Clusters in light nuclear systems: a multi-method approach

Clustering phenomena affect many aspects of nature and social sciences. They consist in the creation of groups of correlated objects which modify the behaviour of a given system introducing symmetries and order. As an example, in the largest scale known to humans, cluster effects determine the formation of congregate of galaxies. On human being scales, clustering is widely present in everyday aspects, leading to collective social behaviours as \emph{consensus} in social and technological networks and \emph{synchronization} in biological systems. In nuclear physics, clustering is one of the most fascinating results of the Pauli exclusion principle and characterizes a large variety of nuclear states, especially in light nuclear systems. Nuclear structures resulting from these phenomena are quite unusual and peculiar, and their investigation is extremely important in the understanding of nuclear forces and their related properties. As an example, cluster structures evolve from \emph{self-conjugated} nuclei to neutron-rich ones with the appearance of highly deformed structures. In the latter case, the cluster centers are bounded together by means of extra-neutrons, which act in a glue-like effect increasing the stability of the structure. Clustering plays also a role in nuclear astrophysics, where it is involved in the creation of elements in stars. In this thesis, we experimentally investigate clustering aspects of light nuclear systems with a \emph{multi-method} approach and by using different and complementary techniques. In Chapter one, we show how the appearance of clustering phenomena is naturally encouraged by independent-particle approaches to nuclear structure and how, for a detailed description of such aspects, further, collective models, are required. After a comprehensive overview of theoretical models attempting to describe clustering phenomena in nuclei, such as the $\alpha$-particle model, shell-like model approaches, and microscopic models, and their predictions within physical cases of recent interest, we make a systematic discussion of the experimental techniques which are usually applied to point out such phenomena. In Chapter 2 we describe the results of our experimental campaign, carried out in different laboratories and facilities, aimed to improve the present knowledge of clusters in light nuclei and their evolution with the neutron excess. These studies have been performed by using nuclear reactions involving light nuclear systems. We started from the $^{10}$Be nucleus. It is associated to a two $\alpha$-like structure coupled to two valence neutrons: it presents nice properties of symmetry. The structure of this nucleus is explored by means of direct reactions which involve the population of highly-excited states in $^{10}$Be and their subsequent in-flight decay. The experiment was performed by using a fragmentation cocktail beam at the FRIBs facility of INFN-LNS (Catania) and the CHIMERA $4\pi$ multi-detector. Invariant mass techniques are used to reconstruct the spectroscopy of $^{10}$Be, giving the hint for the existence of a new state, possibly associated to a new member of the molecular rotational band. While the effects of clusterization are well visible and quite well understood in beryllium isotopes, they are much less known in carbon isotopes. For this reason, different neutron-poor and neutron-rich carbon isotopes are here investigated, providing interesting information on the carbon isotopic chain $^{11,12,13,16}$C. $^{11}$C, as well as $^{13}$C, are studied by means of low energy compound nucleus reactions; respectively, we measured the $^{10}$B(p,$\alpha)$ reaction ($\textrm{E}_p=0.6$-$1.0$ MeV) and the $^{9}$Be($\alpha$,$\alpha$) resonant elastic scattering (E$_\alpha=3.3$-$10$ MeV) at the Tandem accelerator in Naples. We analyzed the differential cross section with a comprehensive $R$-matrix approach, also by including other data published in the literature. We succeeded in refining their spectroscopy above the $\alpha$-disintegration thresholds, with interesting speculation on the existence of molecular rotational bands. The structure of the neutron-rich $^{16}$C isotope is studied with the same experimental apparatus of the $^{10}$Be case by using the most intense $^{16}$C beam produced up to date for nuclear physics experiments at intermediate energies. We provide signatures of the possible existence of high-lying excited states of this poorly known nucleus never observed before. To conclude our studies of clustering in carbon isotopes, the Hoyle state in $^{12}$C ($7.654$ MeV, $0^+$) was investigated via a high-precision dedicated experiment. The cluster properties of this state are quite crucial; as an example, it has been predicted that its three constituent $\alpha$-particles may form a \emph{Bose-Einstein} condensate. We proved, with an unprecedented precision, the fully sequential decay width of this state by using the $^{14}$N(d,$\alpha$) reaction at $10.5$ MeV at the Tandem accelerator of INFN-LNS. To achieve a such high precision we developed a new hodoscope detector. Our result is important since it provides stringent constraints on microscopic theoretical calculations which describe clustering in nuclei, as well as to nuclear astrophysics for the production of carbon and heavier elements in the universe. Clustering phenomena in $^{19}$F and $^{20}$Ne have been studied by means of the $^{19}$F(p,$\alpha$) reaction at deeply sub-Coulomb energies ($\textrm{E}_{cm}=0.18$-$0.60$ MeV) at the AN-2000 Van der Graff accelerator of INFN-LNL. An analysis of angular distributions at various energies gives signatures of possible cluster structures in $^{19}$F. The compound nucleus $^{20}$Ne spectroscopy is instead studied by means of a $R$-matrix approach; the astrophysical relevance of our work is also discussed. Chapter 3 is finally dedicated to a different, complementary, point of view in the study of clustering phenomena: the analysis of Heavy Ion Collisions (HICs) at intermediate energies. Cluster states, produced by overlapping zones formed in HICs and characterized by high temperatures and low densities, can be used as a suitable probe for nuclear structure and dynamics. We implemented a thermal model aimed to reproduce in-flight resonance decay phenomena in HICs. This model has been applied to the case of $\alpha$-$\alpha$ correlations in $^{36}\textrm{Ar}+ {^{58}\textrm{Ni}}$ central collisions data at various bombarding energies ($32$-$95$ AMeV); they have been measured with the INDRA $4\pi$ multi-detector at the GANIL. The comparisons of data with thermal model predictions allows us to make interesting speculations on the processes contributing to the formation of $^{8}$Be states in such highly excited and diluted environments

