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Although CSI and GS are established prediction metrics in meteorological literature,3-6, 8, 10-12 few texts have translated them into medical literature.9, 13 We provide here the first translation of CSI and GS into epilepsy literature. We suggest CSI may be an appropriate measure to complement Sens, Spec, PPV and NPV, particularly as it allows combined interpretation of PPV and Sens whilst also avoiding the inflation of NPV and Spec when there are many TNs. GS may be a better metric when there are fewer TN and more CH. Based on the current findings, we suggest a CSI of ≥0.8 would be a reasonable threshold score for achieving diagnostic accuracy. Optimal diagnostic thresholds for GS remain to be elucidated.

This manuscript describes the structure, management and outcomes of a multi-institutional clinical and research medical physics residency program (Harvard Medical Physics Residency Program, or HMPRP) to provide potentially useful information to the centers considering a multi-institutional approach for their training programs.Data from the program documents and public records was used to describe HMPRP and obtain statistics about participating faculty, enrolled residents, and graduates. Challenges associated with forming and managing a multi-institutional program and developed solutions for effective coordination between several clinical centers are described.HMPRP was formed in 2009 and was accredited by the Commission on Accreditation of Medical Physics Education Programs (CAMPEP) in 2011. It is a 3-year therapy program, with a dedicated year of research and the 2 years of clinical training at three academic hospitals. A CAMPEP-accredited Certificate Program is embedded in HMPRP to allow enrolled residents to complete a formal didactic training in medical physics if necessary. The clinical training covers the material required by CAMPEP. In addition, training in protons, CyberKnife, MR-linac, and at network locations is included. The clinical training and academic record of the residents is outstanding. All graduates have found employment within clinical medical physics, mostly at large academic centers and graduates had a 100% pass rate at the oral American Board of Radiology exams. On average, three manuscripts per resident are published during residency, and multiple abstracts are presented at conferences.A multi-institutional medical physics residency program can be successfully formed and managed. With a collaborative administrative structure, the program creates an environment for high-quality clinical training of the residents and high productivity in research. The main advantage of such program is access to a wide variety of resources. The main challenge is creating a structure for efficient management of multiple resources at different locations. This report may provide valuable information to centers considering starting a multi-institutional residency program.

Hydroxymethylnitrofurazone (NFOH) is a nitrofurazone prodrug effective in vivo during acute infections, and it has less hepatotoxicity effect than the standard drug benznidazole (BZN) which has been used during short- and long-term treatment. In the present study, we induced the indeterminate form of Chagas disease in mice with a Y strain of Trypanosoma cruzi and analysed the histopathological data about the effects of NFOH and BZN on different tissues, including the heart, skeletal muscle, liver, kidney, colon, spleen and brain. After infection, BALB/c mice were treated with NFOH (150 mg/kg) and BZN (60 mg/kg) for 60 days and then submitted to immunosuppression using dexamethasone (5 mg/kg) for 14 days. Two trained analysts, as part of a blind evaluation, examined the results using serial sections of 3 mm diameter in two different moments. The results showed reactivation of the disease only in the infected nontreated group (POS). After treatment, amastigote nests were found in the heart, colon, liver and skeletal muscle in the POS group and in the heart and liver of the BZN group. Interestingly, amastigote nests were not found in the NFOH and NEG groups. The histopathological analysis showed fewer tissue lesions and parasite infiltrates in the NFOH group when compared with the BZN and POS groups. We have not observed any increase in the levels of hepatocellular injury biomarkers (AST/ALT) in the NFOH group. These in vivo studies show the potential for NFOH as an effective and safe compound useful as an anti-T. cruzi agent.

Dynamic and reversible assembly of molecules is ubiquitous in the hierarchical superstructures of living systems and plays a key role in cellular functions. In article number 2004042 by Samuel I. Stupp and co‐workers, host ‐guest interactions between b‐cyclodextrin and adamantane‐functionalized peptide amphiphiles led to analogous superstructure formation among nanofibers. The cover displays this hierarchical superstructure formation of fluorescently labelled peptide amphiphile nanofibers captured by confocal microscopy. [Image: see text]

Multisegmented poly(methacrylate)s were synthesized using one pot reversible addition fragmentation chain transfer polymerization. Initially, a series of triblock copolymers were synthesized with different ratios of trimethylsilyl methacrylate, di(ethylene oxide) methacrylate, and oligo(ethylene oxide) methacrylate, and different total polymer molecular weights. Additionally, a polymer containing seven distinct blocks of methacrylic monomers was synthesized in one pot. For the triblock copolymers, the trimethylsilyl group was subsequently hydrolyzed, and the self-assembly of the triblock copolymer was studied in water, under different pH and thermal conditions. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2548–2555

Aim: Existing clinical guidelines have not yet identified an optimal duration of maintenance antipsychotic drug treatment for stable, remitted first-episode psychosis patients. This study compares the perception of relapse risk and attitudes towards maintenance medication among professionals in nursing and social work fields who have direct clinical experience with first-episode psychosis patients. We explore a perception model that identifies the decision-making factors in the clinical dilemma between relapse and maintenance. Methods: A specially designed survey addressing perceptions of relapse risk and optimal duration of maintenance treatment was conducted among 63 experienced health-care professionals (30 nurses and 33 social workers) in the field of early psychosis in Hong Kong. Results: Two clinically relevant themes were identified that affected professionals' judgment on the optimal duration of maintenance treatment in stable, remitted first-episode psychosis patients: (i) the remission period; and (ii) professionals' perceptions of relapse risk involved in medication discontinuation. The remission period was a significant predictor of the perceived relapse risk. Compared with social workers, mental health nurses perceived a higher relapse risk for patients before Bonferroni adjustment. Conclusions: The three key clinical components discussed – remission period, perceived relapse risk and perceived optimal duration of maintenance treatment – are interconnected, collectively influencing health-care professionals' attitudes towards relapse and maintenance for patients. Our study identified differences between the perceptions of nursing and social work professionals, indicating a need for communication and discussion among professional groups in order to arrive at a coherent, efficacious team consensus.

