Electronic portal imaging registration in breast cancer radiotherapy verification: analysis of inter-observer agreement among different categories of health practitioners.

Electronic portal imaging (EPI) is commonly used to identify and correct for inter-fraction variability in tangential breast irradiation. Based on the institutional policy, EPI registration is performed by either radiation oncologist or therapist. Little data is available on the inter-observer agreement in EPI registration among different health practitioners. The aim of our study was to analyze inter-observer agreement among radiation oncologists and therapists in the evaluation of EPI for breast cancer radiotherapy verification. EPI data of 40 patients treated with tangential fields were independently reviewed by a radiation oncologist (on-line, just before treatment) and off-line by junior and senior therapists. Displacement of each EPI image with respect to the digital reconstructed radiographs (DRRs) was quantified using manual EPI registration based on bony marks with the corresponding DRRs. Agreement between observers was evaluated using weighted Cohen's Kappa statistics. In 95% out of 720 EPI-DRR comparisons, the EPI-DRR misalignment was < 5 mm. The difference between observers was < 2 mm in 666 (92.5%) out of all 720 delta values. High inter-observer agreement was found, with weighted Cohen's Kappa values attesting evaluation overlaps ranging from moderate (among therapists) to almost perfect (among radiation oncologist and therapists). The high agreement among the observers demonstrated the precision of breast localization using EPI. These findings suggest that routine EPI-based patient set-up verification in breast cancer radiotherapy can be safely entrusted to trained therapists (supervision should be assured based on the local tasks definition). Our study might be useful in quality assurance and in the optimization of workload in the radiotherapy departments. They might allow for wider implementation of complex and evolving radiotherapy technologies.

Production and characterization of 111Ag radioisotope for medical use in a TRIGA Mark II nuclear research reactor.

Radio Pharmaceutical Therapy (RPT) comes forth as a promising technique to treat a wide range of tumors while ensuring low collateral damage to nearby healthy tissues. This kind of cancer therapy exploits the radiation following the decay of a specific radionuclide to deliver a lethal dose to tumor tissues. In the framework of the ISOLPHARM project of INFN, 111Ag was recently proposed as a promising core of a therapeutic radiopharmaceutical. In this paper, the production of 111Ag via neutron activation of 110Pd-enriched samples inside a TRIGA Mark II nuclear research reactor is studied. The radioisotope production is modeled using two different Monte Carlo codes (MCNPX and PHITS) and a stand-alone inventory calculation code FISPACT-II, with different cross section data libraries. The whole process is simulated starting from an MCNP6-based reactor model producing the neutron spectrum and flux in the selected irradiation facility. Moreover, a cost-effective, robust and easy-to-use spectroscopic system, based on a Lanthanum Bromo-Chloride (LBC) inorganic scintillator, is designed and characterized, with the aim of using it, in the future, for the quality control of the ISOLPHARM irradiated targets at the SPES facility of the Legnaro National Laboratories of INFN. natPd and 110Pd-enriched samples are irradiated in the reactor main irradiation facility and spectroscopically characterized using the LBC-based setup and a multiple-fit analysis procedure. Experimental results are compared with theoretical predictions of the developed models, showing that inaccuracies in the available cross section libraries prevent an accurate reproduction of the generated radioisotope activities. Nevertheless, models are normalized to our experimental data allowing for a reliable planning of the 111Ag production in a TRIGA Mark II reactor.

New solid state laser system for SPES: Selective Production of Exotic Species project at Laboratori Nazionali di Legnaro.

The Selective Production of Exotic Species project is under construction at Laboratori Nazionali di Legnaro-INFN. The aim of the collaboration is to produce highly pure Radioactive Ion Beams (RIBs) from fission fragments of a uranium carbide (UCx) target activated by a cyclotron proton beam. In order to select a specific atomic species, the main tool to be applied is the resonant laser ionization technique. We have just completed the installation of a dedicated all solid state laser system whose elements are tunable to transitions of all the elements/isotopes of interest for the project. The new laser system is based on three Titanium:sapphire laser sources, independently pumped by three Nd:YLF pump lasers, and it can be coupled to two high harmonic generation (second harmonic generation, third harmonic generation, and fourth harmonic generation) setups. The power, wavelength, and position of the laser beams are continuously monitored and stabilized by using automated active systems to improve the beam production stability of RIBs. This paper presents the main features of the laser system and examples of application of a laser ion source, including a first demonstration of photoionization of stable silver, one of the most requested elements for RIB application.

