby could improve postimplant urinary incontinence. This study indicates that the curvilinear implantation approach is dosimetrically superior to conventional rectilinear implantation technique.« less

Different doses of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

PubMed Central

Estcourt, Lise J; Stanworth, Simon; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Blanco, Patricia; Murphy, Michael F

2015-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. This is an update of a Cochrane review first published in 2004, and updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews; this review compares different platelet transfusion doses. Objectives To determine whether different doses of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect their efficacy and safety in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy with or without haematopoietic stem cell transplantation (HSCT). Search methods We searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015. Selection criteria Randomised controlled trials involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with malignant haematological disorders or undergoing HSCT that compared different platelet component doses (low dose 1.1 × 1011/m2 ± 25%, standard dose 2.2 × 1011/m2 ± 25%, high dose 4.4 × 1011/m2 ± 25%). Data collection and analysis We used the standard methodological procedures expected by The Cochrane Collaboration. Main results We included seven trials (1814 participants) in this review; six were conducted during one course of treatment (chemotherapy or HSCT). Overall the methodological quality of studies was low to moderate across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity. Five studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no difference in the number of participants with a clinically significant bleeding episode between the low-dose and standard-dose groups (four studies; 1170 participants; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.95 to 1.13; moderate-quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence); or high-dose and standard-dose groups (two studies; 951 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence). Three studies reported the number of days with a clinically significant bleeding event per participant. There was no difference in the number of days of bleeding per participant between the low-dose and standard-dose groups (two studies; 230 participants; mean difference −0.17, 95% CI −0.51 to 0.17; low quality evidence). One study (855 participants) showed no difference in the number of days of bleeding per participant between high-dose and standard-dose groups, or between low-dose and high-dose groups (849 participants). Three studies reported the number of participants with severe or life-threatening bleeding. There was no difference in the number of participants with severe or life-threatening bleeding between a low-dose and a standard-dose platelet transfusion policy (three studies; 1059 participants; RR 1.33, 95% CI 0.91 to 1.92; low-quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.20, 95% CI 0.82 to 1.77; low-quality evidence); or high-dose and standard-dose groups (one study; 855 participants; RR 1.11, 95% CI 0.73 to 1.68; low-quality evidence). Two studies reported the time to first bleeding episodes; we were unable to perform a meta-analysis. Both studies (959 participants) individually found that the time to first bleeding episode was either the same, or longer, in the low-dose group compared to the standard-dose group. One study (855 participants) found that the time to the first bleeding episode was the same in the high-dose group compared to the standard-dose group. Three studies reported all-cause mortality within 30 days from the start of the study. There was no difference in all-cause mortality between treatment arms (low-dose versus standard-dose: three studies; 1070 participants; RR 2.04, 95% CI 0.70 to 5.93; low-quality evidence; low-dose versus high-dose: one study; 849 participants; RR 1.33, 95% CI 0.50 to 3.54; low-quality evidence; and high-dose versus standard-dose: one study; 855 participants; RR 1.71, 95% CI 0.51 to 5.81; low-quality evidence). Six studies reported the number of platelet transfusions; we were unable to perform a meta-analysis. Two studies (959 participants) out of three (1070 participants) found that a low-dose transfusion strategy led to more transfusion episodes than a standard-dose. One study (849 participants) found that a low-dose transfusion strategy led to more transfusion episodes than a high-dose strategy. One study (855 participants) out of three (1007 participants) found no difference in the number of platelet transfusions between the high-dose and standard-dose groups. One study reported on transfusion reactions. This study’s authors suggested that a high-dose platelet transfusion strategy may lead to a higher rate of transfusion-related adverse events. None of the studies reported quality-of-life. Authors’ conclusions In haematology patients who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT, we found no evidence to suggest that a low-dose platelet transfusion policy is associated with an increased bleeding risk compared to a standard-dose or high-dose policy, or that a high-dose platelet transfusion policy is associated with a decreased risk of bleeding when compared to a standard-dose policy. A low-dose platelet transfusion strategy leads to an increased number of transfusion episodes compared to a standard-dose strategy. A high-dose platelet transfusion strategy does not decrease the number of transfusion episodes per participant compared to a standard-dose regimen, and it may increase the number of transfusion-related adverse events. Findings from this review would suggest a change from current practice, with low-dose platelet transfusions used for people receiving in-patient treatment for their haematological disorder and high-dose platelet transfusion strategies not being used routinely. PMID:26505729

Unit-Dose Bags For Formulating Intravenous Solutions

NASA Technical Reports Server (NTRS)

Finley, Mike; Kipp, Jim; Scharf, Mike; Packard, Jeff; Owens, Jim

1993-01-01

Smaller unit-dose flowthrough bags devised for use with large-volume parenteral (LVP) bags in preparing sterile intravenous solutions. Premeasured amount of solute stored in such unit-dose bag flushed by predetermined amount of water into LVP bag. Relatively small number of LVP bags used in conjunction with smaller unit-dose bags to formulate large number of LVP intravenous solutions in nonsterile environment.

SU-E-T-503: IMRT Optimization Using Monte Carlo Dose Engine: The Effect of Statistical Uncertainty.

PubMed

Tian, Z; Jia, X; Graves, Y; Uribe-Sanchez, A; Jiang, S

2012-06-01

With the development of ultra-fast GPU-based Monte Carlo (MC) dose engine, it becomes clinically realistic to compute the dose-deposition coefficients (DDC) for IMRT optimization using MC simulation. However, it is still time-consuming if we want to compute DDC with small statistical uncertainty. This work studies the effects of the statistical error in DDC matrix on IMRT optimization. The MC-computed DDC matrices are simulated here by adding statistical uncertainties at a desired level to the ones generated with a finite-size pencil beam algorithm. A statistical uncertainty model for MC dose calculation is employed. We adopt a penalty-based quadratic optimization model and gradient descent method to optimize fluence map and then recalculate the corresponding actual dose distribution using the noise-free DDC matrix. The impacts of DDC noise are assessed in terms of the deviation of the resulted dose distributions. We have also used a stochastic perturbation theory to theoretically estimate the statistical errors of dose distributions on a simplified optimization model. A head-and-neck case is used to investigate the perturbation to IMRT plan due to MC's statistical uncertainty. The relative errors of the final dose distributions of the optimized IMRT are found to be much smaller than those in the DDC matrix, which is consistent with our theoretical estimation. When history number is decreased from 108 to 106, the dose-volume-histograms are still very similar to the error-free DVHs while the error in DDC is about 3.8%. The results illustrate that the statistical errors in the DDC matrix have a relatively small effect on IMRT optimization in dose domain. This indicates we can use relatively small number of histories to obtain the DDC matrix with MC simulation within a reasonable amount of time, without considerably compromising the accuracy of the optimized treatment plan. This work is supported by Varian Medical Systems through a Master Research Agreement. © 2012 American Association of Physicists in Medicine.

The Impact of Implementing a Demand Forecasting System into a Low-Income Country’s Supply Chain

PubMed Central

Mueller, Leslie E.; Haidari, Leila A.; Wateska, Angela R.; Phillips, Roslyn J.; Schmitz, Michelle M.; Connor, Diana L.; Norman, Bryan A.; Brown, Shawn T.; Welling, Joel S.; Lee, Bruce Y.

2016-01-01

OBJECTIVE To evaluate the potential impact and value of applications (e.g., ordering levels, storage capacity, transportation capacity, distribution frequency) of data from demand forecasting systems implemented in a lower-income country’s vaccine supply chain with different levels of population change to urban areas. MATERIALS AND METHODS Using our software, HERMES, we generated a detailed discrete event simulation model of Niger’s entire vaccine supply chain, including every refrigerator, freezer, transport, personnel, vaccine, cost, and location. We represented the introduction of a demand forecasting system to adjust vaccine ordering that could be implemented with increasing delivery frequencies and/or additions of cold chain equipment (storage and/or transportation) across the supply chain during varying degrees of population movement. RESULTS Implementing demand forecasting system with increased storage and transport frequency increased the number of successfully administered vaccine doses and lowered the logistics cost per dose up to 34%. Implementing demand forecasting system without storage/transport increases actually decreased vaccine availability in certain circumstances. DISCUSSION The potential maximum gains of a demand forecasting system may only be realized if the system is implemented to both augment the supply chain cold storage and transportation. Implementation may have some impact but, in certain circumstances, may hurt delivery. Therefore, implementation of demand forecasting systems with additional storage and transport may be the better approach. Significant decreases in the logistics cost per dose with more administered vaccines support investment in these forecasting systems. CONCLUSION Demand forecasting systems have the potential to greatly improve vaccine demand fulfillment, and decrease logistics cost/dose when implemented with storage and transportation increases direct vaccines. Simulation modeling can demonstrate the potential health and economic benefits of supply chain improvements. PMID:27219341

The impact of implementing a demand forecasting system into a low-income country's supply chain.

PubMed

Mueller, Leslie E; Haidari, Leila A; Wateska, Angela R; Phillips, Roslyn J; Schmitz, Michelle M; Connor, Diana L; Norman, Bryan A; Brown, Shawn T; Welling, Joel S; Lee, Bruce Y

2016-07-12

To evaluate the potential impact and value of applications (e.g. adjusting ordering levels, storage capacity, transportation capacity, distribution frequency) of data from demand forecasting systems implemented in a lower-income country's vaccine supply chain with different levels of population change to urban areas. Using our software, HERMES, we generated a detailed discrete event simulation model of Niger's entire vaccine supply chain, including every refrigerator, freezer, transport, personnel, vaccine, cost, and location. We represented the introduction of a demand forecasting system to adjust vaccine ordering that could be implemented with increasing delivery frequencies and/or additions of cold chain equipment (storage and/or transportation) across the supply chain during varying degrees of population movement. Implementing demand forecasting system with increased storage and transport frequency increased the number of successfully administered vaccine doses and lowered the logistics cost per dose up to 34%. Implementing demand forecasting system without storage/transport increases actually decreased vaccine availability in certain circumstances. The potential maximum gains of a demand forecasting system may only be realized if the system is implemented to both augment the supply chain cold storage and transportation. Implementation may have some impact but, in certain circumstances, may hurt delivery. Therefore, implementation of demand forecasting systems with additional storage and transport may be the better approach. Significant decreases in the logistics cost per dose with more administered vaccines support investment in these forecasting systems. Demand forecasting systems have the potential to greatly improve vaccine demand fulfilment, and decrease logistics cost/dose when implemented with storage and transportation increases. Simulation modeling can demonstrate the potential health and economic benefits of supply chain improvements. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessment of Some Immune Parameters in Occupationally Exposed Nuclear Power Plants Workers

PubMed Central

Panova, Delyana; Djounova, Jana; Rupova, Ivanka; Penkova, Kalina

2015-01-01

The purpose of this article is to analyze the results of a 10-year survey of the radiation effects of some immune parameters of occupationally exposed personnel from the Nuclear Power Plant “Kozloduy”, Bulgaria. 438 persons working in NPP with cumulative doses between 0.06 mSv and 766.36mSv and a control group with 65 persons were studied. Flow cytometry measurements of T, B, natural killer (NK) and natural killer T (NKT) cell lymphocyte populations were performed. Data were interpreted with regard to cumulative doses, length of service and age. The average values of the studied parameters of cellular immunity were in the reference range relative to age and for most of the workers were not significantly different from the control values. Low doses of ionizing radiation showed some trends of change in the number of CD3+CD4+ helper-inducer lymphocytes, CD3+ CD8+ and NKT cell counts. The observed changes in some of the studied parameters could be interpreted in terms of adaptation processes at low doses. At doses above 100–200 mSv, compensatory mechanisms might be involved to balance deviations in lymphocyte subsets. The observed variations in some cases could not be attributed only to the radiation exposure because of the impact of a number of other exogenous and endogenous factors on the immune system. PMID:26675014

SU-F-T-53: Treatment Planning with Inhomogeneity Correction for Intraoperative Radiotherapy Using KV X-Ray Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Y; Ghaly, M; Souri, S

Purpose: The current standard in dose calculation for intraoperative radiotherapy (IORT) using the ZEISS Intrabeam 50 kV x-ray system is based on depth dose measurements in water and no heterogeneous tissue effect has been taken into account. We propose an algorithm for pre-treatment planning including inhomogeneity correction based on data of depth dose measurements in various tissue phantoms for kV x-rays. Methods: Direct depth dose measurements were made in air, water, inner bone and cortical bone phantoms for the Intrabeam 50 kV x-rays with a needle applicator. The data were modelled by a function of power law combining exponential withmore » different parameters. Those phantom slabs used in the measurements were scanned to obtain CT numbers. The x-ray beam initiated from the source isocenter is ray-traced through tissues. The corresponding doses will be deposited/assigned at different depths. On the boundary of tissue/organ changes, the x-ray beam will be re-traced in new tissue/organ starting at an equivalent depth with the same dose. In principle, a volumetric dose distribution can be generated if enough directional beams are traced. In practice, a several typical rays traced may be adequate in providing estimates of maximum dose to the organ at risk and minimum dose in the target volume. Results: Depth dose measurements and modeling are shown in Figure 1. The dose versus CT number is shown in Figure 2. A computer program has been written for Kypho-IORT planning using those data. A direct measurement through 2 mm solid water, 2 mm inner bone, and 1 mm solid water yields a dose rate of 7.7 Gy/min. Our calculation shows 8.1±0.4 Gy/min, consistent with the measurement within 5%. Conclusion: The proposed method can be used to more accurately calculate the dose by taking into account the heterogeneous effect. The further validation includes comparison with Monte Carlo simulation.« less

Optimized image acquisition for breast tomosynthesis in projection and reconstruction space.

PubMed

Chawla, Amarpreet S; Lo, Joseph Y; Baker, Jay A; Samei, Ehsan

2009-11-01

Breast tomosynthesis has been an exciting new development in the field of breast imaging. While the diagnostic improvement via tomosynthesis is notable, the full potential of tomosynthesis has not yet been realized. This may be attributed to the dependency of the diagnostic quality of tomosynthesis on multiple variables, each of which needs to be optimized. Those include dose, number of angular projections, and the total angular span of those projections. In this study, the authors investigated the effects of these acquisition parameters on the overall diagnostic image quality of breast tomosynthesis in both the projection and reconstruction space. Five mastectomy specimens were imaged using a prototype tomosynthesis system. 25 angular projections of each specimen were acquired at 6.2 times typical single-view clinical dose level. Images at lower dose levels were then simulated using a noise modification routine. Each projection image was supplemented with 84 simulated 3 mm 3D lesions embedded at the center of 84 nonoverlapping ROIs. The projection images were then reconstructed using a filtered backprojection algorithm at different combinations of acquisition parameters to investigate which of the many possible combinations maximizes the performance. Performance was evaluated in terms of a Laguerre-Gauss channelized Hotelling observer model-based measure of lesion detectability. The analysis was also performed without reconstruction by combining the model results from projection images using Bayesian decision fusion algorithm. The effect of acquisition parameters on projection images and reconstructed slices were then compared to derive an optimization rule for tomosynthesis. The results indicated that projection images yield comparable but higher performance than reconstructed images. Both modes, however, offered similar trends: Performance improved with an increase in the total acquisition dose level and the angular span. Using a constant dose level and angular span, the performance rolled off beyond a certain number of projections, indicating that simply increasing the number of projections in tomosynthesis may not necessarily improve its performance. The best performance for both projection images and tomosynthesis slices was obtained for 15-17 projections spanning an angular are of approximately 45 degrees--the maximum tested in our study, and for an acquisition dose equal to single-view mammography. The optimization framework developed in this framework is applicable to other reconstruction techniques and other multiprojection systems.

Systems Biology Approach for Understanding MOA, Dose-Response and Susceptibility to Environmental Chemicals

EPA Science Inventory

There is an increasing need for assays for the rapid and efficient assessment of toxicities of large numbers of environmental chemicals. To meet this need, we have developed a battery of cell-based reporter assays that measure the activation of key cellular stress pathways. These...

Gestational Lead Exposure Selectively Decreases Retinal Dopamine Amacrine Cells and Dopamine Content in Adult Mice

PubMed Central

Fox, Donald A.; Hamilton, W. Ryan; Johnson, Jerry E.; Xiao, Weimin; Chaney, Shawntay; Mukherjee, Shradha; Miller, Diane B.; O’Callaghan, James P.

2011-01-01

Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was ≤1, ≤10, ~25 and ~40 µg/dL, respectively, on PN10 and by PN30 all were ≤1 µg/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity. PMID:21703292

Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice.

PubMed

Fox, Donald A; Hamilton, W Ryan; Johnson, Jerry E; Xiao, Weimin; Chaney, Shawntay; Mukherjee, Shradha; Miller, Diane B; O'Callaghan, James P

2011-11-01

Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was ≤ 1, ≤ 10, ~25 and ~40 μg/dL, respectively, on PN10 and by PN30 all were ≤ 1 μg/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity. Copyright © 2011 Elsevier Inc. All rights reserved.

SU-E-I-43: Pediatric CT Dose and Image Quality Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stevens, G; Singh, R

2014-06-01

Purpose: To design an approach to optimize radiation dose and image quality for pediatric CT imaging, and to evaluate expected performance. Methods: A methodology was designed to quantify relative image quality as a function of CT image acquisition parameters. Image contrast and image noise were used to indicate expected conspicuity of objects, and a wide-cone system was used to minimize scan time for motion avoidance. A decision framework was designed to select acquisition parameters as a weighted combination of image quality and dose. Phantom tests were used to acquire images at multiple techniques to demonstrate expected contrast, noise and dose.more » Anthropomorphic phantoms with contrast inserts were imaged on a 160mm CT system with tube voltage capabilities as low as 70kVp. Previously acquired clinical images were used in conjunction with simulation tools to emulate images at different tube voltages and currents to assess human observer preferences. Results: Examination of image contrast, noise, dose and tube/generator capabilities indicates a clinical task and object-size dependent optimization. Phantom experiments confirm that system modeling can be used to achieve the desired image quality and noise performance. Observer studies indicate that clinical utilization of this optimization requires a modified approach to achieve the desired performance. Conclusion: This work indicates the potential to optimize radiation dose and image quality for pediatric CT imaging. In addition, the methodology can be used in an automated parameter selection feature that can suggest techniques given a limited number of user inputs. G Stevens and R Singh are employees of GE Healthcare.« less

Infantile hemangioma: treatment with short course systemic corticosteroid therapy as an alternative for propranolol.

PubMed

Nieuwenhuis, Klaske; de Laat, Peter C J; Janmohamed, Sherief R; Madern, Gerard C; Oranje, Arnold P

2013-01-01

Infantile hemangiomas (IHs) are increasingly being treated with propranolol or other beta-blockers, but before this therapeutic option was available, oral glucocorticosteroids (GCSs) were the criterion standard treatment and are still the alternative modality in problematic cases. Nevertheless, there is no standard treatment protocol for the dose and duration of GCSs. Long-term treatment with GCSs is associated with unwanted side effects such as growth suppression, behavioral changes, and reflux. Twenty-one children with troublesome IHs were treated according to an algorithm with 3 mg/kg/day of oral prednisolone divided three times per day with varying duration and number of GCS courses. Two blinded investigators independently interpreted therapy results using the Hemangioma Activity Score (HAS). Side effects were determined according to reports in patient charts and parental questionnaires. The median duration of a short course of GCSs was 2 weeks (range 1-6 weeks). The number of courses was 2 (range 1-5). The median cumulative dose was 91 mg/kg. Growth stabilized in all patients, with a good response (>50% reduction in HAS) in 62% and a favorable response (30-50% reduction is HAS) in 23%. Twelve of the 21 children (57%) had minor side effects. Persistent side effects did not occur. Intermittent short course, systemic, high-dose GCS therapy is an effective and safe treatment modality for IH, with a substantially lower cumulative dose of GCSs compared to prolonged therapy and no major side effects. This treatment is an alternative in cases in which propranolol fails or is contraindicated. © 2012 Wiley Periodicals, Inc.

Orally administered fructose increases the numbers of peripheral lymphocytes reduced by exposure of mice to gamma or SPE-like proton radiation

NASA Astrophysics Data System (ADS)

Romero-Weaver, A. L.; Ni, J.; Lin, L.; Kennedy, A. R.

2014-07-01

Exposure of the whole body or a major portion of the body to ionizing radiation can result in Acute Radiation Sickness (ARS), which can cause symptoms that range from mild to severe, and include death. One of the syndromes that can occur during ARS is the hematopoietic syndrome, which is characterized by a reduction in bone marrow cells as well as the number of circulating blood cells. Doses capable of causing this syndrome can result from conventional radiation therapy and accidental exposure to ionizing radiation. It is of concern that this syndrome could also occur during space exploration class missions in which astronauts could be exposed to significant doses of solar particle event (SPE) radiation. Of particular concern is the reduction of lymphocytes and granulocytes, which are major components of the immune system. A significant reduction in their numbers can compromise the immune system, causing a higher risk for the development of infections which could jeopardize the success of the mission. Although there are no specific countermeasures utilized for the ARS resulting from exposure to space radiation(s), granulocyte colony-stimulating factor (G-CSF) has been proposed as a countermeasure for the low number of neutrophils caused by SPE radiation, but so far no countermeasure exists for a reduced number of circulating lymphocytes. The present study demonstrates that orally administered fructose significantly increases the number of peripheral lymphocytes reduced by exposure of mice to 2 Gy of gamma- or SPE-like proton radiation, making it a potential countermeasure for this biological end-point.

In vivo dose verification of IMRT treated head and neck cancer patients.

PubMed

Engström, Per E; Haraldsson, Pia; Landberg, Torsten; Sand Hansen, Hanne; Aage Engelholm, Svend; Nyström, Håkan

2005-01-01

An independent in vivo dose verification procedure for IMRT treatments of head and neck cancers was developed. Results of 177 intracavitary TLD measurements from 10 patients are presented. The study includes data from 10 patients with cancer of the rhinopharynx or the thyroid treated with dynamic IMRT. Dose verification was performed by insertion of a flexible naso-oesophageal tube containing TLD rods and markers for EPID and simulator image detection. Part of the study focussed on investigating the accuracy of the TPS calculations in the presence of inhomogeneities. Phantom measurements and Monte Carlo simulations were performed for a number of geometries involving lateral electronic disequilibrium and steep density shifts. The in vivo TLD measurements correlated well with the predictions of the treatment planning system with a measured/calculated dose ratio of 1.002+/-0.051 (1 SD, N=177). The measurements were easily performed and well tolerated by the patients. We conclude that in vivo intracavitary dosimetry with TLD is suitable and accurate for dose determination in intensity-modulated beams.

TU-EF-204-07: Add Tube Current Modulation to a Low Dose Simulation Tool for CT Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, Y.; Department of Physics, University of Arizona, Tucson, AZ; Wen, G.

2015-06-15

Purpose: We extended the capabilities of a low dose simulation tool to model Tube-Current Modulation (TCM). TCM is widely used in clinical practice to reduce radiation dose in CT scans. We expect the tool to be valuable for various clinical applications (e.g., optimize protocols, compare reconstruction techniques and evaluate TCM methods). Methods: The tube current is input as a function of z location, instead of a fixed value. Starting from the line integrals of a scan, a new Poisson noise realization at a lower dose is generated for each view. To validate the new functionality, we compared simulated scans withmore » real scans in image space. Results: First we assessed noise in the difference between the low-dose simulations and the original high-dose scan. When the simulated tube current is a step function of z location, the noise at each segment matches the noise of 3 separate constant-tube-current-simulations. Secondly, with a phantom that forces TCM, we compared a low-dose simulation with an equivalent real low-dose scan. The mean CT number of the simulated scan and the real low-dose scan were 137.7±0.6 and 137.8±0.5 respectively. Furthermore, with 240 ROIs, the noise of the simulated scan and the real low-dose scan were 24.03±0.45 and 23.99±0.43 respectively, and they were not statistically different (2-sample t-test, p-value=0.28). The facts that the noise reflected the trend of the TCM curve, and that the absolute noise measurements were not statistically different validated the TCM function. Conclusion: We successfully added tube-current modulation functionality in an existing low dose simulation tool. We demonstrated that the noise reflected an input tube-current modulation curve. In addition, we verified that the noise and mean CT number of our simulation agreed with a real low dose scan. The authors are all employees of Philips. Yijun Ding is also supported by NIBIB P41EB002035 and NIBIB R01EB000803.« less

In vivo prostate IMRT dosimetry with MOSFET detectors using brass buildup caps

PubMed Central

Varadhan, Raj; Miller, John; Garrity, Brenden; Weber, Michael

2006-01-01

The feasibility of using dual bias metal oxide semiconductor field effect transistor (MOSFET) detectors with the new hemispherical brass buildup cap for in vivo dose measurements in prostate intensity‐modulated radiotherapy (IMRT) treatments was investigated and achieved. In this work, MOSFET detectors with brass buildup caps placed on the patient's skin surface on the central axis of the individual IMRT beams are used to determine the maximum entrance dose (Dmax) from the prostate IMRT fields. A general formalism with various correction factors taken into account to predict Dmax entrance dose for the IMRT fields with MOSFETs was developed and compared against predicted dose from the treatment‐planning system (TPS). We achieved an overall accuracy of better than ±5% on all measured fields for both 6‐MV and 10‐MV beams when compared to predicted doses from the Philips Pinnacle 3 and CMS XiO TPSs, respectively. We also estimate the total uncertainty in estimation of MOSFET dose in the high‐sensitivity mode for IMRT therapy to be 4.6%. PACS numbers: 87.53Xd, 87.56Fc PMID:17533354

A simple 3-day "rush" venom immunotherapy protocol: documentation of safety.

PubMed

Kalogeromitros, D; Makris, M; Koti, I; Chliva, C; Mellios, A; Avgerinou, G; Theoharides, T C

2010-01-01

Venom immunotherapy (VIT) is the only effective treatment for hymenoptera hypersensitivity, but conventional protocols require a few weeks. We present the safety of a 3-day "rush" protocol that requires only 7 injections and 255 mgr cumulative dose before the 100 microg maintenance dose. Forty-nine patients (33 males, 16 females) of mean age 43.57+/-12.9 yrs received "rush" VIT. Only 7 injections were required until the maintenance dose of 100 mgr was reached on Day 5. On Day 1, four injections were administered with initial dose of 5 mgr and total dose of 75 microg. On Day 3 a cumulative dose of 180 mgr was administered in three injections (40 mgr, 60 mgr and 80 mgr). A dose of 100 mgr was administered on Day 5. Twenty-nine individuals were treated with Honey-Bee venom; 18 with Common wasp; 5 with Paper Wasp; while 13 patients received Mixed Vespid preparation. Inclusion criteria were documented IgE-mediated allergy with intradermal sensitivity to < or =0.1 mgr/ml venom concentration and concomitant detection of specific venom IgE > or =0.35 kU/l. All patients reached the maintenance dose. Forty-nine patients received 65 immunotherapy courses, resulting in 1520 injections. Thirty-three systemic reactions: 7 during building phase (1.5%); and 26 in the maintenance dose (2.4%) were observed in 9 patients. The percentage of reactions/total injection number was 2.2%; all reactions were mild-to-moderate. Fourteen patients reported documented field stings at least two months after VIT onset with only one reported mild systemic reaction. We propose a simple "rush" VIT protocol in an outpatient setting as an easy-to-perform alternative option for VIT induction phase. Copyright 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

Randomized Double-Blinded Dose Escalation Trial of Triptorelin for Ovary Protection in Childhood-Onset Systemic Lupus Erythematosus

PubMed Central

Brunner, Hermine I.; Silva, Clovis A; Reiff, Andreas; Higgins, Gloria C.; Imundo, Lisa; Williams, Calvin B.; Wallace, Carol A; Aikawa, Nadia E.; Nelson, Shannen; Klein-Gitelman, Marisa S.; Rose, Susan R.

2015-01-01

Objectives To determine for females with childhood-onset systemic lupus erythematosus (cSLE) who require cyclophosphamide the dose of triptorelin that suffices to maintain complete ovarian suppression (COS); measure the time needed to achieve ovarian suppression after triptorelin initiation, and explore the safety of triptorelin. Methods In this randomized double-blind placebo-controlled dose-escalation study females (< 21 years) were randomized 4:1 to receive triptorelin or placebo (25 triptorelin, 6 placebo). Starting doses of triptorelin between 25 and 100 microgram/kg/dose were used. Triptorelin dosage was escalated until COS was maintained. The primary outcome was the weight-adjusted dose of triptorelin that for at least 90% of the patients provides COS based on Gonadotropin-releasing-hormone Agonist Stimulation Testing. Secondary outcomes were time to ovarian suppression measured by unstimulated FSH and LH levels after study drug initiation. Results Triptorelin dosed at 120 microgram/kg bodyweight led to sustained COS in 90% of the patients. After the initial dose of triptorelin 22 days were needed for achieve COS. Rates of adverse events (AE) and serious adverse events (SAE) per 100 patient-month of follow-up were not higher in the triptorelin group as compared to the placebo group (triptorelin vs. placebo; AE: 189 vs. 362; SAE: 2.05 vs. 8.48). Conclusions For achieving and maintaining COS high doses of triptorelin are needed but appear to be well tolerated in adolescent females with cSLE. Our data suggest that a lag time of 22 days after triptorelin initiation is required before starting or continuing cyclophosphamide-therapy. Trial Registration Number clinicaltrials.gov identifier: NCT00124514 PMID:25676588

Comparison of pediatric radiation dose and vessel visibility on angiographic systems using piglets as a surrogate: antiscatter grid removal vs. lower detector air kerma settings with a grid — a preclinical investigation

PubMed Central

Racadio, John M.; Abruzzo, Todd A.; Johnson, Neil D.; Patel, Manish N.; Kukreja, Kamlesh U.; den Hartog, Mark. J. H.; Hoornaert, Bart P.A.; Nachabe, Rami A.

2015-01-01

The purpose of this study was to reduce pediatric doses while maintaining or improving image quality scores without removing the grid from X‐ray beam. This study was approved by the Institutional Animal Care and Use Committee. Three piglets (5, 14, and 20 kg) were imaged using six different selectable detector air kerma (Kair) per frame values (100%, 70%, 50%, 35%, 25%, 17.5%) with and without the grid. Number of distal branches visualized with diagnostic confidence relative to the injected vessel defined image quality score. Five pediatric interventional radiologists evaluated all images. Image quality score and piglet Kair were statistically compared using analysis of variance and receiver operating curve analysis to define the preferred dose setting and use of grid for a visibility of 2nd and 3rd order vessel branches. Grid removal reduced both dose to subject and imaging quality by 26%. Third order branches could only be visualized with the grid present; 100% detector Kair was required for smallest pig, while 70% detector Kair was adequate for the two larger pigs. Second order branches could be visualized with grid at 17.5% detector Kair for all three pig sizes. Without the grid, 50%, 35%, and 35% detector Kair were required for smallest to largest pig, respectively. Grid removal reduces both dose and image quality score. Image quality scores can be maintained with less dose to subject with the grid in the beam as opposed to removed. Smaller anatomy requires more dose to the detector to achieve the same image quality score. PACS numbers: 87.53.Bn, 87.57.N‐, 87.57.cj, 87.59.cf, 87.59.Dj PMID:26699297

Boiling histotripsy lesion characterization on a clinical magnetic resonance imaging-guided high intensity focused ultrasound system

PubMed Central

Eranki, Avinash; Farr, Navid; Partanen, Ari; V. Sharma, Karun; Chen, Hong; Rossi, Christopher T.; Kothapalli, Satya V. V. N.; Oetgen, Matthew; Kim, AeRang; H. Negussie, Ayele; Woods, David; J. Wood, Bradford; C. W. Kim, Peter; S. Yarmolenko, Pavel

2017-01-01

Purpose High intensity focused ultrasound (HIFU) is a non-invasive therapeutic technique that can thermally ablate tumors. Boiling histotripsy (BH) is a HIFU approach that can emulsify tissue in a few milliseconds. Lesion volume and temperature effects for different BH sonication parameters are currently not well characterized. In this work, lesion volume, temperature distribution, and area of lethal thermal dose were characterized for varying BH sonication parameters in tissue-mimicking phantoms (TMP) and demonstrated in ex vivo tissues. Methods The following BH sonication parameters were varied using a clinical MR-HIFU system (Sonalleve V2, Philips, Vantaa, Finland): acoustic power, number of cycles/pulse, total sonication time, and pulse repetition frequency (PRF). A 3×3×3 pattern was sonicated inside TMP’s and ex vivo tissues. Post sonication, lesion volumes were quantified using 3D ultrasonography and temperature and thermal dose distributions were analyzed offline. Ex vivo tissues were sectioned and stained with H&E post sonication to assess tissue damage. Results Significant increase in lesion volume was observed while increasing the number of cycles/pulse and PRF. Other sonication parameters had no significant effect on lesion volume. Temperature full width at half maximum at the end of sonication increased significantly with all parameters except total sonication time. Positive correlation was also found between lethal thermal dose and lesion volume for all parameters except number of cycles/pulse. Gross pathology of ex vivo tissues post sonication displayed either completely or partially damaged tissue at the focal region. Surrounding tissues presented sharp boundaries, with little or no structural damage to adjacent critical structures such as bile duct and nerves. Conclusion Our characterization of effects of HIFU sonication parameters on the resulting lesion demonstrates the ability to control lesion morphologic and thermal characteristics with a clinical MR-HIFU system in TMP’s and ex vivo tissues. We demonstrate that this system can produce spatially precise lesions in both phantoms and ex vivo tissues. The results provide guidance on a preliminary set of BH sonication parameters for this system, with a potential to facilitate BH translation to the clinic. PMID:28301597

A study of structural and mechanical properties of nano-crystalline tungsten nitride film synthesis by plasma focus

NASA Astrophysics Data System (ADS)

Hussnain, Ali; Singh Rawat, Rajdeep; Ahmad, Riaz; Hussain, Tousif; Umar, Z. A.; Ikhlaq, Uzma; Chen, Zhong; Shen, Lu

2015-02-01

Nano-crystalline tungsten nitride thin films are synthesized on AISI-304 steel at room temperature using Mather-type plasma focus system. The surface properties of the exposed substrate against different deposition shots are examined for crystal structure, surface morphology and mechanical properties using X-ray diffraction (XRD), atomic force microscope, field emission scanning electron microscope and nano-indenter. The XRD results show the growth of WN and WN2 phases and the development of strain/stress in the deposited films by varying the number of deposition shots. Morphology of deposited films shows the significant change in the surface structure with different ion energy doses (number of deposition shots). Due to the effect of different ion energy doses, the strain/stress developed in the deposited film leads to an improvement of hardness of deposited films.

Microglial disruption in young mice with early chronic lead exposure☆

PubMed Central

Sobin, Christina; Montoya, Mayra Gisel Flores; Parisi, Natali; Schaub, Tanner; Cervantes, Miguel; Armijos, Rodrigo X.

2013-01-01

The mechanisms by which early chronic lead (Pb) exposure alter brain development have not been identified. We examined neuroimmune system effects in C57BL/6J mice with Pb exposure, including levels that may be common among children in lower socioeconomic income environments. Pups were exposed via dams’ drinking water from birth to post-natal day 28 to low, high or no Pb conditions. We compared gene expression of neuroinflammatory markers (study 1); and microglial mean cell body volume and mean cell body number in dentate gyrus, and dentate gyrus volume (study 2). Blood Pb levels in exposed animals at sacrifice (post-natal day 28) ranged from 2.66 to 20.31 μg/dL. Only interleukin-6 (IL6) differed between groups and reductions were dose-dependent. Microglia cell body number also differed between groups and reductions were dose-dependent. As compared with controls, microglia cell body volume was greater but highly variable in only low-dose animals; dentate gyri volumes in low- and high-dose animals were reduced. The results did not support a model of increased neuroinflammation. Instead, early chronic exposure to Pb disrupted microglia via damage to, loss of, or lack of proliferation of microglia in the developing brains of Pb-exposed animals. PMID:23598043

Optimal field-splitting algorithm in intensity-modulated radiotherapy: Evaluations using head-and-neck and female pelvic IMRT cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dou, Xin; Kim, Yusung, E-mail: yusung-kim@uiowa.edu; Bayouth, John E.

2013-04-01

To develop an optimal field-splitting algorithm of minimal complexity and verify the algorithm using head-and-neck (H and N) and female pelvic intensity-modulated radiotherapy (IMRT) cases. An optimal field-splitting algorithm was developed in which a large intensity map (IM) was split into multiple sub-IMs (≥2). The algorithm reduced the total complexity by minimizing the monitor units (MU) delivered and segment number of each sub-IM. The algorithm was verified through comparison studies with the algorithm as used in a commercial treatment planning system. Seven IMRT, H and N, and female pelvic cancer cases (54 IMs) were analyzed by MU, segment numbers, andmore » dose distributions. The optimal field-splitting algorithm was found to reduce both total MU and the total number of segments. We found on average a 7.9 ± 11.8% and 9.6 ± 18.2% reduction in MU and segment numbers for H and N IMRT cases with an 11.9 ± 17.4% and 11.1 ± 13.7% reduction for female pelvic cases. The overall percent (absolute) reduction in the numbers of MU and segments were found to be on average −9.7 ± 14.6% (−15 ± 25 MU) and −10.3 ± 16.3% (−3 ± 5), respectively. In addition, all dose distributions from the optimal field-splitting method showed improved dose distributions. The optimal field-splitting algorithm shows considerable improvements in both total MU and total segment number. The algorithm is expected to be beneficial for the radiotherapy treatment of large-field IMRT.« less

Stabilization of Tetanus Toxoid Encapsulated in PLGA Microspheres

PubMed Central

Jiang, Wenlei; Schwendeman, Steven P.

2014-01-01

Delivery of vaccine antigens from controlled-release poly(lactic/glycolic acid) (PLGA) microspheres is a novel approach to reduce the number of antigen doses required for protection against infection. A major impediment to developing single-shot vaccines is encapsulated antigen instability during months of exposure to physiological conditions. For example, efforts to control neonatal tetanus in developing countries with a single-dose TT vaccine have been plagued by poor stability of the 150 kDa formaldehyde-detoxified protein antigen, tetanus toxoid (TT) in PLGA microspheres. We examined the denatured states of PLGA-encapsulated TT, revealing two primary TT instability mechanisms: 1) protein aggregation mediated by formaldehyde and 2) acid-induced protein unfolding and epitope damage. Further, we systemically identified excipients which can efficiently inhibit TT aggregation and retain TT antigenicity under simulated deleterious conditions, i.e., elevated temperature and humidity. By employing these novel additives in the PLGA system, we report the slow and continuous release of high doses of TT for one month with retained antigen stability during bioerosion of PLGA. PMID:18710256

Bulgarian experience in the establishment of reference dose levels and implementation of a quality control system in diagnostic radiology.

PubMed

Vassileva, J; Dimov, A; Slavchev, A; Karadjov, A

2005-01-01

Results from a Bulgarian patient dose survey in diagnostic radiology are presented. Reference levels for entrance surface dose (ESD) were 0.9 mGy for chest radiography (PA), 30 mGy for lumbar spine (Lat), 10 mGy for pelvis, 5 mGy for skull (AP), 3 mGy for skull (Lat) and 13 mGy for mammography. Quality control (QC) programmes were proposed for various areas of diagnostic radiology. Film processing QC warranted special attention. Proposed QC programmes included parameters to be tested, level of expertise needed and two action levels: remedial and suspension. Programmes were tested under clinical conditions to assess initial results and draw conclusions for further QC system development. On the basis of international experience, measurement protocols were developed for all parameters tested. QC equipment was provided as part of the PHARE project. A future problem for QC programme implementation may be the small number of medical physics experts in diagnostic radiology.

New method for estimation of fluence complexity in IMRT fields and correlation with gamma analysis

NASA Astrophysics Data System (ADS)

Hanušová, T.; Vondráček, V.; Badraoui-Čuprová, K.; Horáková, I.; Koniarová, I.

2015-01-01

A new method for estimation of fluence complexity in Intensity Modulated Radiation Therapy (IMRT) fields is proposed. Unlike other previously published works, it is based on portal images calculated by the Portal Dose Calculation algorithm in Eclipse (version 8.6, Varian Medical Systems) in the plane of the EPID aS500 detector (Varian Medical Systems). Fluence complexity is given by the number and the amplitudes of dose gradients in these matrices. Our method is validated using a set of clinical plans where fluence has been smoothed manually so that each plan has a different level of complexity. Fluence complexity calculated with our tool is in accordance with the different levels of smoothing as well as results of gamma analysis, when calculated and measured dose matrices are compared. Thus, it is possible to estimate plan complexity before carrying out the measurement. If appropriate thresholds are determined which would distinguish between acceptably and overly modulated plans, this might save time in the re-planning and re-measuring process.

[Do poor-responder patients benefit from increasing the daily gonadotropin dose from 300 to 450 IU during controlled ovarian hyperstimulation for IVF?].

PubMed

Haas, Jigal; Zilberberg, Eran; Kedem, Alon; Dar, Shir; Orvieto, Raoul

2015-02-01

We aim to evaluate the IVF-ET outcome in patients receiving a high daily dose (300 IU) of gonadotropins during controlled ovarian hyperstimulation (COH) for IVF and to assess the role of increasing the daily dose to 450 IU on improving outcome. All consecutive women admitted to our IVF unit during an 11 year period who underwent COH consisting of daily gonadotropin dose of 300 IU were included in the study. The ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate were assessed. We also evaluated the subsequent cycle, using daily gonadotropin doses of 450 IU, among those patients who did not conceive using the 300 IU daily gonadotropin dose. Nine hundred and forty-nine consecutive IVF cycles were evaluated. Patients who conceived using the daily gonadotropin dose of 300 IU (n = 133, 14% pregnancy rate) had significantly longer stimulation, yielded higher numbers of oocytes retrieved, fertilization rate and number of embryos transferred, compared to those who did not conceive. Moreover, while comparing IVF cycles using daily gonadotropin doses of 300 IU to 450 IU (n = 117), no in-between group differences were observed, except for significantly higher yields of oocytes retrieved. Moreover, cycles using daily gonadotropin doses of 450 IU resulted in a 7.7 live-birth rate. In poor responders undergoing COH with a daily gonadotropin dose of 300 IU, increasing the dose to 450 IU resulted in significantly higher oocyte yields and a reasonable live birth rate.

SU-E-J-135: Feasibility of Using Quantitative Cone Beam CT for Proton Adaptive Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jingqian, W; Wang, Q; Zhang, X

2015-06-15

Purpose: To investigate the feasibility of using scatter corrected cone beam CT (CBCT) for proton adaptive planning. Methods: Phantom study was used to evaluate the CT number difference between the planning CT (pCT), quantitative CBCT (qCBCT) with scatter correction and calibrated Hounsfield units using adaptive scatter kernel superposition (ASKS) technique, and raw CBCT (rCBCT). After confirming the CT number accuracy, prostate patients, each with a pCT and several sets of weekly CBCT, were investigated for this study. Spot scanning proton treatment plans were independently generated on pCT, qCBCT and rCBCT. The treatment plans were then recalculated on all images. Dose-volume-histogrammore » (DVH) parameters and gamma analysis were used to compare between dose distributions. Results: Phantom study suggested that Hounsfield unit accuracy for different materials are within 20 HU for qCBCT and over 250 HU for rCBCT. For prostate patients, proton dose could be calculated accurately on qCBCT but not on rCBCT. When the original plan was recalculated on qCBCT, tumor coverage was maintained when anatomy was consistent with pCT. However, large dose variance was observed when patient anatomy change. Adaptive plan using qCBCT was able to recover tumor coverage and reduce dose to normal tissue. Conclusion: It is feasible to use qu antitative CBCT (qCBCT) with scatter correction and calibrated Hounsfield units for proton dose calculation and adaptive planning in proton therapy. Partly supported by Varian Medical Systems.« less

Antipsychotic treatment dosing profile in patients with schizophrenia evaluated with electronic monitoring (MEMS®).

PubMed

Acosta, Francisco J; Ramallo-Fariña, Yolanda; Bosch, Esperanza; Mayans, Teresa; Rodríguez, Carlos J; Caravaca, Ana

2013-05-01

Although the Medication Event Monitoring System (MEMS®) device offers accurate information on treatment dosing profile, such profile has never been studied in patients with schizophrenia. Enhancing our knowledge on this issue would help in developing intervention strategies to improve adherence to antipsychotic treatment in these patients. 74 outpatients with schizophrenia were monitored with the MEMS device for a 3-month period, for evaluation of antipsychotic treatment dosing profile, possible influence of medication schedule-related variables, adherence to treatment--considering dose intake within prescribed timeframes--and possible Hawthorne's effect of using the MEMS device. Dose-omission gaps occurred in 18.7% of monitoring days, most frequently during weekends, almost significantly. Almost one-third of prescribed doses were taken out of prescribed time. Neither the prescribed number of daily doses nor the indicated time of the day for dose intake (breakfast, dinner), were associated with correct antipsychotic dosing. Excess-dose was rare in general, and more frequent out of prescribed dose timeframe. No Hawthorne's effect was found for the MEMS device. Adherence reached only 35% according to a definition that included dose intake within prescribed timeframes. Antipsychotic treatment dosing was considerably irregular among patients with schizophrenia. Strategies to reduce dose-omission gaps and increase dosing within prescribed timeframes seem to be necessary. Gaining knowledge on precise oral antipsychotic dosing profiles or the influence of schedule-related variables may be useful to design strategies towards enhancing adherence. There appears to be no Hawthorne's effect associated with the use of MEMS devices in outpatients with schizophrenia. Copyright © 2013 Elsevier B.V. All rights reserved.

SU-F-BRE-07: Experimental Validation of a Lung SBRT Technique Using a Novel, True Volumetric Plenoptic-Plastic-Scintillator Detector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goulet, M; Rilling, M; Gingras, L

2014-06-15

Purpose: Lung SBRT is being used by an increasing number of clinics, including our center which recently treated its first patient. In order to validate this technique, the 3D dose distribution of the SBRT plan was measured using a previously developed 3D detector based on plenoptic camera and plastic scintillator technology. The excellent agreement between the detector measurement and the expected dose from the treatment planning system Pinnacle{sup 3} shows great promise and amply justify the development of the technique. Methods: The SBRT treatment comprised 8 non-coplanar 6MV photon fields with a mean field size of 12 cm{sup 2} atmore » isocentre and a total prescription dose of 12Gy per fraction for a total of 48Gy. The 3D detector was composed of a 10×10×10 cm{sup 2} EJ-260 water-equivalent plastic scintillator embedded inside a truncated cylindrical acrylic phantom of 10cm radius. The scintillation light was recorded using a static R5 light-field camera and the 3D dose was reconstructed at a 2mm resolution in all 3 dimensions using an iterative backprojection algorithm. Results: The whole 3D dose distribution was recorded at a rate of one acquisition per second. The mean absolute dose difference between the detector and Pinnacle{sup 3} was 1.3% over the region with more than 10% of the maximum dose. 3D gamma tests performed over the same region yield passing rates of 98.8% and 96.6% with criteria of 3%/1mm and 2%/1mm, respectively. Conclusion: Experimental results showed that our beam modeling and treatment planning system calculation was adequate for the safe administration of small field/high dose techniques such as SBRT. Moreover, because of the real-time capability of the detector, further validation of small field rotational, dynamic or gated technique can be monitored or verified by this system.« less

A Comparison of Four Indices for Combining Distance and Dose Differences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, Simon J., E-mail: simon.thomas@addenbrookes.nhs.uk; Cowley, Ian R.

2012-04-01

Purpose: When one is comparing two dose distributions, a number of methods have been published to combine dose difference and distance to agreement into a single measure. Some have been defined as pass/fail indices and some as numeric indices. We show that the pass/fail indices can all be used to derive numeric indices, and we compare the results of using these indices to evaluate one-dimensional (1D) and three-dimensional (3D) dose distributions, with the aim of selecting the most appropriate index for use in different circumstances. Methods and Materials: The indices compared are the gamma index, the kappa index, the indexmore » in International Commission on Radiation Units and Measurements Report 83, and a box index. Comparisons are made for 1D and 3D distributions. The 1D distribution is chosen to have a variety of dose gradients. The 3D distribution is taken from a clinical treatment plan. The effect of offsetting distributions by known distances and doses is studied. Results: The International Commission on Radiation Units and Measurements Report 83 index causes large discontinuities unless the dose gradient cutoff is set to equal the ratio of the dose tolerance to the distance tolerance. If it is so set, it returns identical results to the kappa index. Where the gradient is very high or very low, all the indices studied in this article give similar results for the same tolerance values. For moderate gradients, they differ, with the box index being the least strict, followed by the gamma index, and with the kappa index being the most strict. Conclusions: If the clinical tolerances are much greater than the uncertainties of the measuring system, the kappa index should be used, with tolerance values determined by the clinical tolerances. In cases where the uncertainties of the measuring system dominate, the box index will be best able to determine errors in the delivery system.« less

Comparative Iron Oxide Nanoparticle Cellular Dosimetry and Response in Mice by the Inhalation and Liquid Cell Culture Exposure Routes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teeguarden, Justin G.; Mikheev, Vladimir B.; Minard, Kevin R.

testing the rapidly growing number of nanomaterials requires large scale use of in vitro systems under the presumption that these systems are sufficiently predictive or descriptive of responses in in vivo systems for effective use in hazard ranking. We hypothesized that improved relationships between in vitro and in vivo models of experimental toxicology for nanomaterials would result from placing response data in vitro and in vivo on the same dose scale, the amount of material associated with cells (target cell dose). Methods: Balb/c mice were exposed nose-only to an aerosol of 12.8 nm (68.6 nm CMD, 19.9 mg/m3, 4 hours)more » super paramagnetic iron oxide particles, target cell doses were calculated and biomarkers of response anchored with histological evidence were identified by global transcriptomics. Representative murine epithelial and macrophage cell types were exposed in vitro to the same material in liquid suspension for four hours and levels nanoparticle regulated cytokine transcripts identified in vivo were quantified as a function of measured nanoparticle cellular dose. Results. Target tissue doses of 0.009-0.4 μg SPIO/cm2 lung led to an inflammatory response in the alveolar region characterized by interstitial inflammation and macrophage infiltration. In vitro, higher target tissue doses of ~1.2-4 μg SPIO/ cm2 of cells were required to induce transcriptional regulation of markers of inflammation, CXCL2 CCL3, in C10 lung epithelial cells. Estimated in vivo macrophage SPIO nanoparticle doses ranged from 1-100 pg/cell, and induction of inflammatory markers was observed in vitro in macrophages at doses of 8-35 pg/cell. Conclusions: Application of target tissue dosimetry revealed good correspondence between target cell doses triggering inflammatory processes in vitro and in vivo in the alveolar macrophage population, but not in the epithelial cells of the alveolar region. These findings demonstrate the potential for target tissue dosimetry to enable the more quantitative comparison of in vitro and in vivo systems advance their use for hazard assessment and extrapolation to humans. The mildly inflammogentic cellular doses experienced by mice were similar those calculated for humans exposed to the same at the existing permissible exposure limit of 10 mg/m3 iron oxide (as Fe).« less

Development and evaluation of a system to assess antimicrobial drug use in farm animals: results of an Austrian study.

PubMed

Ferner, C; Obritzhauser, W; Fuchs, K; Schmerold, I

2014-11-01

The objective of this study was to develop and evaluate a feasible system for the collection of antimicrobial consumption data in farm animals in Austria. An electronic registry of all antibacterial pharmaceuticals approved in Austria for use in farm animals was created, listing product name, marketing authorisation number, active ingredient, package unit, strength, target species (cattle, swine, poultry), route of administration and indication, and allocating the corresponding code of the World Health Organization (WHO) Anatomical Therapeutic Chemical classification system for veterinary medicines to each substance (ATCvet-code). Different units (absolute quantities, animal daily dose, assumed daily product dose) enabled computation of the amounts of antimicrobials as pure substance, the constituents of a veterinary medicinal product, or the number of administrations. Two data collection systems were evaluated: (1) data transfer from the management software of veterinary practices or the Austrian Poultry Health Service; and (2) on-site data collection by manual data input from prescription records into an electronic registry. A total of 14,267 data sets provided by 18 practices were documented during the period January 2008 to March 2010. The total weight of active substances reported amounted to more than 5.4 tonnes for all species studied. The systems proved suitable for routine data acquisition and were considered in a recent national regulation on the surveillance of sale and consumption of veterinary antimicrobial substances. British Veterinary Association.

[Dose loads on and radiation risk values for cosmonauts on a mission to Mars estimated from actual Martian vehicle engineering development].

PubMed

Shafirkin, A V; Kolomenskiĭ, A V; Mitrikas, V G; Petrov, V M

2010-01-01

The current design philosophy of a Mars orbiting vehicle, takeoff and landing systems and the transport return vehicle was taken into consideration for calculating the equivalent doses imparted to cosmonaut's organs and tissues by galactic cosmic rays, solar rays and the Earth's radiation belts, values of the total radiation risk over the lifespan following the mission and over the whole career period, and possible shortening of life expectancy. There are a number of uncertainties that should be evaluated, and radiation limits specified before setting off to Mars.

Linac-based extracranial radiosurgery with Elekta volumetric modulated arc therapy and an anatomy-based treatment planning system: Feasibility and initial experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cilla, Savino, E-mail: savinocilla@gmail.com; Deodato, Francesco; Macchia, Gabriella

We reported our initial experience in using Elekta volumetric modulated arc therapy (VMAT) and an anatomy-based treatment planning system (TPS) for single high-dose radiosurgery (SRS-VMAT) of liver metastases. This study included a cohort of 12 patients treated with a 26-Gy single fraction. Single-arc VMAT plans were generated with Ergo++ TPS. The prescription isodose surface (IDS) was selected to fulfill the 2 following criteria: 95% of planning target volume (PTV) reached 100% of the prescription dose and 99% of PTV reached a minimum of 90% of prescription dose. A 1-mm multileaf collimator (MLC) block margin was added around the PTV. Formore » a comparison of dose distributions with literature data, several conformity indexes (conformity index [CI], conformation number [CN], and gradient index [GI]) were calculated. Treatment efficiency and pretreatment dosimetric verification were assessed. Early clinical data were also reported. Our results reported that target and organ-at-risk objectives were met for all patients. Mean and maximum doses to PTVs were on average 112.9% and 121.5% of prescribed dose, respectively. A very high degree of dose conformity was obtained, with CI, CN, and GI average values equal to 1.29, 0.80, and 3.63, respectively. The beam-on-time was on average 9.3 minutes, i.e., 0.36 min/Gy. The mean number of monitor units was 3162, i.e., 121.6 MU/Gy. Pretreatment verification (3%-3 mm) showed an optimal agreement with calculated values; mean γ value was 0.27 and 98.2% of measured points resulted with γ < 1. With a median follow-up of 16 months complete response was observed in 12/14 (86%) lesions; partial response was observed in 2/14 (14%) lesions. No radiation-induced liver disease (RILD) was observed in any patients as well no duodenal ulceration or esophagitis or gastric hemorrhage. In conclusion, this analysis demonstrated the feasibility and the appropriateness of high-dose single-fraction SRS-VMAT in liver metastases performed with Elekta VMAT and Ergo++ TPS. Preliminary clinical outcomes showed a high rate of local control and minimum incidence of acute toxicity.« less

Preclinical dose number and its application in understanding drug absorption risk and formulation design for preclinical species.

PubMed

Wuelfing, W Peter; Daublain, Pierre; Kesisoglou, Filippos; Templeton, Allen; McGregor, Caroline

2015-04-06

In the drug discovery setting, the ability to rapidly identify drug absorption risk in preclinical species at high doses from easily measured physical properties is desired. This is due to the large number of molecules being evaluated and their high attrition rate, which make resource-intensive in vitro and in silico evaluation unattractive. High-dose in vivo data from rat, dog, and monkey are analyzed here, using a preclinical dose number (PDo) concept based on the dose number described by Amidon and other authors (Pharm. Res., 1993, 10, 264-270). PDo, as described in this article, is simply calculated as dose (mg/kg) divided by compound solubility in FaSSIF (mg/mL) and approximates the volume of biorelevant media per kilogram of animal that would be needed to fully dissolve the dose. High PDo values were found to be predictive of difficulty in achieving drug exposure (AUC)-dose proportionality in in vivo studies, as could be expected; however, this work analyzes a large data set (>900 data points) and provides quantitative guidance to identify drug absorption risk in preclinical species based on a single solubility measurement commonly carried out in drug discovery. Above the PDo values defined, >50% of all in vivo studies exhibited poor AUC-dose proportionality in rat, dog, and monkey, and these values can be utilized as general guidelines in discovery and early development to rapidly assess risk of solubility-limited absorption for a given compound. A preclinical dose number generated by biorelevant dilutions of formulated compounds (formulated PDo) was also evaluated and defines solubility targets predictive of suitable AUC-dose proportionality in formulation development efforts. Application of these guidelines can serve to efficiently identify compounds in discovery that are likely to present extreme challenges with respect to solubility-limited absorption in preclinical species as well as reduce the testing of poor formulations in vivo, which is a key ethical and resource matter.

TH-AB-207A-04: Assessment of Patients’ Cumulative Effective Dose From CT Examinations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bostani, M; Cagnon, C; Sepahdari, A

Purpose: The Joint Commission requires institutions to consider patient’s age and recent imaging exams when deciding on the most appropriate type of imaging exam. Additionally, knowing patient’s imaging history can help prevent duplicate scans. Radiation dose management software affords new opportunities to identify and utilize patients with high cumulative doses as one proxy for subsequent review of imaging history and opportunities in avoiding redundant exams. Methods: Using dose management software (Radimetrics, Bayer Healthcare) a total of 72073 CT examinations performed from Jan 2015 to Jan 2016 were examined to categorize patients with a cumulative effective dose of 100 mSv andmore » above. This threshold was selected based on epidemiological studies on populations exposed to radiation, which demonstrate a statistical increase of cancer risk at doses above 100 mSv. Histories of patients with highest cumulative dose and highest number of exams were further investigated by a Radiologist for appropriateness of recurrent studies and potential opportunities for reduction. Results: Out of 34762 patients, 927 (2.7%) were identified with a cumulative dose of 100 mSv and above. The highest cumulative dose (842 mSv) belonged to an oncology patient who underwent 2 diagnostic exams and 9 interventional ablative CT guided procedures. The patient with highest number of exams (56 counts) and cumulative dose of 170 mSv was a 17 year old trauma patient. An imaging history review of these two patients did not suggest any superfluous scans. Conclusion: Our limited pilot study suggests that recurrent CT exams for patients with oncologic or severe trauma history may be warranted and appropriate. As a result, for future studies we will be focusing on high dose patient cohorts not associated with oncology or severe trauma. Additionally, the review process itself has suggested areas for potential improvement in patient care, including improved documentation and Radiologist involvement in patient management. Dr. McNitt-Gray’s disclosures: Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics.« less

A review of measles supplementary immunization activities and the implications for Pacific Island countries and territories.

PubMed

Clements, C John; Soakai, Taniela Sunia; Sadr-Azodi, Nahad

2017-02-01

Standard measles control strategies include achieving high levels of measles vaccine coverage using routine delivery systems, supplemented by mass immunization campaigns as needed to close population immunity gaps. Areas covered: This review looks at how supplementary immunization activities (SIAs) have contributed to measles control globally, and asks whether such a strategy has a place in Pacific Islands today. Expert commentary: Very high coverage with two doses of measles vaccine seems to be the optimal strategy for controlling measles. By 2015, all but two Pacific Islands had introduced a second dose in the routine schedule; however, a number of countries have not yet reached high coverage with their second dose. The literature and the country reviews reported here suggest that a high coverage SIA combined with one dose of measles vaccine given in the routine system will also do the job. The arguments for and against the use of SIAs are complex, but it is clear that to be effective, SIAs need to be well designed to meet specific needs, must be carried out effectively and safely with very high coverage, and should, when possible, carry with them other public health interventions to make them even more cost-effective.

The effects of chronic oral methyl mercury exposure on the lysosome system of rat kidney. Morphometric and biochemical studies.

PubMed

Fowler, B A; Brown, H W; Lucier, G W; Krigman, M R

1975-03-01

This report describes morphometric and biochemical changes in the renal lysosome system of rats exposed to 3, 5, or 10 p.p.m. concentrations of methyl mercury hydroxide in their drinking water for 4 weeks. Increased numbers of dense, granular lysosomes, previously found to contain mercury, were observed in tubule cells of rats receiving the 3 and 5 p.p.m. dose levels but not those of the 10 p.p.m. group. Tubule cells from animals given the 10 p.p;m. dose level displayed proteinaceous vacuoles with dense crystalloid structures, apical cytoplasmic extrusion, and cellular degeneration; Mitochondrial swelling within tubule cells of treated animals showed a marked dose-response relationship. Renal microsomal activity levels of ss-glucuronidase were strongly inhibited by methyl mercury hydroxide exposure at all dose levels, whereas the activity levels of acid phosphatase were unchanged. Lysosomal beta-glucuronidase was also inhibited by methyl mercury hydroxide exposure, whereas lysosomal acid phosphatase showed approximately a 2-fold increase in activity. The results are discussed in relation to the role of lysosomes in mediating the nephrotoxic effects of methyl mercury and other toxic trace metals.

High Efficacy of Methotrexate in Patients with Recurrent Idiopathic Acute Anterior Uveitis: a Prospective Study.

PubMed

Bachta, Artur; Kisiel, Bartłomiej; Tłustochowicz, Mateusz; Raczkiewicz, Anna; Rękas, Marek; Tłustochowicz, Witold

2017-02-01

To evaluate prospectively the efficacy of methotrexate (MTX) in the treatment of recurrent idiopathic acute anterior uveitis (RIAAU). Nineteen out of 22 RIAAU patients completed the study (two patients withdrew their consent shortly after study initiation, one patient discontinued after 4 weeks because of the adverse effects). All patients were treated with MTX in a starting dose of 15 mg/week, increased to target dose of 25 mg/week after 4 weeks. In patients taking systemic corticosteroids (CS) the dose was gradually tapered (by 2.5 mg every week) until discontinuation. The mean follow-up period was 3.3 years (19-59 months). Sixteen patients (84 %) remained flare-free on MTX therapy. In the remaining three patients the mean interval between flares increased from 4.8 to 18.3 months. Systemic CS were tapered off in all patients. The number of acute anterior uveitis flares in the whole cohort decreased from 2.12 to 0.11/patient-year (p < 0.0001). All flares observed on MTX therapy occurred in HLA-B27-positive patients. MTX dosed at 25 mg/week is highly effective in the treatment of RIAAU.

Neuroprotective effect of Arthrospira (Spirulina) platensis against kainic acid-neuronal death.

PubMed

Pérez-Juárez, Angélica; Chamorro, Germán; Alva-Sánchez, Claudia; Paniagua-Castro, Norma; Pacheco-Rosado, Jorge

2016-08-01

Context Arthrospira (Spirulina) platensis (SP) is a cyanobacterium which has attracted attention because of its nutritional value and pharmacological properties. It was previously reported that SP reduces oxidative stress in the hippocampus and protects against damaging neurobehavioural effects of systemic kainic acid (KA). It is widely known that the systemic administration of KA induces neuronal damage, specifically in the CA3 hippocampal region. Objective The present study determines if the SP sub-chronic treatment has neuroprotective properties against KA. Materials and methods Male SW mice were treated with SP during 24 d, at doses of 0, 200, and 800 mg/kg, once daily, and with KA (35 mg/kg, ip) as a single dose on day 14. After the treatment, a histological analysis was performed and the number of atrophic neuronal cells in CA3 hippocampal region was quantified. Results Pretreatment with SP does not protect against seizures induced by KA. However, mortality in the SP 200 and the SP 800 groups was of 20%, while for the KA group, it was of 60%. A single KA ip administration produced a considerable neuronal damage, whereas both doses of SP sub-chronic treatment reduced the number of atrophic neurons in CA3 hippocampal region with respect to the KA group. Discussion The SP neurobehaviour improvement after KA systemic administration correlates with the capacity of SP to reduce KA-neuronal death in CA3 hippocampal cells. This neuroprotection may be related to the antioxidant properties of SP. Conclusion SP reduces KA-neuronal death in CA3 hippocampal cells.

