Target manufacturing by Spark Plasma Sintering for efficient 89Zr production.

Zirconium-89 (89Zr) is an emerging radionuclide for positron emission tomography (PET), with nuclear properties suitable for imaging slow biological processes in cellular targets. The 89Y(p,n)89Zr nuclear reaction is commonly exploited as the main production route with medical cyclotrons accelerating low-energy (< 20 MeV) and low-current (< 100 µA) proton beams. Usually, natural yttrium solid targets manufactured by different methods, including yttrium electrodeposition, yttrium sputtering, compressed yttrium powders, and foils, were employed. In this study, the Spark Plasma Sintering (SPS) technique has been investigated, for the first time, to manufacture yttrium solid targets for an efficient 89Zr radionuclide yield. The natural yttrium disc was bonded to a niobium backing plate using a commercial SPS apparatus and a prototype machine assembled at the University of Pavia. The resulting targets were irradiated in a TR19 cyclotron with a 12 MeV proton beam at 50 µA. A dedicated dissolution module, obtained from a commercial system, was used to develop an automated process for the purification and recovery of the produced 89Zr radionuclide. The production yield and recovery efficiency were measured and compared to 89Zr produced by irradiating standard yttrium foils. SPS manufactured targets withstand an average heat power density of approximately 650 W∙cm-2 for continuous irradiation up to 5 h without visible damage. A saturation yield of 14.12 ± 0.38 MBq/µAh was measured. The results showed that the obtained 89Zr production yield and quality were comparable to similar data obtained using standard yttrium foil targets. In conclusion, the present work demonstrates that the SPS technique might be a suitable technical manufacturing solution aimed at high-yield 89Zr radioisotope production.

Preliminary dosimetric analysis of DOTA-folate radiopharmaceutical radiolabelled with 47Sc produced through natV(p,x)47Sc cyclotron irradiation.

47Sc is one of the most promising theranostic radionuclides, thanks to its low energy γ-ray emission (159 keV), suitable for single photon emission computed tomography imaging and its intense ß - emission, useful for tumour treatment. Despite promising preclinical results, the translation of 47Sc-therapeutic agents to the clinic is hampered by its limited availability. Among different 47Sc-production routes currently being investigated, the natV(p,x)47Sc reaction has proved to be of particular interest, thanks to the low-cost and easy availability on the market of natV material and the diffusion of medium energy proton cyclotrons. However, the cross section of this specific nuclear reaction is quite low and small amounts of Sc-contaminants are co-produced at energies E P ≤ 45 MeV, namely 48Sc and 46Sc. The main concern with these Sc-contaminants is their contribution to the patient absorbed dose. For such a reason, the absorbed dose contributions to healthy organs and the effective dose contributions by the three radioisotopes, 48Sc, 47Sc and 46Sc, were evaluated using DOTA-folate conjugate (cm10) as an example of radiopharmaceutical product. Considering as acceptable the limits of 99% for the radionuclidic purity and 10% for the contribution of radioactive Sc-contaminants to the total effective dose after 47Sc-cm10 injection, it was obtained that proton beam energies below 35 MeV must be used to produce 47Sc through irradiation of a natV target.

The effectiveness of germicidal wipes and ultraviolet irradiation in reducing bacterial loads on electronic tablet devices used to obtain patient information in orthopaedic clinics: evaluation of tablet cleaning methods.

BACKGROUND: Electronic tablet devices are commonly used in outpatient clinics to obtain patient information for both clinical and research purposes. These devices are often colonized with bacteria; there are many cleaning methods to reduce this bacterial load. AIM: The primary purpose of this study was to evaluate whether regular cleaning with either germicidal wipes or ultraviolet (UV) irradiation leads to lower bacterial levels compared with irregular cleaning. METHODS: A randomized blinded trial was conducted of tablet cleaning strategies between each patient encounter in orthopaedic clinics. The cleaning method was randomized to either germicidal wipes, UV irradiation, or cleaning only when the tablet was visibly soiled. Research assistants (blinded to the treatment) obtained bacterial cultures from the tablets at the beginning and end of each clinic day. FINDINGS: Using germicidal wipes between each patient encounter vs no routine cleaning resulted in a marked decrease in the amount of bacterial contamination (risk ratio (RR) = 0.17 (0.04-0.67)). Similarly, using UV irradiation between each patient encounter led to significantly lower bacterial contamination rates (RR = 0.29 (95% confidence interval (CI) = 0.09-0.95)) compared with no routine cleaning. The majority of bacteria identified were normal skin flora. No meticillin-resistant Staphylococcus aureus was identified and only sparse colonies of meticillin-sensitive S. aureus. CONCLUSION: Electronic tablets used in orthopaedic trauma clinics are colonized with bacteria if no routine cleaning is performed. Routine use of either UV irradiation or germicidal wipes significantly decreases this bacterial burden. Providers should implement routine cleaning of tablets between each patient encounter to minimize exposure to potential pathogens.

Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using direct 100Mo(p,2n) reaction.

Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets at low proton energies (i.e. within 15-20 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states (9xTc) present in the pertechnetate saline Na99mTcO4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate (99mTc) injection 4801-3). Moreover, the impact of 9xTc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99mTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E γ > 200 keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction at a proton beam energy in the range 15.7-19.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99mTc.

Assessment of the ozone tolerance of two soybean cultivars (Glycine max cv. Sambaíba and Tracajá) cultivated in Amazonian areas.

Brazilian soybean cultivars (Glycine max Sambaíba and Tracajá) routinely grown in Amazonian areas were exposed to filtered air (FA) and filtered air enriched with ozone (40 and 80 ppb, 6 h/day for 5 days) to assess their level of tolerance to this pollutant by measuring changes in key biochemical, physiological, and morphological indicators of injury and in enzymatic and non-enzymatic antioxidants. Sambaíba plants were more sensitive to ozone than Tracajá plants, as revealed by comparing indicator injury responses and antioxidant stimulations. Sambaíba exhibited higher visible leaf injury, higher stomatal conductance, and a severe decrease in the carbon assimilation rate. Higher ozone level (80 ppb) caused an increase in cell death in both cultivars. Levels of malondialdehyde and hydrogen peroxide also increased in Tracajá exposed under 80 ppb. Sambaíba plants exhibited decreases in ascorbate and glutathione levels and in enzymatic activities associated with these antioxidants. The higher tolerance of the Tracajá soybean appeared to be indicated by reduced physiological injuries and lower stomatal conductance, which might decrease the influx of ozone and enhance oxidation-reduction reactions involving catalase, ascorbate peroxidase, ascorbate, and glutathione, most likely stimulated by higher hydrogen peroxide.

Application of a Bonner sphere spectrometer for the determination of the angular neutron energy spectrum of an accelerator-based BNCT facility.

Experimental activities are underway at INFN Legnaro National Laboratories (LNL) (Padua, Italy) and Pisa University aimed at angular-dependent neutron energy spectra measurements produced by the (9)Be(p,xn) reaction, under a 5MeV proton beam. This work has been performed in the framework of INFN TRASCO-BNCT project. Bonner Sphere Spectrometer (BSS), based on (6)LiI (Eu) scintillator, was used with the shadow-cone technique. Proper unfolding codes, coupled to BSS response function calculated by Monte Carlo code, were finally used. The main results are reported here.

Negative Feedback for Small Capacitive Touchscreen Interfaces: A Usability Study for Data Entry Tasks.

Touchscreen technology has become pervasive in the consumer product arena over the last decade, offering some distinct advantages such as software reconfigurable interfaces and the removal of space consuming mice and keyboards. However, there are significant drawbacks to these devices that have limited their adoption by some users. Most notably, standard touchscreens demand the user's visual attention and require them to look at the input device to avoid pressing the wrong button. This issue is particularly important for mobile, capacitive sensing, nonstylus devices, such as the iPhone where small button sizes can generate high error rates. While previous work has shown the benefits of augmenting such interfaces with audio or vibrotactile feedback, only positive feedback (confirmation of button presses) has been considered. In this paper, we present a simple prototype interface that provides negative vibrotactile feedback. By negative, we mean feedback is generated when an inactive or ambiguous part of the screen, such as the area between two buttons, is touched. First, we present a usability study comparing positive and negative vibrotactile feedback for a benchmark numerical data entry task. The difference in performance is not statistically significant, implying negative feedback provides comparable benefits. Next, based on the experimenter's observations and the users comments, we introduce a multimodal feedback strategy-combining complementary positive audio and negative vibrotactile signals. User tests on a text entry experiment show that, with multimodal feedback, users exhibit a (statistically significant) 24 percent reduction in corrective key presses, as compared to positive audio feedback alone. Exit survey comments indicate that users favor multimodal feedback.

