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Manuela Farris,1,2 Carlo Bastianelli,1 Elena Rosato,1 Ivo Brosens,3 Giuseppe Benagiano1 1Department of Gynecology, Obstetrics and Urology, Sapienza, University of Rome, Rome, Italy; 2The Italian Association for Demographic Education, Rome, Italy; 3Faculty of Medicine, KU Leuven, Leuven, Belgium Abstract: Uterine fibroids are the most common gynecological disorder, classically requiring surgery when symptomatic. Although attempts at finding a nonsurgical cure date back to centuries, it is only around the middle of the last century that serious attempts at a medical treatment were carried out. Initially, both progestins and estrogen–progestin combinations have been utilized, although proof of their usefulness is lacking. A major step forward was achieved when peptide analogs of the GnRH were introduced, first those with superagonist properties and subsequently those acting as antagonists. Initially, the latter produced side effects preventing their routine utilization; eventually, this problem was overcome following the synthesis of cetrorelix. Because both types of analogs produce hypoestrogenism, their use is limited to a maximum of 6 months and, for this reason, today they are utilized as an adjuvant treatment before surgery with overall good results. Over the last decade, new, nonpeptidic, orally active GnRH-receptor blockers have also been synthesized. One of them, Elagolix, is in the early stages of testing in women with fibroids. Another fundamental development has been the utilization of the so-called selective progesterone receptor modulators, sometimes referred to as “antiprogestins”. The first such compound to be applied to the long-term treatment of fibroids was Mifepristone; today, this compound is mostly used outside of Western Countries, where the substance of choice is Ulipristal acetate. Large clinical trials have proven the effectiveness of Ulipristal in the long-term medical therapy of fibroids, although some caution must be exercised because of the rare occurrence of liver complications. All selective progesterone receptor modulators produce unique endometrial changes that are today considered benign, reversible, and without negative consequences. In conclusion, long-term medical treatment of fibroids seems possible today, especially in premenopausal women. Keywords: uterine myomas, progestin, gonadotropin-releasing hormone receptor blockers, selective progesterone receptor modulators, antiestrogens

The ASY-EOS experiment at GSI laboratory measured the direct and elliptic flow of neutrons and light charged particles in the reaction 197Au+197 Au at 400 A MeV incident energy. The ratio of elliptic flow of neutrons with respect to that of the light charged particles was used as main experimental observable to probe the density dependence of the symmetry energy term of the nuclear equation of state. Results, obtained by comparison of the experimental data with the UrQMD model predictions, strongly support a moderately soft to linear density dependence of the symmetry energy at suprasaturation densities below 2ρ0.

Two and multi particle correlations from the decay of sources produced in 12C+24Mg and 12C+208Pb collisions at E=35 AMeV have been studied by using the forward part (1° < θlab < 30°) of the CHIMERA multi-detector. Correlations and invariant mass spectroscopy are used to explore simultaneous and sequential decays of resonances in light isotopes with Z∼3-6, produced in peripheral collisions via the break-up of excited quasi-projectiles. Among them we mention 5Li, 6Li, 6Be, 8Be and the astrophysically important state in 12C decaying into three alpha particles. Results and future perspectives at the INFN-LNS will be presented.

The elliptic-flow ratio of neutrons with respect to protons or light complex particles in reactions of heavy ions at pre-relativistic energies has been proposed as an observable sensitive to the strength of the symmetry term of the nuclear equation of state at supra-saturation densities. In the ASY-EOS experiment at the GSI laboratory, flows of neutrons and light charged particles were measured for 197Au+197Au collisions at 400 MeV/nucleon. Flow results obtained for the Au+Au system, in comparison with predictions of the UrQMD transport model, confirm the moderately soft to linear density dependence of the symmetry energy deduced from the earlier FOPI-LAND data.

