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A Ottolenghi

Publications and source records attributed to A Ottolenghi.

At least 19 recordsLinked to original sources

The FLUKA code: new developments and application to 1 GeV/n iron beams.

The modeling of ion transport and interactions in matter is a subject of growing interest, driven by the continuous increase of possible application fields. These include hadron therapy, dosimetry, and space missions, but there are also several issues involving fundamental research, accelerator physics, and cosmic ray physics, where a reliable description of heavy ion induced cascades is important. In the present work, the capabilities of the FLUKA code for ion beams will be briefly recalled and some recent developments presented. Applications of the code to the simulation of therapeutic carbon, nitrogen and oxygen ion beams, and of iron beams, which are of direct interest for space mission related experiments, will be also presented together with interesting consideration relative to the evaluation of dosimetric quantities. Both applications involve ion beams in the AGeV range.

Carbon↗

DNA DSB induced in human cells by charged particles and gamma rays: experimental results and theoretical approaches.

PURPOSE: To quantify the role played by radiation track structure and background fragments in modulating DNA fragmentation in human cells exposed to gamma-rays and light ions. MATERIALS AND METHODS: Human fibroblasts were exposed in vitro to different doses (in the range from 40 - 200 Gy) of (60)Co gamma-rays and 0.84 MeV protons (Linear Energy Transfer, LET, in tissue 28.5 keV/microm). The resulting DNA fragments were scored under two electrophoretic conditions, in order to optimize separation in the size ranges 0.023 - 1.0 Mbp and 1.0 - 5.7 Mbp. In parallel, DNA fragmentation was simulated both with a phenomenological approach based on the "generalized broken-stick" model, and with a mechanistic approach based on the PARTRAC (acronym of PARticle TRACk) Monte Carlo code (1.32 MeV photons were used for the simulation of (60)Co gamma-rays). RESULTS: For both gamma-rays and protons, the experimental dose response in the range 0.023 - 5.7 Mbp could be approximated as a straight line, the slope of which provided a yield of (5.3 +/- 0.4) x 10(-9) Gy(-1) bp(-1) for gamma-rays and (7.1 +/- 0.6) x 10(-9) Gy(-1) bp(-1) for protons, leading to a Relative Biological Effectiveness (RBE) of 1.3 +/- 0.2. From both theoretical analyses it appeared that, while gamma-ray data were consistent with double-strand breaks (DSB) random induction, protons at low doses showed significant deviation from randomness, implying enhanced production of small fragments in the low molecular weight part of the experimental range. The theoretical analysis of fragment production was then extended to ranges where data were not available, i.e. to fragments larger than 5.7 Mbp and smaller than 23 kbp. The main outcome was that small fragments (<23 kbp) are produced almost exclusively via non-random processes, since their number is considerably higher than that produced by a random insertion of DSB. Furthermore, for protons the number of these small fragments is a significant fraction (about 20%) of the total number of fragments; these fragments remain undetected in these experiments. Calculations for 3.3 MeV alpha particle irradiation (for which no experimental data were available) were performed to further investigate the role of fragments smaller than 23 kbp; in this case, besides the non-random character of their production, their number resulted to be at least as much as half of the total number of fragments. CONCLUSION: Comparison between experimental data and two different theoretical approaches provided further support to the hypothesis of an important role of track structure in modulating DNA damage. According to the theoretical approaches, non-randomness of fragment production was found for proton irradiation for the smaller fragments in the experimental size range and, in a significantly larger extent, for fragments of size less than 23 kbp, both for protons and alpha particles.

Cells, Cultured↗

The application of FLUKA to dosimetry and radiation therapy.

The FLUKA Monte Carlo code has been evolving over the last several decades and is now widely used for radiation shielding calculations. In order to facilitate the use of FLUKA in dosimetry and therapy applications, supporting software has been developed to allow the direct conversion of the output files from standard CT-scans directly into a voxel geometry for transport within FLUKA. Since the CT-scan information essentially contains only the electron density information over the scanned volume, one needs the specific compositions for each voxel individually. We present here the results of a simple algorithm to assign tissues in the human body to one of four categories: soft-tissue, hard-bone, trabecular-bone and porous-lung. In addition, we explore the problem of the pathlength distributions in porous media such as trabecular bone. A mechanism will be implemented within FLUKA to allow for variable multipal fixed density materials to accommodate the pathlength distributions discovered.

Algorithms↗

The FLUKA code for space applications: recent developments.

