Many-body correlations in a multistep variational approach

We discuss a multistep variational approach for the study of many-body correlations. The approach is developed in a boson formalism (bosons representing particle-hole excitations) and based on an iterative sequence of diagonalizations in subspaces of the full boson space. Purpose of these diagonalizations is that of searching for the best approximation of the ground state of the system. The procedure also leads us to define a set of excited states and, at the same time, of operators which generate these states as a result of their action on the ground state. We examine the cases in which these operators carry one-particle one-hole and up to two-particle two-hole excitations. We also explore the possibility of associating bosons to Tamm-Dancoff excitations and of describing the spectrum in terms of only a selected group of these. Tests within an exactly solvable three-level model are provided.Comment: 24 pages, 6 figures, to appear in Phys. Rev.

Coexistence of quartets and pairs in even-even N>ZN>Z nuclei

We analyse the structure of the ground states of even-even $N>Z$ nuclei with nucleons moving in the same major shell and interacting via realistic two-body forces of shell-model type. We express the ground states of these nuclei as a product of a quartet term, which represents the $N = Z$ subsystem, and a pair condensate built with the excess neutrons. The accuracy of this approximation is discussed for nuclei with valence nucleons in the $sd$ and $pf$ major shells.Comment: 9 pages, 4 figure

Multipair approach to pairing in nuclei

The ground state of a general pairing Hamiltonian for a finite nuclear system is constructed as a product of collective, real, distinct pairs. These are determined sequentially via an iterative variational procedure that resorts to diagonalizations of the Hamiltonian in restricted model spaces. Different applications of the method are provided that include comparisons with exact and projected BCS results. The quantities that are examined are correlation energies, occupation numbers and pair transfer matrix elements. In a first application within the picket-fence model, the method is seen to generate the exact ground state for pairing strengths confined in a given range. Further applications of the method concern pairing in spherically symmetric mean fields and include simple exactly solvable models as well as some realistic calculations for middle-shell Sn isotopes. In the latter applications, two different ways of defining the pairs are examined: either with J=0 or with no well-defined angular momentum. The second choice reveals to be more effective leading, under some circumstances, to solutions that are basically exact.Comment: To appear in Physical Review

AB0563 AORTIC ROOT DILATION IN ASSOCIATED WITH THE REDUCTION OF CAPILLARY DENSITY OBSERVED AT NAILFOLD CAPILLAROSCOPY IN SSC PATIENTS

Background:Systemic sclerosis (SSc) in a chronic autoimmune disease characterized by endothelial dysfunction and diffuse microangiopathy, leading to tissue ischemia and inducing fibrosis of skin and visceral organs. Furthermore, it was demonstrated the impairment of wall elasticity of large-medium vessels, such as aorta and its branches (1). SSc-related microangiopathy of vasa vasorum of the aortic wall could also be supposed. However no data on this hypothesis are available in literature.SSc microangiopathy may be easily studied at the nailfold by means of videocapillaroscopy. Indeed, capillaroscopic findings are representative of the microvascular damage caused by SSc troughout the body.Objectives:we aimed to investigate the presence of aortic root dilation, classical sign of aortic wall damage, in a cohort of SSc patients, and to correlate these findings with the capillaroscopic patterns (early, active, and late, according to Cutolo's classification (2)).Methods:we recruited 125 SSc patients (M/F: 14/111, mean age 55+/-12.7 years, median disease duration 11 years) in 3 Rheumatology Centres in Sicily, Italy, from January to December 2019.Transthoracic echocardiogram with aortic root diameter measurement was carried out in all patients. Moreover, videocapillaroscopy with identification of early, active, or late SSc patterns was performed in the whole case series. Patients with early SSc pattern formed the subgroup 1, while those with the active or late patterns (both characterized by the reduction of capillary density) the subgroup 2.Results:we identified 8 (6.4%) SSc patients with aortic root dilation (diameter > 35 mm). Their age and their frequencies of cardiovascular risk factors were similar to the whole series. Moreover, videocapillaroscopy showed 62 (49.6%) early, 47 (37.6%) active, and 16 (12.8%) late SSc patterns.Aortic root dilation was observed in only one patient in the subgroup 1 (1/62, 1.6%), and in 7 cases of the subgroup 2 (7/63, 11.1%); p=0.03.Conclusion:in this multicentre study, we found that aortic root dilation is significantly associated with the reduction of capillary density at nailfold capillaroscopy (active or late SSc patterns). On the basis of these findings, we might argue that SSc-related microangiopathy of vasa vasorum could contribute to aortic wall damage, at least in a subset of SSc patients.References:[1]Bartoloni E, Pucci G, Cannarile F, Battista F, Alunno A, Giuliani M, Cafaro G, Gerli R, Schillaci G. Central hemodynamics and arterial stiffness in systemic sclerosis. Hypertension 2016; 68:1504-1511. 2.Cutolo M, Matucci-Cerinic M. Nailfold capillaroscopy and classification criteria for systemic sclerosis. Clin Exp Rheumatol 2007; 25:663-665.Disclosure of Interests:Michele Colaci: None declared, Ylenia Dal Bosco: None declared, Claudia Schinocca: None declared, Maria Letizia Aprile: None declared, Giuliana Guggino Grant/research support from: Pfizer, Celgene, Speakers bureau: Celgene, Sandoz, Pfizer, Ilenia De Andres: None declared, Alessandra Azzurra Russo: None declared, Gianluca Sambataro: None declared, Domenico Sambataro: None declared, Lorenzo Malatino: None declare

