Changing Beliefs About Emotions in IBS: A Single Case Design.

BACKGROUND: Previous research suggests benefits of targeting beliefs about the unacceptability of emotions in treatment for irritable bowel syndrome (IBS). AIMS: The current study developed and tested an intervention focusing on beliefs and behaviours around emotional expression. METHOD: Four participants with IBS attended five group sessions using cognitive behavioural techniques focusing on beliefs about the unacceptability of expressing emotions. Bi-weekly questionnaires were completed and a group interview was conducted. This study used an AB design with four participants. RESULTS: Averages indicate that participants showed decreases in beliefs about unacceptability of emotions and emotional suppression during the intervention, although this was not reflected in any of the individual trends in Beliefs about Emotions Scale scores and was significant in only one individual case for Courtauld Emotional Control Scale scores. Affective distress and quality of life improved during follow-up, with only one participant not improving with regard to distress. Qualitative data suggest that participants felt that the intervention was beneficial, referencing the value in sharing their emotions. CONCLUSIONS: This study suggests the potential for beliefs about emotions and emotional suppression to be addressed in cognitive behavioural interventions in IBS. That beliefs and behaviours improved before outcomes suggests they may be important processes to investigate in treatment for IBS.

Combined Effects of Low-Dose Proton Radiation and Simulated Microgravity on the Mouse Retina and the Hematopoietic System.

The purpose of the current study was to characterize the effects of simulated microgravity and radiation-induced changes in retina and retinal vasculature, and to assess the accompanying early changes in immune cells and hematological parameters. To better understand the effects of spaceflight, we used a combination of treatments designed to simulate both the radiation and low-gravity aspects of space conditions. To simulate the broad energy spectrum of a large solar particle event (SPE) and galactic cosmic ray (GCR) radiation, male C57BL/6J mice were exposed to whole-body irradiation using fully modulated beams of 150-MeV protons containing particles of energy from 0 to 150 MeV and a uniform dose-vs.-depth profile. The mice were also hindlimb-unloaded (HLU) by tail suspension. Mice were unloaded for 7 days, exposed to 50 cGy, unloaded for an additional 7 days and then sacrificed for tissue isolation at days 4 and 30 after the combined treatments. Increases in the number of apoptotic cells were observed in the endothelial cells of mice that received radiation alone or with HLU compared to controls at both days 4 and 30 (P < 0.05). Endothelial nitric oxide synthase (eNOS) levels were significantly elevated in the retina after irradiation only or combined with HLU compared to controls at the 30-day time point (P < 0.05). The most robust changes were observed in the combination group, suggesting a synergistic response to radiation and unloading. For hematopoietic parameters, our analysis indicated the main effects for time and radiation at day 4 after treatments (day 11 postirradiation) (P < 0.05), but a smaller influence of HLU for both white blood cell and lymphocyte counts. The group treated with both radiation and HLU showed greater than 50% reduction in lymphocyte counts compared to controls. Radiation-dependent differences were also noted in specific lymphocyte subpopulations (T, B, natural killer cells). This study shows indications of an early effect of low-dose radiation and spaceflight conditions on retina and immune populations.

Glomerular filtration rate: new age- and gender- specific reference ranges and thresholds for living kidney donation.

BACKGROUND: There is a need for a large, contemporary, multi-centre series of measured glomerular filtration rates (mGFR) from healthy individuals to determine age- and gender-specific reference ranges for GFR. We aimed to address this and to use the ranges to provide age- and gender-specific advisory GFR thresholds considered acceptable for living kidney donation. METHODS: Individual-level data including pre-donation mGFR from 2974 prospective living kidney donors from 18 UK renal centres performed between 2003 and 2015 were amalgamated. Age- and gender-specific GFR reference ranges were determined by segmented multiple linear regression and presented as means ± two standard deviations. RESULTS: Males had a higher GFR than females (92.0 vs 88.1 mL/min/1.73m2, P < 0.0001). Mean mGFR was 100 mL/min/1.73m2 until 35 years of age, following which there was a linear decline that was faster in females compared to males (7.7 vs 6.6 mL/min/1.73m2/decade, P = 0.013); 10.5% of individuals aged > 60 years had a GFR < 60 mL/min/1.73m2. The GFR ranges were used along with other published evidence to provide advisory age- and gender-specific GFR thresholds for living kidney donation. CONCLUSIONS: These data suggest that GFR declines after 35 years of age, and the decline is faster in females. A significant proportion of the healthy population over 60 years of age have a GFR < 60 mL/min/1.73m2 which may have implications for the definition of chronic kidney disease. Age and gender differences in normal GFR can be used to determine advisory GFR thresholds for living kidney donation.