The FLUKA Monte Carlo transport code is widely used for fundamental research, radioprotection and dosimetry, hybrid nuclear energy system and cosmic ray calculations. The validity of its physical models has been benchmarked against a variety of experimental data over a wide range of energies, ranging from accelerator data to cosmic ray showers in the earth atmosphere. The code is presently undergoing several developments in order to better fit the needs of space applications. The generation of particle spectra according to up-to-date cosmic ray data as well as the effect of the solar and geomagnetic modulation have been implemented and already successfully applied to a variety of problems. The implementation of suitable models for heavy ion nuclear interactions has reached an operational stage. At medium/high energy FLUKA is using the DPMJET model. The major task of incorporating heavy ion interactions from a few GeV/n down to the threshold for inelastic collisions is also progressing and promising results have been obtained using a modified version of the RQMD-2.4 code. This interim solution is now fully operational, while waiting for the development of new models based on the FLUKA hadron-nucleus interaction code, a newly developed QMD code, and the implementation of the Boltzmann master equation theory for low energy ion interactions.

Computer Simulation↗

Role of shielding in modulating the effects of solar particle events: Monte Carlo calculation of absorbed dose and DNA complex lesions in different organs.

Distributions of absorbed dose and DNA clustered damage yields in various organs and tissues following the October 1989 solar particle event (SPE) were calculated by coupling the FLUKA Monte Carlo transport code with two anthropomorphic phantoms (a mathematical model and a voxel model), with the main aim of quantifying the role of the shielding features in modulating organ doses. The phantoms, which were assumed to be in deep space, were inserted into a shielding box of variable thickness and material and were irradiated with the proton spectra of the October 1989 event. Average numbers of DNA lesions per cell in different organs were calculated by adopting a technique already tested in previous works, consisting of integrating into "condensed-history" Monte Carlo transport codes--such as FLUKA--yields of radiobiological damage, either calculated with "event-by-event" track structure simulations, or taken from experimental works available in the literature. More specifically, the yields of "Complex Lesions" (or "CL", defined and calculated as a clustered DNA damage in a previous work) per unit dose and DNA mass (CL Gy-1 Da-1) due to the various beam components, including those derived from nuclear interactions with the shielding and the human body, were integrated in FLUKA. This provided spatial distributions of CL/cell yields in different organs, as well as distributions of absorbed doses. The contributions of primary protons and secondary hadrons were calculated separately, and the simulations were repeated for values of Al shielding thickness ranging between 1 and 20 g/cm2. Slight differences were found between the two phantom types. Skin and eye lenses were found to receive larger doses with respect to internal organs; however, shielding was more effective for skin and lenses. Secondary particles arising from nuclear interactions were found to have a minor role, although their relative contribution was found to be larger for the Complex Lesions than for the absorbed dose, due to their higher LET and thus higher biological effectiveness.

Astronauts↗

Complete pancreatic ectopia in a gastric duplication cyst: a case report and review of the literature.

Ectopic tissue can be histologically detected in gastric duplication cysts. The authors describe the case of a complete pancreatic ectopia in a prenatally diagnosed symptomatic gastric duplication cyst in a 6-month-old male infant. Surgical removal of the cystic formation was curative. In view of the rarity of the lesion, a full clinical and diagnostic classification of the condition proved possible only after radical surgical resection and histological examination. Immunohistochemical investigation enabled us to detect the complete pancreatic ectopia.

Choristoma↗

Models of chromosome aberration induction: an example based on radiation track structure.

A few examples of models of chromosome aberration induction are summarised and discussed on the basis of the three main theories of aberration formation, that is "breakage-and-reunion", "exchange" and "one-hit". A model and code developed at the Universities of Milan and Pavia is then presented in detail. The model provides dose-response curves for different aberration types (dicentrics, translocations, rings, complex exchanges and deletions) induced in human lymphocytes by gamma rays, protons and alpha particles of different energies, both as monochromatic fields and as mixed fields. The main assumptions are that only clustered - and thus severe - DNA breaks ("Complex Lesions", CL) can participate in the production of aberrations, and that only break free ends in neighbouring chromosome territories can interact and form exchanges. The yields of CLs induced by the various radiation types of interest are taken from a previous modelling work. These lesions are distributed within a sphere representing the cell nucleus according to the radiation track structure, e.g. randomly for gamma rays and along straight lines for light ions. Interphase chromosome territories are explicitly simulated and configurations are obtained in which each chromosome occupies an intranuclear domain with volume proportional to its DNA content. In order to allow direct comparisons with experimental data, small fragments can be neglected since usually they cannot be detected in experiments. The presence of a background level of aberrations is also taken into account. The results of the simulations are in good agreement with experimental dose-response curves available in the literature, that provides a validation of the model both in terms of the adopted assumptions and in terms of the simulation techniques. To address the question of "true" incompleteness, simulations were also run in which all fragments were assumed to be visible.