The authors report the development of a new procedure for mechanical quality assurance of linear accelerators using an infrared-guided system. The system consists of an infrared (IR) camera and an IR-reflective marker that can be attached to a gantry, a collimator, or a treatment table. The trace of this marker can be obtained in three dimensions (3D) for a full or partial rotation of the mechanical devices. The software is written to localize rotational axes of the gantry, collimator, and the treatment table based on the marker traces. The separation of these axes characterizes the size of the sphere defining the mechanical isocenter. Additional information on anomalies in gantry movement such as degree of gantry sag and hysteresis can also be obtained. An intrinsic uncertainty of the system to localize rotational axis is 0.35 mm or less. Tests on a linear accelerator demonstrated the ability of this system to detect the separation between rotational axes of less than 1 mm and to confirm orthogonality of the planes of gantry, collimator, and table rotation.

Although the severity of haemophilic arthropathy is commonly assessed using established radiographic scoring systems, there is limited available information about their inter- and intra-observer reliability. The purpose of the present study was to establish the inter-observer reliability (IEOR) and intra-observer reliability (IAOR) of three different methods available for the classification of haemophilic arthropathy, including the Arnold and Hilgartner classification, a modification to the Arnold and Hilgartner system described by Luck et al., and the classification described by Pettersson et al. Antero-posterior and lateral radiographs of 54 haemophilic joints were included for the analysis. To determine the IEOR for each one of the three radiographic systems, the radiographs were randomly evaluated by four observers, including two orthopaedic surgeons, one orthopaedic resident and one haematologist. For the determination of IAOR, all four reviewers repeated the assessment in a similar fashion, after a period of at least 2 weeks. IEOR and IAOR for the three classification systems was established using kappa (kappa) statistics. A Spearman rank correlation was used to determine the similarities between each reviewer's own interpretative scales. The IEOR was low for the Arnold and Hilgartner system (kappa = 0.35, P < or = 0.001) and the Luck system (kappa = 0.38, P < or = 0.001), but even lower for the Pettersson system (kappa = 0.06, P = 0.1). For the Pettersson system, particularly low kappa values were observed for the presence or absence of osteoporosis (kappa = 0.11, P = 0.0027), enlarged epiphysis (kappa = 0.10, P = 0.0039), erosion of joint margins (kappa = 0.11, P = 0.0018), and joint deformity (kappa = 0.16, P = 0.00001). However, a relatively high Spearman rank correlation for all three scales [r(s) = 0.75 (P < 0.001) for Arnold and Hilgartner system, r(s) = 0.74 (P < 0.001) for the Luck system and r(s) = 0.81 (P < 0.001) for Pettersson system] indicated an overall, general agreement among the reviewers with regard to the severity of the haemophilic arthropathy. There was a moderate IAOR value for both, the Arnold and Hilgartner system (kappa = 0.57, P = 0.00001) and the Luck system (kappa = 0.62, P = 0.00001) with a low IAOR value for the Pettersson system [kappa = 0.22, P = 0.00001). Currently available radiographic scoring systems for haemophilic arthropathy have low inter- and intra-observer reliability rates. Improvements, either through education or modification of the scoring systems, are critical in an era where correlations between clinical and radiographic scores have received significant attention.

Interplay between organ motion and leaf motion has been shown to generally have a small dosimetric impact for most clinical intensity-modulated radiation therapy treatments. However, it has also been shown that for some MLC sequences there can be large daily variations in the delivered dose, depending on details of patient motion or the number of fractions. This study investigates guidelines for dynamic MLC sequences that will keep daily dose variations due to the interplay between organ motion and leaf motion within 10%. Dose distributions for a range of MLC separations (0.2-5.0 cm) and displacements between adjacent MLCs (0-1.5 cm) were exported from ECLIPSE to purpose-written software, which simulated the dose distribution delivered to a moving target. Target motion parallel and perpendicular to the MLC motion was investigated for a range of amplitudes (0.5-4.0 cm), periods (1.5-10 s), and MLC speeds (0.1-3.0 cm/s) with target motions modeled as sin. Results were confirmed experimentally by measuring the dose delivered to an ion chamber array in a moving phantom for different MLC sequences. The simulation results were used to identify MLC sequences that kept dose variations within 10% compared to the dose delivered with no motion. The maximum allowable MLC speed, when target motion is parallel to the MLC motion, was found to be a simple function of target period and MLC separation. When the target motion is perpendicular to MLC motion, the maximum allowable MLC speed can be described as a function of MLC separation and the displacement of adjacent MLCs. These guidelines were successfully applied to two-dimensional motion, and a simple program was written to import MLC sequence files and evaluate whether the maximum daily dose discrepancy caused by the interplay effect will be larger than 10%. This software was experimentally evaluated, and found to conservatively predict whether a given MLC sequence could give large daily dose discrepancies.

Quality assurance (QA) systems for intensity‐modulated radiation therapy (IMRT) have become standard tools in modern clinical medical physics departments. However, because formalized industry standards or recommendations from professional societies have yet to be defined, methods of IMRT QA analysis vary from institution to institution. Understanding where matters stand today is an important step toward improving the effectiveness of IMRT QA and developing standards. We therefore conducted an IMRT QA survey. This particular survey was limited to users of an electronic two‐dimensional diode array device, but we took care to keep the questions as general and useful as possible. The online survey polled institutions (one survey per institution) on a collection of questions about methods of IMRT QA. The topics were general to the IMRT QA analysis methods common to all IMRT systems; none of the questions was vendor‐ or product‐specific. Survey results showed that a significant proportion of responding institutions (32.8%) use the single‐gantry‐angle composite method for IMRT QA analysis instead of field‐by‐field analysis. Most institutions perform absolute dose comparisons rather than relative dose comparisons, with the 3% criterion being used most often for the percentage difference analysis, and the 3 mm criterion for distance‐to‐agreement analysis. The most prevalent standard for acceptance testing is the combined 3% and 3 mm criteria. A significant percentage of responding institutions report not yet having standard benchmarks for acceptance testing—specifically, 26.6%, 35.3%, and 67.6% had not yet established standard acceptance criteria for prostate, head and neck, and breast IMRT respectively. This survey helps in understanding how institutions perform IMRT QA analysis today. This understanding will help to move institutions toward more standardized acceptance testing. But before standards are defined, it would be useful to connect the conventional planar QA analyses to their resulting impact on the overall plan, using clinically relevant metrics (such as estimated deviations in dose–volume histograms). PACS numbers: 87.50.Gi, 87.52.Df, 87.52.Px, 87.53.Dq, 87.53.Tf, 87.53.Kn, 87.56.Fc

