Report on G4-Med, a Geant4 benchmarking system for medical physics applications developed by the Geant4 Medical Simulation Benchmarking Group.

BACKGROUND: Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro- and nanodosimetry, imaging, radiation protection, and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing. AIMS: To respond to these needs, we developed G4-Med, a benchmarking and regression testing system of Geant4 for medical physics. MATERIALS AND METHODS: G4-Med currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the prebuilt Geant4 physics lists are tested. The tests included in G4-Med are executed on the CERN computing infrastructure via the use of the geant-val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes. RESULTS: This paper describes the tests included in G4-Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data. DISCUSSION: Our results indicate that the Geant4 electromagnetic physics constructor G4EmStandardPhysics_option4 gives a good agreement with the reference data for all the tests. The QGSP_BIC_HP physics list provided an overall adequate description of the physics involved in hadron therapy, including proton and carbon ion therapy. New tests should be included in the next stage of the project to extend the benchmarking to other physical quantities and application scenarios of interest for medical physics. CONCLUSION: The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application.

Preliminary results in using Deep Learning to emulate BLOB, a nuclear interaction model.

PURPOSE: A reliable model to simulate nuclear interactions is fundamental for Ion-therapy. We already showed how BLOB ("Boltzmann-Langevin One Body"), a model developed to simulate heavy ion interactions up to few hundreds of MeV/u, could simulate also 12C reactions in the same energy domain. However, its computation time is too long for any medical application. For this reason we present the possibility of emulating it with a Deep Learning algorithm. METHODS: The BLOB final state is a Probability Density Function (PDF) of finding a nucleon in a position of the phase space. We discretised this PDF and trained a Variational Auto-Encoder (VAE) to reproduce such a discrete PDF. As a proof of concept, we developed and trained a VAE to emulate BLOB in simulating the interactions of 12C with 12C at 62 MeV/u. To have more control on the generation, we forced the VAE latent space to be organised with respect to the impact parameter (b) training a classifier of b jointly with the VAE. RESULTS: The distributions obtained from the VAE are similar to the input ones and the computation time needed to use the VAE as a generator is negligible. CONCLUSIONS: We show that it is possible to use a Deep Learning approach to emulate a model developed to simulate nuclear reactions in the energy range of interest for Ion-therapy. We foresee the implementation of the generation part in C++ and to interface it with the most used Monte Carlo toolkit: Geant4.

Preliminary results coupling "Stochastic Mean Field" and "Boltzmann-Langevin One Body" models with Geant4.

PURPOSE: Monte Carlo (MC) simulations are widely used for medical applications and nuclear reaction models are fundamental for the simulation of the particle interactions with patients in ion therapy. Therefore, it is of utmost importance to have reliable models in MC simulations for such interactions. Geant4 is one of the most used toolkits for MC simulation. However, its models showed severe limitations in reproducing the yields measured in the interaction of ion beams below 100 MeV/u with thin targets. For this reason, we interfaced two models, SMF ("Stochastic Mean Field") and BLOB ("Boltzmann-Langevin One Body"), dedicated to simulate such reactions, with Geant4. METHODS: Both SMF and BLOB are semi-classical, one-body approaches to solve the Boltzmann-Langevin equation. They include an identical treatment of the mean-field propagation, on the basis of the same effective interaction, but they differ in the way fluctuations are included. Furthermore, we tested a correction to the excitation energy calculated for the light fragments emerging from the simulations and a simple coalescence model. RESULTS: While both SMF and BLOB have been developed to simulate heavy ion interactions, they show very good results in reproducing the experimental yields of light fragments, up to alpha particles, obtained in the interaction of 12C with a thin carbon target at 62 MeV/u. CONCLUSIONS: BLOB in particular gives promising results and this stresses the importance of integrating it into the Geant4 toolkit.

Well-differentiated giant scrotal liposarcoma: case presentation and management.

Scrotal liposarcoma is an uncommon disease, usually found after the fifth decade. We describe the case of a well-differentiated scrotal liposarcoma associated with a considerable inflammatory reaction, treated with surgical ablation.

Eating behavior of ballet dancers.

Ballet dancers are frequently regarded as having a higher risk of developing eating disorders (ED). This paper describes the eating habits and prevalence of ED in a group of female students from a dance academy in Rome, Italy. Participants were assessed with an array of measures conventionally employed (usually singly) in epidemiological studies of ED, namely: an anthropometrical-nutritional evaluation, the EAT, EDI, and BUT questionnaires, and the EDE interview. The 160 students who agreed to participate were evaluated anthropometrically, nutritionally and psychometrically and 83 underwent the EDE structured interview. Their calorie intake was insufficient in all age groups in terms of the nutritional standards required by their daily physical activity. EAT, EDI and BUT enhanced concerns about dieting, food intake control and body image. The significance of the correlations between calorie intake and the EAT Dieting and the EDI Perfectionism and Interceptive Awareness scores increased in function of age. Food, weight and body image concerns increased with age and length of time in the ballet environment The reduced calorie intake was not necessarily linked to the presence of psychopathological signs.