Acute Effect of Low-Dose Space Radiation on Mouse Retina and Retinal Endothelial Cells.

There is concern that degradation of vision as a result of space flight may compromise both mission goals and long-term quality of life after space travel. The visual disturbances may be due to a combination of intracerebral pressure changes and exposure to ionizing radiation. The retina and the retinal vasculature play important roles in vision, yet have not been studied extensively in relationship to space travel and space radiation. The goal of the current study was to characterize oxidative damage and apoptosis in retinal endothelial cells after whole-body gamma-ray, proton and oxygen (16O) ion radiation exposure at 0.1 to 1 Gy. Six-month-old male C57Bl/6J mice were whole-body irradiated with 600 MeV/n 16O ions (0, 0.1, 0.25, 1 Gy), solar particle event (SPE)-like protons (0, 0.1, 0.25, 0.5 Gy) or 60Co gamma rays (0, 0.1, 0.25, 0.5 Gy). Eyes were isolated for examining endothelial nitric oxide synthase (eNOS) expression and characterization of apoptosis in retina and retinal endothelial cells at two weeks postirradiation. The expression of eNOS was significantly increased in the retina after proton and 16O ion exposure. 16O ions induced over twofold increase in eNOS expression compared to proton exposure at two weeks postirradiation ( P < 0.05). TUNEL assays showed dose-dependent increases in apoptosis in the retina after irradiation. Low doses of 16O ions elicited apoptosis in the mouse retinal endothelial cells with the most robust changes observed after 0.1 Gy irradiation ( P < 0.05) compared to controls. Data also showed that 16O ions induced a higher frequency of apoptosis in retinal endothelial cells compared to protons ( P < 0.05). In summary, our study revealed that exposure to low-dose ionizing radiation induced oxidative damage and apoptosis in the retina. Significant changes in retinal endothelial cells occur at doses as low as 0.1 Gy. There were significant differences in the responses of endothelial cells among the radiation types examined here.

Water equivalent thickness analysis of immobilization devices for clinical implementation in proton therapy.

Immobilization devices can impact not only the inter- and intra-fraction motion of the patient, but also the range uncertainty of the treatment beam in proton therapy. In order to limit additional range uncertainty, the water equivalent thickness (WET) of the immobilization device needs to be well known and accurately reflected in the calculations by the treatment planning system (TPS). The method presented here focusses on the use of a nozzle-mounted variable range shifter and precision-machined polystyrene blocks of known WET to evaluate commercial immobilization devices prior to clinical implementation. CT studies were also completed to evaluate the internal uniformity of the immobilization devices under study. Mul- tiple inserts of the kVue platform (Qfix Systems, Avondale, PA) were evaluated as part of this study. The results indicate that the inserts are largely interchangeable across a given design type and that the measured WET values agree with those generated by the TPS with a maxi- mum difference less than 1 mm. The WET of the devices, as determined by the TPS, was not impacted by CT beam hardening normally experienced during clinical use. The reproduc- ibility of the WET method was also determined to be better than ±0.02 mm. In conclusion, the testing of immobilization prior to implementation in proton therapy is essential in order to ascertain their impact on the proton treatment and the methodology described here can also be applied to other immobilization systems.

Effects of solar particle event proton radiation on parameters related to ferret emesis.

The effectiveness of simulated solar particle event (SPE) proton radiation to induce retching and vomiting was evaluated in the ferret experimental animal model. The endpoints measured in the study included: (1) the fraction of animals that retched or vomited, (2) the number of retches or vomits observed, (3) the latency period before the first retch or vomit and (4) the duration between the first and last retching or vomiting events. The results demonstrated that γ ray and proton irradiation delivered at a high dose rate of 0.5 Gy/min induced dose-dependent changes in the endpoints related to retching and vomiting. The minimum radiation doses required to induce statistically significant changes in retching- and vomiting-related endpoints were 0.75 and 1.0 Gy, respectively, and the relative biological effectiveness (RBE) of proton radiation at the high dose rate did not significantly differ from 1. Similar but less consistent and smaller changes in the retching- and vomiting-related endpoints were observed for groups irradiated with γ rays and protons delivered at a low dose rate of 0.5 Gy/h. Since this low dose rate is similar to a radiation dose rate expected during a SPE, these results suggest that the risk of SPE radiation-induced vomiting is low and may reach statistical significance only when the radiation dose reaches 1 Gy or higher.