The present status and the perspectives of the FAZIA project are presented. The main achievements in terms of identification thresholds and isotopic resolution are discussed, together with the adopted technical solutions. The detector is particularly well suited for the investigation of isospin transport phenomena at intermediate beam energies; perspectives to reduce the identification thresholds to cope with lower energy ISOL beams are briefly introduced. Some experimental results concerning isospin transport effects obtained with a test telescope are presented. The study of isospin transport phenomena can give information on the symmetry energy term of the nuclear equation of state by comparing the experimental results on isospin related observables with the predictions of transport codes.

The binary break-up of projectile-like fragments in non central heavy-ion collisions follows different decay patterns, from equilibrated emission towards dynamical (prompt) fission. Recently, comparing two systems with different N/Z in the entrance channel, it has been shown that the dynamical emission cross-section is enhanced for the most neutron rich system while the statistical emission cross-section is independent from the isotopic composition. In order to understand this dependence and disentangle it from the initial size of the nuclei, we have studied the two isobaric systems 124Xe+64 Zn and 124Xe+64 Ni at 35 A MeV (InKiIsSy experiment), in comparison with the previous studied reactions (124Sn +64 Ni and 112Sn +58 Ni) at the same bombarding energy. We present the first results evidencing a striking similar effect in the dynamical decay as a function of the N/Z of the target for equal size systems.

Projectile break-up reactions induced on polyethylene (CH2) target are used in order to study the spectroscopy of 10Be and 16C nuclei. For the present experiment we used 10Be and 16C beams delivered by the FRIBs facility at INFN-LNS, and the CHIMERA 4π multi-detector. 10Be and 16C structures are studied via a relative energy analysis of break-up fragments. The 4He+6He break-up channel allowed us to study the spectroscopy of 10Be; in particular we find evidence of a new state in 10Be at 13.5 MeV excitation energy. The 16C nucleus is studied via 6He-10Be correlation; we find the fingerprint of a possible state at about 20.6 MeV

Relatively large yields of various exotic beams produced through in-flight fragmentation are available at LNS. Using the CHIMERA detector, we performed various experiments to study elastic and inelastic scattering, transfer, break-up, and reaction dynamics with targets from proton and deuteron to carbon and heavier. For reactions with relatively light systems we used the kinematical coincidence method to extract high resolution angular distributions of binary reactions from the measured light particle energy spectra. We also used the CsI detectors of CHIMERA to detect gamma rays emitted in the reactions. Some of most recent results are presented together with future perspectives with the coupling of CHIMERA with FARCOS array.

The elliptic-flow ratio of neutrons with respect to protons or light complex particles in reactions of heavy ions at pre-relativistic energies has been proposed as an observable sensitive to the strength of the symmetry term of the nuclear equation of state at supra-saturation densities. In the ASY-EOS experiment at the GSI laboratory, flows of neutrons and light charged particles were measured for 197Au+197Au, 96Zr+96Zr and 96Ru+96Ru collisions at 400 MeV/nucleon with the Large Area Neutron Detector LAND as part of a setup with several additional detection systems used for the event characterization. Flow results obtained for the Au+Au system, in comparison with predictions of the UrQMD transport model, confirm the moderately soft to linear density dependence of the symmetry energy deduced from the earlier FOPI-LAND data.

A study of the identification properties and of the energy response of a Si-Si-CsI(Tl) ΔE-E telescope exploiting a partially depleted second Si stage has been performed. Five different bias voltages have been applied to the second stage of the telescope, one corresponding to full depletion, the others associated with a depleted layer ranging from 60% to 90% of the detector thickness. Fragment identification has been obtained using either the ΔE-E technique or the Pulse Shape Analysis (PSA). Charge collection efficiency has been evaluated. The ΔE-E performance is not affected by incomplete depletion. Isotopic separation capability improves at lower bias voltages with respect to full depletion, though charge identification thresholds increase.

