Synergies of THESEUS with the large facilities of the 2030s and guest observer opportunities.

The proposed THESEUS mission will vastly expand the capabilities to monitor the high-energy sky. It will specifically exploit large samples of gamma-ray bursts to probe the early universe back to the first generation of stars, and to advance multi-messenger astrophysics by detecting and localizing the counterparts of gravitational waves and cosmic neutrino sources. The combination and coordination of these activities with multi-wavelength, multi-messenger facilities expected to be operating in the 2030s will open new avenues of exploration in many areas of astrophysics, cosmology and fundamental physics, thus adding considerable strength to the overall scientific impact of THESEUS and these facilities. We discuss here a number of these powerful synergies and guest observer opportunities.

Development and installation of a radio frequency quadrupole cooler test.

A Radio Frequency Quadrupole Cooler (RFQC) prototype was adapted for insertion into a high uniformity magnetic field, with Bz up to 0.2 T, to improve radial confinement. While the RFQC purpose is to reduce (by gas collisions) the energy spread and emittance of a beam of radioactive nuclei, to finely select ion mass in nuclear physics, the prototype is tested in a setup including a stable ion source, a pepper pot emittance meter, and two Faraday cups; this makes a precise characterization of the RFQC feasible. The ion extraction was studied in detail by simulations, both to match it to the emittance meter granularity and to verify the effect of the typical nonuniformity of the longitudinal electric field Ez inside the RFQC; an average motion description (including friction force from gas collisions) was used, introducing the ballistic and diffusive regimes. With a preliminary optimization of the electrode shape, buffer gas pressure pg, and radio frequency voltage, the ion beam can be extracted with a significant cooling margin.

Could beta-myrcene be an alternative to albendazole for the treatment of experimental cystic echinococcosis?

Echinococcus granulosus causes hydatidosis or cystic echinococcosis in humans and livestock. In humans, this disease can be managed with surgery, percutaneous treatment, chemotherapy and/or observation. The chemotherapeutic agents used and approved for treatment of hydatidosis are benzimidazoles. Because of the difficulties in achieving successful treatment, considerable efforts have been made to find new natural compounds against hydatid disease. Beta-myrcene is a monoterpene presented in the essential oils of different plants. It is the principal component of essential oil of Rosmarinus officinalis (rosemary). The goal of the present study was to evaluate the in vitro effects of beta-myrcene against germinal cells, protoscoleces and murine cyst of E. granulosus, as well also, investigate its chemoprophylactic activity in a murine model of cystic echinococcosis. For the in vitro assays, the parasites were incubated with beta-myrcene at 10, 5 and 1 µg/mL. The treatments were dose and time-dependent, and consistent with the observed morphological alterations. In the chemoprophylactic efficacy study, the effect of beta-myrcene was similar to albendazole, the reference drug for human echinococcosis treatment.

Integration of RFQ beam coolers and solenoidal magnetic fields.

Electromagnetic traps are a flexible and powerful method of controlling particle beams, possibly of exotic nuclei, with cooling (of energy spread and transverse oscillations) provided by collisions with light gases as in the Radio Frequency Quadrupole Cooler (RFQC). A RFQC prototype can be placed inside the existing Eltrap solenoid, capable of providing a magnetic flux density component B(z) up to 0.2 T, where z is the solenoid axis. Confinement in the transverse plane is provided both by B(z) and the rf voltage V(rf) (up to 1 kV at few MHz). Transport is provided by a static electric field E(z) (order of 100 V/m), while gas collisions (say He at 1 Pa, to be maintained by differential pumping) provide cooling or heating depending on V(rf). The beamline design and the major parameters V(rf), B(z) (which affect the beam transmission optimization) are here reported, with a brief description of the experimental setup.

Chemoprophylactic and therapeutic efficacy of thymol in murine cystic echinococcosis.

Cystic echinococcosis is a zoonotic disease caused by the larval stage of the cestode Echinococcus granulosus. The drugs commonly used against cystic echinococcosis are benzimidazoles. Unfortunately, 20%-40% of cases do not respond favorably to such chemotherapy. Consequently, the search of new therapeutic alternatives such as the use of traditional medicinal plants has been increased. The aim of the current experimental work was to investigate the chemoprophylactic and clinical efficacy of thymol on mice infected with E. granulosus metacestodes. Thymol (40 mg/kg) was administered under two different therapeutic schemes: dosing every 24h over 20 days and treatment every 12h for 10 days. Thymol demonstrated efficacy against experimental murine cystic echinococcosis. The chemoprophylactic and therapeutic effects of thymol were comparable to that of albendazole. Due to the lack of toxicity observed in mice at the tested doses; we consider that thymol is a potential alternative to be applied for the treatment of human hydatid disease.