Acute hematological effects of solar particle event proton radiation in the porcine model.

Acute radiation sickness (ARS) is expected to occur in astronauts during large solar particle events (SPEs). One parameter associated with ARS is the hematopoietic syndrome, which can result from decreased numbers of circulating blood cells in those exposed to radiation. The peripheral blood cells are critical for an adequate immune response, and low blood cell counts can result in an increased susceptibility to infection. In this study, Yucatan minipigs were exposed to proton radiation within a range of skin dose levels expected for an SPE (estimated from previous SPEs). The proton-radiation exposure resulted in significant decreases in total white blood cell count (WBC) within 1 day of exposure, 60% below baseline control value or preirradiation values. At the lowest level of the blood cell counts, lymphocytes, neutrophils, monocytes and eosinophils were decreased up to 89.5%, 60.4%, 73.2% and 75.5%, respectively, from the preirradiation values. Monocytes and lymphocytes were decreased by an average of 70% (compared to preirradiation values) as early as 4 h after radiation exposure. Skin doses greater than 5 Gy resulted in decreased blood cell counts up to 90 days after exposure. The results reported here are similar to studies of ARS using the nonhuman primate model, supporting the use of the Yucatan minipig as an alternative. In addition, the high prevalence of hematologic abnormalities resulting from exposure to acute, whole-body SPE-like proton radiation warrants the development of appropriate countermeasures to prevent or treat ARS occurring in astronauts during space travel.

Proton beam scattering system optimization for clinical and research applications.

PURPOSE: To develop and test a method for optimizing and constructing a dual scattering system in passively scattered proton therapy. METHODS: A beam optics optimization algorithm was developed to optimize the thickness of the first scatterer (S1) and the profile (of both the high-Z material and Lexan) of the second scatterer (S2) to deliver a proton beam matching a given set of parameters, including field diameter, fluence, flatness, and symmetry. A new manufacturing process was also tested that allows the contoured second scattering foil to be created much more economically and quickly using Cerrobend casting. Two application-specific scattering systems were developed and tested using both experimental and Monte Carlo techniques to validate the optimization process described. RESULTS: A scattering system was optimized and constructed to deliver large uniform irradiations of radiobiology samples at low dose rates. This system was successfully built and tested using film and ionization chambers. The system delivered a uniform radiation field of 50 cm diameter (to a dose of ± 7% of the central axis) while the depth dose profile could be tuned to match the specifications of the particular investigator using modulator wheels and range shifters. A second scattering system for intermediate field size (4 cm < diameter < 10 cm) stereotactic radiosurgery and radiation therapy (SRS and SRT) treatments was also developed and tested using GEANT4. This system improved beam efficiency by over 70% compared with existing scattering systems while maintaining field flatness and depth dose profile. In both cases the proton range uniformity across the radiation field was maintained, further indicating the accuracy of the energy loss formalism in the optimization algorithm. CONCLUSIONS: The methods described allow for rapid prototyping of scattering foils to meet the demands of both research and clinical beam delivery applications in proton therapy.

Monte Carlo simulation of single-plane magnetically focused narrow proton beams.