Study of the radioactive contamination of the ion source complex in the Selective Production of Exotic Species (SPES) facility.

The Isotope Separation On-Line (ISOL) technique is today established as one of the primary methods to produce high-intensity and high-quality radioactive beams. This technique produces, for a given amount of the desired isotope, many orders of magnitude of other radioactive species. Due to the activation generated by interactions of the primary beam, intense neutron fields, and deposition of the produced radioactive ions inside beam line elements, an ISOL facility in operation becomes an intense radioactive source. Therefore, the biological hazard imposes severe radiological safety challenges to the design, operation, maintenance, and final decommissioning of such facilities. A challenging component is the ion source complex, where the ion extraction electrode provides the extraction of radioactive ions from the ion source and the first acceleration to the extracted beam. The radioactive contamination of this sub-component is studied, by means of the FLUKA code, in the case of the Selective Production of Exotic Species facility, which is in the advanced construction phase at Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali di Legnaro, Padua, Italy. The developed model includes isotope production by the interactions of a 40 MeV energy proton beam on a 238UCx target, selection of radioactive isotopes that are able to stick on the electrode tip, time evolution of the deposited isotopes during the operation and cooling periods before maintenance interventions, and evaluation of the ambient dose equivalent rate generated by the contamination of the electrode tip. Based on these results, the possibility of manual interventions for maintenance and emergency vs the use of remote handling systems is discussed.

Development of implantation substrates for the collection of radionuclides of medical interest produced via ISOL technique at INFN-LNL.

Accelerator-based techniques with electromagnetic mass separation are considered among the most innovative and promising strategies to produce non-conventional radionuclides for nuclear medicine. Such approach was successfully used at CERN, where the dedicated MEDICIS facility was built, and at TRIUMF, where the ISAC radioactive beam facility was used to produce unconventional α-emitters. In such framework, the Legnaro National Laboratories of the Italian Institute of Nuclear Physics (INFN-LNL) proposed the ISOLPHARM project (ISOL technique for radioPHARMaceuticals), which will exploit radionuclides producible with the SPES (Selective Production of Exotic Species) ISOL (Isotope Separation On-Line) facility to develop novel radiopharmaceuticals. The ISOL technique utilizes the irradiation with a primary beam of particles/nuclei of a production target where radionuclides are produced. A radioactive ion beam is subsequently extracted from the production target unit, and transported up to an analyzing magnet, where non-isobaric contaminants are filtered out. The so-obtained purified radioactive beam is dumped onto an implantation substrate, referred as collection target. Then, the desired nuclides can be chemically harvested from the collected isobars, and the isotopically pure atom collection can be employed to radiolabel high specific activity radiopharmaceuticals. Metallic deposition targets in the form of coated metal foils were mostly used at TRIUMF and CERN. At ISOLPHARM, a different approach is under investigation which foresees the use of soluble cold-pressed collection targets, possibly facilitating the chemical purification process of the collected radionuclides. In this study, the production and characterization of some of the ISOLPHARM collection targets is presented, in particular, soluble salts (NaCl and NaNO3) and organic materials widely used for pharmaceutical tablets production are considered. All such materials proved to be potentially suitable as collection targets, since solid samples were easily produced and resulted compatible with the vacuum conditions required for the ion implantation process. Furthermore, some of the selected substrates were used for proof-of-concept deposition tests with stable silver, to prove their suitability as ISOLPHARM deposition substrates for silver-111, a promising candidate for radiotherapy. Such tests highlighted possible scenarios useful for the development of new alternative materials, as the use of insoluble organic targets.