Characterization of the energy distribution of neutrons generated by 5 MeV protons on a thick beryllium target at different emission angles.

Neutron energy spectra at different emission angles, between 0° and 120° from the Be(p,xn) reaction generated by a beryllium thick-target bombarded with 5 MeV protons, have been measured at the Legnaro Laboratories (LNL) of the Italian National Institute for Nuclear Physics research (INFN). A new and quite compact recoil-proton spectrometer, based on a monolithic silicon telescope, coupled to a polyethylene converter, was efficiently used with respect to the traditional Time-of-Flight (TOF) technique. The measured distributions of recoil-protons were processed through an iterative unfolding algorithm in order to determine the neutron energy spectra at all the angles accounted for. The neutron energy spectrum measured at 0° resulted to be in good agreement with the only one so far available at the requested energy and measured years ago with TOF technique. Moreover, the results obtained at different emission angles resulted to be consistent with detailed past measurements performed at 4 MeV protons at the same angles by TOF techniques.

Towards the final BSA modeling for the accelerator-driven BNCT facility at INFN LNL.

Some remarkable advances have been made in the last years on the SPES-BNCT project of the Istituto Nazionale di Fisica Nucleare (INFN) towards the development of the accelerator-driven thermal neutron beam facility at the Legnaro National Laboratories (LNL), aimed at the BNCT experimental treatment of extended skin melanoma. The compact neutron source will be produced via the (9)Be(p,xn) reactions using the 5 MeV, 30 mA beam driven by the RFQ accelerator, whose modules construction has been recently completed, into a thick beryllium target prototype already available. The Beam Shaping Assembly (BSA) final modeling, using both neutron converter and the new, detailed, Be(p,xn) neutron yield spectra at 5 MeV energy recently measured at the CN Van de Graaff accelerator at LNL, is summarized here.

Long-term weight loss maintenance in the United States.

CONTEXT: Although the rise in overweight and obesity in the United States is well documented, long-term weight loss maintenance (LTWLM) has been minimally explored. OBJECTIVE: The aim of this study is to estimate the prevalence and correlates of LTWLM among US adults. DESIGN, SETTING AND PARTICIPANTS: We examined weight data from 14 306 participants (age 20-84 years) in the 1999-2006 National Health and Nutrition Examination Survey (NHANES). We defined LTWLM as weight loss maintained for at least 1 year. We excluded individuals who were not overweight or obese at their maximum weight. RESULTS: Among US adults who had ever been overweight or obese, 36.6, 17.3, 8.5 and 4.4% reported LTWLM of at least 5, 10, 15 and 20%, respectively. Among the 17.3% of individuals who reported an LTWLM of at least 10%, the average and median weight loss maintained was 19.1 kg (42.1 pounds) and 15.5 kg (34.1 pounds), respectively. LTWLM of at least 10% was higher among adults of ages 75-84 years (vs ages 20-34, adjusted odds ratio (OR): 1.5; 95% confidence interval (CI): 1.2, 1.8), among those who were non-Hispanic white (vs Hispanic, adjusted OR: 1.6; 95% CI: 1.3, 2.0) and among those who were female (vs male, adjusted OR: 1.2; 95% CI: 1.1, 1.3). CONCLUSIONS: More than one out of every six US adults who has ever been overweight or obese has accomplished LTWLM of at least 10%. This rate is significantly higher than those reported in clinical trials and many other observational studies, suggesting that US adults may be more successful at sustaining weight loss than previously thought.

Angle and energy differential neutron spectrometry for the SPES BNCT facility.