Experimental results concerning isospin transport phenomena and odd-even staggering in Z and N distributions are presented. Data refer to 84Kr+112,124Sn collisions at 35AMeV and they were collected with a high resolution FAZIA telescope, able to isotopically resolve ions up to Z ∼ 20. Evidences of isospin diffusion and drift obtained from the < N > /Z behaviour of the detected fragments are discussed. The odd-even staggering both in Z and N is compared with experimental data available in literature, finding that it shows a common trend in different reaction types.

The systems 124Sn+64Ni and 112Sn+58Ni at 35 AMeV were analyzed in previous experiments, by using the 4π multi-detector CHIMERA in order to investigate the time-scale and mechanisms of fragments formation. By comparing the two systems, effects that have been correlated to Isospin transport in reaction dynamics and symmetry energy term of nuclear equation of state at sub-saturation density were found. Recently, in order to disentangle the Isospin effects from size effects the 124Xe+64Ni reaction was investigated at the same beam energy of 35 AMeV.

Recent results of the INDRA collaboration are presented in this contribution. They concern the evolution of reaction dynamics from the first stage of the collision to the production of fragments. Different probes are used to evidence the stopping/transparency, collective flow and the symmetry energy term of the nuclear equation of state.

Nuclear matter under extreme conditions can be studied in the laboratory with heavy-ion collisions. In this case one can indeed vary the incident energy and explore different impact parameter and rapidity regions to access densities that extend above and below saturation. This opportunity allows one to learn about the nuclear equation of state and its implications in astrophysics phenomena such as supernovae explosions and neutron stars properties. All these phenomena involve time scales that need to be accessed with two- and multi-particle correlation measurements. In this contribution a brief report of the FARCOS array will be presented. In particular, tests with alpha sources and beams and preliminary results from a recent experiment INKIISSY performed using a FARCOS prototype made of four telescopes will be presented.

Decay modes of excited compound systems 118Ba and 134Ba, produced respectively in the 78Kr+40Ca and 86Kr+48Ca collisions at 10 A·MeV, are investigated. In particular, the competition between the various disintegration path of medium mass compound nuclei, formed by fusion processes, the production of the so referred Intermediate Mass Fragments (IMF), and the isospin dependence of the decay process are studied. Data were taken at the INFN-Laboratori Nazionali del Sud (LNS) by using the CHIMERA array. Data analysis is in progress; a first indication on the average-energy angular distributions suggests pre-equilibrium effects affecting the data and the presence of isotopical effects.

The european Fazia collaboration aims at building a new modular array for charged product identification to be employed for heavy-ion studies. The elementary module of the array is a Silicon-Silicon-CsI telescope, optimized for ion identification including pulse shape analysis, too. The achievement of top performances imposes specific electronics which has been developed by the FAZIA collaboration and includes high quality charge and current preamplifiers, coupled to fully digital front-end. During the initial R&D phase, original and novel solutions have been tested in prototypes, obtaining unprecedented ion identification capabilities. FAZIA is now constructing a demonstrator array consisting of about two hundreds telescopes arranged in a compact and transportable configuration. In this contribution, we mainly summarize some aspects studied by FAZIA to improve the ion identification. Then we will briefly discuss the FAZIA program focused on experiments to be done with the demonstrator. First results on the isospin dynamics obtained with a reduced set-up demonstrate well the performance of the telescope and represent a good starting point towards future investigations with both stable and exotic beams.

Semi-peripheral collisions of 64Ni + 124Sn in direct and inverse kinematics, at 35 A MeV incident energy, are studied to characterize the dynamical origin and align-ments properties of fragments emission at midrapidity. This emission is partly due to the fragmentation of a transient neck joining the projectile and target in the early stages of the reaction. Recently we exploited observable from neck fragmentation to constraint the density dependence of the symmetry energy. In this contribution we focus on the density evolution of the mid-rapidity source. An experimental survey is suggested to check if data are consistent with the formation of neck fragments in a dilute density region in contact with the projectile-like and target-like spectators at normal saturation density.