In Vitro Cestocidal Activity of Thymol on Mesocestoides corti Tetrathyridia and Adult Worms.

Nothing is known about the possible effect of thymol or other compounds of essential oils against the adult worms of cestodes. The aim of the present work was to determine in vitro cestodicidal activity of thymol against Mesocestoides corti adult worms. Moreover, the in vitro effect on tetrathyridia was also demonstrated. Tetrathyridia exposed to different concentrations of thymol showed a concentration and time-dependent effect. At lower concentrations, the main change observed was mainly in morphology, with larvae exhibiting an elongation of the body. When tetrathyridia were exposed to higher concentrations, increased surface alterations and damage were detected. The body appeared elongated and flattened, and a complete loss of morphology and microtriches was observed. Thymol was able to kill M. corti tetrathyridia, since following inoculation of treated parasites in mice no parasites could be recovered. The effect on M. corti adult worms was dose and time-dependent. Changes in motility coincide with the tissue damage were observed at the structural and ultrastructural level. Thymol caused severe damages to both developmental stages analyzed. Damages were more significant in fully segmented worms. The data reported in this paper demonstrate a clear in vitro effect of thymol against M. corti tetrathyridia and adult worms.

Efficacy of Essential Oils of Thymus vulgaris and Origanum vulgare on Echinococcus granulosus.

The aim of the present work was to determine the in vitro effect of T. vulgaris and O. vulgare essential oils against E. granulosus protoscoleces and cysts. Essential oils were added to the medium resulting in thymol final concentrations of 10 µg/mL. The essential oils had a time-dependent effect provoking the complete loss of protoscolex viability after 72 days of postincubation. The results were confirmed at the ultrastructure level. Loss of infectivity in protoscoleces incubated with O. vulgare after 60 days was observed. On the other hand, the weight of cysts recorded in mice inoculated with T. vulgaris treated protoscoleces was significantly lower than that obtained in control group. Gamma-glutamyl-transpeptidase activity was readily detected in the culture supernatant of protoscoleces treated either with the essential oils or thymol. T. vulgaris and O. vulgare essential oils and thymol can induce cell apoptosis of protoscoleces after short incubation times. The efficacy of T. vulgaris and O. vulgare essential oils was also demonstrated in vitro on E. granulosus murine cysts. Our data suggest that essential oils of T. vulgaris and O. vulgare have anthelmintic effect against protoscoleces and cysts of E. granulosus.

The charge breeder beam line for the selective production of exotic species project at INFN-Legnaro National Laboratories.

SPES (Selective Production of Exotic Species) is an INFN (Istituto Nazionale di Fisica Nucleare) project with the aim at producing and post-accelerating exotic beams to perform forefront research in nuclear physics. To allow post-acceleration of the radioactive ions, an ECR-based Charge Breeder (CB) developed on the basis of the Phoenix booster was chosen. The design of the complete beam line for the SPES-CB will be described: a system for stable 1+ beams production was included; special attention was paid to the medium resolution mass spectrometer after the CB to limit possible superposition of the exotic beams with the impurities present in the ECR plasma.

Plasma-beam traps and radiofrequency quadrupole beam coolers.

Two linear trap devices for particle beam manipulation (including emittance reduction, cooling, control of instabilities, dust dynamics, and non-neutral plasmas) are here presented, namely, a radiofrequency quadrupole (RFQ) beam cooler and a compact Penning trap with a dust injector. Both beam dynamics studies by means of dedicated codes including the interaction of the ions with a buffer gas (up to 3 Pa pressure), and the electromagnetic design of the RFQ beam cooler are reported. The compact multipurpose Penning trap is aimed to the study of multispecies charged particle samples, primarily electron beams interacting with a background gas and/or a micrometric dust contaminant. Using a 0.9 T solenoid and an electrode stack where both static and RF electric fields can be applied, both beam transport and confinement operations will be available. The design of the apparatus is presented.

Lymphatic mapping and sentinel node identification in squamous cell carcinoma and melanoma of the head and neck.