An accelerator-driven thermal neutron facility for boron neutron capture therapy of skin melanoma is currently under construction at the Legnaro National Laboratories, Italy. The installation relies on the production of neutrons from a thick beryllium target bombarded with 5 MeV protons. A complete set of double differential data, i.e. angle- and energy-differential neutron spectra produced by the beryllium target, is necessary for the Monte Carlo-based design of the installation. For this purpose, double differential fluence measurements are currently performed with the "BINS" neutron spectrometer using 5 MeV protons at the "CN" Van de Graaf accelerator. This spectrometer uses a superheated emulsion of dichlorotetrafluoroethane which is sequentially operated at 25, 30, 35, 40, 45, 50 and 55 degrees C and thus provides a series of seven sharp thresholds covering the 0.1-10 MeV neutron energy interval. Deconvolution of the data is performed with the code "MAXED", which is based on the maximum entropy principle. The analysis of our first neutron spectrometry measurements at angles of 0 degrees, 40 degrees, 80 degrees and 120 degrees supports the viability of the BINS spectrometry method for the generation of the required double differential data.

The BSA modeling for the accelerator-based BNCT facility at INFN LNL for treating shallow skin melanoma.

The SPES-BNCT ongoing project of the Istituto Nazionale di Fisica Nucleare (INFN) is aimed at the construction at the Laboratori Nazionali di Legnaro (LNL) of an accelerator-based (AB), high-flux thermal neutron beam facility devoted to boron neutron capture therapy (BNCT) experimental treatment of extended skin melanoma, in the framework of SPES (selective production of exotic species) project. The neutron source will be produced via the (9)Be(p,xn) reactions by a 5 MeV, 30 mA proton beam into a thick beryllium target. The resulting neutron spectrum is slowed down using a beam shaping assembly (BSA), for which modeling is in an advanced neutronic design stage. An overview on the BSA current status, based on the Be neutron converter prototype designed and already constructed, is reported.

BNCT dosimetry performed with a mini twin tissue-equivalent proportional counters (TEPC).

The BNCT radiation field is complex because different beam components are mixed, each one having different relative biological effectiveness (RBE). Microdosimetry with tissue-equivalent proportional counters (TEPC) has proven to be an ideal dosimetric technique for mixed radiation fields, because it is able both to measure the absorbed dose and to assess the radiation field relative biological effectiveness with good accuracy. An ideal detector for BNCT should contain two TEPCs, one detector loaded with, while the other one without (10)B in order to record all beam components with a unique measurement. Moreover, such a detector should be of tiny size in order to be able to measure in the intense BNCT radiation fields without significant pile-up effects. TEPCs have been shown to be pretty good dosimeters for mixed radiation fields. In this paper the first mini twin TEPC counter for BNCT is presented, as well as first measurement at the new HYTHOR thermal irradiation facility at TAPIRO nuclear reactor and comparison with related Monte Carlo calculations.

A novel boronated-porphyrin as a radio-sensitizing agent for boron neutron capture therapy of tumours: in vitro and in vivo studies.

A water-soluble [meso-tetra(4-nido-carboranylphenyl)porphyrin] (H(2)TCP) bearing 36 boron atoms was studied for its accumulation and its radio/photo-sensitization efficiency towards murine melanotic melanoma cells. The amount of H(2)TCP in the cells increased with the porphyrin dose in the incubation medium up to 100 microM with no significant dark toxicity. Fluorescence microscopy observations showed that the porphyrin was largely localized intracellularly. Based on these "in vitro" results our investigations were pursued using the B16F1 melanotic melanoma subcutaneously transplanted in C57BL6 mice as "in vivo" model. Phormacokinetic studies were performed by injection of H(2)TCP intratumorally (1 mg/kg) and intravenously (10 mg/kg). At 0.5h after i.t. administration or at 24 h after i.v. injection, the amounts of (10)B in the tumour were about 60 ppm and about 6 ppm, respectively. The distribution of H(2)TCP in the tumour after intravenous or intratumoural injection was also assessed by fluorescence microscopy analyses. Under these conditions, preliminary BNCT studies were carried out using a new thermal column called HYTOR (HYbrid Thermal spectrum sHifter TapirO Reactor) inserted in the fast nuclear reactor Tapiro at Enea Casaccia, Italy. The mice were exposed to HYTHOR radiation field for 20 min at a reactor power of 5 kW. In spite of different amounts of (10)B in the tumour at the irradiation time, a similar significant delay in tumour growth (5-6 days) was induced by neutron irradiation in intratoumorally and intravenously injected mice. The response of the melanotic melanoma to H(2)TCP-BNCT was compared with that obtained by irradiation after intraperitoneal injection of boron-phenylalanine.

Be target development for the accelerator-based SPES-BNCT facility at INFN Legnaro.