Study on the impregnation of archaeological waterlogged wood with consolidation treatments using synchrotron radiation microtomography.

In favourable conditions of low temperature and low oxygen concentration, archaeological waterlogged wooden artefacts, such as shipwrecks, can survive with a good state of preservation. Nevertheless, anaerobic bacteria can considerably degrade waterlogged wooden objects with a significant loss in polysaccharidic components. Due to these decay processes, wood porosity and water content increase under ageing. In such conditions, the conservation treatments of archaeological wooden artefacts often involve the replacement of water with substances which fill the cavities and help to prevent collapse and stress during drying. The treatments are very often expensive and technically difficult, and their effectiveness very much depends on the chemical and physical characteristics of the substances used for impregnation. Also important are the degree of cavity-filling, penetration depth and distribution in the structure of the wood. In this study, the distribution in wood cavities of some mixtures based on polyethylene glycols and colophony, used for the conservation of waterlogged archaeological wood, was investigated using synchrotron radiation X-ray computed microtomography (SR-microCT). This non-destructive imaging technique was useful for the study of the degraded waterlogged wood and enabled us to visualise the morphology of the wood and the distribution of the materials used in the wood treatments. The study has shown how deposition is strictly related to the dimension of the wooden cavities. The work is currently proceeding with the comparison of synchrotron observations with the data of the solutions viscosity and with those of the properties imparted to the wood by the treatments.

Clinical aspects and therapeutic outcome in thyrotropin-secreting pituitary adenomas: a single center experience.

BACKGROUND AND AIM: The management of pituitary adenomas secreting TSH has evolved considerably over the last decades.We report the clinical features, management, and outcome of a large monocentric series. MATERIAL AND METHODS: A monocentric retrospective cohort of 26 patients admitted to our Department of Endocrinology between 1983 and 2007, followed for a period up to 204 months. The diagnosis of TSH-secreting adenoma was based on clinical and biochemical findings of central hyperthyroidism. Evaluation of basal and dynamic pituitary function, magnetic resonance imaging or computerized tomography scan were performed in all patients. Twenty-two patients, of whom 15 pre-treated by somatostatin analogs (SSA), underwent trans-sphenoidal surgery and were regularly re-evaluated. RESULTS: The number of cases increased over the years. Age at diagnosis, micro- to macroadenoma ratio, and mean estimated latency between first symptoms and diagnosis did not appreciably change over time. Latency was significantly shorter in macroadenomas. Following surgery, 55% of patients obtained remission (success rate of 40 and 67% in macro- and microadenomas, respectively). SSA pre-treatment led to an apparent although not statistically- significant increase in success rate in micro- but not in macroadenomas. CONCLUSIONS: In a monocentric group of 26 TSH-secreting adenomas the high ratio between micro- and macroadenomas remained stable over time with a significantly shorter diagnosis latency in macroadenomas. A more precocious recognition of the tumors and possibly the use of presurgical SSA allowed a high remission rate. A varied combination of neurosurgery, SSA, radiotherapy, and thyroid ablation led to the control of the disease in all the patients studied.

The effect of uric acid on outdoor copper and bronze.

Bird droppings are often quoted as a decay agent for outdoor goods, in particular buildings and statues. Undoubtedly, they represent one of the major causes of aesthetic damage on outdoor materials, but the real chemical damage they are able to induce, in particular on metals, is not so well studied. This work focused on the short term role of uric acid, the main constituent of bird urine, with respect to copper, which make such an important contribution to architectural elements of buildings and outdoor sculpture. Preliminary results of laboratory tests and analyses on real exposed samples showed that uric acid chemically affects copper and bronzes: the surface of the metal is modified and copper urates formed. Also natural patina, formed on statues and roof, react with uric acid, even if it seems to afford some protection toward bird droppings. In general, experimental results confirm that the potential chemical damage by bird droppings is significant when considering external cultural heritage such as statues, metal monuments and buildings with historic copper roofs.

Primary hyperparathyroidism is associated with marked impairment of GH response to acylated ghrelin.