This work is intended to investigate the application and accuracy of micro-MOSFET for superficial dose measurement under clinically used MV x-ray beams. Dose response of micro-MOSFET in the build-up region and on surface under MV x-ray beams were measured and compared to Monte Carlo calculations. First, percentage-depth-doses were measured with micro-MOSFET under 6 and 10 MV beams of normal incidence onto a flat solid water phantom. Micro-MOSFET data were compared with the measurements from a parallel plate ionization chamber and Monte Carlo dose calculation in the build-up region. Then, percentage-depth-doses were measured for oblique beams at 0 degrees-80 degrees onto the flat solid water phantom with micro-MOSFET placed at depths of 2 cm, 1 cm, and 2 mm below the surface. Measurements were compared to Monte Carlo calculations under these settings. Finally, measurements were performed with micro-MOSFET embedded in the first 1 mm layer of bolus placed on a flat phantom and a curved phantom of semi-cylindrical shape. Results were compared to superficial dose calculated from Monte Carlo for a 2 mm thin layer that extends from the surface to a depth of 2 mm. Results were (1) Comparison of measurements with MC calculation in the build-up region showed that micro-MOSFET has a water-equivalence thickness (WET) of 0.87 mm for 6 MV beam and 0.99 mm for 10 MV beam from the flat side, and a WET of 0.72 mm for 6 MV beam and 0.76 mm for 10 MV beam from the epoxy side. (2) For normal beam incidences, percentage depth dose agree within 3%-5% among micro-MOSFET measurements, parallel-plate ionization chamber measurements, and MC calculations. (3) For oblique incidence on the flat phantom with micro-MOSFET placed at depths of 2 cm, 1 cm, and 2 mm, measurements were consistent with MC calculations within a typical uncertainty of 3%-5%. (4) For oblique incidence on the flat phantom and a curved-surface phantom, measurements with micro-MOSFET placed at 1.0 mm agrees with the MC calculation within 6%, including uncertainties of micro-MOSFET measurements of 2%-3% (1 standard deviation), MOSFET angular dependence of 3.0%-3.5%, and 1%-2% systematical error due to phantom setup geometry asymmetry. Micro-MOSFET can be used for skin dose measurements in 6 and 10 MV beams with an estimated accuracy of +/- 6%.

Cumulative dose distributions in fractionated radiation therapy depict the dose to normal tissues and therefore may permit an estimation of the risk of normal tissue complications. However, calculation of these distributions is highly challenging because of interfractional changes in the geometry of patient anatomy. This work presents an algorithm for deformable structure registration of the bladder and the verification of the accuracy of the algorithm using phantom and patient data. In this algorithm, the registration process involves conformal mapping of genus zero surfaces using finite element analysis, and guided by three control landmarks. The registration produces a correspondence between fractions of the triangular meshes used to describe the bladder surface. For validation of the algorithm, two types of balloons were inflated gradually to three times their original size, and several computerized tomography(CT) scans were taken during the process. The registration algorithm yielded a local accuracy of 4 mm along the balloon surface. The algorithm was then applied to CT data of patients receiving fractionated high-dose-rate brachytherapy to the vaginal cuff, with the vaginal cylinder in situ. The patients’ bladder filling status was intentionally different for each fraction. The three required control landmark points were identified for the bladder based on anatomy. Out of an Institutional Review Board (IRB) approved study of 20 patients, 3 had radiographically identifiable points near the bladder surface that were used for verification of the accuracy of the registration. The verification point as seen in each fraction was compared with its predicted location based on affine as well as deformable registration. Despite the variation in bladder shape and volume, the deformable registration was accurate to 5 mm , consistently outperforming the affine registration. We conclude that the structure registration algorithm presented works with reasonable accuracy and provides a means of calculating cumulative dose distributions.

We have designed and implemented a new stereotactic linac QA test with stereotactic precision. The test is used to characterize gantry sag, couch wobble, cone placement, MLC offsets, and room lasers' positions relative to the radiation isocenter. Two MLC star patterns, a cone pattern, and the laser line patterns are recorded on the same imaging medium. Phosphor plates are used as imaging medium due to their sensitivity to red light. The red light of room lasers erases some of the irradiation information stored on the phosphor plates enabling accurate and direct measurements for the position of room lasers and radiation isocenter. Using film instead of the phosphor plate as imaging medium is possible, however, it is less practical. The QA method consists of irradiating four phosphor plates that record the gantry sag between the 0 deg.and 180 deg.gantry angles, the position and stability of couch rotational axis, the sag between the 90 deg.and 270 deg.gantry angles, the accuracy of cone placement on the collimator, the MLC offsets from the collimator rotational axis, and the position of laser lines relative to the radiation isocenter. The estimated accuracy of the method is {+-}0.2 mm. The observed reproducibility of the method is aboutmore » {+-}0.1 mm. The total irradiation/illumination time is about 10 min per image. Data analysis, including the phosphor plate scanning, takes less than 5 min for each image. The method characterizes the radiation isocenter geometry with the high accuracy required for the stereotactic radiosurgery. In this respect, it is similar to the standard ball test for stereotactic machines. However, due to the usage of the MLC instead of the cross-hair/ball, it does not depend on the cross-hair/ball placement errors with respect to the lasers and it provides more information on the mechanical integrity of the linac/couch/laser system. Alternatively, it can be used as a highly accurate QA procedure for the nonstereotactic machines. Noteworthy is its ability to characterize the MLC position accuracy, which is an important factor in IMRT delivery.« less