BAFF/APRIL pathway in Sjögren syndrome and systemic lupus erythematosus: relationship with chronic inflammation and disease activity

Objectives: BAFF and APRIL belong to the tumor necrosis factor (TNF) superfamily and are crucial for the survival, maturation, and differentiation of B cells. Aim of the study is to evaluate BAFF and APRIL in patients affected by Sjögren syndrome (SS) and systemic lupus erythematosus (SLE). Methods: Sixty patients, (40 SLE, 20 SS) and 20 healthy subjects were enrolled in this study. All subjects were evaluated for laboratory data (ESR, CRP, immunoglobulin G, A and M, complement fragments C3 and C4, LDH, beta2microglobulin, serum levels of rheumatoid factor), autoantibodies (ANA; ENA-SSA, -SSB, -Sm) and lymphocytes subpopulations. For patients, disease activity and damage indexes were assessed with the use of SLEDAI and SLICC and SSDAI and SSDDI for SLE and SS, respectively. BAFF and APRIL were determined by commercial sandwich ELISA kit (R&D Systems, Bender MedSystem). Statistical analysis has been performed with software Prism (Graphpad Instat, version 5.00). Results: APRIL levels were higher among SLE and SS patients compared to controls (p<0.0001, and p0.0001, respectively). BAFF levels in SLE were significantly higher than in SS (p<0.0001). We found higher BAFF levels in SLE and SS compared to controls (p<0.0001). Among SLE patients APRIL correlated with SLEDAI (r 0.3, p 0.04), SLICC (r 0.5,p 0.001), ESR (r 0.3, p 0.005) and CRP (r 0.4, p 0.02). Among SS patients APRIL correlated with SSDAI (r 0.4, p 0.02), SSDDI (r 0.4, p0.01), IgG (r 0.5, p0.01), ESR (r 0.6, p 0.01), CRP (r 0.6, p 0.02) and CD19 B lymphocytes absolute count (r 0.4, p 0.04); BAFF correlated with SSDDI (r 0.7, p 0.004) and CD19 B lymphocytes absolute count (r 0.5, p 0.04). Conclusions: In this study we showed a correlation between disease activity, damage indexes and BAFF/APRIL levels in SLE and SS patients suggesting a role in the strong activation of the immune system in patients with active disease

Second- and Third-Line Chemotherapy in Advanced Gastric Cancer: a Real-Life Clinical Picture

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Age-related alterations in default mode network: Impact on working memory performance