Animals↗

[Primary ad secondary gastro-esophageal reflux in pediatric age].

AIM: This study takes into consideration children traited for: a) "primary" gastro-esophageal reflux (GER); b) GER "secondary" to delayed gastric emptying; c) some congenital anomalies which can cause or favour GER in pediatric age. METHODS: During 2002, 21 infants or children operated on for "primary" or "secondary" GER and 62 patients operated on for esophageal atresia, diaphragmatic hernia or abdominal wall defect were followed-up to evaluate the frequency and the course of post-operative GER. RESULTS: Patients with "primary" GER had 14% relapses after partial or total fundoplication; all patients with "secondary" GER submitted to fundoplication, usually associated to pyloroplasty, had 0% relapses. One child, after Bianchi's operation, developed an erosive gastritis. Variable degrees of GER developed in 43% of patients operated on for esophageal atresia, in 25% for congenital diaphragmatic hernia and in 0% for abdominal wall defect. In 90% of GER occurred after treatment of esophageal atresia and in 100% of diaphragmatic hernia (predominantely "acquired") an exclusively medical therapy was successfully performed. CONCLUSION: The conclusion is drawn that: a) the relatively high percentage of relapses after fundoplication in "primary" GER may be related to an incorrect classification of a few number of cases ("secondary" GER considered--and treated--like "primary" GER in the '70s and '80s years?); b) fundoplication associated to a best gastric-emptying operation (pyloroplasty) may lead to excellent results in secondary GER; c) esophageal atresia and congenital diaphragmatic hernia (not including the abdominal wall defects) can cause GER in most cases responsive to simple medical therapy.

Child↗

Chromosome aberrations as biomarkers of radiation exposure: modelling basic mechanisms.

The space radiation environment is a mixed field consisting of different particles having different energies, including high charge and energy (HZE) ions. Conventional measurements of absorbed doses may not be sufficient to completely characterise the radiation field and perform reliable estimates of health risks. Biological dosimetry, based on the observation of specific radiation-induced endpoints (typically chromosome aberrations), can be a helpful approach in case of monitored exposure to space radiation or other mixed fields, as well as in case of accidental exposure. Furthermore, various ratios of aberrations (e.g. dicentric chromosomes to centric rings and complex exchanges to simple exchanges) have been suggested as possible fingerprints of radiation quality, although all of them have been subjected to some criticisms. In this context a mechanistic model and a Monte Carlo code for the simulation of chromosome aberration induction were developed. The model, able to provide dose-responses for different aberrations (e.g. dicentrics, rings, fragments, translocations, insertions and other complex exchanges), was further developed to assess the dependence of various ratios of aberrations on radiation quality. The predictions of the model were compared with available data, whose experimental conditions were faithfully reproduced. Particular attention was devoted to the scoring criteria adopted in different laboratories and to possible biases introduced by interphase death and mitotic delay. This latter aspect was investigated by taking into account both metaphase data and data obtained with Premature Chromosome Condensation (PCC).

Alpha Particles↗

Microsurgical spermatico-epigastric venous anastomosis in the treatment of varicocele in children: assessment of long-term patency.

AIM: To demonstrate the long-term patency of microsurgical anastomoses between the internal spermatic vein and the inferior epigastric vein, constructed in the treatment of essential varicocele in paediatric patients to supplement ligation of the spermatic veins. MATERIALS AND METHODS: We submitted 66 patients to inguinopelvic colour-flow Doppler ultrasonography. The patients had been treated 18 - 36 months earlier for essential varicocele by microsurgical inguinal ligation of the testicular venous pedicle and anastomosis between the internal spermatic vein and the inferior epigastric vein. RESULTS: Preoperatively, the 66 patients operated on at ages ranging from 10 to 16 years (13 +/- 1.4) presented with Dubin and Amelar grade II (14 patients) or grade III (52 patients) left varicocele with ipsilateral testicular hypotrophy. The postoperative follow-up showed 2 cases of persistence of disease and 3 cases of persistence of "medium" spermatic vein reflux without clinical evidence of varicocele. Seven patients developed left hydrocele which resolved spontaneously in 5 cases, whereas in 2 cases it proved necessary to perform an eversion of the tunica vaginalis of the testis. The results obtained in patients treated for Coolsaet type I varicocele (64 patients) were as follows: long-term patency of the anastomosis was observed in 58/64 patients (90.6 %); in 4 patients (6.2 %) the left inferior epigastric vein presented a position in relation to the homologous artery that prevented adequate sampling and thus made it impossible to assess the patency of the anastomosis; in 2 patients (3.1 %) the anastomosis was closed. In the two patients who had submitted to anastomosis for Coolsaet type III varicocele, colour-flow Doppler failed to identify the shunt. CONCLUSIONS: The results of this study demonstrate that microsurgical anastomosis between the internal spermatic vein, and the inferior epigastric vein remains competent in the long term, thus confirming the validity of this technique for the treatment of essential varicocele in children.