The elliptic-flow ratio of neutrons with respect to protons or light complex particles in reactions of heavy-ions at pre-relativistic energies has been proposed as an observable sensitive to the strength of the symmetry term of the nuclear equation of state at supra-saturation densities. The results obtained from the existing FOPI/LAND data for 197Au+197Au collisions at 400 MeV/nucleon in comparison with the UrQMD model simulations favoured a moderately soft symmetry term, but suffer from a considerable statistical uncertainty. These results have been confirmed by an independent analysis based on the Tübingen QMD simulations. In order to obtain an improved data set for Au+Au collisions and to extend the study to other systems, a new experiment was carried out at the GSI laboratory by the ASY-EOS collaboration. The present status of the data analysis is reported

Isospin transport phenomena in dissipative heavy ion collisions have been investigated at Fermi energies with a beam of 84Kr at 35AMeV. A comparison of the 〈N〉/Z of light and medium products forward-emitted in the centre of mass frame when the beam impinges on two different targets, the n-poor 112Sn and the n-rich 124Sn, is presented. Data were collected by means of a three-layer telescope with very good performances in terms of mass identification (full isotopic resolution up to Z ~ 20 for ions punching through the first detector layer) built by the FAZIA Collaboration and located just beyond the grazing angle for both reactions. The 〈N〉/Z of the products detected when the n-rich target is used is always higher than that associated to the n-poor one; since the detector was able to measure only fragments coming from the QuasiProjectile decay and/or neck emission, the observed behaviour can be ascribed to the isospin diffusion process, driven by the isospin gradient between QuasiProjectile and QuasiTarget. Moreover, for light fragments the 〈N〉/Z as a function of the lab velocity of the fragment is observed to increase when we move from the QuasiProjectile velocity to the centre of mass (neck zone). This effect can be interpreted as an evidence of isospin drift driven by the density gradient between the QuasiProjectile zone (at normal density) and the more diluted neck zone.

The elliptic-flow ratio of neutrons with respect to protons in reactions of neutron rich Heavy-Ion at intermediate energies has been recently proposed as an observable sensitive to the strength of the symmetry term in the nuclear equation of state (EOS) at supra-saturation densities. The recent results obtained from the existing FOPI/LAND data for 197Au+197Au collisions at 400 MeV/nucleon in comparison with the UrQMD model allowed a first estimate of the symmetry term of the EOS but suffer from a considerable statistical uncertainty. In order to obtain an improved data set for Au+Au collisions and to extend the study to other systems, a new experiment was carried out at the GSI laboratory by the ASY-EOS collaboration in May 2011.

Preliminary outcome of ISODEC experiment, performed at INFNLNS with the CHIMERA array, are presented. Disintegration path dependence on the entrance-channel N/Z ratios (isospin asymmetries) for the reactions 78Kr+40Ca and 86Kr+48Ca at 10 A·MeV, which give origin to the intermediate systems 118Ba and 134Ba, is being investigated. Staggering effects seem to be present as it was the case of a complementary measurement performed at GANIL at lower energy, i.e. 78,82Kr+40Ca at 5.5 A·MeV.

The recent intensity upgrade of the LNS fragmentation beam is discussed. The available beams, the tagging procedures and details on the beam quality are reported. The experimental program started with the CHIMERA detector using such beams is also discussed with preliminary results and future perspectives.

Effects related to the neutron to proton ratio (N/Z) degree of freedom in 40,48Ca+40,48Ca reactions at 25 MeV/nucleon have been investigated. Isotopic effect and even-odd staggering characterize the emission of light fragments at forward angles. The study of isobaric ratio 7Li/7Be for quasi-projectile source in semi-peripheral event of reactions allows moreover to investigate isospin diffusion effects in heavy ion collisions.

