Somatic insulin signaling regulates a germline starvation response in Drosophila egg chambers.

Egg chambers from starved Drosophila females contain large aggregates of processing (P) bodies and cortically enriched microtubules. As this response to starvation is rapidly reversed upon re-feeding females or culturing egg chambers with exogenous bovine insulin, we examined the role of endogenous insulin signaling in mediating the starvation response. We found that systemic Drosophila insulin-like peptides (dILPs) activate the insulin pathway in follicle cells, which then regulate both microtubule and P body organization in the underlying germline cells. This organization is modulated by the motor proteins Dynein and Kinesin. Dynein activity is required for microtubule and P body organization during starvation, while Kinesin activity is required during nutrient-rich conditions. Blocking the ability of egg chambers to form P body aggregates in response to starvation correlated with reduced progeny survival. These data suggest a potential mechanism to maximize fecundity even during periods of poor nutrient availability, by mounting a protective response in immature egg chambers.

Reversible response of protein localization and microtubule organization to nutrient stress during Drosophila early oogenesis.

The maturation of animal oocytes is highly sensitive to nutrient availability. During Drosophila oogenesis, a prominent metabolic checkpoint occurs at the onset of yolk uptake (vitellogenesis): under nutrient stress, egg chambers degenerate by apoptosis. To investigate additional responses to nutrient deprivation, we studied the intercellular transport of cytoplasmic components between nurse cells and the oocyte during previtellogenic stages. Using GFP protein-traps, we showed that Ypsilon Schachtel (Yps), a putative RNA binding protein, moved into the oocyte by both microtubule (MT)-dependent and -independent mechanisms, and was retained in the oocyte in a MT-dependent manner. These data suggest that oocyte enrichment is accomplished by a combination of MT-dependent polarized transport and MT-independent flow coupled with MT-dependent trapping within the oocyte. Under nutrient stress, Yps and other components of the oskar ribonucleoprotein complex accumulated in large processing bodies in nurse cells, accompanied by MT reorganization. This response was detected as early as 2h after starvation, suggesting that young egg chambers rapidly respond to nutrient stress. Moreover, both Yps aggregation and MT reorganization were reversed with re-feeding of females or the addition of exogenous insulin to cultured egg chambers. Our results suggest that egg chambers rapidly mount a stress response by altering intercellular transport upon starvation. This response implies a mechanism for preserving young egg chambers so that egg production can rapidly resume when nutrient availability improves.

Preliminary evaluations of the undesirable patient dose from a BNCT treatment at the ENEA-TAPIRO reactor.

Boron neutron capture therapy (BNCT) is an experimental technique for the treatment of certain kinds of tumors. Research in BNCT is performed utilizing both thermal and epithermal neutron beams. Epithermal neutrons (0.4 eV-10 keV) penetrate more deeply into tissue and are thus used in non-superficial clinical applications such as the brain glioma. In the last few years, the fast reactor TAPIRO (ENEA-Casaccia Rome) has been employed as a neutron source for research into BNCT applications. Recently, an 'epithermal therapeutic column' has been designed and its construction has been completed. The Monte Carlo code MCNPX was employed to optimize the design of the column and to evaluate the dose profiles and the therapeutic parameters in the cranium of the anthropomorphic phantom ADAM. In the same context, some preliminary evaluations of the undesirable doses to the patient were performed with MCNPX. A hermaphrodite phantom derived from ADAM and EVA was employed to evaluate the energy deposition in some organs during a standard BNCT treatment. The total dose consists of the contributions from the primary neutron beam, the neutron interactions with boron and the neutron induced photons generated in the epithermal column structures and in the patient's tissues. The paper summarizes the computational procedure and provides a general dosimetric framework of the patient radiological protection aspects related to a BNCT treatment scenario at the TAPIRO reactor.

Treating voxel geometries in radiation protection dosimetry with a patched version of the Monte Carlo codes MCNP and MCNPX.