The role of 13C excited states in α+9Be reaction and scattering cross sections

The spectroscopy of 13 C excited states above the alpha emission threshold has been investigated by studying data on 9 Be( α,α ) 9 Be and 9 Be( α ,n) 12 C collisions at bombarding energies in the range E α ≈2-10 MeV. A multichannel R -matrix fit allowed us to better constrain the spectroscopy of 13 C states above the α threshold (10.65 MeV). Preliminary results on this analysis will be discussed

Impact of Epiretinal Membrane on Optical Coherence Tomography Tools Used for Monitoring Glaucoma

Background: Retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) measurements can be influenced by many factors including the presence of concomitant retinal diseases. The aim of this study it to assess the impact of epiretinal membrane (ERM) on RNFL and GCL assessment using optical coherence tomography (OCT). Methods: GCL, peripapillary RNFL (pRNFL), and Bruch's Membrane Opening Minimum Rim Width (BMO-MRW) thicknesses were analysed using an SD-OCT (Spectralis OCT) in eyes with idiopathic ERM and compared with a control group. Results: 161 eyes were included, 73 eyes in the control group and 88 eyes with idiopathic ERM. The pRNFL analysis revealed a statistically significant difference between the two groups in overall and temporal sector thicknesses. For GCL thickness report, the percentage of scans in which the GCL was erroneously segmented by automatic segmentation was assessed for each eye. A statistically significant difference was found in all sectors (p < 0.001), with the exception of external nasal sector. A statistically significant difference (p < 0.001) in the GCL total volume report was found in ERM group compared to the control group. For MRW at BMO analysis, there was no statistically significant difference in MRW thickness in any sector. Conclusion: In eyes with ERM, the GCL and pRNFL analysis seemed affected by the morphological retinal layers' modification. MRW-BMO did not appear to be directly affected by the presence of ERM

Clinical utility of plasma KRAS, NRAS and BRAF mutational analysis with real time PCR in metastatic colorectal cancer patients -The importance of tissue/plasma discordant cases