We report the development of a new system for interactive patient posture, position, and respiratory control during radiation therapy treatment. The system consists of an infrared (IR) camera, retroreflective markers, and dedicated software that makes it practical to use in the clinic. The system is designed to be used with multiple retroreflective markers to monitor not only the position, but also the posture of the patient in real time. Specific features of the system include the following: (1) The system reports an absolute misalignment at several points on a patient and also provides feedback on any necessary adjustments in terms of site‐specific setup parameters, such as focus‐to‐surface distance (PIN), superior and inferior alignment, and chest‐wall angle. (2) The system is based on a set of predefined templates containing the number and position of control points and feedback parameters developed for different treatment sites. (3) A noninvasive IR‐based “virtual portal vision” procedure projects organ contours in the beam's‐eye‐view (BEV) based on the IR marker locations obtained in real time and compares them with digitally reconstructed radiographs (DRRs) from CT simulation. Assuming good correlation between external markers and internal anatomy, the system offers the possibility of mimicking a verification procedure without taking port‐films, which can potentially reduce the setup time. In this paper, we concentrate on the system properties and performance while initial applications on a number of clinical sites are ongoing. Accuracy and precision of this system are evaluated in the context of breast/chest treatments using rigid phantoms. The system has an intrinsic uncertainty of ±1mm. When two systems in different rooms (CT and treatment rooms) are used for correlating positional information, the uncertainty is less than 2 mm. PACS number: 87.56.Da

The reaction of toluene diisocyanate with 2,2,3,3-tetrafluoro-1-propanol (fluoro compound) or 3-glycidoxypropyl trimethoxysilane(siloxane compound) and other additives to form the structure of the fluoro-based or siloxane-based polyurethane (PU) ionomer has been proven by infrared spectra. Experimental results indicated that the amount of water vapor permeability of the film made by fluoro-based or siloxane-based PU ionomer appeared to gradually increase with increasing concentration of the siloxane compound or fluoro compound, as a result of the formation of more porosities. Our experimental results also showed that the water vapor absorption was seen to be larger for the film made by siloxane-based PU ionomer film than for the film made by fluoro-based PU ionomer film, as a result of increased hydrophilic groups attached to the backbone of the PU ionomer molecule. For the film prepared by siloxane-based PU ionomer, both tensile strength and elongation appeared to increase with an increase in the concentration of siloxane compound. This may be the result of the intermolecular interaction between siloxane-based PU ionomer molecules themselves, thus enhancing the crosslinking capability of the ionomer molecules. On the other hand, both tensile strength and elongation for the film prepared by fluoro-based PU ionomer decreased with increasing concentration of the fluoro compound, as a result of intramolecular interaction greatly reducing the crosslinking capability of the ionomer molecules. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3767–3773, 2006

The analysis of dynamic multileaf collimator (MLC) positions for the delivered intensity‐modulated radiotherapy (IMRT) plans is crucial in that it may capture dose delivery problems otherwise difficult to observe and quantify in the conventional dosimetric measurements with film or with an ionization chamber. In some IMRT systems, delivery of IMRT fields starts with a maximum MLC opening (roughly the shape of the target in the beam's‐eye view) and then proceeds to the subsequent dynamic MLC subfields. No irradiation is required in going from the initial segment (maximum opening) to the next one, and theoretically, no dose should be delivered in that initial moment. However, due to a finite sampling time of the MLC controller, the finite speed of the MLC, and a finite leaf tolerance, there may be some dose delivered between the first and the second segment. The amount of the excess dose is higher for larger dose rates and for a smaller number of the total monitor units per IMRT field. The magnitude of the dose errors could be in the order of a few percent. Effects similar to the maximum MLC opening may occur in other situations as well, for instance, when leaves are forced to move over large distances in a short time. Confounding this are dose errors due to the uncertainty in the MLC transmission. The analysis of the actual leaf positions recorded in the dynamic MLC log file is helpful in differentiating between the two types of errors and in determining the optimal dynamic MLC delivery parameters. PACS numbers: 87.53.‐j, 87.90.+y

Coronary artery brachytherapy may require treatment of lesions longer than a single source length. A treatment option is tandem positioning of the single source. This study presents relative dosimetric measurements of a cardiovascular brachytherapy source and the dosimetric characteristics in the junction region of tandem treatments. Measurements were carried out using a Novoste Beta Cath 90Sr/90Y 40 mm beta source in a plastic water phantom. Radiochromic MD-55-2 film, calibrated using both 6 MV photon and 6 MeV electron beams from a linear accelerator, was used as the dosimeter. Dose distributions around a single source and in the junction region of tandem irradiation were measured. Measurements of the near field dose as close as 1.2 mm from the source are presented. Significant over- or underdoses in the junction region of tandem irradiation were quantified. At a radial distance of 2 mm from the longitudinal axis of the source, the dose value in the middle of the junction region, normalized to the dose at 2 mm midline single source, was about 182% for a 2-seed overlap and 16% for a 2-seed gap, respectively. Dose distributions in the junction region as a function of source overlap and radial distance have fairly high gradients and exhibit characteristic patterns. The fraction of prescription dose was found to have a sigmoidal dependence on overlap size, for radial distances ranging between 1.2 and 3 mm. The parameters of these sigmoids, quantified as functions of radial distance, could be used to provide quick and reasonable over/underdose estimates, given any potential overlap or gap in the junction area, with an uncertainty within 10%.