We present Monte Carlo simulations of magnetically focused proton beams shaped by a single quadrapole magnet. Such beams are narrowly focused in one longitudinal plane but fan out in the perpendicular plane producing elongated elliptical beam spots (a 'screwdriver' shape). The focused beams were compared to passively collimated beams (the current standard of delivery for small radiosurgery beams). Beam energies considered were relevant to functional radiosurgery and standard radiosurgery clinical applications. Three monoenergetic beams (100, 125, and 150 MeV) and a modulated beam were simulated. Monoenergetic magnetically focused beams demonstrated 28 to 32% lower entrance doses, 31 to 47% larger central peak to entrance depth dose ratios, 26 to 35% smaller integral dose, 25 to 32% smaller estimated therapeutic ratios, 19 to 37% smaller penumbra volumes, and 38 to 65% smaller vertical profile lateral penumbras at Bragg depth, compared to the collimated beams. Focused modulated beams showed 31% larger central peak to entrance dose ratio, and 62 to 65% smaller vertical lateral penumbras over the plateau of the spread out Bragg peak. These advantages can be attributed to the directional acceleration of protons in the transverse plane due to the magnetic field. Such beams can be produced using commercially available assemblies of permanent rare earth magnets that do not require electric power or cryrogenic cooling. Our simulations suggest that these magnets can be inexpensively incorporated into the beam line to deliver reduced dose to normal tissue, and enhanced dose to elongated elliptical targets with major and minor axes on the order of a few centimeters and millimeters, respectively. Such beams may find application in novel proton functional and standard radiosurgery treatments in and around critical structures.

Water-equivalent path length calibration of a prototype proton CT scanner.

PURPOSE: The authors present a calibration method for a prototype proton computed tomography (pCT) scanner. The accuracy of these measurements depends upon careful calibration of the energy detector used to measure the residual energy of the protons that passed through the object. METHODS: A prototype pCT scanner with a cesium iodide (CsI(Tl)) crystal calorimeter was calibrated by measuring the calorimeter response for protons of 200 and 100 MeV initial energies undergoing degradation in polystyrene plates of known thickness and relative stopping power (RSP) with respect to water. Calibration curves for the two proton energies were obtained by fitting a second-degree polynomial to the water-equivalent path length versus calorimeter response data. Using the 100 MeV calibration curve, the RSP values for a variety of tissue-equivalent materials were measured and compared to values obtained from a standard depth-dose range shift measurement using a water-tank. A cylindrical water phantom was scanned with 200 MeV protons and its RSP distribution was reconstructed using the 200 MeV calibration. RESULTS: It is shown that this calibration method produces measured RSP values of various tissue-equivalent materials that agree to within 0.5% of values obtained using an established water-tank method. The mean RSP value of the water phantom reconstruction was found to be 0.995 ± 0.006. CONCLUSIONS: The method presented provides a simple and reliable procedure for calibration of a pCT scanner.

SU-E-T-300: Monte Carlo Simulation of Single-Plane Magnetically Focused Narrow Proton Beams.

Purpose To investigate narrow, elongated magnetically focused proton beams and compare their properties with passively collimated beams using Monte Carlo simulation. METHODS: We performed Geant4 Monte Carlo simulations involving a single quadrapole focusing magnet, thereby creating a flattened beam with an elongated elliptical cross section. The parameters of the magnet were chosen to mimic k=3 (quadrapole) Halbach cylinders that are available commercially as assemblies of rare earth permanent magnetic materials. For comparison, simulations were also performed with the same beam line components and passively collimated beams (using an elliptically shaped collimator). To facilitate fair comparison, efforts were made to closely match the planned treatment volumes (PTV) for each simulation case in dose, volume, and major and minor diameters of the elliptically shaped PTV at Bragg depth. RESULTS: Magnetic focusing delivered significantly better dose localization to the target over collimated beams which are the current beam delivery modality. Compared to collimated beams, the magnetically focused beams showed a 31% smaller therapeutic ratio, a 31% smaller integrated dose, a 34% smaller entrance dose, a 30% larger peak-to-entrance central depth dose ratio, a 37% smaller penumbra volume, and were 35% more efficient in dose delivery (based on proton number). CONCLUSIONS: The clinically relevant advantages of the magnetically focused beams compared to the collimated beams (the current standard of care) can be attributed to the preferential directional acceleration of protons due to the magnetic field. Our simulations suggest such magnets can be used to deliver tissue sparing doses to normal and at-risk tissue, and enhanced dose to elongated, narrow targets. Future work to characterize and test prototype magnets is in progress. Such beams my find application in novel proton treatments including application to the spinal cord.

SU-E-T-232: Proton Source Modeling for Geant4 Monte Carlo Simulations.