Hexamethyidisiloxane: A 13-week subchronic whole-body vapor inhalation toxicity study in Fischer 344 rats.

Hexamethyldisiloxane (HMDS) is a volatile linear siloxane dimer used in many applications, including precision cleaning, active ingredient carrier, and as a manufacturing intermediate. The purpose of this study was to characterize the subchronic vapor inhalation toxicity of the material as part of a comprehensive toxicology program. Groups of 20 male and 20 female Fischer 344 (F344) rats were exposed to nominal (and mean actual) vapor concentrations of 0, 50 (50), 200 (194), 600 (593), 1,500 (1,509) and 5,000 (5,012) ppm of HMDS, 6 hours per day, 5 days per week, for 13 weeks. No treatment-related signs of clinical toxicity or mortality, statistically significant effects upon body weight gain or food consumption, ophthalmoscopic changes, gross macroscopic necropsy findings, or organ weight changes were noted. Minor hematological, clinical biochemical, and urinalysis changes were seen but were not considered to be of toxicological relevance. Histological lesions in the kidney apparently consistent with male rat-specific alpha-2-urinary globulin nephropathy were observed in male rats exposed to 593, 1,509, and 5,012 ppm of HMDS, accompanied by slightly increased plasma urea and creatinine concentrations. No other treatment-related histological changes were seen in HMDS-exposed rats.

Expression of p53 and bcl-2 in clinically localized prostate cancer before and after neo-adjuvant hormonal therapy.

The prognostic significance of p53 and bcl-2 expression in prostate carcinoma is currently under investigation. The aim of the present study was to analyze their expression in diagnostic biopsies and in prostatectomies performed after neo-adjuvant hormonal therapy to investigate their role in hormone resistance. One hundred and six patients with advanced prostate carcinoma were treated for 3 months with LHRH analogues before radical surgery. The expression of p53 and bcl-2 was analyzed by immunohistochemistry in all cases of prostatectomy and in available biopsies obtained before treatment, and was correlated with clinicopathologic parameters and follow-up. A significant increase in p53 expression was found following hormonal therapy, whereas no changes were observed in the expression of bcl-2. The increase in p53 did not correlate with the presence of therapy-induced morphological changes in prostate cancers, but it did correlate significantly with histologic grade and pathologic stage, biochemical progression of the disease, and short overall survival. At multivariate analysis, only grade and stage proved to be independent predictors of shorter survival. There were no correlations between bcl-2 and clinicopathologic variables whether in biopsies or in prostatectomies. The unfavorable clinical course associated with p53-positive carcinomas suggests that neo-adjuvant hormonal therapy may cause the selection of minor p53 mutated clones, rather than the induction of wild-type p53. In any case, the enhanced expression of p53 could label hormone-resistant cancers for further adjuvant therapy.

Validation and reliability of the Italian EAT-26.

The Italian from of the short, 26-item Eating Attitudes Test (EAT-26) has been administered to 1277 Roman high-school students, mostly females, as a screening device. Ninety-five students with a total score > 20 and 40 students with a low score, were randomly selected, interviewed and diagnosed. The EAT-26 proved to be more sensitive to the presence of an eating disorder than to a specific clinical entity. Item analysis performed on the EAT-26 variables showed satisfactory reliability coefficients. Factor analysis using an oblique rotation was similar to that obtained by Garner et al. (1). Factor analysis with an orthogonal rotation (Cattell's screen test) identified five factors. Results suggested that the EAT-26 isolates cases at risk of clinical spectrum eating disorders.

Does p53 immunostaining improve diagnostic accuracy in urine cytology?

The frequent change of the transitional cell carcinoma of the urinary tract accounts for the fact that cytological abnormalities in urinary specimens are often not sufficient to enable a definitive diagnosis of malignancy. The purpose of this work was to evaluate the possible use of p53 protein in increasing the diagnostic accuracy of urinary cytology. The expression of p53 was investigated by immunocytochemistry in two groups of urinary specimens, one cytologically positive and the other cytologically negative for cancer. Immunostaining was carried out using a monoclonal antibody to p53. In the positive group, in which bladder cancer was confirmed by cystoscopy and biopsy (31 cases), positive reaction for p53 was found in 55% of the cases (17 cases). In the negative group (92 cases), presence of cancer was histologically ascertained in 64 cases and in this group 15 cases (23.4%) showed positive p53 staining. In the remaining 28 cases of this group, where TCC was not present, 7 cases showed p53 positivity in non-neoplastic urothelial cells. This result shows that, while immunocytochemical detection of p53 in urinary specimens may be used for prognostic evaluation of patients with bladder cancer, it does not contribute to the diagnostic accuracy in cases with morphologically inconclusive or negative cytology. The sensitivity and specificity of the method in detecting bladder carcinoma were 23.5 and 75%, respectively.