Lipoxygenase-free soybeans were processed into flour, concentrate, and isolate and compared to normal soybeans in bread, meat patties, and a beverage, respectively. Bread made with 20% normal or lipoxygenase-free soy flour had greater (P< 0.05) beany flavor than control yeast bread. There were no differences in beany flavor scores between soy flour types, normal and lipoxygenase-free. Ground beef patties made with 5% acid-washed or ethanol-washed soy protein concentrate had greater (P

We report a method to project a virtual light field over the patient during CT-simulations of external beam radiotherapy. It can be used to perform all the tasks associated with the physical light field of a conventional simulator. The system consists of a three-dimensional sonic digitizer interfacing with a window-based software on a personal computer. The digitizer can provide the three-dimensional coordinates of any point in space accessible by the digitizer probe. When these coordinates are transformed into the beam's eye view, the position of the digitized point relative to the beam can readily be displayed. Thus, the system establishes a virtual light field in space, which can be "seen" only by the digitizer probe. For any digitized point, the system can immediately show, by the beam's eye view display, whether the point is inside the field, outside of the field, or on the field border. Moreover, this virtual field projection allows one to evaluate external target coverage (or external normal tissue sparing) conveniently and interactively. By simply digitizing the concerned area and viewing its position in the beam's eye view display, one can immediately assess the coverage and if necessary, modify the treatment field accordingly. The system also provides an efficient and essential procedure in CT-simulations for marking treatment portals on the patient. By cruising the digitizer probe on the patient's skin surface under visual and audio guidances, one can promptly find the projection of the field center, field corners, etc., on the patient. Measurements have been performed to study the accuracy of the GP-12 sonic digitizer using rigid phantoms. Based on the measured data, the overall accuracy of the portal localization system is estimated to be +/-2 mm. The system has been in clinical use for our CT simulator.

Sixth-five 14-thalassaemia genes from 14 unrelated Chinese β-thalassaemia major patients and 37 Chinese β-carriers were analysed by allele-specific oligonucleotide (ASO) hybridization after DNA amplification by the polymerase chain reaction (PGR). Six mutations were studied and are represented by 49.2% of codon 41-42, 30.8% of IVSII #654, 6.2% of 17β 3.1% of IVSI #5 (G→G) and 1.5% of -28 TATA box. The complete mutations responsible for β-thalassaemia major in 13 of our 14 affected families were identified. For these families prenatal diagnosis at 10 weeks gestation using DNA amplification and ASO hybridization will replace the globin chain biosynthesis technique at 19 weeks gestation

X-ray diffraction analysis at 1.5 A resolution has confirmed the helical conformation of a de novo designed 18-residue peptide. However, the crystal structure reveals the formation of continuous molecular layers of parallel-packed amphiphilic helices as a result of much more extensive helix-helix interactions than predicted. The crystal packing arrangement, by virtue of distinct antiparallel packing interactions, segregates the polar and apolar surfaces of the helices into discrete and well-defined interfacial regions. An extensive "ridges-into-grooves" interdigitation characterizes the hydrophobic interface, whereas an extensive network of salt bridges and hydrogen bonds dominates the corresponding hydrophilic interface.

Non‐water solid phantoms are often used in the determination of absorbed dose to water for electron beams. Protocols have been established and widely accepted. In these procedures, several assumptions in addition to the Spencer–Attix conditions are required, and several correction factors are needed. A direct approach, in which the conversion is carried out in a single step using a modified Spencer–Attix formula, is studied in this paper. The approach is consistent with the protocols for water phantom, and the conversion factors can be calculated using Monte Carlo simulation. The behavior of the conversion factors is described by comparing the results from the AAPM protocol and experiment data for three electron energies (6, 12, and 16 MeV). This study demonstrates that for beam calibration at d max, the results from the new approach agree with those from the protocol with a maximum discrepancy of 1% for PMMA and 1.3% for polystyrene. For the depth dose measurement from near the surface to R 80, the agreement is within 1.5% for PMMA, 2.5% for polystyrene, and 2.8% for electron solid water. It also demonstrates that for electron solid water, the new approach provides better agreement with experiment data for the beam calibration at d max.

A sample of 44 adults with severe disabilities completed a randomized single-blind cross-over study testing chlorhexidine swabbing under various conditions: with/without prior dental prophylaxis, reduced frequency of application (2 vs. 5 times per week), and prolonged use (42 weeks). All subjects received therapeutic doses of 10 mL 0.12% chlorhexidine gluconate (Peridex, Procter & Gamble) and 10 mL 0.05% NaF applied with a Toothette®xs (Sage Products). Clinical effectiveness of chlorhexidine swabbing compared with placebo was previously reported. In the present study, while initial benefits were observed to be independent of dental prophylaxis, significant reductions in periodontal scores were sustained by a combination of dental prophylaxis and swabbing protocol, at reduced frequency of application and over prolonged time. High levels of acceptance and compliance by subjects/caregivers were maintained. Subjects/caregivers reported improvements in dental health as well as in attitude, quality of life, and smile. Chlorhexidine swabbing at maintenance frequency, combined with periodic dental prophylaxis, may offer an effective and pragmatic long-term preventive regimen for persons with disabilities.

Prototype miniature dosimeter probes have been designed, built, and characterized employing a small, radiation sensitive metal oxide semiconductor field effect transistor (MOSFET) chip to measure, in vivo, the total accumulated dose and dose rate as a function of time after internal administration of long range beta particle radiolabeled antibodies and in external high energy photon and electron beams. The MOSFET detector is mounted on a long narrow alumina substrate to facilitate electrical connection. The MOSFET, alumina substrate, and lead wires are inserted into a 16 gauge flexineedle, which, in turn, may be inserted into tissue. The radiation dosimeter probe has overall dimensions of 1.6 mm diam and 3.5 cm length. The MOSFET probe signals are read, stored, and analyzed using an automated data collection and analysis system. Initially, we have characterized the probe's response to long range beta particle emission from 90Y sources in solution and to high energy photon and electron beams from linear accelerators. Since the prototype has a finite substrate thickness, the angular dependence has been studied using beta particle emission from a 90Sr source. Temperature dependence and signal drift have been characterized and may be corrected for. Measurements made in spherical volumes containing 90Y with diameters less than the maximum electron range, to simulate anticipated geometries in animal models, agree well with Berger point kernel and EGS4 Monte Carlo calculations. The results from the prototype probes lead to design requirements for detection of shorter range beta particles used in radioimmunotherapy and lower photon energies used in brachytherapy.