Abdominal Muscles↗

Modelling study on the protective role of OH radical scavengers and DNA higher-order structures in induction of single- and double-strand break by gamma-radiation.

PURPOSE: To quantify the protective effects of (non-histonic) OH-radical scavengers and DNA higher-order structures in induction of single- (ssbs) and double-strand breaks (dsbs) by gamma-rays. MATERIALS AND METHODS: Spatial distributions of energy depositions by gamma-rays in liquid water were modelled with the track structure modules of the biophysical simulation code PARTRAC. Such distributions were superimposed on different DNA structure models (e.g. linear DNA, SV40 'minichromosomes' and compact chromatin), and direct energy depositions in the sugar-phosphate were considered as potential (direct) ssbs. The diffusion and interaction of the main chemical species produced in liquid water radiolysis were explicitly simulated, and reactions of *OH with the sugar-phosphate were considered as potential (indirect) ssbs. Two ssb on opposite DNA strands within 10 base pairs were considered as one dsb. Yields of ssb and dsb Gy(-1) Dalton(-1) in different DNA target structures were calculated as a function of the *OH mean lifetime, whose inverse value was taken as representative of the scavenging capacity of the DNA environment. RESULTS AND CONCLUSIONS: A further validation of the models implemented in the PARTRAC code has been provided, thus allowing a better understanding of the mechanisms underlying DNA damage. More specifically, the protection due to *OH scavengers was separately quantified with respect to that due to histones and chromatin folding, which could be 'switched off' in the simulations. As expected, for a given value of the environment scavenging capacity, linear DNA was more susceptible to strand breakage than SV40 minichromosomes, which in turn showed higher damage yields with respect to cellular DNA due to the larger accessibility offered to *OH. Furthermore, by increasing the scavenging capacity, the break yields decreased in all structures and tended to coincide with direct damage yields. Very good agreement was found with available experimental data. Comparisons with data on 'nucleoid' DNA (i.e. unfolded and histone-depleted DNA) also suggested that the experimental procedures used to obtain such structures might lower the environment scavenging capacity owing to the loss of cellular scavengers.

DNA↗

Estimating mixed field effects: an application supporting the lack of a non-linear component for chromosome aberration induction by neutrons.

The action of neutron fields on biological structures was investigated on the basis of chromosome aberration induction in human cells. Available experimental data on aberration induction by neutrons and their interaction products were reviewed. Present criteria adopted in neutron radiation protection were discussed. The linear coefficient alpha and the quadratic coefficient beta describing dose-response curves for dicentric chromosomes induced by neutrons of different energies were calculated via integration of experimental data on dicentric induction by photons and charged particles into the Monte Carlo transport code FLUKA. The predicted values of the linear coefficients for neutron beams of different energies showed good agreement with the corresponding experimental values, whereas the data themselves indicated that the neutron quadratic coefficient cannot be obtained by 'averaging' the beta values of recoil ions and other nuclear reaction products. This supports the hypothesis that neutron induced aberrations increase substantially linearly with dose, a question that has been object of debate for a long time and is still open.

Chromosome Aberrations↗

Secondary omental torsion in children: report of two cases and review of the literature.

Torsion of the greater omentum (TGO) may be due to a congenital abnormal attachment of its free edge. There are no specific symptoms that allow a preoperative differential diagnosis of this condition from common pathologies such as acute appendicitis. Attachment of the omentum to the large bowel and the absence of concomitant diseases make it possible to distinguish TGO secondary to a congenital attachment anomaly from omental infarction, primary TGO, and TGO secondary to an acquired attachment anomaly (attachment to cysts, tumours, hernias, surgical scars, or perforated bowel segments). Resection of the ischaemic portion of the omentum permits complete resolution of the clinical symptoms. The authors report two cases of TGO in children due to abnormal attachment of the greater omentum to the ascending and transverse colon, respectively.