The first results of the ISODEC experiment, performed at the INFN Laboratori Nazionali del Sud (LNS) by using the CHIMERA detector, are presented. The principal aim of this experiment is to explore the isospin dependence of the decay modes of medium mass compound nuclei formed by fusion processes, by studying the competition between the various disintegration modes of 118,134Ba nuclei produced in the reactions 78Kr+40Ca and 86Kr+48Ca at 10 AMeV. The studied systems allow in fact to produce compound nuclei with a large variation of N/Z, and such data will also provide new constraint on sophisticated models attempting to describe statistical and/or dynamical properties of excited nuclei. The experiment complements data already obtained at 5.5 AMeV for 78,82Kr+40Ca reactions, previously realized at GANIL by using the INDRA detector. First results show a strong staggering effects in the Z distributions, as well as different isotopic composition and enrichment for the reaction products in the two systems.

The cross section, kinetic energy distribution and angular distribution of fragments with atomic number 3 ≤ Z ≤ 28 emitted in the reaction 78Kr + 40Ca at the bombarding energy of 5.5 MeV/nucleon and coincidence between light charged particles and fragments were measured by means of the 4π-INDRA array to study the decay mechanism of medium mass excited nucleus. Global features indicate a high degree of relaxation and are compatible with a binary fission from compound nucleus. The mean value of the kinetic energy distributions of fragments indicates dominance of Coulomb interaction, while the width of the distribution signals large fluctuations. Inclusive cross-section distributions of fragments with charge 3 ≤ Z ≤ 28 are bell-shaped and a strong even-odd-staggering (o-es) is observed for 3 ≤ Z ≤ 12. Coincidence measurements suggest that the light partners in very asymmetric fission are emitted at excitation energies below the particle emission thresholds. Data were confronted to the predictions of statistical model describing the decay of compound nuclei by emission of light particles and fragments. Calculations assuming spherical fission fragments and finite-range liquid drop fission barriers are not able to explain the experimental features. Attempts have been made to improve the agreement with experimental data. The analysis indicates the strong influence of the shape parameterization of the potential energy surface in describing the fission process of intermediate mass compound nuclei.

We present the first results of the ISODEC experiment, performed at the INFN-LNS with the CHIMERA device, in order to study the competition between the various disintegration modes of 118,134Ba compound nuclei produced by bombarding 40,48Ca targets with beams of 78,86Kr at 10 AMeV. This work aims thus to explore the isospin dependence of the decay modes of medium mass compound nuclei formed by fusion processes. The experiment complements data already obtained at 5.5 MeV/A for 78,82Kr+40Ca reactions, studied by Ademard et al. with beams delivered by GANIL facility and by using the INDRA detector.

Decay modes of excited nuclei are studied in 78,82Kr + 40Ca reactions at 5.5 MeV/nucleon by means of light-charged particles measured in coincidence with intermediate mass fragments and fission-like fragments. Inclusive cross-section distributions of fragments with charge 3 ≤ Z ≤ 28 are bell-shaped and a strong oddeven-staggering (o-e-s) is observed for 3 ≤ Z ≤ 12. Coincidence measurements suggest that the light partners in very asymmetric fission are emitted at excitation energies below the particle emission thresholds. Data were confronted to the predictions of statistical models describing the decay of compound nuclei by emission of light particles and fragments. Comparison with models suggests that the o-e-s of the light-fragment yields is mainly due to the successive steps of compound nucleus disintegration.

The influence of the neutron richness on binary decays is investigated in 78,82Kr+ 40Ca reactions at 5.5 MeV/A incident energy. Kinetic energy distributions and angular distributions of fragments with atomic number 6 ≤ Z ≤ 28 were measured using the 4π-INDRA array. Global features are compatible with an emission from a long-lived system. The yields around the symmetric splitting are about 30The persistence of strong structural effects is evidenced from elemental cross-sections of the light fragments. The cross-sections for odd-Z fragments are higher for the neutron rich CN while cross-sections for even-Z fragments are higher for the neutron poor CN. Calculations assuming two different potential energy surfaces are presented.