The question of Monte Carlo simulation of radiation transport in voxel geometries is addressed. Patched versions of the MCNP and MCNPX codes are developed aimed at transporting radiation both in the standard geometry mode and in the voxel geometry treatment. The patched code reads an unformatted FORTRAN file derived from DICOM format data and uses special subroutines to handle voxel-to-voxel radiation transport. The various phases of the development of the methodology are discussed together with the new input options. Examples are given of employment of the code in internal and external dosimetry and comparisons with results from other groups are reported.

The TRADE experiment: shielding calculations for the building hosting the subcritical system.

The TRADE project (TRiga Accelerator Driven Experiment), to be performed at the existing TRIGA reactor at ENEA Casaccia, has been proposed as a validation of the accelerator-driven system (ADS) concept. TRADE will be the first experiment in which the three main components of an ADS--the accelerator, spallation target and sub-critical blanket--are coupled at a power level sufficient to encounter reactivity feedback effects. As such, TRADE represents the necessary intermediate step in the development of hybrid transmutation systems, its expected outcomes being considered crucial--in terms of proof of stability of operation, dynamic behaviour and licensing issues--for the subsequent realisation of an ADS Transmutation Demonstrator. An essential role in the feasibility study of the experiment is played by radioprotection calculations. Such a system exhibits new characteristics with respect to a traditional reactor, owing to the presence of the proton accelerator. As beam losses always occur under normal operating conditions of an accelerator, shielding studies need to be performed not only around the reactor but also along the beam line from the accelerator to the spallation target. This paper illustrates a preliminary evaluation, using Monte Carlo methods, of the additional shielding to be located around the reactor structures, the beam transport line and the existing reactor building to allow access into the reactor hall and to restrict the doses outside to their legal limits.

Test of a bubble passive spectrometer for neutron dosimetry.

A passive system for neutron spectrometry has been tested in view of neutron dose evaluation in mixed radiation fields. This system, based on bubble detectors (Bubble Technology Industries, Ontario, Canada), is suitable to evaluate the neutron energy distribution in the range 10 keV-20 MeV even in the presence of intense gamma radiation, as required in various fields: medical x-ray accelerators, nuclear reactors, cosmic ray exposures on commercial high-altitude flights and space missions. A new unfolding code BUNTO has been especially developed for this application. In the present work, the results of two experimental tests are summarized. In the first one, the device has been exposed to a standard AmBe neutron source (Joint Research Centre, Ispra, Varese, Italy). In the second one, measurements have been carried out at the MAX-Lab photonuclear facility in Sweden, with a bremsstrahlung photon beam impinging on thick targets of different materials and generating a giant dipole resonance neutron spectrum. Simulations of the experimental apparatus have been performed with MCNP4B (AmBe source) and with MCNP4B-GN (MAX-Lab). Results of the comparison between experimental and calculated spectra are shown and discussed. A good agreement between measurements and simulation data is obtained in both the experiments.

Monte Carlo optimisation of a BNCT facility for treating brain gliomas at the TAPIRO reactor.

An epithermal boron neutron capture therapy facility for treating brain gliomas is currently under construction at the 5 kW fast-flux reactor TAPIRO located at ENEA, Casaccia, near Rome. In this work, the sensitivity of the results to the boron concentrations in healthy tissue and tumour is investigated and the change in beam quality on modifying the moderator thickness (within design limits) is studied. The Monte Carlo codes MCNP and MCNPX were used together with the DSA in-house variance reduction patch. Both usual free beam parameters and the in-phantom treatment planning figures-of-merit have been calculated in a realistic anthropomorphic phantom ('ADAM').

Neutron spectra in a tissue equivalent phantom during photon radiotherapy treatment by LINACS.

Bremsstrahlung photon beams produced by LINAC accelerators are currently the most used radiotherapy method for tumour treatments. When the photon energy exceeds the (gamma,n) reaction threshold energy, the patient receives an undesired dose due to photoneutron production both in the accelerator head and in the human body. In this paper, a method is presented for the assessment of the photoneutron spectra produced by Giant Dipole Resonance (GDR) during cancer radiotherapy with energetic photon beams. Experimental and numerical results have been obtained for the facility at Onkologik Klinik, Lund (Sweden), which is based on an ELEKTA 18 MV LINAC. Neutron spectra are evaluated both at the patient plane and inside an anthropomorphic phantom.