Accurate low-dose iterative CT reconstruction from few projections by Generalized Anisotropic Total Variation minimization for industrial CT.

PubMed

Debatin, Maurice; Hesser, Jürgen

2015-01-01

Reducing the amount of time for data acquisition and reconstruction in industrial CT decreases the operation time of the X-ray machine and therefore increases the sales. This can be achieved by reducing both, the dose and the pulse length of the CT system and the number of projections for the reconstruction, respectively. In this paper, a novel generalized Anisotropic Total Variation regularization for under-sampled, low-dose iterative CT reconstruction is discussed and compared to the standard methods, Total Variation, Adaptive weighted Total Variation and Filtered Backprojection. The novel regularization function uses a priori information about the Gradient Magnitude Distribution of the scanned object for the reconstruction. We provide a general parameterization scheme and evaluate the efficiency of our new algorithm for different noise levels and different number of projection views. When noise is not present, error-free reconstructions are achievable for AwTV and GATV from 40 projections. In cases where noise is simulated, our strategy achieves a Relative Root Mean Square Error that is up to 11 times lower than Total Variation-based and up to 4 times lower than AwTV-based iterative statistical reconstruction (e.g. for a SNR of 223 and 40 projections). To obtain the same reconstruction quality as achieved by Total Variation, the projection number and the pulse length, and the acquisition time and the dose respectively can be reduced by a factor of approximately 3.5, when AwTV is used and a factor of approximately 6.7, when our proposed algorithm is used.

Contribution of semen trait selection, artificial insemination technique, and semen dose to the profitability of pig production systems: A simulation study.

PubMed

Gonzalez-Pena, Dianelys; Knox, Robert V; Rodriguez-Zas, Sandra L

2016-01-15

The economic impact of selection for semen traits on pig production systems and potential interaction with artificial insemination (AI) technique and semen dose remains partially understood. The objectives of this study were to compare the financial indicators (gross return, net profit, cost) in a three-tier pig production system under one of two selection strategies: a traditional strategy including nine paternal and maternal traits (S9) and an advanced strategy that adds four semen traits (S13). Maternal traits included the number of pigs born alive, litter birth weight, adjusted 21-day litter weight, and the number of pigs at 21 days, and paternal traits included days to 113.5 kg, back fat, average daily gain, feed efficiency, and carcass lean percentage. The four semen traits included volume, concentration, progressive motility of spermatozoa, and abnormal spermatozoa. Simultaneously, the impact of two AI techniques and a range of fresh refrigerated semen doses including cervical AI with 3 × 10(9) (CAI3) and 2 × 10(9) (CAI2) sperm cells/dose, and intrauterine AI with 1.5 × 10(9) (IUI1.5), 0.75 × 10(9) (IUI0.75), and 0.5 × 10(9) (IUI0.5) sperm cells/dose were evaluated. These factors were also evaluated using a range of farrowing rates (60%-90%), litter sizes (8-14 live-born pigs), and a selected semen collection frequency. The financial impact of the factors was assessed through simulation of a three-way crossbreeding system (maternal nucleus lines A and B and paternal nucleus line C) using ZPLAN. The highest return on investment (profit/cost) of boars was observed at 2.33 collections/wk (three periods of 24 hours between collections). Under this schedule, a significant (P < 0.0001) interaction between the selection strategy and the AI technique-dose combination was identified for the gross return; meanwhile, significant (P < 0.0001) additive effects of the selection strategy and AI technique-dose combination were observed for the net profit. The highest gross return was obtained under S13 with IUI0.75 and IUI0.5. The net profit of S13 was 34.37% higher than the traditional S9 (P < 0.0001). The net profit favored IUI0.5 with relative differences of 4.13%, 2.41%, 1.72%, and 0.43% compared to CAI3, CAI2, IUI1.5, and IUI0.75, respectively. The advanced selection strategy proposed including four semen traits is recommended on the basis of the higher profitability relative to the traditional strategy. Copyright © 2016 Elsevier Inc. All rights reserved.

Preliminary analysis of the implications of natural radiations on geostationary operations

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Denn, F. M.

1976-01-01

The natural radiations present at geostationary orbit are discussed. Low-level galactic cosmic rays are important for careers spending a year or more at geostationary altitude. Trapped radiation will on occasion require interruption of extravehicular activity (EVA). The spacesuit shield requirements are strongly affected by the number of interruptions allowed. EVA cannot proceed during a large solar event and maximum allowable doses are exceeded in a few hours unless a heavily shielded area is provided. A shelter of 10 g/sq cm with personal shielding for the eyes and testes would contain exposure to within the presently accepted exposure constraints. Since radiation levels can increase unexpectedly to serious levels, an onboard radiation monitoring system with rate and integration capabilities is required for both surface-dose and depth-dose monitoring.

Low level laser therapy on injured rat muscle

NASA Astrophysics Data System (ADS)

Mantineo, M.; Pinheiro, J. P.; Morgado, A. M.

2013-06-01

Although studies show the clinical effectiveness of low level laser therapy (LLLT) in facilitating the muscle healing process, scientific evidence is still required to prove the effectiveness of LLLT and to clarify the cellular and molecular mechanisms triggered by irradiation. Here we evaluate the effect of different LLLT doses, using continuous illumination (830 nm), in the treatment of inflammation induced in the gastrocnemius muscle of Wistar rats, through the quantification of cytokines in systemic blood and histological analysis of muscle tissue. We verified that all applied doses produce an effect on reducing the number of inflammatory cells and the concentration of pro-inflammatory TNF-α and IL-1β cytokines. The best results were obtained for 40 mW. The results may suggest a biphasic dose response curve.

The development of remote wireless radiation dose monitoring system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Jin-woo; Chonbuk National University, Jeonjoo-Si; Jeong, Kyu-hwan

Internet of things (IoT) technology has recently shown a large flow of IT trends in human life. In particular, our lives are now becoming integrated with a lot of items around the 'smart-phone' with IoT, including Bluetooth, Near Field Communication (NFC), Beacons, WiFi, and Global Positioning System (GPS). Our project focuses on the interconnection of radiation dosimetry and IoT technology. The radiation workers at a nuclear facility should hold personal dosimeters such as a Thermo-Luminescence Dosimeter (TLD), an Optically Stimulated Luminescence Dosimeter (OSL), pocket ionization chamber dosimeters, an Electronic Personal Dosimeter (EPD), or an alarm dosimeter on their body. Somemore » of them have functions that generate audible or visible alarms to radiation workers in a real working area. However, such devices used in radiation fields these days have no functions for communicating with other areas or the responsible personnel in real time. In particular, when conducting a particular task in a high dose area, or a number of repair works within a radiation field, radiation dose monitoring is important for the health of the workers and the work efficiency. Our project aims at the development of a remote wireless radiation dose monitoring system (RWRD) that can be used to monitor the radiation dose in a nuclear facility for radiation workers and a radiation protection program In this project, a radiation dosimeter is the detection device for personal radiation dose, a smart phone is the mobile wireless communication tool, and, Beacon is the wireless starter for the detection, communication, and position of the worker using BLE (Bluetooth Low Energy). In this report, we report the design of the RWRD and a demonstration case in a real radiation field. (authors)« less

Effect of radiation dose reduction and iterative reconstruction on computer-aided detection of pulmonary nodules: Intra-individual comparison.

PubMed

Den Harder, Annemarie M; Willemink, Martin J; van Hamersvelt, Robbert W; Vonken, Evert-Jan P A; Milles, Julien; Schilham, Arnold M R; Lammers, Jan-Willem; de Jong, Pim A; Leiner, Tim; Budde, Ricardo P J

2016-02-01

To evaluate the effect of radiation dose reduction and iterative reconstruction (IR) on the performance of computer-aided detection (CAD) for pulmonary nodules. In this prospective study twenty-five patients were included who were scanned for pulmonary nodule follow-up. Image acquisition was performed at routine dose and three reduced dose levels in a single session by decreasing mAs-values with 45%, 60% and 75%. Tube voltage was fixed at 120 kVp for patients ≥ 80 kg and 100 kVp for patients < 80 kg. Data were reconstructed with filtered back projection (FBP), iDose(4) (levels 1,4,6) and IMR (levels 1-3). All noncalcified solid pulmonary nodules ≥ 4 mm identified by two radiologists in consensus served as the reference standard. Subsequently, nodule volume was measured with CAD software and compared to the reference consensus. The numbers of true-positives, false-positives and missed pulmonary nodules were evaluated as well as the sensitivity. Median effective radiation dose was 2.2 mSv at routine dose and 1.2, 0.9 and 0.6 mSv at respectively 45%, 60% and 75% reduced dose. A total of 28 pulmonary nodules were included. With FBP at routine dose, 89% (25/28) of the nodules were correctly identified by CAD. This was similar at reduced dose levels with FBP, iDose(4) and IMR. CAD resulted in a median number of false-positives findings of 11 per scan with FBP at routine dose (93% of the CAD marks) increasing to 15 per scan with iDose(4) (95% of the CAD marks) and 26 per scan (96% of the CAD marks) with IMR at the lowest dose level. CAD can identify pulmonary nodules at submillisievert dose levels with FBP, hybrid and model-based IR. However, the number of false-positive findings increased using hybrid and especially model-based IR at submillisievert dose while dose reduction did not affect the number of false-positives with FBP. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnston, H; UT Southwestern Medical Center, Dallas, TX; Hilts, M

Purpose: To commission a multislice computed tomography (CT) scanner for fast and reliable readout of radiation therapy (RT) dose distributions using CT polymer gel dosimetry (PGD). Methods: Commissioning was performed for a 16-slice CT scanner using images acquired through a 1L cylinder filled with water. Additional images were collected using a single slice machine for comparison purposes. The variability in CT number associated with the anode heel effect was evaluated and used to define a new slice-by-slice background image subtraction technique. Image quality was assessed for the multislice system by comparing image noise and uniformity to that of the singlemore » slice machine. The consistency in CT number across slices acquired simultaneously using the multislice detector array was also evaluated. Finally, the variability in CT number due to increasing x-ray tube load was measured for the multislice scanner and compared to the tube load effects observed on the single slice machine. Results: Slice-by-slice background subtraction effectively removes the variability in CT number across images acquired simultaneously using the multislice scanner and is the recommended background subtraction method when using a multislice CT system. Image quality for the multislice machine was found to be comparable to that of the single slice scanner. Further study showed CT number was consistent across image slices acquired simultaneously using the multislice detector array for each detector configuration of the slice thickness examined. In addition, the multislice system was found to eliminate variations in CT number due to increasing x-ray tube load and reduce scanning time by a factor of 4 when compared to imaging a large volume using a single slice scanner. Conclusion: A multislice CT scanner has been commissioning for CT PGD, allowing images of an entire dose distribution to be acquired in a matter of minutes. Funding support provided by the Natural Sciences and Engineering Research Council of Canada (NSERC)« less

In vivo dose measurement using TLDs and MOSFET dosimeters for cardiac radiosurgery

PubMed Central

Sumanaweera, Thilaka S.; Blanck, Oliver; Iwamura, Alyson K.; Steel, James P.; Dieterich, Sonja; Maguire, Patrick

2012-01-01

In vivo measurements were made of the dose delivered to animal models in an effort to develop a method for treating cardiac arrhythmia using radiation. This treatment would replace RF energy (currently used to create cardiac scar) with ionizing radiation. In the current study, the pulmonary vein ostia of animal models were irradiated with 6 MV X‐rays in order to produce a scar that would block aberrant signals characteristic of atrial fibrillation. The CyberKnife radiosurgery system was used to deliver planned treatments of 20–35 Gy in a single fraction to four animals. The Synchrony system was used to track respiratory motion of the heart, while the contractile motion of the heart was untracked. The dose was measured on the epicardial surface near the right pulmonary vein and on the esophagus using surgically implanted TLD dosimeters, or in the coronary sinus using a MOSFET dosimeter placed using a catheter. The doses measured on the epicardium with TLDs averaged 5% less than predicted for those locations, while doses measured in the coronary sinus with the MOSFET sensor nearest the target averaged 6% less than the predicted dose. The measurements on the esophagus averaged 25% less than predicted. These results provide an indication of the accuracy with which the treatment planning methods accounted for the motion of the target, with its respiratory and cardiac components. This is the first report on the accuracy of CyberKnife dose delivery to cardiac targets. PACS numbers: 87.53.Ly, 87.53.Bn PMID:22584173

Adapting Dry Cask Storage for Aging at a Geologic Repository

DOE Office of Scientific and Technical Information (OSTI.GOV)

C. Sanders; D. Kimball

2005-08-02

A Spent Nuclear Fuel (SNF) Aging System is a crucial part of operations at the proposed Yucca Mountain repository in the United States. Incoming commercial SNF that does not meet thermal limits for emplacement will be aged on outdoor pads. U.S. Department of Energy SNF will also be managed using the Aging System. Proposed site-specific designs for the Aging System are closely based upon designs for existing dry cask storage (DCS) systems. This paper evaluates the applicability of existing DCS systems for use in the SNF Aging System at Yucca Mountain. The most important difference between existing DCS facilities andmore » the Yucca Mountain facility is the required capacity. Existing DCS facilities typically have less than 50 casks. The current design for the aging pad at Yucca Mountain calls for a capacity of over 2,000 casks (20,000 MTHM) [1]. This unprecedented number of casks poses some unique problems. The response of DCS systems to off-normal and accident conditions needs to be re-evaluated for multiple storage casks. Dose calculations become more complicated, since doses from multiple or very long arrays of casks can dramatically increase the total boundary dose. For occupational doses, the geometry of the cask arrays and the order of loading casks must be carefully considered in order to meet ALARA goals during cask retrieval. Due to the large area of the aging pad, skyshine must also be included when calculating public and worker doses. The expected length of aging will also necessitate some design adjustments. Under 10 CFR 72.236, DCS systems are initially certified for a period of 20 years [2]. Although the Yucca Mountain facility is not intended to be a storage facility under 10 CFR 72, the operational life of the SNF Aging System is 50 years [1]. Any cask system selected for use in aging will have to be qualified to this design lifetime. These considerations are examined, and a summary is provided of the adaptations that must be made in order to use DCS technologies successfully at a geologic repository.« less

Leishmanicidal activity of amphotericin B encapsulated in PLGA-DMSA nanoparticles to treat cutaneous leishmaniasis in C57BL/6 mice.

PubMed

de Carvalho, Ricardo Fontoura; Ribeiro, Ieler Ferreira; Miranda-Vilela, Ana Luisa; de Souza Filho, José; Martins, Olímpia Paschoal; Cintra e Silva, Débora de Oliveira; Tedesco, Antônio Cláudio; Lacava, Zulmira Guerrero Marques; Báo, Sônia Nair; Sampaio, Raimunda Nonata Ribeiro

2013-10-01

The major goal of this work was to design a new nanoparticle drug delivery system for desoxycholate amphotericin B (D-AMB), based on controlled particle size, looking for the most successful release of the active agents in order to achieve the best site-specific action of the drug at the therapeutically optimal rate and dose regimen. For this, AMB nanoencapsulated in poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) nanoparticles (Nano-D-AMB) has been developed, and its efficacy was evaluated in the treatment of experimental cutaneous leishmaniasis in C57BL/6 mice, to test if our nano-drug delivery system could favor the reduction of the dose frequency required to achieve the same therapeutic level of free D-AMB, and so, an extended dosing interval. Magnetic citrate-coated maghemite nanoparticles were added to this nanosystem (Nano-D-AMB-MG) aiming to increase controlled release of AMB by magnetohyperthermia. Female mice (N=6/group) were infected intradermally in the right footpad with promastigotes of Leishmania amazonensis in the metacyclic phase, receiving the following intraperitoneal treatments: 1% PBS for 10 consecutive days; D-AMB at 2 mg/kg/day for 10 days (totalizing 20 mg/kg/animal); Nano-D-AMB and Nano-D-AMB-MG at 6 mg/kg on the 1st, 4th and 7th days and at 2 mg/kg on the 10th day, also totalizing 20 mg/kg/animal by treatment end. The Nano-D-AMB-MG group was submitted to an AC magnetic field, allowing the induction of magnetohyperthermia. The evaluations were through paw diameter measurements; parasite number and cell viability were investigated by limiting dilution assay. D-AMB-coated PLGA-DMSA nanoparticles showed the same efficacy as free D-AMB to reduce paw diameter; however, the Nano-D-AMB treatment also promoted a significantly greater reduction in parasite number and cell viability compared with free D-AMB. The nano-drug AMB delivery system appeared more effective than free D-AMB therapy to reduce the dose frequency required to achieve the same therapeutic level. It thus favors a longer interval between doses, as expected with development of a new nano drug delivery system, and may be useful in the treatment of many different pathologies, from cancer to neurodegenerative diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

Segmenting data sets for RIP.

PubMed

de Sanctis, Daniele; Nanao, Max H

2012-09-01

Specific radiation damage can be used for the phasing of macromolecular crystal structures. In practice, however, the optimization of the X-ray dose used to `burn' the crystal to induce specific damage can be difficult. Here, a method is presented in which a single large data set that has not been optimized in any way for radiation-damage-induced phasing (RIP) is segmented into multiple sub-data sets, which can then be used for RIP. The efficacy of this method is demonstrated using two model systems and two test systems. A method to improve the success of this type of phasing experiment by varying the composition of the two sub-data sets with respect to their separation by image number, and hence by absorbed dose, as well as their individual completeness is illustrated.

Output-driven feedback system control platform optimizes combinatorial therapy of tuberculosis using a macrophage cell culture model.

PubMed

Silva, Aleidy; Lee, Bai-Yu; Clemens, Daniel L; Kee, Theodore; Ding, Xianting; Ho, Chih-Ming; Horwitz, Marcus A

2016-04-12

Tuberculosis (TB) remains a major global public health problem, and improved treatments are needed to shorten duration of therapy, decrease disease burden, improve compliance, and combat emergence of drug resistance. Ideally, the most effective regimen would be identified by a systematic and comprehensive combinatorial search of large numbers of TB drugs. However, optimization of regimens by standard methods is challenging, especially as the number of drugs increases, because of the extremely large number of drug-dose combinations requiring testing. Herein, we used an optimization platform, feedback system control (FSC) methodology, to identify improved drug-dose combinations for TB treatment using a fluorescence-based human macrophage cell culture model of TB, in which macrophages are infected with isopropyl β-D-1-thiogalactopyranoside (IPTG)-inducible green fluorescent protein (GFP)-expressing Mycobacterium tuberculosis (Mtb). On the basis of only a single screening test and three iterations, we identified highly efficacious three- and four-drug combinations. To verify the efficacy of these combinations, we further evaluated them using a methodologically independent assay for intramacrophage killing of Mtb; the optimized combinations showed greater efficacy than the current standard TB drug regimen. Surprisingly, all top three- and four-drug optimized regimens included the third-line drug clofazimine, and none included the first-line drugs isoniazid and rifampin, which had insignificant or antagonistic impacts on efficacy. Because top regimens also did not include a fluoroquinolone or aminoglycoside, they are potentially of use for treating many cases of multidrug- and extensively drug-resistant TB. Our study shows the power of an FSC platform to identify promising previously unidentified drug-dose combinations for treatment of TB.

Pharmacokinetics and safety of imiquimod 5% cream in the treatment of actinic keratoses of the face, scalp, or hands and arms.

PubMed

Harrison, Lester I; Skinner, Shari L; Marbury, Thomas C; Owens, Mary L; Kurup, Sarala; McKane, Scott; Greene, Robert J

2004-06-01

The safety and efficacy of imiquimod 5% cream is being evaluated for the treatment of dysplastic lesions of the epidermis (actinic keratoses, AK). The objective of this clinical study was to describe the pharmacokinetics and safety of topical imiquimod during multiple dosing of AK subjects. A total of 58 adult subjects with 5 to 20 AK lesions at the treatment site applied imiquimod cream three times per week for up to 16 weeks as follows: 12 males and 11 females applied 12.5 mg imiquimod to the face; 11 males applied 25 mg to the entire balding area of the scalp; and 12 males and 12 females applied 75 mg to both hands and forearms. Pharmacokinetics and safety were assessed after the first and last doses, as well as biweekly. Imiquimod and its metabolites were measured in the serum and urine using sensitive liquid chromatography/mass spectrometry methods. Less than 0.6% of the applied doses was recovered in the urine of all subjects. Serum imiquimod levels were low, reflecting minimal dermal absorption, and increased with dose, although not proportionally. Peak levels at the end of dosing were 0.1, 0.2, and 1.6 ng/ml for the face, scalp, and hands/arms groups, respectively. A two- to fourfold accumulation was seen at the end of dosing. Local application site reactions were the most common adverse event, reported by approximately 50% of the subjects in each treatment group. The small number of systemic adverse events, including 'flu-like symptoms, were mostly mild and did not show a dose response. Thus, minimal systemic absorption and good safety margins for topical imiquimod were seen in AK subjects with doses as high as 75 mg three times per week for 16 weeks.

Dosimetric measurements and comparison studies in digital imaging system

NASA Astrophysics Data System (ADS)

Jung, Ji-Young; Kim, Hee-Joung; Lee, Chang-Lae; Cho, Hyo-Min; Nam, Sora

2008-03-01

Number of radiologic exams using digital imaging systems has rapidly increased with advanced imaging technologies. However, it has not been paid attention to the radiation dose in clinical situations. It was the motivation to study radiation dosimetry in the DR system. The objective of this study was to measure beam quality and patient's dose using DR system and to compare them to both IEC standard and IAEA guidelines. The measured average dose for chest and abdomen was 1.376 mGy and 9.501 mGy, respectively, compared to 0.4 mGy and 10.0 mGy in IAEA guidelines. The results also indicated that the DR system has a lower radiation beam quality than that of the IEC standard. The results showed that the patients may be exposed higher radiation for chest exams and lower radiation for abdomen exams using DR system. IAEA Guidelines were prepared based on western people which may be different weight and height for patients compared them to Korean. In conclusion, a new guideline for acceptable DR dosimetry for Korean patients may need to be developed with further studies for large populations. We believe that this research greatly help to introduce the importance of the dosimetry in diagnostic radiology in Korea. And, a development of database for dosimetry in diagnostic radiology will become an opportunity of making aware of radiation safety of medical examination to patient.

Real space channelization for generic DBT system image quality evaluation with channelized Hotelling observer

NASA Astrophysics Data System (ADS)

Petrov, Dimitar; Cockmartin, Lesley; Marshall, Nicholas; Vancoillie, Liesbeth; Young, Kenneth; Bosmans, Hilde

2017-03-01

Digital breast tomosynthesis (DBT) is a relatively new 3D mammography technique that promises better detection of low contrast masses than conventional 2D mammography. The parameter space for DBT is large however and finding an optimal balance between dose and image quality remains challenging. Given the large number of conditions and images required in optimization studies, the use of human observers (HO) is time consuming and certainly not feasible for the tuning of all degrees of freedom. Our goal was to develop a model observer (MO) that could predict human detectability for clinically relevant details embedded within a newly developed structured phantom for DBT applications. DBT series were acquired on GE SenoClaire 3D, Giotto Class, Fujifilm AMULET Innovality and Philips MicroDose systems at different dose levels, Siemens Inspiration DBT acquisitions were reconstructed with different algorithms, while a larger set of DBT series was acquired on Hologic Dimensions system for first reproducibility testing. A channelized Hotelling observer (CHO) with Gabor channels was developed The parameters of the Gabor channels were tuned on all systems at standard scanning conditions and the candidate that produced the best fit for all systems was chosen. After tuning, the MO was applied to all systems and conditions. Linear regression lines between MO and HO scores were calculated, giving correlation coefficients between 0.87 and 0.99 for all tested conditions.

Biomonitoring of 2,4-Dichlorophenoxyacetic Acid Exposure and Dose in Farm Families

PubMed Central

Alexander, Bruce H.; Mandel, Jack S.; Baker, Beth A.; Burns, Carol J.; Bartels, Michael J.; Acquavella, John F.; Gustin, Christophe

2007-01-01

Objective We estimated 2,4-dichlorophenoxyacetic acid (2,4-D) exposure and systemic dose in farm family members following an application of 2,4-D on their farm. Methods Farm families were recruited from licensed applicators in Minnesota and South Carolina. Eligible family members collected all urine during five 24-hr intervals, 1 day before through 3 days after an application of 2,4-D. Exposure profiles were characterized with 24-hr urine 2,4-D concentrations, which then were related to potential predictors of exposure. Systemic dose was estimated using the urine collections from the application day through the third day after application. Results Median urine 2,4-D concentrations at baseline and day after application were 2.1 and 73.1 μ g/L for applicators, below the limit of detection, and 1.2 μ g/L for spouses, and 1.5 and 2.9 μ g/L for children. The younger children (4–11 years of age) had higher median post-application concentrations than the older children (≥ 12 years of age) (6.5 vs. 1.9 μ g/L). The geometric mean systemic doses (micrograms per kilogram body weight) were 2.46 (applicators), 0.8 (spouses), 0.22 (all children), 0.32 (children 4–11 years of age), and 0.12 (children ≥ 12 years of age). Exposure to the spouses and children was primarily determined by direct contact with the application process and the number of acres treated. Multivariate models identified glove use, repairing equipment, and number of acres treated as predictors of exposure in the applicators. Conclusions We observed considerable heterogeneity of 2,4-D exposure among farm family members, primarily attributable to level of contact with the application process. Awareness of this variability and the actual magnitude of exposures are important for developing exposure and risk characterizations in 2,4-D–exposed agricultural populations. PMID:17431485

Traffic aerosol lobar doses deposited in the human respiratory system.

PubMed

Manigrasso, Maurizio; Vernale, Claudio; Avino, Pasquale

2017-06-01

Aerosol pollution in urban environments has been recognized to be responsible for important pathologies of the cardiovascular and respiratory systems. In this perspective, great attention has been addressed to Ultra Fine Particles (UFPs < 100 nm), because they efficiently penetrate into the respiratory system and are capable of translocating from the airways into the blood circulation. This paper describes the aerosol regional doses deposited in the human respiratory system in a high-traffic urban area. The aerosol measurements were carried out on a curbside in downtown Rome, on a street characterized by a high density of autovehicular traffic. Aerosol number-size distributions were measured by means of a Fast Mobility Particle Sizer in the range from 5.6 to 560 nm with a 1 s time resolution. Dosimetry estimates were performed with the Multiple-Path Particle Dosimetry model by means of the stochastic lung model. The exposure scenario close to traffic is represented by a sequence of short-term peak exposures: about 6.6 × 10 10 particles are deposited hourly into the respiratory system. After 1 h of exposure in proximity of traffic, 1.29 × 10 10 , 1.88 × 10 10 , and 3.45 × 10 10 particles are deposited in the head, tracheobronchial, and alveolar regions. More than 95 % of such doses are represented by UFPs. Finally, according to the greater dose estimated, the right lung lobes are expected to be more susceptible to respiratory pathologies than the left lobes.

Impact of external carbon dose on the removal of micropollutants using methanol and ethanol in post-denitrifying Moving Bed Biofilm Reactors.

PubMed

Torresi, Elena; Escolà Casas, Mònica; Polesel, Fabio; Plósz, Benedek G; Christensson, Magnus; Bester, Kai

2017-01-01

Addition of external carbon sources to post-denitrification systems is frequently used in wastewater treatment plants to enhance nitrate removal. However, little is known about the fate of micropollutants in post-denitrification systems and the influence of external carbon dosing on their removal. In this study, we assessed the effects of two different types and availability of commonly used carbon sources -methanol and ethanol- on the removal of micropollutants in biofilm systems. Two laboratory-scale moving bed biofilm reactors (MBBRs), containing AnoxKaldnes K1 carriers with acclimated biofilm from full-scale systems, were operated in continuous-flow using wastewater dosed with methanol and ethanol, respectively. Batch experiments with 22 spiked pharmaceuticals were performed to assess removal kinetics. Acetyl-sulfadiazine, atenolol, citalopram, propranolol and trimethoprim were easily biotransformed in both MBBRs (biotransformations rate constants k bio between 1.2 and 12.9 L g biomass -1  d -1 ), 13 compounds were moderately biotransformed (rate constants between 0.2 and 2 L g biomass -1  d -1 ) and 4 compounds were recalcitrant. The methanol-dosed MBBR showed higher k bio (e.g., 1.5-2.5-fold) than in the ethanol-dosed MBBR for 9 out of the 22 studied compounds, equal k bio for 10 compounds, while 3 compounds (i.e., targeted sulfonamides) were biotransformed faster in the ethanol-dosed MBBR. While biotransformation of most of the targeted compounds followed first-order kinetics, removal of venlafaxine, carbamazepine, sulfamethoxazole and sulfamethizole could be described with a cometabolic model. Analyses of the microbial composition in the biofilms using 16S rRNA amplicon sequencing revealed that the methanol-dosed MBBR contained higher microbial richness than the one dosed with ethanol, suggesting that improved biotransformation of targeted compounds could be associated with higher microbial richness. During continuous-flow operation, at conditions representative of full-scale denitrification systems (hydraulic residence time = 2 h), the removal efficiencies of micropollutants were below 35% in both MBBRs, with the exception of atenolol and trimethoprim (>80%). Overall, this study demonstrated that MBBRs used for post-denitrification could be optimized to enhance the biotransformation of a number of micropollutants by accounting for optimal carbon sources and extended residence time. Copyright © 2016 Elsevier Ltd. All rights reserved.

SU-F-T-479: Estimation of the Accuracy in Respiratory-Gated Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurosawa, T; Miyakawa, S; Sato, M

Purpose: Irregular respiratory patterns affects dose outputs in respiratorygated radiotherapy and there is no commercially available quality assurance (QA) system for it. We designed and developed a patient specific QA system for respiratory-gated radiotherapy to estimate irradiated output. Methods: Our in-house QA system for gating was composed of a personal computer with the USB-FSIO electronic circuit connecting to the linear accelerator (ONCOR-K, Toshiba Medical Systems). The linac implements a respiratory gating system (AZ-733V, Anzai Medical). During the beam was on, 4.2 V square-wave pulses were continually sent to the system. Our system can receive and count the pulses. At first,more » our system and an oscilloscope were compared to check the performance of our system. Next, basic estimation models were generated when ionization-chamber measurements were performed in gating using regular sinusoidal wave patterns (2.0, 2.5, 4.0, 8.0, 15 sec/cycle). During gated irradiation with the regular patterns, the number of the pulses per one gating window was measured using our system. Correlation between the number of the pulses per one gating and dose per the gating window were assessed to generate the estimation model. Finally, two irregular respiratory patterns were created and the accuracy of the estimation was evaluated. Results: Compared to the oscilloscope, our system worked similarly. The basic models were generated with the accuracy within 0.1%. The results of the gated irradiations with two irregular respiratory patterns show good agreement within 0.4% estimation accuracy. Conclusion: Our developed system shows good estimation for even irregular respiration patterns. The system would be a useful tool to verify the output for respiratory-gated radiotherapy.« less

Beam perturbation characteristics of a 2D transmission silicon diode array, Magic Plate

PubMed Central

Alrowaili, Ziyad A.; Lerch, Michael L.F.; Petasecca, Marco; Carolan, Martin G.; Metcalfe, Peter E.

2016-01-01

The main objective of this study is to demonstrate the performance characteristics of the Magic Plate (MP) system when operated upstream of the patient in transmission mode (MPTM). The MPTM is an essential component of a real‐time QA system designed for operation during radiotherapy treatment. Of particular interest is a quantitative study into the influence of the MP on the radiation beam quality at several field sizes and linear accelerator potential differences. The impact is measured through beam perturbation effects such as changes in the skin dose and/or percentage depth dose (PDD) (both in and out of field). The MP was placed in the block tray of a Varian linac head operated at 6, 10 and 18 MV beam energy. To optimize the MPTM operational setup, two conditions were investigated and each setup was compared to the case where no MP is positioned in place (i.e., open field): (i) MPTM alone and (ii) MPTM with a thin passive contamination electron filter. The in‐field and out‐of‐field surface doses of a solid water phantom were investigated for both setups using a Markus plane parallel (Model N23343) and Attix parallel‐plate, MRI model 449 ionization chambers. In addition, the effect on the 2D dose distribution measured by the Delta4 QA system was also investigated. The transmission factor for both of these MPTM setups in the central axis was also investigated using a Farmer ionization chamber (Model 2571A) and an Attix ionization chamber. Measurements were performed for different irradiation field sizes of 5×5 cm2 and 10×10 cm2. The change in the surface dose relative to dmax was measured to be less than 0.5% for the 6 MV, 10 MV, and 18 MV energy beams. Transmission factors measured for both set ups (i & ii above) with 6 MV, 10 MV, and 18 MV at a depth of dmax and a depth of 10 cm were all within 1.6% of open field. The impact of both the bare MPTM and the MPTM with 1 mm buildup on 3D dose distribution in comparison to the open field investigated using the Delta4 system and both the MPTM versions passed standard clinical gamma analysis criteria. Two MPTM operational setups were studied and presented in this article. The results indicate that both versions may be suitable for the new real‐time megavoltage photon treatment delivery QA system under development. However, the bare MPTM appears to be slightly better suited of the two MP versions, as it minimally perturbs the radiation field and does not lead to any significant increase in skin dose to the patient. PACS number(s): 87.50.up, 87.53.Bn, 87.55.N, 87.55.Qr, 87.56.Fc. PMID:27074475

Reducing absorbed dose to eye lenses in head CT examinations: the effect of bismuth shielding.

PubMed

Ciarmatori, Alberto; Nocetti, L; Mistretta, G; Zambelli, G; Costi, T

2016-06-01

The eye lens is considered to be among the most radiosensitive human tissues. Brain CT scans may unnecessarily expose it to radiation even if the area of clinical interest is far from the eyes. The aim of this study is to implement a bismuth eye lens shielding system for Head-CT acquisitions in these cases. The study is focused on the assessment of the dosimetric characteristics of the shielding system as well as on its effect on image quality. The shielding system was tested in two set-ups which differ for distance ("contact" and "4 cm" Set up respectively). Scans were performed on a CTDI phantom and an anthropomorphic phantom. A reference set up without shielding system was acquired to establish a baseline. Image quality was assessed by signal (not HU converted), noise and contrast-to-noise ratio (CNR) evaluation. The overall dose reduction was evaluated by measuring the CTDIvol while the eye lens dose reduction was assessed by placing thermoluminescent dosimeters (TLDs) on an anthropomorphic phantom. The image quality analysis exhibits the presence of an artefact that mildly increases the CT number up to 3 cm below the shielding system. Below the artefact, the difference of the Signal and the CNR are negligible between the three different set-ups. Regarding the CTDI, the analysis demonstrates a decrease by almost 12 % (in the "contact" set-up) and 9 % (in the "4 cm" set-up). TLD measurements exhibit an eye lens dose reduction by 28.5 ± 5 and 21.1 ± 5 % respectively at the "contact" and the "4 cm" distance. No relevant artefact was found and image quality was not affected by the shielding system. Significant dose reductions were measured. These features make the shielding set-up useful for clinical implementation in both studied positions.

Successful withdrawal from high-dose benzodiazepine in a young patient through electronic monitoring of polypharmacy: a case report in an ambulatory setting.

PubMed

Loscertales, Hèctor R; Wentzky, Valerie; Dürsteler, Kenneth; Strasser, Johannes; Hersberger, Kurt E; Arnet, Isabelle

2017-05-01

Dependence on high-dose benzodiazepines (BZDs) is well known and discontinuation attempts are generally unsuccessful. A well established protocol for high-dose BZD withdrawal management is lacking. We present the case of withdrawal from high-dose lorazepam (>20 mg daily) in an unemployed 35-year-old male outpatient through agonist substitution with long-acting clonazepam and electronic monitoring over 28 weeks. All medicines were repacked into weekly 7 × 4 cavity multidose punch cards with an electronic monitoring system. The prescribed daily dosages of BZDs were translated into an optimal number of daily tablets, divided into up to four units of use. Withdrawal was achieved by individual leftover of a small quantity of BZDs that was placed in a separate compartment. Feedback with visualization of intake over the past week was given during weekly psychosocial sessions. Stepwise reduction was obtained by reducing the mg content of the cavities proportionally to the leftovers, keeping the number of cavities in order to maintain regular intake behavior, and to determine the dosage decrease. At week 28, the primary objectives were achieved, that is, lorazepam reduction to 5 mg daily and cannabis abstinence. Therapy was continued using multidrug punch cards without electronic monitoring to maintain the management system. At week 48, a smaller size weekly pill organizer with detachable daily containers was dispensed. At week 68, the patient's therapy was constant with 1.5 mg clonazepam + 5 mg lorazepam daily for anxiety symptoms and the last steps of withdrawal were started. Several key factors led to successful withdrawal from high-dose BZD in this outpatient, such as the use of weekly punch cards coupled with electronic monitoring, the patient's empowerment over the withdrawal process, and the collaboration of several healthcare professionals. The major implication for clinical care is reduction by following the leftovers, and not a diktat from the healthcare professionals.

Vial usage, device dead space, vaccine wastage, and dose accuracy of intradermal delivery devices for inactivated poliovirus vaccine (IPV).

PubMed

Jarrahian, Courtney; Rein-Weston, Annie; Saxon, Gene; Creelman, Ben; Kachmarik, Greg; Anand, Abhijeet; Zehrung, Darin

2017-03-27

Intradermal delivery of a fractional dose of inactivated poliovirus vaccine (IPV) offers potential benefits compared to intramuscular (IM) delivery, including possible cost reductions and easing of IPV supply shortages. Objectives of this study were to assess intradermal delivery devices for dead space, wastage generated by the filling process, dose accuracy, and total number of doses that can be delivered per vial. Devices tested included syringes with staked (fixed) needles (autodisable syringes and syringes used with intradermal adapters), a luer-slip needle and syringe, a mini-needle syringe, a hollow microneedle device, and disposable-syringe jet injectors with their associated filling adapters. Each device was used to withdraw 0.1-mL fractional doses from single-dose IM glass vials which were then ejected into a beaker. Both vial and device were weighed before and after filling and again after expulsion of liquid to record change in volume at each stage of the process. Data were used to calculate the number of doses that could potentially be obtained from multidose vials. Results show wide variability in dead space, dose accuracy, overall wastage, and total number of doses that can be obtained per vial among intradermal delivery devices. Syringes with staked needles had relatively low dead space and low overall wastage, and could achieve a greater number of doses per vial compared to syringes with a detachable luer-slip needle. Of the disposable-syringe jet injectors tested, one was comparable to syringes with staked needles. If intradermal delivery of IPV is introduced, selection of an intradermal delivery device can have a substantial impact on vaccine wasted during administration, and thus on the required quantity of vaccine that needs to be purchased. An ideal intradermal delivery device should be not only safe, reliable, accurate, and acceptable to users and vaccine recipients, but should also have low dead space, high dose accuracy, and low overall wastage to maximize the potential number of doses that can be withdrawn and delivered. Copyright © 2017 PATH. Published by Elsevier Ltd.. All rights reserved.

Suggesting a possible role of CA1 histaminergic system in harmane-induced amnesia.

PubMed

Nasehi, Mohammad; Mashaghi, Elham; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza

2013-11-27

A number of tremorogenic β-carboline alkaloids such as harmane are naturally present in the human food chain. They are derived from medicinal plants such as Peganum harmala that have been used as folk medicine in anticancer therapy. In the present study, effects of the histaminergic system of the dorsal hippocampus (CA1) on harmane-induced amnesia were examined. One-trial step-down was used to assess memory retention in adult male mice. The results showed that pre-training intra-CA1 administration of histamine (5μg/mouse), ranitidine (H2 receptor antagonist; at the doses of 0.25 and 0.5μg/mouse) and pyrilamine (H1 receptor antagonist; at the dose of 5μg/mouse) decreased memory formation. Pre-training intraperitoneal (i.p.) administration of harmane (12mg/kg) also decreased memory formation. Moreover, pre-training intra-CA1 injection of a sub-threshold dose of histamine (2.5μg/mouse) could reverse harmane (12mg/kg, i.p.)-induced impairment of memory. On the other hand, pre-training intra-CA1 injection of sub-threshold doses of ranitidine (0.0625μg/mouse) and pyrilamine (2.5μg/mouse) increased harmane-induced impairment of memory. In conclusion, the present findings suggest the involvement of the CA1 histaminergic system in harmane-induced impairment of memory formation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Schedule Dependence in Cancer Therapy: Intravenous Vitamin C and the Systemic Saturation Hypothesis

PubMed Central

Miranda Massari, Jorge R.; Duconge, Jorge; Riordan, Neil H.; Ichim, Thomas

2013-01-01

Despite the significant number of in vitro and in vivo studies to assess vitamin C effects on cancer following the application of large doses and its extensive use by alternative medicine practitioners in the USA; the precise schedule for successful cancer therapy is still unknown. Based on interpretation of the available data, we postulate that the relationship between Vitamin C doses and plasma concentration x time, the capability of tissue stores upon distribution, and the saturable mechanism of urinary excretion are all important determinants to understand the physiology of high intravenous vitamin C dose administration and its effect on cancer. Practitioners should pay more attention to the cumulative vitamin C effect instead of the vitamin C concentrations to account for observed discrepancy in antitumor response. We suggest that multiple, intermittent, short-term intravenous infusions of vitamin C over a longer time period will correlate with greater antitumor effects than do single continuous IV doses of the same total exposure. This approach would be expected to minimize saturation of renal reabsorption, providing a continuous “dynamic flow” of vitamin C in the body for optimal systemic exposure and clinical outcomes. This prevents the “systemic saturation” phenomena, which may recycle vitamin C and render it less effective as an anticancer agent. Nonetheless, more pharmacokinetic and pharmacodynamic studies are needed to fully understand this schedule-dependence phenomenon. PMID:24860238

Dose fractionation and single subject studies in PET

NASA Astrophysics Data System (ADS)

Balakrishnan, Karthikayan

Conventional positron emission tomography (PET) for cognitive brain studies typically relies on information collected from the distribution of decays following an injection of 15O-labeled water. The number of injections that can be administered to the subject are constrained by radiation dose to the subject and total length of the PET scan. The standard protocol involves 8--10 injections of H152O separated by approximately 5--7 half-lives of 15O. The number of activation conditions that can be realistically studied in a standard PET session is between 8 and 10. This work investigates the physiological response of a simulated subject to H152O injections that are administered in small doses (1--5 mCi) with short inter-injection intervals (40--180 seconds). A larger number of activation conditions are presented to the subject with a wider variation in the activation paradigm. Repeat conditions are studies. Signal averaging methods are feasible with this method of dose administration. Sinograms from scans with similar activation conditions are summed together before reconstruction. The signal in the primary activation region of the brain is shown to increase while suppressing the contribution of secondary activation regions in the brain. The contrast of the final image is similarly increased which leads to easier identification of the primary activation region. An automated H152O -production unit controlled by a PC running LabView software was developed to produce the dose required for the injection sequence by controlling the flow of H152O -vapor that diffuses across a semi-permeable membrane into saline. The unit is capable of producing H152O rapidly for both the standard and the proposed dose administration methods. The system also detects the bolus arrival time at the subject's lungs using a small external plastic detector. Activation sequence commences with the rise in radioactivity observed by the detector. The simulations indicate that inter-injection intervals should be approximately 90 seconds apart. Contrast in the resulting images are higher than the standard methods. Secondary activation regions that confound primary activations are absent in the low-dose method. The results also indicate that the automated H152O maker is capable of producing and injecting the dose in the required succession under appropriate computer control.

An Open-Label, Multicenter, Phase I/II Study of JNJ-40346527, a CSF-1R Inhibitor, in Patients with Relapsed or Refractory Hodgkin Lymphoma.

PubMed

von Tresckow, Bastian; Morschhauser, Franck; Ribrag, Vincent; Topp, Max S; Chien, Caly; Seetharam, Shobha; Aquino, Regina; Kotoulek, Sonja; de Boer, Carla J; Engert, Andreas

2015-04-15

This phase I/II study investigated JNJ-40346527, a selective inhibitor of the colony-stimulating factor-1 receptor (CSF-1R) tyrosine kinase as treatment for relapsed or refractory classical Hodgkin lymphoma (cHL). Patients ≥18 years with histopathologically confirmed initial diagnosis of cHL that had relapsed or was refractory after ≥1 appropriate therapies were assigned to sequential cohorts of oral daily doses of JNJ-40346527 (150, 300, 450, 600 mg every day, and 150 mg twice a day). For the dose-escalation phase, the primary endpoint was to establish the recommended phase II dose. Secondary endpoints included safety, pharmacokinetics, and pharmacodynamics. Twenty-one patients [(150 mg: 3; 300 mg: 5; 450 mg: 3, 600 mg: 3) every day, and 150 mg twice a day: 7] were enrolled, 10 men, median age 40 (range, 19-75) years, median number of prior systemic therapies 6 (range, 3-14). No dose-limiting toxicities were observed; maximum-tolerated dose was not established. Best overall response was complete remission in 1 patient (duration, +352 days) and stable disease in 11 patients: (duration, 1.5-8 months). Median number of cycles: 4 (range, 1-16). Most common (≥20% patients) possibly drug-related adverse events (per investigator assessment) were nausea (n = 6), headache, and pyrexia (n = 5 each). JNJ-40346527 exposure increased in near dose-proportional manner over a dose range of 150 to 450 mg every day, but plateaued at 600 mg every day. Target engagement was confirmed (>80% inhibition of CSF-1R phosphorylation, 4 hours after dosing). JNJ-40346527, a selective inhibitor of CSF-1R was well tolerated, and preliminary antitumor results suggested limited activity in monotherapy for the treatment of cHL. ©2015 American Association for Cancer Research.

Combination of behaviorally sub-effective doses of glutamate NMDA and dopamine D1 receptor antagonists impairs executive function.

PubMed

Desai, Sagar J; Allman, Brian L; Rajakumar, Nagalingam

2017-04-14

Impairment of executive function is a core feature of schizophrenia. Preclinical studies indicate that injections of either N-methyl d-aspartate (NMDA) or dopamine D 1 receptor blockers impair executive function. Despite the prevailing notion based on postmortem findings in schizophrenia that cortical areas have marked suppression of glutamate and dopamine, recent in vivo imaging studies suggest that abnormalities of these neurotransmitters in living patients may be quite subtle. Thus, we hypothesized that modest impairments in both glutamate and dopamine function can act synergistically to cause executive dysfunction. In the present study, we investigated the effect of combined administration of "behaviorally sub-effective" doses of NMDA and dopamine D 1 receptor antagonists on executive function. An operant conditioning-based set-shifting task was used to assess behavioral flexibility in rats that were systemically injected with NMDA and dopamine D 1 receptor antagonists individually or in combination prior to task performance. Separate injections of the NMDA receptor antagonist, MK-801, and the dopamine D 1 receptor antagonist, SCH 23390, at low doses did not impair set-shifting; however, the combined administration of these same behaviorally sub-effective doses of the antagonists significantly impaired the performance during set-shifting without affecting learning, retrieval of the memory of the initial rule, latency of responses or the number of omissions. The combined treatment also produced an increased number of perseverative errors. Our results indicate that NMDA and D 1 receptor blockade act synergistically to cause behavioral inflexibility, and as such, subtle abnormalities in glutamatergic and dopaminergic systems may act cooperatively to cause deficits in executive function. Copyright © 2017 Elsevier B.V. All rights reserved.

Low-dose CT imaging of a total hip arthroplasty phantom using model-based iterative reconstruction and orthopedic metal artifact reduction.

PubMed

Wellenberg, R H H; Boomsma, M F; van Osch, J A C; Vlassenbroek, A; Milles, J; Edens, M A; Streekstra, G J; Slump, C H; Maas, M

2017-05-01

To compare quantitative measures of image quality, in terms of CT number accuracy, noise, signal-to-noise-ratios (SNRs), and contrast-to-noise ratios (CNRs), at different dose levels with filtered-back-projection (FBP), iterative reconstruction (IR), and model-based iterative reconstruction (MBIR) alone and in combination with orthopedic metal artifact reduction (O-MAR) in a total hip arthroplasty (THA) phantom. Scans were acquired from high- to low-dose (CTDI vol : 40.0, 32.0, 24.0, 16.0, 8.0, and 4.0 mGy) at 120- and 140- kVp. Images were reconstructed using FBP, IR (iDose 4 level 2, 4, and 6) and MBIR (IMR, level 1, 2, and 3) with and without O-MAR. CT number accuracy in Hounsfield Units (HU), noise or standard deviation, SNRs, and CNRs were analyzed. The IMR technique showed lower noise levels (p < 0.01), higher SNRs (p < 0.001) and CNRs (p < 0.001) compared with FBP and iDose 4 in all acquisitions from high- to low-dose with constant CT numbers. O-MAR reduced noise (p < 0.01) and improved SNRs (p < 0.01) and CNRs (p < 0.001) while improving CT number accuracy only at a low dose. At the low dose of 4.0 mGy, IMR level 1, 2, and 3 showed 83%, 89%, and 95% lower noise values, a factor 6.0, 9.2, and 17.9 higher SNRs, and 5.7, 8.8, and 18.2 higher CNRs compared with FBP respectively. Based on quantitative analysis of CT number accuracy, noise values, SNRs, and CNRs, we conclude that the combined use of IMR and O-MAR enables a reduction in radiation dose of 83% compared with FBP and iDose 4 in the CT imaging of a THA phantom.

A decade of Australian methotrexate dosing errors.

PubMed

Cairns, Rose; Brown, Jared A; Lynch, Ann-Maree; Robinson, Jeff; Wylie, Carol; Buckley, Nicholas A

2016-06-06

Accidental daily dosing of methotrexate can result in life-threatening toxicity. We investigated methotrexate dosing errors reported to the National Coronial Information System (NCIS), the Therapeutic Goods Administration Database of Adverse Event Notifications (TGA DAEN) and Australian Poisons Information Centres (PICs). A retrospective review of coronial cases in the NCIS (2000-2014), and of reports to the TGA DAEN (2004-2014) and Australian PICs (2004-2015). Cases were included if dosing errors were accidental, with evidence of daily dosing on at least 3 consecutive days. Events per year, dose, consecutive days of methotrexate administration, reasons for the error, clinical features. Twenty-two deaths linked with methotrexate were identified in the NCIS, including seven cases in which erroneous daily dosing was documented. Methotrexate medication error was listed in ten cases in the DAEN, including two deaths. Australian PIC databases contained 92 cases, with a worrying increase seen during 2014-2015. Reasons for the errors included patient misunderstanding and incorrect packaging of dosette packs by pharmacists. The recorded clinical effects of daily dosage were consistent with those previously reported for methotrexate toxicity. Dosing errors with methotrexate can be lethal and continue to occur despite a number of safety initiatives in the past decade. Further strategies to reduce these preventable harms need to be implemented and evaluated. Recent suggestions include further changes in packet size, mandatory weekly dosing labelling on packaging, improving education, and including alerts in prescribing and dispensing software.

Protection of the public in situations of prolonged radiation exposure. The application of the Commission's system of radiological protection to controllable radiation exposure due to natural sources and long-lived radioactive residues.

PubMed

1999-01-01

This report provides guidance on the application of the ICRP system of radiological protection to prolonged exposure situations affecting members of the public. It addresses the general application of the Commission's system to the control of prolonged exposures resulting from practices and to the undertaking of interventions in prolonged exposure situations. Additionally, it provides recommendations on generic reference levels for such interventions. The report also considers some specific situations and discusses a number of issues that have been of concern, namely: natural radiation sources that may give rise to high doses; the restoration and rehabilitation of sites where human activities involving radioactive substances have been carried out; the return to 'normality' following an accident that has released radioactive substances to the environment; and the global marketing of commodities for public consumption that contain radioactive substances. Annexes provide some examples of prolonged exposure situations and discuss the radiological protection quantities, radiation-induced health effects and aspects of the Commission's system of radiological protection relevant to prolonged exposure. Quantitative recommendations for prolonged exposures are provided in the report. They must be interpreted with extreme caution; Chapters 4 and 5 stress the upper bound nature of the following values: Generic reference levels for intervention, in terms of existing total annual doses, are given as < approximately 100 mSv, above which intervention is almost always justifiable (situations for which the annual dose threshold for deterministic effects in relevant organs is exceeded will almost always require intervention), and < approximately 10 mSv, below which intervention is not likely to be justifiable (and above which it may be necessary). Intervention exemption levels for commodities, especially building materials, are expressed as an additional annual dose of approximately 1 mSv. The dose limit for exposures of the public from practices is expressed as aggregated (prolonged and transitory) additional annual doses from all relevant practices of 1 mSv. Dose constraints for sources within practices are expressed as an additional annual dose lower than 1 mSv (e.g. of approximately 0.3 mSv), which could be approximately 0.1 mSv for the prolonged exposure component. An exemption level for practices is expressed as an additional annual dose of approximately 0.01 mSv.

SU-F-I-53: Coded Aperture Coherent Scatter Spectral Imaging of the Breast: A Monte Carlo Evaluation of Absorbed Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morris, R; Lakshmanan, M; Fong, G

Purpose: Coherent scatter based imaging has shown improved contrast and molecular specificity over conventional digital mammography however the biological risks have not been quantified due to a lack of accurate information on absorbed dose. This study intends to characterize the dose distribution and average glandular dose from coded aperture coherent scatter spectral imaging of the breast. The dose deposited in the breast from this new diagnostic imaging modality has not yet been quantitatively evaluated. Here, various digitized anthropomorphic phantoms are tested in a Monte Carlo simulation to evaluate the absorbed dose distribution and average glandular dose using clinically feasible scanmore » protocols. Methods: Geant4 Monte Carlo radiation transport simulation software is used to replicate the coded aperture coherent scatter spectral imaging system. Energy sensitive, photon counting detectors are used to characterize the x-ray beam spectra for various imaging protocols. This input spectra is cross-validated with the results from XSPECT, a commercially available application that yields x-ray tube specific spectra for the operating parameters employed. XSPECT is also used to determine the appropriate number of photons emitted per mAs of tube current at a given kVp tube potential. With the implementation of the XCAT digital anthropomorphic breast phantom library, a variety of breast sizes with differing anatomical structure are evaluated. Simulations were performed with and without compression of the breast for dose comparison. Results: Through the Monte Carlo evaluation of a diverse population of breast types imaged under real-world scan conditions, a clinically relevant average glandular dose for this new imaging modality is extrapolated. Conclusion: With access to the physical coherent scatter imaging system used in the simulation, the results of this Monte Carlo study may be used to directly influence the future development of the modality to keep breast dose to a minimum while still maintaining clinically viable image quality.« less

Basic PK/PD principles of drug effects in circular/proliferative systems for disease modelling.

PubMed

Jacqmin, Philippe; McFadyen, Lynn; Wade, Janet R

2010-04-01

Disease progression modelling can provide information about the time course and outcome of pharmacological intervention on the disease. The basic PK/PD principles of proliferative and circular systems within the context of modelling disease progression and the effect of treatment thereupon are illustrated with the goal to better understand/predict eventual clinical outcome. Circular/proliferative systems can be very complex. To facilitate the understanding of how a dosing regimen can be defined in such systems we have shown the derivation of a system parameter named the Reproduction Minimum Inhibitory Concentration (RMIC) which represents the critical concentration at which the system switches from growth to extinction. The RMIC depends on two parameters (RMIC = (R(0) - 1) x IC(50)): the basic reproductive ratio (R(0)) a fundamental parameter of the circular/proliferative system that represents the number of offspring produced by one replicating species during its lifespan, and the IC(50), the potency of the drug to inhibit the proliferation of the system. The RMIC is constant for a given system and a given drug and represents the lowest concentration that needs to be achieved for eradication of the system. When exposure is higher than the RMIC, success can be expected in the long term. Time varying inhibition of replicating species proliferation is a natural consequence of the time varying inhibitor drug concentrations and when combined with the dynamics of the circular/proliferative system makes it difficult to predict the eventual outcome. Time varying inhibition of proliferative/circular systems can be handled by calculating the equivalent effective constant concentration (ECC), the constant plasma concentration that would give rise to the average inhibition at steady state. When ECC is higher than the RMIC, eradication of the system can be expected. In addition, it is shown that scenarios that have the same steady state ECC whatever the dose, dosage schedule or PK parameters have also the same average R (0) in the presence of the inhibitor (i.e. R (0-INH)) and therefore lead to the same outcome. This allows predicting equivalent active doses and dosing schedules in circular and proliferative systems when the IC(50) and pharmacokinetic characteristics of the drugs are known. The results from the simulations performed demonstrate that, for a given system (defined by its RMIC), treatment success depends mainly on the pharmacokinetic characteristics of the drug and the dosing schedule.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siauw, Timmy; Cunha, Adam; Berenson, Dmitry

Purpose: In this study, the authors introduce skew line needle configurations for high dose rate (HDR) brachytherapy and needle planning by integer program (NPIP), a computational method for generating these configurations. NPIP generates needle configurations that are specific to the anatomy of the patient, avoid critical structures near the penile bulb and other healthy structures, and avoid needle collisions inside the body. Methods: NPIP consisted of three major components: a method for generating a set of candidate needles, a needle selection component that chose a candidate needle subset to be inserted, and a dose planner for verifying that the finalmore » needle configuration could meet dose objectives. NPIP was used to compute needle configurations for prostate cancer data sets from patients previously treated at our clinic. NPIP took two user-parameters: a number of candidate needles, and needle coverage radius, {delta}. The candidate needle set consisted of 5000 needles, and a range of {delta} values was used to compute different needle configurations for each patient. Dose plans were computed for each needle configuration. The number of needles generated and dosimetry were analyzed and compared to the physician implant. Results: NPIP computed at least one needle configuration for every patient that met dose objectives, avoided healthy structures and needle collisions, and used as many or fewer needles than standard practice. These needle configurations corresponded to a narrow range of {delta} values, which could be used as default values if this system is used in practice. The average end-to-end runtime for this implementation of NPIP was 286 s, but there was a wide variation from case to case. Conclusions: The authors have shown that NPIP can automatically generate skew line needle configurations with the aforementioned properties, and that given the correct input parameters, NPIP can generate needle configurations which meet dose objectives and use as many or fewer needles than the current HDR brachytherapy workflow. Combined with robot assisted brachytherapy, this system has the potential to reduce side effects associated with treatment. A physical trial should be done to test the implant feasibility of NPIP needle configurations.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mandapaka, A; Ghebremedhin, A; Patyal, B

Purpose: To validate the treatment planning system predicted proton dose beyond a heterogeneity (n-BCA glue) by making a measurement in a custom acrylic phantom. Methods: A custom cubic acrylic phantom was designed for this experiment. A container was designed to fit in the phantom. This container was filled with TRUFILL™ n-Butyl Cyanoacrylate(n-BCA) glue. When the container was placed in the phantom, its center was at a distance of 7.4cm from the entrance. This depth allows us to make measurements around the center of modulation of a 126 MeV proton beam with a 3cm spread-out-Bragg peak. To make measurements at othermore » beam energies, additional acrylic can be added in front of the phantom, to adjust the depth of the heterogeneity. A diamond detector was cross calibrated against a standard cylindrical ion chamber in a 126MeV beam. The diamond detector was then used to make dose measurements beyond the inhomogeneity. The measurement was repeated with the container filled with water. Several measurements were made at each setup, to check reproducibility of measurements. Results: For the same number of Tic3R1 counts, the dose measured with the diamond detector beyond n-BCA glue was 1.053 times the dose measured beyond the water filled container. This result is in agreement with the measured stopping power of glue (1.06). These measurements were in agreement with the dose predicted by the treatment planning system when the electron density of the heterogeneity was replaced with 1.06 before the dose calculation. Conclusion: Our initial measurements validate the dose predicted by our treatment plan in the presence of heterogeneity in a phantom. The material tested (n-BCA glue) is commonly used in the treatment of AVM’s prior to an SRS treatment. An error in dose predicted by the treatment plan in the presence of the glue can be detrimental in a single fraction high dose SRS treatment I received the n-BCA liquid embolic system samples from Codman and Shurtleff, Inc.« less

A dose optimization method for electron radiotherapy using randomized aperture beams

NASA Astrophysics Data System (ADS)

Engel, Konrad; Gauer, Tobias

2009-09-01

The present paper describes the entire optimization process of creating a radiotherapy treatment plan for advanced electron irradiation. Special emphasis is devoted to the selection of beam incidence angles and beam energies as well as to the choice of appropriate subfields generated by a refined version of intensity segmentation and a novel random aperture approach. The algorithms have been implemented in a stand-alone programme using dose calculations from a commercial treatment planning system. For this study, the treatment planning system Pinnacle from Philips has been used and connected to the optimization programme using an ASCII interface. Dose calculations in Pinnacle were performed by Monte Carlo simulations for a remote-controlled electron multileaf collimator (MLC) from Euromechanics. As a result, treatment plans for breast cancer patients could be significantly improved when using randomly generated aperture beams. The combination of beams generated through segmentation and randomization achieved the best results in terms of target coverage and sparing of critical organs. The treatment plans could be further improved by use of a field reduction algorithm. Without a relevant loss in dose distribution, the total number of MLC fields and monitor units could be reduced by up to 20%. In conclusion, using randomized aperture beams is a promising new approach in radiotherapy and exhibits potential for further improvements in dose optimization through a combination of randomized electron and photon aperture beams.

Thin-film-based scintillators for hard x-ray microimaging detectors: the ScinTAX Project

NASA Astrophysics Data System (ADS)

Rack, A.; Cecilia, A.; Douissard, P.-A.; Dupré, K.; Wesemann, V.; Baumbach, T.; Couchaud, M.; Rochet, X.; Riesemeier, H.; Radtke, M.; Martin, T.

2014-09-01

The project ScinTAX developed novel thin scintillating films for the application in high performance X-ray imaging and subsequent introduced new X-ray detectors to the market. To achieve this aim lutetium orthosilicate (LSO) scintillators doped with different activators were grown successfully by liquid phase epitaxy. The high density of LSO (7.4 g/cm3), the effective atomic number (65.2) and the high light yield make this scintillator highly applicable for indirect X-ray detection in which the ionizing radiation is converted into visible light and then registered by a digital detector. A modular indirect detection system has been developed to fully exploit the potential of this thin film scintillator for radiographic and tomographic imaging. The system is compatible for high-resolution imaging with moderate dose as well as adaptable to intense high-dose applications where radiation hard microimaging detectors are required. This proceedings article shall review the achieved performances and technical details on this high-resolution detector system which is now available. A selected example application demonstrates the great potential of the optimized detector system for hard X-ray microimaging, i.e. either to improve image contrast due to the availability of efficient thin crystal films or to reduce the dose to the sample.

Dose-Response for Multiple Biomarkers of Exposure and Genotoxic Effect Following Repeated Treatment of Rats with the Alkylating Agents, MMS and MNU.