Adolescent↗

Nuclear architecture and radiation induced chromosome aberrations: models and simulations.

Knowledge of radiation track structure and its interaction with biological targets is a fundamental starting point in understanding the mechanisms underlying the induction of biological damage. In this context Monte Carlo codes are a powerful tool of investigation, allowing one to simulate both track structure and the features of the target(s) of interest at different scales, from nanometres (linear dimensions of DNA) to micrometres (linear dimensions of human cell nuclei and interphase chromosome territories). In the light of recent experimental findings on nuclear architecture, different approaches in modelling chromosome structure and aberration induction are discussed. In particular, a model is presented in which chromosome territories were explicitly described as subnuclear regions and aberration induction was modelled by coupling the structure of the target with that of the radiation track. Comparisons between model predictions and experimental results from the literature are also reported.

Cell Nucleus↗

[The role of continent perineal colostomy in surgical emergencies of the distal bowel].

Diverting colostomy is commonly required in surgical emergencies of the distal colon, especially if the patient is in poor condition. This paper shows that the colostomy could be unnecessary in most cases. In the last 10 years, 6 patients (4 with high-risk or postoperative complicated Hirschsprung disease, 1 with intestinal neuronal dysplasia and 1 with iatrogenic rectal stenosis obstruction) have been submitted to primary continent perineal colostomy-modified Duhamel's procedure. The modified technique consists of the exteriorization of the normal colon or ileum by a retrorectal and trans-anal way, while the excision of redundant tissue and rectal spur section are postponed at least for 10 days. In personal experience this peculiar surgical approach allows to avoid not only the complications due to the fashioning of a contraindicated primary anastomosis, but even those due to stomy performance and its closure, promoting good anatomo-functional results in all patients. The advantages of modified Duhamel's operation compared to other procedures (Swenson-Pellerin or Soave pull-through) depend on the rapidity of execution and on the quality of short and long term outcome.

Adolescent↗

Modelling chromosomal aberration induction by ionising radiation: the influence of interphase chromosome architecture.

Several advances have been achieved in the knowledge of nuclear architecture and functions during the last decade, thus allowing the identification of interphase chromosome territories and sub-chromosomal domains (e.g. arm and band domains). This is an important step in the study of radiation-induced chromosome aberrations; indeed, the coupling between track-structure simulations and reliable descriptions of the geometrical properties of the target is one of the main tasks in modelling aberration induction by radiation, since it allows one to clarify the role of the initial positioning of two DNA lesions in determining their interaction probability. In the present paper, the main recent findings on nuclear and chromosomal architecture are summarised. A few examples of models based on different descriptions of interphase chromosome organisation (random-walk models, domain models and static models) are presented, focussing on how the approach adopted in modelling the target nuclei and chromosomes can influence the simulation of chromosomal aberration yields. Each model is discussed by taking into account available experimental data on chromosome aberration induction and/or interphase chromatin organisation. Preliminary results from a mechanistic model based on a coupling between radiation track-structure features and explicitly-modelled, non-overlapping chromosome territories are presented.

Animals↗

[Cryptohypospadias: Surgical approach and long-term results].

BACKGROUND: Chordee without hypospadias is a rare morphological abnormality of the penis capable of interfering with sexual function. Usually, cases of chordee without hypospadias require surgical correction, and the aim of this study is to assess the efficacy of the techniques normally used in this pathology. METHODS: The authors analyze the surgical outcomes achieved in 34 patients presenting various degrees of ventral or lateral curvature of the erect penis and operated on in our department over the past 22 years. Twenty-nine subjects attended for follow-up, including 13 who have now reached adulthood. RESULTS: The milder forms of chordee without hypospadias (Horton and Devine type III and lateral deviations of the penis) all benefited from minor surgery (dermal grafts and Nesbit dorsal plication of the contralateral penile tunica albuginea) and were corrected with a single operation. The most serious forms of chordee without hypospadias where the hypoplasia variously affected the corpus spongiosum, Buck's fascia and the dartos fascia (Horton and Devine types I and II), were submitted to a supplementary extensive urethral mobilization or occasionally a urethroplasty and one-third of them presented persistent residual curvature. CONCLUSIONS: The authors advocate a more aggressive surgical approach (urethroplasty and/or patches on the ventral tunica albuginea as an alternative to urethral mobilisation) in subjects with more pronounced defects.

Adolescent↗