The default mode network (DMN) is a set of functionally connected brain regions which shows deactivation (task-induced deactivation, TID) during a cognitive task. Evidence shows an age-related decline in task-load-related modulation of the activity within the DMN during cognitive tasks. However, the effect of age on the functional coupling within the DMN and their relation to cognitive performance has hitherto been unexplored. Using functional magnetic resonance imaging, we investigated functional connectivity within the DMN in older and younger subjects during a working memory task with increasing task load. Older adults showed decreased connectivity and ability to suppress low frequency oscillations of the DMN. Additionally, the strength of the functional coupling of posterior cingulate (pCC) with medial prefrontal cortex (PFC) correlated positively with performance and was lower in older adults. pCC was also negatively coupled with task-related regions, namely the dorsolateral PFC and cingulate regions. Our results show that in addition to changes in canonical task-related brain regions, normal aging is also associated with alterations in the activity and connectivity of brain regions within the DMN. These changes may be a reflection of a deficit in cognitive control associated with advancing age that results in deficient resource allocation to the task at hand

New Frontiers in the Treatment of Patients with HER2+ Cancer and Brain Metastases: Is Radiotherapy Always Useful?

Brain metastases (BM) pose a significant challenge in the management of HER2+ breast cancer since almost 50% of patients with HER2+ breast cancer develop brain tumors. The complex process of brain metastases involves genetic mutations, adaptations and mechanisms to overcome the blood–brain barrier. While radiotherapy is still fundamental in local therapy, its use is associated with cognitive adverse effects and limited long-term control, necessitating the exploration of alternative treatments. Targeted therapies, including tyrosine kinase inhibitors, monoclonal antibodies, and antibody–drug conjugates, offer promising options for HER2+ breast cancer patients with BM. Clinical trials have demonstrated the efficacy of these agents in controlling tumor growth and improving patient outcomes, posing the question of whether radiotherapy is always the unique choice in treating this cancer. Ongoing research into novel anti-HER2 antibodies and innovative combination therapies holds promise for advancing treatment outcomes and enhancing patient care in this clinical scenario. This narrative review provides a comprehensive overview of traditional medical treatments, molecularly targeted therapy and investigational agents in the management of HER2+ breast cancer with BM, highlighting the evolving landscape and potential future directions in treatment strategies to improve patient survival and quality of life

Extension of random-phase approximation preserving energy weighted sum rules: an application to a 3-level Lipkin model

A limitation common to all extensions of random-phase approximation including only particle-hole configurations is that they violate to some extent the energy weighted sum rules. Considering one such extension, the improved RPA (IRPA), already used to study the electronic properties of metallic clusters, we show how it can be generalized in order to eliminate this drawback. This is achieved by enlarging the configuration space, including also elementary excitations corresponding to the annihilation of a particle (hole) and the creation of another particle (hole) on the correlated ground state. The approach is tested within a solvable 3-level model.Comment: 2 figure

Contribution of pulmonary function tests (PFTs) to the diagnosis and follow up of connective tissue diseases

Introduction: Connective Tissue Diseases (CTDs) are systemic autoimmune conditions characterized by frequent lung involvement. This usually takes the form of Interstitial Lung Disease (ILD), but Obstructive Lung Disease (OLD) and Pulmonary Artery Hypertension (PAH) can also occur. Lung involvement is often severe, representing the first cause of death in CTD. The aim of this study is to highlight the role of Pulmonary Function Tests (PFTs) in the diagnosis and follow up of CTD patients. Main body: Rheumatoid Arthritis (RA) showed mainly an ILD with a Usual Interstitial Pneumonia (UIP) pattern in High-Resolution Chest Tomography (HRCT). PFTs are able to highlight a RA-ILD before its clinical onset and to drive follow up of patients with Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DL CO ). In the course of Scleroderma Spectrum Disorders (SSDs) and Idiopathic Inflammatory Myopathies (IIMs), DL CO appears to be more sensitive than FVC in highlighting an ILD, but it can be compromised by the presence of PAH. A restrictive respiratory pattern can be present in IIMs and Systemic Lupus Erythematosus due to the inflammatory involvement of respiratory muscles, the presence of fatigue or diaphragm distress. Conclusions: The lung should be carefully studied during CTDs. PFTs can represent an important prognostic tool for diagnosis and follow up of RA-ILD, but, on their own, lack sufficient specificity or sensitivity to describe lung involvement in SSDs and IIMs. Several composite indexes potentially able to describe the evolution of lung damage and response to treatment in SSDs are under investigation. Considering the potential severity of these conditions, an HRCT jointly with PFTs should be performed in all new diagnoses of SSDs and IIMs. Moreover, follow up PFTs should be interpreted in the light of the risk factor for respiratory disease related to each disease