Characterisation of the TAPIRO BNCT epithermal facility.

A collimated epithermal beam for boron neutron capture therapy (BNCT) research has been designed and built at the TAPIRO fast research reactor. A complete experimental characterisation of the radiation field in the irradiation chamber has been performed, to verify agreement with IAEA requirements. Slow neutron fluxes have been measured by means of an activation technique and with thermoluminescent detectors (TLDs). The fast neutron dose has been determined with gel dosemeters, while the fast neutron spectrum has been acquired by means of a neutron spectrometer based on superheated drop detectors. The gamma-dose has been measured with gel dosemeters and TLDs. For an independent verification of the experimental results, fluxes, doses and neutron spectra have been calculated with Monte Carlo simulations using the codes MCNP4B and MCNPX_2.1.5 with the direct statistical approach (DSA). The results obtained confirm that the epithermal beams achievable at TAPIRO are of suitable quality for BNCT purposes.

An epithermal facility for treating brain gliomas at the TAPIRO reactor.

An epithermal facility for treating patients with brain gliomas has been designed and is under construction at the fast reactor TAPIRO at ENEA Casaccia (Italy). The calculational design tools employed were the Monte Carlo codes MCNP/MCNPX together with the DSA in-house variance reduction patch. A realistic anthropomorphic phantom ("ADAM") was included to optimise dose profiles and in-phantom treatment-planning figures-of-merit. The adopted approach was to minimise the treatment time whilst maintaining a reasonable therapeutic ratio. It is shown that TAPIRO, in spite of its low power of 5 kW, is able to provide an epithermal beam that is of good quality and of sufficient intensity to allow a single beam patient irradiation, under conservative assumptions, of 50 min.

Monte Carlo simulation of the photoneutron field in linac radiotherapy treatments with different collimation systems.

Bremsstrahlung photon beams produced by linac accelerators are currently the most commonly used method of radiotherapy for tumour treatments. When the photon energy exceeds 10 MeV the patient receives an undesired dose due to photoneutron production in the accelerator head. In the last few decades, new sophisticated techniques such as multileaf collimators have been used for a better definition of the target volume. In this case it is crucial to evaluate the photoneutron dose produced after giant dipole resonance (GDR) excitation of the high Z materials (mainly tungsten and lead) constituting the collimator leaves in view of the optimization of the radiotherapy treatment. A Monte Carlo approach has been used to calculate the photoneutron dose arising from the GDR reaction during radiotherapy with energetic photon beams. The simulation has been performed using the code MCNP4B-GN which is based on MCNP4B, but includes a new routine GAMMAN to model photoneutron production. Results for the facility at IRCC (Istituto per la Ricerca e la Cura del Cancro) Candiolo (Turin), which is based on 18 MV x-rays from a Varian Clinac 2300 C/D, are presented for a variety of different collimator configurations.

Analysis of photoneutron spectra produced in medical accelerators.

A complete method is presented for the evaluation of photoneutron spectra produced in linear accelerators for cancer radiotherapy. It consists of a computer simulation code based on the MCNP4B Monte Carlo code, in which the new routine GAMMAN was implemented, allowing the accurate study of photoneutron production in high Z elements. In addition an experimental method based on a passive bubble spectrometer allows direct measurements of the photoneutron spectrum at the patient plane, also under the photon beam. The results are presented both for a 15 MeV linac with a traditional collimator system and for an 18 MeV linac equipped with a multileaf collimator, used in conformational radiotherapy.

Audit of neural blockade for palliative care patients in an acute unit.