A 42-year-old woman was referred by neurology colleagues to our outpatient urology clinics. She presented with a non-monosymptomatic secondary enuresis, which started at 20 years of age When she was twenty-two she presented a single episode of a generalised tonic-clonic seizure, and she was treated with Carbamazepine (CBZ) with resolution of enuresis that reappeared when CBZ was stopped. Therefore, a video-EEG was performed, which documented an episode of enuresis during stage 1 of non-REM sleep without epileptic discharges and made it difficult for the patient to reach the deeper stages of sleep. According to these findings, the epileptic genesis of the enuresis was ruled out. A urodynamic invasive study was performed, and a normal active bladder associated with sleep disturbances was diagnosed as the combined cause of the non-monosymptomatic secondary nocturnal enuresis.Behavioural therapy and/or antimuscarinic treatments, alone or in combination, were used without success. Then the patient restarted CBZ at a low dose (200 mg/day), and a significant reduction of enuresis episodes (1 wet night every 9–10) was obtained with no changes in the bladder diary.CBZ effectiveness in such a case on an overactive bladder (OAB) could depend on its modulating effect in the central nervous system.

Objective To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort.Methods Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets.Results Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud’s phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1–16.5) than lcSSc (2 years, IQR 0–7), and dcSSc (1 year, IQR 0–3) (p

The kinematical coincidence method is used to extract angular distribution of elastic scattering and transfer reactions. The detected light particle energy spectra are used to extract the angular distribution with around 1° resolution in the Center of Mass (CM) system. Examples with 10Be beam are presented. In the case of proton scattering, γ-ray coincidences are used to discriminate excited levels population from elastic scattering.

Abstract Background All crustaceans periodically moult to renew their exoskeleton. In krill this involves partial digestion and resorption of the old exoskeleton and synthesis of new cuticle. Molecular events that underlie the moult cycle are poorly understood in calcifying crustaceans and even less so in non-calcifying organisms such as krill. To address this we constructed an Antarctic krill cDNA microarray in order to generate gene expression profiles across the moult cycle and identify possible activation pathways. Results A total of 26 different cuticle genes were identified that showed differential gene expression across the moult cycle. Almost all cuticle genes were up regulated during premoult and down regulated during late intermoult. There were a number of transcripts with significant sequence homology to genes potentially involved in the synthesis, breakdown and resorption of chitin. During early premoult glutamine synthetase, a gene involved in generating an amino acid used in the synthesis of glucosamine, a constituent of chitin, was up regulated more than twofold. Mannosyltransferase 1, a member of the glycosyltransferase family of enzymes that includes chitin synthase was also up regulated during early premoult. Transcripts homologous to a β-N-acetylglucosaminidase (β-NAGase) precursor were expressed at a higher level during late intermoult (prior to apolysis) than during premoult. This observation coincided with the up regulation during late intermoult, of a coatomer subunit epsilon involved in the production of vesicles that maybe used to transport the β-NAGase precursors into the exuvial cleft. Trypsin, known to activate the β-NAGase precursor, was up regulated more than fourfold during premoult. The up regulation of a predicted oligopeptide transporter during premoult may allow the transport of chitin breakdown products across the newly synthesised epi- and exocuticle layers. Conclusion We have identified many genes differentially expressed across the moult cycle of krill that correspond with known phenotypic structural changes. This study has provided a better understanding of the processes involved in krill moulting and how they may be controlled at the gene expression level.

Abstract Introduction Three-dimensional techniques for radiotherapy have expanded possibilities for partial volume liver radiotherapy. Characteristic, transient radiographic changes can occur in the absence of clinical radiation-induced liver disease after hepatic radiotherapy and must be distinguished from local recurrence. Case presentation In this report, we describe computed tomography changes after chemoradiotherapy for cholangiocarcinoma as an example of collaboration to determine the clinical significance of the radiographic finding. Conclusion Because of improved three-dimensional, conformal radiotherapy techniques, consultation across disciplines may be necessary to interpret post-treatment imaging findings.