PubMed

Ji, Zhiying; LeBaron, Matthew J; Schisler, Melissa R; Zhang, Fagen; Bartels, Michael J; Gollapudi, B Bhaskar; Pottenger, Lynn H

2016-05-01

The nature of the dose-response relationship for various in vivo endpoints of exposure and effect were investigated using the alkylating agents, methyl methanesulfonate (MMS) and methylnitrosourea (MNU). Six male F344 rats/group were dosed orally with 0, 0.5, 1, 5, 25 or 50mg/kg bw/day (mkd) of MMS, or 0, 0.01, 0.1, 1, 5, 10, 25 or 50 mkd of MNU, for 4 consecutive days and sacrificed 24h after the last dose. The dose-responses for multiple biomarkers of exposure and genotoxic effect were investigated. In MMS-treated rats, the hemoglobin adduct level, a systemic exposure biomarker, increased linearly with dose (r (2) = 0.9990, P < 0.05), indicating the systemic availability of MMS; however, the N7MeG DNA adduct, a target exposure biomarker, exhibited a non-linear dose-response in blood and liver tissues. Blood reticulocyte micronuclei (MN), a genotoxic effect biomarker, exhibited a clear no-observed-genotoxic-effect-level (NOGEL) of 5 mkd as a point of departure (PoD) for MMS. Two separate dose-response models, the Lutz and Lutz model and the stepwise approach using PROC REG both supported a bilinear/threshold dose-response for MN induction. Liver gene expression, a mechanistic endpoint, also exhibited a bilinear dose-response. Similarly, in MNU-treated rats, hepatic DNA adducts, gene expression changes and MN all exhibited clear PoDs, with a NOGEL of 1 mkd for MN induction, although dose-response modeling of the MNU-induced MN data showed a better statistical fit for a linear dose-response. In summary, these results provide in vivo data that support the existence of clear non-linear dose-responses for a number of biologically significant events along the pathway for genotoxicity induced by DNA-reactive agents. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of maternal and lactational exposure to 2-hydroxy-4-methoxybenzone on development and reproductive organs in male and female rat offspring

PubMed Central

Nakamura, Noriko; Inselman, Amy L.; White, Gene A.; Chang, Ching-Wei; Trbojevich, Raul A.; Sepehr, Estatira; Voris, Kristie L.; Patton, Ralph E.; Bryant, Matthew S.; Harrouk, Wafa; McIntyre, Barry; Foster, Paul M.; Hansen, Deborah K.

2015-01-01

BACKGROUND 2-hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV)-absorbing compound used in many cosmetic products as a UV-protecting agent and in plastics for preventing UV-induced photodecomposition. HMB has been detected in over 95% of randomly collected human urine samples from adults and from premature infants, and it may have estrogenic potential. METHODS To determine the effects of maternal and lactational exposure to HMB on development and reproductive organs of offspring, time-mated female Harlan Sprague-Dawley rats were dosed with 0, 1,000, 3,000, 10,000, 25,000, or 50,000 ppm HMB (7-8 per group) added to chow from gestation day 6 until weaning on postnatal day (PND) 23. RESULTS AND CONCLUSION Exposure to HMB was associated with reduced body and organ weights in female and male offspring. No significant differences were observed in the number of implantation sites/litter, mean resorptions/litter, % litters with resorptions, number and weights of live fetuses, or sex ratios between the control and HMB dose groups. Normalized anogenital distance in male pups at PND 23 was decreased in the highest dose group. Spermatocyte development was impaired in testes of male offspring in the highest dose group. In females, follicular development was delayed in the highest dose group. However, by evaluating levels of the compound in rat serum, the doses at which adverse events occurred are much higher than usual human exposure levels. Thus, exposure to less than 10,000 ppm HMB does not appear to be associated with adverse effects on the reproductive system in rats. PMID:25707689

SU-E-I-33: Initial Evaluation of Model-Based Iterative CT Reconstruction Using Standard Image Quality Phantoms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gingold, E; Dave, J

2014-06-01

Purpose: The purpose of this study was to compare a new model-based iterative reconstruction with existing reconstruction methods (filtered backprojection and basic iterative reconstruction) using quantitative analysis of standard image quality phantom images. Methods: An ACR accreditation phantom (Gammex 464) and a CATPHAN600 phantom were scanned using 3 routine clinical acquisition protocols (adult axial brain, adult abdomen, and pediatric abdomen) on a Philips iCT system. Each scan was acquired using default conditions and 75%, 50% and 25% dose levels. Images were reconstructed using standard filtered backprojection (FBP), conventional iterative reconstruction (iDose4) and a prototype model-based iterative reconstruction (IMR). Phantom measurementsmore » included CT number accuracy, contrast to noise ratio (CNR), modulation transfer function (MTF), low contrast detectability (LCD), and noise power spectrum (NPS). Results: The choice of reconstruction method had no effect on CT number accuracy, or MTF (p<0.01). The CNR of a 6 HU contrast target was improved by 1–67% with iDose4 relative to FBP, while IMR improved CNR by 145–367% across all protocols and dose levels. Within each scan protocol, the CNR improvement from IMR vs FBP showed a general trend of greater improvement at lower dose levels. NPS magnitude was greatest for FBP and lowest for IMR. The NPS of the IMR reconstruction showed a pronounced decrease with increasing spatial frequency, consistent with the unusual noise texture seen in IMR images. Conclusion: Iterative Model Reconstruction reduces noise and improves contrast-to-noise ratio without sacrificing spatial resolution in CT phantom images. This offers the possibility of radiation dose reduction and improved low contrast detectability compared with filtered backprojection or conventional iterative reconstruction.« less

How much does it cost to get a dose of vaccine to the service delivery location? Empirical evidence from Vietnam's Expanded Program on Immunization.

PubMed

Mvundura, Mercy; Kien, Vu Duy; Nga, Nguyen Tuyet; Robertson, Joanie; Cuong, Nguyen Van; Tung, Ho Thanh; Hong, Duong Thi; Levin, Carol

2014-02-07

Few studies document the costs of operating vaccine supply chains, but decision-makers need this information to inform cost projections for investments to accommodate new vaccine introduction. This paper presents empirical estimates of vaccine supply chain costs for Vietnam's Expanded Program on Immunization (EPI) for routine vaccines at each level of the supply chain, before and after the introduction of the pentavalent vaccine. We used micro-costing methods to collect resource-use data associated with storage and transportation of vaccines and immunization supplies at the national store, the four regional stores, and a sample of provinces, districts, and commune health centers. We collected stock ledger data on the total number of doses of vaccines handled by each facility during the assessment year. Total supply chain costs were estimated at approximately US$65,000 at the national store and an average of US$39,000 per region, US$5800 per province, US$2200 per district, and US$300 per commune health center. Across all levels, cold chain equipment capital costs and labor were the largest drivers of costs. The cost per dose delivered was estimated at US$0.19 before the introduction of pentavalent and US$0.24 cents after introduction. At commune health centers, supply chain costs were 104% of the value of vaccines before introduction of pentavalent vaccine and 24% after introduction, mainly due to the higher price per dose of the pentavalent vaccine. The aggregated costs at the last tier of the health system can be substantial because of the large number of facilities. Even in countries with high-functioning systems, empirical evidence on current costs from all levels of the system can help estimate resource requirements for expanding and strengthening resources to meet future immunization program needs. Other low- and middle-income countries can benefit from similar studies, in view of new vaccine introductions that will put strains on existing systems. Copyright © 2013 Elsevier Ltd. All rights reserved.

TU-H-CAMPUS-JeP3-05: Adaptive Determination of Needle Sequence HDR Prostate Brachytherapy with Divergent Needle-By-Needle Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borot de Battisti, M; Maenhout, M; Lagendijk, J J W

Purpose: To develop a new method which adaptively determines the optimal needle insertion sequence for HDR prostate brachytherapy involving divergent needle-by-needle dose delivery by e.g. a robotic device. A needle insertion sequence is calculated at the beginning of the intervention and updated after each needle insertion with feedback on needle positioning errors. Methods: Needle positioning errors and anatomy changes may occur during HDR brachytherapy which can lead to errors in the delivered dose. A novel strategy was developed to calculate and update the needle sequence and the dose plan after each needle insertion with feedback on needle positioning errors. Themore » dose plan optimization was performed by numerical simulations. The proposed needle sequence determination optimizes the final dose distribution based on the dose coverage impact of each needle. This impact is predicted stochastically by needle insertion simulations. HDR procedures were simulated with varying number of needle insertions (4 to 12) using 11 patient MR data-sets with PTV, prostate, urethra, bladder and rectum delineated. Needle positioning errors were modeled by random normally distributed angulation errors (standard deviation of 3 mm at the needle’s tip). The final dose parameters were compared in the situations where the needle with the largest vs. the smallest dose coverage impact was selected at each insertion. Results: Over all scenarios, the percentage of clinically acceptable final dose distribution improved when the needle selected had the largest dose coverage impact (91%) compared to the smallest (88%). The differences were larger for few (4 to 6) needle insertions (maximum difference scenario: 79% vs. 60%). The computation time of the needle sequence optimization was below 60s. Conclusion: A new adaptive needle sequence determination for HDR prostate brachytherapy was developed. Coupled to adaptive planning, the selection of the needle with the largest dose coverage impact increases chances of reaching the clinical constraints. M. Borot de Battisti is funded by Philips Medical Systems Nederland B.V.; M. Moerland is principal investigator on a contract funded by Philips Medical Systems Nederland B.V.; G. Hautvast and D. Binnekamp are fulltime employees of Philips Medical Systems Nederland B.V.« less

THE EFFECT OF X IRRADIATION ON THE SPREAD OF TICK-BORNE ENCEPHALITIS VIRUS THROUGH THE REGIONAL LYMPHATIC SYSTEM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malkova, D.

1962-09-01

Studies were made to ascertain whether changes caused in the lymphatic system by x radiation would affect penetration of the virus through the lymphatic system into the blood stream. Mice given 300 or 600 r were inoculated intraplantarly either on the 5th or 13th day after irradiation. Irradintion with either single dose led to a decrease in virus in regional lymph nodes and blood. if the animals were inoculated 5 days after irradiation. The decrease in virus titer was most marked in mice irradiated with a dose of 600 r and inoculated with 1500 LD/sub 50/ of virus. The titermore » of virus in the organs examined remained unaffected as long as the virus did not penetrate the regional lymphatic system into blood. The slower penetration of virus through the lymphatic system of irradiated mice was apparently caused by general changes in the lymphatic system, although it appears probable that an important factor was also the decreased number of lymphocytes, which may act as carriers of virus. (H.H.D.)« less

Radiation protection issues in galactic cosmic ray risk assessment

NASA Technical Reports Server (NTRS)

Sinclair, W. K.

1994-01-01

Radiation protection involves the limitation of exposure to below threshold doses for direct (or deterministic) effects and a knowledge of the risk of stochastic effects after low doses. The principal stochastic risk associated with low dose rate galactic cosmic rays is the increased risk of cancer. Estimates of this risk depend on two factors (a) estimates of cancer risk for low-LET radiation and (b) values of the appropriate radiation weighting factors, WR, for the high-LET radiations of galactic cosmic rays. Both factors are subject to considerable uncertainty. The low-LET cancer risk derived from the late effects of the atomic bombs is vulnerable to a number of uncertainties including especially that from projection in time, and from extrapolation from high to low dose rate. Nevertheless, recent low dose studies of workers and others tend to confirm these estimates. WR, relies on biological effects studied mainly in non-human systems. Additional laboratory studies could reduce the uncertainties in WR and thus produce a more confident estimate of the overall risk of galactic cosmic rays.

Radiation protection issues in galactic cosmic ray risk assessment.

PubMed

Sinclair, W K

1994-01-01

Radiation protection involves the limitation of exposure to below threshold doses for direct (or deterministic) effects and a knowledge of the risk of stochastic effects after low doses. The principal stochastic risk associated with low dose rate galactic cosmic rays is the increased risk of cancer. Estimates of this risk depend on two factors (a) estimates of cancer risk for low-LET radiation and (b) values of the appropriate radiation weighting factors, WR, for the high-LET radiations of galactic cosmic rays. Both factors are subject to considerable uncertainty. The low-LET cancer risk derived from the late effects of the atomic bombs is vulnerable to a number of uncertainties including especially that from projection in time, and from extrapolation from high to low dose rate. Nevertheless, recent low dose studies of workers and others tend to confirm these estimates. WR, relies on biological effects studied mainly in non-human systems. Additional laboratory studies could reduce the uncertainties in WR and thus produce a more confident estimate of the overall risk of galactic cosmic rays.

Formulation design, challenges, and development considerations for fixed dose combination (FDC) of oral solid dosage forms.

PubMed

Desai, Divyakant; Wang, Jennifer; Wen, Hong; Li, Xuhong; Timmins, Peter

2013-01-01

Fixed dose combination (FDC) products are common in the treatment of hypertension, diabetes, human immunodeficiency virus, and tuberculosis. They make it possible to combine two or more drug molecules with different modes of pharmacological actions in a single dosing unit and optimize the treatment. From a patient perspective, they offer convenience, reduced dosing unit burden, and cost savings. From a clinical perspective, aging population in developed countries will need multiple medications to treat age related diseases and co-morbidities. FDC products simplify dosing regimen and enhance patient compliance. As outlined in the article, the number of FDC products has grown over the years and the trend is likely to continue. This review article gives an overview to pharmaceutical scientists about recent trends in the formulation development of the FDC products and provides decision trees to select most optimum formulation development strategy. While some formulation technologies such as multi-layer tablets, multiparticulate systems, active film coating, and hot-melt granulation are discussed in more detail, a few specialized technologies are also introduced briefly to the readers.

Comparison of the Pharmacoeconomics of Calfactant and Poractant Alfa in Surfactant Replacement erapy.

PubMed

Zayek, Michael M; Eyal, Fabien G; Smith, Robert C

2018-01-01

To compare the pharmacy costs of calfactant (Infasurf, ONY, Inc.) and poractant alfa (Curosurf, Chiesi USA, Inc., Cary, NC). The University of South Alabama Children's and Women's Hospital switched from calfactant to poractant alfa in 2013 and back to calfactant in 2015. Retrospectively, we used deidentified data from pharmacy records that provided type of surfactant administered, gestational age, birth weight, and number of doses on each patient. We examined differences in the number of doses by gestational ages and the differences in costs by birth weight cohorts because cost per dose is based on weight. There were 762 patients who received calfactant and 432 patients who received poractant alfa. The average number of doses required per patient was 1.6 administrations for calfactant-treated patients and 1.7 administrations for poractant alfa-treated patients, p = 0.03. A higher percentage of calfactant patients needed only 1 dose (53%) than poractant alfa patients (47%). The distribution of the number of doses for calfactant-treated patients was significantly lower than for the poractant alfa-patients, p < 0.001. Gestational age had no consistent effect on the number of doses required for either calfactant or poractant alfa. Per patient cost was higher for poractant alfa than for calfactant in all birth weight cohorts. Average per patient cost was $1160.62 for poractant alfa, 38% higher than the average per patient cost for calfactant ($838.34). Using poractant alfa for 22 months is estimated to have cost $202,732.75 more than it would have cost if the hospital had continued using calfactant. Our experience showed a strong pharmacoeconomic advantage for the use of calfactant compared to the use of poractant alfa because of similar average dosing and lower per patient drug costs.

The dependence of the growth rate and meat content of young boars on semen parameters and conception rate.

PubMed

Knecht, D; Jankowska-Mąkosa, A; Duziński, K

2017-05-01

Boars have a decisive impact on the progress in pig production, however, there is no recent information about the optimal growth parameters during the rearing period for modern breed later used in artificial insemination (AI) stations. Therefore, the objective of the research was to conduct semen parameter and conception rate analyses on the basis of growth rate and meat content assessments made during the rearing of AI boars of different genotypes. The study was carried out between 2010 and 2014 and included 184 boars in five breed combinations: 46 Polish Large White, 50 Polish Landrace, 27 Pietrain, 36 Duroc×Pietrain and 25 Hampshire×Pietrain. Boars were qualified by daily gains and meat content assessment (between 170 and 210 days of life). A total number of 38 272 ejaculates were examined (semen volume (ml), spermatozoa concentration (×106 ml-1), total number of spermatozoa (×109) and number of insemination doses from one ejaculate (n)). The fertility was determined by the conception rate (%). Semen volume, spermatozoa concentration and conception rate (P<0.01), followed by the total number of spermatozoa and insemination doses (P<0.05) were characterized by the highest variability in relation to breed of boars. The effect of daily gains was reported for spermatozoa concentration, number of insemination doses, conception rate (all P<0.01) and total number of spermatozoa (P<0.05). The peak of growth for spermatozoa concentration, total number of spermatozoa, insemination doses and conception rate was achieved for 800 to 850 g gains. Meat content affected semen volume, number of insemination doses and conception rate (P<0.05). Rearing boars while maintaining daily gains at the 800 to 850 g level and 62.5% to 65% meat content helps AI stations to increase the efficiency and economic profitability, and the number of insemination doses to increase by up to 300 doses/boar within a year. The analyses of growth parameters may help increase the efficiency and economic viability of AI stations.

Effect of anti-vertigo granule on the opening number and blood flow of mouse ear capillary network

NASA Astrophysics Data System (ADS)

Li, Chongxian; Liu, Xiaobin; Li, Jun; Hao, Shaojun; Wang, Xidong; Li, Wenjun; Zhang, Zhengchen

2018-04-01

To observe the effects of anti-glare particles on the open number and blood flow in the auricle of mice with microcirculation disturbance model. Sixty mice, half male and half female, were randomly divided into 6 groups. The mice were given Kangxuan granule suspension, serum brain granule suspension and normal saline of the same volume, respectively, once a day. The mice were anesthetized by intraperitoneal injection of chloral hydrate at 1 hour after the last administration. The mouse was fixed on the observation platform and the auricle was placed on the transmission stage. BZ-2000 microcirculation microscope and microcirculation analysis system were used to observe the changes of blood velocity and capillary opening volume in auricle of mice before administration. The changes of blood velocity and capillaries opening volume of mouse auricle were observed 2 min after epinephrine injection into tail vein of mice. Bear fruit: Compared with those before epinephrine, the opening number of capillary reticulum of auricle in large dose Kangxuan granule group was significantly decreased (P<0.05), and in normal saline group and middle group. In the small dose Kangxuan granule group, the opening number of capillary network of auricle decreased significantly (P<0.01). Compared with the model group, the large dose Kangxuan granule group could significantly increase the opening number of the auricle capillary network in mice (P<0.01). Yangxuannao granule group could significantly increase the opening number of auricle capillary reticulum in mice (P<0.05), compared with the model group by Ridit test. Both Kangxuan granule group and Yangxuannao granule group could significantly improve the auricle hair of mice with microcirculation disorder. The blood flow in fine blood vessels (P<0.01). Kangxuan granule has a good effect on the opening number of capillary network of auricle and blood flow in mice with microcirculation disorder.

The effects of two different doses of hydrocortisone on cognition in patients with secondary adrenal insufficiency--results from a randomized controlled trial.

PubMed

Werumeus Buning, Jorien; Brummelman, Pauline; Koerts, Janneke; Dullaart, Robin P F; van den Berg, Gerrit; van der Klauw, Melanie M; Tucha, Oliver; Wolffenbuttel, Bruce H R; van Beek, André P

2015-05-01

A wide variety in hydrocortisone (HC) substitution dose-regimens are considered physiological for patients with secondary adrenal insufficiency (SAI). However, it is likely that cognition is negatively influenced by higher cortisol exposure to the brain. To examine the effects of a high physiological HC dose in comparison to a low physiological HC dose on cognition. This study was a randomized double blind cross-over study at the University Medical Center Groningen. This study is registered with ClinicalTrials.gov, number NCT01546922. Forty-seven patients (29 males, 18 females; mean [SD] age, 51 [14] years, range 19-73) with SAI participated. Patients randomly received first a low dose of HC (0.2-0.3 mg/kg body weight/day) during 10 weeks followed by a high dose (0.4-0.6 mg/kg body weight/day) for another 10 weeks, or vice versa. HC substitution was given in three divided doses with the highest dose in the morning. Cognitive performance (memory, attention, executive functioning and social cognition) of patients was measured at baseline and after each treatment period using a battery of 12 standardized cognitive tests. The higher dose of HC resulted in significantly higher systemic cortisol exposure for example measured at 1h after first dose ingestion (mean [SD], low dose: 653 [281] nmol/L; high dose: 930 [148] nmol/L; P<0.001). No differences in cognitive performance were found between the two dose regimens. No negative influence on memory, attention, executive functioning and social cognition was observed after 10 weeks of treatment with a higher physiological dose of HC in patients with SAI when compared to a lower dose. Copyright © 2015 Elsevier Ltd. All rights reserved.

A treatment planning study to assess the feasibility of laser-driven proton therapy using a compact gantry design.

PubMed

Hofmann, Kerstin M; Masood, Umar; Pawelke, Joerg; Wilkens, Jan J

2015-09-01

Laser-driven proton acceleration is suggested as a cost- and space-efficient alternative for future radiation therapy centers, although the properties of these beams are fairly different compared to conventionally accelerated proton beams. The laser-driven proton beam is extremely pulsed containing a very high proton number within ultrashort bunches at low bunch repetition rates of few Hz and the energy spectrum of the protons per bunch is very broad. Moreover, these laser accelerated bunches are subject to shot-to-shot fluctuations. Therefore, the aim of this study was to investigate the feasibility of a compact gantry design for laser-driven proton therapy and to determine limitations to comply with. Based on a published gantry beam line design which can filter parabolic spectra from an exponentially decaying broad initial spectrum, a treatment planning study was performed on real patient data sets. All potential parabolic spectra were fed into a treatment planning system and numerous spot scanning proton plans were calculated. To investigate limitations in the fluence per bunch, the proton number of the initial spectrum and the beam width at patient entrance were varied. A scenario where only integer shots are delivered as well as an intensity modulation from shot to shot was studied. The resulting plans were evaluated depending on their dosimetric quality and in terms of required treatment time. In addition, the influence of random shot-to-shot fluctuations on the plan quality was analyzed. The study showed that clinically relevant dose distributions can be produced with the system under investigation even with integer shots. For small target volumes receiving high doses per fraction, the initial proton number per bunch must remain between 1.4 × 10(8) and 8.3 × 10(9) to achieve acceptable delivery times as well as plan qualities. For larger target volumes and standard doses per fraction, the initial proton number is even more restricted to stay between 1.4 × 10(9) and 2.9 × 10(9). The lowest delivery time that could be reached for such a case was 16 min for a 10 Hz system. When modulating the intensity from shot to shot, the delivery time can be reduced to 6 min for this scenario. Since the shot-to-shot fluctuations are of random nature, a compensation effect can be observed, especially for higher laser shot numbers. Therefore, a fluctuation of ± 30% within the proton number does not translate into a dosimetric deviation of the same size. However, for plans with short delivery times these fluctuations cannot cancel out sufficiently, even for ± 10% fluctuations. Under the analyzed terms, it is feasible to achieve clinically relevant dose distributions with laser-driven proton beams. However, to keep the delivery times of the proton plans comparable to conventional proton plans for typical target volumes, a device is required which can modulate the bunch intensity from shot to shot. From the laser acceleration point of view, the proton number per bunch must be kept under control as well as the reproducibility of the bunches.

A treatment planning study to assess the feasibility of laser-driven proton therapy using a compact gantry design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hofmann, Kerstin M., E-mail: kerstin.hofmann@lrz.tu-muenchen.de; Wilkens, Jan J.; Masood, Umar

Purpose: Laser-driven proton acceleration is suggested as a cost- and space-efficient alternative for future radiation therapy centers, although the properties of these beams are fairly different compared to conventionally accelerated proton beams. The laser-driven proton beam is extremely pulsed containing a very high proton number within ultrashort bunches at low bunch repetition rates of few Hz and the energy spectrum of the protons per bunch is very broad. Moreover, these laser accelerated bunches are subject to shot-to-shot fluctuations. Therefore, the aim of this study was to investigate the feasibility of a compact gantry design for laser-driven proton therapy and tomore » determine limitations to comply with. Methods: Based on a published gantry beam line design which can filter parabolic spectra from an exponentially decaying broad initial spectrum, a treatment planning study was performed on real patient data sets. All potential parabolic spectra were fed into a treatment planning system and numerous spot scanning proton plans were calculated. To investigate limitations in the fluence per bunch, the proton number of the initial spectrum and the beam width at patient entrance were varied. A scenario where only integer shots are delivered as well as an intensity modulation from shot to shot was studied. The resulting plans were evaluated depending on their dosimetric quality and in terms of required treatment time. In addition, the influence of random shot-to-shot fluctuations on the plan quality was analyzed. Results: The study showed that clinically relevant dose distributions can be produced with the system under investigation even with integer shots. For small target volumes receiving high doses per fraction, the initial proton number per bunch must remain between 1.4 × 10{sup 8} and 8.3 × 10{sup 9} to achieve acceptable delivery times as well as plan qualities. For larger target volumes and standard doses per fraction, the initial proton number is even more restricted to stay between 1.4 × 10{sup 9} and 2.9 × 10{sup 9}. The lowest delivery time that could be reached for such a case was 16 min for a 10 Hz system. When modulating the intensity from shot to shot, the delivery time can be reduced to 6 min for this scenario. Since the shot-to-shot fluctuations are of random nature, a compensation effect can be observed, especially for higher laser shot numbers. Therefore, a fluctuation of ±30% within the proton number does not translate into a dosimetric deviation of the same size. However, for plans with short delivery times these fluctuations cannot cancel out sufficiently, even for ±10% fluctuations. Conclusions: Under the analyzed terms, it is feasible to achieve clinically relevant dose distributions with laser-driven proton beams. However, to keep the delivery times of the proton plans comparable to conventional proton plans for typical target volumes, a device is required which can modulate the bunch intensity from shot to shot. From the laser acceleration point of view, the proton number per bunch must be kept under control as well as the reproducibility of the bunches.« less

A comprehensive study on the relationship between the image quality and imaging dose in low-dose cone beam CT

NASA Astrophysics Data System (ADS)

Yan, Hao; Cervino, Laura; Jia, Xun; Jiang, Steve B.

2012-04-01

While compressed sensing (CS)-based algorithms have been developed for the low-dose cone beam CT (CBCT) reconstruction, a clear understanding of the relationship between the image quality and imaging dose at low-dose levels is needed. In this paper, we qualitatively investigate this subject in a comprehensive manner with extensive experimental and simulation studies. The basic idea is to plot both the image quality and imaging dose together as functions of the number of projections and mAs per projection over the whole clinically relevant range. On this basis, a clear understanding of the tradeoff between the image quality and imaging dose can be achieved and optimal low-dose CBCT scan protocols can be developed to maximize the dose reduction while minimizing the image quality loss for various imaging tasks in image-guided radiation therapy (IGRT). Main findings of this work include (1) under the CS-based reconstruction framework, image quality has little degradation over a large range of dose variation. Image quality degradation becomes evident when the imaging dose (approximated with the x-ray tube load) is decreased below 100 total mAs. An imaging dose lower than 40 total mAs leads to a dramatic image degradation, and thus should be used cautiously. Optimal low-dose CBCT scan protocols likely fall in the dose range of 40-100 total mAs, depending on the specific IGRT applications. (2) Among different scan protocols at a constant low-dose level, the super sparse-view reconstruction with the projection number less than 50 is the most challenging case, even with strong regularization. Better image quality can be acquired with low mAs protocols. (3) The optimal scan protocol is the combination of a medium number of projections and a medium level of mAs/view. This is more evident when the dose is around 72.8 total mAs or below and when the ROI is a low-contrast or high-resolution object. Based on our results, the optimal number of projections is around 90 to 120. (4) The clinically acceptable lowest imaging dose level is task dependent. In our study, 72.8 mAs is a safe dose level for visualizing low-contrast objects, while 12.2 total mAs is sufficient for detecting high-contrast objects of diameter greater than 3 mm.

Optimization of Monte Carlo dose calculations: The interface problem

NASA Astrophysics Data System (ADS)

Soudentas, Edward

1998-05-01

High energy photon beams are widely used for radiation treatment of deep-seated tumors. The human body contains many types of interfaces between dissimilar materials that affect dose distribution in radiation therapy. Experimentally, significant radiation dose perturbations has been observed at such interfaces. The EGS4 Monte Carlo code was used to calculate dose perturbations at boundaries between dissimilar materials (such as bone/water) for 60Co and 6 MeV linear accelerator beams using a UNIX workstation. A simple test of the reliability of a random number generator was also developed. A systematic study of the adjustable parameters in EGS4 was performed in order to minimize calculational artifacts at boundaries. Calculations of dose perturbations at boundaries between different materials showed that there is a 12% increase in dose at water/bone interface, and a 44% increase in dose at water/copper interface. with the increase mainly due to electrons produced in water and backscattered from the high atomic number material. The dependence of the dose increase on the atomic number was also investigated. The clinically important case of using two parallel opposed beams for radiation therapy was investigated where increased doses at boundaries has been observed. The Monte Carlo calculations can provide accurate dosimetry data under conditions of electronic non-equilibrium at tissue interfaces.

Dosimetric advantages of generalised equivalent uniform dose-based optimisation on dose–volume objectives in intensity-modulated radiotherapy planning for bilateral breast cancer

PubMed Central

Lee, T-F; Ting, H-M; Chao, P-J; Wang, H-Y; Shieh, C-S; Horng, M-F; Wu, J-M; Yeh, S-A; Cho, M-Y; Huang, E-Y; Huang, Y-J; Chen, H-C; Fang, F-M

2012-01-01

Objective We compared and evaluated the differences between two models for treating bilateral breast cancer (BBC): (i) dose–volume-based intensity-modulated radiation treatment (DV plan), and (ii) dose–volume-based intensity-modulated radiotherapy with generalised equivalent uniform dose-based optimisation (DV-gEUD plan). Methods The quality and performance of the DV plan and DV-gEUD plan using the Pinnacle3® system (Philips, Fitchburg, WI) were evaluated and compared in 10 patients with stage T2–T4 BBC. The plans were delivered on a Varian 21EX linear accelerator (Varian Medical Systems, Milpitas, CA) equipped with a Millennium 120 leaf multileaf collimator (Varian Medical Systems). The parameters analysed included the conformity index, homogeneity index, tumour control probability of the planning target volume (PTV), the volumes V20 Gy and V30 Gy of the organs at risk (OAR, including the heart and lungs), mean dose and the normal tissue complication probability. Results Both plans met the requirements for the coverage of PTV with similar conformity and homogeneity indices. However, the DV-gEUD plan had the advantage of dose sparing for OAR: the mean doses of the heart and lungs, lung V20 Gy, and heart V30 Gy in the DV-gEUD plan were lower than those in the DV plan (p<0.05). Conclusions A better result can be obtained by starting with a DV-generated plan and then improving it by adding gEUD-based improvements to reduce the number of iterations and to improve the optimum dose distribution. Advances to knowledge The DV-gEUD plan provided superior dosimetric results for treating BBC in terms of PTV coverage and OAR sparing than the DV plan, without sacrificing the homogeneity of dose distribution in the PTV. PMID:23091290

SU-E-T-182: Feasibility of Dose Painting by Numbers in Proton Therapy with Contour-Driven Plan Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montero, A Barragan; Differding, S; Lee, J

Purpose: The work aims to 1) prove the feasibility of dose painting by numbers (DPBN) in proton therapy with usual contour-driven plan optimization and 2) compare the achieved plan quality to that of rotational IMRT. Methods: For two patients with head and neck cancers, voxel-by-voxel prescription to the target volume (PTV-PET) was calculated from {sup 18} FDG-PET images and converted to contour-based prescription by defining several sub-contours. Treatments were planned with RayStation (RaySearch Laboratories, Sweden) and proton pencil beam scanning modality. In order to determine the optimal plan parameters to approach the DPBN prescription, the effect of the number ofmore » fields, number of sub-contours and use of range shifter were tested separately on each patient. The number of sub-contours were increased from 3 to 11 while the number of fields were set to 3, 5, 7 and 9. Treatment plans were also optimized on two rotational IMRT systems (TomoTherapy and Varian RapidArc) using previously published guidelines. Results: For both patients, more than 99% of the PTV-PET received at least 95% of the prescribed dose while less than 1% of the PTV-PET received more than 105%, which demonstrates the feasibility of the treatment. Neither the use of a range shifter nor the increase of the number of fields had a significant influence on PTV coverage. Plan quality increased when increasing number of fields up to 7 or 9 and slightly decreased for a bigger number of sub-contours. Good OAR sparing is achieved while keeping high plan quality. Finally, proton therapy achieved significantly better plan quality than rotational IMRT. Conclusion: Voxel-by-voxel prescriptions can be approximated accurately in proton therapy using a contour-driven optimization. Target coverage is nearly insensitive to the number of fields and the use of a range shifter. Finally, plan quality assessment confirmed the superiority of proton therapy compared to rotational IMRT.« less

The Impact of Dose Rate on the Accuracy of Step-and-Shoot Intensity-modulated Radiation Therapy Quality Assurance Using Varian 2300CD.

PubMed

Njeh, Christopher F; Salmon, Howard W; Schiller, Claire

2017-01-01

Intensity-modulated radiation therapy (IMRT) delivery using "step-and-shoot" technique on Varian C-Series linear accelerator (linac) is influenced by the communication frequency between the multileaf collimator and linac controllers. Hence, the dose delivery accuracy is affected by the dose rate. Our aim was to quantify the impact of using two dose rates on plan quality assurance (QA). Twenty IMRT patients were selected for this study. The plan QA was measured at two different dose rates. A gamma analysis was performed, and the degree of plan modulation on the QA pass rate was also evaluated in terms of average monitor unit per segment (MU/segment) and the total number of segments. The mean percentage gamma pass rate of 94.9% and 93.5% for 300 MU/min and 600 MU/min dose rate, respectively, was observed. There was a significant ( P = 0.001) decrease in percentage gamma pass rate when the dose rate was increased from 300 MU/min to 600 MU/min. There was a weak, but significant association between the percentage pass rate at both dose rate and total number of segments. The total number of MU was significantly correlated to the total number of segments ( r = 0.59). We found a positive correlation between the percentage pass rate and mean MU/segment, r = 0.52 and r = 0.57 for 300 MU/min and 600 MU/min, respectively. IMRT delivery using step-and-shoot technique on Varian 2300CD is impacted by the dose rate and the total amount of segments.

Influence of beam efficiency through the patient-specific collimator on secondary neutron dose equivalent in double scattering and uniform scanning modes of proton therapy.

PubMed

Hecksel, D; Anferov, V; Fitzek, M; Shahnazi, K

2010-06-01

Conventional proton therapy facilities use double scattering nozzles, which are optimized for delivery of a few fixed field sizes. Similarly, uniform scanning nozzles are commissioned for a limited number of field sizes. However, cases invariably occur where the treatment field is significantly different from these fixed field sizes. The purpose of this work was to determine the impact of the radiation field conformity to the patient-specific collimator on the secondary neutron dose equivalent. Using a WENDI-II neutron detector, the authors experimentally investigated how the neutron dose equivalent at a particular point of interest varied with different collimator sizes, while the beam spreading was kept constant. The measurements were performed for different modes of dose delivery in proton therapy, all of which are available at the Midwest Proton Radiotherapy Institute (MPRI): Double scattering, uniform scanning delivering rectangular fields, and uniform scanning delivering circular fields. The authors also studied how the neutron dose equivalent changes when one changes the amplitudes of the scanned field for a fixed collimator size. The secondary neutron dose equivalent was found to decrease linearly with the collimator area for all methods of dose delivery. The relative values of the neutron dose equivalent for a collimator with a 5 cm diameter opening using 88 MeV protons were 1.0 for the double scattering field, 0.76 for rectangular uniform field, and 0.6 for the circular uniform field. Furthermore, when a single circle wobbling was optimized for delivery of a uniform field 5 cm in diameter, the secondary neutron dose equivalent was reduced by a factor of 6 compared to the double scattering nozzle. Additionally, when the collimator size was kept constant, the neutron dose equivalent at the given point of interest increased linearly with the area of the scanned proton beam. The results of these experiments suggest that the patient-specific collimator is a significant contributor to the secondary neutron dose equivalent to a distant organ at risk. Improving conformity of the radiation field to the patient-specific collimator can significantly reduce secondary neutron dose equivalent to the patient. Therefore, it is important to increase the number of available generic field sizes in double scattering systems as well as in uniform scanning nozzles.

Missed doses of oral antihyperglycemic medications in US adults with type 2 diabetes mellitus: prevalence and self-reported reasons.

PubMed

Vietri, Jeffrey T; Wlodarczyk, Catherine S; Lorenzo, Rose; Rajpathak, Swapnil

2016-09-01

Adherence to antihyperglycemic medication is thought to be suboptimal, but the proportion of patients missing doses, the number of doses missed, and reasons for missing are not well described. This survey was conducted to estimate the prevalence of and reasons for missed doses of oral antihyperglycemic medications among US adults with type 2 diabetes mellitus, and to explore associations between missed doses and health outcomes. The study was a cross-sectional patient survey. Respondents were contacted via a commercial survey panel and completed an on-line questionnaire via the Internet. Respondents provided information about their use of oral antihyperglycemic medications including doses missed in the prior 4 weeks, personal characteristics, and health outcomes. Weights were calculated to project the prevalence to the US adult population with type 2 diabetes mellitus. Outcomes were compared according to number of doses missed in the past 4 weeks using bivariate statistics and generalized linear models. Approximately 30% of adult patients with type 2 diabetes mellitus reported missing or reducing ≥1 dose of oral antihyperglycemic medication in the prior 4 weeks. Accidental missing was more commonly reported than purposeful skipping, with forgetting the most commonly reported reason. The timing of missed doses suggested respondents had also forgotten about doses missed, so the prevalence of missed doses is likely higher than reported. Outcomes were poorer among those who reported missing three or more doses in the prior 4 weeks. A substantial number of US adults with type 2 diabetes mellitus miss doses of their oral antihyperglycemic medications.

Sodium oxybate for cataplexy.

PubMed

Lemon, Michael D; Strain, Joe D; Farver, Debra K

2006-03-01

To review the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, precautions, dosing recommendations, and patient counseling of sodium oxybate for the treatment of cataplexy in patients with narcolepsy. OVID and PubMed databases were searched (1966-January 2006) using the key words sodium oxybate, gamma-hydroxybutyrate, narcolepsy, and cataplexy. Only English-language articles were selected. All information on sodium oxybate related to narcolepsy and cataplexy was considered. Study selection included human trials evaluating safety and efficacy of sodium oxybate for the treatment of cataplexy. Sodium oxybate is approved by the Food and Drug Administration for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. In placebo-controlled trials, sodium oxybate demonstrated efficacy in reducing the number of cataplexy attacks. The dosing regimen includes a split dose given at bedtime and 2.5-4 hours later due to its short elimination half-life. The drug is generally well tolerated, with headache, nausea, dizziness, pain, and somnolence being the most common adverse events. Sodium oxybate is safe and effective for the treatment of cataplexy. Potential disadvantages include a multiple dosing regimen, abuse potential, cost, and a closed distribution system. Potential advantages demonstrated in clinical trials include significant decreases in the number of weekly cataplexy attacks, improvement in daytime sleepiness, and improvement in the Clinical Global Impression of Change score and nighttime awakenings. Overall, sodium oxybate provides a new option for the treatment of cataplexy.

Dose and dose rate effects of whole-body gamma-irradiation: I. Lymphocytes and lymphoid organs

NASA Technical Reports Server (NTRS)

Pecaut, M. J.; Nelson, G. A.; Gridley, D. S.

2001-01-01

The major goal of part I of this study was to compare varying doses and dose rates of whole-body gamma-radiation on lymphoid cells and organs. C57BL/6 mice (n = 75) were exposed to 0, 0.5, 1.5, and 3.0 Gy gamma-rays (60Co) at 1 cGy/min (low-dose rate, LDR) and 80 cGy/min (high-dose rate, HDR) and euthanized 4 days later. A significant dose-dependent loss of spleen mass was observed with both LDR and HDR irradiation; for the thymus this was true only with HDR. Decreasing leukocyte and lymphocyte numbers occurred with increasing dose in blood and spleen at both dose rates. The numbers (not percentages) of CD3+ T lymphocytes decreased in the blood in a dose-dependent manner at both HDR and LDR. Splenic T cell counts decreased with dose only in HDR groups; percentages increased with dose at both dose rates. Dose-dependent decreases occurred in CD4+ T helper and CD8+ T cytotoxic cell counts at HDR and LDR. In the blood the percentages of CD4+ cells increased with increasing dose at both dose rates, whereas in the spleen the counts decreased only in the HDR groups. The percentages of the CD8+ population remained stable in both blood and spleen. CD19+ B cell counts and percentages in both compartments declined markedly with increasing HDR and LDR radiation. NK1.1+ natural killer cell numbers and proportions remained relatively stable. Overall, these data indicate that the observed changes were highly dependent on the dose, but not dose rate, and that cells in the spleen are more affected by dose rate than those in blood. The results also suggest that the response of lymphocytes in different body compartments may be variable.

Quantitative evaluation of 3D dosimetry for stereotactic volumetric‐modulated arc delivery using COMPASS

PubMed Central

Manigandan, Durai; Karrthick, Karukkupalayam Palaniappan; Sambasivaselli, Raju; Senniandavar, Vellaingiri; Ramu, Mahendran; Rajesh, Thiyagarajan; Lutz, Muller; Muthukumaran, Manavalan; Karthikeyan, Nithyanantham; Tejinder, Kataria

2014-01-01

The purpose of this study was to evaluate quantitatively the patient‐specific 3D dosimetry tool COMPASS with 2D array MatriXX detector for stereotactic volumetric‐modulated arc delivery. Twenty‐five patients CT images and RT structures from different sites (brain, head & neck, thorax, abdomen, and spine) were taken from CyberKnife Multiplan planning system for this study. All these patients underwent radical stereotactic treatment in CyberKnife. For each patient, linac based volumetric‐modulated arc therapy (VMAT) stereotactic plans were generated in Monaco TPS v3.1 using Elekta Beam Modulator MLC. Dose prescription was in the range of 5–20 Gy per fraction. Target prescription and critical organ constraints were tried to match the delivered treatment plans. Each plan quality was analyzed using conformity index (CI), conformity number (CN), gradient Index (GI), target coverage (TC), and dose to 95% of volume (D95). Monaco Monte Carlo (MC)‐calculated treatment plan delivery accuracy was quantitatively evaluated with COMPASS‐calculated (CCA) dose and COMPASS indirectly measured (CME) dose based on dose‐volume histogram metrics. In order to ascertain the potential of COMPASS 3D dosimetry for stereotactic plan delivery, 2D fluence verification was performed with MatriXX using MultiCube phantom. Routine quality assurance of absolute point dose verification was performed to check the overall delivery accuracy. Quantitative analyses of dose delivery verification were compared with pass and fail criteria of 3 mm and 3% distance to agreement and dose differences. Gamma passing rate was compared with 2D fluence verification from MatriXX with MultiCube. Comparison of COMPASS reconstructed dose from measured fluence and COMPASS computed dose has shown a very good agreement with TPS calculated dose. Each plan was evaluated based on dose volume parameters for target volumes such as dose at 95% of volume (D95) and average dose. For critical organs dose at 20% of volume (D20), dose at 50% of volume (D50), and maximum point doses were evaluated. Comparison was carried out using gamma analysis with passing criteria of 3 mm and 3%. Mean deviation of 1.9%±1% was observed for dose at 95% of volume (D95) of target volumes, whereas much less difference was noticed for critical organs. However, significant dose difference was noticed in two cases due to the smaller tumor size. Evaluation of this study revealed that the COMPASS 3D dosimetry is efficient and easy to use for patient‐specific QA of VMAT stereotactic delivery. 3D dosimetric QA with COMPASS provides additional degrees of freedom to check the high‐dose modulated stereotactic delivery with very high precision on patient CT images. PACS numbers: 87.55.Qr, 87.56.Fc PMID:25679152

Influence of dose calculation algorithms on the predicted dose distribution and NTCP values for NSCLC patients.

PubMed

Nielsen, Tine B; Wieslander, Elinore; Fogliata, Antonella; Nielsen, Morten; Hansen, Olfred; Brink, Carsten

2011-05-01

To investigate differences in calculated doses and normal tissue complication probability (NTCP) values between different dose algorithms. Six dose algorithms from four different treatment planning systems were investigated: Eclipse AAA, Oncentra MasterPlan Collapsed Cone and Pencil Beam, Pinnacle Collapsed Cone and XiO Multigrid Superposition, and Fast Fourier Transform Convolution. Twenty NSCLC patients treated in the period 2001-2006 at the same accelerator were included and the accelerator used for treatments were modeled in the different systems. The treatment plans were recalculated with the same number of monitor units and beam arrangements across the dose algorithms. Dose volume histograms of the GTV, PTV, combined lungs (excluding the GTV), and heart were exported and evaluated. NTCP values for heart and lungs were calculated using the relative seriality model and the LKB model, respectively. Furthermore, NTCP for the lungs were calculated from two different model parameter sets. Calculations and evaluations were performed both including and excluding density corrections. There are found statistical significant differences between the calculated dose to heart, lung, and targets across the algorithms. Mean lung dose and V20 are not very sensitive to change between the investigated dose calculation algorithms. However, the different dose levels for the PTV averaged over the patient population are varying up to 11%. The predicted NTCP values for pneumonitis vary between 0.20 and 0.24 or 0.35 and 0.48 across the investigated dose algorithms depending on the chosen model parameter set. The influence of the use of density correction in the dose calculation on the predicted NTCP values depends on the specific dose calculation algorithm and the model parameter set. For fixed values of these, the changes in NTCP can be up to 45%. Calculated NTCP values for pneumonitis are more sensitive to the choice of algorithm than mean lung dose and V20 which are also commonly used for plan evaluation. The NTCP values for heart complication are, in this study, not very sensitive to the choice of algorithm. Dose calculations based on density corrections result in quite different NTCP values than calculations without density corrections. It is therefore important when working with NTCP planning to use NTCP parameter values based on calculations and treatments similar to those for which the NTCP is of interest.

RIFM fragrance ingredient safety assessment, α-Ionone, CAS Registry Number 127-41-3.

PubMed

Api, A M; Belsito, D; Bhatia, S; Bruze, M; Calow, P; Dagli, M L; Dekant, W; Fryer, A D; Kromidas, L; La Cava, S; Lalko, J F; Lapczynski, A; Liebler, D C; Miyachi, Y; Politano, V T; Ritacco, G; Salvito, D; Schultz, T W; Shen, J; Sipes, I G; Wall, B; Wilcox, D K

2016-11-01

The use of this material under current use conditions is supported by the existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity, skin sensitization potential, as well as, environmental safety. Repeated dose toxicity was determined to have the most conservative systemic exposure derived NO[A]EL of 10 mg/kg/day. A dietary 90-day subchronic toxicity study conducted in rats resulted in a MOE of 182 while assuming 100% absorption from skin contact and inhalation. A MOE of >100 is deemed acceptable. Copyright © 2015 Elsevier Ltd. All rights reserved.

RIFM fragrance ingredient safety assessment, isoeugenol, CAS Registry Number 97-54-1.

PubMed

Api, A M; Belsito, D; Bhatia, S; Bruze, M; Calow, P; Dagli, M L; Dekant, W; Fryer, A D; Kromidas, L; La Cava, S; Lalko, J F; Lapczynski, A; Liebler, D C; Miyachi, Y; Politano, V T; Ritacco, G; Salvito, D; Schultz, T W; Shen, J; Sipes, I G; Wall, B; Wilcox, D K

2016-11-01

The use of this material under current use conditions is supported by the existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity, skin sensitization potential, as well as, environmental safety. Repeated dose toxicity was determined to have the most conservative systemic exposure derived NO[A]EL of 37.5 mg/kg/day. A gavage 13-week subchronic toxicity study conducted in mice resulted in a MOE of 5769 while considering 38.4% absorption from skin contact and 100% from inhalation. A MOE of >100 is deemed acceptable. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genetic gain and economic values of selection strategies including semen traits in three- and four-way crossbreeding systems for swine production.

PubMed

González-Peña, D; Knox, R V; MacNeil, M D; Rodriguez-Zas, S L

2015-03-01

Four semen traits: volume (VOL), concentration (CON), progressive motility of spermatozoa (MOT), and abnormal spermatozoa (ABN) provide complementary information on boar fertility. Assessment of the impact of selection for semen traits is hindered by limited information on economic parameters. Objectives of this study were to estimate economic values for semen traits and to evaluate the genetic gain when these traits are incorporated into traditional selection strategies in a 3-tier system of swine production. Three-way (maternal nucleus lines A and B and paternal nucleus line C) and 4-way (additional paternal nucleus line D) crossbreeding schemes were compared. A novel population structure that accommodated selection for semen traits was developed. Three selection strategies were simulated. Selection Strategy I (baseline) encompassed selection for maternal traits: number of pigs born alive (NBA), litter birth weight (LBW), adjusted 21-d litter weight (A21), and number of pigs at 21 d (N21); and paternal traits: number of days to 113.5 kg (D113), backfat (BF), ADG, feed efficiency (FE), and carcass lean % (LEAN). Selection Strategy II included Strategy I and the number of usable semen doses per collection (DOSES), a function of the 4 semen traits. Selection Strategy III included Strategy I and the 4 semen traits individually. The estimated economic values of VOL, CON, MOT, ABN, and DOSES for 7 to 1 collections/wk ranged from $0.21 to $1.44/mL, $0.12 to $0.83/10 spermatozoa/mm, $0.61 to $12.66/%, -$0.53 to -$10.88/%, and $2.01 to $41.43/%, respectively. The decrease in the relative economic values of semen traits and DOSES with higher number of collections per wk was sharper between 1 and 2.33 collections/wk than between 2.33 and 7 collections/wk. The higher economic value of MOT and ABN relative to VOL and CON could be linked to the genetic variances and covariances of these traits. Average genetic gains for the maternal traits were comparable across strategies. Genetic gains for paternal traits, excluding semen traits, were greater in selection Strategy I than Strategies III and II. Genetic gains for paternal and maternal traits were greater in the 4- and 3-way schemes, respectively. The selection strategy including the 4 semen traits is recommended because this approach enables genetic gains for these traits without compromising the genetic gains for maternal traits and with minimal losses in genetic gains for paternal traits.

Sporophytic nondisjunction of the maize B chromosome at high copy numbers.

PubMed

Masonbrink, Rick E; Birchler, James A

2010-01-01

It has been known for decades that the maize B chromosome undergoes nondisjunction at the second pollen mitosis. Fluorescence in-situ hybridization (FISH) was used to undertake a quantitative study of maize plants with differing numbers of B chromosomes to observe if instability increases by increasing B dosage in root tip tissue. B chromosome nondisjunction was basically absent at low copy number, but increased at higher B numbers. Thus, B nondisjunction rates are dependent on the dosage of B's in the sporophyte. Differences in nondisjunction were also documented between odd and even doses of the B. In plants that have inherited odd numbered doses of the B chromosome, B loss is nearly twice as likely as B gain in a somatic division. When comparing plants with even doses of B's to plants with odd doses of B's, plants with even numbers had a significantly higher chance to increase in number. Therefore, the B's non-disjunctive capacity, previously thought to be primarily restricted to the gametophyte, is present in sporophytic cells. Copyright 2010 Institute of Genetics and Developmental Biology and the Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Impact of Thiamethoxam on Honey Bee Queen (Apis mellifera carnica) Reproductive Morphology and Physiology.

PubMed

Gajger, Ivana Tlak; Sakač, Martina; Gregorc, Aleš

2017-09-01

High honey bee losses around the world have been linked in part by the regular use of neonicotinoids in agriculture. In light of the current situation, the aim of this study was to investigate the effects of thiamethoxam on the development of the reproductive system and physiology in the honey bee queen. Two experimental groups of honey bee queen larvae were treated with thiamethoxam during artificial rearing, applied via artificial feed in two cycles. In the first rearing cycle, honey bee larvae received a single treatment dose (4.28 ng thiamethoxam/queen larva on the 4th day after larvae grafting in artificial queen cells), while the second honey bee queen rearing cycle received a double treatment dose (total of 8.56 ng thiamethoxam/queen larva on the 4th and 5th day after larvae grafting in artificial queen cells). After emerging, queens were anesthetized and weighed, and after mating with drones were anesthetized, weighed, and sectioned. Ovary mass and number of stored sperm were determined. Body weight differed between untreated and treated honey bee queens. The results also show a decrease in the number of sperm within honey bee queen spermathecae that received the double thiamethoxam dose.

A noise power spectrum study of a new model‐based iterative reconstruction system: Veo 3.0

PubMed Central

Li, Guang; Liu, Xinming; Dodge, Cristina T.; Jensen, Corey T.

2016-01-01

The purpose of this study was to evaluate performance of the third generation of model‐based iterative reconstruction (MBIR) system, Veo 3.0, based on noise power spectrum (NPS) analysis with various clinical presets over a wide range of clinically applicable dose levels. A CatPhan 600 surrounded by an oval, fat‐equivalent ring to mimic patient size/shape was scanned 10 times at each of six dose levels on a GE HD 750 scanner. NPS analysis was performed on images reconstructed with various Veo 3.0 preset combinations for comparisons of those images reconstructed using Veo 2.0, filtered back projection (FBP) and adaptive statistical iterative reconstruction (ASiR). The new Target Thickness setting resulted in higher noise in thicker axial images. The new Texture Enhancement function achieved a more isotropic noise behavior with less image artifacts. Veo 3.0 provides additional reconstruction options designed to allow the user choice of balance between spatial resolution and image noise, relative to Veo 2.0. Veo 3.0 provides more user selectable options and in general improved isotropic noise behavior in comparison to Veo 2.0. The overall noise reduction performance of both versions of MBIR was improved in comparison to FBP and ASiR, especially at low‐dose levels. PACS number(s): 87.57.‐s, 87.57.Q‐, 87.57.C‐, 87.57.nf, 87.57.C‐, 87.57.cm PMID:27685118

Pediatric Biopharmaceutical Classification System: Using Age-Appropriate Initial Gastric Volume.

PubMed

Shawahna, Ramzi

2016-05-01

Development of optimized pediatric formulations for oral administration can be challenging, time consuming, and financially intensive process. Since its inception, the biopharmaceutical classification system (BCS) has facilitated the development of oral drug formulations destined for adults. At least theoretically, the BCS principles are applied also to pediatrics. A comprehensive age-appropriate BCS has not been fully developed. The objective of this work was to provisionally classify oral drugs listed on the latest World Health Organization's Essential Medicines List for Children into an age-appropriate BCS. A total of 38 orally administered drugs were included in this classification. Dose numbers were calculated using age-appropriate initial gastric volume for neonates, 6-month-old infants, and children aging 1 year through adulthood. Using age-appropriate initial gastric volume and British National Formulary age-specific dosing recommendations in the calculation of dose numbers, the solubility classes shifted from low to high in pediatric subpopulations of 12 years and older for amoxicillin, 5 years, 12 years and older for cephalexin, 9 years and older for chloramphenicol, 3-4 years, 9-11 and 15 years and older for diazepam, 18 years and older (adult) for doxycycline and erythromycin, 8 years and older for phenobarbital, 10 years and older for prednisolone, and 15 years and older for trimethoprim. Pediatric biopharmaceutics are not fully understood where several knowledge gaps have been recently emphasized. The current biowaiver criteria are not suitable for safe application in all pediatric populations.

Considerations for a Pediatric Biopharmaceutics Classification System (BCS): application to five drugs.

PubMed

Gandhi, Shivani V; Rodriguez, William; Khan, Mansoor; Polli, James E

2014-06-01

It has been advocated that biopharmaceutic risk assessment should be conducted early in pediatric product development and synchronized with the adult product development program. However, we are unaware of efforts to classify drugs into a Biopharmaceutics Classification System (BCS) framework for pediatric patients. The objective was to classify five drugs into a potential BCS. These five drugs were selected since both oral and intravenous pharmacokinetic data were available for each drug, and covered the four BCS classes in adults. Literature searches for each drug were conducted using Medline and applied to classify drugs with respect to solubility and permeability in pediatric subpopulations. Four pediatric subpopulations were considered: neonates, infants, children, and adolescents. Regarding solubility, dose numbers were calculated using a volume for each subpopulation based on body surface area (BSA) relative to 250 ml for a 1.73 m(2) adult. Dose numbers spanned a range of values, depending upon the pediatric dose formula and subpopulation. Regarding permeability, pharmacokinetic literature data required assumptions and decisions about data collection. Using a devised pediatric BCS framework, there was agreement in adult and pediatric BCS class for two drugs, azithromycin (class 3) and ciprofloxacin (class 4). There was discordance for the three drugs that have high adult permeability since all pediatric permeabilities were low: dolasetron (class 3 in pediatric), ketoprofen (class 4 in pediatric), and voriconazole (class 4 in pediatric). A main contribution of this work is the identification of critical factors required for a pediatric BCS.

The polyGeVero® software for fast and easy computation of 3D radiotherapy dosimetry data

NASA Astrophysics Data System (ADS)

Kozicki, Marek; Maras, Piotr

2015-01-01

The polyGeVero® software package was elaborated for calculations of 3D dosimetry data such as the polymer gel dosimetry. It comprises four workspaces designed for: i) calculating calibrations, ii) storing calibrations in a database, iii) calculating dose distribution 3D cubes, iv) comparing two datasets e.g. a measured one with a 3D dosimetry with a calculated one with the aid of a treatment planning system. To accomplish calculations the software was equipped with a number of tools such as the brachytherapy isotopes database, brachytherapy dose versus distance calculation based on the line approximation approach, automatic spatial alignment of two 3D dose cubes for comparison purposes, 3D gamma index, 3D gamma angle, 3D dose difference, Pearson's coefficient, histograms calculations, isodoses superimposition for two datasets, and profiles calculations in any desired direction. This communication is to briefly present the main functions of the software and report on the speed of calculations performed by polyGeVero®.

The net fractional depth dose: a basis for a unified analytical description of FDD, TAR, TMR, and TPR.

PubMed

van de Geijn, J; Fraass, B A

1984-01-01

The net fractional depth dose (NFD) is defined as the fractional depth dose (FDD) corrected for inverse square law. Analysis of its behavior as a function of depth, field size, and source-surface distance has led to an analytical description with only seven model parameters related to straightforward physical properties. The determination of the characteristic parameter values requires only seven experimentally determined FDDs. The validity of the description has been tested for beam qualities ranging from 60Co gamma rays to 18-MV x rays, using published data from several different sources as well as locally measured data sets. The small number of model parameters is attractive for computer or hand-held calculator applications. The small amount of required measured data is important in view of practical data acquisition for implementation of a computer-based dose calculation system. The generating function allows easy and accurate generation of FDD, tissue-air ratio, tissue-maximum ratio, and tissue-phantom ratio tables.

Microbeam studies of the sensitivity of structures within living cells

NASA Technical Reports Server (NTRS)

Braby, L. A.

1992-01-01

Determining the biological effects of low doses of radiation with high linear energy transfer (LET) is complicated by the stochastic nature of charged-particle interactions. Populations of cells exposed to very low radiation doses contain a few cells which have been hit by a charged particle, while the majority of the cells receive no radiation damage. At somewhat higher doses, a few cells receive two or more events. Because the effects of damage produced by separate events can interact in the cell, we have had to make assumptions about the nature of these interactions in order to interpret the results of the experiments. Many of those assumptions can be tested if we can be sure of the number of charged-particle events which occur in individual cells, and correlate this number with the biological effect. We have developed a special irradiation facility at Pacific Northwest Laboratory (PNL) to control the actual number of charged particle tracks that pass through cell nuclei. The beam from a 2 MeV tandem accelerator is collimated to approximately 5 microns. Cells, grown in special dishes with 1.5 microns thick plastic bottoms, are positioned so that the desired portion of the cell aligns with the collimator. A shutter in the beam line is opened and closed after the desired number of particle tracks has been counted. This approach can be used to investigate the effects of the interaction between irradiated and unirradiated cells in an organized system, as well as to study the effects of spatial and temporal distribution of radiation damage within single cells.(ABSTRACT TRUNCATED AT 250 WORDS).

Skin dosimetry of patients during interventional cardiology procedures in the Czech Republic

NASA Astrophysics Data System (ADS)

Sukupova, Lucie; Novak, Leos

2008-01-01

The aim of the study is to determine distribution of air kerma-area product, fluoro time and number of frames values for the two most frequent procedures in the interventional cardiology, to reconstruct skin dose distributions for some patients undergoing coronarography and percutaneous transluminal coronary angioplasty procedures. Patient dose data were obtained from X-ray unit dose monitoring software report from one hospital and the reconstructions were performed in MATLAB. Dependence of maximum skin dose on air kerma-area product, fluoro time and number of frames was determined to assess trigger levels of these quantities, which can indicate possible exceeding of the 2 Gy skin dose threshold.

Improvements in dose calculation accuracy for small off-axis targets in high dose per fraction tomotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding

2012-08-15

Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed 'Super Sampling' involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receivingmore » a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.« less

A MULTIMODEL APPROACH FOR CALCULATING BENCHMARK DOSE

EPA Science Inventory

A Multimodel Approach for Calculating Benchmark Dose
Ramon I. Garcia and R. Woodrow Setzer

In the assessment of dose response, a number of plausible dose- response models may give fits that are consistent with the data. If no dose response formulation had been speci...

North Carolina's Operation Medicine Drop: Results From One of the Nation's Largest Drug Disposal Programs.

PubMed

Fleming, Eleanor; Proescholdbell, Scott; Sachdeva, Nidhi; Alexandridis, Apostolos A; Margolis, Lewis; Ransdell, Kelly

2016-01-01

In 2013, a total of 1,085 North Carolina residents died due to unintentional poisoning; 91% of these deaths were attributed to medications or drugs (over-the-counter, prescription, or illicit). Proper disposal of unused, unneeded, and/or expired medications is an essential part of preventing these unintentional deaths, as well as averting the other adverse consequences of these drugs on the environment and population health. Operation Medicine Drop is a medication take-back program coordinated by Safe Kids North Carolina, a county-level, coalition-based injury prevention organization. The Operation Medicine Drop program and event registration system were used to review and validate the number of events, the counties where the events were held, and the number of unit doses (pills) collected from March 2010 to June 2014. SAS version 9.4 was used to generate basic counts and frequencies of events and doses, and ArcGIS version 10.0 was used to create the map. From March 2010 to June 2014, Operation Medicine Drop held 1,395 events with 245 different participating law enforcement agencies in 91 counties in North Carolina, and it collected 69.6 million unit doses of medication. More than 60 local Safe Kids North Carolina community coalitions had participated as of June 2014. Every year, Operation Medicine Drop has witnessed increases in events, participating agencies, participating counties, and the number of doses collected. Operation Medicine Drop is an excellent example of a successful and ongoing collaboration to improve public health. Medication take-back programs may play an important role in preventing future overdose deaths in North Carolina. ©2016 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.

Exposure cell number during feeder cell growth-arrest by Mitomycin C is a critical pharmacological aspect in stem cell culture system.