PURPOSE: To investigate the effect of initial proton beam source placement, distribution and angle on the proton dose distribution in a therapeutic nozzle using Geant4. METHODS: We performed Geant4 Monte Carlo simulations of a passively scattered proton treatment nozzle. Accurate geometry including all elements in the treatment room was used. Protons were generated just inside the vacuum pipe using one of two models. First, a standard two dimensional Gaussian distribution of proton starting position was used with a small random angle added to the initial direction. The size of the Gaussian distribution and the random angle were set to match measured beam spot size and angular spread at the exit window. Second, a point source of protons further back in the vacuum pipe with a small random angle was used. The distance of the point source to exit window and the random angle were set to match the spot size and angular deviation used for the Gaussian distribution. Depth dose curves and orthogonal beam profiles were examined to determine changes between the two models. RESULTS: Orthogonal beam profiles for large apertures showed changes of up to 6.5% between the two models with the point source showing much better agreement with measured data. Depth dose curves and orthogonal profiles for small apertures were unaffected. For large apertures, the average difference compared to measured data was of 1.9% and 0.7% and the max difference was 5.0% and 1.6% for Gaussian and point sources, respectively. CONCLUSIONS: The point source more realistically models the proton distribution in the vacuum pipe by correlating the proton position with the direction. For certain scattering setups and large apertures point source modeling is necessary to accurate match measured data with Monte Carlo simulations.

MO-A-213AB-10: Scattering System Optimization for Proton Therapy.

PURPOSE: To describe a method for optimization and production of a dual scattering system for proton beam delivery. METHODS: Dual-foil passive scattering is currently the prevalent modality for proton therapy delivery. Large uniform proton fields are created using a 2-stage scattering system comprising an upstream uniform lead foil (stage 1) followed by a contoured lead/Lexan foil to provide beam and range uniformity (stage 2). Optimizing the parameters of these foils, including thickness, contour and placement, provides not only a flat and symmetrical radiation field with a uniform range, but also affects the overall efficiency of the beam line. An analytical method for optimizing the scattering system design was applied and validated with GEANT4 simulations. This method has been used to create passively scattered therapeutic and research proton fields at our proton therapy facility. A novel Cerrobend casting method is described that allows for cost-effective and accurate production of this important beam-line component. RESULTS: A number of dual scattering foil combinations for research and therapeutic purposes have been created and were evaluated with GEANT4 simulations. We demonstrated that the use of this system can generate passively scattered proton fields up to 60cm diameter with improved efficiency and beam flatness over existing dual-scattering systems. Scattering system performance was verified using physical measurements including Gafchromic film and ion chamber data. CONCLUSIONS: This analytical method allows the user to optimize the proton dual scattering system with respect to specific input parameters, while the casting method provides a cost-effective way to create a unique scattering system for a given application.

An experimental investigation of factors involved in the decision to undertake genetic testing for schizophrenia.

BACKGROUND: The psychological issues surrounding genetic testing, particularly decision-making processes, are not well understood. Previous studies suggest that apparently "nondirective" strategies intended to help individuals consider the consequences of undergoing predictive testing for physical illness can influence the decision. AIMS: To investigate the influence of selectively focussing on different aspects of previously provided information concerning genetic testing for schizophrenia. METHOD: Community participants (n = 120) rated how likely they would be to arrange to have a genetic test for schizophrenia if it were available, before and after being given detailed information about schizophrenia and the implications of testing. Participants were then randomly allocated to four groups, and were implicitly focused on the negative issues (negative group), the positive issues (positive group), both the negative and positive issues (all-focusing group) or schizophrenia-irrelevant health-related issues (control group). All issues on which the experimental groups focussed were included in the information provided and the form of questioning meets current definitions of nondirectiveness. RESULTS: Hypothetical decisions whether to arrange a genetic test for schizophrenia were influenced by the issues on which participants had focused; the positive group were more likely to say they would be tested relative to the other groups. CONCLUSIONS: Decisions about genetic testing for schizophrenia were influenced by the specific issues on which individuals were encouraged to focus at that time.

Ion-counting nanodosemeter with particle tracking capabilities.