BACKGROUND: Impaired GH secretion is a common finding in patients with primary hyperparathyroidism (PHP). Ghrelin displays strong GH-releasing action, mainly at the hypothalamic level. OBJECTIVE: To evaluate secretory response of GH to ghrelin in PHP patients. PATIENTS: Fifteen patients [11 women/4 men, mean age 54 years, range 32-70 years, body mass index (BMI) 25.0 +/- 0.7 kg/m(2)] affected with PHP due to single parathyroid adenoma and 35 normal age-matched subjects (23 women/12 men, mean age 58 years, range 35-68 years, BMI 24.1 +/- 1.1 kg/m(2)). METHODS: A measure of 1 microg/kg body weight i.v. acylated ghrelin or 1 microg/kg body weight i.v. GH releasing hormone (GHRH) followed by 0.5 g/kg body weight i.v. arginine (ARG) hydrochloride were administered to all subjects on alternate days in order to evaluate GH response. RESULTS: Mean serum GH peak after GHRH + ARG was 32.6 +/- 7.8 and 17.4 +/- 4.0 microg/l, in controls and PHP patients, respectively (P < 0.05). Mean serum GH peak after ghrelin was 70.4 +/- 31.5 and 16.8 +/- 1.9 microg/l, in controls and PHP patients, respectively, (P < 0.001). Using ROC curves, a serum GH peak > 22 microg/l after ghrelin stimulation might be considered as a cut-off value for identifying normal subjects. Ten (67%) PHP patients have impaired GH response to GHRH + ARG and 13 (87%) to ghrelin. Serum GH peak after ghrelin or GHRH + ARG was unrelated to serum IGF-1, PTH or ionized calcium concentrations. CONCLUSIONS: The present data confirm that GH secretion is impaired in PHP patients using the potent GH secretagogue ghrelin and suggest that impaired GH secretion is likely due to a deleterious effect of hypercalcaemia at the hypothalamic level in PHP patients.

Reuse of incinerator bottom and fly ashes to obtain glassy materials.

Bottom and fly ashes coming from the urban wastes incineration represent a by-product nowadays landfilled. By mixing different amount of these residues with others inert materials, such as glass cullet and feldspar waste, two vitrifiable mixtures are tailored. Glasses, obtained by means of vitrification process, are chemically stable with low leachability of contaminants and show comparable properties to those of commercial soda-lime glasses. Moreover, from the thermal and mechanical characterisation the tendency of these glasses to crystallise, for their transformation into glass-ceramic materials, has been evidenced.

Impairment of GH secretion in amyotrophic lateral sclerosis is not affected by riluzole treatment.

Amyotrophic lateral sclerosis (ALS), the most common motor neurone disorder in human adults, is characterized by selective and progressive degeneration of upper and lower motor neurones in the central nervous system. The main currently available drug for ALS treatment is riluzole, a compound that acts through inhibition of glutamate release, postsynaptic receptor activation, and voltage-sensitive channel inhibition. GH secretion, evaluated by GHRH+arginine (ARG) test, has recently been reported to be impaired in most untreated ALS patients. The aim of the present study was to evaluate whether riluzole administration could interfere with GH secretion and therefore with the diagnosis of adult GH deficiency. Ten patients (6 males, 4 females, mean age 59+/-11 yr) were studied performing GHRH+ARG test before and 3 months after starting riluzole treatment (100 mg/day). Blood samples for GH were collected at baseline, at 30 and 60 min. Both before and during riluzole treatment, 5 patients showed GH deficiency and 5 patients had a normal GH response according to body mass index (BMI). Mean peak GH levels were similar before and during riluzole treatment (13.4+/-10 vs 14.2+/-10.1 microg/l, p=ns). No significant correlation was observed between GH concentrations and age, BMI, disease duration, severity or clinical (bulbar/spinal) form. In conclusion, the present data confirm that GH secretion is impaired in a new series of ALS patients and indicate that riluzole treatment does not interfere with GH secretion. Thus, evaluation of GH secretion in ALS patients can also be performed without withdrawing riluzole treatment.