PubMed

Chugh, Rishi Man; Chaturvedi, Madhusudan; Yerneni, Lakshmana Kumar

2016-01-01

Growth-arrested feeder cells following Mitomycin C treatment are instrumental in stem cell culture allowing development of regenerative strategies and alternatives to animal testing in drug discovery. The concentration of Mitomycin C and feeder cell type was described to affect feeder performance but the criticality of feeder cell exposure density was not addressed. We hypothesize that the exposure cell density influences the effectiveness of Mitomycin C in an arithmetic manner. Three different exposure cell densities of Swiss 3T3 fibroblasts were treated with a range of Mitomycin C concentrations for 2h. The cells were replaced and the viable cells counted on 3, 6, 9, 12 and 20days. The cell extinctions were compared with doses per cell which were derived by dividing the product of concentration and volume of Mitomycin C solution with exposure cell number. The periodic post-treatment feeder cell extinctions were not just dependent on Mitomycin C concentration but also on dose per cell. Analysis of linearity between viable cell number and Mitomycin C dose per cell derived from the concentrations of 3 to 10μg/ml revealed four distinct categories of growth-arrest. Confluent cultures exposed to low concentration showed growth-arrest failure. The in vitro cell density titration can facilitate prediction of a compound's operational in vivo dosing. For containing the growth arrest failure, an arithmetic volume derivation strategy is proposed by fixing the exposure density to a safe limit. The feeder extinction characteristics are critical for streamlining the stem cell based pharmacological and toxicological assays. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of male and female sex steroids on the development of normal and the transient Froriep's dorsal root ganglia of the chick embryo.

PubMed

Liu, Jiali; Chen, Dawei; Goldstein, Ronald S; Cui, Sheng

2005-03-22

Sex steroids can influence developmental processes and support the survival of neurons in the embryonic central nervous system. Recent studies have shown that estrogen receptors are also expressed in the peripheral nervous system, in the dorsal root ganglia (DRG) of chick embryos. However, no studies have examined the effects of sex steroids on development of embryonic DRG. In the present study, 0.2 microg, 1.0 microg, 5.0 microg 10 microg, 20 microg, 25 microg, and 40 microg doses of testosterone or estradiol were delivered to chick embryos at Hamburger and Hamilton stage 18 (E3). The actions of these doses of sex steroids on the development of the C5DRG (fifth cervical ganglion, a "normal" DRG) and C2DRG (a transient ganglion known as a "Froriep's DRG") were then evaluated by quantifying ganglionic volumes, cell number, proliferation, and apoptosis after 1 day of growth to stage 23. We found that both testosterone and estradiol promoted proliferation of cells in both normal DRG and the Froriep's ganglia. By contrast, estradiol significantly increased the number of apoptotic cells, while testosterone strongly inhibited apoptosis. These actions of sex steroids on DRG development were dose-dependent, and C5DRG and C2DRG showed different sensitivities to the applied sex steroids. In addition, the present results demonstrated that specific ER and AR inhibitors (tamoxifen and flutamide) did not influence the effects of 5 microg E2 and 5 microg T on C2 and C5DRG significantly. These results demonstrate that male and female sex steroids can modulate DRG development through an epigenetic mechanism, as had been shown for the central nervous system.

Developmental and genetic toxicity of stannous chloride in mouse dams and fetuses.

PubMed

El-Makawy, Aida I; Girgis, Shenouda M; Khalil, Wagdy K B

2008-12-08

Humans are exposed to stannous chloride (SnCl2) present in packaged food, soft drinks, biocides, dentifrices, etc. Health effects in children exposed to tin and tin compounds have not been investigated yet. Therefore, we evaluated the possible teratogenic and genotoxic effects of SnCl2 in pregnant female mice and their fetuses. Teratogenic effects including morphological malformation of the fetus and its skeleton were observed. Exposures to environmental stressors including toxic chemicals that have the potential of modulating the immune system can often be linked to ecologically relevant endpoints, such as reduced resistance to disease. Therefore, the semi-quantitative reverse-transcription PCR (RT-PCR) assay was used to evaluate the expression of immune-response genes in the liver of SnCl2-treated dams and their fetuses. Bone-marrow cells of dams and fetuses were investigated for the presence of aberrant chromosomes. Three oral doses of SnCl2 (2, 10 and 20 mg/kg bw) were tested. The results of the teratological study show that SnCl2 induced a significant decrease in the number of living fetuses and a significant increase in the number of post-implantation losses. The high dose of SnCl2 induced complete post-implantation loss. Furthermore, SnCl2 caused reduction in the ossification of the fetal skeleton. The RT-PCR assay showed that the immune-response genes GARP and SIMP were not expressed in the liver of dams and fetuses in the controls or in the group treated with SnCl2 at 2 mg/kg bw. However, the expression of these genes was up-regulated in the groups treated with the other doses of SnCl2. Regarding the chromosome analysis, SnCl2 induced a dose-dependent increase in the frequency of individual and total chromosomal aberrations (P

Influence of the number of daily pills and doses on adherence to antiretroviral treatment: a 7-year study.

PubMed

Hernández Arroyo, M J; Cabrera Figueroa, S E; Sepúlveda Correa, R; Valverde Merino, M P; Luna Rodrigo, G; Domínguez-Gil Hurlé, A

2016-02-01

Antiretroviral treatment (ART) is hampered by complicated regimens, high pill burden, drug-drug interactions, and frequent short- and long-term adverse effects, leading to decreased adherence. Over recent years, considerable effort has been directed at developing regimens that are less burdening. We undertook a 7-year retrospective study of the records of 264 HIV-infected subjects enrolled in a pharmaceutical care programme to document the progress made and to study the influence of the number of ART pills and doses on the level of treatment adherence. Antiretroviral dispensing records were analysed for the number of pills and doses administered and the ART adherence rate estimated. In 2005, the patients took a mean of 6·2 pills daily (CI 95%: 5·9-6·6), and 92·9% of them were on a twice-a-day (BID) dosage regimen. By 2012, the mean number of pills was reduced to 4·1 (CI 95%: 3·8-4·4), and only 50·9% were on a BID regimen. No statistically significant relation was observed between number of daily pills and doses and ART adherence reached by the patients in any of the analyses performed. There has been a continuous reduction in the number of pills and doses of antiretrovirals taken by individual patients over the last 7 years due largely to the introduction of improved treatments and regimens. More daily pills or doses was not associated with worse ART adherence in our pharmaceutical care programme. © 2015 John Wiley & Sons Ltd.

Vitamin E can improve behavioral tests impairment, cell loss, and dendrite changes in rats' medial prefrontal cortex induced by acceptable daily dose of aspartame.

PubMed

Rafati, Ali; Noorafshan, Ali; Jahangir, Mahboubeh; Hosseini, Leila; Karbalay-Doust, Saied

2018-01-01

Aspartame is an artificial sweetener used in about 6000 sugar-free products. Aspartame consumption could be associated with various neurological disorders. This study aimed to evaluate the effect of aspartame onmedial Prefrontal Cortex (mPFC) as well as neuroprotective effects of vitamin E. The rats were divided into seven groups, including distilled water, corn oil, vitamin E (100mg/kg/day), and low (acceptable daily dose) and high doses of aspartame (40 and 200mg/kg/day) respectively, with or without vitamin E consumption, for 8 weeks. Behavioral tests were recorded and the brain was prepared for stereological assessments. Novel objects test and eight-arm radial maze showed impairmentoflong- and short-termmemoriesin aspartame groups. Besides, mPFC volume, infralimbic volume, neurons number, glial cells number, dendrites length per neuron,and number of spines per dendrite length were decreased by 7-61% in the rats treated with aspartame. However, neurons' number, glial cells number, and rats' performance in eight-arm radial mazes were improved by concomitant consumption of vitamin E and aspartame. Yet, the mPFC volume and infralimbic cortex were protected only in the rats receiving the low dose of aspartame+vitamin E. On the other hand, dendrites length, spines number,and novel object recognition were not protected by treatment with vitamin E+aspartame. The acceptable daily dose or higher doses of aspartame could induce memory impairments and cortical cells loss in mPFC. However, vitamin E could ameliorate some of these changes. Copyright © 2017 Elsevier GmbH. All rights reserved.

Development and Prospective Federal State-Wide Evaluation of a Device for Height-Based Dose Recommendations in Prehospital Pediatric Emergencies: A Simple Tool to Prevent Most Severe Drug Errors.

PubMed

Kaufmann, Jost; Roth, Bernhard; Engelhardt, Thomas; Lechleuthner, Alex; Laschat, Michael; Hadamitzky, Christoph; Wappler, Frank; Hellmich, Martin

2018-01-01

Drug dosing errors pose a particular threat to children in prehospital emergency care. With the Pediatric emergency ruler (PaedER), we developed a simple height-based dose recommendation system and evaluated its effectiveness in a pre-post interventional trial as the Ethics Committee disapproved randomization due to the expected positive effect of the PaedER on outcome. Pre-interventional data were retrospectively retrieved from the electronic records and medical protocols of the Cologne Emergency Medical Service over a two-year period prior to the introduction of the PaedER. Post-interventional data were collected prospectively over a six-year period in a federal state-wide open trial. The administered doses of either intravenous or intraosseous fentanyl, midazolam, ketamine or epinephrine were recorded. Primary outcome measure was the number and severity of drug dose deviation from recommended dose (DRD) based on the patient's weight. Fifty-nine pre-interventional and 91 post-interventional prehospital drug administrations in children were analyzed. The rate of DRD > 300% overall medications were 22.0% in the pre- and 2.2% in the post-interventional group (p < 0.001). All administrations of epinephrine occurred excessive (DRD > 300%) in pre-interventional and none in post-interventional patients (p < 0.001). The use of the PaedER resulted in a 90% reduction of medication errors (95% CI: 57% to 98%; p < 0.001) and prevented all potentially life-threatening errors associated with epinephrine administration. There is an urgent need to increase the safety of emergency drug dosing in children during emergencies. A simple height-based system can support health care providers and helps to avoid life-threatening medication errors.

An accelerated dose escalation with a grass pollen allergoid is safe and well-tolerated: a randomized open label phase II trial.

PubMed

Chaker, A M; Al-Kadah, B; Luther, U; Neumann, U; Wagenmann, M

2015-01-01

The number of injections in the dose escalation of subcutaneous immunotherapy (SCIT) is small for some currently used hypoallergenic allergoids, but can still be inconvenient to patients and can impair compliance. The aim of this trial was to compare safety and tolerability of an accelerated to the conventional dose escalation scheme of a grass pollen allergoid. In an open label phase II trial, 122 patients were 1:1 randomized for SCIT using a grass pollen allergoid with an accelerated dose escalation comprising only 4 weekly injections (Group I) or a conventional dose escalation including 7 weekly injections (Group II). Safety determination included the occurrence of local and systemic adverse events. Tolerability was assessed by patients and physicians. Treatment-related adverse events were observed in 22 (36.1 %) patients in Group I and 15 (24.6 %) in Group II. Local reactions were reported by 18 patients in Group I and 11 in Group II. Five Grade 1 systemic reactions (WAO classification) were observed in Group I and 2 in Group II. Grade 2 reactions occurred 3 times in Group I and 2 times in Group II. Tolerability was rated as "good" or "very good" by 53 (86.9 %) patients in Group I and 59 (100 %) in Group II by investigators. Forty-eight patients in Group I (80.0 %) and 54 in Group II (91.5 %) rated tolerability as "good" or "very good". The dose escalation of a grass pollen allergoid can be accelerated with safety and tolerability profiles comparable to the conventional dose escalation.

Hydroxychloroquine Blood Levels in Systemic Lupus Erythematosus: Clarifying Dosing Controversies and Improving Adherence.

PubMed

Durcan, Laura; Clarke, William A; Magder, Laurence S; Petri, Michelle

2015-11-01

Hydroxychloroquine (HCQ) is used for its effect on systemic lupus erythematosus (SLE) disease activity and longterm benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is disagreement about dosing; rheumatologists recommend weight-based dosing while some other specialists advocate height-based "ideal body weight" dosing. Patients were prescribed HCQ not exceeding 6.5 mg/kg (max 400 mg/day). In hemodialysis, the dose was 200 mg after each session, and in renal insufficiency it was 200 mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the effect of measurement and counseling on adherence, we compared the proportion of patients with a level of 500 ng/ml or higher based on the number of prior assessments. The proportion of patients with HCQ levels in the therapeutic range differed significantly by age, sex, and Vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, subtherapeutic, and therapeutic levels, disease activity decreased (SLE Disease Activity Index 2.92, 2.36, and 2.20, p = 0.04 for trend). At first, 56% were therapeutic, and by the third measurement this increased to 80% (p ≤ 0.0001). There was a trend toward higher disease activity with lower HCQ levels. Renal failure dosing led to suboptimum levels. We show that weight-based dosing (max 400 mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling, and repeated testing can increase adherence rates.

Plasma methylphenidate concentrations in youths treated with high-dose osmotic release oral system formulation.

PubMed

Stevens, Jonathan R; George, Robert A; Fusillo, Steven; Stern, Theodore A; Wilens, Timothy E

2010-02-01

Children and adolescents are being treated increasingly for attention-deficit/hyperactivity disorder (ADHD) with a variety of stimulants in higher than Food and Drug Administration (FDA)-approved doses and in combination with other medications. We sought to determine methylphenidate (MPH) concentrations in children and adolescents treated with high-dose, extended-release osmotic release oral system (OROS) MPH plus concomitant medications, and to examine MPH concentrations with respect to the safety and tolerability of treatment. Plasma MPH concentrations were measured by liquid chromatography-mass spectrometry 4-5 hours after administration of medication in a sample of youths diagnosed with ADHD. These youths were treated naturalistically with higher than FDA-approved doses of OROS MPH in addition to their concomitant medications. Markers of safety and tolerability (e.g., measures of blood pressure and heart rate) were also examined. Among the 17 patients (with a mean age of 16.2 +/- 2 years and a mean number of concurrent medications of 2.23 +/- 0.94), the mean plasma MPH concentration was 28 +/- 9.1 ng/mL, despite a mean daily dose of OROS MPH of 169 +/- 5 mg (3.0 +/- 0.8 mg/kg per day). No patient had a plasma MPH level >or=50 ng/mL or clinical signs of stimulant toxicity. No correlation was found between plasma MPH concentrations and OROS MPH dose or changes in vital signs. High-dose OROS MPH, used in combination with other medications, was not associated with either unusually elevated plasma MPH concentrations or with clinically meaningful changes in vital signs. Study limitations include a single time-point sampling of MPH concentrations, a small sample size, and a lack of outcome measures to address treatment effectiveness.

Improved vascularization of planar membrane diffusion devices following continuous infusion of vascular endothelial growth factor.

PubMed

Trivedi, N; Steil, G M; Colton, C K; Bonner-Weir, S; Weir, G C

2000-01-01

Improving blood vessel formation around an immunobarrier device should improve the survival of the encapsulated tissue. In the present study we investigated the formation of new blood vessels around a planar membrane diffusion device (the Baxter Theracyte System) undergoing a continuous infusion of vascular endothelial growth factor through the membranes and into the surrounding tissue. Each device (20 microl) had both an inner immunoisolation membrane and an outer vascularizing membrane. Human recombinant vascular endothelial growth factor-165 was infused at 100 ng/day (low dose: n = 6) and 500 ng/day (high dose: n = 7) for 10 days into devices implanted s.c. in Sprague-Dawley rats; noninfused devices transplanted for an identical period were used as controls (n = 5). Two days following the termination of VEGF infusion, devices were loaded with 20 microl of Lispro insulin (1 U/kg) and the kinetics of insulin release from the lumen of the device was assessed. Devices were then explanted and the number of blood vessels (capillary and noncapillary) was quantified using morphometry. High-dose vascular endothelial growth factor infusion resulted in two- to threefold more blood vessels around the device than that obtained with the noninfused devices and devices infused with low-dose vascular endothelial growth factor. This increase in the number of blood vessels was accompanied by a modest increase in insulin diffusion from the device in the high-dose vascular endothelial growth factor infusion group. We conclude that vascular endothelial growth factor can be used to improve blood vessel formation adjacent to planar membrane diffusion devices.

Sensitivity and specificity of dosing alerts for dosing errors among hospitalized pediatric patients

PubMed Central

Stultz, Jeremy S; Porter, Kyle; Nahata, Milap C

2014-01-01

Objectives To determine the sensitivity and specificity of a dosing alert system for dosing errors and to compare the sensitivity of a proprietary system with and without institutional customization at a pediatric hospital. Methods A retrospective analysis of medication orders, orders causing dosing alerts, reported adverse drug events, and dosing errors during July, 2011 was conducted. Dosing errors with and without alerts were identified and the sensitivity of the system with and without customization was compared. Results There were 47 181 inpatient pediatric orders during the studied period; 257 dosing errors were identified (0.54%). The sensitivity of the system for identifying dosing errors was 54.1% (95% CI 47.8% to 60.3%) if customization had not occurred and increased to 60.3% (CI 54.0% to 66.3%) with customization (p=0.02). The sensitivity of the system for underdoses was 49.6% without customization and 60.3% with customization (p=0.01). Specificity of the customized system for dosing errors was 96.2% (CI 96.0% to 96.3%) with a positive predictive value of 8.0% (CI 6.8% to 9.3). All dosing errors had an alert over-ridden by the prescriber and 40.6% of dosing errors with alerts were administered to the patient. The lack of indication-specific dose ranges was the most common reason why an alert did not occur for a dosing error. Discussion Advances in dosing alert systems should aim to improve the sensitivity and positive predictive value of the system for dosing errors. Conclusions The dosing alert system had a low sensitivity and positive predictive value for dosing errors, but might have prevented dosing errors from reaching patients. Customization increased the sensitivity of the system for dosing errors. PMID:24496386

Survey of distribution of seasonal influenza vaccine doses in 201 countries (2004-2015): The 2003 World Health Assembly resolution on seasonal influenza vaccination coverage and the 2009 influenza pandemic have had very little impact on improving influenza control and pandemic preparedness.

PubMed

Palache, A; Abelin, A; Hollingsworth, R; Cracknell, W; Jacobs, C; Tsai, T; Barbosa, P

2017-08-24

There is no global monitoring system for influenza vaccination coverage, making it difficult to assess progress towards the 2003 World Health Assembly (WHA) vaccination coverage target. In 2008, the IFPMA Influenza Vaccine Supply International Task Force (IVS) developed a survey method to assess the global distribution of influenza vaccine doses as a proxy for vaccination coverage rates. The latest dose distribution data for 2014 and 2015 was used to update previous analyses. Data were confidentially collected and aggregated by the IFPMA Secretariat, and combined with previous IFPMA IVS survey data (2004-2013). Data were available from 201 countries over the 2004-2015 period. A "hurdle" rate was defined as the number of doses required to reach 15.9% of the population in 2008. Overall, the number of distributed doses progressively increased between 2004 and 2011, driven by a 150% increase in AMRO, then plateaued. One percent fewer doses were distributed in 2015 than in 2011. Twenty-three countries were above the hurdle rate in 2015, compared to 15 in 2004, but distribution was highly uneven in and across all WHO regions. Three WHO regions (AMRO, EURO and WPRO) accounted for about 95% of doses distributed. But in EURO and WPRO, distribution rates in 2015 were only marginally higher than in 2004, and in EURO there was an overall downward trend in dose distribution. The vast majority of countries cannot meet the 2003WHA coverage targets and are inadequately prepared for a global influenza pandemic. With only 5% of influenza vaccine doses being distributed to 50% of the world's population, there is urgency to redress the gross inequities in disease prevention and in pandemic preparedness. The 2003WHA resolution must be reviewed and revised and a call issued for the renewed commitment of Member States to influenza vaccination coverage targets. Copyright © 2017. Published by Elsevier Ltd.

TH-AB-BRA-02: Automated Triplet Beam Orientation Optimization for MRI-Guided Co-60 Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, D; Thomas, D; Cao, M

2016-06-15

Purpose: MRI guided Co-60 provides daily and intrafractional MRI soft tissue imaging for improved target tracking and adaptive radiotherapy. To remedy the low output limitation, the system uses three Co-60 sources at 120° apart, but using all three sources in planning is considerably unintuitive. We automate the beam orientation optimization using column generation, and then solve a novel fluence map optimization (FMO) problem while regularizing the number of MLC segments. Methods: Three patients—1 prostate (PRT), 1 lung (LNG), and 1 head-and-neck boost plan (H&NBoost)—were evaluated. The beamlet dose for 180 equally spaced coplanar beams under 0.35 T magnetic field wasmore » calculated using Monte Carlo. The 60 triplets were selected utilizing the column generation algorithm. The FMO problem was formulated using an L2-norm minimization with anisotropic total variation (TV) regularization term, which allows for control over the number of MLC segments. Our Fluence Regularized and Optimized Selection of Triplets (FROST) plans were compared against the clinical treatment plans (CLN) produced by an experienced dosimetrist. Results: The mean PTV D95, D98, and D99 differ by −0.02%, +0.12%, and +0.44% of the prescription dose between planning methods, showing same PTV dose coverage. The mean PTV homogeneity (D95/D5) was at 0.9360 (FROST) and 0.9356 (CLN). R50 decreased by 0.07 with FROST. On average, FROST reduced Dmax and Dmean of OARs by 6.56% and 5.86% of the prescription dose. The manual CLN planning required iterative trial and error runs which is very time consuming, while FROST required minimal human intervention. Conclusions: MRI guided Co-60 therapy needs the output of all sources yet suffers from unintuitive and laborious manual beam selection processes. Automated triplet orientation optimization is shown essential to overcome the difficulty and improves the dosimetry. A novel FMO with regularization provides additional controls over the number of MLC segments and treatment time. Varian Medical Systems; NIH grant R01CA188300; NIH grant R43CA183390.« less

An optically stimulated luminescence system to measure dose profiles in x-ray computed tomography

NASA Astrophysics Data System (ADS)

Yukihara, E. G.; Ruan, C.; Gasparian, P. B. R.; Clouse, W. J.; Kalavagunta, C.; Ahmad, S.

2009-10-01

This paper describes an LED-based optically stimulated luminescence (OSL) system for dose profile measurements using OSL detector strips and investigates its performance in x-ray computed tomography (CT) dosimetry. To compensate for the energy response of the Al2O3:C OSL detectors, which have an effective atomic number of 11.28, field-specific energy correction factors were determined using two methods: (a) comparing the OSL profiles with ionization chamber point measurements (0.3 cm3 ionization chamber) and (b) comparing the OSL profiles integrated over a 100 mm length with 100 mm long pencil ionization chamber measurements. These correction factors were obtained for the CT body and head phantoms, central and peripheral positions and three x-ray tube potential differences (100 kVp, 120 kVp and 140 kVp). The OSL dose profiles corrected by the energy dependence agreed with the ionization chamber point measurements over the entire length of the phantom (300 mm). For 120 kVp x-ray tube potential difference, the CTDI100 values calculated using the OSL dose profiles corrected for the energy dependence and those obtained from an independent measurement with a 100 mm long pencil ionization chamber also agreed within ±5%.

NOTE: MCDE: a new Monte Carlo dose engine for IMRT

NASA Astrophysics Data System (ADS)

Reynaert, N.; DeSmedt, B.; Coghe, M.; Paelinck, L.; Van Duyse, B.; DeGersem, W.; DeWagter, C.; DeNeve, W.; Thierens, H.

2004-07-01

A new accurate Monte Carlo code for IMRT dose computations, MCDE (Monte Carlo dose engine), is introduced. MCDE is based on BEAMnrc/DOSXYZnrc and consequently the accurate EGSnrc electron transport. DOSXYZnrc is reprogrammed as a component module for BEAMnrc. In this way both codes are interconnected elegantly, while maintaining the BEAM structure and only minimal changes to BEAMnrc.mortran are necessary. The treatment head of the Elekta SLiplus linear accelerator is modelled in detail. CT grids consisting of up to 200 slices of 512 × 512 voxels can be introduced and up to 100 beams can be handled simultaneously. The beams and CT data are imported from the treatment planning system GRATIS via a DICOM interface. To enable the handling of up to 50 × 106 voxels the system was programmed in Fortran95 to enable dynamic memory management. All region-dependent arrays (dose, statistics, transport arrays) were redefined. A scoring grid was introduced and superimposed on the geometry grid, to be able to limit the number of scoring voxels. The whole system uses approximately 200 MB of RAM and runs on a PC cluster consisting of 38 1.0 GHz processors. A set of in-house made scripts handle the parallellization and the centralization of the Monte Carlo calculations on a server. As an illustration of MCDE, a clinical example is discussed and compared with collapsed cone convolution calculations. At present, the system is still rather slow and is intended to be a tool for reliable verification of IMRT treatment planning in the case of the presence of tissue inhomogeneities such as air cavities.

Evaluation of imaging quality for flat-panel detector based low dose C-arm CT system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seo, Chang-Woo; Cha, Bo Kyung; Jeon, Sungchae

The image quality associated with the extent of the angle of gantry rotation, the number of projection views, and the dose of X-ray radiation was investigated in flat-panel detector (FPD) based C-arm cone-beam computed tomography (CBCT) system for medical applications. A prototype CBCT system for the projection acquisition used the X-ray tube (A-132, Varian inc.) having rhenium-tungsten molybdenum target and flat panel a-Si X-ray detector (PaxScan 4030CB, Varian inc.) having a 397 x 298 mm active area with 388 μm pixel pitch and 1024 x 768 pixels in 2 by 2 binning mode. The performance comparison of X-ray imaging qualitymore » was carried out using the Feldkamp, Davis, and Kress (FDK) reconstruction algorithm between different conditions of projection acquisition. In this work, head-and-dental (75 kVp/20 mA) and chest (90 kVp/25 mA) phantoms were used to evaluate the image quality. The 361 (30 fps x 12 s) projection data during 360 deg. gantry rotation with 1 deg. interval for the 3D reconstruction were acquired. Parke weighting function were applied to handle redundant data and improve the reconstructed image quality in a mobile C-arm system with limited rotation angles. The reconstructed 3D images were investigated for comparison of qualitative image quality in terms of scan protocols (projection views, rotation angles and exposure dose). Furthermore, the performance evaluation in image quality will be investigated regarding X-ray dose and limited projection data for a FPD based mobile C-arm CBCT system. (authors)« less

SU-F-P-07: Applying Failure Modes and Effects Analysis to Treatment Planning System QA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mathew, D; Alaei, P

2016-06-15

Purpose: A small-scale implementation of Failure Modes and Effects Analysis (FMEA) for treatment planning system QA by utilizing methodology of AAPM TG-100 report. Methods: FMEA requires numerical values for severity (S), occurrence (O) and detectability (D) of each mode of failure. The product of these three values gives a risk priority number (RPN). We have implemented FMEA for the treatment planning system (TPS) QA for two clinics which use Pinnacle and Eclipse TPS. Quantitative monthly QA data dating back to 4 years for Pinnacle and 1 year for Eclipse have been used to determine values for severity (deviations from predeterminedmore » doses at points or volumes), and occurrence of such deviations. The TPS QA protocol includes a phantom containing solid water and lung- and bone-equivalent heterogeneities. Photon and electron plans have been evaluated in both systems. The dose values at multiple distinct points of interest (POI) within the solid water, lung, and bone-equivalent slabs, as well as mean doses to several volumes of interest (VOI), have been re-calculated monthly using the available algorithms. Results: The computed doses vary slightly month-over-month. There have been more significant deviations following software upgrades, especially if the upgrade involved re-modeling of the beams. TG-100 guidance and the data presented here suggest an occurrence (O) of 2 depending on the frequency of re-commissioning the beams, severity (S) of 3, and detectability (D) of 2, giving an RPN of 12. Conclusion: Computerized treatment planning systems could pose a risk due to dosimetric errors and suboptimal treatment plans. The FMEA analysis presented here suggests that TPS QA should immediately follow software upgrades, but does not need to be performed every month.« less

Reference air kerma rate calibration system for high dose rate Ir-192 brachytherapy sources in Taiwan

NASA Astrophysics Data System (ADS)

Chu, Wei-Han; Yuan, Ming-Chen; Lee, Jeng-Hung; Lin, Yi-Chun

2017-11-01

Ir-192 sources are widely used in brachytherapy and the number of treatments is around seven thousand for the use of the high dose rate (HDR) Ir-192 brachytherapy source per year in Taiwan. Due to its physical half-life of 73.8 days, the source should be replaced four times per year to maintain the HDR treatment mode (DDEP, 2005; Coursey et al., 1992). When doing this work, it must perform the source dose trace to assure the dose accuracy. To establish the primary measurement standard of reference air kerma rate(RAKR) for the HDR Ir-192 brachytherapy sources in Taiwan, the Institute of Nuclear Energy Research (INER) fabricated a dual spherical graphite-walled cavity ionization chambers system to directly measure the RAKR of the Ir-192 brachytherapy source. In this system, the ion-charge was accumulated by the two ionization chambers and after correction for the ion recombination, temperature, atmosphere pressure, room scattering, graphite-wall attenuation, air attenuation, source decay, stem effect, and so on. The RAKR of the Ir-192 source was obtained in the ambient conditions of 22 °C and one atmosphere. The measurement uncertainty of the system was around 0.92% in 96% confidence level (k=2.0). To verify the accuracy of the result, the source calibration comparison has been made at the National Radiation Standard Laboratory (NRSL) of INER and Physikalisch-Technische Bundesanstalt (PTB, Germany) in 2015. The ratio of the measurement results between INER and PTB, INER/PTB, was 0.998±0.027 (k=2) which showed good consistency and the performance of the system was verified.

Results of a 10-year survey of workload for 10 treatment vaults at a high-throughput comprehensive cancer center.

PubMed

Saleh, Ziad H; Jeong, Jeho; Quinn, Brian; Mechalakos, James; St Germain, Jean; Dauer, Lawrence T

2017-05-01

The workload for shielding purposes of modern linear accelerators (linacs) consists of primary and scatter radiation which depends on the dose delivered to isocenter (cGy) and leakage radiation which depends on the monitor units (MUs). In this study, we report on the workload for 10 treatment vaults in terms of dose to isocenter (cGy), monitor units delivered (MUs), number of treatment sessions (Txs), as well as, use factors (U) and modulation factors (CI) for different treatment techniques. The survey was performed for the years between 2006 and 2015 and included 16 treatment machines which represent different generations of Varian linear accelerators (6EX, 600C, 2100C, 2100EX, and TrueBeam) operating at different electron and x-ray energies (6, 9, 12, 16 and 20 MeV electrons and, 6 and 15 MV x-rays). An institutional review board (IRB) approval was acquired to perform this study. Data regarding patient workload, dose to isocenter, number of monitor units delivered, beam energies, gantry angles, and treatment techniques were exported from an ARIA treatment management system (Varian Medical Systems, Palo Alto, Ca.) into Excel spreadsheets and data analysis was performed in Matlab. The average (± std-dev) number of treatment sessions, dose to isocenter, and number of monitor units delivered per week per machine in 2006 was 119 ± 39 Txs, (300 ± 116) × 10 2 cGys, and (78 ± 28) × 10 3 MUs respectively. In contrast, the workload in 2015 was 112 ± 40 Txs, (337 ± 124) × 10 2 cGys, and (111 ± 46) × 10 3 MUs. 60% of the workload (cGy) was delivered using 6 MV and 30% using 15 MV while the remaining 10% was delivered using electron beams. The modulation factors (MU/cGy) for IMRT and VMAT were 5.0 (± 3.4) and 4.6 (± 1.6) respectively. Use factors using 90° gantry angle intervals were equally distributed (~0.25) but varied considerably among different treatment techniques. The workload, in terms of dose to isocenter (cGy) and subsequently monitor units (MUs), has been steadily increasing over the past decade. This increase can be attributed to increased use of high dose hypo-fractionated regimens (SBRT, SRS) and the increase in use of IMRT and VMAT, which require higher MUs per cGy as compared to more conventional treatment (3DCRT). Meanwhile, the patient workload in terms of treatment sessions per week remained relatively constant. The findings of this report show that variables used for shielding purposes still fall within the recommendation of NCRP Report 151. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

A standard dose of radiation for microscopic disease is not appropriate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marks, L.B.

1990-12-15

Elective irradiation of sites of potential occult tumor spread is often part of a patient's radiation therapy program. The required radiation dose (D) depends on the probability that occult disease exists (P(occ)), the number of sites at risk (A), the number of tumor clonogens present (Ni), their radiation sensitivity, and the desired control rate. An exponential model of cell survival is used to quantify the importance of these factors. Control Probability = (1 - Pocc x (1 - e-Ni x (SF2)D/2))A; SF2 = surviving fraction after 2 Gy. Implications for clinical radiation therapy include: 1. Since the number of clonogensmore » in an occult site may vary from 10 degrees to 10(8), Ni is the major determinant of the required dose. The intrinsic radiation sensitivity of the clonogens (SF2) is also extremely important in determining the dose. Other factors are less influential since they vary less. 2. The variability of Ni (8 logs) is larger than the variation in cell number seen with gross disease (1 cm3 versus 1000 cm3, 3 logs). When Ni approximately 10(8), the required dose approaches that needed for small volume gross disease (10(9) cells, 1 cm3). 3. The dose prescribed to elective sites should reflect the risk of occult disease based on the primary tumor site, stage, and grade. 4. Regions where clinicoradiologic evaluation is difficult (e.g., pelvis and obese neck) require higher doses because macroscopic tumor deposits may exist. 5. Relatively low doses (10 to 30 Gy) are often thought to be inadequate for microscopic tumor. However, similar doses have been reported to sterilize microscopic tumor in ovarian, rectal, bladder, breast, and head and neck carcinomas. Relatively low doses should not be discounted since they may be useful in select cases when normal tissue tolerances and/or previous irradiation treatment limit the radiation dose.« less

Application of the concept of biologically effective dose (BED) to patients with Vestibular Schwannomas treated by radiosurgery

PubMed Central

Millar, William T.; Lindquist, Christer; Nordström, Håkan; Lidberg, Pär; Gårding, Jonas

2013-01-01

In the application of stereotactic radiosurgery, using the Gamma Knife, there are large variations in the overall treatment time for the same prescription dose, given in a single treatment session, for different patients. This is due to not only changes in the activity of the Cobolt-60 sources, but also to variations in the number of iso-centers used, the collimator size for a particular iso-center, and the time gap between the different iso-centers. Although frequently viewed as a single dose treatment the concept of biologically effective dose (BED), incorporating concurrent fast and a slow components of repair of sublethal damage, would imply potential variations in BED because of the influence of these different variables associated with treatment. This was investigated in 26 patients, treated for Vestibular Schwannomas, using the Series B Gamma-Knife, between 1999 and 2005. The iso-center number varied between 2 and 13, and the overall treatment time from 25.4–129.58 min. The prescription doses varied from 10–14 Gy. To obtain physical dose and dose-rates from each iso-center, in a number of locations in the region of interest, a prototype version of the Leksell GammaPlan® was used. For an individual patient, BED values varied by up to 15% for a given physical iso-dose. This was due to variation in the dose prescription at different locations on that iso-dose. Between patients there was a decline in the range of BED values as the overall treatment time increased. This increased treatment time was partly a function of the slow decline in the activity of the sources with time but predominantly due to changes in the number of iso-centers used. Thus, variations in BED values did not correlate with prescription dose but was modified by the overall treatment time. PMID:29296371

Quantitative Comparison of Virtual Monochromatic Images of Dual Energy Computed Tomography Systems: Beam Hardening Artifact Correction and Variance in Computed Tomography Numbers: A Phantom Study.

PubMed

Wu, Rongli; Watanabe, Yoshiyuki; Satoh, Kazuhiko; Liao, Yen-Peng; Takahashi, Hiroto; Tanaka, Hisashi; Tomiyama, Noriyuki

2018-05-21

The aim of this study was to quantitatively compare the reduction in beam hardening artifact (BHA) and variance in computed tomography (CT) numbers of virtual monochromatic energy (VME) images obtained with 3 dual-energy computed tomography (DECT) systems at a given radiation dose. Five different iodine concentrations were scanned using dual-energy and single-energy (120 kVp) modes. The BHA and CT number variance were evaluated. For higher iodine concentrations, 40 and 80 mgI/mL, BHA on VME imaging was significantly decreased when the energy was higher than 50 keV (P = 0.003) and 60 keV (P < 0.001) for GE, higher than 80 keV (P < 0.001) and 70 keV (P = 0.002) for Siemens, and higher than 40 keV (P < 0.001) and 60 keV (P < 0.001) for Toshiba, compared with single-energy CT imaging. Virtual monochromatic energy imaging can decrease BHA and improve CT number accuracy in different dual-energy computed tomography systems, depending on energy levels and iodine concentrations.

Increased measles-mumps-rubella (MMR) vaccine uptake in the context of a targeted immunisation campaign during a measles outbreak in a vaccine-reluctant community in England.

PubMed

Le Menach, Arnaud; Boxall, Naomi; Amirthalingam, Gayatri; Maddock, Liz; Balasegaram, Sooria; Mindlin, Miranda

2014-02-26

Following a measles outbreak in a vaccine-rejecting community between April and September 2011 in South-East England, local health agencies implemented a two-pronged measles-mumps-rubella (MMR) immunisation campaign from August to October offered at the local general practice where most cases were registered. The campaign included (a) accelerated vaccination of children earlier than scheduled (1st dose at 6-11 months, or 2nd dose at 18-39 months), (b) catch-up of those aged over 18 months who had had no MMR immunisations or were late for second MMR. We investigated the impact of the outbreak and campaign on the number of MMR doses given. In January 2012, we collected information on MMR vaccination for children registered at the practice aged 6 months-16 years on 1 August 2011, through the child health information system. We counted the number of MMR doses administered in 2011 and compared it to 2008-2010 data. We estimated the proportion vaccinated among the children eligible for the accelerated and catch-up campaign. The local practice administered 257 MMR doses in 2011, a 114% increase on the average for 2008-2010. Among children eligible for earlier MMR vaccination 5/26 (19%) received a first dose, and 34/57 (60%) a second dose. Among children eligible for catch-up, 20/329 (6%) received their first MMR and 39/121 (32%) their second. Of 1538 children, the proportion completely unimmunised for MMR declined by 3 percentage-points after the outbreak. Uptake of MMR vaccination significantly increased during the outbreak following the immunisation campaign. Those amenable to MMR vaccination seem to have benefited from the campaign more than those with no previous vaccinations. Future evaluations should address what made a few parents change their mind and have their children vaccinated for the first time during the outbreak. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of di-amphetamine injected into N. Accumbens on ethanol self-administration in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samson, H.H.; Tolliver, G.A.; Haraguchi, M.

1991-03-11

Adult, male Long-Evans rats were initiated to lever press with 10% (v/v) ethanol reinforcement using the sucrose-fading technique. Following initiation and the development of stable ethanol self-administration behavior, bilateral cannula guides directed at the N.Accumbens were surgically implanted. Following recovery, the animals received microinjections once a week of either saline, 4, 10 or 20 ug/brain of dl-amphetamine sulfate dissolved in saline. Injections were 10 minutes prior to the daily 30min ethanol self-administration session.; At all doses tested, amphetamine had no significant effect upon the number of responses or ethanol. Reinforcements received during the session. However, a clear alteration in themore » pattern of responding was found at the 10 and 20 ug dose, with some animals showing effects at 4 ug. This alteration in response pattern with no effect upon total responding is different from prior work using systemic amphetamine injections, where both pattern and number of responses were affected. The data suggest that some but not all of the systemic effects could be related to amphetamine's actions on the N. Accumbens.« less

RADIATION PROTECTION CABIN FOR CATHETER-DIRECTED LIVER INTERVENTIONS: OPERATOR DOSE ASSESSMENT.

PubMed

Maleux, Geert; Bergans, Niki; Bosmans, Hilde; Bogaerts, Ria

2016-09-01

The number and complexity of interventional radiological procedures and in particular catheter-directed liver interventions have increased substantially. The current study investigates the reduction of personal doses when using a dedicated radiation protection cabin (RPC) for these procedures. Operator and assistant doses were assessed for 3 series of 20 chemoinfusion/chemoembolisation interventions, including an equal number of procedures with and without RPC. Whole body doses, finger doses and doses at the level of knees and eyes were evaluated with different types of TLD-100 Harshaw dosemeters. Dosemeters were also attached on the three walls of the RPC. The operator doses were significantly reduced by the RPC, but also without RPC, the doses appear to be limited as a result of thorough optimisation with existing radiation protection tools. The added value of the RPC should thus be determined by the outcome of balancing dose reduction and other aspects such as ergonomic benefits. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Clinical Decision Support Improves Initial Dosing and Monitoring of Tobramycin and Amikacin

PubMed Central

Cox, Zachary L.; Nelsen, Cori L.; Waitman, Lemuel R.; McCoy, Jacob A.; Peterson, Josh F.

2010-01-01

Purpose Clinical decision support (CDS) systems could be valuable tools in reducing aminoglycoside prescribing errors. We evaluated the impact of CDS on initial dosing, interval, and pharmacokinetic outcomes of amikacin and tobramycin therapy. Methods A complex CDS advisor to provide guidance on initial dosing and monitoring, using both traditional and extended interval dosing strategies, was integrated into computerized provider order entry (CPOE) and compared to a control group which featured close pharmacy monitoring of all aminoglycoside orders. A random sample of 118 patients from an academic, tertiary care medical center prescribed amikacin and tobramycin prior to advisor implementation was compared to 98 patients admitted following advisor implementation. Primary outcome was an initial dose within 10% of a dose calculated to be adherent to published dose guidelines. Secondary outcomes were a guideline-adherent interval, trough and peak concentrations in goal range, and incidence of nephrotoxicity. Results Of 216 patients studied, 97 were prescribed amikacin and 119 were prescribed tobramycin. The primary outcome of initial dosing consistent with guideline-based care increased from 40% in the pre-advisor arm to 80% in the post-advisor arm (p<0.001), with a number needed to treat of 3 patients to prevent one incorrect dose. Correct initial interval based on renal function also increased from 63% to 87% (p<0.001). The changes in initial dosing and interval resulted in an increase of trough concentrations in the goal range from 59% pre-advisor to 89% post-advisor implementation (p=0.0004). There was no significant difference in peak concentrations in goal range or incidence of nephrotoxicity (25% vs. 17%, p=0.2). Conclusion An advisor for aminoglycoside dosing and monitoring integrated into CPOE significantly improves initial dosing, selection of interval, and trough concentrations at goal compared to unassisted physician dosing. PMID:21411805

Common errors of drug administration in infants: causes and avoidance.

PubMed

Anderson, B J; Ellis, J F

1999-01-01

Drug administration errors are common in infants. Although the infant population has a high exposure to drugs, there are few data concerning pharmacokinetics or pharmacodynamics, or the influence of paediatric diseases on these processes. Children remain therapeutic orphans. Formulations are often suitable only for adults; in addition, the lack of maturation of drug elimination processes, alteration of body composition and influence of size render the calculation of drug doses complex in infants. The commonest drug administration error in infants is one of dose, and the commonest hospital site for this error is the intensive care unit. Drug errors are a consequence of system error, and preventive strategies are possible through system analysis. The goal of a zero drug error rate should be aggressively sought, with systems in place that aim to eliminate the effects of inevitable human error. This involves review of the entire system from drug manufacture to drug administration. The nuclear industry, telecommunications and air traffic control services all practise error reduction policies with zero error as a clear goal, not by finding fault in the individual, but by identifying faults in the system and building into that system mechanisms for picking up faults before they occur. Such policies could be adapted to medicine using interventions both specific (the production of formulations which are for children only and clearly labelled, regular audit by pharmacists, legible prescriptions, standardised dose tables) and general (paediatric drug trials, education programmes, nonpunitive error reporting) to reduce the number of errors made in giving medication to infants.

Estimating systemic exposure to ethinyl estradiol from an oral contraceptive.

PubMed

Westhoff, Carolyn L; Pike, Malcolm C; Tang, Rosalind; DiNapoli, Marianne N; Sull, Monica; Cremers, Serge

2015-05-01

This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive with steady-state values and to assess whether any simpler measures could provide an adequate proxy of the "gold standard" 24-hour steady-state area under the curve (AUC) value. Identification of a simple, less expensive measure of systemic ethinyl estradiol exposure would be useful for larger studies that are designed to assess the relationship between an individual's ethinyl estradiol exposure and side-effects. We collected 13 samples over 24 hours for pharmacokinetic analysis on days 1 and 21 of the first cycle of a monophasic oral contraceptive that contained 30 μg ethinyl estradiol and 150 μg levonorgestrel in 17 nonobese healthy white women. We also conducted an abbreviated single-dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of a full 13-sample steady-state pharmacokinetic analysis with results that had been calculated with the use of fewer samples (9 or 5) and after the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure. The AUC, maximum, and 24-hour values were similar after the 2 single oral contraceptive doses (AUC; r=0.92). The steady-state 13-sample 24-hour AUC value was correlated highly with the average 9-sample AUC value after the 2 single doses (r=0.81; P=.0002). This correlation remained the same if the number of single-dose samples was reduced to 4, taken at time 1, 2.5, 4, and 24 hours. The 24-hour value at steady-state was correlated highly with the 24-hour steady-state AUC value (r=0.92; P<.0001). The average of the 24-hour values after the 2 single doses was also correlated quite highly with the steady-state AUC value (r=0.72; P=.0026). Limited blood sampling, including results from 2 single doses, gave highly correlated estimates of an oral contraceptive user's steady-state ethinyl estradiol exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

Commissioning and quality assurance for the treatment delivery components of the AccuBoost system.

PubMed

Iftimia, Ileana; Talmadge, Mike; Ladd, Ron; Halvorsen, Per

2015-03-08

The objective for this work was to develop a commissioning methodology for the treatment delivery components of the AccuBoost system, as well as to establish a routine quality assurance program and appropriate guidance for clinical use based on the commissioning results. Various tests were developed: 1) assessment of the accuracy of the displayed separation value; 2) validation of the dwell positions within each applicator; 3) assessment of the accuracy and precision of the applicator localization system; 4) assessment of the combined dose profile of two opposed applicators to confirm that they are coaxial; 5) measurement of the absolute dose delivered with each applicator to confirm acceptable agreement with dose based on Monte Carlo modeling; 6) measurements of the skin-to-center dose ratio using optically stimulated luminescence dosimeters; and 7) assessment of the mammopad cushion's effect on the center dose. We found that the difference between the measured and the actual paddle separation is < 0.1 cm for the separation range of 3 cm to 7.5 cm. Radiochromic film measurements demonstrated that the number of dwell positions inside the applicators agree with the values from the vendor, for each applicator type and size. The shift needed for a good applicator-grid alignment was within 0.2 cm. The dry-run test using film demonstrated that the shift of the dosimetric center is within 0.15 cm. Dose measurements in water converted to polystyrene agreed within 5.0% with the Monte Carlo data in polystyrene for the same applicator type, size, and depth. A solid water-to-water (phantom) factor was obtained for each applicator, and all future annual quality assurance tests will be performed in solid water using an average value of 1.07 for the solid water-to-water factor. The skin-to-center dose ratio measurements support the Monte Carlo-based values within 5.0% agreement. For the treatment separation range of 4 cm to 8cm, the change in center dose would be < 1.0% for all applicators when using a compressed pad of 0.2 cm to 0.3 cm. The tests performed ensured that all treatment components of the AccuBoost system are functional and that a treatment plan can be delivered with acceptable accuracy. Based on the commissioning results, a quality assurance manual and guidance documents for clinical use were developed.

Dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study.

PubMed

Miner, Philip B; Silberg, Debra G; Ruth, Magnus; Miller, Frank; Pandolfino, John

2014-11-18

The γ-aminobutyric acid type B-receptor agonist lesogaberan (AZD3355) has been developed for use in patients with gastroesophageal reflux disease (GERD) symptoms despite proton pump inhibitor (PPI) therapy (partial responders). This study aimed to explore the dose-response effect of lesogaberan on reflux episodes in partial responders. In this randomized, single-centre, double-blind, crossover, placebo-controlled study, partial responders taking optimised PPI therapy were given 30, 90, 120 and 240 mg doses of lesogaberan. Each dose was given twice (12 h apart) during a 24-h period, during which impedance-pH measurements were taken. Twenty-five patients were included in the efficacy analysis and 27 in the safety analysis. The effect of lesogaberan on the mean number of reflux episodes was dose-dependent, and all doses significantly reduced the mean number of reflux episodes relative to placebo. Lesogaberan also dose-dependently reduced the mean number of acid reflux episodes (except the 30 mg dose) and weakly acid reflux episodes (all doses) significantly, relative to placebo. Regardless of dose, lesogaberan had a similar effect on the percentage of time with esophageal pH < 4 [mean reduction: 68.5% (30 mg), 54.2% (90 mg), 65.9% (120 mg), 72.1% (240 mg); p < 0.05 except 90 mg dose]. No adverse events led to discontinuation and no serious adverse events occurred during active treatment. Lesogaberan inhibited reflux in a dose-dependent manner in partial responders taking optimised PPI therapy, and these effects were significant versus placebo. All lesogaberan doses were well tolerated and were not associated with clinically relevant adverse events. ClinicalTrials.gov identifier: NCT01043185.

Fascia iliaca compartment nerve block versus systemic pain control for acute femur fractures in the pediatric emergency department.

PubMed

Neubrand, Tara L; Roswell, Kelley; Deakyne, Sara; Kocher, Kendra; Wathen, Joseph

2014-07-01

To compare management of acute femur fractures in children who received a fascia iliaca compartment nerve block (FICNB) to those who received systemic intravenously administered analgesics in the pediatric emergency department. The comparison evaluated frequency of use, effectiveness, and associated adverse event profiles. Study population was derived from a retrospective chart review of pediatric patients sustaining acute femur fractures between 2005 and 2009. Cases (received FICNB) were compared with controls (only systemic analgesia) in terms of effectiveness and adverse event. Outcomes included total doses of systemic medications received and comparison of preintervention and postintervention pain scores. Two hundred fifty-nine charts were reviewed: 158 who received FICNB versus 101 who did not. The median dose of systemic medications was 1 dose lower in the FICNB group compared with the systemic medications group. This remained significant after controlling for age and preintervention pain scores (P = 0.02). Median postintervention pain scores in the FICNB group were 1.5 points lower than those in the systemic medications group. This remained significant while controlling for preintervention pain scores and age (P < 0.01). There was no difference in the total adverse events between the FICNB and the control group in either the unadjusted or adjusted analyses (P = 0.08). The FICNB group had 2 seizure episodes, one of which had associated subarachnoid hemorrhage. No patient in either group experienced bradycardia, arrhythmia, visual disturbance, abnormal hearing, mouth numbness, motor tremors, pain or bleeding at injection site, or prolonged nerve block. We report on the largest number of FICNBs administered in a pediatric emergency department for acute femur fractures. Effectiveness, as measured by pain scores and total doses of systemic analgesia, was improved in the FICNB group versus the control. There was no difference in adverse events between the groups.

SU-E-J-205: Dose Distribution Differences Caused by System Related Geometric Distortion in MRI-Guided Radiation Treatment System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, J; Yang, J; Wen, Z

2015-06-15

Purpose: MRI has superb soft tissue contrast but is also known for geometric distortions. The concerns and uncertainty about MRI’s geometric distortion have contributed to the hesitation of using only MRI for simulation in radiation therapy. There are two major categories of geometric distortion in MRI; system related and patient related. In this presentation, we studied the impact of system-related geometric distortion on dose distribution in a digital body phantom under an MR-Linac environment. Methods: Residual geometric distortion (after built-in geometric correction) was modeled based on phantom measurements of the system-related geometric distortions of a MRI scanner of a combinedmore » MR guided Radiation Therapy (MRgRT) system. A digital oval shaped phantom (40×25 cm) as well as one ellipsoid shaped tumor volume was created to simulate a simplified human body. The simulated tumor volume was positioned at several locations between the isocenter and the body surface. CT numbers in HUs that approximate soft tissue and tumor were assigned to the respective regions in the digital phantom. To study the effect of geometric distortion caused by system imperfections, an IMRT plan was optimized with the distorted image set with the B field. Dose distributions were re-calculated on the undistorted image set with the B field (as in MR-Linac). Results: The maximum discrepancies in both body contour and tumor boundary was less than 2 mm, which leads to small dose distribution change. For the target in the center, coverage was reduced from 98.8% (with distortion) to 98.2%; for the other peripheral target coverage was reduced from 98.4% to 95.9%. Conclusion: System related geometric distortions over the 40×25 area were within 2mm and the resulted dosimetric effects were minor for the two tumor locations in the phantom. Patient study will be needed for further investigation. The authors received a corporate research grant from Elekta.« less

Gamma irradiation to improve plant vigour, grain development, and yield attributes of wheat

NASA Astrophysics Data System (ADS)

Singh, Bhupinder; Datta, P. S.

2010-02-01

Utilizing low dose gamma radiation holds promise for physiological crop improvement. Seed treatment of low dose gamma radiation 0.01-0.10 kGy reduced plant height, improved plant vigour, flag leaf area, total and number of EBT. Gamma irradiation increased grain yield due to an increase in number of EBT and grain number while 1000 grain weight was negatively affected. Further uniformity in low dose radiation response in wheat in the field suggests that the affect is essentially at physiological than at genetic level and that role of growth hormones could be crucial.

System of radiographic control or an imaging system for personal radiographic inspection

NASA Astrophysics Data System (ADS)

Babichev, E. A.; Baru, S. E.; Neustroev, V. A.; Leonov, V. V.; Porosev, V. V.; Savinov, G. A.; Ukraintsev, Yu. G.

2004-06-01

The security system of personal radiographic inspection for detection of explosive materials and plastic weapons was developed in BINP recently. Basic system parameters are: maximum scanning height— 2000 mm, image width— 800 mm, number of detector channels—768, channel size— 1.05×1 mm, charge collecting time for one line—2, 5 ms, scanning speed— 40 cm/s, maximum scanning time— 5 s, radiation dose per one inspection <5 μSv. The detector is a multichannel ionization Xe chamber. The image of inspected person will appear on the display just after scanning. The pilot sample of this system was put into operation in March, 2003.b

SU-E-T-222: Computational Optimization of Monte Carlo Simulation On 4D Treatment Planning Using the Cloud Computing Technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chow, J

Purpose: This study evaluated the efficiency of 4D lung radiation treatment planning using Monte Carlo simulation on the cloud. The EGSnrc Monte Carlo code was used in dose calculation on the 4D-CT image set. Methods: 4D lung radiation treatment plan was created by the DOSCTP linked to the cloud, based on the Amazon elastic compute cloud platform. Dose calculation was carried out by Monte Carlo simulation on the 4D-CT image set on the cloud, and results were sent to the FFD4D image deformation program for dose reconstruction. The dependence of computing time for treatment plan on the number of computemore » node was optimized with variations of the number of CT image set in the breathing cycle and dose reconstruction time of the FFD4D. Results: It is found that the dependence of computing time on the number of compute node was affected by the diminishing return of the number of node used in Monte Carlo simulation. Moreover, the performance of the 4D treatment planning could be optimized by using smaller than 10 compute nodes on the cloud. The effects of the number of image set and dose reconstruction time on the dependence of computing time on the number of node were not significant, as more than 15 compute nodes were used in Monte Carlo simulations. Conclusion: The issue of long computing time in 4D treatment plan, requiring Monte Carlo dose calculations in all CT image sets in the breathing cycle, can be solved using the cloud computing technology. It is concluded that the optimized number of compute node selected in simulation should be between 5 and 15, as the dependence of computing time on the number of node is significant.« less

SU-E-J-93: Parametrisation of Dose to the Mucosa of the Anterior Rectal Wall in Transrectal Ultrasound Guided High-Dose-Rate Brachytherapy of the Prostate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aitkenhead, A; Hamlett, L; Wood, D

2014-06-01

Purpose: In high-dose-rate (HDR) brachytherapy of the prostate, radiation is delivered from a number of radioactive sources which are inserted via catheter into the target volume. The rectal mucosa also receives dose during the treatment, which may lead to late toxicity effects. To allow possible links between rectal dose and toxicity to be investigated, suitable methods of parametrising the rectal dose are needed. Methods: During treatment of a series of 95 patients, anatomy and catheter locations were monitored by transrectal ultrasound, and target volume positions were contoured on the ultrasound scan by the therapist. The anterior rectal mucosal wall wasmore » identified by contouring the transrectal ultrasound balloon within the ultrasound scan. Source positions and dwell times, along with the dose delivered to the patient were computed using the Oncentra Prostate treatment planning system (TPS). Data for the series of patients were exported from the TPS in Dicom format, and a series of parametrisation methods were developed in a Matlab environment to assess the rectal dose. Results: Contours of the anterior rectal mucosa were voxelised within Matlab to allow the dose to the rectal mucosa to be analysed directly from the 3D dose grid. Dose parametrisations based on dose-surface (DSH) and dose-line (DLH) histograms were obtained. Both lateral and longitudinal extents of the mucosal dose were parametrised using dose-line histograms in the relevant directions. Conclusion: We have developed a series of dose parametrisations for quantifying the dose to the rectal mucosa during HDR prostate brachytherapy which are suitable for future studies investigating potential associations between mucosal dose and late toxicity effects. The geometry of the transrectal probe standardises the rectal anatomy, making this treatment technique particularly suited to studies of this nature.« less

SU-F-T-428: An Optimization-Based Commissioning Tool for Finite Size Pencil Beam Dose Calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Y; Tian, Z; Song, T

Purpose: Finite size pencil beam (FSPB) algorithms are commonly used to pre-calculate the beamlet dose distribution for IMRT treatment planning. FSPB commissioning, which usually requires fine tuning of the FSPB kernel parameters, is crucial to the dose calculation accuracy and hence the plan quality. Yet due to the large number of beamlets, FSPB commissioning could be very tedious. This abstract reports an optimization-based FSPB commissioning tool we have developed in MatLab to facilitate the commissioning. Methods: A FSPB dose kernel generally contains two types of parameters: the profile parameters determining the dose kernel shape, and a 2D scaling factors accountingmore » for the longitudinal and off-axis corrections. The former were fitted using the penumbra of a reference broad beam’s dose profile with Levenberg-Marquardt algorithm. Since the dose distribution of a broad beam is simply a linear superposition of the dose kernel of each beamlet calculated with the fitted profile parameters and scaled using the scaling factors, these factors could be determined by solving an optimization problem which minimizes the discrepancies between the calculated dose of broad beams and the reference dose. Results: We have commissioned a FSPB algorithm for three linac photon beams (6MV, 15MV and 6MVFFF). Dose of four field sizes (6*6cm2, 10*10cm2, 15*15cm2 and 20*20cm2) were calculated and compared with the reference dose exported from Eclipse TPS system. For depth dose curves, the differences are less than 1% of maximum dose after maximum dose depth for most cases. For lateral dose profiles, the differences are less than 2% of central dose at inner-beam regions. The differences of the output factors are within 1% for all the three beams. Conclusion: We have developed an optimization-based commissioning tool for FSPB algorithms to facilitate the commissioning, providing sufficient accuracy of beamlet dose calculation for IMRT optimization.« less

Biodosimetry estimate for high-LET irradiation.

PubMed

Wang, Z Z; Li, W J; Zhi, D J; Jing, X G; Wei, W; Gao, Q X; Liu, B

2007-08-01

The purpose of this paper is to prepare for an easy and reliable biodosimeter protocol for radiation accidents involving high-linear energy transfer (LET) exposure. Human peripheral blood lymphocytes were irradiated using carbon ions (LET: 34.6 keV microm(-1)), and the chromosome aberrations induced were analyzed using both a conventional colcemid block method and a calyculin A induced premature chromosome condensation (PCC) method. At a lower dose range (0-4 Gy), the measured dicentric (dics) and centric ring chromosomes (cRings) provided reasonable dose information. At higher doses (8 Gy), however, the frequency of dics and cRings was not suitable for dose estimation. Instead, we found that the number of Giemsa-stained drug-induced G2 prematurely condensed chromosomes (G2-PCC) can be used for dose estimation, since the total chromosome number (including fragments) was linearly correlated with radiation dose (r = 0.99). The ratio of the longest and the shortest chromosome length of the drug-induced G2-PCCs increased with radiation dose in a linear-quadratic manner (r = 0.96), which indicates that this ratio can also be used to estimate radiation doses. Obviously, it is easier to establish the dose response curve using the PCC technique than using the conventional metaphase chromosome method. It is assumed that combining the ratio of the longest and the shortest chromosome length with analysis of the total chromosome number might be a valuable tool for rapid and precise dose estimation for victims of radiation accidents.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benahmed, A.; Elkarch, H.

This new portable radiological environmental monitor consists of 2 main components, Gamma ionization chamber and a FPGA-based electronic enclosure linked to convivial software for treatment and analyzing. The HPIC ion chamber is the heart of this radiation measurement system and is running in range from 0 to 100 mR/h, so that the sensitivity at the output is 20 mV/μR/h, with a nearly flat energy response from 0,07 to 10 MEV. This paper presents a contribution for developing a new nuclear measurement data acquisition system based on Cyclone III FPGA Starter Kit ALTERA, and a user-friendly software to run real-time controlmore » and data processing. It was developed to substitute the older radiation monitor RSS-112 PIC installed in CNESTEN's Laboratory in order to improve some of its functionalities related to acquisition time and data memory capacity. As for the associated acquisition software, it was conceived under the virtual LabView platform from National Instrument, and offers a variety of system setup for radiation environmental monitoring. It gives choice to display both the statistical data and the dose rate. Statistical data shows a summary of current data, current time/date and dose integrator values, and the dose rate displays the current dose rate in large numbers for viewing from a distance as well as the date and time. The prototype version of this new instrument and its data processing software has been successfully tested and validated for viewing and monitoring the environmental radiation of Moroccan nuclear center. (authors)« less

A Comprehensive Assessment of Toxicities in Patients with Central Nervous System Lymphoma Undergoing Autologous Stem Cell Transplantation Using Thiotepa, Busulfan, and Cyclophosphamide Conditioning.