During the period from September 1990 to March 1992, 155 nerve blocks were performed for 125 patients as part of the clinical management of pain due to malignant disease. The efficacy, in terms of pain score reduction, and spontaneously reported side effects secondary to these procedures were prospectively audited. Neural blockade was undertaken in accordance with strict clinical criteria, and medication was optimized with the aim of achieving maximum analgesia with minimum side effects at all times. Pain was assessed before the block, 24 hours after the block and at follow-up (two to six weeks) using visual analogue scores or verbal rating scales. All patients were audited. The total (all patients, all blocks) median (lower-upper quartile) pain score dropped from 8 (6-10) cm before the block to 2 (0-4) cm at 24 hours after the block (p < 0.05) and to 1 (0-4) cm at follow-up (p < 0.005). A concomitant reduction in analgesic requirements was observed. The incidence of serious side effects was low (two patients in this series). The results indicate the usefulness of these techniques for patients in the palliative care setting.

Avian tuberculosis in pigs: Mycobacterium intracellulare infection in a breeding herd.

Lymphadenitis of pigs caused by Mycobacterium intracellulare is widely recognised in continental Europe but this is the first report of it in England. No disease was seen on the farm but condemnations of tissues and organs at the slaughterhouse were often than 100 a week and in one week were in excess of 200. The loss was greater to the slaughterhouse than to the farmer because of the constant disruption to the production line. There was no evidence that diseased pigs performed less well than healthy pigs. M intracellulare types 4 and 6 and M xenopi were isolated from diseased pigs. The source of the infection was traced to the sawdust bedding supplied by a local sawmill set in the middle of a forest. Changing the bedding to straw halted the outbreak. From the sawdust M avium types 1 and 4, M fortuitum and M intracellulare type 4 were isolated. The wildlife round the sawmill was investigated as a source of infection. Although M intracellulare type 4 and M avium were isolated from moles and a hedgehog, it was concluded that the wildlife was not involved. There was no evidence of pig to pig transmission.

Avian tuberculosis in pigs: miliary lesions in bacon pigs.

An outbreak of tuberculosis caused by Mycobacterium avium type 2 is described which resulted in the total condemnation of 26 carcasses and partial condemnation of tissues and organs of a further 200 animals. Circumstantial evidence is presented that hens running in the farmyard were the source of the infection. Examinations of the carcasses and organs of the diseased pigs suggested that the accepted pathogenesis of the disease is incorrect and a new hypothesis is presented. The problems for the meat inspector in differentiating tuberculosis from 'milk-spot liver' are discussed and recommendations made. The findings of the study are discussed in the light of 'The Meat Inspection Regulations 1963' and it is recommended that where tuberculosis is suspected there is no longer any necessity to split the carcasses. The public health implications of this study are discussed.

Tuberculosis in wild badgers (Meles meles) in Gloucestershire: pathology.

The gross and histological appearances of the lesions of tuberculosis in 36 wild badgers found to be infected with Mycobacterium bovis are described. These badgers were examined over a period of two years during an investigation into the possible epidemiological association of tuberculosis in badgers and cattle. The possible significance of the lesions in transmission of M bovis to cattle and other badgers is discussed. The histological appearance of the lesions was considered to be indicative of a lesser hypersensitivity reaction than is seen in the bovine.

Comparison of the specificty of human and bovine tuberculin PPD for testing cattle. 1--Republic of Ireland.

A tuberculin testing trial in cattle was carried out in the Republic of Ireland to compare the specificity for bovine tuberculosis of a human purified protein derivative (PPD) tuberculin (Weybridge) with that of a bovine PPD (Rotterdam), and to determine whether discrimination between specific and non-specific reactions to mammalian tuberculin is better with doses of tuberculins smaller than those traditonally used for testing cattle. Tests were carried out in 510 cattle, 395 of which were shown by post mortem examination to be tuberculous and 115 non-tuberculous. Three dilutions at five-fold intervals of both mammalian tuberculins were used together with two dose levels of avian tuberculin PPD (Weybridge), and all reactions were measured both by increase in skin fold thickness and by diameter of induration. In the environment of this trial, the bovine PPD was shown to be more specific for bovine tuberculosis than the human PPD, and particularly in differentiating from "skin tuberculosis". There was no indication of greater specificity at lower doses of tuberculin. Measurement of induration diameter proved a satisfactory alternative method of reading tuberculin reactions in cattle under field conditions.