An ion-counting nanodosemeter (ND) yielding the distribution of radiation-induced ions in a low-pressure gas within a millimetric, wall-less sensitive volume (SV) was equipped with a silicon microstrip telescope that tracks the primary particles, allowing correlation of nanodosimetric data with particle position relative to the SV. The performance of this tracking ND was tested with a broad 250 MeV proton beam at Loma Linda University Medical Center. The high-resolution tracking capability made it possible to map the ion registration efficiency distribution within the SV, for which only calculated data were available before. It was shown that tracking information combined with nanodosimetric data can map the ionisation pattern of track segments within 150 nm-equivalent long SVs with a longitudinal resolution of approximately 5 tissue-equivalent nanometers. Data acquired in this work were compared with results of Monte Carlo track structure simulations. The good agreement between 'tracking nanodosimetry' data acquired with the new system and simulated data supports the application of ion-counting nanodosimetry in experimental track-structure studies.

Charge collection imaging of a monolithic DeltaE-E telescope for radiation protection applications.

The development of microdosimeters and particle telescopes is important for risk assessment in space and aviation applications. The charge collection properties of a monolithic particle telescope, suitable for both microdosimetry and fluence based approaches, were studied using an ion microprobe.

Neutralizing increases discomfort associated with obsessional thoughts: an experimental study with obsessional patients.

Cognitive-behavioral theories suggest that the development of neutralizing is crucial in the development and persistence of obsessional problems (OCD). Twenty-nine patients with a Diagnostic and Statistical Manual of Mental Disorders (4th ed., American Psychiatric Association, 1994) diagnosis of OCD were randomly allocated to 2 conditions. Both listened to repeated recorded presentations of their intrusive thoughts and either neutralized (experimental group) or distracted themselves (control). Discomfort was rated during this 1st phase and then during a 2nd phase without neutralizing or distraction. The experimental group showed a similar level of discomfort in the 1st phase, which significantly reduced during the period compared with controls. The experimental group experienced significantly more discomfort during the 2nd phase, and significantly stronger urges to neutralize and distract at the end of this phase than controls.

Causing harm and allowing harm: a study of beliefs in obsessional problems.

This study investigates two factors hypothesised as relevant to obsessional problems because of the way in which they influence decisions whether or not to act to prevent harm. These are (i) the way in which intrusive thoughts increase the internal awareness of harm, and confront the person with the possibility of taking action to prevent such harm and (ii) the extent to which there is some obvious external factor which increases awareness of the possibility of preventing harm. Obsessional patients, anxious and non-clinical controls completed a scale which systematically measured these factors across a wide range of situations. Results across all situations evaluated confirmed previous findings that both obsessionals and nonobsessionals were more likely to report acting to prevent harm when awareness of it is prompted by an intrusion than when it is not. It was also found that participants in all groups acted more 'obsessionally' when a scenario is described in ways which suggest that harm may be by 'commission' than when it is described in terms of an 'omission'. When scenarios about which each individual is most disturbed were analysed, anxious and non-clinical controls continued to differentially rate omission and commission situations; as predicted, this differential was not present for obsessional patients. It is concluded that obsessionals are more sensitive to omission than are nonobsessionals when considering scenarios about which they are concerned, and that this sensitivity is one factor influencing the decision whether to act to prevent harm.

Responsibility attitudes and interpretations are characteristic of obsessive compulsive disorder.

The cognitive-behavioural theory of Obsessive Compulsive Disorder (OCD) proposes that a key factor influencing obsessional behaviour is the way in which the intrusive cognitions are interpreted. The present paper reports an investigation of links between clinical symptoms (of anxiety, depression and obsessionality) and responsibility beliefs. These beliefs include not only measures of general responsibility attitudes (assumptions) but also more specific responsibility appraisals consequent on intrusive cognitions. The characteristics of two new questionnaires specifically designed to measure these beliefs were assessed in patients suffering from Obsessive Compulsive Disorder, in patients suffering from other anxiety disorders and in non-clinical controls. The scales measuring negative beliefs about responsibility were found to have good reliability and internal consistency. Comparisons between criterion groups indicate considerable specificity for both assumptions and appraisals with respect to OCD. There was also good evidence of specificity in the association between responsibility cognitions and obsessional symptoms across groups, and that this association was not a consequence of links with anxiety or depressive symptoms. Although the two measures were correlated, they each made unique contributions to the prediction of obsessional symptoms. Overall, the results are consistent with the hypothesis that responsibility beliefs are important in the experience of obsessional problems.