PubMed

Scordo, Michael; Bhatt, Valkal; Hsu, Meier; Omuro, Antonio M; Matasar, Matthew J; DeAngelis, Lisa M; Dahi, Parastoo B; Moskowitz, Craig H; Giralt, Sergio A; Sauter, Craig S

2017-01-01

High-dose therapy and autologous stem cell transplantation (ASCT) with thiotepa, busulfan, and cyclophosphamide (TBC) conditioning has emerged as an effective postinduction treatment strategy for patients with primary central nervous system lymphoma (PCNSL) or secondary central nervous system lymphoma (SCNSL), but it is associated with considerable toxicity and transplantation-related mortality (TRM) in the modern era. Forty-three adult patients with chemosensitive PCNSL or SCNSL underwent TBC-conditioned ASCT between 2006 and 2015. Twenty-eight of these patients received pharmacokinetically (PK)-targeted busulfan dosing. The median number of clinically relevant individual grade ≥3 nonhematologic toxicities per patient was 5. We found no association between pretransplantation patient characteristics and the presence of more than 5 grade ≥3 nonhematologic toxicities. Patients with elevated first-dose busulfan area under the curve values did not experience more toxicity. Paradoxically, patients treated with more than 2 regimens before undergoing ASCT had lower first-dose busulfan AUC values. With a median follow-up among survivors of 20 months, 1-year progression-free survival (PFS) and overall survival (OS) from the time of ASCT were 83% and 87%, respectively. Although this study reaffirms the favorable PFS and OS associated with TBC-conditioned ASCT for PCNSL or SCNSL, this treatment strategy carries a large toxicity burden. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Adaptive Dose Painting by Numbers for Head-and-Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duprez, Frederic, E-mail: frederic.duprez@ugent.be; De Neve, Wilfried; De Gersem, Werner

Purpose: To investigate the feasibility of adaptive intensity-modulated radiation therapy (IMRT) using dose painting by numbers (DPBN) for head-and-neck cancer. Methods and Materials: Each patient's treatment used three separate treatment plans: fractions 1-10 used a DPBN ([{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography [{sup 18}F-FDG-PET]) voxel intensity-based IMRT plan based on a pretreatment {sup 18}F-FDG-PET/computed tomography (CT) scan; fractions 11-20 used a DPBN plan based on a {sup 18}F-FDG-PET/CT scan acquired after the eighth fraction; and fractions 21-32 used a conventional (uniform dose) IMRT plan. In a Phase I trial, two dose prescription levels were tested: a median dose of 80.9 Gymore » to the high-dose clinical target volume (CTV{sub highdose}) (dose level I) and a median dose of 85.9 Gy to the gross tumor volume (GTV) (dose level II). Between February 2007 and August 2009, 7 patients at dose level I and 14 patients at dose level II were enrolled. Results: All patients finished treatment without a break, and no Grade 4 acute toxicity was observed. Treatment adaptation (i.e., plans based on the second {sup 18}F-FDG-PET/CT scan) reduced the volumes for the GTV (41%, p = 0.01), CTV{sub highdose} (18%, p = 0.01), high-dose planning target volume (14%, p = 0.02), and parotids (9-12%, p < 0.05). Because the GTV was much smaller than the CTV{sub highdose} and target adaptation, further dose escalation at dose level II resulted in less severe toxicity than that observed at dose level I. Conclusion: To our knowledge, this represents the first clinical study that combines adaptive treatments with dose painting by numbers. Treatment as described above is feasible.« less

Does Iterative Reconstruction Lower CT Radiation Dose: Evaluation of 15,000 Examinations

PubMed Central

Noël, Peter B.; Renger, Bernhard; Fiebich, Martin; Münzel, Daniela; Fingerle, Alexander A.; Rummeny, Ernst J.; Dobritz, Martin

2013-01-01

Purpose Evaluation of 15,000 computed tomography (CT) examinations to investigate if iterative reconstruction (IR) reduces sustainably radiation exposure. Method and Materials Information from 15,000 CT examinations was collected, including all aspects of the exams such as scan parameter, patient information, and reconstruction instructions. The examinations were acquired between January 2010 and December 2012, while after 15 months a first generation IR algorithm was installed. To collect the necessary information from PACS, RIS, MPPS and structured reports a Dose Monitoring System was developed. To harvest all possible information an optical character recognition system was integrated, for example to collect information from the screenshot CT-dose report. The tool transfers all data to a database for further processing such as the calculation of effective dose and organ doses. To evaluate if IR provides a sustainable dose reduction, the effective dose values were statistically analyzed with respect to protocol type, diagnostic indication, and patient population. Results IR has the potential to reduce radiation dose significantly. Before clinical introduction of IR the average effective dose was 10.1±7.8mSv and with IR 8.9±7.1mSv (p*=0.01). Especially in CTA, with the possibility to use kV reduction protocols, such as in aortic CTAs (before IR: average14.2±7.8mSv; median11.4mSv /with IR:average9.9±7.4mSv; median7.4mSv), or pulmonary CTAs (before IR: average9.7±6.2mSV; median7.7mSv /with IR: average6.4±4.7mSv; median4.8mSv) the dose reduction effect is significant(p*=0.01). On the contrary for unenhanced low-dose scans of the cranial (for example sinuses) the reduction is not significant (before IR:average6.6±5.8mSv; median3.9mSv/with IR:average6.0±3.1mSV; median3.2mSv). Conclusion The dose aspect remains a priority in CT research. Iterative reconstruction algorithms reduce sustainably and significantly radiation dose in the clinical routine. Our results illustrate that not only in studies with a limited number of patients but also in the clinical routine, IRs provide long-term dose saving. PMID:24303035

Does iterative reconstruction lower CT radiation dose: evaluation of 15,000 examinations.

PubMed

Noël, Peter B; Renger, Bernhard; Fiebich, Martin; Münzel, Daniela; Fingerle, Alexander A; Rummeny, Ernst J; Dobritz, Martin

2013-01-01

Evaluation of 15,000 computed tomography (CT) examinations to investigate if iterative reconstruction (IR) reduces sustainably radiation exposure. Information from 15,000 CT examinations was collected, including all aspects of the exams such as scan parameter, patient information, and reconstruction instructions. The examinations were acquired between January 2010 and December 2012, while after 15 months a first generation IR algorithm was installed. To collect the necessary information from PACS, RIS, MPPS and structured reports a Dose Monitoring System was developed. To harvest all possible information an optical character recognition system was integrated, for example to collect information from the screenshot CT-dose report. The tool transfers all data to a database for further processing such as the calculation of effective dose and organ doses. To evaluate if IR provides a sustainable dose reduction, the effective dose values were statistically analyzed with respect to protocol type, diagnostic indication, and patient population. IR has the potential to reduce radiation dose significantly. Before clinical introduction of IR the average effective dose was 10.1±7.8mSv and with IR 8.9±7.1mSv (p*=0.01). Especially in CTA, with the possibility to use kV reduction protocols, such as in aortic CTAs (before IR: average14.2±7.8mSv; median11.4mSv /with IR:average9.9±7.4mSv; median7.4mSv), or pulmonary CTAs (before IR: average9.7±6.2mSV; median7.7mSv /with IR: average6.4±4.7mSv; median4.8mSv) the dose reduction effect is significant(p*=0.01). On the contrary for unenhanced low-dose scans of the cranial (for example sinuses) the reduction is not significant (before IR:average6.6±5.8mSv; median3.9mSv/with IR:average6.0±3.1mSV; median3.2mSv). The dose aspect remains a priority in CT research. Iterative reconstruction algorithms reduce sustainably and significantly radiation dose in the clinical routine. Our results illustrate that not only in studies with a limited number of patients but also in the clinical routine, IRs provide long-term dose saving.

Intussusception after monovalent rotavirus vaccine-United States, Vaccine Adverse Event Reporting System (VAERS), 2008-2014.

PubMed

Haber, Penina; Parashar, Umesh D; Haber, Michael; DeStefano, Frank

2015-09-11

In 2006 and 2008, two new rotavirus vaccines (RotaTeq [RV5] and Rotarix [RV1]) were introduced in the United States. US data on intussusception have been mostly related to RV5, with limited data on RV1. We assessed intussusception events following RV1 reported to the Vaccine Adverse Event Reporting System (VAERS), a US national passive surveillance system, during February 2008-December 2014. We conducted a self-controlled risk interval analysis using Poisson regression to estimate the daily reporting ratio (DRR) of intussusception after the first 2 doses of RV1 comparing average daily reports 3-6 versus 0-2 days after vaccination. We calculated the excess risk of intussusception per 100,000 vaccinations based on DRRs and background rates of intussusception. Sensitivity analyses were conducted to assess effects of differential reporting completeness and inaccuracy of baseline rates. VAERS received 108 confirmed insusceptible reports after RV1. A significant clustering was observed on days 3-8 after does1 (p=0.001) and days 2-7 after dose 2 (p=0.001). The DRR comparing the 3-6 day and the 0-2 day periods after RV1 dose 1 was 7.5 (95% CI=2.3, 24.6), translating to an excess risk of 1.6 (95% CI=0.3, 5.8) per 100,000 vaccinations. The DRR was elevated but not significant after dose 2 (2.4 [95% CI=0.8,7.5]). The excess risk ranged from 1.2 to 2.8 per 100,000 in sensitivity analysis. We observed a significant increased risk of intussusception 3-6 days after dose 1 of RV1. The estimated small number of intussusception cases attributable to RV1 is outweighed by the benefits of rotavirus vaccination. Published by Elsevier Ltd.

Dermal and inhalation acute toxic class methods: test procedures and biometric evaluations for the Globally Harmonized Classification System.

PubMed

Holzhütter, H G; Genschow, E; Diener, W; Schlede, E

2003-05-01

The acute toxic class (ATC) methods were developed for determining LD(50)/LC(50) estimates of chemical substances with significantly fewer animals than needed when applying conventional LD(50)/LC(50) tests. The ATC methods are sequential stepwise procedures with fixed starting doses/concentrations and a maximum of six animals used per dose/concentration. The numbers of dead/moribund animals determine whether further testing is necessary or whether the test is terminated. In recent years we have developed classification procedures for the oral, dermal and inhalation routes of administration by using biometric methods. The biometric approach assumes a probit model for the mortality probability of a single animal and assigns the chemical to that toxicity class for which the best concordance is achieved between the statistically expected and the observed numbers of dead/moribund animals at the various steps of the test procedure. In previous publications we have demonstrated the validity of the biometric ATC methods on the basis of data obtained for the oral ATC method in two-animal ring studies with 15 participants from six countries. Although the test procedures and biometric evaluations for the dermal and inhalation ATC methods have already been published, there was a need for an adaptation of the classification schemes to the starting doses/concentrations of the Globally Harmonized Classification System (GHS) recently adopted by the Organization for Economic Co-operation and Development (OECD). Here we present the biometric evaluation of the dermal and inhalation ATC methods for the starting doses/concentrations of the GHS and of some other international classification systems still in use. We have developed new test procedures and decision rules for the dermal and inhalation ATC methods, which require significantly fewer animals to provide predictions of toxicity classes, that are equally good or even better than those achieved by using the conventional LD(50)/LC(50) methods. In order to cope with rather narrow dose/concentration classes of the GHS we have, as in our previous publications, combined the outcome of all results that can be obtained during testing for the allocation to one of the defined toxicity classes of the GHS. Our results strongly recommend the deletion of the dermal LD(50) and the inhalation LC(50) test as regulatory tests and the adoption of the dermal and inhalation ATC methods as internationally accepted alternatives.

SU-C-BRC-05: Monte Carlo Calculations to Establish a Simple Relation of Backscatter Dose Enhancement Around High-Z Dental Alloy to Its Atomic Number

DOE Office of Scientific and Technical Information (OSTI.GOV)

Utsunomiya, S; Kushima, N; Katsura, K

Purpose: To establish a simple relation of backscatter dose enhancement around a high-Z dental alloy in head and neck radiation therapy to its average atomic number based on Monte Carlo calculations. Methods: The PHITS Monte Carlo code was used to calculate dose enhancement, which is quantified by the backscatter dose factor (BSDF). The accuracy of the beam modeling with PHITS was verified by comparing with basic measured data namely PDDs and dose profiles. In the simulation, a high-Z alloy of 1 cm cube was embedded into a tough water phantom irradiated by a 6-MV (nominal) X-ray beam of 10 cmmore » × 10 cm field size of Novalis TX (Brainlab). The ten different materials of high-Z alloys (Al, Ti, Cu, Ag, Au-Pd-Ag, I, Ba, W, Au, Pb) were considered. The accuracy of calculated BSDF was verified by comparing with measured data by Gafchromic EBT3 films placed at from 0 to 10 mm away from a high-Z alloy (Au-Pd-Ag). We derived an approximate equation to determine the relation of BSDF and range of backscatter to average atomic number of high-Z alloy. Results: The calculated BSDF showed excellent agreement with measured one by Gafchromic EBT3 films at from 0 to 10 mm away from the high-Z alloy. We found the simple linear relation of BSDF and range of backscatter to average atomic number of dental alloys. The latter relation was proven by the fact that energy spectrum of backscatter electrons strongly depend on average atomic number. Conclusion: We found a simple relation of backscatter dose enhancement around high-Z alloys to its average atomic number based on Monte Carlo calculations. This work provides a simple and useful method to estimate backscatter dose enhancement from dental alloys and corresponding optimal thickness of dental spacer to prevent mucositis effectively.« less

Image acquisition optimization of a limited-angle intrafraction verification (LIVE) system for lung radiotherapy.

PubMed

Zhang, Yawei; Deng, Xinchen; Yin, Fang-Fang; Ren, Lei

2018-01-01

Limited-angle intrafraction verification (LIVE) has been previously developed for four-dimensional (4D) intrafraction target verification either during arc delivery or between three-dimensional (3D)/IMRT beams. Preliminary studies showed that LIVE can accurately estimate the target volume using kV/MV projections acquired over orthogonal view 30° scan angles. Currently, the LIVE imaging acquisition requires slow gantry rotation and is not clinically optimized. The goal of this study is to optimize the image acquisition parameters of LIVE for different patient respiratory periods and gantry rotation speeds for the effective clinical implementation of the system. Limited-angle intrafraction verification imaging acquisition was optimized using a digital anthropomorphic phantom (XCAT) with simulated respiratory periods varying from 3 s to 6 s and gantry rotation speeds varying from 1°/s to 6°/s. LIVE scanning time was optimized by minimizing the number of respiratory cycles needed for the four-dimensional scan, and imaging dose was optimized by minimizing the number of kV and MV projections needed for four-dimensional estimation. The estimation accuracy was evaluated by calculating both the center-of-mass-shift (COMS) and three-dimensional volume-percentage-difference (VPD) between the tumor in estimated images and the ground truth images. The robustness of LIVE was evaluated with varied respiratory patterns, tumor sizes, and tumor locations in XCAT simulation. A dynamic thoracic phantom (CIRS) was used to further validate the optimized imaging schemes from XCAT study with changes of respiratory patterns, tumor sizes, and imaging scanning directions. Respiratory periods, gantry rotation speeds, number of respiratory cycles scanned and number of kV/MV projections acquired were all positively correlated with the estimation accuracy of LIVE. Faster gantry rotation speed or longer respiratory period allowed less respiratory cycles to be scanned and less kV/MV projections to be acquired to estimate the target volume accurately. Regarding the scanning time minimization, for patient respiratory periods of 3-4 s, gantry rotation speeds of 1°/s, 2°/s, 3-6°/s required scanning of five, four, and three respiratory cycles, respectively. For patient respiratory periods of 5-6 s, the corresponding respiratory cycles required in the scan changed to four, three, and two cycles, respectively. Regarding the imaging dose minimization, for patient respiratory periods of 3-4 s, gantry rotation speeds of 1°/s, 2-4°/s, 5-6°/s required acquiring of 7, 5, 4 kV and MV projections, respectively. For patient respiratory periods of 5-6 s, 5 kV and 5 MV projections are sufficient for all gantry rotation speeds. The optimized LIVE system was robust against breathing pattern, tumor size and tumor location changes. In the CIRS study, the optimized LIVE system achieved the average center-of-mass-shift (COMS)/volume-percentage-difference (VPD) of 0.3 ± 0.1 mm/7.7 ± 2.0% for the scanning time priority case, 0.2 ± 0.1 mm/6.1 ± 1.2% for the imaging dose priority case, respectively, among all gantry rotation speeds tested. LIVE was robust against different scanning directions investigated. The LIVE system has been preliminarily optimized for different patient respiratory periods and treatment gantry rotation speeds using digital and physical phantoms. The optimized imaging parameters, including number of respiratory cycles scanned and kV/MV projection numbers acquired, provide guidelines for optimizing the scanning time and imaging dose of the LIVE system for its future evaluations and clinical implementations through patient studies. © 2017 American Association of Physicists in Medicine.

Shielding Development for Nuclear Thermal Propulsion

NASA Technical Reports Server (NTRS)

Caffrey, Jarvis A.; Gomez, Carlos F.; Scharber, Luke L.

2015-01-01

Radiation shielding analysis and development for the Nuclear Cryogenic Propulsion Stage (NCPS) effort is currently in progress and preliminary results have enabled consideration for critical interfaces in the reactor and propulsion stage systems. Early analyses have highlighted a number of engineering constraints, challenges, and possible mitigating solutions. Performance constraints include permissible crew dose rates (shared with expected cosmic ray dose), radiation heating flux into cryogenic propellant, and material radiation damage in critical components. Design strategies in staging can serve to reduce radiation scatter and enhance the effectiveness of inherent shielding within the spacecraft while minimizing the required mass of shielding in the reactor system. Within the reactor system, shield design is further constrained by the need for active cooling with minimal radiation streaming through flow channels. Material selection and thermal design must maximize the reliability of the shield to survive the extreme environment through a long duration mission with multiple engine restarts. A discussion of these challenges and relevant design strategies are provided for the mitigation of radiation in nuclear thermal propulsion.

On the occurrence of hypothyroidism after radioiodine resection (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farschidpur, D.; Meiisel, P.

1963-02-01

An attempt was made to determine the dose of radioiodine in the treatment of hyperthyroidism with reference to the number of Cs and rep values. It was proved desirable to administer no more than 8 mC and 30,000 rep. An analysis of patients treated between 1956 and 1961 revealed six permanent cases of hypothyroidism; each had been treated with a greater dose than the above. The occurrence of hynofunction in cases treated with a dose greater than the above is compared statistically with cases treated with smaller doses. A number of examples are discussed.

SU-E-J-113: The Influence of Optimizing Pediatric CT Simulator Protocols On the Treatment Dose Calculation in Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Y; Zhang, J; Hu, Q

2014-06-01

Purpose: To investigate the possibility of applying optimized scanning protocols for pediatric CT simulation by quantifying the dosimetric inaccuracy introduced by using a fixed HU to density conversion. Methods: The images of a CIRS electron density reference phantom (Model 062) were acquired by a Siemens CT simulator (Sensation Open) using the following settings of tube voltage and beam current: 120 kV/190mA (the reference protocol used to calibrate CT for our treatment planning system (TPS)); Fixed 190mA combined with all available kV: 80, 100, and 140; fixed 120 kV and various current from 37 to 444 mA (scanner extremes) with intervalmore » of 30 mA. To avoid the HU uncertainty of point sampling in the various inserts of known electron densities, the mean CT numbers of the central cylindrical volume were calculated using DICOMan software. The doses per 100 MU to the reference point (SAD=100cm, Depth=10cm, Field=10X10cm, 6MV photon beam) in a virtual cubic phantom (30X30X30cm) were calculated using Eclipse TPS (calculation model: AcurosXB-11031) by assigning the CT numbers to HU of typical materials acquired by various protocols. Results: For the inserts of densities less than muscle, CT number fluctuations of all protocols were within the tolerance of 10 HU as accepted by AAPM-TG66. For more condensed materials, fixed kV yielded stable HU with any mA combination where largest disparities were found in 1750mg/cc insert: HU{sub reference}=1801(106.6cGy), HU{sub minimum}=1799 (106.6cGy, error{sub dose}=0.00%), HU{sub maximum}=1815 (106.8cGy, error{sub dose}=0.19%). Yet greater disagreements were observed with increasing density when kV was modified: HU{sub minimum}=1646 (104.5cGy, error{sub dose}=- 1.97%), HU{sub maximum}=2487 (116.4cGy, error{sub dose}=9.19%) in 1750mg/cc insert. Conclusion: Without affecting treatment dose calculation, personalized mA optimization of CT simulator can be conducted by fixing kV for a better cost-effectiveness of imaging dose and quality especially for children. Unless recalibrated, kV should be constant for all anatomical sites if diagnostic CT scanner is used as a simulator. This work was partially supported by Capital Medical Development Scientific Research Fund of China.« less

NOTE: Reducing the number of segments in unidirectional MLC segmentations

NASA Astrophysics Data System (ADS)

Mellado, X.; Cruz, S.; Artacho, J. M.; Canellas, M.

2010-02-01

In intensity-modulated radiation therapy (IMRT), fluence matrices obtained from a treatment planning system are usually delivered by a linear accelerator equipped with a multileaf collimator (MLC). A segmentation method is needed for decomposing these fluence matrices into segments suitable for the MLC, and the number of segments used is an important factor for treatment time. In this work, an algorithm for reduction of the number of segments (NS) is presented for unidirectional segmentations, where there is no backtracking of the MLC leaves. It uses a geometrical representation of the segmentation output for searching the key values in a fluence matrix that complicate its decomposition. The NS reduction is achieved by performing minor modifications in these values, under the conditions of avoiding substantial modifications of the dose-volume histogram, and does not increase in average the total number of monitor units delivered. The proposed method was tested using two clinical cases planned with the PCRT 3D® treatment planning system.

Comparison of four commercial devices for RapidArc and sliding window IMRT QA

PubMed Central

Chandraraj, Varatharaj; Manickam, Ravikumar; Esquivel, Carlos; Supe, Sanjay S.; Papanikolaou, Nikos

2011-01-01

For intensity‐modulated radiation therapy, evaluation of the measured dose against the treatment planning calculated dose is essential in the context of patient‐specific quality assurance. The complexity of volumetric arc radiotherapy delivery attributed to its dynamic and synchronization nature require new methods and potentially new tools for the quality assurance of such techniques. In the present study, we evaluated and compared the dosimetric performance of EDR2 film and three other commercially available quality assurance devices: IBA I'MatriXX array, PTW Seven29 array and the Delta 4 array. The evaluation of these dosimetric systems was performed for RapidArc and IMRT deliveries using a Varian NovalisTX linear accelerator. The plans were generated using the Varian Eclipse treatment planning system. Our results showed that all four QA techniques yield equivalent results. All patient QAs passed our institutional clinical criteria of gamma index based on a 3% dose difference and 3 mm distance to agreement. In addition, the Bland‐Altman analysis was performed which showed that all the calculated gamma values of all three QA devices were within 5% from those of the film. The results showed that the four QA systems used in this patient‐specific IMRT QA analysis are equivalent. We concluded that the dosimetric systems under investigation can be used interchangeably for routine patient specific QA. PACS numbers: 87.55.Qr, 87.56.Fc

In vivo tumor targeting of gold nanoparticles: effect of particle type and dosing strategy.

PubMed

Puvanakrishnan, Priyaveena; Park, Jaesook; Chatterjee, Deyali; Krishnan, Sunil; Tunnell, James W

2012-01-01

Gold nanoparticles (GNPs) have gained significant interest as nanovectors for combined imaging and photothermal therapy of tumors. Delivered systemically, GNPs preferentially accumulate at the tumor site via the enhanced permeability and retention effect, and when irradiated with near infrared light, produce sufficient heat to treat tumor tissue. The efficacy of this process strongly depends on the targeting ability of the GNPs, which is a function of the particle's geometric properties (eg, size) and dosing strategy (eg, number and amount of injections). The purpose of this study was to investigate the effect of GNP type and dosing strategy on in vivo tumor targeting. Specifically, we investigated the in vivo tumor-targeting efficiency of pegylated gold nanoshells (GNSs) and gold nanorods (GNRs) for single and multiple dosing. We used Swiss nu/nu mice with a subcutaneous tumor xenograft model that received intravenous administration for a single and multiple doses of GNS and GNR. We performed neutron activation analysis to quantify the gold present in the tumor and liver. We performed histology to determine if there was acute toxicity as a result of multiple dosing. Neutron activation analysis results showed that the smaller GNRs accumulated in higher concentrations in the tumor compared to the larger GNSs. We observed a significant increase in GNS and GNR accumulation in the liver for higher doses. However, multiple doses increased targeting efficiency with minimal effect beyond three doses of GNPs. These results suggest a significant effect of particle type and multiple doses on increasing particle accumulation and on tumor targeting ability.

Radiobiology of the acute radiation syndrome.

PubMed

Macià I Garau, Miquel; Lucas Calduch, Anna; López, Enric Casanovas

2011-07-06

ACUTE RADIATION SYNDROME OR ACUTE RADIATION SICKNESS IS CLASSICALLY SUBDIVIDED INTO THREE SUBSYNDROMES: the hematopoietic, gastrointestinal and neurovascular syndrome but many other tissues can be damaged. The time course and severity of clinical signs and symptoms are a function of the overall body volume irradiated, the inhomogeneity of dose exposure, the particle type, the absorbed dose and the dose rate. Classical pathophysiology explain the failure of each of these organs and the timing of appearance of their signs and symptoms due to radiation-induced cytocidal effects of a great number of parenchymal cells of hierarchically organized tissues. Contemporaneously, many other radiation-induced effects has been described and all of them may lead to tissue injury with their corresponding signs and symptoms that can be expressed after short or long period of time. Radiation-induced multi-organ involvement is thought to be due to radiation-induced systemic inflammatory response mediated by released pro-inflammatory cytokines.

Exercise, Insulin Absorption Rates, and Artificial Pancreas Control

NASA Astrophysics Data System (ADS)

Frank, Spencer; Hinshaw, Ling; Basu, Rita; Basu, Ananda; Szeri, Andrew J.

2016-11-01

Type 1 Diabetes is characterized by an inability of a person to endogenously produce the hormone insulin. Because of this, insulin must be injected - usually subcutaneously. The size of the injected dose and the rate at which the dose reaches the circulatory system have a profound effect on the ability to control glucose excursions, and therefore control of diabetes. However, insulin absorption rates via subcutaneous injection are variable and depend on a number of factors including tissue perfusion, physical activity (vasodilation, increased capillary throughput), and other tissue geometric and physical properties. Exercise may also have a sizeable effect on the rate of insulin absorption, which can potentially lead to dangerous glucose levels. Insulin-dosing algorithms, as implemented in an artificial pancreas controller, should account accurately for absorption rate variability and exercise effects on insulin absorption. The aforementioned factors affecting insulin absorption will be discussed within the context of both fluid mechanics and data driven modeling approaches.

Responses to fertility treatment among patients with cancer: a retrospective cohort study.

PubMed

Dolinko, A V; Farland, L V; Missmer, S A; Srouji, S S; Racowsky, C; Ginsburg, E S

2018-01-01

Cancer treatments have significant negative impacts on female fertility, but the impact of cancer itself on fertility remains to be clarified. While some studies have shown that compared with healthy women, those with cancer require higher doses of gonadotropins resulting in decreased oocyte yields, others have shown comparable oocyte yields between the two groups. The purpose of this study is to evaluate whether there is an association between any cancer and/or type of cancer, and response to ovarian stimulation for egg and embryo banking. In this retrospective cohort study, ovarian stimulation cycles performed from June 2007 through October 2014 at a single academic medical center were reviewed to identify those undertaken for women with cancer undergoing fertility preservation ( n  = 147) or women with no cancer undergoing their first cycle due to male factor infertility ( n  = 664). Of the 147 women undergoing fertility preservation, 105 had local cancer (Stage I-III solid malignancies) and 42 had systemic cancer (hematologic or Stage IV solid malignancies). Response to ovarian stimulation was compared among these two groups and women with no cancer. Adjusting for age and BMI, women with systemic cancer had lower baseline antral follicle counts (AFC) than women with no cancer or local cancer. Women with systemic cancer required higher doses of FSH than women with no cancer or local cancer, and they had higher oocyte to AFC ratios than women with no cancer or local cancer, but greater odds of cycle cancellation as compared to women with no cancer or local cancer. No significant differences were observed among the three groups for duration of stimulation, number of oocytes and mature oocytes retrieved, or number of embryos created. Women with cancer achieve similar oocyte and embryo yields as women with no cancer, although those with systemic cancer require higher FSH doses and are at greater risk of cycle cancellation.

SU-F-T-443: Quantification of Dosimetric Effects of Dental Metallic Implant On VMAT Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, C; Jiang, W; Feng, Y

Purpose: To evaluate the dosimetric impact of metallic implant that correlates with the size of targets and metallic implants and distance in between on volumetric-modulated arc therapy (VMAT) plans for head and neck (H&N) cancer patients with dental metallic implant. Methods: CT images of H&N cancer patients with dental metallic implant were used. Target volumes with different sizes and locations were contoured. Metal artifact regions excluding surrounding critical organs were outlined and assigned with CT numbers close to water (0HU). VMAT plans with half-arc, one-full-arc and two-full-arcs were constructed and same plans were applied to structure sets with and withoutmore » CT number assignment of metal artifact regions and compared. D95% was utilized to investigate PTV dose coverage and SNC Patient− Software was used for the analysis of dose distribution difference slice by slice. Results: For different targets sizes, variation of PTV dose coverage (Delta-D95%) with and without CT number replacement reduced with larger target volume for all half-arc, one-arc and two-arc VMAT plans even though there were no clinically significant differences. Additionally, there were no significant variations of the maximum percent difference (max.%diff) of dose distribution. With regard to the target location, Delta-D95% and max. %diff dropped with increasing distance between target and metallic implant. Furthermore, half-arc plans showed greater impact than one-arc plans, and two-arc plans had smallest influence for PTV dose coverage and dose distribution. Conclusion: The target size has less correlation of doseimetric impact than the target location relative to metallic implants. Plans with more arcs alleviate the dosimetric effect of metal artifact because of less contribution to the target dose from beams going through the regions with metallic artifacts. Incorrect CT number causes inaccurate dose distribution, therefore appropriately overwriting metallic artifact regions with reasonable CT numbers is recommended. More patient data are collected and under further analysis.« less

Seeking Beta: Experimental Considerations and Theoretical Implications Regarding the Detection of Curvature in Dose-Response Relationships for Chromosome Aberrations.

PubMed

Shuryak, Igor; Loucas, Bradford D; Cornforth, Michael N

2017-01-01

The concept of curvature in dose-response relationships figures prominently in radiation biology, encompassing a wide range of interests including radiation protection, radiotherapy and fundamental models of radiation action. In this context, the ability to detect even small amounts of curvature becomes important. Standard (ST) statistical approaches used for this purpose typically involve least-squares regression, followed by a test on sums of squares. Because we have found that these methods are not particularly robust, we investigated an alternative information theoretic (IT) approach, which involves Poisson regression followed by information-theoretic model selection. Our first objective was to compare the performances of the ST and IT methods by using them to analyze mFISH data on gamma-ray-induced simple interchanges in human lymphocytes, and on Monte Carlo simulated data. Real and simulated data sets that contained small-to-moderate curvature were deliberately selected for this exercise. The IT method tended to detect curvature with higher confidence than the ST method. The finding of curvature in the dose response for true simple interchanges is discussed in the context of fundamental models of radiation action. Our second objective was to optimize the design of experiments aimed specifically at detecting curvature. We used Monte Carlo simulation to investigate the following parameters. Constrained by available resources (i.e., the total number of cells to be scored) these include: the optimal number of dose points to use; the best way to apportion the total number of cells among these dose points; and the spacing of dose intervals. Counterintuitively, our simulation results suggest that 4-5 radiation doses were typically optimal, whereas adding more dose points may actually prove detrimental. Superior results were also obtained by implementing unequal dose spacing and unequal distributions in the number of cells scored at each dose.

SU-E-I-58: Experiences in Setting Up An Online Fluoroscopy Tracking System in a Large Healthcare System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisher, R; Wunderle, K; Lingenfelter, M

Purpose: Transitioning from a paper based to an online system for tracking fluoroscopic case information required by state regulation and to conform to NCRP patient dose tracking suggestions. Methods: State regulations require documentation of operator, equipment, and some metric of tube output for fluoroscopy exams. This information was previously collected in paper logs, which was cumbersome and inefficient for the large number of fluoroscopic units across multiple locations within the system. The “tech notes” feature within Siemens’ Syngo workflow RIS was utilized to create an entry form for technologists to input case information, which was sent to a third partymore » vendor for archiving and display though an online web based portal. Results: Over 55k cases were logged in the first year of implementation, with approximately 6,500 cases per month once fully online. A system was built for area managers to oversee and correct data, which has increased the accuracy of inputted values. A high-dose report was built to automatically send notifications when patients exceed trigger levels. In addition to meeting regulatory requirements, the new system allows for larger scale QC in fluoroscopic cases by allowing comparison of data from specific procedures, locations, equipment, and operators so that instances that fall outside of reference levels can be identified for further evaluation. The system has also drastically improved identification of operators without documented equipment specific training. Conclusion: The transition to online fluoroscopy logs has improved efficiency in meeting state regulatory requirements as well as allowed for identification of particular procedures, equipment, and operators in need of additional attention in order to optimize patient and personnel doses, while high dose alerts improve patient care and follow up. Future efforts are focused on incorporating case information from outside of radiology, as well as on automating processes for increased efficiencies.« less

A Model for Precise and Uniform Pelvic- and Limb-Sparing Abdominal Irradiation to Study the Radiation-Induced Gastrointestinal Syndrome in Mice Using Small Animal Irradiation Systems.

PubMed

Brodin, N Patrik; Velcich, Anna; Guha, Chandan; Tomé, Wolfgang A

2017-01-01

Currently, no readily available mitigators exist for acute abdominal radiation injury. Here, we present an animal model for precise and homogenous limb-sparing abdominal irradiation (LSAIR) to study the radiation-induced gastrointestinal syndrome (RIGS). The LSAIR technique was developed using the small animal radiation research platform (SARRP) with image guidance capabilities. We delivered LSAIR at doses between 14 and 18 Gy on 8- to 10-week-old male C57BL/6 mice. Histological analysis was performed to confirm that the observed mortality was due to acute abdominal radiation injury. A steep dose-response relationship was found for survival, with no deaths seen at doses below 16 Gy and 100% mortality at above 17 Gy. All deaths occurred between 6 and 10 days after irradiation, consistent with the onset of RIGS. This was further confirmed by histological analysis showing clear differences in the number of regenerative intestinal crypts between animals receiving sublethal (14 Gy) and 100% lethal (18 Gy) radiation. The developed LSAIR technique provides uniform dose delivery with a clear dose response, consistent with acute abdominal radiation injury on histological examination. This model can provide a useful tool for researchers investigating the development of mitigators for accidental or clinical high-dose abdominal irradiation.

Photo-activated disinfection based on indocyanine green against cell viability and biofilm formation of Porphyromonas gingivalis.

PubMed

Pourhajibagher, Maryam; Chiniforush, Nasim; Ghorbanzadeh, Roghayeh; Bahador, Abbas

2017-03-01

Photo-activated disinfection (PAD) is a novel treatment approach, in which bacteria in the root canal system may be exposed to sub-lethal doses of PAD. Such exposure can affect bacterial survival and virulence features, such as biofilm formation ability. The aim of this study was to evaluate the effects of sub-lethal doses of PAD (sPAD) using indocyanine green (ICG) on load and biofilm formation ability of Porphyromonas gingivalis as an anaerobic bacterium associated with endodontic infection. The anti-bacterial and anti-biofilm potential of sPAD against P. gingivalis at sub-lethal doses of ICG as a photosensitizer and using 810nm wavelength of diode laser light via colony forming unit and crystal violet assays, respectively, was determined. High concentrations of ICG and light irradiation time significantly reduced bacteria. High doses of sPAD markedly reduced the number of bacteria and the formation of biofilm, up to 30.4% and 25.1%, respectively. High doses of sPAD affected cell viability and the biofilm formation ability of P. gingivalis; lower doses did not. Thus, selection of appropriate PAD dosage should be considered for the successful treatment of endodontic in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion.

PubMed

Min, Yugang; Santhanam, Anand; Neelakkantan, Harini; Ruddy, Bari H; Meeks, Sanford L; Kupelian, Patrick A

2010-09-07

In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan

NASA Astrophysics Data System (ADS)

Inaniwa, Taku; Kanematsu, Nobuyuki; Matsufuji, Naruhiro; Kanai, Tatsuaki; Shirai, Toshiyuki; Noda, Koji; Tsuji, Hiroshi; Kamada, Tadashi; Tsujii, Hirohiko

2015-04-01

At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy-1 and β = 0.0615 Gy-2 as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both physical and clinical dose distributions were compared with regard to the prescribed dose level, beam energy, and SOBP width. Both systems provided uniform clinical dose distributions within the targets consistent with the prescriptions. The mean physical doses delivered to targets by the updated system agreed with the doses by the original system within ±1.5% for all tested conditions. The updated system reflects the physical and biological characteristics of the therapeutic C-ion beam more accurately than the original system, while at the same time allowing the continued use of the dose-fractionation protocols established with the original system at NIRS.

Assessment of the dose distribution inside a cardiac cath lab using TLD measurements and Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Baptista, M.; Teles, P.; Cardoso, G.; Vaz, P.

2014-11-01

Over the last decade, there was a substantial increase in the number of interventional cardiology procedures worldwide, and the corresponding ionizing radiation doses for both the medical staff and patients became a subject of concern. Interventional procedures in cardiology are normally very complex, resulting in long exposure times. Also, these interventions require the operator to work near the patient and, consequently, close to the primary X-ray beam. Moreover, due to the scattered radiation from the patient and the equipment, the medical staff is also exposed to a non-uniform radiation field that can lead to a significant exposure of sensitive body organs and tissues, such as the eye lens, the thyroid and the extremities. In order to better understand the spatial variation of the dose and dose rate distributions during an interventional cardiology procedure, the dose distribution around a C-arm fluoroscopic system, in operation in a cardiac cath lab at Portuguese Hospital, was estimated using both Monte Carlo (MC) simulations and dosimetric measurements. To model and simulate the cardiac cath lab, including the fluoroscopic equipment used to execute interventional procedures, the state-of-the-art MC radiation transport code MCNPX 2.7.0 was used. Subsequently, Thermo-Luminescent Detector (TLD) measurements were performed, in order to validate and support the simulation results obtained for the cath lab model. The preliminary results presented in this study reveal that the cardiac cath lab model was successfully validated, taking into account the good agreement between MC calculations and TLD measurements. The simulated results for the isodose curves related to the C-arm fluoroscopic system are also consistent with the dosimetric information provided by the equipment manufacturer (Siemens). The adequacy of the implemented computational model used to simulate complex procedures and map dose distributions around the operator and the medical staff is discussed, in view of the optimization principle (and the associated ALARA objective), one of the pillars of the international system of radiological protection.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qu, H; Yu, N; Qi, P

Purpose: In commercial secondary dose calculation system, an average effective depth is used to calculate the Monitor Units for an arc beam from the volumetric modulated arc (VMAT) plans. Typically, an arithmetic mean of the effective depths (AMED) of a VMAT arc beam is used, which may result in large MU discrepancy from that of the primary treatment planning system. This study is to demonstrate the use of a dose weighted mean effective depth (DWED) can improve accuracy of MU calculation for the secondary MU verification. Methods: In-house scripts were written in the primary treatment planning system (TPS) to firstmore » convert a VMAT arc beam to a series of static step & shoot beams (every 4 degree). The computed dose and effective depth of each static beam were then used to obtain the dose weighted mean effective depth (DWED) for the VMAT beam. The DWED was used for the secondary MU calculation for VMAT plans. Six lung SBRT VMAT plans, eight head and neck VMAT plans and ten prostate VMAT plans that had > 5% MU deviations (failed MU verification) using the AMED method were recalculated with the DWED. For comparison, same number VMAT plans that had < 5% MU deviations (passed MU verification) using AMED method were also reevaluated with the dose weighted mean effective depth method. Results: For MU verification passed plans, the mean and standard deviation of MU differences between the TPS and the secondary calculation program were 2.2%±1.5% for the AMED and 2.1%±1.7% for the DMED method. For the failed plans, the mean and standard deviation of MU differences of TPS to the secondary calculation program were 9.9%±4.7% and 4.7%±2.6, respectively. Conclusion: The dose weighted mean effective depth improved MU calculation accuracy which can be used for the pre-treatment MU verification of VMAT plans.« less

SU-F-T-115: Uncertainty in the Esophagus Dose in Retrospective Epidemiological Study of Breast Cancer Radiotherapy Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mosher, E; Kim, S; Lee, C

Purpose: Epidemiological studies of second cancer risks in breast cancer radiotherapy patients often use generic patient anatomy to reconstruct normal tissue doses when CT images of patients are not available. To evaluate the uncertainty involved in the dosimetry approach, we evaluated the esophagus dose in five sample patients by simulating breast cancer treatments. Methods: We obtained the diagnostic CT images of five anonymized adult female patients in different Body Mass Index (BMI) categories (16– 36kg/m2) from National Institutes of Health Clinical Center. We contoured the esophagus on the CT images and imported them into a Treatment Planning System (TPS) tomore » create treatment plans and calculate esophagus doses. Esophagus dose was calculated once again via experimentally-validated Monte Carlo (MC) transport code, XVMC under the same geometries. We compared the esophagus doses from TPS and the MC method. We also investigated the degree of variation in the esophagus dose across the five patients and also the relationship between the patient characteristics and the esophagus doses. Results: Eclipse TPS using Analytical Anisotropic Algorithm (AAA) significantly underestimates the esophagus dose in breast cancer radiotherapy compared to MC. In the worst case, the esophagus dose from AAA was only 40% of the MC dose. The Coefficient of Variation across the patients was 48%. We found that the maximum esophagus dose was up to 2.7 times greater than the minimum. We finally observed linear relationship (Dose = 0.0218 × BMI – 0.1, R2=0.54) between patient’s BMI and the esophagus doses. Conclusion: We quantified the degree of uncertainty in the esophagus dose in five sample breast radiotherapy patients. The results of the study underscore the importance of individualized dose reconstruction for the study cohort to avoid misclassification in the risk analysis of second cancer. We are currently extending the number of patients up to 30.« less

AAV5-Factor VIII Gene Transfer in Severe Hemophilia A.

PubMed

Rangarajan, Savita; Walsh, Liron; Lester, Will; Perry, David; Madan, Bella; Laffan, Michael; Yu, Hua; Vettermann, Christian; Pierce, Glenn F; Wong, Wing Y; Pasi, K John

2017-12-28

Patients with hemophilia A rely on exogenous factor VIII to prevent bleeding in joints, soft tissue, and the central nervous system. Although successful gene transfer has been reported in patients with hemophilia B, the large size of the factor VIII coding region has precluded improved outcomes with gene therapy in patients with hemophilia A. We infused a single intravenous dose of a codon-optimized adeno-associated virus serotype 5 (AAV5) vector encoding a B-domain-deleted human factor VIII (AAV5-hFVIII-SQ) in nine men with severe hemophilia A. Participants were enrolled sequentially into one of three dose cohorts (low dose [one participant], intermediate dose [one participant], and high dose [seven participants]) and were followed through 52 weeks. Factor VIII activity levels remained at 3 IU or less per deciliter in the recipients of the low or intermediate dose. In the high-dose cohort, the factor VIII activity level was more than 5 IU per deciliter between weeks 2 and 9 after gene transfer in all seven participants, and the level in six participants increased to a normal value (>50 IU per deciliter) that was maintained at 1 year after receipt of the dose. In the high-dose cohort, the median annualized bleeding rate among participants who had previously received prophylactic therapy decreased from 16 events before the study to 1 event after gene transfer, and factor VIII use for participant-reported bleeding ceased in all the participants in this cohort by week 22. The primary adverse event was an elevation in the serum alanine aminotransferase level to 1.5 times the upper limit of the normal range or less. Progression of preexisting chronic arthropathy in one participant was the only serious adverse event. No neutralizing antibodies to factor VIII were detected. The infusion of AAV5-hFVIII-SQ was associated with the sustained normalization of factor VIII activity level over a period of 1 year in six of seven participants who received a high dose, with stabilization of hemostasis and a profound reduction in factor VIII use in all seven participants. In this small study, no safety events were noted, but no safety conclusions can be drawn. (Funded by BioMarin Pharmaceutical; ClinicalTrials.gov number, NCT02576795 ; EudraCT number, 2014-003880-38 .).

Comparison of peripheral and central effects of single and repeated oral dose administrations of bilastine, a new H1 antihistamine: a dose-range study in healthy volunteers with hydroxyzine and placebo as control treatments.

PubMed

García-Gea, Consuelo; Martínez-Colomer, Joan; Antonijoan, Rosa M; Valiente, Román; Barbanoj, Manuel-José

2008-12-01

Peripheral anti-H1 and central nervous system (CNS) activities after single (day 1) and repeated (day 7) administrations of increasing doses of bilastine (BIL) were assessed in 20 healthy volunteers throughout a crossover, randomized, double-blind, placebo (PLA)-controlled study. Repeated doses of BIL 20, 40, or 80 mg and hydroxyzine 25 mg (HYD) as positive standard were administered on 7 consecutive days. Before and at several time points after drug intake, skin reactivity to the intradermal injection of histamine, objective tests of psychomotor performance, and subjective mood scales were evaluated. All active treatments led to a significant and similar reduction in the wheal reaction in relation to PLA after both the single (P < 0.001) and repeated administrations (P < 0.001). No delay was observed in the onset of its peripheral activity after the first dose of BIL as compared with HYD. No tolerance or sensitization was seen when comparing acute and repetitive assessments. Central nervous system effects showed that HYD induced the greatest psychomotor impairment (P < 0.05). Repeated HYD intake showed a lower number of significant alterations in comparison to acute administration. Bilastine 80 mg also showed some impairment (P < 0.05). Subjectively, the only active treatment that could not be differentiated from PLA was BIL 20 mg. Hydroxyzine 25 mg showed the greatest differentiation (P < 0.01). A clear dissociation between peripheral anti-H1 and CNS activity was found after BIL treatment. Significant and sustained peripheral H1-blocking effects were observed after both single and repeated administrations of the therapeutic dose of 20 mg BIL. The 40-mg dose of BIL produced subjective report of sedation, whereas unwanted objective CNS side effects were observed only with the 80-mg dose.

75 FR 25279 - Device Improvements to Reduce the Number of Under-Doses, Over-Doses, and Misaligned Exposures...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-07

... obtain information on a number of questions regarding steps manufacturers of radiation therapy devices... on this topic and requests comments on a number of related questions. Date and Time: The public meeting will be held on June 9 and 10, 2010, from 8 a.m. to 5 p.m. Location: The public meeting will be...

Evaluation of Gafchromic EBT-XD film, with comparison to EBT3 film, and application in high dose radiotherapy verification.

PubMed

Palmer, Antony L; Dimitriadis, Alexis; Nisbet, Andrew; Clark, Catharine H

2015-11-21

There is renewed interest in film dosimetry for the verification of dose delivery of complex treatments, particularly small fields, compared to treatment planning system calculations. A new radiochromic film, Gafchromic EBT-XD, is available for high-dose treatment verification and we present the first published evaluation of its use. We evaluate the new film for MV photon dosimetry, including calibration curves, performance with single- and triple-channel dosimetry, and comparison to existing EBT3 film. In the verification of a typical 25 Gy stereotactic radiotherapy (SRS) treatment, compared to TPS planned dose distribution, excellent agreement was seen with EBT-XD using triple-channel dosimetry, in isodose overlay, maximum 1.0 mm difference over 200-2400 cGy, and gamma evaluation, mean passing rate 97% at 3% locally-normalised, 1.5 mm criteria. In comparison to EBT3, EBT-XD gave improved evaluation results for the SRS-plan, had improved calibration curve gradients at high doses, and had reduced lateral scanner effect. The dimensions of the two films are identical. The optical density of EBT-XD is lower than EBT3 for the same dose. The effective atomic number for both may be considered water-equivalent in MV radiotherapy. We have validated the use of EBT-XD for high-dose, small-field radiotherapy, for routine QC and a forthcoming multi-centre SRS dosimetry intercomparison.

Evaluation of Gafchromic EBT-XD film, with comparison to EBT3 film, and application in high dose radiotherapy verification

NASA Astrophysics Data System (ADS)

Palmer, Antony L.; Dimitriadis, Alexis; Nisbet, Andrew; Clark, Catharine H.

2015-11-01

There is renewed interest in film dosimetry for the verification of dose delivery of complex treatments, particularly small fields, compared to treatment planning system calculations. A new radiochromic film, Gafchromic EBT-XD, is available for high-dose treatment verification and we present the first published evaluation of its use. We evaluate the new film for MV photon dosimetry, including calibration curves, performance with single- and triple-channel dosimetry, and comparison to existing EBT3 film. In the verification of a typical 25 Gy stereotactic radiotherapy (SRS) treatment, compared to TPS planned dose distribution, excellent agreement was seen with EBT-XD using triple-channel dosimetry, in isodose overlay, maximum 1.0 mm difference over 200-2400 cGy, and gamma evaluation, mean passing rate 97% at 3% locally-normalised, 1.5 mm criteria. In comparison to EBT3, EBT-XD gave improved evaluation results for the SRS-plan, had improved calibration curve gradients at high doses, and had reduced lateral scanner effect. The dimensions of the two films are identical. The optical density of EBT-XD is lower than EBT3 for the same dose. The effective atomic number for both may be considered water-equivalent in MV radiotherapy. We have validated the use of EBT-XD for high-dose, small-field radiotherapy, for routine QC and a forthcoming multi-centre SRS dosimetry intercomparison.

In Vivo Differentiation of Uric Acid Versus Non-Uric Acid Urinary Calculi With Third-Generation Dual-Source Dual-Energy CT at Reduced Radiation Dose.

PubMed

Franken, Axelle; Gevenois, Pierre Alain; Muylem, Alain Van; Howarth, Nigel; Keyzer, Caroline

2018-02-01

The objective of our study was to evaluate in vivo urinary calculus characterization with third-generation dual-source dual-energy CT (DECT) at reduced versus standard radiation dose. One hundred fifty-three patients requiring unenhanced CT for suspected or known urolithiasis were prospectively included in our study. They underwent two acquisitions at reduced-dose CT (90 kV and 50 mAs ref ; Sn150 kV and 31 mAs ref , where Sn denotes the interposition of a tin filter in the high-energy beam) and standard-dose CT (90 kV and 50 mAs ref ; Sn150 kV and 94 mAs ref ). One radiologist interpreted the reduced-dose examinations before the standard-dose examinations during the same session. Among 103 patients (23 women, 80 men; mean age ± SD, 50 ± 15 years; age range, 18-82 years) with urolithiasis, dedicated DECT software measured the maximal diameter and CT numbers, calculated the DECT number ratio, and labeled with a color code each calculus visualized by the radiologist as uric acid (UA) or non-UA. Volume CT dose index (CTDI vol ) and dose-length product (DLP) were recorded. The radiologist visualized 279 calculi on standard-dose CT and 262 on reduced-dose CT; 17 calculi were missed on reduced-dose CT, all of which were ≤ 3 mm. Among the 262 calculi visualized at both doses, the CT number ratio was obtained with the software for 227 calculi and was not different between the doses (p = 0.093). Among these 262 calculi, 197 were labeled at both doses; 194 of the 197 labeled calculi were labeled with the same color code. Among the 65 remaining calculi, 48 and 61 (all ≤ 5 mm) were not labeled at standard-dose and reduced-dose CT (p = 0.005), respectively. At reduced-dose CT, the mean CTDI vol was 2.67 mGy and the mean DLP was 102.2 mGy × cm. With third-generation dual-source DECT, a larger proportion of calculi ≤ 5 mm are not characterized as UA or non-UA at a reduced dose.

The usefulness of sLORETA in evaluating the effect of high-dose ARA-C on brain connectivity in patients with acute myeloid leukemia: an exploratory study

PubMed Central

Zarabla, Alessia; Ungania, Sara; Cacciatore, Alessandra; Maialetti, Andrea; Petreri, Gianluca; Mengarelli, Andrea; Spadea, Antonio; Marchesi, Francesco; Renzi, Daniela; Gumenyuk, Svitlana; Strigari, Lidia; Maschio, Marta

2017-01-01

Summary Cytosine arabinoside (Ara-C) is one of the key drugs for treating acute myeloid leukemia (AML). High intravenous doses may produce a number of central nervous system (CNS) toxicities and contribute to modifications in brain functional connectivity. sLORETA is a software used for localizing brain electrical activity and functional connectivity. The aim of this study was to apply sLORETA in the evaluation of possible effects of Ara-C on brain connectivity in patients with AML without CNS involvement. We studied eight patients with AML; four were administered standard doses of Ara-C while the other four received high doses. sLORETA was computed from computerized EEG data before treatment and after six months of treatment. Three regions of interest, corresponding to specific combinations of Brodmann areas, were defined. In the patients receiving high-dose Ara-C, a statistically significant reduction in functional connectivity was observed in the frontoparietal network, which literature data suggest is involved in attentional processes. Our data highlight the possibility of using novel techniques to study potential CNS toxicity of cancer therapy.

Cell-based dose responses from open-well microchambers.

PubMed

Hamon, Morgan; Jambovane, Sachin; Bradley, Lauren; Khademhosseini, Ali; Hong, Jong Wook

2013-05-21

Cell-based assays play a critical role in discovery of new drugs and facilitating research in cancer, immunology, and stem cells. Conventionally, they are performed in Petri dishes, tubes, or well plates, using milliliters of reagents and thousands of cells to obtain one data point. Here, we are introducing a new platform to realize cell-based assay capable of increased throughput and greater sensitivity with a limited number of cells. We integrated an array of open-well microchambers into a gradient generation system. Consequently, cell-based dose responses were examined with a single device. We measured IC50 values of three cytotoxic chemicals, Triton X-100, H2O2, and cadmium chloride, as model compounds. The present system is highly suitable for the discovery of new drugs and studying the effect of chemicals on cell viability or mortality with limited samples and cells.

Protective effects of amphetamine on gastric ulcerations induced by indomethacin in rats

PubMed Central

Sandor, Vlaicu; Cuparencu, Barbu; Dumitrascu, Dan L; Birt, Mircea A; Krausz, Tibor L

2006-01-01

AIM: To study the effects of amphetamine, an indirect-acting adrenomimetic compound on the indomethacin-induced gastric ulcerations in rats. METHODS: Male Wistar-Bratislava rats were randomly divided into four groups: Group 1 (control), received an ulcerogenic dose of indomethacin (50 μmol/kg) and Groups 2, 3 and 4, treated with amphetamine (10, 25 and 50 μmol/kg). The drug was administered simultaneously with indomethacin and once again 4 h later. The animals were sacrificed 8 h after indomethacin treatment. The stomachs were opened and the incidence, the number of lesions and their severity were evaluated. The results were expressed as percentage and as mean ± standard error (mean ± SE). RESULTS: The incidence of ulceration in the control group was 100%. Amphetamine, at doses of 10, 25 and 50 μmol/kg, lowered the incidence to 88.89%, 77.78% and 37.5% respectively. The protection ratio was positive: 24.14%, 55.17% and 80.6% respectively. The total number of ulcerations/rat was 12.44 ± 3.69 in the control group. It decreased to 7.33 ± 1.89, 5.33 ± 2.38 and 2.25 ± 1.97 under the effects of the above-mentioned doses of amphetamine. CONCLUSION: Amphetamine affords a significant dose-dependent protection against the indomethacin-induced gastric ulcerations in rats. It is suggested that the adrenergic system is involved in the gastric mucosa protection. PMID:17131481

DNA microarray unravels rapid changes in transcriptome of MK-801 treated rat brain

PubMed Central

Kobayashi, Yuka; Kulikova, Sofya P; Shibato, Junko; Rakwal, Randeep; Satoh, Hiroyuki; Pinault, Didier; Masuo, Yoshinori

2015-01-01

AIM: To investigate the impact of MK-801 on gene expression patterns genome wide in rat brain regions. METHODS: Rats were treated with an intraperitoneal injection of MK-801 [0.08 (low-dose) and 0.16 (high-dose) mg/kg] or NaCl (vehicle control). In a first series of experiment, the frontoparietal electrocorticogram was recorded 15 min before and 60 min after injection. In a second series of experiments, the whole brain of each animal was rapidly removed at 40 min post-injection, and different regions were separated: amygdala, cerebral cortex, hippocampus, hypothalamus, midbrain and ventral striatum on ice followed by DNA microarray (4 × 44 K whole rat genome chip) analysis. RESULTS: Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline gamma frequency (30-80 Hz) oscillations in the frontoparietal electroencephalogram. DNA microarray analysis showed the largest number (up- and down- regulations) of gene expressions in the cerebral cortex (378), midbrain (376), hippocampus (375), ventral striatum (353), amygdala (301), and hypothalamus (201) under low-dose (0.08 mg/kg) of MK-801. Under high-dose (0.16 mg/kg), ventral striatum (811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region. CONCLUSION: Acute MK-801 treatment increases synchrony of baseline gamma oscillations, and causes very early changes in gene expressions in six individual rat brain regions, a first report. PMID:26629322

Vulnerability assessment of a space based weapon platform electronic system exposed to a thermonuclear weapon detonation

NASA Astrophysics Data System (ADS)

Perez, C. L.; Johnson, J. O.

Rapidly changing world events, the increased number of nations with inter-continental ballistic missile capability, and the proliferation of nuclear weapon technology will increase the number of nuclear threats facing the world today. Monitoring these nation's activities and providing an early warning and/or intercept system via reconnaissance and surveillance satellites and space based weapon platforms is a viable deterrent against a surprise nuclear attack. However, the deployment of satellite and weapon platform assets in space will subject the sensitive electronic equipment to a variety of natural and man-made radiation environments. These include Van Allen Belt protons and electrons; galactic and solar flare protons; and neutrons, gamma rays, and x-rays from intentionally detonated fission and fusion weapons. In this paper, the MASH vl.0 code system is used to estimate the dose to the critical electronics components of an idealized space based weapon platform from neutron and gamma-ray radiation emitted from a thermonuclear weapon detonation in space. Fluence and dose assessments were performed for the platform fully loaded, and in several stages representing limited engagement scenarios. The results indicate vulnerabilities to the Command, Control, and Communication bay instruments from radiation damage for a nuclear weapon detonation for certain source/platform orientations. The distance at which damage occurs will depend on the weapon yield (n,(gamma)/kiloton) and size (kilotons).

Simulation approach for the evaluation of tracking accuracy in radiotherapy: a preliminary study.

PubMed

Tanaka, Rie; Ichikawa, Katsuhiro; Mori, Shinichiro; Sanada, Sigeru

2013-01-01

Real-time tumor tracking in external radiotherapy can be achieved by diagnostic (kV) X-ray imaging with a dynamic flat-panel detector (FPD). It is important to keep the patient dose as low as possible while maintaining tracking accuracy. A simulation approach would be helpful to optimize the imaging conditions. This study was performed to develop a computer simulation platform based on a noise property of the imaging system for the evaluation of tracking accuracy at any noise level. Flat-field images were obtained using a direct-type dynamic FPD, and noise power spectrum (NPS) analysis was performed. The relationship between incident quantum number and pixel value was addressed, and a conversion function was created. The pixel values were converted into a map of quantum number using the conversion function, and the map was then input into the random number generator to simulate image noise. Simulation images were provided at different noise levels by changing the incident quantum numbers. Subsequently, an implanted marker was tracked automatically and the maximum tracking errors were calculated at different noise levels. The results indicated that the maximum tracking error increased with decreasing incident quantum number in flat-field images with an implanted marker. In addition, the range of errors increased with decreasing incident quantum number. The present method could be used to determine the relationship between image noise and tracking accuracy. The results indicated that the simulation approach would aid in determining exposure dose conditions according to the necessary tracking accuracy.

MACROMOLECULAR ADDUCT FORMATION AND METABOLISM OF HETEROCYCLIC AMINES IN HUMANS AND RODENTS AT LOW DOSES. (R825280)

EPA Science Inventory

Abstract

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are heterocyclic amines formed during the cooking of meat and fish. Both are genotoxic in a number of test systems and are carcinogen...

Mineral composition of pulp and production of the yellow passion fruit with organic and conventional fertilizers.

PubMed

Pacheco, Anália Lúcia Vieira; Pagliarini, Mateus Francisco; de Freitas, Gilberto Bernardo; Santos, Ricardo Henrique Silva; Serrão, José Eduardo; Zanuncio, José Cola

2017-02-15

The use of organic foods has been increased in the world. Organic fertilizers, like cattle manure, have emerged as an important component of the organic system production. The production, mass, size, and mineral composition of passion fruit pulp were evaluated when treated with a mineral fertilizer (control) (MIN) or cattle manure at a single dose equivalent to potassium fertilizer (ORG) or double dose (2×ORG). The production and the numbers of fruits of plants treated with MIN and 2×ORG was higher than with ORG. The level of nitrogen (N), phosphorus (P), zinc (Zn), iron (Fe), and copper (Cu) in the fruit pulp was similar with all three fertilizers, but the calcium (Ca) and magnesium (Mg) was higher with ORG and 2×ORG. The number and weight of the fruits of passion fruit treated with 2×ORG were similar to those with MIN fertilizer, but they contained more Ca and Mg. Copyright © 2016 Elsevier Ltd. All rights reserved.

The development of a decision support system with an interactive clinical user interface for estimating treatment parameters in radiation therapy in order to reduce radiation dose in head and neck patients

NASA Astrophysics Data System (ADS)

Verma, Sneha; Liu, Joseph; Deshpande, Ruchi; DeMarco, John; Liu, Brent J.

2017-03-01

The primary goal in radiation therapy is to target the tumor with the maximum possible radiation dose while limiting the radiation exposure of the surrounding healthy tissues. However, in order to achieve an optimized treatment plan, many constraints, such as gender, age, tumor type, location, etc. need to be considered. The location of the malignant tumor with respect to the vital organs is another possible important factor for treatment planning process which can be quantified as a feature making it easier to analyze its effects. Incorporation of such features into the patient's medical history could provide additional knowledge that could lead to better treatment outcomes. To show the value of features such as relative locations of tumors and surrounding organs, the data is first processed in order to calculate the features and formulate a feature matrix. Then these feature are matched with retrospective cases with similar features to provide the clinician with insight on delivered dose in similar cases from past. This process provides a range of doses that can be delivered to the patient while limiting the radiation exposure of surrounding organs based on similar retrospective cases. As the number of patients increase, there will be an increase in computations needed for feature extraction as well as an increase in the workload for the physician to find the perfect dose amount. In order to show how such algorithms can be integrated we designed and developed a system with a streamlined workflow and interface as prototype for the clinician to test and explore. Integration of the tumor location feature with the clinician's experience and training could play a vital role in designing new treatment algorithms and better outcomes. Last year, we presented how multi-institutional data into a decision support system is incorporated. This year the presentation is focused on the interface and demonstration of the working prototype of informatics system.

Impact of Spot Size and Spacing on the Quality of Robustly Optimized Intensity Modulated Proton Therapy Plans for Lung Cancer.

PubMed

Liu, Chenbin; Schild, Steven E; Chang, Joe Y; Liao, Zhongxing; Korte, Shawn; Shen, Jiajian; Ding, Xiaoning; Hu, Yanle; Kang, Yixiu; Keole, Sameer R; Sio, Terence T; Wong, William W; Sahoo, Narayan; Bues, Martin; Liu, Wei

2018-06-01

To investigate how spot size and spacing affect plan quality, robustness, and interplay effects of robustly optimized intensity modulated proton therapy (IMPT) for lung cancer. Two robustly optimized IMPT plans were created for 10 lung cancer patients: first by a large-spot machine with in-air energy-dependent large spot size at isocenter (σ: 6-15 mm) and spacing (1.3 σ), and second by a small-spot machine with in-air energy-dependent small spot size (σ: 2-6 mm) and spacing (5 mm). Both plans were generated by optimizing radiation dose to internal target volume on averaged 4-dimensional computed tomography scans using an in-house-developed IMPT planning system. The dose-volume histograms band method was used to evaluate plan robustness. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effects with randomized starting phases for each field per fraction. Patient anatomy voxels were mapped phase-to-phase via deformable image registration, and doses were scored using in-house-developed software. Dose-volume histogram indices, including internal target volume dose coverage, homogeneity, and organs at risk (OARs) sparing, were compared using the Wilcoxon signed-rank test. Compared with the large-spot machine, the small-spot machine resulted in significantly lower heart and esophagus mean doses, with comparable target dose coverage, homogeneity, and protection of other OARs. Plan robustness was comparable for targets and most OARs. With interplay effects considered, significantly lower heart and esophagus mean doses with comparable target dose coverage and homogeneity were observed using smaller spots. Robust optimization with a small spot-machine significantly improves heart and esophagus sparing, with comparable plan robustness and interplay effects compared with robust optimization with a large-spot machine. A small-spot machine uses a larger number of spots to cover the same tumors compared with a large-spot machine, which gives the planning system more freedom to compensate for the higher sensitivity to uncertainties and interplay effects for lung cancer treatments. Copyright © 2018 Elsevier Inc. All rights reserved.