Tools for evaluation of impact associated with MSW incineration: LCA and integrated environmental monitoring system.

The identification of significant pollutants emitted from the contamination source is the first step in evaluating the impact associated with anthropic activity. Municipal solid waste (MSW) incinerators are still generally perceived as great pollutant sources, in particular due to their gaseous emissions from the stack, which constitute the major effluent from the plant. In this work a life cycle assessment and an integrated environmental monitoring system were applied together, in order to obtain complete information about the incineration process and its environmental impact. The former is a proven methodology, but its application to waste management systems constitutes a relatively new field of application with a great developmental potential. The contribution of the incineration process to the different environmental impact categories was investigated, finding many avoided impacts due to energy recovery. The latter is an innovative approach that allows a remarkable understanding of impact due to a contamination source; interesting correlations were found between heavy metals both in gas emissions and in natural matrices in the surroundings.

Body fat distribution has weight-independent effects on clinical, hormonal, and metabolic features of women with polycystic ovary syndrome.

This study was performed to investigate whether different patterns of body fat distribution may have distinct effects on the clinical, hormonal, and metabolic features of women with clinical hyperandrogenism such as polycystic ovary syndrome (PCOS). Ninety-seven consecutive women with PCOS were included in the study after assessment of gynecological and obesity history and careful clinical examination. Women were divided into three tertile groups based on the waist to hip ratio (WHR). Those with peripheral body fat distribution (P-BFD) had a WHR of less than 0.80, those with intermediate body fat distribution (I-BFD) had a WHR of 0.81 to 0.90, and those with abdominal body fat distribution (A-BFD) had a WHR exceeding 0.90. Baseline blood and urine samples were obtained for several hormone and lipid determinations, and the response of glucose, insulin, and C-peptide to a glucose oral challenge (75 g) was investigated. In the PCOS group, WHR values were higher than those used to define P-BFD and A-BFD in the normal female population. As WHR values increased, a significantly greater prevalence of obesity and acanthosis nigricans and a lower prevalence of acne was present. No significant differences were present in any of the other clinical features between the three groups. Ovarian morphology and volumes were similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Pah determination in samples of environmental interest.

Several compounds of the PAH class were determined in samples of various origin: from an urban solid waste incinerator (USWI), electric power plants, atmospheric precipitation, and from samples of soil close to pollution sources. Different analytical procedures were tested and employed to attain the most reliable data. In analyzing a variety of samples with respect to origin or mode of formation, the study demonstrated the ubiquitous nature of PAH and determined their quantitative and qualitative profile.

Application of an integrated environmental monitoring system to an incineration plant.

An integrated environmental monitoring system is an innovative approach which allows remarkable understanding of impacts due to a contamination source. Here we report results from environmental monitoring near a typical Italian incinerator plant. By means of mathematical dispersion models, zones of maximum pollutant depositions were determined; according to these simulations, a defined monitoring network was established. Heavy metals, chosen as environmental indicators, showed a wide flux range in gas emissions from the incinerator, over different sampling years. In particular, emissions in the year 2000 were marked by high Pb and Cd concentrations. Correspondingly, soil samples also exhibited a greater concentration of the same metals in 2000, than in previous years. Principal component analysis allowed a better visualisation of these similarities, also showing an interesting correlation between heavy metals observed both in gas emissions and in soil samples. Soil distant from the incinerator was found to be less affected by heavy metal contamination. Also atmospheric wet and dry depositions indicated a significant dependence on distance from incinerator, though extremely variable metal fluxes were registered during different months. Finally, vegetation samples, seasonal or evergreen, did not provide evidence of a significant heavy metal enrichment, apart from an apparent dependence on contamination source distance.

Characterization of the precipitation in an urban area of the Po valley, Italy.

Rain samples from two stations equipped with both bulk and wet/dry samplers were collected weekly for a year, and analyzed according to standardized monitoring programs. Several correlations among ions were found: these findings, especially when compared with the corresponding wind-frequency distribution, emphasize differences in the chemical composition of the rain that are related to the sampling site, to the kind of sampler (bulk or wet/dry) and to pollution source; they represent a useful means of assessing the environmental condition of the Po valley.