Combination treatment versus LHRH alone in advanced prostatic cancer.

Androgen deprivation based on hormone manipulation is the treatment of choice in advanced prostatic cancer. The unequivocal role of adrenal androgens in the growth of prostatic cancer after medical or surgical castration requires a new logical approach (complete androgen blockade) in the treatment of advanced prostate cancer. One hundred and fifty patients with biopsy-proven advanced prostatic cancer were randomized into two groups. One group (74 patients) received leuprolide + flutamide (complete androgen blockade); the second group (76 patients) received only leuprolide and, during the first 3 weeks of treatment, cyproterone acetate (150 mg/day) to prevent flare-up phenomena. The aim of the study was to evaluate the differences between the two groups on overall survival and time to progression (log-rank test). One hundred and twenty-five patients were evaluable, 62 in the leuprolide-only group and 63 in the leuprolide + flutamide group. Median duration of follow-up was 102 weeks. No statistical difference between the two groups was observed in overall survival, in time to disease progression, and in time to treatment failure. In the combination (leuprolide + flutamide) treatment group, a positive trend for overall survival and in time to progression was observed in a subgroup of patients with good performance status and no bone metastases. We observed mild gastrointestinal toxicity (diarrhea, nausea) in the group treated with leuprolide + flutamide. The aim of this study was to compare the effectiveness of total androgen withdrawal with medical testicular suppression in advanced prostatic cancer. No significant statistical difference was observed between the two groups in overall survival and in time to progression, but probably too few patients were enrolled in each treatment arm to give a statistical interpretation of our results. We conclude that there is a positive trend in the combination treatment arm in patients with good prognostic factors.

Styles of regulation in the bipolar spectrum.

Styles of regulation were assessed with the Serial Color-Word Test in a group of 35 compensated DSM-III--R bipolar patients (Bipolar) and in 3 control groups: Major Depression (n = 35), Schizophrenia (n = 50), and self-rated Personality Disorder (n = 40). On several measures of nonlinear change (V), patients in the Bipolar group had mean scores between those of the Personality Disorder and the Schizophrenic groups, and overlapped with those of the Major Depression group. Patients in the Bipolar group with clearcut temperaments (hyperthymic or depressive) were significantly more dissociative and less stabilized than other patients in the same group. A further group of nonclinical subjects with hyperthymic temperament (n = 20) was significantly more dissociative than the Personality Disorder group.

Combination treatment in M1 prostate cancer.

The treatment of advanced prostate cancer is based on hormone manipulation to eliminate the trophic effect of testosterone on sensitive androgen tissue of the tumor. In this study, we evaluated the efficacy of the partial androgen blockage versus the complete androgen blockage. One hundred, twenty-two patients were entered in this study and randomly were treated with buserelin alone or with buserelin and flutamide. The group that received buserelin was given cyproterone acetate (200 mg/day) during first 3 weeks of treatment to avoid "flare-up". During the follow-up (range 0-244 +/- 1 weeks), we evaluated 59 patients (61.4%) that had positive response and 37 patients (38.6%) that showed progressive disease: There were no statistically significant differences between the two treatment groups, not even in the evaluation of median time to response and of median time to treatment failure. In conclusion, the results emphasize that total androgenic blockage is as effective as a luteinizing hormone-releasing hormone analog used alone.

Effects of acute hypoxia on the normal and diseased sinus node.

We have studied the effects of breathing 12% oxygen in three groups of patients with sinus bradycardia: 11 with intrinsic sick sinus syndrome, 11 with extrinsic sick sinus syndrome and 11 without any evidence of sinus dysfunction. During hypoxia, the heart rate increased by an average of 6.7 beats/min in the patients with intrinsic sick sinus syndrome, 15.7 beats/min in the patients with extrinsic sick sinus syndrome and 14.3 beats/min in those with normal sinus node function. The difference in response of the heart rate between the two groups with sick sinus syndrome was highly significant (P less than 0.001). There was no difference between the three groups in the response of the blood pressure, ventilation, and partial pressures of oxygen and carbon dioxide. The increased heart rate which accompanies hypoxia is thought to be mediated through sympathetic mechanisms consequent on hyperventilation. In the intrinsic sick sinus syndrome, there is evidence that the sympathetic tone is already increased and this may limit the extent of the tachycardia due to hypoxia. Hypoxia may be a useful clinical test to distinguish between the two forms of sick sinus syndrome.