Bringing influenza vaccines into the 21st century

PubMed Central

Settembre, Ethan C; Dormitzer, Philip R; Rappuoli, Rino

2014-01-01

The recent H7N9 influenza outbreak in China highlights the need for influenza vaccine production systems that are robust and can quickly generate substantial quantities of vaccines that target new strains for pandemic and seasonal immunization. Although the influenza vaccine system, a public-private partnership, has been effective in providing vaccines, there are areas for improvement. Technological advances such as mammalian cell culture production and synthetic vaccine seeds provide a means to increase the speed and accuracy of targeting new influenza strains with mass-produced vaccines by dispensing with the need for egg isolation, adaptation, and reassortment of vaccine viruses. New influenza potency assays that no longer require the time-consuming step of generating sheep antisera could further speed vaccine release. Adjuvants that increase the breadth of the elicited immune response and allow dose sparing provide an additional means to increase the number of available vaccine doses. Together these technologies can improve the influenza vaccination system in the near term. In the longer term, disruptive technologies, such as RNA-based flu vaccines and ‘universal’ flu vaccines, offer a promise of a dramatically improved influenza vaccine system. PMID:24378716

Bringing influenza vaccines into the 21st century.

PubMed

Settembre, Ethan C; Dormitzer, Philip R; Rappuoli, Rino

2014-01-01

The recent H7N9 influenza outbreak in China highlights the need for influenza vaccine production systems that are robust and can quickly generate substantial quantities of vaccines that target new strains for pandemic and seasonal immunization. Although the influenza vaccine system, a public-private partnership, has been effective in providing vaccines, there are areas for improvement. Technological advances such as mammalian cell culture production and synthetic vaccine seeds provide a means to increase the speed and accuracy of targeting new influenza strains with mass-produced vaccines by dispensing with the need for egg isolation, adaptation, and reassortment of vaccine viruses. New influenza potency assays that no longer require the time-consuming step of generating sheep antisera could further speed vaccine release. Adjuvants that increase the breadth of the elicited immune response and allow dose sparing provide an additional means to increase the number of available vaccine doses. Together these technologies can improve the influenza vaccination system in the near term. In the longer term, disruptive technologies, such as RNA-based flu vaccines and 'universal' flu vaccines, offer a promise of a dramatically improved influenza vaccine system.

Using operational equipment to read accident dosemeters.

PubMed

Devine, R T; Vigil, M M; Martinez, W A

2004-01-01

Analysis of accident dosemeters usually involves the use of laboratory-based counting equipment. Gamma spectrometers are used for indium, copper and gold, and alpha-beta detectors for sulphur. This equipment is usually not easily transported due to the shielding required and the weight and delicacy of the counters. For intercomparison studies that require reading the dosemeters on site, a transportable system is required unless the site operating the study can count samples for all the participants. In the case of an actual accident these systems would have a difficulty in counting a large number of accident dosemeters. In an accident, personnel are usually subdivided according to their level of exposure. Those exposed to higher doses are treated immediately. An alternate system should be made available to handle the dosemeters worn by those personnel are likely to receive lower doses. Improvements in portable operational equipment for gamma and beta monitoring allow their use as spectrometers. Such a system was used for the SILENE intercomparison conducted at IRSN Valduc on 12 June and 19, 2002, and the preliminary results compared well with the other participants.

Low-dose CT for the diagnosis of appendicitis in adolescents and young adults (LOCAT): a pragmatic, multicentre, randomised controlled non-inferiority trial.

PubMed

2017-11-01

CT radiation is arguably carcinogenic. Results from single-centre studies, mostly retrospective, have advocated lowering the CT radiation dose for the diagnosis of appendicitis. However, adoption of low-dose CT has been slow. We aimed to assess the effectiveness of low-dose CT compared with standard-dose CT in the diagnosis of appendicitis in adolescents and young adults. We did this pragmatic, multicentre, randomised controlled non-inferiority trial at 20 South Korean teaching hospitals with little experience with low-dose CT. Patients aged 15-44 years with suspected appendicitis were randomly assigned (1:1), via computer-generated random assignments (permuted block sizes of two, four, six, and eight) concealed in sequentially numbered envelopes, to receive low-dose CT (2 mSv) or standard-dose CT (≤8 mSv). Randomisation was stratified by site. Group allocation was concealed from patients, outcome assessors, and adverse event adjudicators; care providers, site pathologists, and data collectors were aware of allocation. The primary endpoint was the negative (unnecessary) appendectomy rate among all appendectomies, with a non-interiority margin of 4·5% for low-dose versus standard-dose CT. Primary analysis was by modified intention to treat, which included all patients who received an appendectomy in the group to which they were assigned. This trial is registered with ClinicalTrials.gov, number NCT01925014. Between Dec 4, 2013, and Aug 18, 2016, we assigned 1535 patients to the low-dose CT group and 1539 patients to the standard-dose CT group. 22 (3·9%) of 559 patients had a negative appendectomy in the low-dose group versus 16 (2·7%) of 601 patients in the standard-dose group (difference 1·3%, 95% CI -0·8 to 3·3; p=0·0022 for the non-inferiority test). We recorded 43 adverse events in 43 (2·8%) of 1535 patients in the low-dose group and 41 adverse events in 40 (2·6%) of 1539 patients in the standard-dose group. One life-threatening adverse event of anaphylaxis caused by an iodinated contrast material occurred in the low-dose group. Radiation dose of appendiceal CT for adolescents and young adults can be reduced to 2 mSv without impairing clinical outcomes. In view of the vast number of appendiceal CT examinations done worldwide, use of low-dose CT could prevent a sizeable number of radiation-associated cancers in the future. Korea Health Industry Development Institute, Seoul National University Bundang Hospital, Dasol Life Science, and Bracco Imaging Korea. Copyright © 2017 Elsevier Ltd. All rights reserved.

Treating primary dysmenorrhoea with acupuncture: a narrative review of the relationship between acupuncture 'dose' and menstrual pain outcomes.

PubMed

Armour, Mike; Smith, Caroline A

2016-12-01

A number of randomised controlled trials have been performed to determine the effectiveness or efficacy of acupuncture in primary dysmenorrhoea. The objective of this review was to explore the relationship between the 'dose' of the acupuncture intervention and menstrual pain outcomes. Eight databases were systematically searched for trials examining penetrating body acupuncture for primary dysmenorrhoea published in English up to September 2015. Dose components for each trial were extracted, assessed by the two authors and categorised by neurophysiological dose (number of needles, retention time and mode of stimulation), cumulative dose (total number and frequency of treatments), needle location and treatment timing. Eleven trials were included. Components of acupuncture dose were well reported across all trials. The relationship between needle location and menstrual pain demonstrated conflicting results. Treatment before the menses appeared to produce greater reductions in pain than treatment starting at the onset of menses. A single needle during menses may provide greater pain reduction compared to multiple needles. Conversely, multiple needles before menses were superior to a single needle. Electroacupuncture may provide more rapid pain reduction compared to manual acupuncture but may not have a significantly different effect on overall menstrual pain. There appear to be relationships between treatment timing and mode of needle stimulation, and menstrual pain outcomes. Needle location, number of needles used and frequency of treatment show clear dose-response relationships with menstrual pain outcomes. Current research is insufficient to make definitive clinical recommendations regarding optimum dose parameters for treating primary dysmenorrhoea. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Quality assurance of proton beams using a multilayer ionization chamber system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhanesar, Sandeep; Sahoo, Narayan; Kerr, Matthew

2013-09-15

Purpose: The measurement of percentage depth-dose (PDD) distributions for the quality assurance of clinical proton beams is most commonly performed with a computerized water tank dosimetry system with ionization chamber, commonly referred to as water tank. Although the accuracy and reproducibility of this method is well established, it can be time-consuming if a large number of measurements are required. In this work the authors evaluate the linearity, reproducibility, sensitivity to field size, accuracy, and time-savings of another system: the Zebra, a multilayer ionization chamber system.Methods: The Zebra, consisting of 180 parallel-plate ionization chambers with 2 mm resolution, was used tomore » measure depth-dose distributions. The measurements were performed for scattered and scanned proton pencil beams of multiple energies delivered by the Hitachi PROBEAT synchrotron-based delivery system. For scattered beams, the Zebra-measured depth-dose distributions were compared with those measured with the water tank. The principal descriptors extracted for comparisons were: range, the depth of the distal 90% dose; spread-out Bragg peak (SOBP) length, the region between the proximal 95% and distal 90% dose; and distal-dose fall off (DDF), the region between the distal 80% and 20% dose. For scanned beams, the Zebra-measured ranges were compared with those acquired using a Bragg peak chamber during commissioning.Results: The Zebra demonstrated better than 1% reproducibility and monitor unit linearity. The response of the Zebra was found to be sensitive to radiation field sizes greater than 12.5 × 12.5 cm; hence, the measurements used to determine accuracy were performed using a field size of 10 × 10 cm. For the scattered proton beams, PDD distributions showed 1.5% agreement within the SOBP, and 3.8% outside. Range values agreed within −0.1 ± 0.4 mm, with a maximum deviation of 1.2 mm. SOBP length values agreed within 0 ± 2 mm, with a maximum deviation of 6 mm. DDF values agreed within 0.3 ± 0.1 mm, with a maximum deviation of 0.6 mm. For the scanned proton pencil beams, Zebra and Bragg peak chamber range values demonstrated agreement of 0.0 ± 0.3 mm with a maximum deviation of 1.3 mm. The setup and measurement time for all Zebra measurements was 3 and 20 times less, respectively, compared to the water tank measurements.Conclusions: Our investigation shows that the Zebra can be useful not only for fast but also for accurate measurements of the depth-dose distributions of both scattered and scanned proton beams. The analysis of a large set of measurements shows that the commonly assessed beam quality parameters obtained with the Zebra are within the acceptable variations specified by the manufacturer for our delivery system.« less

Feasibility of TCP-based dose painting by numbers applied to a prostate case with (18)F-choline PET imaging.

PubMed

Dirscherl, Thomas; Rickhey, Mark; Bogner, Ludwig

2012-02-01

A biologically adaptive radiation treatment method to maximize the TCP is shown. Functional imaging is used to acquire a heterogeneous dose prescription in terms of Dose Painting by Numbers and to create a patient-specific IMRT plan. Adapted from a method for selective dose escalation under the guidance of spatial biology distribution, a model, which translates heterogeneously distributed radiobiological parameters into voxelwise dose prescriptions, was developed. At the example of a prostate case with (18)F-choline PET imaging, different sets of reported values for the parameters were examined concerning their resulting range of dose values. Furthermore, the influence of each parameter of the linear-quadratic model was investigated. A correlation between PET signal and proliferation as well as cell density was assumed. Using our in-house treatment planning software Direct Monte Carlo Optimization (DMCO), a treatment plan based on the obtained dose prescription was generated. Gafchromic EBT films were irradiated for evaluation. When a TCP of 95% was aimed at, the maximal dose in a voxel of the prescription exceeded 100Gy for most considered parameter sets. One of the parameter sets resulted in a dose range of 87.1Gy to 99.3Gy, yielding a TCP of 94.7%, and was investigated more closely. The TCP of the plan decreased to 73.5% after optimization based on that prescription. The dose difference histogram of optimized and prescribed dose revealed a mean of -1.64Gy and a standard deviation of 4.02Gy. Film verification showed a reasonable agreement of planned and delivered dose. If the distribution of radiobiological parameters within a tumor is known, this model can be used to create a dose-painting by numbers plan which maximizes the TCP. It could be shown, that such a heterogeneous dose distribution is technically feasible. Copyright © 2012. Published by Elsevier GmbH.

Effect of Acute Gamma Irradiation on Curcuma alismatifolia Varieties and Detection of DNA Polymorphism through SSR Marker

PubMed Central

Taheri, Sima; Abdullah, Thohirah Lee; Ahmad, Zaiton; Abdullah, Nur Ashikin Psyquay

2014-01-01

The effects of eight different doses (0, 10, 20, 25, 35, 40, 60, and 100 Gy) of acute gamma irradiation on 44 (three varieties of Curcuma alismatifolia: Chiang Mai Red, Sweet Pink, Kimono Pink, and one Curcuma hybrid (Doi Tung 554) individual plants were investigated. Radiation sensitivity tests revealed that the LD50 values of the varieties were achieved at 21 Gy for Chiang Mai Red, 23 Gy for Sweet Pink, 25 Gy for Kimono Pink, and 28 Gy for Doi Tung 554. From the analysis of variance (ANOVA), significant variations were observed for vegetative traits, flowering development, and rhizome characteristics among the four varieties of Curcuma alismatifolia and dose levels as well as the dose × variety interaction. In irradiated plants, the leaf length, leaf width, inflorescence length, the number of true flowers, the number of pink bracts, number of shoots, plant height, rhizome size, number of storage roots, and number of new rhizomes decreased significantly (P < 0.05) as the radiation dose increased. The cophenetic correlation coefficient (CCC) between genetic dissimilarity matrix estimated from the morphological characters and the UPGMA clustering method was r = 0.93, showing a proof fit. In terms of genetic variation among the acutely irradiated samples, the number of presumed alleles revealed by simple sequence repeats ranged from two to seven alleles with a mean value of 3.1, 4.5, and 5.3 alleles per locus for radiation doses of 0, 10, and 20 Gy, respectively. The average values of the effective number of alleles, Nei's gene diversity, and Shannon's information index were 2.5–3.2, 0.51–0.66, and 0.9–1.3, respectively. The constructed dendrogram grouped the entities into seven clusters. Principal component analysis (PCA) supported the clustering results. Consequently, it was concluded that irradiation with optimum doses of gamma rays efficiently induces mutations in Curcuma alismatifolia varieties. PMID:24719878

Effect of acute gamma irradiation on Curcuma alismatifolia varieties and detection of DNA polymorphism through SSR marker.

PubMed

Taheri, Sima; Abdullah, Thohirah Lee; Ahmad, Zaiton; Abdullah, Nur Ashikin Psyquay

2014-01-01

The effects of eight different doses (0, 10, 20, 25, 35, 40, 60, and 100 Gy) of acute gamma irradiation on 44 (three varieties of Curcuma alismatifolia: Chiang Mai Red, Sweet Pink, Kimono Pink, and one Curcuma hybrid (Doi Tung 554) individual plants were investigated. Radiation sensitivity tests revealed that the LD50 values of the varieties were achieved at 21 Gy for Chiang Mai Red, 23 Gy for Sweet Pink, 25 Gy for Kimono Pink, and 28 Gy for Doi Tung 554. From the analysis of variance (ANOVA), significant variations were observed for vegetative traits, flowering development, and rhizome characteristics among the four varieties of Curcuma alismatifolia and dose levels as well as the dose × variety interaction. In irradiated plants, the leaf length, leaf width, inflorescence length, the number of true flowers, the number of pink bracts, number of shoots, plant height, rhizome size, number of storage roots, and number of new rhizomes decreased significantly (P < 0.05) as the radiation dose increased. The cophenetic correlation coefficient (CCC) between genetic dissimilarity matrix estimated from the morphological characters and the UPGMA clustering method was r = 0.93, showing a proof fit. In terms of genetic variation among the acutely irradiated samples, the number of presumed alleles revealed by simple sequence repeats ranged from two to seven alleles with a mean value of 3.1, 4.5, and 5.3 alleles per locus for radiation doses of 0, 10, and 20 Gy, respectively. The average values of the effective number of alleles, Nei's gene diversity, and Shannon's information index were 2.5-3.2, 0.51-0.66, and 0.9-1.3, respectively. The constructed dendrogram grouped the entities into seven clusters. Principal component analysis (PCA) supported the clustering results. Consequently, it was concluded that irradiation with optimum doses of gamma rays efficiently induces mutations in Curcuma alismatifolia varieties.

A low, adaptive dose of gamma-rays reduced the number and altered the spectrum of S1- mutants in human-hamster hybrid AL cells

NASA Technical Reports Server (NTRS)

Ueno, A. M.; Vannais, D. B.; Gustafson, D. L.; Wong, J. C.; Waldren, C. A.

1996-01-01

We examined the effects of a low, adaptive dose of 137Cs-gamma-irradiation (0.04 Gy) on the number and kinds of mutants induced in AL human-hamster hybrid cells by a later challenge dose of 4 Gy. The yield of S1- mutants was significantly less (by 53%) after exposure to both the adaptive and challenge doses compared to the challenge dose alone. The yield of hprt- mutants was similarly decreased. Incubation with cycloheximide (CX) or 3-aminobenzamide largely negated the decrease in mutant yield. The adaptive dose did not perturb the cell cycle, was not cytotoxic, and did not of itself increase the mutant yield above background. The adaptive dose did, however, alter the spectrum of S1- mutants from populations exposed only to the adaptive dose, as well as affecting the spectrum of S1- mutants generated by the challenge dose. The major change in both cases was a significant increase in the proportion of complex mutations compared to small mutations and simple deletions.

Two-year experience with the commercial Gamma Knife Check software.

PubMed

Xu, Andy Yuanguang; Bhatnagar, Jagdish; Bednarz, Greg; Novotny, Josef; Flickinger, John; Lunsford, L Dade; Huq, M Saiful

2016-07-08

The Gamma Knife Check software is an FDA approved second check system for dose calculations in Gamma Knife radiosurgery. The purpose of this study was to evaluate the accuracy and the stability of the commercial software package as a tool for independent dose verification. The Gamma Knife Check software version 8.4 was commissioned for a Leksell Gamma Knife Perfexion and a 4C unit at the University of Pittsburgh Medical Center in May 2012. Independent dose verifications were performed using this software for 319 radiosurgery cases on the Perfexion and 283 radiosurgery cases on the 4C units. The cases on each machine were divided into groups according to their diagnoses, and an averaged absolute percent dose difference for each group was calculated. The percentage dose difference for each treatment target was obtained as the relative difference between the Gamma Knife Check dose and the dose from the tissue maximum ratio algorithm (TMR 10) from the GammaPlan software version 10 at the reference point. For treatment plans with imaging skull definition, results obtained from the Gamma Knife Check software using the measurement-based skull definition method are used for comparison. The collected dose difference data were also analyzed in terms of the distance from the treatment target to the skull, the number of treatment shots used for the target, and the gamma angles of the treatment shots. The averaged percent dose differences between the Gamma Knife Check software and the GammaPlan treatment planning system are 0.3%, 0.89%, 1.24%, 1.09%, 0.83%, 0.55%, 0.33%, and 1.49% for the trigeminal neuralgia, acoustic neuroma, arteriovenous malformation (AVM), meningioma, pituitary adenoma, glioma, functional disorders, and metastasis cases on the Perfexion unit. The corresponding averaged percent dose differences for the 4C unit are 0.33%, 1.2%, 2.78% 1.99%, 1.4%, 1.92%, 0.62%, and 1.51%, respectively. The dose difference is, in general, larger for treatment targets in the peripheral regions of the skull owing to the difference in the numerical methods used for skull shape simulation in the GammaPlan and the Gamma Knife Check software. Larger than 5% dose differences were observed on both machines for certain targets close to patient skull surface and for certain targets in the lower half of the brain on the Perfexion, especially when shots with 70 and/or 110 gamma angles are used. Out of the 1065 treatment targets studied, a 5% cutoff criterion cannot always be met for the dose differences between the studied versions of the Gamma Knife Check software and the planning system for 40 treatment targets. © 2016 The Authors.

SU-E-T-618: Dosimetric Comparison of Manual and Beam Angle Optimization of Gantry Angles in IMRT for Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, X; Sun, T; Liu, T

2014-06-01

Purpose: To evaluate the dosimetric characteristics of intensity-modulated radiotherapy (IMRT) treatment plan with beam angle optimization. Methods: Ten post-operation patients with cervical cancer were included in this analysis. Two IMRT plans using seven beams were designed in each patient. A standard coplanar equi-space beam angles were used in the first plan (plan 1), whereas the selection of beam angle was optimized by beam angle optimization algorithm in Varian Eclipse treatment planning system for the same number of beams in the second plan (plan 2). Two plans were designed for each patient with the same dose-volume constraints and prescription dose. Allmore » plans were normalized to the mean dose to PTV. The dose distribution in the target, the dose to the organs at risk and total MU were compared. Results: For conformity and homogeneity in PTV, no statistically differences were observed in the two plans. For the mean dose in bladder, plan 2 were significantly lower than plan 1(p<0.05). No statistically significant differences were observed between two plans for the mean doses in rectum, left and right femur heads. Compared with plan1, the average monitor units reduced 16% in plan 2. Conclusion: The IMRT plan based on beam angle optimization for cervical cancer could reduce the dose delivered to bladder and also reduce MU. Therefore there were some dosimetric advantages in the IMRT plan with beam angle optimization for cervical cancer.« less

In utero and Lactational Exposure to Acetamiprid Induces Abnormalities in Socio-Sexual and Anxiety-Related Behaviors of Male Mice

PubMed Central

Sano, Kazuhiro; Isobe, Tomohiko; Yang, Jiaxin; Win-Shwe, Tin-Tin; Yoshikane, Mitsuha; Nakayama, Shoji F.; Kawashima, Takaharu; Suzuki, Go; Hashimoto, Shunji; Nohara, Keiko; Tohyama, Chiharu; Maekawa, Fumihiko

2016-01-01

Neonicotinoids, a widely used group of pesticides designed to selectively bind to insect nicotinic acetylcholine receptors, were considered relatively safe for mammalian species. However, they have been found to activate vertebrate nicotinic acetylcholine receptors and could be toxic to the mammalian brain. In the present study, we evaluated the developmental neurotoxicity of acetamiprid (ACE), one of the most widely used neonicotinoids, in C57BL/6J mice whose mothers were administered ACE via gavage at doses of either 0 mg/kg (control group), 1.0 mg/kg (low-dose group), or 10.0 mg/kg (high-dose group) from gestational day 6 to lactation day 21. The results of a battery of behavior tests for socio-sexual and anxiety-related behaviors, the numbers of vasopressin-immunoreactive cells in the paraventricular nucleus of the hypothalamus, and testosterone levels were used as endpoints. In addition, behavioral flexibility in mice was assessed in a group-housed environment using the IntelliCage, a fully automated mouse behavioral analysis system. In adult male mice exposed to ACE at both low and high doses, a significant reduction of anxiety level was found in the light-dark transition test. Males in the low-dose group also showed a significant increase in sexual and aggressive behaviors. In contrast, neither the anxiety levels nor the sexual behaviors of females were altered. No reductions in the testosterone level, the number of vasopressin-immunoreactive cells, or behavioral flexibility were detected in either sex. These results suggest the possibility that in utero and lactational ACE exposure interferes with the development of the neural circuits required for executing socio-sexual and anxiety-related behaviors in male mice specifically. PMID:27375407

Characteristics of a large mumps outbreak: Clinical severity, complications and association with vaccination status of mumps outbreak cases.

PubMed

Zamir, C Stein; Schroeder, H; Shoob, H; Abramson, N; Zentner, G

2015-01-01

In recent years, large mumps outbreaks, involving mainly adolescents and young adults, have re-emerged in several countries. We investigated a large mumps outbreak, evaluated the association between mumps clinical severity (complications, hospitalization) and vaccination status (number of previous measles, mumps and rubella - MMR vaccine doses), and assessed vaccine effectiveness. The first mumps cases emerged in an ultra-orthodox boys' school in Jerusalem and were epidemiologically linked to the mumps outbreak in New York. Overall, 3130 mumps cases were notified in the Jerusalem district during September 2009-August 2011 (median age 13y, 64% males). Most cases were reported from community clinics. Patients with systemic symptoms and/or complications (419, 13.4%) were either hospitalized (n = 79) or treated in an emergency medical center (n = 340). The main complications included orchitis (3.8% males> age 12y) and meningoencephalitis (0.5%). The mumps virus genotype was G5. The distribution of previous MMR vaccine doses (n = 0,1,2) was: 24.8%, 28.3% and 46.9%, respectively. The number of previous vaccine doses was inversely associated with clinical severity. Adjusted values for MMR vaccine effectiveness against complications were estimated as 52.1% (95% CI -4 -78%) for one vaccine dose and 62.7% (95% CI 25.7-81.3%) for 2 doses. The outbreak was characterized by predominance of male students; the majority of whom had been previously vaccinated. The reported complication rate was relatively low. Vaccination status was associated with age and disease severity. The combination of limited mumps vaccine effectiveness and the specific school setting (dense learning and living conditions) probably contributed to the disease spread.

Characteristics of a large mumps outbreak: Clinical severity, complications and association with vaccination status of mumps outbreak cases

PubMed Central

Zamir, C Stein; Schroeder, H; Shoob, H; Abramson, N; Zentner, G

2015-01-01

In recent years, large mumps outbreaks, involving mainly adolescents and young adults, have re-emerged in several countries. We investigated a large mumps outbreak, evaluated the association between mumps clinical severity (complications, hospitalization) and vaccination status (number of previous measles, mumps and rubella - MMR vaccine doses), and assessed vaccine effectiveness. The first mumps cases emerged in an ultra-orthodox boys' school in Jerusalem and were epidemiologically linked to the mumps outbreak in New York. Overall, 3130 mumps cases were notified in the Jerusalem district during September 2009-August 2011 (median age 13y, 64% males). Most cases were reported from community clinics. Patients with systemic symptoms and/or complications (419, 13.4%) were either hospitalized (n = 79) or treated in an emergency medical center (n = 340). The main complications included orchitis (3.8% males> age 12y) and meningoencephalitis (0.5%). The mumps virus genotype was G5. The distribution of previous MMR vaccine doses (n = 0,1,2) was: 24.8%, 28.3% and 46.9%, respectively. The number of previous vaccine doses was inversely associated with clinical severity. Adjusted values for MMR vaccine effectiveness against complications were estimated as 52.1% (95% CI −4 −78%) for one vaccine dose and 62.7% (95% CI 25.7–81.3%) for 2 doses. The outbreak was characterized by predominance of male students; the majority of whom had been previously vaccinated. The reported complication rate was relatively low. Vaccination status was associated with age and disease severity. The combination of limited mumps vaccine effectiveness and the specific school setting (dense learning and living conditions) probably contributed to the disease spread. PMID:25874726

In vivo dosimetry and shielding disk alignment verification by EBT3 GAFCHROMIC film in breast IOERT treatment

PubMed Central

de Denaro, Mario; Bortul, Marina; Vidali, Cristiana; Beorchia, Aulo

2014-01-01

Intraoperative electron radiation therapy (IOERT) cannot usually benefit, as conventional external radiotherapy, from software systems of treatment planning based on computed tomography and from common dose verify procedures. For this reason, in vivo film dosimetry (IVFD) proves to be an effective methodology to evaluate the actual radiation dose delivered to the target. A practical method for IVFD during breast IOERT was carried out to improve information on the dose actually delivered to the tumor target and on the alignment of the shielding disk with respect to the electron beam. Two EBT3 GAFCHROMIC films have been positioned on the two sides of the shielding disk in order to obtain the dose maps at the target and beyond the disk. Moreover the postprocessing analysis of the dose distribution measured on the films provides a quantitative estimate of the misalignment between the collimator and the disk. EBT3 radiochromic films have been demonstrated to be suitable dosimeters for IVD due to their linear dose‐optical density response in a narrow range around the prescribed dose, as well as their capability to be fixed to the shielding disk without giving any distortion in the dose distribution. Off‐line analysis of the radiochromic film allowed absolute dose measurements and this is indeed a very important verification of the correct exposure to the target organ, as well as an estimate of the dose to the healthy tissue underlying the shielding. These dose maps allow surgeons and radiation oncologists to take advantage of qualitative and quantitative feedback for setting more accurate treatment strategies and further optimized procedures. The proper alignment using elastic bands has improved the absolute dose accuracy and the collimator disk alignment by more than 50%. PACS number: 87.55.kh

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marin, A.; Meneghini, C.; Mezzanotte, S.

The tongue was examined microscopically with various staining techniques 5, 15, and 30 days postirradiation. The mucous glands were consistently reduced in thickness, independent of the dose. As seen by the periodic acid-Schiff (PAS) reaction, the polysaccharide material took on a homogeneous appearance after irradiation in contrast to its granular form in control sections. The number of capillary vessels appeared to be increased 5 days after irradiation at all dose levels, whereas after 15 days the number was fewer than in control specimens. At 30 days, further changes were noted: with the 2000-r dose the number of vessels was normalmore » but with the 2 higher doses the number was below normal and many vessels were occluded. The occlusion resulted from hypertrophy of endothelial cells, and the basement membrane was thickened and stained more intensely than normal. The early apparent increase in the number of capillaries could not be traced to newly formed vessels but to dilatation of pre-existing ones. This increase in luminal diameter following irradiation was subsequently (at 15 to 30 days) obliterated by swelling of endothelium. Hemorrhagic changes were present at 5 days after all 3 doses but at 30 days were evident only after 5000 and 10 000 r. The findings are interpreted as indicating that interstitial polysaccharides are depolymerized by radiation and that the thickening of the capillary basement membrane represents increased permeability and accumulation of glycoproteins from the blood. (TCO)« less

MRI-based treatment planning with pseudo CT generated through atlas registration.

PubMed

Uh, Jinsoo; Merchant, Thomas E; Li, Yimei; Li, Xingyu; Hua, Chiaho

2014-05-01

To evaluate the feasibility and accuracy of magnetic resonance imaging (MRI)-based treatment planning using pseudo CTs generated through atlas registration. A pseudo CT, providing electron density information for dose calculation, was generated by deforming atlas CT images previously acquired on other patients. The authors tested 4 schemes of synthesizing a pseudo CT from single or multiple deformed atlas images: use of a single arbitrarily selected atlas, arithmetic mean process using 6 atlases, and pattern recognition with Gaussian process (PRGP) using 6 or 12 atlases. The required deformation for atlas CT images was derived from a nonlinear registration of conjugated atlas MR images to that of the patient of interest. The contrasts of atlas MR images were adjusted by histogram matching to reduce the effect of different sets of acquisition parameters. For comparison, the authors also tested a simple scheme assigning the Hounsfield unit of water to the entire patient volume. All pseudo CT generating schemes were applied to 14 patients with common pediatric brain tumors. The image similarity of real patient-specific CT and pseudo CTs constructed by different schemes was compared. Differences in computation times were also calculated. The real CT in the treatment planning system was replaced with the pseudo CT, and the dose distribution was recalculated to determine the difference. The atlas approach generally performed better than assigning a bulk CT number to the entire patient volume. Comparing atlas-based schemes, those using multiple atlases outperformed the single atlas scheme. For multiple atlas schemes, the pseudo CTs were similar to the real CTs (correlation coefficient, 0.787-0.819). The calculated dose distribution was in close agreement with the original dose. Nearly the entire patient volume (98.3%-98.7%) satisfied the criteria of chi-evaluation (<2% maximum dose and 2 mm range). The dose to 95% of the volume and the percentage of volume receiving at least 95% of the prescription dose in the planning target volume differed from the original values by less than 2% of the prescription dose (root-mean-square, RMS < 1%). The PRGP scheme did not perform better than the arithmetic mean process with the same number of atlases. Increasing the number of atlases from 6 to 12 often resulted in improvements, but statistical significance was not always found. MRI-based treatment planning with pseudo CTs generated through atlas registration is feasible for pediatric brain tumor patients. The doses calculated from pseudo CTs agreed well with those from real CTs, showing dosimetric accuracy within 2% for the PTV when multiple atlases were used. The arithmetic mean process may be a reasonable choice over PRGP for the synthesis scheme considering performance and computational costs.

MRI-based treatment planning with pseudo CT generated through atlas registration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uh, Jinsoo, E-mail: jinsoo.uh@stjude.org; Merchant, Thomas E.; Hua, Chiaho

2014-05-15

Purpose: To evaluate the feasibility and accuracy of magnetic resonance imaging (MRI)-based treatment planning using pseudo CTs generated through atlas registration. Methods: A pseudo CT, providing electron density information for dose calculation, was generated by deforming atlas CT images previously acquired on other patients. The authors tested 4 schemes of synthesizing a pseudo CT from single or multiple deformed atlas images: use of a single arbitrarily selected atlas, arithmetic mean process using 6 atlases, and pattern recognition with Gaussian process (PRGP) using 6 or 12 atlases. The required deformation for atlas CT images was derived from a nonlinear registration ofmore » conjugated atlas MR images to that of the patient of interest. The contrasts of atlas MR images were adjusted by histogram matching to reduce the effect of different sets of acquisition parameters. For comparison, the authors also tested a simple scheme assigning the Hounsfield unit of water to the entire patient volume. All pseudo CT generating schemes were applied to 14 patients with common pediatric brain tumors. The image similarity of real patient-specific CT and pseudo CTs constructed by different schemes was compared. Differences in computation times were also calculated. The real CT in the treatment planning system was replaced with the pseudo CT, and the dose distribution was recalculated to determine the difference. Results: The atlas approach generally performed better than assigning a bulk CT number to the entire patient volume. Comparing atlas-based schemes, those using multiple atlases outperformed the single atlas scheme. For multiple atlas schemes, the pseudo CTs were similar to the real CTs (correlation coefficient, 0.787–0.819). The calculated dose distribution was in close agreement with the original dose. Nearly the entire patient volume (98.3%–98.7%) satisfied the criteria of chi-evaluation (<2% maximum dose and 2 mm range). The dose to 95% of the volume and the percentage of volume receiving at least 95% of the prescription dose in the planning target volume differed from the original values by less than 2% of the prescription dose (root-mean-square, RMS < 1%). The PRGP scheme did not perform better than the arithmetic mean process with the same number of atlases. Increasing the number of atlases from 6 to 12 often resulted in improvements, but statistical significance was not always found. Conclusions: MRI-based treatment planning with pseudo CTs generated through atlas registration is feasible for pediatric brain tumor patients. The doses calculated from pseudo CTs agreed well with those from real CTs, showing dosimetric accuracy within 2% for the PTV when multiple atlases were used. The arithmetic mean process may be a reasonable choice over PRGP for the synthesis scheme considering performance and computational costs.« less

MRI-based treatment planning with pseudo CT generated through atlas registration

PubMed Central

Uh, Jinsoo; Merchant, Thomas E.; Li, Yimei; Li, Xingyu; Hua, Chiaho

2014-01-01

Purpose: To evaluate the feasibility and accuracy of magnetic resonance imaging (MRI)-based treatment planning using pseudo CTs generated through atlas registration. Methods: A pseudo CT, providing electron density information for dose calculation, was generated by deforming atlas CT images previously acquired on other patients. The authors tested 4 schemes of synthesizing a pseudo CT from single or multiple deformed atlas images: use of a single arbitrarily selected atlas, arithmetic mean process using 6 atlases, and pattern recognition with Gaussian process (PRGP) using 6 or 12 atlases. The required deformation for atlas CT images was derived from a nonlinear registration of conjugated atlas MR images to that of the patient of interest. The contrasts of atlas MR images were adjusted by histogram matching to reduce the effect of different sets of acquisition parameters. For comparison, the authors also tested a simple scheme assigning the Hounsfield unit of water to the entire patient volume. All pseudo CT generating schemes were applied to 14 patients with common pediatric brain tumors. The image similarity of real patient-specific CT and pseudo CTs constructed by different schemes was compared. Differences in computation times were also calculated. The real CT in the treatment planning system was replaced with the pseudo CT, and the dose distribution was recalculated to determine the difference. Results: The atlas approach generally performed better than assigning a bulk CT number to the entire patient volume. Comparing atlas-based schemes, those using multiple atlases outperformed the single atlas scheme. For multiple atlas schemes, the pseudo CTs were similar to the real CTs (correlation coefficient, 0.787–0.819). The calculated dose distribution was in close agreement with the original dose. Nearly the entire patient volume (98.3%–98.7%) satisfied the criteria of chi-evaluation (<2% maximum dose and 2 mm range). The dose to 95% of the volume and the percentage of volume receiving at least 95% of the prescription dose in the planning target volume differed from the original values by less than 2% of the prescription dose (root-mean-square, RMS < 1%). The PRGP scheme did not perform better than the arithmetic mean process with the same number of atlases. Increasing the number of atlases from 6 to 12 often resulted in improvements, but statistical significance was not always found. Conclusions: MRI-based treatment planning with pseudo CTs generated through atlas registration is feasible for pediatric brain tumor patients. The doses calculated from pseudo CTs agreed well with those from real CTs, showing dosimetric accuracy within 2% for the PTV when multiple atlases were used. The arithmetic mean process may be a reasonable choice over PRGP for the synthesis scheme considering performance and computational costs. PMID:24784377

Age- and gender-specific estimates of cumulative CT dose over 5 years using real radiation dose tracking data in children.

PubMed

Lee, Eunsol; Goo, Hyun Woo; Lee, Jae-Yeong

2015-08-01

It is necessary to develop a mechanism to estimate and analyze cumulative radiation risks from multiple CT exams in various clinical scenarios in children. To identify major contributors to high cumulative CT dose estimates using actual dose-length product values collected for 5 years in children. Between August 2006 and July 2011 we reviewed 26,937 CT exams in 13,803 children. Among them, we included 931 children (median age 3.5 years, age range 0 days-15 years; M:F = 533:398) who had 5,339 CT exams. Each child underwent at least three CT scans and had accessible radiation dose reports. Dose-length product values were automatically extracted from DICOM files and we used recently updated conversion factors for age, gender, anatomical region and tube voltage to estimate CT radiation dose. We tracked the calculated CT dose estimates to obtain a 5-year cumulative value for each child. The study population was divided into three groups according to the cumulative CT dose estimates: high, ≥30 mSv; moderate, 10-30 mSv; and low, <10 mSv. We reviewed clinical data and CT protocols to identify major contributors to high and moderate cumulative CT dose estimates. Median cumulative CT dose estimate was 5.4 mSv (range 0.5-71.1 mSv), and median number of CT scans was 4 (range 3-36). High cumulative CT dose estimates were most common in children with malignant tumors (57.9%, 11/19). High frequency of CT scans was attributed to high cumulative CT dose estimates in children with ventriculoperitoneal shunt (35 in 1 child) and malignant tumors (range 18-49). Moreover, high-dose CT protocols, such as multiphase abdomen CT (median 4.7 mSv) contributed to high cumulative CT dose estimates even in children with a low number of CT scans. Disease group, number of CT scans, and high-dose CT protocols are major contributors to higher cumulative CT dose estimates in children.

Involvement of monoaminergic systems in anxiolytic and antidepressive activities of the standardized extract of Cocos nucifera L.

PubMed

Lima, Eliane Brito Cortez; de Sousa, Caren Nádia Soares; Meneses, Lucas Nascimento; E Silva Pereira, Yuri Freitas; Matos, Natália Castelo Branco; de Freitas, Rayanne Brito; Lima, Nycole Brito Cortez; Patrocínio, Manoel Cláudio Azevedo; Leal, Luzia Kalyne Almeida Moreira; Viana, Glauce Socorro Barros; Vasconcelos, Silvânia Maria Mendes

2017-01-01

Extracts from the husk fiber of Cocos nucifera are used in folk medicine, but their actions on the central nervous system have not been studied. Here, the anxiolytic and antidepressant effects of the standardized hydroalcoholic extract of C. nucifera husk fiber (HECN) were evaluated. Male Swiss mice were treated with HECN (50, 100, or 200 mg/kg) 60 min before experiments involving the plus maze test, hole-board test, tail suspension test, and forced swimming test (FST). HECN was administered orally (p.o.) in acute and repeated-dose treatments. The forced swimming test was performed with dopaminergic and noradrenergic antagonists, as well as a serotonin release inhibitor. Administration of HECN in the FST after intraperitoneal (i.p.) pretreatment of mice with sulpiride (50 mg/kg), prazosin (1 mg/kg), or p-chlorophenylalanine (PCPA, 100 mg/kg) caused the actions of these three agents to be reversed. However, this effect was not observed after pretreating the animals with SCH23390 (15 µg/kg, i.p.) or yohimbine (1 mg/kg, i.p.) The dose chosen for HECN was 100 mg/kg, p.o., which increased the number of entries as well as the permanence in the open arms of the maze after acute and repeated doses. In both the forced swimming and the tail suspension tests, the same dose decreased the time spent immobile but did not disturb locomotor activity in an open-field test. The anxiolytic effect of HECN appears to be related to the GABAergic system, while its antidepressant effect depends upon its interaction with the serotoninergic, noradrenergic (α1 receptors), and dopaminergic (D2 dopamine receptors) systems.

[Diagnostic reference levels in interventional radiology].

PubMed

Vañó Carruana, E; Fernández Soto, J M; Sánchez Casanueva, R M; Ten Morón, J I

2013-12-01

This article discusses the diagnostic reference levels for radiation exposure proposed by the International Commission on Radiological Protection (ICRP) to facilitate the application of the optimization criteria in diagnostic imaging and interventional procedures. These levels are normally established as the third quartile of the dose distributions to patients in an ample sample of centers and are supposed to be representative of good practice regarding patient exposure. In determining these levels, it is important to evaluate image quality as well to ensure that it is sufficient for diagnostic purposes. When the values for the dose received by patients are systematically higher or much lower than the reference levels, an investigation should determine whether corrective measures need to be applied. The European and Spanish regulations require the use of these reference values in quality assurance programs. For interventional procedures, the dose area product (or kerma area product) values are usually used as reference values together with the time under fluoroscopy and the total number of images acquired. The most modern imaging devices allow the value of the accumulated dose at the entrance to the patient to be calculated to optimize the distribution of the dose on the skin. The ICRP recommends that the complexity of interventional procedures be taken into account when establishing reference levels. In the future, diagnostic imaging departments will have automatic systems to manage patient dosimetric data; these systems will enable continuous dosage auditing and alerts about individual procedures that might involve doses several times above the reference values. This article also discusses aspects that need to be clarified to take better advantage of the reference levels in interventional procedures. Copyright © 2013 SERAM. Published by Elsevier Espana. All rights reserved.

Prediction of Individual Serum Infliximab Concentrations in Inflammatory Bowel Disease by a Bayesian Dashboard System.

PubMed

Eser, Alexander; Primas, Christian; Reinisch, Sieglinde; Vogelsang, Harald; Novacek, Gottfried; Mould, Diane R; Reinisch, Walter

2018-01-30

Despite a robust exposure-response relationship of infliximab in inflammatory bowel disease (IBD), attempts to adjust dosing to individually predicted serum concentrations of infliximab (SICs) are lacking. Compared with labor-intensive conventional software for pharmacokinetic (PK) modeling (eg, NONMEM) dashboards are easy-to-use programs incorporating complex Bayesian statistics to determine individual pharmacokinetics. We evaluated various infliximab detection assays and the number of samples needed to precisely forecast individual SICs using a Bayesian dashboard. We assessed long-term infliximab retention in patients being dosed concordantly versus discordantly with Bayesian dashboard recommendations. Three hundred eighty-two serum samples from 117 adult IBD patients on infliximab maintenance therapy were analyzed by 3 commercially available assays. Data from each assay was modeled using NONMEM and a Bayesian dashboard. PK parameter precision and residual variability were assessed. Forecast concentrations from both systems were compared with observed concentrations. Infliximab retention was assessed by prediction for dose intensification via Bayesian dashboard versus real-life practice. Forecast precision of SICs varied between detection assays. At least 3 SICs from a reliable assay are needed for an accurate forecast. The Bayesian dashboard performed similarly to NONMEM to predict SICs. Patients dosed concordantly with Bayesian dashboard recommendations had a significantly longer median drug survival than those dosed discordantly (51.5 versus 4.6 months, P < .0001). The Bayesian dashboard helps to assess the diagnostic performance of infliximab detection assays. Three, not single, SICs provide sufficient information for individualized dose adjustment when incorporated into the Bayesian dashboard. Treatment adjusted to forecasted SICs is associated with longer drug retention of infliximab. © 2018, The American College of Clinical Pharmacology.

Effects of GABAergic modulators on food and cocaine self-administration in baboons.

PubMed

Weerts, Elise M; Froestl, Wolfgang; Griffiths, Roland R

2005-12-12

Drugs that indirectly alter dopaminergic systems may alter the reinforcing effects of cocaine. The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) has extensive neural connections in mesolimbic regions that appear to modulate dopamine. The current study evaluated the effects of GABA(B) receptor agonists baclofen and CGP44532, the benzodiazepine agonist alprazolam, and the GABA reuptake inhibitor tiagabine on lever responding maintained by low dose cocaine injections (0.032 mg/kg) or by food pellet (1 g) delivery in baboons. The benzodiazepine antagonist flumazenil was tested as a negative control. Cocaine or food was available under a fixed ratio (FR 10) schedule of reinforcement during daily 2-h sessions. During baseline conditions, cocaine and pellets maintained similar numbers of reinforcers per session. Baclofen, CGP44532 and tiagabine dose-dependently reduced the number of cocaine injections, where as the benzodiazepine antagonist flumazenil did not. Baclofen, CGP44532 and tiagabine also produced dose-related decreases in food-maintained behavior. In contrast, the benzodiazepine agonist alprazolam, which positively modulates GABA(A) receptors via the benzodiazepine site, produced decreases in cocaine self-injection, but not food-maintained behavior. Thus, the effects of alprazolam were specific for cocaine-maintained behavior, where as the effects of baclofen and CGP44532 were not.

[Cooperation with the electronic medical record and accounting system of an actual dose of drug given by a radiology information system].

PubMed

Yamamoto, Hideo; Yoneda, Tarou; Satou, Shuji; Ishikawa, Toru; Hara, Misako

2009-12-20

By input of the actual dose of a drug given into a radiology information system, the system converting with an accounting system into a cost of the drug from the actual dose in the electronic medical record was built. In the drug master, the first unit was set as the cost of the drug, and we set the second unit as the actual dose. The second unit in the radiology information system was received by the accounting system through electronic medical record. In the accounting system, the actual dose was changed into the cost of the drug using the dose of conversion to the first unit. The actual dose was recorded on a radiology information system and electronic medical record. The actual dose was indicated on the accounting system, and the cost for the drug was calculated. About the actual dose of drug, cooperation of the information in a radiology information system and electronic medical record were completed. It was possible to decide the volume of drug from the correct dose of drug at the previous inspection. If it is necessary for the patient to have another treatment of medicine, it is important to know the actual dose of drug given. Moreover, authenticity of electronic medical record based on a statute has also improved.

Zoledronate Effects on Systemic and Jaw Osteopenias in Ovariectomized Periostin-Deficient Mice

PubMed Central

Bonnet, Nicolas; Lesclous, Philippe; Saffar, Jean Louis; Ferrari, Serge

2013-01-01

Osteoporosis and periodontal disease (PD) are frequently associated in the elderly, both concurring to the loss of jaw alveolar bone and finally of teeth. Bisphosphonates improve alveolar bone loss but have also been associated with osteonecrosis of the jaw (ONJ), particularly using oncological doses of zoledronate. The effects and therapeutic margin of zoledronate on jaw bone therefore remain uncertain. We reappraised the efficacy and safety of Zoledronate (Zol) in ovariectomized (OVX) periostin (Postn)-deficient mice, a unique genetic model of systemic and jaw osteopenia. Compared to vehicle, Zol 1M (100 µg/kg/month) and Zol 1W (100 µg/kg/week) for 3 months both significantly improved femur BMD, trabecular bone volume on tissue volume (BV/TV) and cortical bone volume in both OVX Postn+/+ and Postn−/− (all p<0.01). Zol 1M and Zol 1W also improved jaw alveolar and basal BV/TV, although the highest dose (Zol 1W) was less efficient, particularly in Postn−/−. Zol decreased osteoclast number and bone formation indices, i.e. MAR, MPm/BPm and BFR, independently in Postn−/− and Postn+/+, both in the long bones and in deep jaw alveolar bone, without differences between Zol doses. Zol 1M and Zol 1W did not reactivate inflammation nor increase fibrous tissue in the bone marrow of the jaw, whereas the distance between the root and the enamel of the incisor (DRI) remained high in Postn−/− vs Postn+/+ confirming latent inflammation and lack of crestal alveolar bone. Zol 1W and Zol 1M decreased osteocyte numbers in Postn−/− and Postn+/+ mandible, and Zol 1W increased the number of empty lacunae in Postn−/−, however no areas of necrotic bone were observed. These results demonstrate that zoledronate improves jaw osteopenia and suggest that in Postn−/− mice, zoledronate is not sufficient to induce bone necrosis. PMID:23505553

Noise reduction in spectral CT: reducing dose and breaking the trade-off between image noise and energy bin selection.

PubMed

Leng, Shuai; Yu, Lifeng; Wang, Jia; Fletcher, Joel G; Mistretta, Charles A; McCollough, Cynthia H

2011-09-01

Our purpose was to reduce image noise in spectral CT by exploiting data redundancies in the energy domain to allow flexible selection of the number, width, and location of the energy bins. Using a variety of spectral CT imaging methods, conventional filtered backprojection (FBP) reconstructions were performed and resulting images were compared to those processed using a Local HighlY constrained backPRojection Reconstruction (HYPR-LR) algorithm. The mean and standard deviation of CT numbers were measured within regions of interest (ROIs), and results were compared between FBP and HYPR-LR. For these comparisons, the following spectral CT imaging methods were used:(i) numerical simulations based on a photon-counting, detector-based CT system, (ii) a photon-counting, detector-based micro CT system using rubidium and potassium chloride solutions, (iii) a commercial CT system equipped with integrating detectors utilizing tube potentials of 80, 100, 120, and 140 kV, and (iv) a clinical dual-energy CT examination. The effects of tube energy and energy bin width were evaluated appropriate to each CT system. The mean CT number in each ROI was unchanged between FBP and HYPR-LR images for each of the spectral CT imaging scenarios, irrespective of bin width or tube potential. However, image noise, as represented by the standard deviation of CT numbers in each ROI, was reduced by 36%-76%. In all scenarios, image noise after HYPR-LR algorithm was similar to that of composite images, which used all available photons. No difference in spatial resolution was observed between HYPR-LR processing and FBP. Dual energy patient data processed using HYPR-LR demonstrated reduced noise in the individual, low- and high-energy images, as well as in the material-specific basis images. Noise reduction can be accomplished for spectral CT by exploiting data redundancies in the energy domain. HYPR-LR is a robust method for reducing image noise in a variety of spectral CT imaging systems without losing spatial resolution or CT number accuracy. This method improves the flexibility to select energy bins in the manner that optimizes material identification and separation without paying the penalty of increased image noise or its corollary, increased patient dose.

Pill content, dose and resulting plasma concentrations of 3,4-methylendioxymethamphetamine (MDMA) in recreational 'ecstasy' users.

PubMed

Morefield, Kate M; Keane, Michael; Felgate, Peter; White, Jason M; Irvine, Rodney J

2011-07-01

To improve our understanding of the pharmacology of 'ecstasy' in recreational environments; in particular, to describe the composition of ecstasy pills, patterns of ecstasy use and the relationship between dose of 3,4-methylendioxymethamphetamine (MDMA) and resulting plasma concentrations. A naturalistic observational study of 56 experienced 'ecstasy' users in recreational settings in Australia. Drug use patterns (number of pills consumed, other drugs consumed). drug content of pills and resultant plasma concentrations of MDMA and related drugs were assessed by gas chromatography/mass spectrometry (GC/MS). Ecstasy pills generally contained MDMA, but this was often combined with other drugs such as 3,4-ethylendioxyethylamphetamine (MDEA) and methamphetamine. The dose of MDMA per pill ranged from 0 to 245 mg and users consumed from one-half to five pills, with the total dose consumed ranging up to 280 mg. Plasma concentrations of MDMA increased with number of pills consumed and cumulative MDMA dose. Use of larger numbers of pills was associated with extended exposure to the drug. MDMA is the major active drug in ecstasy pills, but there is a high degree of variation in doses. Use of multiple pills over the course of one session is common and results in a sustained increase in MDMA plasma concentrations over a number of hours. This is likely to lead to a much greater exposure of the brain to MDMA than would be predicted from controlled single-dose pharmacokinetic studies. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

A review of protocols for 308 nm excimer laser phototherapy in psoriasis.

PubMed

Mudigonda, Tejaswi; Dabade, Tushar S; Feldman, Steven R

2012-01-01

308 nm excimer laser phototherapy is efficacious in the treatment of localized psoriasis. Different approaches regarding dose fluency, number of treatments, and maintenance have been utilized, and there is yet to be a consensus on standard protocol. To characterize treatment parameters for 308 nm excimer laser phototherapy. We performed a PubMed search for studies describing excimer laser treatment protocol with particular attention to dosage determination, dose adjustment, dose fluency, number of treatments, and maintenance. Seven prospective studies were found describing the excimer efficacy for psoriasis. All studies determined the initial treatment dose using either the minimal erythema dose (MED) or induration. Fluency ranged from 0.5 MED (low) to 16 MED (high); one study demonstrated that medium to high fluencies yielded better improvement in fewer number of treatments. Fluency adjustments during the course of treatment were important to minimize phototherapy-associated side effects. The use of higher fluencies was reported to result in higher occurrences of blistering. One study implemented a maintenance tapering of dose-frequency phase to better manage psoriasis flare-ups. The 308 nm excimer laser is an effective therapy for psoriasis regardless of the method used to determine initial dosage, dose fluency, or number of treatments. As its usage as a targeted monotherapy increases, future trials should consider evaluating and modifying these parameters to determine the most optimal management of localized psoriasis. Based on our reviewed studies, there is no consensus for a single excimer laser therapy protocol and as a result, patient preferences should continue to be an important consideration for phototherapy regimen planning.

ESTIMATING SYSTEMIC EXPOSURE TO ETHINYL ESTRADIOL FROM AN ORAL CONTRACEPTIVE

PubMed Central

WESTHOFF, Carolyn L.; PIKE, Malcolm C.; TANG, Rosalind; DINAPOLI, Marianne N.; SULL, Monica; CREMERS, Serge

2015-01-01

Objectives This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive to steady-state values, and to assess whether any simpler measures could provide an adequate proxy of the ‘gold standard’ 24-hour steady-state area-under-the-curve. Identifying a simple, less expensive, measure of systemic ethinyl estradiol exposure would be useful for larger studies designed to assess the relationship between an individual’s ethinyl estradiol exposure and her side effects. Study Design We conducted a 13 samples over 24 hours pharmacokinetic analysis on day 1 and day 21 of the first cycle of a monophasic oral contraceptive containing 30 mcg ethinyl estradiol and 150 mcg levonorgestrel in 17 non-obese healthy white women. We also conducted an abbreviated single dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of full 13-sample steady-state pharmacokinetic analysis with results calculated using fewer samples (9 or 5) and following the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure. Results The area-under-the-curve, maximum (Cmax), and 24-hour (C24) values were similar following the two single oral contraceptive doses (area-under-the-curve, r = 0.92). The steady-state 13-sample 24-hour area-under-the-curve was highly correlated with the average 9-sample area-under-the-curve after the two single doses (r = 0.81, p = 0.0002). This correlation remained the same if the number of samples was reduced to 4, taken at time 1, 2.5, 4 and 24 hours. The C24 at steady-state was highly correlated with the 24-hour steady-state area-under-the-curve (r = 0.92, p < 0.0001). The average of the C24 values following the two single doses was also quite highly correlated with the steady-state area-under-the-curve (r = 0.72, p = 0.0026). Conclusions Limited blood sampling, including results from two single doses, gave highly correlated estimates of an oral contraceptive user’s steady-state ethinyl estradiol exposure. PMID:25511238

Hormonal priming, induction of ovulation and in-vitro fertilization of the endangered Wyoming toad (Bufo baxteri)

PubMed Central

Browne, Robert K; Seratt, Jessica; Vance, Carrie; Kouba, Andrew

2006-01-01

The endangered Wyoming toad (Bufo baxteri) is the subject of an extensive captive breeding and reintroduction program. Wyoming toads in captivity rarely ovulate spontaneously and hormonal induction is used to ovulate females or to stimulate spermiation in males. With hormonal induction, ovulation is unreliable and egg numbers are low. The sequential administration of anovulatory doses of hormones (priming) has increased egg numbers and quality in both anurans and fish. Consequently, we tested the efficacy of a combination of human Chorionic Gonadotrophin (hCG) and Luteinizing Hormone Releasing Hormone analogue (LHRHa) administered as one dose, or two or three sequential doses to Bufo baxteri on egg numbers, fertilization and early embryo development. Spawning toads deposited eggs into Simplified Amphibian Ringers (SAR) solution to enable controlled in-vitro fertilization (IVF) with sperm from hormonally induced male toads. Unprimed females receiving a single mixed normally ovulatory dose of 500 IU hCG plus 4 micrograms of LHRHa produced no eggs. Whereas females primed with this dose and an anovulatory dose (100 IU hCG and 0.8 micrograms of LHRHa) of the same hormones, or primed only with an anovulatory dose, spawned after then receiving an ovulatory dose. Higher total egg numbers were produced with two primings than with one priming. Moreover, two primings produced significantly more eggs from each individual female than one priming. The cleavage rate of eggs was not found to differ between one or two primings. Nevertheless, embryo development with eggs from two primings gave a significantly greater percentage neurulation and swim-up than those from one priming. Of the male toads receiving a single dose of 300 IU hCG, 80% produced spermic urine with the greatest sperm concentration 7 hours post-administration (PA). However, peak sperm motility (95%) was achieved at 5 hours PA and remained relatively constant until declining 20 hours PA. In conclusion, Bufo baxteri egg numbers and quality benefited from sequential priming with LHRHa and hCG whereas spermic urine for IVF was produced from males with a single dose of hCG. The power of assisted reproduction technology in the conservation of endangered amphibians is shown by the release of nearly 2000 tadpoles produced by IVF during this study. PMID:16790071

Patient‐specific CT dosimetry calculation: a feasibility study

PubMed Central

Xie, Huchen; Cheng, Jason Y.; Ning, Holly; Zhuge, Ying; Miller, Robert W.

2011-01-01

Current estimation of radiation dose from computed tomography (CT) scans on patients has relied on the measurement of Computed Tomography Dose Index (CTDI) in standard cylindrical phantoms, and calculations based on mathematical representations of “standard man”. Radiation dose to both adult and pediatric patients from a CT scan has been a concern, as noted in recent reports. The purpose of this study was to investigate the feasibility of adapting a radiation treatment planning system (RTPS) to provide patient‐specific CT dosimetry. A radiation treatment planning system was modified to calculate patient‐specific CT dose distributions, which can be represented by dose at specific points within an organ of interest, as well as organ dose‐volumes (after image segmentation) for a GE Light Speed Ultra Plus CT scanner. The RTPS calculation algorithm is based on a semi‐empirical, measured correction‐based algorithm, which has been well established in the radiotherapy community. Digital representations of the physical phantoms (virtual phantom) were acquired with the GE CT scanner in axial mode. Thermoluminescent dosimeter (TLDs) measurements in pediatric anthropomorphic phantoms were utilized to validate the dose at specific points within organs of interest relative to RTPS calculations and Monte Carlo simulations of the same virtual phantoms (digital representation). Congruence of the calculated and measured point doses for the same physical anthropomorphic phantom geometry was used to verify the feasibility of the method. The RTPS algorithm can be extended to calculate the organ dose by calculating a dose distribution point‐by‐point for a designated volume. Electron Gamma Shower (EGSnrc) codes for radiation transport calculations developed by National Research Council of Canada (NRCC) were utilized to perform the Monte Carlo (MC) simulation. In general, the RTPS and MC dose calculations are within 10% of the TLD measurements for the infant and child chest scans. With respect to the dose comparisons for the head, the RTPS dose calculations are slightly higher (10%–20%) than the TLD measurements, while the MC results were within 10% of the TLD measurements. The advantage of the algebraic dose calculation engine of the RTPS is a substantially reduced computation time (minutes vs. days) relative to Monte Carlo calculations, as well as providing patient‐specific dose estimation. It also provides the basis for a more elaborate reporting of dosimetric results, such as patient specific organ dose volumes after image segmentation. PACS numbers: 87.55.D‐, 87.57.Q‐, 87.53.Bn, 87.55.K‐ PMID:22089016

User Performance Evaluation of Four Blood Glucose Monitoring Systems Applying ISO 15197:2013 Accuracy Criteria and Calculation of Insulin Dosing Errors.

PubMed

Freckmann, Guido; Jendrike, Nina; Baumstark, Annette; Pleus, Stefan; Liebing, Christina; Haug, Cornelia

2018-04-01

The international standard ISO 15197:2013 requires a user performance evaluation to assess if intended users are able to obtain accurate blood glucose measurement results with a self-monitoring of blood glucose (SMBG) system. In this study, user performance was evaluated for four SMBG systems on the basis of ISO 15197:2013, and possibly related insulin dosing errors were calculated. Additionally, accuracy was assessed in the hands of study personnel. Accu-Chek ® Performa Connect (A), Contour ® plus ONE (B), FreeStyle Optium Neo (C), and OneTouch Select ® Plus (D) were evaluated with one test strip lot. After familiarization with the systems, subjects collected a capillary blood sample and performed an SMBG measurement. Study personnel observed the subjects' measurement technique. Then, study personnel performed SMBG measurements and comparison measurements. Number and percentage of SMBG measurements within ± 15 mg/dl and ± 15% of the comparison measurements at glucose concentrations < 100 and ≥ 100 mg/dl, respectively, were calculated. In addition, insulin dosing errors were modelled. In the hands of lay-users three systems fulfilled ISO 15197:2013 accuracy criteria with the investigated test strip lot showing 96% (A), 100% (B), and 98% (C) of results within the defined limits. All systems fulfilled minimum accuracy criteria in the hands of study personnel [99% (A), 100% (B), 99.5% (C), 96% (D)]. Measurements with all four systems were within zones of the consensus error grid and surveillance error grid associated with no or minimal risk. Regarding calculated insulin dosing errors, all 99% ranges were between dosing errors of - 2.7 and + 1.4 units for measurements in the hands of lay-users and between - 2.5 and + 1.4 units for study personnel. Frequent lay-user errors were not checking the test strips' expiry date and applying blood incorrectly. Data obtained in this study show that not all available SMBG systems complied with ISO 15197:2013 accuracy criteria when measurements were performed by lay-users. The study was registered at ClinicalTrials.gov (NCT02916576). Ascensia Diabetes Care Deutschland GmbH.

An evaluation system for electronic retrospective analyses in radiation oncology: implemented exemplarily for pancreatic cancer

NASA Astrophysics Data System (ADS)

Kessel, Kerstin A.; Jäger, Andreas; Bohn, Christian; Habermehl, Daniel; Zhang, Lanlan; Engelmann, Uwe; Bougatf, Nina; Bendl, Rolf; Debus, Jürgen; Combs, Stephanie E.

2013-03-01

To date, conducting retrospective clinical analyses is rather difficult and time consuming. Especially in radiation oncology, handling voluminous datasets from various information systems and different documentation styles efficiently is crucial for patient care and research. With the example of patients with pancreatic cancer treated with radio-chemotherapy, we performed a therapy evaluation by using analysis tools connected with a documentation system. A total number of 783 patients have been documented into a professional, web-based documentation system. Information about radiation therapy, diagnostic images and dose distributions have been imported. For patients with disease progression after neoadjuvant chemoradiation, we designed and established an analysis workflow. After automatic registration of the radiation plans with the follow-up images, the recurrence volumes are segmented manually. Based on these volumes the DVH (dose-volume histogram) statistic is calculated, followed by the determination of the dose applied to the region of recurrence. All results are stored in the database and included in statistical calculations. The main goal of using an automatic evaluation system is to reduce time and effort conducting clinical analyses, especially with large patient groups. We showed a first approach and use of some existing tools, however manual interaction is still necessary. Further steps need to be taken to enhance automation. Already, it has become apparent that the benefits of digital data management and analysis lie in the central storage of data and reusability of the results. Therefore, we intend to adapt the evaluation system to other types of tumors in radiation oncology.