An accelerator-driven thermal neutron source for BNCT, planned to be installed at the INFN Laboratori Nazionali di Legnaro (LNL), is in progress in the framework of the SPES (selective production of exotic species) research program. The most critical element of such a facility is the construction of a reliable neutron converter based on the (9)Be(p,xn) nuclear reaction, working at a high power level (150 kW) and 5 MeV beam energy, due to the SPES driver constraints. Two original, beryllium-based, target concepts have been designed for such a purpose. The present status of the neutron converter, as well as the test results performed so far on prototypes constructed, is reported here.

Cortical responses associated with the preparation and reaction to full-body perturbations to upright stability.

OBJECTIVE: To examine the cortical activity associated with 'central set' preparations for induced whole-body instability. METHODS: Self-initiated and temporally unpredictable perturbations to standing balance were caused by the release of a load coupled to a cable affixed to a harness while participants stood on a force plate. Electroencephalographic and electromyographic signals were recorded. RESULTS: Peak activity was located at the Cz electrode. The predictable condition elicited a DC shift 950 ms prior to perturbation onset and was 18.0+/-10.5 micro V in magnitude. Pre-perturbation activity was not associated with the motor act of perturbation initiation and was dissociable from cortical activity related to anticipatory postural muscle activation. Following perturbation onset, N1 potentials were observed with a peak amplitude of 17.6+/-7.2 micro V and peak latency of 140.1+/-25.9 ms. In unpredictable trials, pre-perturbation activity was absent. The peak amplitude (32.0+/-14.8 micro V) and latency (156.5+/-11.8 ms) of the post-perturbation N1 potential were significantly larger (p=0.002) and later (p<0.001) than for predictable trials. CONCLUSIONS: Self-initiated postural instability evokes cortical activity prior to and following perturbation onset. Pre-perturbation cortical activity is associated with changing central set to modulate appropriate perturbation-evoked balance responses. SIGNIFICANCE: These findings establish a link between reactive balance control and cortical activity that precedes and follows perturbations to stability.

The new hybrid thermal neutron facility at TAPIRO reactor for BNCT radiobiological experiments.

A new thermal neutron irradiation facility, devoted to carry out both dosimetric and radiobiological studies on boron carriers, which are being developed in the framework of INFN BNCT project, has been installed at the ENEA Casaccia TAPIRO research fast reactor. The thermal column, based on an original, hybrid, neutron spectrum shifter configuration, has been recently become operative. In spite of its low power (5 kW), the new facility is able to provide a high thermal neutron flux level, uniformly distributed inside the irradiation cavity, with a quite low gamma background. The main features and preliminary benchmark measurements of the Beam-shaping assembly are here presented and discussed.

Preliminary design of a Gd-NCT neutron beam based on compact D-T neutron source.

Gadolinium has been recently proposed, as neutron capture agent in NCT (Neutron Capture Therapy), due to both the nuclide high neutron capture cross section, and the remarkable selective uptake inside tumour tissue that Gd-loaded compounds, can provide. When a neutron external source is supplied, different Gd nuclear reactions, and the generated Auger electrons in particular, cause a high local energy deposition, which results in a tumour cell inactivation. Preliminary micro- as well as macrodosimetric Monte Carlo computational investigations show that the tumour-to-healthy tissue biological damage ratio is in close relation to the neutron beam energy spectrum. The results points out that the optimum neutron spectrum, to be used for Gd-NCT, seems to lie in the 1 to 10 keV energy range. In order to 'tailor' such spectra, an original, accelerator-driven, neutron source and spectrum shaping assembly for hospital-based Gd-NCT are presented and preliminary results are reported.

BNCT microdosimetry at the tapiro reactor thermal column.

A thermal column is available for dosimetric and radiobiological studies by the fast reactor TAPIRO, located at the ENEA research centre Casaccia. The TAPIRO neutron field has been studied (in the frame of LNL BNCT project) with a tissue-equivalent proportional counter, which has worked alternatively with an ordinary tissue-equivalent cathode and with a boron-enriched cathode. Measurements have been performed with polyethylene caps of different thickness. Both the absorbed dose and the microdosimetric-calculated biological effective dose show a maximum at approximately 0.5 mg cm(-2) of depth. The different dose components have been calculated and the results are discussed.