Background: Tumor tissue (T) mutational analysis represents the standard for metastatic colorectal cancer (mCRC); however, circulating tumor DNA (ctDNA) detected by liquid biopsy in plasma (PL) can better represent tumor heterogeneity. Methods: mCRC patients undergoing standard first-line chemotherapy with known T-KRAS/NRAS/BRAF status were enrolled in the present prospective study. PL mutations were assessed within 2 weeks before chemotherapy start with real time PCR and correlated with T status and Progression free survival (PFS). Clinical and biochemical variables including also total number of tumor lesions (TNL) and the sum of maximum diameter (SMD) of all lesions were assessed as potential predictors of T/PL discordance. RESULTS: Among 45 enrolled patients, all BRAF mutations were concordant between T and PL and there were 20% of patients RAS discordant: 9% wild type in T and mutated in PL and 11% mutated in T and wild type in PL. T mutations were significantly associated to median PFS (mPFS of 4.5, 8.3 and 22.9 months for T-BRAF mutated, T-RAS mutated, and T-wild type patients, respectively, p for trend 0.00014). PL mutations further refined prognosis: RAS wild type in T and mutated in PL had significantly shorter PFS than concordant RAS wild type in T and PL: mPFS 9.6 vs. 23.3 months, respectively, p = 0.02. Patients RAS mutated in T and wild type in PL had longer PFS than concordant RAS mutated in T and PL: 24.4 vs. 7.8 months, respectively, p = 0.008. At a multivariate cox regression analysis for PFS, PL mutations were independent prognostic factor superior to T analysis (HR 0.13, p = 0.0008). At multivariate logistic regression analysis TNL and SMD were significant predictors of discordant cases. Conclusions: PL mutational analysis allows a better prognostication than T analysis alone and could help in mCRC treatment management

Prognostic significance of KRAS mutation rate in metastatic colorectal cancer patients.

No abstract availabl

Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients

none24noIntroduction: Activating mutations of K-Ras gene have a well-established role as predictors of resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. Their prognostic value is controversial, and no data regarding the prognostic value of mutation rate, defined as the percentage of mutated alleles/ tumor sample, are available. We aimed to evaluate the prognostic value of K-Ras mutation rate in a homogenous cohort of mCRC patients receiving first-line doublet plus bevacizumab. Patients and Methods: This retrospective study enrolled 397 K-Ras mutant mCRC patients from 6 Italian centers, and 263 patients were fully evaluable for our analysis. K-Ras mutation rate was assessed by pyrosequencing. Patients with less than 60% of cancer cells in tumor tissue were excluded. No patients received anti-EGFR containing anticancer therapy, at any time. Median mutation rate was 40% and was adopted as cut-off. The primary and secondary endpoints were PFS and OS respectively. Results: At univariate analysis, K-Ras mutation rate higher than 40% was significantly associated with lower PFS (7.3 vs 9.1 months; P < 0.0001) and OS (21 vs 31 months; P = 0.004). A multivariate model adjusted for age at diagnosis, site of origin of tumor tissue (primary vs metastases), referral center, number of metastatic sites, and first-line chemotherapy backbone, showed that K-Ras mutation rate remained a significant predictor of PFS and OS in the whole population. Discussion: Our data demonstrate an association between K-Ras mutation rate and prognosis in mCRC patients treated with bevacizumab-containing first-line therapy. These data deserve to be verified in an independent validation set.openVincenzi B.; Cremolini C.; Sartore-Bianchi A.; Russo A.; Mannavola F.; Perrone G.; Pantano F.; Loupakis F.; Rossini D.; Ongaro E.; Bonazzina E.; Dell'Aquila E.; Imperatori M.; Zoccoli A.; Bronte G.; Maglio G.D.; Fontanini G.; Natoli C.; Falcone A.; Santini D.; Onetti-Muda A.; Siena S.; Tonini G.; Aprile G.Vincenzi, B.; Cremolini, C.; Sartore-Bianchi, A.; Russo, A.; Mannavola, F.; Perrone, G.; Pantano, F.; Loupakis, F.; Rossini, D.; Ongaro, E.; Bonazzina, E.; Dell'Aquila, E.; Imperatori, M.; Zoccoli, A.; Bronte, G.; Maglio, G. D.; Fontanini, G.; Natoli, C.; Falcone, A.; Santini, D.; Onetti-Muda, A.; Siena, S.; Tonini, G.; Aprile, G