Induction of protective immunity against toxoplasmosis in mice by immunization with Toxoplasma gondii RNA.

PubMed

Dimier-Poisson, Isabelle; Aline, Fleur; Bout, Daniel; Mévélec, Marie-Noëlle

2006-03-06

Toxoplasma gondii enters the mucosal surfaces of the host, and so immunity at these sites is of major interest. Due to the compartmentalization of the immune response, systemic immunization does not induce high levels of immunity at mucosal surfaces. Intranasal immunization has been shown to be very effective in inducing both systemic and mucosal immune responses. Immunization with mRNA can induce both humoral and cell-mediated immune responses, both of which are important in conferring immunity to T. gondii. The efficacy of RNA vaccination by the nasal route with T. gondii RNA was evaluated. We assessed the percentage of cumulative survival after an oral challenge with a lethal dose of T. gondii cysts (40 cysts), and the number of brain cysts following a challenge with a sublethal dose of T. gondii 76 K cysts (15 cysts). Vaccinated mice were found to be significantly better protected than non-immunized mice after a challenge with a lethal dose of cysts; and a challenge with a sublethal dose also resulted in fewer brain cysts than in non-immunized mice. Sera and intestinal secretions of immunized mice recognized T. gondii antigens, suggesting that a specific humoral immune response may occur. Moreover, a specific lymphoproliferative response observed in cervical lymph nodes may confer protection. These preliminary findings suggest that RNA vaccination by a mucosal route could be feasible.

Sperm shape abnormality and urine mutagenicity in mice treated with niclosamide.

PubMed

Vega, S G; Guzmán, P; García, L; Espinosa, J; Cortinas de Nava, C

1988-02-01

Niclosamide, a widely used anthelmintic drug in underdeveloped countries, is known to be mutagenic in the Salmonella typhimurium microsomal test system. The urine obtained from mice treated with niclosamide is mutagenic in the TA98 and TA1538 strains. Its effects on mouse-sperm morphology were evaluated in CD1 and (BALB/cJ x DBA/2J) F1 mice after 5 daily oral niclosamide doses of either 60, 80, 100 or 120 mg/kg. A statistically significant increase in abnormal sperm morphology was detected in both CD1 and (BALB/cJ x DBA/2J) F1 mice. No drug-related effects on testis weight nor on sperm count were observed in either genotype. Urine samples obtained from niclosamide-treated F1 mice were assayed with the Salmonella typhimurium strain TA1538 both in the absence and presence of beta-glucuronidase. In the absence of glucuronidase, urine mutagenicity increased with increasing dose and the highest doses were toxic. In the presence of glucuronidase, urine mutagenicity and toxicity also increased. Only at the highest dose (120 mg/kg), however, was there a positive correlation between the urine mutagenic activity and an increase in the number of abnormal sperm. The results of this study suggest that the increase in abnormal sperm depends on the systemic presence of non-conjugated niclosamide metabolites.

Effects of irradiation of Aplysia pacemaker neurons with 20-MeV electrons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carpenter, D.O.; Gaubatz, G.; Willis, J.A.

1978-10-01

Aplysia pacemaker neurons are excited by irradiation with 20-MeV electrons. The response is an increase in discharge frequency occurring immediately after exposure and decaying within a few seconds to minutes except at very high exposures. The threshold is on the order of 1000 rad, and cell inactivation occurs acutely only at doses on the order of 20,000 rad. Within these limits the excitatory effect is more or less linear with dose. The acute effect is not associated with dramatic resistance changes, although the resulting depolarization indicates an increase in Na/sup +/ permeability. Synaptic transmission in this preparation does not appearmore » to be more sensitive than impulse propagation. At very high doses, spike generation is blocked. Neurons recorded for a number of hours following irradiation show a hyperpolarization prior to final depolarization, which suggests that one terminal event may be an accumulation of intracellular Ca/sup 2 +/ leading to increased K/sup +/ conductance. These studies confirm and extend previous observations on the relative radioresistance of Aplysia neurons. With respect to mammalian studies on nervous system susceptibility to high doses of radiation, no events were found which correlate in time with early transient incapacitation. However, the depressed excitability occurring several hours after exposure may correlate with the occurrence of death due to the central nervous system syndrome which is seen in higher aminals.« less

Radiation-induced second cancers: the impact of 3D-CRT and IMRT

NASA Technical Reports Server (NTRS)

Hall, Eric J.; Wuu, Cheng-Shie

2003-01-01

Information concerning radiation-induced malignancies comes from the A-bomb survivors and from medically exposed individuals, including second cancers in radiation therapy patients. The A-bomb survivors show an excess incidence of carcinomas in tissues such as the gastrointestinal tract, breast, thyroid, and bladder, which is linear with dose up to about 2.5 Sv. There is great uncertainty concerning the dose-response relationship for radiation-induced carcinogenesis at higher doses. Some animal and human data suggest a decrease at higher doses, usually attributed to cell killing; other data suggest a plateau in dose. Radiotherapy patients also show an excess incidence of carcinomas, often in sites remote from the treatment fields; in addition there is an excess incidence of sarcomas in the heavily irradiated in-field tissues. The transition from conventional radiotherapy to three-dimensional conformal radiation therapy (3D-CRT) involves a reduction in the volume of normal tissues receiving a high dose, with an increase in dose to the target volume that includes the tumor and a limited amount of normal tissue. One might expect a decrease in the number of sarcomas induced and also (less certain) a small decrease in the number of carcinomas. All around, a good thing. By contrast, the move from 3D-CRT to intensity-modulated radiation therapy (IMRT) involves more fields, and the dose-volume histograms show that, as a consequence, a larger volume of normal tissue is exposed to lower doses. In addition, the number of monitor units is increased by a factor of 2 to 3, increasing the total body exposure, due to leakage radiation. Both factors will tend to increase the risk of second cancers. Altogether, IMRT is likely to almost double the incidence of second malignancies compared with conventional radiotherapy from about 1% to 1.75% for patients surviving 10 years. The numbers may be larger for longer survival (or for younger patients), but the ratio should remain the same.

Adaptation of the CVT algorithm for catheter optimization in high dose rate brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poulin, Eric; Fekete, Charles-Antoine Collins; Beaulieu, Luc

2013-11-15

Purpose: An innovative, simple, and fast method to optimize the number and position of catheters is presented for prostate and breast high dose rate (HDR) brachytherapy, both for arbitrary templates or template-free implants (such as robotic templates).Methods: Eight clinical cases were chosen randomly from a bank of patients, previously treated in our clinic to test our method. The 2D Centroidal Voronoi Tessellations (CVT) algorithm was adapted to distribute catheters uniformly in space, within the maximum external contour of the planning target volume. The catheters optimization procedure includes the inverse planning simulated annealing algorithm (IPSA). Complete treatment plans can then bemore » generated from the algorithm for different number of catheters. The best plan is chosen from different dosimetry criteria and will automatically provide the number of catheters and their positions. After the CVT algorithm parameters were optimized for speed and dosimetric results, it was validated against prostate clinical cases, using clinically relevant dose parameters. The robustness to implantation error was also evaluated. Finally, the efficiency of the method was tested in breast interstitial HDR brachytherapy cases.Results: The effect of the number and locations of the catheters on prostate cancer patients was studied. Treatment plans with a better or equivalent dose distributions could be obtained with fewer catheters. A better or equal prostate V100 was obtained down to 12 catheters. Plans with nine or less catheters would not be clinically acceptable in terms of prostate V100 and D90. Implantation errors up to 3 mm were acceptable since no statistical difference was found when compared to 0 mm error (p > 0.05). No significant difference in dosimetric indices was observed for the different combination of parameters within the CVT algorithm. A linear relation was found between the number of random points and the optimization time of the CVT algorithm. Because the computation time decrease with the number of points and that no effects were observed on the dosimetric indices when varying the number of sampling points and the number of iterations, they were respectively fixed to 2500 and to 100. The computation time to obtain ten complete treatments plans ranging from 9 to 18 catheters, with the corresponding dosimetric indices, was 90 s. However, 93% of the computation time is used by a research version of IPSA. For the breast, on average, the Radiation Therapy Oncology Group recommendations would be satisfied down to 12 catheters. Plans with nine or less catheters would not be clinically acceptable in terms of V100, dose homogeneity index, and D90.Conclusions: The authors have devised a simple, fast and efficient method to optimize the number and position of catheters in interstitial HDR brachytherapy. The method was shown to be robust for both prostate and breast HDR brachytherapy. More importantly, the computation time of the algorithm is acceptable for clinical use. Ultimately, this catheter optimization algorithm could be coupled with a 3D ultrasound system to allow real-time guidance and planning in HDR brachytherapy.« less

Exposure to fine particulate, black carbon, and particle number concentration in transportation microenvironments

NASA Astrophysics Data System (ADS)

Morales Betancourt, R.; Galvis, B.; Balachandran, S.; Ramos-Bonilla, J. P.; Sarmiento, O. L.; Gallo-Murcia, S. M.; Contreras, Y.

2017-05-01

This research determined intake dose of fine particulate matter (PM2.5), equivalent black carbon (eBC), and number of sub-micron particles (Np) for commuters in Bogotá, Colombia. Doses were estimated through measurements of exposure concentration, a surrogate of physical activity, as well as travel times and speeds. Impacts of travel mode, traffic load, and street configuration on dose and exposure were explored. Three road segments were selected because of their different traffic loads and composition, and dissimilar street configuration. The transport modes considered include active modes (walking and cycling) and motorized modes (bus, car, taxi, and motorcycle). Measurements were performed simultaneously in the available modes at each road segment. High average eBC concentrations were observed throughout the campaign, ranging from 20 to 120 μgm-3 . Commuters in motorized modes experienced significantly higher exposure concentrations than pedestrians and bicyclists. The highest average concentrations of PM2.5, eBC , and Np were measured inside the city's Bus Rapid Transit (BRT) system vehicles. Pedestrians and bicycle users in an open street configuration were exposed to the lowest average concentrations of PM2.5 and eBC , six times lower than those experienced by commuters using the BRT in the same street segment. Pedestrians experienced the highest particulate matter intake dose in the road segments studied, despite being exposed to lower concentrations than commuters in motorized modes. Average potential dose of PM2.5 and eBC per unit length traveled were nearly three times higher for pedestrians in a street canyon configuration compared to commuters in public transport. Slower travel speed and elevated inhalation rates dominate PM dose for pedestrians. The presence of dedicated bike lanes on sidewalks has a significant impact on reducing the exposure concentration for bicyclists compared to those riding in mixed traffic lanes. This study proposes a simple method to perform loading effect correction for measurements of black carbon using multiple portable aethalometers.

NCICT: a computational solution to estimate organ doses for pediatric and adult patients undergoing CT scans.

PubMed

Lee, Choonsik; Kim, Kwang Pyo; Bolch, Wesley E; Moroz, Brian E; Folio, Les

2015-12-01

We developed computational methods and tools to assess organ doses for pediatric and adult patients undergoing computed tomography (CT) examinations. We used the International Commission on Radiological Protection (ICRP) reference pediatric and adult phantoms combined with the Monte Carlo simulation of a reference CT scanner to establish comprehensive organ dose coefficients (DC), organ absorbed dose per unit volumetric CT Dose Index (CTDIvol) (mGy/mGy). We also developed methods to estimate organ doses with tube current modulation techniques and size specific dose estimates. A graphical user interface was designed to obtain user input of patient- and scan-specific parameters, and to calculate and display organ doses. A batch calculation routine was also integrated into the program to automatically calculate organ doses for a large number of patients. We entitled the computer program, National Cancer Institute dosimetry system for CT(NCICT). We compared our dose coefficients with those from CT-Expo, and evaluated the performance of our program using CT patient data. Our pediatric DCs show good agreements of organ dose estimation with those from CT-Expo except for thyroid. Our results support that the adult phantom in CT-Expo seems to represent a pediatric individual between 10 and 15 years rather than an adult. The comparison of CTDIvol values between NCICT and dose pages from 10 selected CT scans shows good agreements less than 12% except for two cases (up to 20%). The organ dose comparison between mean and modulated mAs shows that mean mAs-based calculation significantly overestimates dose (up to 2.4-fold) to the organs in close proximity to lungs in chest and chest-abdomen-pelvis scans. Our program provides more realistic anatomy based on the ICRP reference phantoms, higher age resolution, the most up-to-date bone marrow dosimetry, and several convenient features compared to previous tools. The NCICT will be available for research purpose in the near future.

Cell irradiation setup and dosimetry for radiobiological studies at ELBE

NASA Astrophysics Data System (ADS)

Zeil, K.; Beyreuther, E.; Lessmann, E.; Wagner, W.; Pawelke, J.

2009-07-01

The radiation source ELBE delivers different types of secondary radiation, which is used for cell irradiation studies in radiobiological research. Thereby an important issue is the determination of the biological effectiveness of photon radiation as a function of photon energy by using low-energetic, monochromatic channeling radiation (10-100 keV) and high-energetic bremsstrahlung (up to 40 MV). Radiobiological studies at the research facility ELBE demand special technical and dosimetric prerequisites. Therefore, a cell irradiation system (CIS) has been designed, constructed and installed at the beam line. The CIS allows automatic irradiation of a larger cell sample number and the compensation of spatial inhomogeneity of the dose distribution within the beam spot. The recently introduced GafChromic ® EBT radiochromic film model has been used to verify the cell irradiation dose deposition achieving a dose uncertainty of <5%. Both, the installed cell irradiation system and the developed dosimetric procedure based on the use of the EBT film have been experimentally tested at ELBE. The biological effectiveness of 34 MV bremsstrahlung with respect to 200 kV X-rays from a conventional X-ray tube has been determined. An RBE value of 0.75 has been measured in good agreement with literature.

Effects of whole-body, ionizing radiation on the semen in beagle dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Day, P.A.

1988-01-01

Six beagle dogs were exposed to a total dose of 183 R of gamma radiation at a dose rate of 1 R/day, while three other dogs were exposed to a single dose of 100 R. Weekly semen analysis was performed on all irradiated dogs plus four nonirradiated dogs. Semen volume, sperm concentration, total sperm count, sperm motility and sperm head morphometry were examined. Dogs exposed to chronic radiation showed a severe decline in sperm numbers, detected after seven weeks of exposure. Sperm concentration and total sperm count were the first parameters affected and were the only parameters consistently affected. Themore » dogs exposed to 100 R as a single dose, did not show a significant decline in sperm numbers. During a 36 week recovery period, the chronically irradiated dogs did show a slight increase in sperm numbers, but they never approached pre-exposure levels.« less

Frame average optimization of cine-mode EPID images used for routine clinical in vivo patient dose verification of VMAT deliveries

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCowan, P. M., E-mail: pmccowan@cancercare.mb.ca; McCurdy, B. M. C.; Medical Physics Department, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, Manitoba R3E 0V9

Purpose: The in vivo 3D dose delivered to a patient during volumetric modulated arc therapy (VMAT) delivery can be calculated using electronic portal imaging device (EPID) images. These images must be acquired in cine-mode (i.e., “movie” mode) in order to capture the time-dependent delivery information. The angle subtended by each cine-mode EPID image during an arc can be changed via the frame averaging number selected within the image acquisition software. A large frame average number will decrease the EPID’s angular resolution and will result in a decrease in the accuracy of the dose information contained within each image. Alternatively, lessmore » EPID images acquired per delivery will decrease the overall 3D patient dose calculation time, which is appealing for large-scale clinical implementation. Therefore, the purpose of this study was to determine the optimal frame average value per EPID image, defined as the highest frame averaging that can be used without an appreciable loss in 3D dose reconstruction accuracy for VMAT treatments. Methods: Six different VMAT plans and six different SBRT-VMAT plans were delivered to an anthropomorphic phantom. Delivery was carried out on a Varian 2300ix model linear accelerator (Linac) equipped with an aS1000 EPID running at a frame acquisition rate of 7.5 Hz. An additional PC was set up at the Linac console area, equipped with specialized frame-grabber hardware and software packages allowing continuous acquisition of all EPID frames during delivery. Frames were averaged into “frame-averaged” EPID images using MATLAB. Each frame-averaged data set was used to calculate the in vivo dose to the patient and then compared to the single EPID frame in vivo dose calculation (the single frame calculation represents the highest possible angular resolution per EPID image). A mean percentage dose difference of low dose (<20% prescription dose) and high dose regions (>80% prescription dose) was calculated for each frame averaged scenario for each plan. The authors defined their unacceptable loss of accuracy as no more than a ±1% mean dose difference in the high dose region. Optimal frame average numbers were then determined as a function of the Linac’s average gantry speed and the dose per fraction. Results: The authors found that 9 and 11 frame averages were suitable for all VMAT and SBRT-VMAT treatments, respectively. This resulted in no more than a 1% loss to any of the dose region’s mean percentage difference when compared to the single frame reconstruction. The optimized number was dependent on the treatment’s dose per fraction and was determined to be as high as 14 for 12 Gy/fraction (fx), 15 for 8 Gy/fx, 11 for 6 Gy/fx, and 9 for 2 Gy/fx. Conclusions: The authors have determined an optimal EPID frame averaging number for multiple VMAT-type treatments. These are given as a function of the dose per fraction and average gantry speed. These optimized values are now used in the authors’ clinical, 3D, in vivo patient dosimetry program. This provides a reduction in calculation time while maintaining the authors’ required level of accuracy in the dose reconstruction.« less

Beam angle selection incorporation of anatomical heterogeneities for pencil beam scanning charged-particle therapy

NASA Astrophysics Data System (ADS)

Toramatsu, Chie; Inaniwa, Taku

2016-12-01

In charged particle therapy with pencil beam scanning (PBS), localization of the dose in the Bragg peak makes dose distributions sensitive to lateral tissue heterogeneities. The sensitivity of a PBS plan to lateral tissue heterogeneities can be reduced by selecting appropriate beam angles. The purpose of this study is to develop a fast and accurate method of beam angle selection for PBS. The lateral tissue heterogeneity surrounding the path of the pencil beams at a given angle was quantified with the heterogeneity number representing the variation of the Bragg peak depth across the cross section of the beams using the stopping power ratio of body tissues with respect to water. To shorten the computation time, one-dimensional dose optimization was conducted along the central axis of the pencil beams as they were directed by the scanning magnets. The heterogeneity numbers were derived for all possible beam angles for treatment. The angles leading to the minimum mean heterogeneity number were selected as the optimal beam angle. Three clinical cases of head and neck cancer were used to evaluate the developed method. Dose distributions and their robustness to setup and range errors were evaluated for all tested angles, and their relation to the heterogeneity numbers was investigated. The mean heterogeneity number varied from 1.2 mm-10.6 mm in the evaluated cases. By selecting a field with a low mean heterogeneity number, target dose coverage and robustness against setup and range errors were improved. The developed method is simple, fast, accurate and applicable for beam angle selection in charged particle therapy with PBS.

Chronic inhalation of carbon monoxide: effects on the respiratory and cardiovascular system at doses corresponding to tobacco smoking.

PubMed

Sørhaug, Sveinung; Steinshamn, Sigurd; Nilsen, Odd G; Waldum, Helge L

2006-12-07

Carbon monoxide (CO) is a dangerous poison in high concentrations, but the long-term effects of low doses of CO, as in the gaseous component of tobacco smoke, are not well known. The aims of our study were to evaluate the long-term effects of inhaled CO on the respiratory and cardiovascular system at doses corresponding to tobacco smoking and its effect on tumourigenesis and pulmonary neuroendocrine (NE) cells. Female Wistar rats were exposed to either CO (200 ppm) for 20 h/day (n=51) or air (n=26) for 72 weeks. Carboxyhaemoglobin was 14.7+/-0.3% in CO exposed animals and 0.3+/-0.1% in controls. In the lungs, no signs of pathology similar to that associated with cigarette smoking were observed, and no differences in number of pulmonary NE cells were observed between the groups. Chronic CO inhalation induced a 20% weight increase of the right ventricle (p=0.001) and a 14% weight increase of the left ventricle and interventricular septum (p<0.001). Histological examination of the myocardium did not reveal any signs of scarring. In the aorta and femoral artery, no signs of atherosclerosis were observed in CO exposed rats. No exposure related carcinogenic effects were observed. Spontaneous tumours were identified in 29% of CO exposed animals and in 28% of the controls. Our results suggest that low dose CO exposure is probably not responsible for the respiratory pathology associated with tobacco smoking. The effects on the cardiovascular system seem to involve myocardial hypertrophy, but not atherogenesis.

MO-D-BRB-02: SBRT Treatment Planning and Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Y.

2016-06-15

Increased use of SBRT and hypofractionation in radiation oncology practice has posted a number of challenges to medical physicist, ranging from planning, image-guided patient setup and on-treatment monitoring, to quality assurance (QA) and dose delivery. This symposium is designed to provide current knowledge necessary for the safe and efficient implementation of SBRT in various linac platforms, including the emerging digital linacs equipped with high dose rate FFF beams. Issues related to 4D CT, PET and MRI simulations, 3D/4D CBCT guided patient setup, real-time image guidance during SBRT dose delivery using gated/un-gated VMAT/IMRT, and technical advancements in QA of SBRT (inmore » particular, strategies dealing with high dose rate FFF beams) will be addressed. The symposium will help the attendees to gain a comprehensive understanding of the SBRT workflow and facilitate their clinical implementation of the state-of-art imaging and planning techniques. Learning Objectives: Present background knowledge of SBRT, describe essential requirements for safe implementation of SBRT, and discuss issues specific to SBRT treatment planning and QA. Update on the use of multi-dimensional and multi-modality imaging for reliable guidance of SBRT. Discuss treatment planning and QA issues specific to SBRT. Provide a comprehensive overview of emerging digital linacs and summarize the key geometric and dosimetric features of the new generation of linacs for substantially improved SBRT. NIH/NCI; Varian Medical Systems; F. Yin, Duke University has a research agreement with Varian Medical Systems. In addition to research grant, I had a technology license agreement with Varian Medical Systems.« less

Performance of dose calculation algorithms from three generations in lung SBRT: comparison with full Monte Carlo‐based dose distributions

PubMed Central

Kapanen, Mika K.; Hyödynmaa, Simo J.; Wigren, Tuija K.; Pitkänen, Maunu A.

2014-01-01

The accuracy of dose calculation is a key challenge in stereotactic body radiotherapy (SBRT) of the lung. We have benchmarked three photon beam dose calculation algorithms — pencil beam convolution (PBC), anisotropic analytical algorithm (AAA), and Acuros XB (AXB) — implemented in a commercial treatment planning system (TPS), Varian Eclipse. Dose distributions from full Monte Carlo (MC) simulations were regarded as a reference. In the first stage, for four patients with central lung tumors, treatment plans using 3D conformal radiotherapy (CRT) technique applying 6 MV photon beams were made using the AXB algorithm, with planning criteria according to the Nordic SBRT study group. The plans were recalculated (with same number of monitor units (MUs) and identical field settings) using BEAMnrc and DOSXYZnrc MC codes. The MC‐calculated dose distributions were compared to corresponding AXB‐calculated dose distributions to assess the accuracy of the AXB algorithm, to which then other TPS algorithms were compared. In the second stage, treatment plans were made for ten patients with 3D CRT technique using both the PBC algorithm and the AAA. The plans were recalculated (with same number of MUs and identical field settings) with the AXB algorithm, then compared to original plans. Throughout the study, the comparisons were made as a function of the size of the planning target volume (PTV), using various dose‐volume histogram (DVH) and other parameters to quantitatively assess the plan quality. In the first stage also, 3D gamma analyses with threshold criteria 3%/3 mm and 2%/2 mm were applied. The AXB‐calculated dose distributions showed relatively high level of agreement in the light of 3D gamma analysis and DVH comparison against the full MC simulation, especially with large PTVs, but, with smaller PTVs, larger discrepancies were found. Gamma agreement index (GAI) values between 95.5% and 99.6% for all the plans with the threshold criteria 3%/3 mm were achieved, but 2%/2 mm threshold criteria showed larger discrepancies. The TPS algorithm comparison results showed large dose discrepancies in the PTV mean dose (D50%), nearly 60%, for the PBC algorithm, and differences of nearly 20% for the AAA, occurring also in the small PTV size range. This work suggests the application of independent plan verification, when the AAA or the AXB algorithm are utilized in lung SBRT having PTVs smaller than 20‐25 cc. The calculated data from this study can be used in converting the SBRT protocols based on type ‘a’ and/or type ‘b’ algorithms for the most recent generation type ‘c’ algorithms, such as the AXB algorithm. PACS numbers: 87.55.‐x, 87.55.D‐, 87.55.K‐, 87.55.kd, 87.55.Qr PMID:24710454

The cellular immune response of Daphnia magna under host-parasite genetic variation and variation in initial dose

PubMed Central

Auld, Stuart K. J. R; Edel, Kai H.; Little, Tom J.

2013-01-01

In invertebrate-parasite systems, the likelihood of infection following parasite exposure is often dependent on the specific combination of host and parasite genotypes (termed genetic specificity). Genetic specificity can maintain diversity in host and parasite populations and is a major component of the Red Queen hypothesis. However, invertebrate immune systems are thought to only distinguish between broad classes of parasite. Using a natural host-parasite system with a well-established pattern of genetic specificity, the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we found that only hosts from susceptible host-parasite genetic combinations mounted a cellular response following exposure to the parasite. These data are compatible with the hypothesis that genetic specificity is attributable to barrier defenses at the site of infection (the gut), and that the systemic immune response is general, reporting the number of parasite spores entering the hemocoel. Further supporting this, we found that larger cellular responses occurred at higher initial parasite doses. By studying the natural infection route, where parasites must pass barrier defenses before interacting with systemic immune responses, these data shed light on which components of invertebrate defense underlie genetic specificity. PMID:23025616

SU-F-T-46: The Effect of Inter-Seed Attenuation and Tissue Composition in Prostate 125I Brachytherapy Dose Calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamura, K; Araki, F; Ohno, T

Purpose: To investigate the difference of dose distributions with/without the effect of inter-seed attenuation and tissue compositions in prostate {sup 125}I brachytherapy dose calculations, using Monte Carlo simulations of Particle and Heavy Ion Transport code System (PHITS). Methods: The dose distributions in {sup 125}I prostate brachytherapy were calculated using PHITS for non-simultaneous and simultaneous alignments of STM1251 sources in water or prostate phantom for six patients. The PHITS input file was created from DICOM-RT file which includes source coordinates and structures for clinical target volume (CTV) and organs at risk (OARs) of urethra and rectum, using in-house Matlab software. Photonmore » and electron cutoff energies were set to 1 keV and 100 MeV, respectively. The dose distributions were calculated with the kerma approximation and the voxel size of 1 × 1 × 1 mm{sup 3}. The number of incident photon was set to be the statistical uncertainty (1σ) of less than 1%. The effect of inter-seed attenuation and prostate tissue compositions was evaluated from dose volume histograms (DVHs) for each structure, by comparing to results of the AAPM TG-43 dose calculation (without the effect of inter-seed attenuation and prostate tissue compositions). Results: The dose reduction due to the inter-seed attenuation by source capsules was approximately 2% for CTV and OARs compared to those of TG-43. In additions, by considering prostate tissue composition, the D{sub 90} and V{sub 100} of CTV reduced by 6% and 1%, respectively. Conclusion: It needs to consider the dose reduction due to the inter-seed attenuation and tissue composition in prostate {sup 125}I brachytherapy dose calculations.« less

Evaluation of hybrid inverse planning and optimization (HIPO) algorithm for optimization in real-time, high-dose-rate (HDR) brachytherapy for prostate.

PubMed

Pokharel, Shyam; Rana, Suresh; Blikenstaff, Joseph; Sadeghi, Amir; Prestidge, Bradley

2013-07-08

The purpose of this study is to investigate the effectiveness of the HIPO planning and optimization algorithm for real-time prostate HDR brachytherapy. This study consists of 20 patients who underwent ultrasound-based real-time HDR brachytherapy of the prostate using the treatment planning system called Oncentra Prostate (SWIFT version 3.0). The treatment plans for all patients were optimized using inverse dose-volume histogram-based optimization followed by graphical optimization (GRO) in real time. The GRO is manual manipulation of isodose lines slice by slice. The quality of the plan heavily depends on planner expertise and experience. The data for all patients were retrieved later, and treatment plans were created and optimized using HIPO algorithm with the same set of dose constraints, number of catheters, and set of contours as in the real-time optimization algorithm. The HIPO algorithm is a hybrid because it combines both stochastic and deterministic algorithms. The stochastic algorithm, called simulated annealing, searches the optimal catheter distributions for a given set of dose objectives. The deterministic algorithm, called dose-volume histogram-based optimization (DVHO), optimizes three-dimensional dose distribution quickly by moving straight downhill once it is in the advantageous region of the search space given by the stochastic algorithm. The PTV receiving 100% of the prescription dose (V100) was 97.56% and 95.38% with GRO and HIPO, respectively. The mean dose (D(mean)) and minimum dose to 10% volume (D10) for the urethra, rectum, and bladder were all statistically lower with HIPO compared to GRO using the student pair t-test at 5% significance level. HIPO can provide treatment plans with comparable target coverage to that of GRO with a reduction in dose to the critical structures.

Assessment of Apixaban Prescribing Patterns for Nonvalvular Atrial Fibrillation in Hospitalized Patients.

PubMed

Gibson, Caitlin M; Smith, Carmen B; Davis, Sondra; Scalese, Michael J

2018-01-01

Apixaban is a direct oral anticoagulant (DOAC) for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). Other DOACs require renal dose adjustments based solely on creatinine clearance. Apixaban differs in that its dose adjustments are more complex, potentially leading to prescribing errors. To determine if adherence to Food and Drug Administration (FDA)-approved dosing for apixaban is maintained in hospitalized patients with NVAF. Patients ≥18 years old with NVAF who received apixaban during admission to 1 of 3 hospitals were evaluated. The primary outcome was to determine if providers order apixaban in accordance with FDA-approved dosages. Secondary outcomes included determining if pharmacist review increased the number of orders in accordance with FDA-approved dosing, which of the 3 criteria (age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL) were met in patients receiving off-label dosing, and the rationale for off-label prescribing. A total of 556 patients met inclusion criteria. Apixaban was dosed according to FDA labeling by providers in 83.4% (n = 464) of orders. After pharmacist review, 87.0% (n = 484) of orders were at the approved dose, 12.2% (n = 68) were underdosed, and 0.7% (n = 4) were overdosed. Most patients who were underdosed met only 1 dose reduction criterion-most commonly age ≥80 years (56.0%). Reasons for off-label dosing included home dose continuation (39.0%), history of or perceived bleeding risk (30.5%), or unspecified/other (30.5%). The majority of apixaban orders for NVAF were based on FDA-approved dosages after provider entry and pharmacist review.

Monte Carlo based estimation of organ and effective doses to patients undergoing hysterosalpingography and retrograde urethrography fluoroscopy procedures

NASA Astrophysics Data System (ADS)

Ngaile, J. E.; Msaki, P. K.; Kazema, R. R.

2018-04-01

Contrast investigations of hysterosalpingography (HSG) and retrograde urethrography (RUG) fluoroscopy procedures remain the dominant diagnostic tools for the investigation of infertility in females and urethral strictures in males, respectively, owing to the scarcity and high cost of services of alternative diagnostic technologies. In light of the radiological risks associated with contrast based investigations of the genitourinary tract systems, there is a need to assess the magnitude of radiation burden imparted to patients undergoing HSG and RUG fluoroscopy procedures in Tanzania. The air kerma area product (KAP), fluoroscopy time, number of images, organ dose and effective dose to patients undergoing HSG and RUG procedures were obtained from four hospitals. The KAP was measured using a flat transmission ionization chamber, while the organ and effective doses were estimated using the knowledge of the patient characteristics, patient related exposure parameters, geometry of examination, KAP and Monte Carlo calculations (PCXMC). The median values of KAP for the HSG and RUG were 2.2 Gy cm2 and 3.3 Gy cm2, respectively. The median organ doses in the present study for the ovaries, urinary bladder and uterus for the HSG procedures, were 1.0 mGy, 4.0 mGy and 1.6 mGy, respectively, while for urinary bladder and testes of the RUG were 3.4 mGy and 5.9 mGy, respectively. The median values of effective doses for the HSG and RUG procedures were 0.65 mSv and 0.59 mSv, respectively. The median values of effective dose per hospital for the HSG and RUG procedures had a range of 1.6-2.8 mSv and 1.9-5.6 mSv, respectively, while the overall differences between individual effective doses across the four hospitals varied by factors of up to 22.0 and 46.7, respectively for the HSG and RUG procedures. The proposed diagnostic reference levels (DRLs) for the HSG and RUG were for KAP 2.8 Gy cm2 and 3.9 Gy cm2, for fluoroscopy time 0.8 min and 0.9 min, and for number of images 5 and 4, respectively. The suggested DRLs for the HSG and RUG procedures may be used by the radiology departments in Tanzania for management of attained dose levels until the national DRLs are established.

Dose in x-ray computed tomography

NASA Astrophysics Data System (ADS)

Kalender, Willi A.

2014-02-01

Radiation dose in x-ray computed tomography (CT) has become a topic of high interest due to the increasing numbers of CT examinations performed worldwide. This review aims to present an overview of current concepts for both scanner output metrics and for patient dosimetry and will comment on their strengths and weaknesses. Controversial issues such as the appropriateness of the CT dose index (CTDI) are discussed in detail. A review of approaches to patient dose assessment presently in practice, of the dose levels encountered and options for further dose optimization are also given and discussed. Patient dose assessment remains a topic for further improvement and for international consensus. All approaches presently in use are based on Monte Carlo (MC) simulations. Estimates for effective dose are established, but they are crude and not patient-specific; organ dose estimates are rarely available. Patient- and organ-specific dose estimates can be provided with adequate accuracy and independent of CTDI phantom measurements by fast MC simulations. Such information, in particular on 3D dose distributions, is important and helpful in optimization efforts. Dose optimization has been performed very successfully in recent years and even resulted in applications with effective dose values of below 1 mSv. In general, a trend towards lower dose values based on technical innovations has to be acknowledged. Effective dose values are down to clearly below 10 mSv on average, and there are a number of applications such as cardiac and pediatric CT which are performed routinely below 1 mSv on modern equipment.

Side effects of methylphenidate in childhood cancer survivors: a randomized placebo-controlled trial.

PubMed

Conklin, Heather M; Lawford, Joanne; Jasper, Bruce W; Morris, E Brannon; Howard, Scott C; Ogg, Susan W; Wu, Shengjie; Xiong, Xiaoping; Khan, Raja B

2009-07-01

To investigate the frequency and severity of side effects of methylphenidate among childhood survivors of acute lymphoblastic leukemia and brain tumors and identify predictors of higher adverse effect levels. Childhood cancer survivors (N = 103) identified as having attention and learning problems completed a randomized, double-blind, 3-week, home-crossover trial of placebo, low-dose methylphenidate (0.3 mg/kg; 10 mg twice daily maximum) and moderate-dose methylphenidate (0.6 mg/kg; 20 mg twice daily maximum). Caregivers completed the Barkley Side Effects Rating Scale (SERS) at baseline and each week during the medication trial. Siblings of cancer survivors (N = 49) were recruited as a healthy comparison group. There was a significantly higher number and severity of symptoms endorsed on the SERS when patients were taking moderate dose compared with placebo or low dose, but not low dose compared with placebo. The number of side effects endorsed on the SERS was significantly lower during all 3 home-crossover weeks (placebo, low dose, moderate dose) when compared with baseline symptom scores. The severity of side effects was also significantly lower, compared with baseline screening, during placebo and low-dose weeks but not moderate-dose weeks. Both the number and severity of symptoms endorsed at baseline were significantly higher for patients compared with siblings. Female gender and lower IQ were associated with higher adverse effect levels. Methylphenidate is generally well tolerated by childhood cancer survivors. There is a subgroup at increased risk for side effects that may need to be closely monitored or prescribed a lower medication dose. The seemingly paradoxical findings of increased "side effects" at baseline must be considered when monitoring side effects and designing clinical trials.

Overcoming the Practical Barriers to Spinal Cord Cell Transplantation for ALS

DTIC Science & Technology

2012-10-01

ABSTRACT: This grant will provide critical data on tolerance and toxicity of cell dosing and numbers of permissible spinal cord injections. Rigorous...Surgical Technique) will provide critical data on tolerance and toxicity of cell dosing and numbers of permissible spinal cord injections. Aim 2 (Graft...connected to a rigid needle of the same gauge as the floating cannula one – Figure 7) using the maximum volume/number of injections could result in

Ipilimumab-induced colitis in patients with metastatic melanoma.

PubMed

De Felice, Kara M; Gupta, Arjun; Rakshit, Sagar; Khanna, Sahil; Kottschade, Lisa A; Finnes, Heidi D; Papadakis, Konstantinos A; Loftus, Edward V; Raffals, Laura E; Markovic, Svetomir N

2015-08-01

Ipilimumab is used for the treatment of metastatic melanoma and is associated with serious immune-related colitis. We aimed to report the clinical features, treatment, and outcomes of patients with ipilimumab-induced colitis. In this retrospective observational study, we identified patients with unresectable melanoma treated with ipilimumab between March 2011 and September 2013. Diarrhea was assessed using the Common Terminology Criteria for Adverse Events, v3.0. Colitis was defined by diarrhea (grade≥2) requiring steroids with or without endoscopic/histologic/radiologic evidence of colitis. A total of 103 patients with metastatic melanoma treated with ipilimumab were identified. Of these, 30 patients (29%) developed diarrhea (all grades), and 23 patients (22%) developed colitis requiring systemic corticosteroid therapy. The median number of ipilimumab doses before onset of diarrhea was 2 (range, 1-4). Six of 23 patients responded to less than 1 mg/kg daily prednisone alone. Fifteen patients required high-dose oral and/or intravenous prednisone (1-2 mg/kg body weight). Six patients had diarrhea refractory to prednisone; five required rescue therapy with budesonide (9-12 mg daily) and one was treated with infliximab (5 mg/kg, three doses). There was one case of severe diarrhea (grade 3) treated successfully with high-dose budesonide (12 mg) monotherapy. Ipilimumab-induced colitis requires early and aggressive medical therapy. Most patients can be successfully managed with systemic corticosteroids. High-dose budesonide is an attractive steroid-sparing agent, however further studies of its efficacy in this setting are needed. Infliximab should be used in refractory cases to avoid colectomy. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

The cost of implementing inpatient bar code medication administration.

PubMed

Sakowski, Julie Ann; Ketchel, Alan

2013-02-01

To calculate the costs associated with implementing and operating an inpatient bar-code medication administration (BCMA) system in the community hospital setting and to estimate the cost per harmful error prevented. This is a retrospective, observational study. Costs were calculated from the hospital perspective and a cost-consequence analysis was performed to estimate the cost per preventable adverse drug event averted. Costs were collected from financial records and key informant interviews at 4 not-for profit community hospitals. Costs included direct expenditures on capital, infrastructure, additional personnel, and the opportunity costs of time for existing personnel working on the project. The number of adverse drug events prevented using BCMA was estimated by multiplying the number of doses administered using BCMA by the rate of harmful errors prevented by interventions in response to system warnings. Our previous work found that BCMA identified and intercepted medication errors in 1.1% of doses administered, 9% of which potentially could have resulted in lasting harm. The cost of implementing and operating BCMA including electronic pharmacy management and drug repackaging over 5 years is $40,000 (range: $35,600 to $54,600) per BCMA-enabled bed and $2000 (range: $1800 to $2600) per harmful error prevented. BCMA can be an effective and potentially cost-saving tool for preventing the harm and costs associated with medication errors.

[Potentially addictive drugs on reimbursable prescription for chronic severe pain].

PubMed

Persheim, Marthe Sæther; Helland, Arne; Spigset, Olav; Slørdal, Lars

2013-01-22

Changes in the Norwegian drug reimbursement system in 2008 included the establishment of a new reimbursement code (-71) which authorises coverage of expenditures for potentially addictive drugs in patients with severe, predominantly non-malignant, chronic pain. This reform has hitherto not been evaluated. We assessed national data on drug reimbursements in accordance with code -71 for the period 2008-2011, and anonymised copies of all confirmation letters granting reimbursements according to code -71 in Central Norway (three counties) for 2010. Approximately 1300 individual applicants' gender and age, diagnosis, potentially addictive drug applied for, drug dose, and identity and specialty of the prescribing physician, were recorded. From the time of establishment, reimbursement code -71 has been utilised by an increasing number of individuals, encompassing close to 10,000 subjects in 3rd quarter 2011. Almost one-third of the approved applications were for pregabalin, and the rest were for various opioids. The diagnoses were most often derived from the musculoskeletal and nervous systems, and were often nonspecific. A considerable number of treatment regimens were not in accordance with current principles for the management of chronic non-malignant pain, and drug doses were at times remarkably high. Aspects of this drug reimbursement regulation should be closely monitored, and may be in need of changes.

Granulocyte colony-stimulating factor in repeated IVF failure, a randomized trial.

PubMed

Aleyasin, Ashraf; Abediasl, Zhila; Nazari, Atefeh; Sheikh, Mahdi

2016-06-01

Recent studies have revealed key roles for granulocyte colony-stimulating factor (GCSF) in embryo implantation process and maintenance of pregnancy, and some studies showed promising results by using local intrauterine infusion of GCSF in patients undergoing in vitro fertilization (IVF). This multicenter, randomized, controlled trial included 112 infertile women with repeated IVF failure to evaluate the efficacy of systemic single-dose subcutaneous GCSF administration on IVF success in these women. In this study, the Long Protocol of ovarian stimulation was used for all participants. Sealed, numbered envelopes assigned 56 patients to receive subcutaneous 300 µg GCSF before implantation and 56 in the control group. The implantation (number of gestational sacs on the total number of transferred embryos), chemical pregnancy (positive serum β-HCG), and clinical pregnancy (gestational sac and fetal heart) rates were compared between the two groups. This trial is registered at www.irct.ir (IRCT201503119568N11). The successful implantation (18% vs 7.2%, P=0.007), chemical pregnancy (44.6% vs 19.6%, P=0.005), and clinical pregnancy (37.5% vs 14.3%, P=0.005) rates were significantly higher in the intervention group than in the control group. After adjustment for participants' age, endometrial thickness, good-quality oocyte counts, number of transferred embryos, and anti-Mullerian hormone levels, GCSF treatment remained significantly associated with successful implantation (OR=2.63, 95% CI=1.09-6.96), having chemical pregnancy (OR= 2.74, 95% CI=1.11-7.38) and clinical pregnancy (OR=2.94, 95% CI=1.23-8.33). In conclusion, administration of single-dose systemic subcutaneous GCSF before implantation significantly increases the IVF success, implantation, and pregnancy rates in infertile women with repeated IVF failure. © 2016 Society for Reproduction and Fertility.

Total target volume is a better predictor of whole brain dose from gamma stereotactic radiosurgery than the number, shape, or location of the lesions

PubMed Central

Narayanasamy, Ganesh; Smith, Adam; Van Meter, Emily; McGarry, Ronald; Molloy, Janelle A.

2013-01-01

Purpose: To assess the hypothesis that the volume of whole brain that receives a certain dose level is primarily dependent on the treated volume rather than on the number, shape, or location of the lesions. This would help a physician validate the suitability of GammaKnife® based stereotactic radiosurgery (GKSR) prior to treatment. Methods: Simulation studies were performed to establish the hypothesis for both oblong and spherical shaped lesions of various numbers and sizes. Forty patients who underwent GKSR [mean age of 54 years (range 7–80), mean number of lesions of 2.5 (range 1–6), and mean lesion volume of 4.4 cm3 (range 0.02–22.2 cm3)] were also studied retrospectively. Following recommendations of QUANTEC, the volume of brain irradiated by the 12 Gy (VB12) isodose line was measured and a power-law based relation is proposed here for estimating VB12 from the known tumor volume and the prescription dose. Results: In the simulation study on oblong, spherical, and multiple lesions, the volume of brain irradiated by 50%, 10%, and 1% of maximum dose was found to have linear, linear, and exponentially increasing dependence on the volume of the treated region, respectively. In the retrospective study on 40 GKSR patients, a similar relationship was found to predict the brain dose with a Spearman correlation coefficient >0.9. In both the studies, the volume of brain irradiated by a certain dose level does not have a statistically significant relationship (p ≥ 0.05) with the number, shape, or position of the lesions. The measured VB12 agrees with calculation to within 1.7%. Conclusions: The results from the simulation and the retrospective clinical studies indicate that the volume of whole brain that receives a certain percentage of the maximum dose is primarily dependent on the treated volume and less on the number, shape, and location of the lesions. PMID:24007147

Effects of a radiation dose reduction strategy for computed tomography in severely injured trauma patients in the emergency department: an observational study.

PubMed

Kim, Soo Hyun; Jung, Seung Eun; Oh, Sang Hoon; Park, Kyu Nam; Youn, Chun Song

2011-11-03

Severely injured trauma patients are exposed to clinically significant radiation doses from computed tomography (CT) imaging in the emergency department. Moreover, this radiation exposure is associated with an increased risk of cancer. The purpose of this study was to determine some effects of a radiation dose reduction strategy for CT in severely injured trauma patients in the emergency department. We implemented the radiation dose reduction strategy in May 2009. A prospective observational study design was used to collect data from patients who met the inclusion criteria during this one year study (intervention group) from May 2009 to April 2010. The prospective data were compared with data collected retrospectively for one year prior to the implementation of the radiation dose reduction strategy (control group). By comparison of the cumulative effective dose and the number of CT examinations in the two groups, we evaluated effects of a radiation dose reduction strategy. All the patients met the institutional adult trauma team activation criteria. The radiation doses calculated by the CT scanner were converted to effective doses by multiplication by a conversion coefficient. A total of 118 patients were included in this study. Among them, 33 were admitted before May 2009 (control group), and 85 were admitted after May 2009 (intervention group). There were no significant differences between the two groups regarding baseline characteristics, such as injury severity and mortality. Additionally, there was no difference between the two groups in the mean number of total CT examinations per patient (4.8 vs. 4.5, respectively; p = 0.227). However, the mean effective dose of the total CT examinations per patient significantly decreased from 78.71 mSv to 29.50 mSv (p < 0.001). The radiation dose reduction strategy for CT in severely injured trauma patients effectively decreased the cumulative effective dose of the total CT examinations in the emergency department. But not effectively decreased the number of CT examinations.

SU-E-T-190: First Integration of Steriotactic Radiotherapy Planning System Iplan with Elekta Linear Accelerator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biplab, S; Soumya, R; Paul, S

2014-06-01

Purpose: For the first time in the world, BrainLAB has integrated its iPlan treatment planning system for clinical use with Elekta linear accelerator (Axesse with a Beam Modulator). The purpose of this study was to compare the calculated and measured doses with different chambers to establish the calculation accuracy of iPlan system. Methods: The iPlan has both Pencil beam (PB) and Monte Carlo (MC) calculation algorithms. Beam data include depth doses, profiles and output measurements for different field sizes. Collected data was verified by vendor and beam modelling was done. Further QA tests were carried out in our clinic. Dosemore » calculation accuracy verified point, volumetric dose measurement using ion chambers of different volumes (0.01cc and 0.125cc). Planner dose verification was done using diode array. Plans were generated in iPlan and irradiated in Elekta Axesse linear accelerator. Results: Dose calculation accuracies verified using ion chamber for 6 and 10 MV beam were 3.5+/-0.33(PB), 1.7%+/-0.7(MC) and 3.9%+/-0.6(PB), 3.4%+/-0.6(MC) respectively. Using a pin point chamber, dose calculation accuracy for 6MV and 10MV was 3.8%+/-0.06(PB), 1.21%+/-0.2(MC) and 4.2%+/-0.6(PB), 3.1%+/-0.7(MC) respectively. The calculated planar dose distribution for 10.4×10.4 cm2 was verified using a diode array and the gamma analysis for 2%-2mm criteria yielded pass rates of 88 %(PB) and 98.8%(MC) respectively. 3mm-3% yields 100% passing for both MC and PB algorithm. Conclusion: Dose calculation accuracy was found to be within acceptable limits for MC for 6MV beam. PB for both beams and MC for 10 MV beam were found to be outside acceptable limits. The output measurements were done twice for conformation. The lower gamma matching was attributed to meager number of measured profiles (only two profiles for PB) and coarse measurement resolution for diagonal profile measurement (5mm). Based on these measurements we concluded that 6 MV MC algorithm is suitable for patient treatment.« less

A new concept of pencil beam dose calculation for 40-200 keV photons using analytical dose kernels.

PubMed

Bartzsch, Stefan; Oelfke, Uwe

2013-11-01

The advent of widespread kV-cone beam computer tomography in image guided radiation therapy and special therapeutic application of keV photons, e.g., in microbeam radiation therapy (MRT) require accurate and fast dose calculations for photon beams with energies between 40 and 200 keV. Multiple photon scattering originating from Compton scattering and the strong dependence of the photoelectric cross section on the atomic number of the interacting tissue render these dose calculations by far more challenging than the ones established for corresponding MeV beams. That is why so far developed analytical models of kV photon dose calculations fail to provide the required accuracy and one has to rely on time consuming Monte Carlo simulation techniques. In this paper, the authors introduce a novel analytical approach for kV photon dose calculations with an accuracy that is almost comparable to the one of Monte Carlo simulations. First, analytical point dose and pencil beam kernels are derived for homogeneous media and compared to Monte Carlo simulations performed with the Geant4 toolkit. The dose contributions are systematically separated into contributions from the relevant orders of multiple photon scattering. Moreover, approximate scaling laws for the extension of the algorithm to inhomogeneous media are derived. The comparison of the analytically derived dose kernels in water showed an excellent agreement with the Monte Carlo method. Calculated values deviate less than 5% from Monte Carlo derived dose values, for doses above 1% of the maximum dose. The analytical structure of the kernels allows adaption to arbitrary materials and photon spectra in the given energy range of 40-200 keV. The presented analytical methods can be employed in a fast treatment planning system for MRT. In convolution based algorithms dose calculation times can be reduced to a few minutes.

Delayed post-treatment with bone marrow-derived mesenchymal stem cells is neurorestorative of striatal medium-spiny projection neurons and improves motor function after neonatal rat hypoxia-ischemia.

PubMed

Cameron, Stella H; Alwakeel, Amr J; Goddard, Liping; Hobbs, Catherine E; Gowing, Emma K; Barnett, Elizabeth R; Kohe, Sarah E; Sizemore, Rachel J; Oorschot, Dorothy E

2015-09-01

Perinatal hypoxia-ischemia is a major cause of striatal injury and may lead to cerebral palsy. This study investigated whether delayed administration of bone marrow-derived mesenchymal stem cells (MSCs), at one week after neonatal rat hypoxia-ischemia, was neurorestorative of striatal medium-spiny projection neurons and improved motor function. The effect of a subcutaneous injection of a high-dose, or a low-dose, of MSCs was investigated in stereological studies. Postnatal day (PN) 7 pups were subjected to hypoxia-ischemia. At PN14, pups received treatment with either MSCs or diluent. A subset of high-dose pups, and their diluent control pups, were also injected intraperitoneally with bromodeoxyuridine (BrdU), every 24h, on PN15, PN16 and PN17. This permitted tracking of the migration and survival of neuroblasts originating from the subventricular zone into the adjacent injured striatum. Pups were euthanized on PN21 and the absolute number of striatal medium-spiny projection neurons was measured after immunostaining for DARPP-32 (dopamine- and cAMP-regulated phosphoprotein-32), double immunostaining for BrdU and DARPP-32, and after cresyl violet staining alone. The absolute number of striatal immunostained calretinin interneurons was also measured. There was a statistically significant increase in the absolute number of DARPP-32-positive, BrdU/DARPP-32-positive, and cresyl violet-stained striatal medium-spiny projection neurons, and fewer striatal calretinin interneurons, in the high-dose mesenchymal stem cell (MSC) group compared to their diluent counterparts. A high-dose of MSCs restored the absolute number of these neurons to normal uninjured levels, when compared with previous stereological data on the absolute number of cresyl violet-stained striatal medium-spiny projection neurons in the normal uninjured brain. For the low-dose experiment, in which cresyl violet-stained striatal medium-spiny neurons alone were measured, there was a lower statistically significant increase in their absolute number in the MSC group compared to their diluent controls. Investigation of behavior in another cohort of animals showed that delayed administration of a high-dose of bone marrow-derived MSCs, at one week after neonatal rat hypoxia-ischemia, improved motor function on the cylinder test. Thus, delayed therapy with a high- or low-dose of adult MSCs, at one week after injury, is effective in restoring the loss of striatal medium-spiny projection neurons after neonatal rat hypoxia-ischemia and a high-dose of MSCs improved motor function. Copyright © 2015 Elsevier Inc. All rights reserved.

Patient radiation dose from computed tomography angiography and digital subtraction angiography of the brain

NASA Astrophysics Data System (ADS)

Netwong, Y.; Krisanachinda, A.

2016-03-01

The 64-row multidetector computed tomography angiography (64-MDCTA) provides vascular image quality of the brain similar to digital subtraction angiography (DSA), but the effective dose of CTA is lower than DSA studied in phantom. The purpose of this study is to evaluate the effective dose from 64-MDCTA and DSA. Effective dose (according to ICRP 103) from 64-MDCTA and DSA flat panel detector for cerebral vessels examination of the brain using standard protocols as recommended by the manufacturer was calculated for 30 cases of MDCTA (15 male and 15 female).The mean patient age was 49.5 (23-89) yrs. 30 cases of DSA (14 male and 16 female), the mean patient age was 46.8 (21-81) yrs. For CTA, the mean effective dose was 3.7 (2.82- 5.19) mSv. For DSA, the mean effective dose was 5.78 (3.3-10.06) mSv. The effective dose of CTA depends on the scanning protocol and scan length. Low tube current can reduce patient dose whereas the number of exposures and number of series in 3D rotational angiography (3D RA) resulted in increasing effective dose in DSA patients.

Practical Advice on Calculating Confidence Intervals for Radioprotection Effects and Reducing Animal Numbers in Radiation Countermeasure Experiments

PubMed Central

Landes, Reid D.; Lensing, Shelly Y.; Kodell, Ralph L.; Hauer-Jensen, Martin

2014-01-01

The dose of a substance that causes death in P% of a population is called an LDP, where LD stands for lethal dose. In radiation research, a common LDP of interest is the radiation dose that kills 50% of the population by a specified time, i.e., lethal dose 50 or LD50. When comparing LD50 between two populations, relative potency is the parameter of interest. In radiation research, this is commonly known as the dose reduction factor (DRF). Unfortunately, statistical inference on dose reduction factor is seldom reported. We illustrate how to calculate confidence intervals for dose reduction factor, which may then be used for statistical inference. Further, most dose reduction factor experiments use hundreds, rather than tens of animals. Through better dosing strategies and the use of a recently available sample size formula, we also show how animal numbers may be reduced while maintaining high statistical power. The illustrations center on realistic examples comparing LD50 values between a radiation countermeasure group and a radiation-only control. We also provide easy-to-use spreadsheets for sample size calculations and confidence interval calculations, as well as SAS® and R code for the latter. PMID:24164553

Operation of commercial R3000 processors in the low earth orbit (LEO) space environment

NASA Astrophysics Data System (ADS)

Kaschmitter, J. L.; Shaeffer, D. L.; Colella, N. J.; McKnett, C. L.; Coakley, P. G.

1991-12-01

Spacecraft processors must operate with minimal degradation of performance in the LEO radiation environment, which includes the effects of total accumulated ionizing dose and single event phenomena (SEP) caused by protons and cosmic rays. Commercially available microprocessors can offer a number of advantages relative to radiation-hardened devices but are not normally designed to tolerate effects induced by the LEO environment. Extensive testing of the MIPS R3000 Reduced Instruction Set Computer (RISC) microprocessor family for operation in LEO environments is reported. The authors have characterized total dose and SEP effects for altitudes and inclinations of interest to systems operating in LEO, and they postulate techniques for detection and alleviation of SEP effects based on experimental results.

28Si total body irradiation injures bone marrow hematopoietic stem cells via induction of cellular apoptosis

NASA Astrophysics Data System (ADS)

Chang, Jianhui; Feng, Wei; Wang, Yingying; Allen, Antiño R.; Turner, Jennifer; Stewart, Blair; Raber, Jacob; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

2017-05-01

Long-term space mission exposes astronauts to a radiation environment with potential health hazards. High-energy charged particles (HZE), including 28Si nuclei in space, have deleterious effects on cells due to their characteristics with high linear energy transfer and dense ionization. The influence of 28Si ions contributes more than 10% to the radiation dose equivalent in the space environment. Understanding the biological effects of 28Si irradiation is important to assess the potential health hazards of long-term space missions. The hematopoietic system is highly sensitive to radiation injury and bone marrow (BM) suppression is the primary life-threatening injuries after exposure to a moderate dose of radiation. Therefore, in the present study we investigated the acute effects of low doses of 28Si irradiation on the hematopoietic system in a mouse model. Specifically, 6-month-old C57BL/6 J mice were exposed to 0.3, 0.6 and 0.9 Gy 28Si (600 MeV) total body irradiation (TBI). The effects of 28Si TBI on BM hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) were examined four weeks after the exposure. The results showed that exposure to 28Si TBI dramatically reduced the frequencies and numbers of HSCs in irradiated mice, compared to non-irradiated controls, in a radiation dose-dependent manner. In contrast, no significant changes were observed in BM HPCs regardless of radiation doses. Furthermore, irradiated HSCs exhibited a significant impairment in clonogenic ability. These acute effects of 28Si irradiation on HSCs may be attributable to radiation-induced apoptosis of HSCs, because HSCs, but not HPCs, from irradiated mice exhibited a significant increase in apoptosis in a radiation dose-dependent manner. However, exposure to low doses of 28Si did not result in an increased production of reactive oxygen species and DNA damage in HSCs and HPCs. These findings indicate that exposure to 28Si irradiation leads to acute HSC damage.

Inhaled corticosteroids in ventilated preterm neonates: a non-randomized dose-ranging study.

PubMed

Raghuram, Kamini; Dunn, Michael; Jangaard, Krista; Reilly, Maureen; Asztalos, Elizabeth; Kelly, Edmond; Vincer, Michael; Shah, Vibhuti

2018-05-07

Inhaled corticosteroids (ICS) offer targeted treatment for bronchopulmonary dysplasia (BPD) with minimal systemic effects compared to systemic steroids. However, dosing of ICS in the management of infants at high-risk of developing BPD is not well established. The objective of this study was to determine an effective dose of ICS for the treatment of ventilator-dependent infants to facilitate extubation or reduce fractional inspired oxygen concentration. Forty-one infants born at < 32 weeks gestational age (GA) or < 1250 g who were ventilator-dependent at 10-28 days postnatal age were included. A non-randomized dose-ranging trial was performed using aerosolized inhaled beclomethasone with hydrofluoralkane propellant (HFA-BDP). Four dosing groups (200, 400, 600 and 800 μg twice daily for 1 week) with 11, 11, 10 and 9 infants in each group, respectively, were studied. The primary outcome was therapeutic efficacy (successful extubation or reduction in FiO 2 of > 75% from baseline) in ≥60% of infants in the group. Oxygen requirements, complications and long-term neurodevelopmental outcomes were also assessed. The median age at enrollment was 22 (10-28) postnatal days. The primary outcome, therapeutic efficacy as defined above, was not achieved in any group. However, there was a significant reduction in post-treatment FiO 2 at a dose of 800 μg bid. No obvious trends were seen in long-term neurodevelopmental outcomes. Therapeutic efficacy was not achieved with all studied doses of ICS. A significant reduction in oxygen requirements was noted in ventilator-dependent preterm infants at 10-28 days of age when given 800 μg of HFA-BDP bid. Larger randomized trials of ICS are required to determine efficacy for the management of infants at high-risk for development of BPD. This clinical trial was registered retrospectively on clinicaltrials.gov. The registration number is NCT03503994 .

SU-E-T-279: A Novel Electron-Beam Combined with Magnetic Field Application for Radiotherapy.

PubMed

Alezra, D; Nardi, E; Koren, S; Bragilovski, D; Orion, I

2012-06-01

The new beam and delivery system consists of an electron accelerator and a system of magnets (one or more). Introducing a transverse magnetic field in and near the tumor, causes the electrons to spiral in this region, thereby producing an effective peak in the depth dose distribution, within the tumor volume. Although the basic idea is not new, we suggest here for the first time, a viable as well as a workable, magnetic field configuration, which in addition to focusing the beam does not interfere with its propagation to the target. The electron accelerator: can be a linear accelerator or any other type electron accelerator, capable of producing different electron energies for different depths and dose absorption accumulation. The Field size can be as small as a pencil beam and as big as any of the other standard field sizes that are used in radiotherapy. The scatter filter can be used or removed. The dose rate accumulation can be as higher as possible.The magnets are able to produce magnetic fields. The order, direction, width, place, shape and number of the magnetic fields define the shape and the Percentage Depth Dose (PDD) curve of the electron beam. Prototypes were successfully tested by means of computer simulation, using:COMSOL-Multiphsics for magnetic fields calculations. FLUKA package, for electron beam MC simulation. Our results suggest that by using an electron beam at different energies, combined with magnetic fields, we could modify the delivered dose. This is caused by manipulating the electron motion via the Lorentz force. The applied magnetic field, will focus the electron beam at a given depth and deposit the energy in a given volume and depth, where otherwise the electron energy will have spread deeper. The direction and magnitude of the magnetic fields will prevent the scattering of the electron beam and its absorption in remote volumes. In practice, we get a pseudo Bragg peak depth dose distribution, applying a relatively low cost system. The therapeutic efficiency induced by the system is of similar efficiency as the ion beam therapy techniques. Our novel concept demonstrates treatment that is almost similar to proton therapy and in some parameters even better performance.Unlike the current high-energy electron therapy, our system's beam deposit almost all of its energy on its target, with a low amount of radiation deposited in tissues from the surface of the skin to the front of tumor, and almost no "exit dose" beyond the tumor. This property will enables to hit tumors with higher, potentially more effective radiation doses, while being considerably less expensive. © 2012 American Association of Physicists in Medicine.

Collection of DICOM RDSR (Digital Imaging and Communication in Medicine, Radiation Dose Structured Report) Information Aimed at Reducing Patient Exposure Dose.

PubMed

Morota, Koichi; Moritake, Takashi; Sun, Lue; Ishihara, Takahiro; Kuma, Natsuyo; Murata, Satomi; Yamada, Takahiro; Okazaki, Ryuji

2016-01-01

The recent progress in angiography technology bestows benefits on patients for minimally invasive than surgery, while there has been an increase in the number of cases involving stochastic effects, such as radiation dermatitis, resulting from upgrading of the procedure because of an extension of the time for fluoroscopy and the number of shots. Recent CT equipment saves the dose data along with image data about the information management for patient exposure dose, which is used for management of individual cumulative dose and the presumed effective dose, using digital imaging and communication in medicine (DICOM). We extracted detailed information about shooting conditions and dose from the DICOM radiation dose structured report (DICOM RDSR) in the angiography area, and evaluated the trend of patient exposure dose in each procedure. As a result, we found that cases exceeding 3 Gy which needed observation in the head region were 16.7% and in the heart region were 27.3%. We also found that angiography had a higher dose of shooting than did fluoroscopy, and that the diagnosis and treatment with tumor involvement required a exposure dose than did vascular lesion. In this paper, we review the shooting conditions as a root of DICOM RDSR information and consider the possibility of planning for further reduction of the exposure dose.