Objective To evaluate, in a prospective study, the demographic profile of patients with benign prostate enlargement who presented in acute urinary retention (AUR). Patients and methods The study comprised all patients admitted for transurethral resection of the prostate and categorised into two groups, i.e. those presenting in AUR or electively. The factors evaluated included the length of hospitalization, the patients' occupation, their duration of symptoms and reasons for not seeking treatment. Results There was no significant difference in the mean age and occupational status of the two groups but those in AUR had more complications and a longer hospital stay after surgery; 60% of these men had had their urinary symptoms for > 1 year. When asked why they did not seek treatment earlier, 35% reported fear of surgery, while 41% thought that their symptoms were a normal part of ageing. Conclusion There is a need to raise the level of public awareness of benign prostatic enlargement because those who present with AUR incur excess morbidity and longer hospitalization that could otherwise be avoided through earlier treatment and elective surgery.

Sampling techniques using randomly distributed points and regular Cartesian grids were compared for the evaluation of volume, dose‐volume histogram, tumorcontrol, and normal tissue complication probabilities in radiation treatments. Particularly, the uncertainties associated with each sampling technique in estimating the dose‐volume histograms for several dose distributions are analyzed in detail. It is found that the estimation of these parameters using sampling points on a regular Cartesian grid is, in general, significantly more efficient than using random points. This finding is different from other published results. The choice of grid size for sampling was analyzed according to the AAPM recommended uncertainty on the dose delivered to the patient. It was concluded that when grid sampling is used, a grid size of 0.5 cm is adequate for most plans to meet the guidelines.

Peptides corresponding to sequences from the amino-terminal "head" regions of the low, middle, and high molecular weight neurofilament proteins (NF-L, NF-M, and NF-H) were synthesized by a modification of the Merrifield solid-phase method, and a panel of polyclonal antibodies to these epitopes were prepared in rabbits by the injection of synthetic peptides conjugated to the carrier protein keyhole limpet hemocyanin (KLH). An additional, monoclonal antibody recognizing both glial fibrillary acidic protein (GFAP) and vimentin was also produced, by fusion of cells of the mouse myeloma line NS-1 with spleen cells from a mouse immunized with cytoskeletal extracts. Antibody specificities were confirmed by a combination of Western blotting against cytoskeletal extracts and immunofluorescence using both rat brain sections and fibroblasts transfected with fully encoding cDNAs for each neurofilament protein, driven by viral promoters.

Metal oxide semiconductor field effect transistors(MOSFET) have been used as radiationdosimeters. Because of their small detector size, minimal power requirements, and signal integration characteristics, they offer unique possibilities as real‐time dose monitors in radiotherapy. An automated data collection and analysis system for use with MOSFETradiationdosimeters has been designed and built. The objective was to design a system which can acquire and process the MOSFET signals in real time, in any radiation field encountered in radiotherapy. In particular, major problems have been solved arising from the intrinsic drifts of the MOSFET signal during low dose rate measurements. These signal drifts are significant when the MOSFETdetector is used in applications such as on‐line monitoring of radiationdosedelivery in brachytherapy or radioimmunotherapy. The data collection and analysis system includes a portable IBM‐compatible personal computer fitted with digital‐to‐analog and analog‐to‐digital converter boards. A single‐chip programmable current supply is used to power the MOSFETdosimeters. Intrinsic and extrinsic drifts in signal due to ion diffusion and electron tunneling are corrected by deconvolution of the collected data in real time or after data collection. The data acquisition system and signal‐processing methodologies are described.

Purpose: MOSFETS were employed in this study for in situ assessment of radiation dose delivered by the Small Animal Radiation Research Platform (SARRP) to mouse anatomical target volumes: brain, left kidney, left lung,liver, pancreas and prostate. Method and Materials:MOSFET detectors were calibrated with conversion factors (CF) determined for each MOSFET as a function of depth in tissue equivalent material. Calibrated MOSFET was surgically implanted post‐euthanasia into the mouse target volume, with minimal organ disruption. Using CBCTimaging and robotic motion, the mouse was then positioned with implanted MOSFET at the isocenter of the SARRP. The depth of the MOSFET from the CBCTimage and corresponding CF were used in the SARRP dose calculation program to calculate the target dose for 220 kVp and 13 mA, without heterogeneity correction. Irradiations were conducted using a 0.15 cm copper filter. Three readings per MOSFET were obtained for each organ of three euthanized male mice. The measured dose was determined by averaging the MOSFET readings for that organ. The percentage difference between the measured and calculated dose was determined. Results: The results showed differences between the calculated and measured dose of between: +1.2 to 4.6 %, −3.3 to +4.8 %, +0.9 to +5.1 %, −5.9 to +2.5 %, ‐2.3 to +1.0 %, and −4.3 to +1.4 %, for the left kidney,liver, pancreas, prostate, left lung, and brain, respectively. Conclusions: The study indicates that, for 220 kVp x‐rays, the radiation dose delivered by the SARRP to characteristic target volumes in mice is within 6% of the calculated dose. The results provide a useful assessment of the need for tissue heterogeneity corrections in SARRP dose calculations for clinically relevant tumor model sites. The work also demonstrates the feasibility of using MOSFET dosimeters for in situ assessment of SARRP radiation dose delivery.