New investigations on the 32S(3He,d)33Cl reaction at 9.6 MeV bombarding energy

The 32S(3He,d)33Cl one-proton transfer reaction is a powerful tool to investigate the spectroscopy of low-lying states in the proton-rich 33Cl nucleus. However, the extraction of firm differential cross-section data at various angles to benchmark and constrain theoretical models is made challenging by the presence of competitive reactions on target contaminants. In this paper we report on arecent measurement using a new generation hodoscope of silicon detectors, capable to detect and identify emitted deuterons down to energies of the order of 2 MeV. The high angular segmentation of our hodoscope combined with a suitable target to control possible contaminants, allowed to unambiguously disentangle the contribution of various states in 33Cl, in particular the 2.352 MeV state lying just few tens of keV above the proton separation energy

Prognostic and predictive role of neutrophil/lymphocytes ratio in metastatic colorectal cancer: a retrospective analysis of the TRIBE study by GONO.

Background Neutrophil/lymphocyte ratio (NLR), defined as absolute neutrophils count divided by absolute lymphocytes count, has been reported as poor prognostic factor in several neoplastic diseases but only a few data are available about unresectable metastatic colorectal cancer (mCRC) patients (pts). The aim of our study was to evaluate the prognostic and predictive role of NLR in the TRIBE trial. Patients and methods Pts enrolled in TRIBE trial were included. TRIBE is a multicentre phase III trial randomizing unresectable and previously untreated mCRC pts to receive FOLFOXIRI or FOLFIRI plus bevacizumab. A cut-off value of 3 was adopted to discriminate pts with low (NLR < 3) versus high (NLR ≥ 3) NLR, as primary analysis. As secondary analysis, NLR was treated as an ordinal variable with three levels based on terciles distribution. Results NLR at baseline was available for 413 patients. After multiple imputation at univariate analysis, patients with high NLR had significantly shorter progression-free survival (PFS) [hazard ratio (HR) 1.27 (95% CI 1.05-1.55), P = 0.017] and overall survival (OS) [HR 1.56 (95% CI 1.25-1.95), P < 0.001] than patients with low NLR. In the multivariable model, NLR retained a significant association with OS [HR 1.44 (95% CI 1.14-1.82), P = 0.014] but not with PFS [HR 1.18 (95% CI 0.95-1.46), P = 0.375]. No interaction effect between treatment arm and NLR was evident in terms of PFS (P for interaction = 0.536) or OS (P for interaction = 0.831). Patients with low [HR 0.84 (95% CI 0.64-1.08)] and high [HR 0.73 (95% CI 0.54-0.97)] NLR achieved similar PFS benefit from the triplet and consistent results were obtained in terms of OS [HR 0.83 (95% CI 0.62-1.12) for low NLR; HR 0.82 (95% CI 0.59-1.12) for high NLR]. Conclusion This study confirmed the prognostic role of NLR in mCRC pts treated with bevacizumab plus chemotherapy in the first line, showing the worse prognosis of pts with high NLR. The advantage of the triplet is independent of NLR at baseline

The 10B(p,α)7Be S(E)-factor from 5 keV to 1.5 MeV using the Trojan Horse Method

The 10 B(p, α ) 7 Be reaction is the main responsible for the 10 B destruction in stellar interior [1]. In such environments this p-capture process occurs at a Gamow energy of 10 keV and takes places mainly through a resonant state (Ex = 8.701 MeV) of the compound 11 C nucleus. Thus a resonance right in the region of the Gamow peak is expected to significantly influence the behavior of the astrophysical S(E)-factor. The 10 B(p, α ) 7 Be reaction was studied via the Trojan Horse Method (THM) applied to the 2 H( 10 B, α 7 Be)n in order to extract the astrophysical S(E)-factor in a wide energy range from 5 keV to 1.5 MeV