Lemna minor plants chronically exposed to ionising radiation: RNA-seq analysis indicates a dose rate dependent shift from acclimation to survival strategies.

PubMed

Van Hoeck, Arne; Horemans, Nele; Nauts, Robin; Van Hees, May; Vandenhove, Hildegarde; Blust, Ronny

2017-04-01

Ecotoxicological research provides knowledge on ionising radiation-induced responses in different plant species. However, the sparse data currently available are mainly extracted from acute exposure treatments. To provide a better understanding of environmental exposure scenarios, the response to stress in plants must be followed in more natural relevant chronic conditions. We previously showed morphological and biochemical responses in Lemna minor plants continuously exposed for 7days in a dose-rate dependent manner. In this study responses on molecular (gene expression) and physiological (photosynthetic) level are evaluated in L. minor plants exposed to ionising radiation. To enable this, we examined the gene expression profiles of irradiated L. minor plants by using an RNA-seq approach. The gene expression data reveal indications that L. minor plants exposed at lower dose rates, can tolerate the exposure by triggering acclimation responses. In contrast, at the highest dose rate tested, a high number of genes related to antioxidative defense systems, DNA repair and cell cycle were differentially expressed suggesting that only high dose rates of ionising radiation drive L. minor plants into survival strategies. Notably, the photosynthetic process seems to be unaffected in L. minor plants among the tested dose rates. This study, supported by our earlier work, clearly indicates that plants shift from acclimation responses towards survival responses at increasing dose rates of ionising radiation. Copyright © 2017 Elsevier B.V. All rights reserved.

Oncocin derivative Onc72 is highly active against Escherichia coli in a systemic septicaemia infection mouse model.

PubMed

Knappe, Daniel; Fritsche, Stefanie; Alber, Gottfried; Köhler, Gabriele; Hoffmann, Ralf; Müller, Uwe

2012-10-01

The antimicrobial oncocin derivative Onc72 is highly active against a number of Gram-negative bacteria, including resistant strains. Here we study its toxicity and efficacy in a lethal mouse infection model. In an acute toxicity study, purified Onc72 was administered to NMRI mice in four consecutive injections within a period of 24 h as an intraperitoneal bolus. The animals' behaviour was monitored for 5 days, before several organs were examined by histopathology. A lethal Escherichia coli infection model was established and the efficacy of Onc72 was evaluated for different peptide doses considering the survival rates of each dose group and the bacterial counts in blood, lavage and organs. Intraperitoneal bolus injections with single doses of 20 or 40 mg of Onc72 per kg of body weight did not result in any abnormal animal behaviour. No mouse became moribund or died within the studied period. Histopathological examinations revealed no toxic effects. When infected with E. coli at a lethal dose, none of the untreated animals survived the next 24 h, whereas all animals treated three times with Onc72 at doses of ≥5 mg/kg survived the observation period of 5 days. No bacteria were detected in the blood of treated animals after day 5 post-infection. The effective dose (ED(50)) was ∼2 mg/kg. No toxic effects were observed for Onc72 within the studied dose range up to 40 mg/kg, indicating a safety margin of >20.

Safety of fluralaner oral solution, a novel systemic antiparasitic treatment for chickens, in laying hens after oral administration via drinking water.

PubMed

Prohaczik, Angella; Menge, Monika; Huyghe, Bruno; Flochlay-Sigognault, Annie; Traon, Gaëlle Le

2017-08-08

Poultry mites are the most significant pest affecting production systems in the egg-laying industry. Fluralaner is a novel systemic insecticide and acaricide that is effective against poultry mites (Dermanyssus gallinae, Ornithonyssus sylviarum) in chickens after oral administration. This study investigated the safety of oral administration of a 1% solution of fluralaner in drinking water to laying hens at the recommended treatment dose and at multiples of this dose. One hundred-twenty healthy 28-week-old laying hens, weighing 1.4-2.1 kg at first administration, were included in the study, and allocated to 4 treatment groups of 30 hens each receiving daily doses of 0, 0.5, 1.5 and 2.5 mg fluralaner/kg body weight, equivalent to 0, 1, 3, and 5 times the recommended dose of fluralaner. The product was administered via drinking water on a total of six occasions, as 3-day treatment periods twice with an interval of 4 days with no treatment (treatment on days 1, 2, 3 and 8, 9, 10), representing 3 times the recommended number of administrations. Hens supplied with non-medicated drinking water served as controls. During the study, all hens were clinically observed, and their health was carefully monitored including body weight, food and water consumption, hematology, clinical chemistry, and withdrawal reflex test. Eggs laid over the study were evaluated for main characteristics (e.g. weight, shape, strength, shell thickness and soundness, albumen height, yolk color, Haugh unit and presence of blood and/or meat spots). Following euthanasia of the hens at the end of the second treatment period (day 11) or 18 days later (day 29), complete gross post-mortem examination, including organ weight determination, and histopathological examination of multiple tissues were conducted. There were no clinical findings related to fluralaner treatment. Statistically significant differences between the treated groups and the control group were observed for some clinical pathology parameters; none of these findings were considered to be of clinical nor zootechnical relevance. Organ weights, gross post mortem and histopathological examinations did not reveal any finding associated with treatment with fluralaner. Oral administration of fluralaner via drinking water at the recommended treatment dose (0.5 mg/kg body weight twice at 1-week interval), is well tolerated and has a high safety margin up to an overall dose of 15 times the recommended one (5 times the daily dose given 3 times the number of days) in healthy adult laying hens. Based on the present results, the use of the new mite treatment based on fluralaner administered via drinking water is expected to be safe for laying hens under industrial conditions, and to have no negative impact on their egg quality and production.

Cost and Effectiveness of Decontamination Strategies in Radiation Contaminated Areas in Fukushima in Regard to External Radiation Dose

PubMed Central

Yasutaka, Tetsuo; Naito, Wataru; Nakanishi, Junko

2013-01-01

The objective of the present study is to evaluate the cost and effectiveness of decontamination strategies in the special decontamination areas in Fukushima in regard to external radiation dose. A geographical information system (GIS) was used to relate the predicted external dose in the affected areas to the number of potential inhabitants and the land use in the areas. A comprehensive review of the costs of various decontamination methods was conducted as part of the analysis. The results indicate that aerial decontamination in the special decontamination areas in Fukushima would be effective for reducing the air dose rate to the target level in a short period of time in some but not all of the areas. In a standard scenario, analysis of cost and effectiveness suggests that decontamination costs for agricultural areas account for approximately 80% of the total decontamination cost, of which approximately 60% is associated with storage. In addition, the costs of decontamination per person per unit area are estimated to vary greatly. Appropriate selection of decontamination methods may significantly decrease decontamination costs, allowing more meaningful decontamination in terms of the limited budget. Our analysis can help in examining the prioritization of decontamination areas from the viewpoints of cost and effectiveness in reducing the external dose. Decontamination strategies should be determined according to air dose rates and future land-use plans. PMID:24069398

The Influence of High and Low Doses of Bisphenol A (BPA) on the Enteric Nervous System of the Porcine Ileum.

PubMed

Szymanska, Kamila; Makowska, Krystyna; Gonkowski, Slawomir

2018-03-20

Bisphenol A, used in the production of plastic, is able to leach from containers into food and cause multidirectional adverse effects in living organisms, including neurodegeneration and metabolic disorders. Knowledge of the impact of BPA on enteric neurons is practically non-existent. The destination of this study was to investigate the influence of BPA at a specific dose (0.05 mg/kg body weight/day) and at a dose ten times higher (0.5 mg/kg body weight/day), given for 28 days, on the porcine ileum. The influence of BPA on enteric neuron immunoreactive to selected neuronal active substances, including substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL), vesicular acetylcholine transporter (VAChT-used here as a marker of cholinergic neurons), and cocaine- and amphetamine-regulated transcript peptide (CART), was studied by the double immunofluorescence method. Both doses of BPA affected the neurochemical characterization of the enteric neurons. The observed changes depended on the type of enteric plexus but were generally characterized by an increase in the number of cells immunoreactive to the particular substances. More visible fluctuations were observed after treatment with higher doses of BPA. The results confirm that even low doses of BPA may influence the neurochemical characterization of the enteric neurons and are not neutral for living organisms.

Cost and effectiveness of decontamination strategies in radiation contaminated areas in Fukushima in regard to external radiation dose.

PubMed

Yasutaka, Tetsuo; Naito, Wataru; Nakanishi, Junko

2013-01-01

The objective of the present study is to evaluate the cost and effectiveness of decontamination strategies in the special decontamination areas in Fukushima in regard to external radiation dose. A geographical information system (GIS) was used to relate the predicted external dose in the affected areas to the number of potential inhabitants and the land use in the areas. A comprehensive review of the costs of various decontamination methods was conducted as part of the analysis. The results indicate that aerial decontamination in the special decontamination areas in Fukushima would be effective for reducing the air dose rate to the target level in a short period of time in some but not all of the areas. In a standard scenario, analysis of cost and effectiveness suggests that decontamination costs for agricultural areas account for approximately 80% of the total decontamination cost, of which approximately 60% is associated with storage. In addition, the costs of decontamination per person per unit area are estimated to vary greatly. Appropriate selection of decontamination methods may significantly decrease decontamination costs, allowing more meaningful decontamination in terms of the limited budget. Our analysis can help in examining the prioritization of decontamination areas from the viewpoints of cost and effectiveness in reducing the external dose. Decontamination strategies should be determined according to air dose rates and future land-use plans.

Monte Carlo calculations of the impact of a hip prosthesis on the dose distribution

NASA Astrophysics Data System (ADS)

Buffard, Edwige; Gschwind, Régine; Makovicka, Libor; David, Céline

2006-09-01

Because of the ageing of the population, an increasing number of patients with hip prostheses are undergoing pelvic irradiation. Treatment planning systems (TPS) currently available are not always able to accurately predict the dose distribution around such implants. In fact, only Monte Carlo simulation has the ability to precisely calculate the impact of a hip prosthesis during radiotherapeutic treatment. Monte Carlo phantoms were developed to evaluate the dose perturbations during pelvic irradiation. A first model, constructed with the DOSXYZnrc usercode, was elaborated to determine the dose increase at the tissue-metal interface as well as the impact of the material coating the prosthesis. Next, CT-based phantoms were prepared, using the usercode CTCreate, to estimate the influence of the geometry and the composition of such implants on the beam attenuation. Thanks to a program that we developed, the study was carried out with CT-based phantoms containing a hip prosthesis without metal artefacts. Therefore, anthropomorphic phantoms allowed better definition of both patient anatomy and the hip prosthesis in order to better reproduce the clinical conditions of pelvic irradiation. The Monte Carlo results revealed the impact of certain coatings such as PMMA on dose enhancement at the tissue-metal interface. Monte Carlo calculations in CT-based phantoms highlighted the marked influence of the implant's composition, its geometry as well as its position within the beam on dose distribution.

Use of high-dose nandrolone aggravates septic shock in a mouse model.

PubMed

Lin, Che; Chen, Shou-Tung; Chien, Su-Yu; Kuo, Shou-Jen; Chen, Dar-Ren

2011-06-01

Nandrolone, an anabolic-androgenic steroid, is widely misused by athletes who wish to rapidly increase muscle mass and performance. An increasing number of reports have indicated that nandrolone may affect and modulate the immune system. This study aimed to investigate the effects of nandrolone on septic shock-caused immune responses and the cellular mechanism of action using a sepsis murine model. Before septic shock induction, BALB/c mice were given a high dose of nandrolone or peanut oil only. After septic shock induction, mice were sacrificed at different time points. Their blood and tissue specimens were analyzed. It was found that the high-dose nandrolone group had significantly increased mortality compared with the control group (p<0.001). The serum malondialdehyde level was significantly increased in the high-dose group compared with the control group. Animals administered a high dose of nandrolone had significantly increased hepatic tumor necrosis factor-α or splenic interferon-γ at 0 and 6 hours. In lung tissue, insulin-like growth factor-1, insulin-like growth factor binding proteins (IGFBPs) and insulin-like growth factor-1 receptor, and IGFBP1 and IGFBP2 mRNA expression were increased in the high-dose nandrolone group at 6 hours. Nandrolone abuse may hasten the death of patients with septic shock and may aggravate septic shock in mice. Copyright © 2011. Published by Elsevier B.V.

Biodosimetry of Persons Chronically Exposed to Low and Therapeutic Doses of Ionizing Radiation

PubMed Central

Zedginidze, Alla; Namchevadze, Ema; Ormocadze, George; Kapanadze, Archil; Nikuradze, Tamara; Lomidze, Darejan

2016-01-01

Dynamic changes of the chromosomal aberrations and the DNA damage were analyzed in individuals exposed to low and therapeutic doses of radiation. The investigation included 37 persons living in areas where the radioactive sources were discovered 10–12 years ago. It was established by biodosimetry methods that the examined persons had absorbed dose of 0.2–0.7 Gy or had increased number of chromosomal aberrations, though insufficient to determine a dose. Clinical examination, chromosomal analysis, and assay of DNA damage by the comet (single-cell gel electrophoresis) assay were carried out. There was no correlation between the doses received 10 years ago and the cytogenetic changes with clinical outcome. The effect of the local fractionated gamma-irradiation with doses of 40–70 Gy was studied in cancer patients with localized head and neck tumors. The study of chromosomal abnormalities, the DNA damages by the comet assay, and the micronuclei detection of the buccal cells revealed a statistically significant correlation between the initial cytogenetic indices in cancer patients and their dynamic changes during and after the radiation exposure. In addition, the correlation was detected between the initial cytogenetic parameters and the functional stage of red blood system. Our results allow us to conclude that there is a need for further research to estimate the individual radiation risk to optimize and individualize the subsequent medical management of radiotherapy. PMID:28217288

Biodosimetry of Persons Chronically Exposed to Low and Therapeutic Doses of Ionizing Radiation.

PubMed

Zedginidze, Alla; Namchevadze, Ema; Ormocadze, George; Kapanadze, Archil; Nikuradze, Tamara; Lomidze, Darejan

2016-01-01

Dynamic changes of the chromosomal aberrations and the DNA damage were analyzed in individuals exposed to low and therapeutic doses of radiation. The investigation included 37 persons living in areas where the radioactive sources were discovered 10-12 years ago. It was established by biodosimetry methods that the examined persons had absorbed dose of 0.2-0.7 Gy or had increased number of chromosomal aberrations, though insufficient to determine a dose. Clinical examination, chromosomal analysis, and assay of DNA damage by the comet (single-cell gel electrophoresis) assay were carried out. There was no correlation between the doses received 10 years ago and the cytogenetic changes with clinical outcome. The effect of the local fractionated gamma-irradiation with doses of 40-70 Gy was studied in cancer patients with localized head and neck tumors. The study of chromosomal abnormalities, the DNA damages by the comet assay, and the micronuclei detection of the buccal cells revealed a statistically significant correlation between the initial cytogenetic indices in cancer patients and their dynamic changes during and after the radiation exposure. In addition, the correlation was detected between the initial cytogenetic parameters and the functional stage of red blood system. Our results allow us to conclude that there is a need for further research to estimate the individual radiation risk to optimize and individualize the subsequent medical management of radiotherapy.

A novel approach to neutron dosimetry.

PubMed

Balmer, Matthew J I; Gamage, Kelum A A; Taylor, Graeme C

2016-11-01

Having been overlooked for many years, research is now starting to take into account the directional distribution of neutron workplace fields. Existing neutron dosimetry instrumentation does not account for this directional distribution, resulting in conservative estimates of dose in neutron workplace fields (by around a factor of 2, although this is heavily dependent on the type of field). This conservatism could influence epidemiological studies on the health effects of radiation exposure. This paper reports on the development of an instrument which can estimate the effective dose of a neutron field, accounting for both the direction and the energy distribution. A 6 Li-loaded scintillator was used to perform neutron assays at a number of locations in a 20 × 20 × 17.5 cm 3 water phantom. The variation in thermal and fast neutron response to different energies and field directions was exploited. The modeled response of the instrument to various neutron fields was used to train an artificial neural network (ANN) to learn the effective dose and ambient dose equivalent of these fields. All experimental data published in this work were measured at the National Physical Laboratory (UK). Experimental results were obtained for a number of radionuclide source based neutron fields to test the performance of the system. The results of experimental neutron assays at 25 locations in a water phantom were fed into the trained ANN. A correlation between neutron counting rates in the phantom and neutron fluence rates was experimentally found to provide dose rate estimates. A radionuclide source behind shadow cone was used to create a more complex field in terms of energy and direction. For all fields, the resulting estimates of effective dose rate were within 45% or better of their calculated values, regardless of energy distribution or direction for measurement times greater than 25 min. This work presents a novel, real-time, approach to workplace neutron dosimetry. It is believed that in the research presented in this paper, for the first time, a single instrument has been able to estimate effective dose.

Intravenous nicotine self-administration in rats: effects of mecamylamine, hexamethonium and naloxone.

PubMed

DeNoble, Victor J; Mele, Paul C

2006-03-01

The rate and pattern of lever pressing were studied in 18 rats during 24-h sessions in which responding resulted in intravenous infusions of nicotine. There were four indications of the positive reinforcing effect of nicotine: (1) a greater number of lever presses when nicotine was response-contingent compared to when saline was available; (2) a greater number of responses on the lever resulting in an infusion of nicotine than on the control lever; (3) systematic decreases in the number of contingent nicotine infusions when nicotine was delivered noncontingently; and (4) systematic changes in the frequency of lever pressing as a function of dose. Under a fixed ratio 1 (FR 1) schedule, the number of infusions first increased and then decreased as the dose of nicotine was decreased (64, 32, 16, and 8 microg/kg infusion) and nicotine intake (mg/kg every 24 h) was directly related to the infusion dose. As the FR size was increased from 1 to 6, the number of lever presses increased and the number of infusions (32 microg/kg) remained stable. At FR values greater than 6, both the number of lever presses and infusions decreased. Presession injections of mecamylamine (0.75, 1.5, and 3.0 mg/kg, s.c.) decreased the number of infusions in a dose-related manner. Presession injections of hexamethonium (1.5 and 3.0 mg/kg, s.c.) or naloxone (0.75, 1.5, and 3.0 mg/kg, s.c.) did not alter the within- or between-session patterns of nicotine self-administration. Under the conditions of the present experiment, nicotine served as an effective reinforcer and the behavior was shown to be sensitive to both FR size and infusion dose. In addition, the results suggest that nicotine self-administration involves central nicotinic receptors and that opioid receptor antagonism has no effect on nicotine's reinforcing effects in rats.

How Does Patient Radiation Exposure Compare With Low-dose O-arm Versus Fluoroscopy for Pedicle Screw Placement in Idiopathic Scoliosis?

PubMed

Su, Alvin W; McIntosh, Amy L; Schueler, Beth A; Milbrandt, Todd A; Winkler, Jennifer A; Stans, Anthony A; Larson, A Noelle

Intraoperative C-arm fluoroscopy and low-dose O-arm are both reasonable means to assist in screw placement for idiopathic scoliosis surgery. Both using pediatric low-dose O-arm settings and minimizing the number of radiographs during C-arm fluoroscopy guidance decrease patient radiation exposure and its deleterious biological effect that may be associated with cancer risk. We hypothesized that the radiation dose for C-arm-guided fluoroscopy is no less than low-dose O-arm scanning for placement of pedicle screws. A multicenter matched-control cohort study of 28 patients in total was conducted. Fourteen patients who underwent O-arm-guided pedicle screw insertion for spinal fusion surgery in 1 institution were matched to another 14 patients who underwent C-arm fluoroscopy guidance in the other institution in terms of the age of surgery, body weight, and number of imaged spine levels. The total effective dose was compared. A low-dose pediatric protocol was used for all O-arm scans with an effective dose of 0.65 mSv per scan. The effective dose of C-arm fluoroscopy was determined using anthropomorphic phantoms that represented the thoracic and lumbar spine in anteroposterior and lateral views, respectively. The clinical outcome and complications of all patients were documented. The mean total effective dose for the O-arm group was approximately 4 times higher than that of the C-arm group (P<0.0001). The effective dose for the C-arm patients had high variability based on fluoroscopy time and did not correlate with the number of imaged spine levels or body weight. The effective dose of 1 low-dose pediatric O-arm scan approximated 85 seconds of the C-arm fluoroscopy time. All patients had satisfactory clinical outcomes without major complications that required returning to the operating room. Radiation exposure required for O-arm scans can be higher than that required for C-arm fluoroscopy, but it depends on fluoroscopy time. Inclusion of more medical centers and surgeons will better account for the variability of C-arm dose due to distinct patient characteristics, surgeon's preference, and individual institution's protocol. Level III-case-control study.

Very low-dose adult whole-body tumor imaging with F-18 FDG PET/CT

NASA Astrophysics Data System (ADS)

Krol, Andrzej; Naveed, Muhammad; McGrath, Mary; Lisi, Michele; Lavalley, Cathy; Feiglin, David

2015-03-01

The aim of this study was to evaluate if effective radiation dose due to PET component in adult whole-body tumor imaging with time-of-flight F-18 FDG PET/CT could be significantly reduced. We retrospectively analyzed data for 10 patients with the body mass index ranging from 25 to 50. We simulated F-18 FDG dose reduction to 25% of the ACR recommended dose via reconstruction of simulated shorter acquisition time per bed position scans from the acquired list data. F-18 FDG whole-body scans were reconstructed using time-of-flight OSEM algorithm and advanced system modeling. Two groups of images were obtained: group A with a standard dose of F-18 FDG and standard reconstruction parameters and group B with simulated 25% dose and modified reconstruction parameters, respectively. Three nuclear medicine physicians blinded to the simulated activity independently reviewed the images and compared diagnostic quality of images. Based on the input from the physicians, we selected optimal modified reconstruction parameters for group B. In so obtained images, all the lesions observed in the group A were visible in the group B. The tumor SUV values were different in the group A, as compared to group B, respectively. However, no significant differences were reported in the final interpretation of the images from A and B groups. In conclusion, for a small number of patients, we have demonstrated that F-18 FDG dose reduction to 25% of the ACR recommended dose, accompanied by appropriate modification of the reconstruction parameters provided adequate diagnostic quality of PET images acquired on time-of-flight PET/CT.

Surface buildup dose dependence on photon field delivery technique for IMRT

PubMed Central

Yokoyama, Shigeru; Roberson, Peter L.; Litzenberg, Dale W.; Moran, Jean M.; Fraass, Benedick A.

2004-01-01

The more complex delivery techniques required for implementation of intensity‐modulated radiotherapy (IMRT) based on inverse planning optimization have changed the relationship between dose at depth and dose at buildup regions near the surface. Surface buildup dose is dependent on electron contamination primarily from the unblocked view of the flattening filter and secondarily from air and collimation systems. To evaluate the impact of beam segmentation on buildup dose, measurements were performed with 10×10 cm2 fields, which were delivered with 3 static 3.5×10 cm2 or 3×10 cm2 strips, 5 static 2×10 cm2 strips, 10 static 1×10 cm2 strips, and 1.1×10 cm2 dynamic delivery, compared with a 10×10 cm2 open field. Measurements were performed in water and Solid Water using parallel plate chambers, a stereotactic diode, and thermoluminescent dosimeters (TLDs) for a 6 MV X‐ray beam. Depth doses at 2 mm depth (relative to dose at 10 cm depth) were lower by 6%, 7%, 11%, and 10% for the above field delivery techniques, respectively, compared to the open field. These differences are most influenced by differences in multileaf collimator (MLC) transmission contributing to the useful beam. An example IMRT field was also studied to assess variations due to delivery technique (static vs. dynamic) and intensity level. Buildup dose is weakly dependent on the multileaf delivery technique for efficient IMRT fields. PACS numbers: 87.53.‐j, 87.53.Dq PMID:15738914

High variability in the dosing of commonly used antibiotics revealed by a Europe-wide point prevalence study: implications for research and dissemination.

PubMed

Metsvaht, Tuuli; Nellis, Georgi; Varendi, Heili; Nunn, Anthony J; Graham, Susan; Rieutord, Andre; Storme, Thomas; McElnay, James; Mulla, Hussain; Turner, Mark A; Lutsar, Irja

2015-04-16

Antibiotic dosing in neonates varies between countries and centres, suggesting suboptimal exposures for some neonates. We aimed to describe variations and factors influencing the variability in the dosing of frequently used antibiotics in European NICUs to help define strategies for improvement. A sub-analysis of the European Study of Neonatal Exposure to Excipients point prevalence study was undertaken. Demographic data of neonates receiving any antibiotic on the study day within one of three two-week periods from January to June 2012, the dose, dosing interval and route of administration of each prescription were recorded. The British National Formulary for Children (BNFC) and Neofax were used as reference sources. Risk factors for deviations exceeding ±25% of the relevant BNFC dosage recommendation were identified by multivariate logistic regression analysis. In 89 NICUs from 21 countries, 586 antibiotic prescriptions for 342 infants were reported. The twelve most frequently used antibiotics - gentamicin, penicillin G, ampicillin, vancomycin, amikacin, cefotaxime, ceftazidime, meropenem, amoxicillin, metronidazole, teicoplanin and flucloxacillin - covered 92% of systemic prescriptions. Glycopeptide class, GA <32 weeks, 5(th) minute Apgar score <5 and geographical region were associated with deviation from the BNFC dosage recommendation. While the doses of penicillins exceeded recommendations, antibiotics with safety concerns followed (gentamicin) or were dosed below (vancomycin) recommendations. The current lack of compliance with existing dosing recommendations for neonates needs to be overcome through the conduct of well-designed clinical trials with a limited number of antibiotics to define pharmacokinetics/pharmacodynamics, efficacy and safety in this population and by efficient dissemination of the results.

Beyond Gaussians: a study of single spot modeling for scanning proton dose calculation

PubMed Central

Li, Yupeng; Zhu, Ronald X.; Sahoo, Narayan; Anand, Aman; Zhang, Xiaodong

2013-01-01

Active spot scanning proton therapy is becoming increasingly adopted by proton therapy centers worldwide. Unlike passive-scattering proton therapy, active spot scanning proton therapy, especially intensity-modulated proton therapy, requires proper modeling of each scanning spot to ensure accurate computation of the total dose distribution contributed from a large number of spots. During commissioning of the spot scanning gantry at the Proton Therapy Center in Houston, it was observed that the long-range scattering protons in a medium may have been inadequately modeled for high-energy beams by a commercial treatment planning system, which could lead to incorrect prediction of field-size effects on dose output. In the present study, we developed a pencil-beam algorithm for scanning-proton dose calculation by focusing on properly modeling individual scanning spots. All modeling parameters required by the pencil-beam algorithm can be generated based solely on a few sets of measured data. We demonstrated that low-dose halos in single-spot profiles in the medium could be adequately modeled with the addition of a modified Cauchy-Lorentz distribution function to a double-Gaussian function. The field-size effects were accurately computed at all depths and field sizes for all energies, and good dose accuracy was also achieved for patient dose verification. The implementation of the proposed pencil beam algorithm also enabled us to study the importance of different modeling components and parameters at various beam energies. The results of this study may be helpful in improving dose calculation accuracy and simplifying beam commissioning and treatment planning processes for spot scanning proton therapy. PMID:22297324

Herbex-kid Inhibits Immediate Hypersensitivity Reactions in Mice and Rats

PubMed Central

Prasad, Rawal; Jogge, Nanjan Mulla; Bhojraj, Suresh; Emerson, Solomon F.; Prabakar, S.

2008-01-01

Herbex-kid (HK), a polyherbal formulation was evaluated in various experimental allergic models of Type I hypersensitivity reactions. Compound 48/80 (C 48/80) has been shown to induce rat mesentery mast cell degranulation and HK (1.07, 10.75 and 107.5 mg ml−1) inhibited the mast cell degranulation in a dose dependent manner. HK (1.07, 10.75 and 107.5 mg kg−1; p.o.) showed dose-dependent protection against C 48/80 induced systemic anaphylaxis in male Balb/C mice. In active anaphylaxis model, male Wistar rats orally administered with 10.75 and 107.5 mg kg−1 of HK showed significant (P < 0.01) protection against mast cell degranulation, while in passive anaphylaxis model, only at 107.5 mg kg−1 showed significant (P < 0.01) reduction in mast cell degranulation. HK at all dose levels was able to significantly decrease the time spent in nasal rubbing in Wistar rats sensitized to ovalbumin, while only at 107.5 mg kg−1 it showed significant (P < 0.01) reduction in number of sneezes. In C 48/80-induced skin itch model, all dose levels of HK significantly (P < 0.001) decreased the time spent in itching and the number of itches. HK did not produce any significant inhibition in histamine induced contraction in guinea pig ileum. From the above findings we conclude that the HK possesses antiallergic activity mediated by reducing of the release mediators from mast cells and also by 5-HT antagonism without the involvement of histamine (H1) receptors. PMID:18830458

Poster - 49: Assessment of Synchrony respiratory compensation error for CyberKnife liver treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ming; Cygler,

The goal of this work is to quantify respiratory motion compensation errors for liver tumor patients treated by the CyberKnife system with Synchrony tracking, to identify patients with the smallest tracking errors and to eventually help coach patient’s breathing patterns to minimize dose delivery errors. The accuracy of CyberKnife Synchrony respiratory motion compensation was assessed for 37 patients treated for liver lesions by analyzing data from system logfiles. A predictive model is used to modulate the direction of individual beams during dose delivery based on the positions of internally implanted fiducials determined using an orthogonal x-ray imaging system and themore » current location of LED external markers. For each x-ray pair acquired, system logfiles report the prediction error, the difference between the measured and predicted fiducial positions, and the delivery error, which is an estimate of the statistical error in the model overcoming the latency between x-ray acquisition and robotic repositioning. The total error was calculated at the time of each x-ray pair, for the number of treatment fractions and the number of patients, giving the average respiratory motion compensation error in three dimensions. The 99{sup th} percentile for the total radial error is 3.85 mm, with the highest contribution of 2.79 mm in superior/inferior (S/I) direction. The absolute mean compensation error is 1.78 mm radially with a 1.27 mm contribution in the S/I direction. Regions of high total error may provide insight into features predicting groups of patients with larger or smaller total errors.« less

A health record integrated clinical decision support system to support prescriptions of pharmaceutical drugs in patients with reduced renal function: design, development and proof of concept.

PubMed

Shemeikka, Tero; Bastholm-Rahmner, Pia; Elinder, Carl-Gustaf; Vég, Anikó; Törnqvist, Elisabeth; Cornelius, Birgitta; Korkmaz, Seher

2015-06-01

To develop and verify proof of concept for a clinical decision support system (CDSS) to support prescriptions of pharmaceutical drugs in patients with reduced renal function, integrated in an electronic health record system (EHR) used in both hospitals and primary care. A pilot study in one geriatric clinic, one internal medicine admission ward and two outpatient healthcare centers was evaluated with a questionnaire focusing on the usefulness of the CDSS. The usage of the system was followed in a log. The CDSS is considered to increase the attention on patients with impaired renal function, provides a better understanding of dosing and is time saving. The calculated glomerular filtration rate (eGFR) and the dosing recommendation classification were perceived useful while the recommendation texts and background had been used to a lesser extent. Few previous systems are used in primary care and cover this number of drugs. The global assessment of the CDSS scored high but some elements were used to a limited extent possibly due to accessibility or that texts were considered difficult to absorb. Choosing a formula for the calculation of eGFR in a CDSS may be problematic. A real-time CDSS to support kidney-related drug prescribing in both hospital and outpatient settings is valuable to the physicians. It has the potential to improve quality of drug prescribing by increasing the attention on patients with renal insufficiency and the knowledge of their drug dosing. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The Comparison Study of Quadratic Infinite Beam Program on Optimization Instensity Modulated Radiation Therapy Treatment Planning (IMRTP) between Threshold and Exponential Scatter Method with CERR® In The Case of Lung Cancer

NASA Astrophysics Data System (ADS)

Hardiyanti, Y.; Haekal, M.; Waris, A.; Haryanto, F.

2016-08-01

This research compares the quadratic optimization program on Intensity Modulated Radiation Therapy Treatment Planning (IMRTP) with the Computational Environment for Radiotherapy Research (CERR) software. We assumed that the number of beams used for the treatment planner was about 9 and 13 beams. The case used the energy of 6 MV with Source Skin Distance (SSD) of 100 cm from target volume. Dose calculation used Quadratic Infinite beam (QIB) from CERR. CERR was used in the comparison study between Gauss Primary threshold method and Gauss Primary exponential method. In the case of lung cancer, the threshold variation of 0.01, and 0.004 was used. The output of the dose was distributed using an analysis in the form of DVH from CERR. The maximum dose distributions obtained were on the target volume (PTV) Planning Target Volume, (CTV) Clinical Target Volume, (GTV) Gross Tumor Volume, liver, and skin. It was obtained that if the dose calculation method used exponential and the number of beam 9. When the dose calculation method used the threshold and the number of beam 13, the maximum dose distributions obtained were on the target volume PTV, GTV, heart, and skin.

Colonization of plants by human pathogenic bacteria in the course of organic vegetable production.

PubMed

Hofmann, Andreas; Fischer, Doreen; Hartmann, Anton; Schmid, Michael

2014-01-01

In recent years, increasing numbers of outbreaks caused by the consumption of vegetables contaminated with human pathogenic bacteria were reported. The application of organic fertilizers during vegetable production is one of the possible reasons for contamination with those pathogens. In this study laboratory experiments in axenic and soil systems following common practices in organic farming were conducted to identify the minimal dose needed for bacterial colonization of plants and to identify possible factors like bacterial species or serovariation, plant species or organic fertilizer types used, influencing the success of plant colonization by human pathogenic bacteria. Spinach and corn salad were chosen as model plants and were inoculated with different concentrations of Salmonella enterica sv. Weltevreden, Listeria monocytogenes sv. 4b and EGD-E sv. 1/2a either directly (axenic system) or via agricultural soil amended with spiked organic fertilizers (soil system). In addition to PCR- and culture-based detection methods, fluorescence in situ hybridization (FISH) was applied in order to localize bacteria on or in plant tissues. Our results demonstrate that shoots were colonized by the pathogenic bacteria at inoculation doses as low as 4 × 10 CFU/ml in the axenic system or 4 × 10(5) CFU/g in the soil system. In addition, plant species dependent effects were observed. Spinach was colonized more often and at lower inoculation doses compared to corn salad. Differential colonization sites on roots, depending on the plant species could be detected using FISH-CLSM analysis. Furthermore, the transfer of pathogenic bacteria to plants via organic fertilizers was observed more often and at lower initial inoculation doses when fertilization was performed with inoculated slurry compared to inoculated manure. Finally, it could be shown that by introducing a simple washing step, the bacterial contamination was reduced in most cases or even was removed completely in some cases.

Colonization of plants by human pathogenic bacteria in the course of organic vegetable production

PubMed Central

Hofmann, Andreas; Fischer, Doreen; Hartmann, Anton; Schmid, Michael

2014-01-01

In recent years, increasing numbers of outbreaks caused by the consumption of vegetables contaminated with human pathogenic bacteria were reported. The application of organic fertilizers during vegetable production is one of the possible reasons for contamination with those pathogens. In this study laboratory experiments in axenic and soil systems following common practices in organic farming were conducted to identify the minimal dose needed for bacterial colonization of plants and to identify possible factors like bacterial species or serovariation, plant species or organic fertilizer types used, influencing the success of plant colonization by human pathogenic bacteria. Spinach and corn salad were chosen as model plants and were inoculated with different concentrations of Salmonella enterica sv. Weltevreden, Listeria monocytogenes sv. 4b and EGD-E sv. 1/2a either directly (axenic system) or via agricultural soil amended with spiked organic fertilizers (soil system). In addition to PCR- and culture-based detection methods, fluorescence in situ hybridization (FISH) was applied in order to localize bacteria on or in plant tissues. Our results demonstrate that shoots were colonized by the pathogenic bacteria at inoculation doses as low as 4 × 10 CFU/ml in the axenic system or 4 × 105 CFU/g in the soil system. In addition, plant species dependent effects were observed. Spinach was colonized more often and at lower inoculation doses compared to corn salad. Differential colonization sites on roots, depending on the plant species could be detected using FISH-CLSM analysis. Furthermore, the transfer of pathogenic bacteria to plants via organic fertilizers was observed more often and at lower initial inoculation doses when fertilization was performed with inoculated slurry compared to inoculated manure. Finally, it could be shown that by introducing a simple washing step, the bacterial contamination was reduced in most cases or even was removed completely in some cases. PMID:24829562

Cost comparison of unit dose and traditional drug distribution in a long-term-care facility.

PubMed

Lepinski, P W; Thielke, T S; Collins, D M; Hanson, A

1986-11-01

Unit dose and traditional drug distribution systems were compared in a 352-bed long-term-care facility by analyzing nursing time, medication-error rate, medication costs, and waste. Time spent by nurses in preparing, administering, charting, and other tasks associated with medications was measured with a stop-watch on four different nursing units during six-week periods before and after the nursing home began using unit dose drug distribution. Medication-error rate before and after implementation of the unit dose system was determined by patient profile audits and medication inventories. Medication costs consisted of patient billing costs (acquisition cost plus fee) and cost of medications destroyed. The unit dose system required a projected 1507.2 hours less nursing time per year. Mean medication-error rates were 8.53% and 0.97% for the traditional and unit dose systems, respectively. Potential annual savings because of decreased medication waste with the unit dose system were $2238.72. The net increase in cost for the unit dose system was estimated at $615.05 per year, or approximately $1.75 per patient. The unit dose system appears safer and more time-efficient than the traditional system, although its costs are higher.

Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children

PubMed Central

Aglipay, Mary; Birken, Catherine S.; Parkin, Patricia C.; Loeb, Mark B.; Thorpe, Kevin; Chen, Yang; Laupacis, Andreas; Mamdani, Muhammad; Macarthur, Colin; Hoch, Jeffrey S.; Mazzulli, Tony

2017-01-01

Importance Epidemiological studies support a link between low 25-hydroxyvitamin D levels and a higher risk of viral upper respiratory tract infections. However, whether winter supplementation of vitamin D reduces the risk among children is unknown. Objective To determine whether high-dose vs standard-dose vitamin D supplementation reduces the incidence of wintertime upper respiratory tract infections in young children. Design, Setting, and Participants A randomized clinical trial was conducted during the winter months between September 13, 2011, and June 30, 2015, among children aged 1 through 5 years enrolled in TARGet Kids!, a multisite primary care practice–based research network in Toronto, Ontario, Canada. Interventions Three hundred forty-nine participants were randomized to receive 2000 IU/d of vitamin D oral supplementation (high-dose group) vs 354 participants who were randomized to receive 400 IU/d (standard-dose group) for a minimum of 4 months between September and May. Main Outcome Measures The primary outcome was the number of laboratory-confirmed viral upper respiratory tract infections based on parent-collected nasal swabs over the winter months. Secondary outcomes included the number of influenza infections, noninfluenza infections, parent-reported upper respiratory tract illnesses, time to first upper respiratory tract infection, and serum 25-hydroxyvitamin D levels at study termination. Results Among 703 participants who were randomized (mean age, 2.7 years, 57.7% boys), 699 (99.4%) completed the trial. The mean number of laboratory-confirmed upper respiratory tract infections per child was 1.05 (95% CI, 0.91-1.19) for the high-dose group and 1.03 (95% CI, 0.90-1.16) for the standard-dose group, for a between-group difference of 0.02 (95% CI, −0.17 to 0.21) per child. There was no statistically significant difference in number of laboratory-confirmed infections between groups (incidence rate ratio [RR], 0.97; 95% CI, 0.80-1.16). There was also no significant difference in the median time to the first laboratory-confirmed infection: 3.95 months (95% CI, 3.02-5.95 months) for the high-dose group vs 3.29 months (95% CI, 2.66-4.14 months) for the standard-dose group, or number of parent-reported upper respiratory tract illnesses between groups (625 for high-dose vs 600 for standard-dose groups, incidence RR, 1.01; 95% CI, 0.88-1.16). At study termination, serum 25-hydroxyvitamin D levels were 48.7 ng/mL (95% CI, 46.9-50.5 ng/mL) in the high-dose group and 36.8 ng/mL (95% CI, 35.4-38.2 ng/mL) in the standard-dose group. Conclusions and Relevance Among healthy children aged 1 to 5 years, daily administration of 2000 IU compared with 400 IU of vitamin D supplementation did not reduce overall wintertime upper respiratory tract infections. These findings do not support the routine use of high-dose vitamin D supplementation in children for the prevention of viral upper respiratory tract infections. Trial Registration clinicaltrials.gov Identifier: NCT01419262 PMID:28719693

Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children.

PubMed

Aglipay, Mary; Birken, Catherine S; Parkin, Patricia C; Loeb, Mark B; Thorpe, Kevin; Chen, Yang; Laupacis, Andreas; Mamdani, Muhammad; Macarthur, Colin; Hoch, Jeffrey S; Mazzulli, Tony; Maguire, Jonathon L

2017-07-18

Epidemiological studies support a link between low 25-hydroxyvitamin D levels and a higher risk of viral upper respiratory tract infections. However, whether winter supplementation of vitamin D reduces the risk among children is unknown. To determine whether high-dose vs standard-dose vitamin D supplementation reduces the incidence of wintertime upper respiratory tract infections in young children. A randomized clinical trial was conducted during the winter months between September 13, 2011, and June 30, 2015, among children aged 1 through 5 years enrolled in TARGet Kids!, a multisite primary care practice-based research network in Toronto, Ontario, Canada. Three hundred forty-nine participants were randomized to receive 2000 IU/d of vitamin D oral supplementation (high-dose group) vs 354 participants who were randomized to receive 400 IU/d (standard-dose group) for a minimum of 4 months between September and May. The primary outcome was the number of laboratory-confirmed viral upper respiratory tract infections based on parent-collected nasal swabs over the winter months. Secondary outcomes included the number of influenza infections, noninfluenza infections, parent-reported upper respiratory tract illnesses, time to first upper respiratory tract infection, and serum 25-hydroxyvitamin D levels at study termination. Among 703 participants who were randomized (mean age, 2.7 years, 57.7% boys), 699 (99.4%) completed the trial. The mean number of laboratory-confirmed upper respiratory tract infections per child was 1.05 (95% CI, 0.91-1.19) for the high-dose group and 1.03 (95% CI, 0.90-1.16) for the standard-dose group, for a between-group difference of 0.02 (95% CI, -0.17 to 0.21) per child. There was no statistically significant difference in number of laboratory-confirmed infections between groups (incidence rate ratio [RR], 0.97; 95% CI, 0.80-1.16). There was also no significant difference in the median time to the first laboratory-confirmed infection: 3.95 months (95% CI, 3.02-5.95 months) for the high-dose group vs 3.29 months (95% CI, 2.66-4.14 months) for the standard-dose group, or number of parent-reported upper respiratory tract illnesses between groups (625 for high-dose vs 600 for standard-dose groups, incidence RR, 1.01; 95% CI, 0.88-1.16). At study termination, serum 25-hydroxyvitamin D levels were 48.7 ng/mL (95% CI, 46.9-50.5 ng/mL) in the high-dose group and 36.8 ng/mL (95% CI, 35.4-38.2 ng/mL) in the standard-dose group. Among healthy children aged 1 to 5 years, daily administration of 2000 IU compared with 400 IU of vitamin D supplementation did not reduce overall wintertime upper respiratory tract infections. These findings do not support the routine use of high-dose vitamin D supplementation in children for the prevention of viral upper respiratory tract infections. clinicaltrials.gov Identifier: NCT01419262.

Monte Carlo dose calculation in dental amalgam phantom

PubMed Central

Aziz, Mohd. Zahri Abdul; Yusoff, A. L.; Osman, N. D.; Abdullah, R.; Rabaie, N. A.; Salikin, M. S.

2015-01-01

It has become a great challenge in the modern radiation treatment to ensure the accuracy of treatment delivery in electron beam therapy. Tissue inhomogeneity has become one of the factors for accurate dose calculation, and this requires complex algorithm calculation like Monte Carlo (MC). On the other hand, computed tomography (CT) images used in treatment planning system need to be trustful as they are the input in radiotherapy treatment. However, with the presence of metal amalgam in treatment volume, the CT images input showed prominent streak artefact, thus, contributed sources of error. Hence, metal amalgam phantom often creates streak artifacts, which cause an error in the dose calculation. Thus, a streak artifact reduction technique was applied to correct the images, and as a result, better images were observed in terms of structure delineation and density assigning. Furthermore, the amalgam density data were corrected to provide amalgam voxel with accurate density value. As for the errors of dose uncertainties due to metal amalgam, they were reduced from 46% to as low as 2% at d80 (depth of the 80% dose beyond Zmax) using the presented strategies. Considering the number of vital and radiosensitive organs in the head and the neck regions, this correction strategy is suggested in reducing calculation uncertainties through MC calculation. PMID:26500401

SU-F-BRD-08: Guaranteed Epsilon-Optimal Treatment Plans with Minimum Number of Beams for SBRT Using RayStation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yarmand, H; Winey, B; Craft, D

2014-06-15

Purpose: To efficiently find quality-guaranteed treatment plans with the minimum number of beams for stereotactic body radiation therapy using RayStation. Methods: For a pre-specified pool of candidate beams we use RayStation (a treatment planning software for clinical use) to identify the deliverable plan which uses all the beams with the minimum dose to organs at risk (OARs) and dose to the tumor and other structures in specified ranges. Then use the dose matrix information for the generated apertures from RayStation to solve a linear program to find the ideal plan with the same objective and constraints allowing use of allmore » beams. Finally we solve a mixed integer programming formulation of the beam angle optimization problem (BAO) with the objective of minimizing the number of beams while remaining in a predetermined epsilon-optimality of the ideal plan with respect to the dose to OARs. Since the treatment plan optimization is a multicriteria optimization problem, the planner can exploit the multicriteria optimization capability of RayStation to navigate the ideal dose distribution Pareto surface and select a plan of desired target coverage versus OARs sparing, and then use the proposed technique to reduce the number of beams while guaranteeing quality. For the numerical experiments two liver cases and one lung case with 33 non-coplanar beams are considered. Results: The ideal plan uses an impractically large number of beams. The proposed technique reduces the number of beams to the range of practical application (5 to 9 beams) while remaining in the epsilon-optimal range of 1% to 5% optimality gap. Conclusion: The proposed method can be integrated into a general algorithm for fast navigation of the ideal dose distribution Pareto surface and finding the treatment plan with the minimum number of beams, which corresponds to the delivery time, in epsilon-optimality range of the desired ideal plan. The project was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center and partially by RaySearch Laboratories.« less

SU-E-T-614: Plan Averaging for Multi-Criteria Navigation of Step-And-Shoot IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, M; Gao, H; Craft, D

2015-06-15

Purpose: Step-and-shoot IMRT is fundamentally discrete in nature, while multi-criteria optimization (MCO) is fundamentally continuous: the MCO planning consists of continuous sliding across the Pareto surface (the set of plans which represent the tradeoffs between organ-at-risk doses and target doses). In order to achieve close to real-time dose display during this sliding, it is desired that averaged plans share many of the same apertures as the pre-computed plans, since dose computation for apertures generated on-the-fly would be expensive. We propose a method to ensure that neighboring plans on a Pareto surface share many apertures. Methods: Our baseline step-and-shoot sequencing methodmore » is that of K. Engel (a method which minimizes the number of segments while guaranteeing the minimum number of monitor units), which we customize to sequence a set of Pareto optimal plans simultaneously. We also add an error tolerance to study the relationship between the number of shared apertures, the total number of apertures needed, and the quality of the fluence map re-creation. Results: We run tests for a 2D Pareto surface trading off rectum and bladder dose versus target coverage for a clinical prostate case. We find that if we enforce exact fluence map recreation, we are not able to achieve much sharing of apertures across plans. The total number of apertures for all seven beams and 4 plans without sharing is 217. With sharing and a 2% error tolerance, this number is reduced to 158 (73%). Conclusion: With the proposed method, total number of apertures can be decreased by 42% (averaging) with no increment of total MU, when an error tolerance of 5% is allowed. With this large amount of sharing, dose computations for averaged plans which occur during Pareto navigation will be much faster, leading to a real-time what-you-see-is-what-you-get Pareto navigation experience. Minghao Guo and Hao Gao were partially supported by the NSFC (#11405105), the 973 Program (#2015CB856000) and the Shanghai Pujiang Talent Program (#14PJ1404500)« less

SU-E-T-545: A MLC-Equipped Robotic Radiosurgery-Radiotherapy Combined System in Treating Hepatic Lesions: Delivery Efficiency as Compared to a Standard Linac for Treating Hepatic Lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, L; Price, R; Wang, L

Purpose: The CyberKnife (CK) M6 Series introduced a mulitleaf collimator (MLC) beam for extending its capability to the conventional radiotherapy. This work is to investigate delivery efficiency of this system as compared to a standard Varian linac when treating hepatic lesions. Methods: Nine previously treated patients were divided into three groups with three patients in each. Group one: fractionated radiotherapy; Group two: SBRT-like treatments and Group three: fractionated radiotherapy targeting two PTVs. The clinically used plans were generated with the Eclipse treatment planning system (TPS). We re-planned these cases using a Mulitplan (MP) TPS for the CK M6 and normalizedmore » to the same PTV dose coverage. CK factors (CF) (defined as modulation scaling factor in this work), number of nodes (NN), number of MLC segments (NS) and beam delivery time (BT) with an estimated image interval of 60 seconds, were used for evaluation of delivery efficiency. Results: Generated plans from the MP and Eclipse TPS demonstrated the similar quality in terms of PTV confomality index, minimum and maximum PTV doses, and doses received by critical structures. Group one: CF ranged from 8.1 to 8.7, NN from 30 to 40, NS from 120 to 155 and BT from 20 to 23 minutes; group two: CF from 4.7 to 8.5, NN from 15 to 19, NS from 82 to 141 and BT from 18 to 24 minutes; and group three: CF from 7.9 to 10, NN from 47 to 49, NS from 110 to 113 and BT from 20 to 22 minutes. Conclusions: Delivery time is longer for the CK M6 than for the Varian linac (7.8 to 13.7 minutes). Further investigation will be necessary to determine if a PTV reduction from the tracking feature will shorten the delivery time without decreasing plan quality.« less

Volumetric modulated arc therapy vs. c-IMRT for the treatment of upper thoracic esophageal cancer.

PubMed

Zhang, Wu-Zhe; Zhai, Tian-Tian; Lu, Jia-Yang; Chen, Jian-Zhou; Chen, Zhi-Jian; Li, De-Rui; Chen, Chuang-Zhen

2015-01-01

To compare plans using volumetric-modulated arc therapy (VMAT) with conventional sliding window intensity-modulated radiation therapy (c-IMRT) to treat upper thoracic esophageal cancer (EC). CT datasets of 11 patients with upper thoracic EC were identified. Four plans were generated for each patient: c-IMRT with 5 fields (5F) and VMAT with a single arc (1A), two arcs (2A), or three arcs (3A). The prescribed doses were 64 Gy/32 F for the primary tumor (PTV64). The dose-volume histogram data, the number of monitoring units (MUs) and the treatment time (TT) for the different plans were compared. All of the plans generated similar dose distributions for PTVs and organs at risk (OARs), except that the 2A- and 3A-VMAT plans yielded a significantly higher conformity index (CI) than the c-IMRT plan. The CI of the PTV64 was improved by increasing the number of arcs in the VMAT plans. The maximum spinal cord dose and the planning risk volume of the spinal cord dose for the two techniques were similar. The 2A- and 3A-VMAT plans yielded lower mean lung doses and heart V50 values than the c-IMRT. The V20 and V30 for the lungs in all of the VMAT plans were lower than those in the c-IMRT plan, at the expense of increasing V5, V10 and V13. The VMAT plan resulted in significant reductions in MUs and TT. The 2A-VMAT plan appeared to spare the lungs from moderate-dose irradiation most effectively of all plans, at the expense of increasing the low-dose irradiation volume, and also significantly reduced the number of required MUs and the TT. The CI of the PTVs and the OARs was improved by increasing the arc-number from 1 to 2; however, no significant improvement was observed using the 3A-VMAT, except for an increase in the TT.

Design of Interrogation Protocols for Radiation Dose Measurements Using Optically-Stimulated Luminescent Dosimeters.

PubMed

Abraham, Sara A; Kearfott, Kimberlee J; Jawad, Ali H; Boria, Andrew J; Buth, Tobias J; Dawson, Alexander S; Eng, Sheldon C; Frank, Samuel J; Green, Crystal A; Jacobs, Mitchell L; Liu, Kevin; Miklos, Joseph A; Nguyen, Hien; Rafique, Muhammad; Rucinski, Blake D; Smith, Travis; Tan, Yanliang

2017-03-01

Optically-stimulated luminescent dosimeters are capable of being interrogated multiple times post-irradiation. Each interrogation removes a fraction of the signal stored within the optically-stimulated luminescent dosimeter. This signal loss must be corrected to avoid systematic errors in estimating the average signal of a series of optically-stimulated luminescent dosimeter interrogations and requires a minimum number of consecutive readings to determine an average signal that is within a desired accuracy of the true signal with a desired statistical confidence. This paper establishes a technical basis for determining the required number of readings for a particular application of these dosimeters when using certain OSL dosimetry systems.

Blood and small intestine cell kinetics under radiation exposures: Mathematical modeling

NASA Astrophysics Data System (ADS)

Smirnova, O. A.

2009-12-01

Mathematical models which describe the dynamics of two vital body systems (hematopoiesis and small intestinal epithelium) in mammals exposed to acute and chronic radiation are developed. These models, based on conventional biological theories, are implemented as systems of nonlinear differential equations. Their variables and constant parameters have clear biological meaning, that provides successful identification and verification of the models in hand. It is shown that the predictions of the models qualitatively and quantitatively agree with the respective experimental data for small laboratory animals (mice, rats) exposed to acute/chronic irradiation in wide ranges of doses and dose rates. The explanation of a number of radiobiological effects, including those of the low-level long-term exposures, is proposed proceeding from the modeling results. All this bears witness to the validity of employment of the developed models, after a proper identification, in investigation and prediction of radiation effects on the hematopoietic and small intestinal epithelium systems in various mammalian species, including humans. In particular, the models can be used for estimating effects of irradiation on astronauts in the long-term space missions, such as Lunar colonies and Mars voyages.

A NEW MEDIUM‐TERM BIOASSAY SYSTEM FOR DETECTION OF ENVIRONMENTAL CARCINOGENS USING DIETHYLNITROSAMINE‐INITIATED RAT LIVER FOLLOWED BY D‐GALACTOSAMINE TREATMENT AND PARTIAL HEPATECTOMY

PubMed Central

Ito, Nobuyuki; Imaida, Katsumi; de Camargo, Joao Lauro V.; Takahashi, Satoru; Asamoto, Makoto; Tsuda, Hiroyuki

1988-01-01

The effects of D‐galactosamine on induction of preneoplastic glutathione S‐transferase placental form positive liver foci were investigated in F344 rats pretreated with diethylnitrosamine (DEN) in an attempt to improve the predictive value of the medium‐term bioassay system developed in our laboratory. Two weeks after the initial single ip dose (200 mg/kg) of DEN, administration of test compounds was commenced simultaneously with an ip injection of D‐galactosamine at a dose of 300 mg/kg body wt. All rats were then subjected to two‐thirds partial hepatectomy (PH) at week 5 and sacrificed for assessment of lesion yield at week 8. Measurement and comparison of the numbers and areas of glutathione S‐transferase placental form positive (GST‐P+) foci per cm2 revealed a positive response to more carcinogens, including non‐hepatocarcinogens, than did the same bioassay system without injection of D‐galactosamine. Thus the results suggest that inclusion of this extra proliferative stimulus may improve the medium‐term detection of carcinogens and modifiers. PMID:3136108

A Novel Method for Studying the Pharmacokinetics of [14C]Umeclidinium After Application to the Axilla or Palm of Healthy Male Subjects

PubMed Central

Santos, LL; Hughes, SC; Pereira, AI; Young, GC; Hussey, E; Charlton, P; Baptiste‐Brown, S; Stuart, JS; Vincent, V; van Marle, SP; Schmith, VD

2016-01-01

Umeclidinium (UMEC), a long‐acting muscarinic antagonist approved for chronic obstructive pulmonary disease (COPD), was investigated for primary hyperhidrosis as topical therapy. This study evaluated the pharmacokinetics, safety, and tolerability of a single dose of [14C]UMEC applied to either unoccluded axilla (UA), occluded axilla (OA), or occluded palm (OP) of healthy males. After 8 h the formulation was removed. [14C]UMEC plasma concentrations (Cp) were quantified by accelerator mass spectrometry. Occlusion increased systemic exposure by 3.8‐fold. Due to UMEC absorption‐limited pharmacokinetics, Cp data from the OA were combined with intravenous data from a phase I study. The data were described by a two‐compartment population model with sequential zero and first‐order absorption and linear elimination. Simulated systemic exposure following q.d. doses to axilla was similar to the exposure from the inhaled therapy, suggesting that systemic safety following dermal administration can be bridged to the inhaled program, and offering the potential for a reduced number of studies and/or subjects. PMID:27304394

Chernobyl Doses. Volume 1. Analysis of Forest Canopy Radiation Response from Multispectral Imagery and the Relationship to Doses

DTIC Science & Technology

1994-09-01

AD-A284 746 Defense Nuclear Agency Alexandria, VA 22310-3398 DNA-TR-92-37-V1 Chernobyl Doses Volume 1-Analysis of Forest Canopy Radiation Response...REPORT DATE 3. REPORT TYPE AND DATES COVERED 940901 Technical 870929- 930930 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Chernobyl Doses Volume 1-Analysis of...volume of the report Chernobyl Doses presents details of a new, quantitative method for remotely sensing ionizing radiation dose to vegetation

SU-G-206-05: A Comparison of Head Phantoms Used for Dose Determination in Imaging Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiong, Z; Vijayan, S; Kilian-Meneghin, J

Purpose: To determine similarities and differences between various head phantoms that might be used for dose measurements in diagnostic imaging procedures. Methods: We chose four frequently used anthropomorphic head phantoms (SK-150, PBU-50, RS-240T and Alderson Rando), a computational patient phantom (Zubal) and the CTDI head phantom for comparison in our study. We did a CT scan of the head phantoms using the same protocol and compared their dimensions and CT numbers. The scan data was used to calculate dose values for each of the phantoms using EGSnrc Monte Carlo software. An .egsphant file was constructed to describe these phantoms usingmore » a Visual C++ program for DOSXYZnrc/EGSnrc simulation. The lens dose was calculated for a simulated CBCT scan using DOSXYZnrc/EGSnrc and the calculated doses were validated with measurements using Gafchromic film and an ionization chamber. Similar calculations and measurements were made for PA radiography to investigate the attenuation and backscatter differences between these phantoms. We used the Zubal phantom as the standard for comparison since it was developed based on a CT scan of a patient. Results: The lens dose for the Alderson Rando phantom is around 9% different than the Zubal phantom, while the lens dose for the PBU-50 phantom was about 50% higher, possibly because its skull thickness and the density of bone and soft tissue are lower than anthropometric values. The lens dose for the CTDI phantom is about 500% higher because of its totally different structure. The entrance dose profiles are similar for the five anthropomorphic phantoms, while that for the CTDI phantom was distinctly different. Conclusion: The CTDI and PBU-50 head phantoms have substantially larger lens dose estimates in CBCT. The other four head phantoms have similar entrance dose with backscatter hence should be preferred for dose measurement in imaging procedures of the head. Partial support from NIH Grant R01-EB002873 and Toshiba Medical Systems Corp.« less

Simultaneously optimizing dose and schedule of a new cytotoxic agent.

PubMed

Braun, Thomas M; Thall, Peter F; Nguyen, Hoang; de Lima, Marcos

2007-01-01

Traditionally, phase I clinical trial designs are based upon one predefined course of treatment while varying among patients the dose given at each administration. In actual medical practice, patients receive a schedule comprised of several courses of treatment, and some patients may receive one or more dose reductions or delays during treatment. Consequently, the overall risk of toxicity for each patient is a function of both actual schedule of treatment and the differing doses used at each adminstration. Our goal is to provide a practical phase I clinical trial design that more accurately reflects actual medical practice by accounting for both dose per administration and schedule. We propose an outcome-adaptive Bayesian design that simultaneously optimizes both dose and schedule in terms of the overall risk of toxicity, based on time-to-toxicity outcomes. We use computer simulation as a tool to calibrate design parameters. We describe a phase I trial in allogeneic bone marrow transplantation that was designed and is currently being conducted using our new method. Our computer simulations demonstrate that our method outperforms any method that searches for an optimal dose but does not allow schedule to vary, both in terms of the probability of identifying optimal (dose, schedule) combinations, and the numbers of patients assigned to those combinations in the trial. Our design requires greater sample sizes than those seen in traditional phase I studies due to the larger number of treatment combinations examined. Our design also assumes that the effects of multiple administrations are independent of each other and that the hazard of toxicity is the same for all administrations. Our design is the first for phase I clinical trials that is sufficiently flexible and practical to truly reflect clinical practice by varying both dose and the timing and number of administrations given to each patient.

Range and trend of expected toxicity level (ETL) in standard A + B designs: a report from the Children's Oncology Group.

PubMed

Chen, Zhengjia; Krailo, Mark D; Sun, Junfeng; Azen, Stanley P

2009-03-01

The traditional algorithm-based 3+3 designs are most widely used for their practical simplicity in phase I clinical trials. At early stage, a common belief was that the expected toxicity level (ETL) at the maximum tolerated dose (MTD) should be 33% [Storer, B. Design and analysis of phase I clinical trials. Biometrics 1989;45;925-937, Gorden, N., Willson, J. Using toxicity grades in the design and analysis of cancer phase I clinical trials. Statistics in Medicine 1992; 11: 2063-2075, Mick, R. Phase I Clinical Trial Design. In Schilsky, R., Milano, G., Ratain, M., eds. Principles of Antineoplastic Drug Development and Pharmacology New York, NY: Marcel Dekker, 1996; 29-36]. Recently, Kang and Ahn [Kang, S., Ahn, C. The expected toxicity rate at the maximum tolerated dose in the standard phase I cancer clinical trial design. Drug Information Journal 2001; 35:1189-1199, Kang, S., Ahn, C. An investigation of the traditional algorithm-based designs for phase I cancer clinical trials. Drug Information Journal 2002; 36:865-873] found that the ETL is between 17% and 21% and He et al [He, W., Liu, J., Binkowitz, B., Quan, H. A model-based approach in the estimation of the maximum tolerated dose in phase I cancer clinical trials. Statistics in Medicine 2006; 25(12):2027-42] further reported that the ETL ranges from 19% to 24%. However they only investigated designs where the number of dose levels was at most 20. It has practical significance in designing and conducting phase I clinical trial to definitely assess the full range and trend of ETL by all possible number of tested dose levels in traditional algorithm-based A+B designs, especially 3+3 designs. In this simulation study, we originally find that the ETL decreases monotonically from about 30% to 0% as the number of dose levels increase from 3 to infinity, which will correct the inaccuracy in the common belief among phase I trial investigators. To help better design and conduct phase I trials, we create a table as a reference for the association between ETL and number of dose levels considered in a design when the exact shape of the dose-toxicity relationship is not well understood. We conclude that the number of specified dose levels is an important factor affecting substantially the ETL at MTD and recommend that fewer than 20 dose levels be designated.