Purpose: Thresholding methods are commonly used to segment lesion volumes in PETimages. However, the presence of motion makes it difficult to determine the optimum threshold. To measure the threshold needed to produce the true volume of a moving target, we have investigated the effect of respiratory motion on the threshold at varying target‐to‐background activity concentration ratios (TBRs) using gated (4D) and ungated (3D) PETimages.Method and Materials: Using a PET/CT scanner with gating capability, spherical targets (0.5–26.5 mL) filled with 18 F ‐ FDG in a NEMA IEC body phantom were imaged with both a 3D‐PET scan corrected with a 3D‐CT attenuation map and a 4D‐PET scan corrected with phase‐matched 4D‐CT maps. . The phantom was either at rest or moving sinusoidally in the superior‐inferior direction with an amplitude of 2 cm and a period of 4.5 s to simulate respiratory motion. The optimum threshold values which give the true volumes of the spheres were derived from the 3D and 4D‐PET images at TBR = 4, 8, and infinite. For the 4D‐PET images, 5‐bin gating data were used in this analysis.Results: The TBR‐threshold‐volume curves show that the optimum threshold exponentially decreases as the volume increases. In addition, the threshold increases as the TBR decreases. The results also illustrate that the threshold values applied to the 4D‐PET images for the moving targets are well correlated with the optimum threshold values applied to the 3D‐PET images for the targets at rest. However, the same thresholds significantly over‐estimate the target volume if applied to the 3D‐PET images of moving targets. Conclusion: The TBR‐threshold‐volume curves clearly demonstrate the advantage of gating for detecting the true volume of moving target. Therefore, respiratory‐gated PET acquisition should be performed in the presence of relatively large organ movement to accurately determine the gross tumor volume for clinical applications.

Purpose: In recent years, quantitative analysis of gated (4D) PET/CT images has been introduced for diagnosis, staging, and prediction of tumor response where internal organ motion is significant. However, the best methodology for applying 4D information to radiotherapy target definition is not currently well established. In order to accurately determine moving target volume, we have investigated the combined effects of target size, respiratory motion, target‐to‐background activity concentration ratio (TBR) on ungated (3D) and 4D PETimages as well as gating methods. Method and Materials: Using a GE Discovery PET/CT scanner, a 3D‐PET scan corrected with a 3D attenuation map from 3D‐CT scan and a 4D‐PET scan corrected with matching attenuation maps from 4D‐CT were performed using spherical targets (0.5–26.5 mL) filled with 18 F ‐ FDG in a NEMA IEC body phantom at different TBRs (infinite, 8, and 4). To simulate respiratory motion, the phantoms were driven sinusoidally in the superior‐inferior direction with amplitudes of 0, 1, and 2 cm and a period of 4.5 s. Recovery coefficients were determined on PETimages. In addition, gating methods using different numbers of gating bins (1–20 bins) were evaluated by determining imagenoise and temporal resolution. Results: Signal loss in 3D‐PET images was measured from both the partial volume effect, due to the limited PET resolution, as well as respiratory motion. The results show that signal loss depends on both the amplitude and shape of respiratory motion. However, 4D‐PET successfully recovers most of the loss induced by respiratory motion. The 5‐bin gating method gives the best temporal resolution with acceptable imagenoise.Conclusion: The results based on the 4D scan protocols can be used to improve the accuracy of gross tumor volume definition in the lung and abdomen.

Purpose: Interplay between organ motion and leaf motion has been shown to generally have a small dosimetric impact for most clinical IMRT treatments. However, it has also been shown that for some MLC sequences there can be large daily variations in the delivered dose, depending on details of the patient motion or number of fractions. This study investigates guidelines for dynamic MLC sequences that will keep daily dose variations within 10%. Materials and Methods: Dose distributions for a range of MLC separations (0.2 – 5.0cm) and displacements between adjacent MLCs (0 – 1.5cm) were exported from Eclipse to purpose‐written software which simulated the dose distribution moving across a moving target. Target motion parallel and perpendicular to the MLC motion was investigated for a range of amplitudes (0.5 – 4.0cm), periods (1.5 – 10s), and MLC speeds (0.1 – 3.0 cm/s). Target motion was modeled as sin6. MLC sequences were identified which kept dose variations within 10% compared to the dose delivered with no motion. Results were confirmed experimentally by measuring the dose delivered to MOSFETs in a moving phantom for a range of MLC sequences. Results: The maximum allowable MLC speed when target motion is parallel to the MLC motion can be conservatively summarized as a simple function of target amplitude and MLC separation. When the target motion is perpendicular to MLC motion the maximum allowable MLC speed can be described as a function of MLC slit width and the displacement of adjacent MLCs. The guidelines were successfully applied to two‐dimensional motion. Rules were less restrictive for periods

Purpose: To develop an intensity‐based deformable image registration solution for detecting and quantifying both rigid and non‐rigid variations typically seen in head‐neck IMRTtreatment, including patient position offsets, involuntary organ movements and anatomical deformations. Methods & Materials: A two‐step deformable image registration solution was developed by implementing a BSpline‐based non‐rigid representation of head‐neck anatomy and similarity metrics of mean square differences and normalized mutual information. kV and MV X‐ray projection images were registered in two successive steps. First, rigid‐body registrations were performed to determine patient position offsets in terms of translations and in‐plane rotations. The outputs were then used to initiate deformable registrations from which non‐rigid local displacements between reference and target images were extracted in the form of deformation vector fields. Validation studies were performed for patient CT simulation data, phantom images, and setup images of 12 head‐neck IMRT patients. The accuracy of the registrations were examined by comparing registration results with known variations in simulation, phantom images, a set of pre‐shift/post‐shift confirmation images, and with a feature‐based registration by subtracting coordinates of well‐identified anatomical points in patient setup images of different fractions. Results: For all three data sets with known changes, the mean (SD) error in rigid‐body registration was 0.3 mm (0.3 mm) for translations and 0.1° (0.1°) for in‐plane rotations. The error in deformable registration of image pairs with known changes was 0.5 mm (0.9 mm). For patient images with unknown non‐rigid local displacements, the agreements between deformable registration and the feature‐based registration were within 2.0 mm (96.5% of registered points). Conclusion: A 2‐step deformable image registration solution was developed and validated for registering kV/MV X‐ray projection images. The accuracy of the registration is adequate for detecting and quantifying both rigid and nonrigid variations typically seen during patient setup and target anatomy localization for head‐neck IMRT delivery.