AIM: The aim of our study was to evaluate the role of scintigraphy in lymphatic mapping and in the identification of the sentinel lymph node (SLN) in patients with head and neck cancer. METHODS: Between September 1999 and February 2001 we enrolled 22 consecutive patients with cancer in the head and neck region: five squamous cell carcinomas, one Merkel cell tumor of the cheek, and 16 malignant melanomas. Lymphoscintigraphy was performed three hours before surgery after injection of 30-50 MBq of 99mTc -Nanocoll in 0.3 mL; the dose was fractionated by injecting the radiotracer at two points around the lesion. Static acquisition (anterior and/or lateral views, 512 x 512 matrix, 5 mins pre-set time) was started immediately after the injections so as to visualize the pathways of lymphatic drainage. The skin projection of the SLN was marked with ink. Intraoperative SLN detection was performed with perilesional injection of patent blue. RESULTS: SLNs were found with lymphoscintigraphy in all patients. Thirty-three SLNs were identified: one occipital node, three nodes at the base of the tongue, 10 superficial lateral nodes (external jugular), five submandibular nodes, five submental nodes, three mastoid nodes and six supraclavicular nodes. Biopsy was performed in 21/22 patients. In 20/22 patients the first lymph nodes were visualized in the proximal cranial regions (retroauricular, jugular and submandibular) at five minutes post injection. The SLN positivity rate was 13.6% (three patients). All patients with tumor-positive SLNs were submitted to radical dissection. Poor concordance in the detection of sentinel nodes was observed with patent blue. CONCLUSIONS: The flow of nanocolloid in the lymph vessels of the head is rapid. In our experience immediate scintigraphic imaging was essential to visualize the pathways of lymphatic drainage and the first SLN. Radioguided SLN biopsy is therefore recommended within three hours. Injection of patent blue is inadvisable because of the poor concordance with lymphoscintigraphy and the risk of permanent tattooing of the face.

Optimization-based learning with bounded error for feedforward neural networks.

An optimization-based learning algorithm for feedforward neural networks is presented, in which the network weights are determined by minimizing a sliding-window cost. The algorithm is particularly well suited for batch learning and allows one to deal with large data sets in a computationally efficient way. An analysis of its convergence and robustness properties is made. Simulation results confirm the effectiveness of the algorithm and its advantages over learning based on backpropagation and extended Kalman filter.

Role played by a natural channel on the quality of bordering environment: a chemical assessment.

Based on a rational and simple chemical approach, a field-investigation aimed to assess the role played by a natural channel "lama" on the quality of underlying groundwater and neighbouring soils has been carried out. The results have demonstrated that: (a) the stream flowing through the "lama" is mainly made up of treated effluent from a nearby municipal wastewater treatment plant; (b) the occurrence of nitrates in the "lama" is due to rain-washing of nitrogen fertilized agricultural soils bordering on the "lama"; (c) hydraulic connections exist between the lama and the underlying groundwater causing contaminants flowing through the "lama" to reach groundwater within less than one week; (d) compared with the values measured in the "lama", the concentrations of TOC, N-NH4 and N-NO3 in groundwater result: lower, far lower and greater, respectively; (e) agricultural soils bordering on the "lama" result significantly contaminated by halogenated organics.

[Determination of urine density: comparison of refractometry and measurement of the period of oscillation using the protocols of the National Committee for Clinical Laboratory Standards]. / Determinazione della densità delle urine: confronto tra rifrattometria e misura del periodo di oscillazione, con l'impiego dei protocolli del National Committee for Clinical Laboratory Standards (NCCLS).

Two methods for the determination of urine density (relative density or specific mass) have been evaluated and compared using NCCLS protocols: the refractometric method and a new method based on the measure of shifts in harmonic oscillation (SHO). Within the range investigated (from 1,000 up to 1,034) the methods were linear. Total imprecision, including the carry-over, was the same for both: the 95% confidence limits, at the level of 1,003, 1,013 and 1,030, were 1,001-1,005, 1,011-1,015 and 1,028-1,032 respectively. In analysing urines having known density, the SHO method was always accurate, while the refractometric method was affected by a significant bias at protein and haemoglobin concentrations greater than 4 and 2 g/L respectively. A direct comparison of the results obtained by the two methods was made on 300 untimed specimens of urine with density ranging from 1,002 to 1,034; the equation of regression line (refractometric method on the x axis, SHO on the y axis), calculated with a non-parametric statistical method, was SHO = refractometric method + 0,001. Despite some urine specimens (24, i.e. 8%) showed density differences (absolute value) of more than 0,003 (between 0,004 and 0,007 relative density units), the good mean agreement observed allows to conclude that both methods give clinically useful analytical results.

The endocrine pattern of late onset adrenal hyperplasia (21-hydroxylase deficiency).

We describe 5 adult women with severe hirsutism due to late onset 21-hydroxylase deficiency. Diagnosis was performed on the finding of high serum 17-hydroxyprogesterone (17OHP) levels with a marked hyperresponse to an ACTH test. The endocrine study showed in most patients a gonadotropin behavior similar to that observed in classical polycystic ovary (PCO) syndrome. Prolactin levels were slightly increased in basal conditions and presented an exaggerated response to TRH stimulation.