Characterisation of odorants emissions from landfills by SPME and GC/MS.

Odorous compounds from a landfill have been characterised by gas-chromatography-mass-spectrometry, identifying about 100 volatile organic compounds. Air samples from different landfill sites and from the environment have been analysed after a solid-phase microextraction on a three-phase fiber, DVB/Carboxen/PDMS, which allowed a preconcentration and the chromatographic data obtained from the most significant emission sources have been submitted to chemometric analysis in order to better establish specific markers of olfactory pollution. For example limonene was a typical tracer of fresh wastes, while p-cymene was characteristic of leachate and biogas. By the developed analytical procedure it has been evaluated the efficiency of a scrubber plant utilised in the landfill in order to remove malodour compounds. The average removal efficiency was not very high (about 23.5%) due to scarce ability in removing low polarity compounds. Furthermore, it has been demonstrated the suitability of a microgas chromatograph for the continuous on-site monitoring of air pollution in order to rapidly individuate emission sources of olfactive nuisances.

Soil quality and vulnerability in a Mediterranean natural ecosystem of Central Italy.

Wet and dry atmospheric depositions and soil chemical and microbiological properties were determined in a Mediterranean natural ecosystem of Central Italy near Rome (Castelporziano Estate). The monitoring of depositions permitted us to quantify the exceedances of S and N compounds (expressed as eqH(+)ha(-1)year(-1)) over the critical loads of acidity. Critical loads, i.e. the quantity of a substance which a part of the environment can tolerate without adverse effects occurring, were determined adopting the level 0 methodology following the UN/ECE Convention on Long-range Transboundary Air Pollution. Deposition data were available for the period 1992-1997, and acidity exceedances were referred to the main vegetation types present in the area. Results showed that most part of the Estate has a medium degree of vulnerability to acidification, and the corresponding risk of acidification deriving from the exceedances of atmospheric deposition was rather low. The study of soil chemical and microbiological properties included mainly total soil organic carbon (SOC), microbial biomass-C, biomass-C/SOC, soil respiration, and metabolic quotient (qCO2). Soil organic C metabolism has been discussed on the basis of the results from eight sampling sites.

Supercritical-fluid extraction as a method for investigating the fate of the organic contaminants in soil.

Supercritical fluid extraction (SFE) has proven to be a method for the extraction of pollutants from the soil having serious difficulties to be standardized. A new possibility to use SFE for investigate the fate of pollutants in the soil structure is suggested. The recovery of the analyte from the soil matrix depends on the mass transfer. This includes the desorption of the analyte from the soil surface, its diffusion through the interior of the soil structure, and its transport within the bulk flow of supercritical fluid through the interstitial pores of the soil. The mass transfer can be expected to depend on both the different types of soil and the different location of the analyte in the soil structure. The analyte extraction is also controlled by thermodynamic factors such as the sorption/desorption equilibrium from the soil. On this basis, a mathematical model based on the supercritical fluid extraction conditions (viz, temperature, pressure, fluid flow, modifier,...), which are directly linked to the status of the analyte in the soil, is developed. The elaboration of the kinetical results using our model would permit to approximate the distribution of the contaminant to a non porous- or to a deep porous-soil structure model as a function of a fresh contamination or an aged contamination. These conditions can be described by spiked or native contaminant extraction time profiles, respectively.

Methodological approach for an integrated environmental monitoring system relative to heavy metals from an incineration plant.

The use of an Integrated Environmental Monitoring System is an innovative and very important approach for the determination of environmental impacts due to a contamination source. In the present work, the methodological approach is described and applied to the case study of a MSW incineration plant. Heavy metals were chosen as Environmental Indicators. Gaseous emissions were measured and correlated to wet and dry depositions, soil and vegetation samples. Results show a good correlation between stack emissions and atmospheric depositions; less with soil and vegetation, but these results are important in order to design a standard procedure for an Integrated Monitoring System.