Introduction: 4‐D PET/CT has potential to greatly improve the accuracy of radiotherapy target definition for treatment sites where internal organ motion is significant. While PET has an inherently greater capacity to detect cancer than CT, the best methodology for applying 4‐D PET to target definition is not currently well understood. In our study, targets of different sizes in a dynamic phantom were imaged using 3‐D and 4‐D PET/CT with the goal of better understanding how to best apply these images to radiotherapy target definition. Materials and Methods: Using a PET/CT scanner with 4‐D capability, 3‐D/4‐D image studies were acquired using a dynamic phantom. Hollow spheres filled with 18 F ‐FDG were inserted into a cavity within the phantom made of material of a density similar to lung. Recovery coefficients (RCs) were determined using 3‐D and 4‐D PETimages acquired with the phantom in static mode and a dynamic mode set to simulate respiratory motion. Results: The activity concentration in the sphere from the 3‐D PETimages can be underestimated by 40% (23%) in 2 cm (1 cm) motion. The 4‐D PET successfully recovers most of the loss of activity concentration resulting from the respiratory motion with 1% (4%) loss in 1 cm (2 cm) motion. We found that the percent recovery slightly varies with minimum 82% (93%) at the middle of expiration and inhalation and maximum 98% (99%) at the end of expiration and inhalation in 2 cm (1 cm) motion in the 4‐D PETimages. Conclusions: We demonstrate that the speed of respiratory motion at phase‐sampling position affects the measured activities of 4‐D PET due to spatial mismatch between the 4‐D PET and 3‐D CTimages for attenuation correction. Therefore, RC loss caused by respiratory motion may be minimized using 4‐D PET with 4‐D CT attenuation correction.

Purpose: The integrated 4DPET/CT scanner has the advantage of accurate body position correspondence between the PET and CT scans as well as 4D acquisition capabilities for both modalities. The former reduces possible errors from misalignment when fusing PET and CT scans taken on different machines, while the latter improves our capability to account for anatomical changes due to respiratory motion. However, owing to the fundamental differences between the scanning techniques, artifacts may differ between the modalities. Materials and Methods: In our investigation we have expanded the advantage of the integrated scanner single reference frame by the improvement of a lung dynamic phantom that can be monitored by both the PET and CT 4D scanning procedures. This was achieved by the development of custom made inserts for the dynamic phantom that can accommodate different sized FDG‐filled spheres. The motion of the dynamic phantom was preprogrammed for trajectories of sine, sine6 and prerecorded traces of lung implanted fiducials from a previous study. In the case of the analytical curves, periods between 3.5 and 8.5 seconds were used along with amplitudes varying from 0.5 to 3cm. Spheres of various sizes filled with FDG of various activities were used. Results: Gated PET and CTimages of the same moving target were obtained within the same frame of reference for various amplitudes and periods of motion and for various sizes and activities of FDG‐filled spheres. Comparison of the images from the two modalities shows differences in the motion artifacts, which should be taken into account in radiotherapy planning. Conclusion: We have successfully developed a phantom system for obtaining highly correlated data sets for PET and CT with and without gated (4D) acquisition. Our preliminary results suggest that motions do have significant impact on the images. Further studies will investigate the clinical implications of this work.

Purpose: To investigate a CT-guided adaptive radiation therapy technique capable of correcting for complex shape changes, including twisting around the longitudinal axis, such as found when treating head and neck patients with a head rotation. Method and Materials: For co-planar beams, the dose in an axial plane is primarily associated with the positions of a single MLC pair. We start with a primary plan, and automatically generate several secondary plans with gantry angles offset by regular increments. MLC sequences for each plan are calculated keeping MUs and number of segments constant for a given beam (fluences are different). Bulk registration (3D) of planning and daily CT images gives global shifts. Slice-by-slice (2D) registration gives local shifts and rotations about the longitudinal axis for each axial slice. The daily MLC sequence is then created for each axial slice/MLC leaf pair combination, by taking the MLC positions from the pre-calculated plan with the nearest rotation, and shifting using a beams-eye-view calculation to account for local linear shifts. A planning study was carried out using two MR images of a healthy volunteer, contoured to simulate a base-of-tongue treatment: One with the head straight (used to simulate the plan image) and one with the head tilted to the left (the daily image). Results: On a slice-by-slice basis, local rotations in the daily image varied from 2 – 31degrees. Local shifts ranged from −0.2 – 0.5cm and −0.4 – 0.0cm in right-left and posterior-anterior directions, respectively. The adapted treatment gave good target coverage, and kept the daily cord dose below the limit used in the original plan (65%, equivalent to 46Gy over 35 fractions). Conclusion: This technique may be useful for adaptive radiation therapy of targets where twisting around the longitudinal axis is significant. These results also demonstrate the feasibility of combining MLC sequences from different pre-approved treatment plans.

Purpose: We have designed and implemented a new stereotactic machine QA test. The method is used to characterize gantry sag, couch wobble, cone placement, MLC offset and room lasers position relative to radiation isocenter. An image containing a series of test patterns is generated in a direct and integrated fashion. Method and Materials: Two MLC star patterns, a cone pattern and the laser lines are recorded on the same imaging medium, enabling 0.1 mm accuracy measurements.Phosphor plates are used as the imaging medium due to their unique property that the red light of wall laser erases the radiation information stored on phosphor plates. The room lasers position relative to the radiation isocenter can be measured. The developed QA method consists of four images that measure the gantry sag between 00 and 1800 gantry angles, the position and stability of couch rotational axis, the sag between 900 and 2700 gantry angles, the accuracy of cone placement on the collimator and the position of laser lines relative radiation isocenter. Results: The inherent precision of the numerical algorithms developed is +/− 0.05mm. The inherent accuracy of the method as a whole is +/− 0.1mm. The total irradiation/illumination time is about 10 min per image. Automating the generation of collimator star patterns can reduce this time. The data analysis (including the phosphor plate scanning) is less than 5min. Conclusion: The presented method reproducibly characterizes the radiation isocenter geometry with the high accuracy required for stereotactic surgery. It can replace the standard ball test and it can provide a highly accurate QA procedure for the non‐stereotactic machines.