Noninvasive assessment of pulmonary hypertension: a simultaneous echo-Doppler hemodynamic study.

Thirty patients with stable chronic obstructive lung disease (COLD) underwent an echo-Doppler examination before and during right heart catheterization. No statistically significant differences between observations for any of two-dimensional echo-Doppler parameters were found. The measurement of all parameters taken during the catheterization correlated better with mean pulmonary artery pressure (mPAP) than those taken before. This difference was most evident for the isovolumetric acceleration time (r = 0.71 before versus r = 0.85 during the catheterization) and relaxation time (r = -0.75 before versus r = -0.87 during the catheterization). The multiple correlation coefficient for all measured parameters and mPAP was 0.83 before and 0.92 during the catheterization. In conclusion, in patients with COLD, it appears possible to get reliable information about PAP using noninvasive techniques.

Ventilatory response during incremental exercise tests in weight lifters and endurance cyclists.

The effect of a progressively increasing work rate (15 W X min-1) up to exhaustion on the time course of O2 uptake (VO2), ventilation (VE) and heart rate (HR) has been studied in weight lifters (WL) in comparison to endurance cyclists (Cycl) and sedentary controls (Sed). VO2 and VE were measured as average value of 30-s intervals by a semiautomatic open circuit method. VO2max was 2.55 +/- 0.33; 4.29 +/- 0.53 and 2.86 +/- 0.19 l X min-1 in WL, Cycl and Sed respectively. With time and work rate, while VO2 and HR increased linearly, VE changed its slope at two levels. The 1st VE change occurred at a work load corresponding to a mean (+/- SD) VO2 of 1.50 +/- 0.26; 1.93 +/- 0.34; and 1.23 +/- 0.14 l X min-1 in WL, Cycl, and Sed respectively. VO2 values corresponding to the second VE change of slope were 2.18 +/- 0.32 in WL; 3.48 +/- 0.53 in Cycl and 2.17 +/- 0.28 l X min-1 in Sed. The first change of slope might be the consequence of the different readjustment of VO2 on-response and hence of early lactate in the different subjects. The second change seems to be comparable to the conventional anaerobic threshold and is achieved in all subjects when VE vs time slope is 7-10 l X min-1/min of exercise.

Determination of serum angiotensin-converting enzyme in sarcoidosis.

Serum angiotensin-converting enzyme activity was measured in 72 patients with sarcoidosis and in 50 normal controls by a radiochemical assay. SACE levels were examined with respect to the 'activity' of the disease, based on clinical, radiographic and physiological assessment. SACE activity in 34 patients with clinical sarcoidosis (147 +/- 44.3 nmol/min/ml) was significantly high (p less than 0.001) when compared to that of 38 patients who had recovered from sarcoidosis (113.9 +/- 26.4 nmol/min/ml) and 50 normal subjects (97.8 +/- 21 nmol/min/ml). SACE levels were significantly different (p less than 0.01) between 15 subjects with 'active' disease (173.9 +/- 51.9 nmol/min/ml) and those with 'inactive' disease (126.1 +/- 26.3 nmol/min/ml). It is concluded that there is a strict correlation between SACE levels and 'activity' of sarcoidosis if multiple criteria (clinical, radiographic and physiological) are employed.

[Oxygen therapy with an oxygen concentrator]. / Ossigenoterapia mediante concentratore di ossigeno.

An account is given of the employment of an O2 concentrator (De VO2 955) in chronic bronchopneumopaths with respiratory insufficiency and pulmonary hypertension. An assessment was made of the gas supply modalities, particularly with Venturi masks. In patients with normal or low ventilation, 24% and 28% FiO2 masks gave suitable results, whereas those with a higher concentration were unusable, since the present FiO2 value was not reached. This was probably due to the fact that there is a fall in O2 concentration at high low flow rates, and as a result of an insufficient Venturi effect.

[Behavior of various indices of respiratory function in the course of mitral valve disease]. / Comportamento di alcuni indici di funzionalità respiratoria in corso di valvulopatia mitralica.

Respiratory function tests carried out on 98 patients with mitral valve disease are reported. The indices were correlated with the N.Y.H.A. classification and mean pulmonary artery pressure values. The patterns were similar for both types of correlation. There were early VC, RV and RV/TLC alterations. In more advanced cases, there were also reductions in DLCO, MEVS, and FEF25-75%. The result is a primarily restrictive dysventilatory picture that is clinically compatible with interstitial pulmonary fibrosis.