Preface: Oceanographic processes on the continental shelf: observations and modeling

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Modified Gravity Away from a Λ\LambdaCDM Background

Within the effective field theory approach to cosmic acceleration, the background expansion can be specified separately from the gravitational modifications. We explore the impact of modified gravity in a background different from a cosmological constant plus cold dark matter ($\Lambda$CDM) on the stability and cosmological observables, including covariance between gravity and expansion parameters. In No Slip Gravity the more general background allows more gravitational freedom, including both positive and negative Planck mass running. We examine the effects on cosmic structure growth, as well as showing that a viable positive integrated Sachs-Wolfe effect crosscorrelation easily arises from this modified gravity theory. Using current data we constrain parameters with a Monte Carlo analysis, finding a maximum running $|\alpha_M|\lesssim 0.03$. We provide the modified {\tt hi\_class} code publicly on GitHub, now enabling computation and inclusion of the redshift space distortion observable $f\sigma_8$ as well as the No Slip Gravity modifications.Comment: 14 pages, 13 figures. Matches published version in JCAP, LCDM discussion adde

Heavy-Fermions in LiV2O4: Kondo-Compensation vs. Spin-Liquid Behavior?

7Li NMR measurements were performed in the metallic spinel LiV2O4. The temperature dependencies of the line width, the Knight shift and the spin-lattice relaxation rate were investigated in the temperature range 30 mK < T < 280 K. For temperatures T < 1 K we observe a spin-lattice relaxation rate which slows down exponentially. The NMR results can be explained by a spin-liquid behavior and the opening of a spin gap of the order 0.6 K

Potential agnostic role of BRCA alterations in patients with several solid tumors: One for all, all for one?

Germline BRCA1/2 alterations in the Homologous Recombination (HR) pathway are considered as main susceptibility biomarkers to Hereditary Breast and Ovarian Cancers (HBOC). The modern molecular biology technologies allowed to characterize germline and somatic BRCA1/2 alterations in several malignancies, broadening the landscape of BRCA1/2-alterated tumors. In the last years, BRCA genetic testing, beyond the preventive value, also assumed a predictive and prognostic significance for patient management. The approval of molecules with agnostic indication is leading to a new clinical model, defined "mutational". Among these drugs, the Poly (ADP)-Ribose Polymerase inhibitors (PARPi) for BRCA1/2-deficient tumors were widely studied leading to increasing therapeutic implications. In this Review we provided an overview of the main clinical studies describing the association between BRCA-mutated tumors and PARPi response, focusing on the controversial evidence about the potential agnostic indication based on BRCA1/2 alterations in several solid tumors

Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel testing: looking over the hedge

Background: Hereditary breast cancer (BC), ovarian cancer (OC), and pancreatic cancer (PC) are the major BRCA-associated tumours. However, some BRCA1/2-wild-type (wt) patients with a strong personal and/or family history of cancer need a further genetic testing through a multi-gene panel containing other high- and moderate-risk susceptibility genes. Patients and methods: Our study was aimed to assess if some BC, OC, or PC patients should be offered multi-gene panel testing, based on well-defined criteria concerning their personal and/or family history of cancer, such as earliness of cancer onset, occurrence of multiple tumours, or presence of at least two or more affected first-degree relatives. For this purpose, 205 out of 915 BC, OC, or PC patients, resulted negative for BRCA1/2 and with significant personal and/or family history of cancer, were genetically tested for germline pathogenic or likely pathogenic variants (PVs/LPVs) in genes different from BRCA1/2. Results: Our investigation revealed that 31 (15.1%) out of 205 patients harboured germline PVs/LPVs in no-BRCA genes, including PALB2, CHEK2, ATM, MUTYH, MSH2, and RAD51C. Interestingly, in the absence of an analysis conducted through multi-gene panel, a considerable percentage (15.1%) of PVs/LPVs would have been lost. Conclusions: Providing a multi-gene panel testing to BRCA1/2-wt BC/OC/PC patients with a strong personal and/or family history of cancer could significantly increase the detection rates of germline PVs/LPVs in other cancer predisposition genes beyond BRCA1/2. The use of a multi-gene panel testing could improve the inherited cancer risk estimation and clinical management of patients and unaffected family members

Prevalence and Spectrum of Germline BRCA1 and BRCA2 Variants of Uncertain Significance in Breast/Ovarian Cancer: Mysterious Signals From the Genome

About 10–20% of breast/ovarian (BC/OC) cancer patients undergoing germline BRCA1/2 genetic testing have been shown to harbor Variants of Uncertain Significance (VUSs). Since little is known about the prevalence of germline BRCA1/2 VUS in Southern Italy, our study aimed at describing the spectrum of these variants detected in BC/OC patients in order to improve the identification of potentially high-risk BRCA variants helpful in patient clinical management. Eight hundred and seventy-four BC or OC patients, enrolled from October 2016 to December 2020 at the “Sicilian Regional Center for the Prevention, Diagnosis and Treatment of Rare and Heredo-Familial Tumors” of University Hospital Policlinico “P. Giaccone” of Palermo, were genetically tested for germline BRCA1/2 variants through Next-Generation Sequencing analysis. The mutational screening showed that 639 (73.1%) out of 874 patients were BRCA-w.t., whereas 67 (7.7%) were carriers of germline BRCA1/2 VUSs, and 168 (19.2%) harbored germline BRCA1/2 pathogenic/likely pathogenic variants. Our analysis revealed the presence of 59 different VUSs detected in 67 patients, 46 of which were affected by BC and 21 by OC. Twenty-one (35.6%) out of 59 variants were located on BRCA1 gene, whereas 38 (64.4%) on BRCA2. We detected six alterations in BRCA1 and two in BRCA2 with unclear interpretation of clinical significance. Familial anamnesis of a patient harboring the BRCA1-c.3367G&gt;T suggests for this variant a potential of pathogenicity, therefore it should be carefully investigated. Understanding clinical significance of germline BRCA1/2 VUS could improve, in future, the identification of potentially high-risk variants useful for clinical management of BC or OC patients and family members

Goal-Driven Structured Argumentation for Patient Management in a Multimorbidity Setting

We use computational argumentation to both analyse and generate solutions for reasoning in multimorbidity about consistent recommendations, according to different patient-centric goals. Reasoning in this setting carries a complexity related to the multiple variables involved. These variables reflect the co-existing health conditions that should be considered when defining a proper therapy. However, current Clinical Decision Support Systems (CDSSs) are not equipped to deal with such a situation. They do not go beyond the straightforward application of the rules that build their knowledge base and simple interpretation of Computer-Interpretable Guidelines (CIGs). We provide a computational argumentation system equipped with goal-seeking mechanisms to combine independently generated recommendations, with the ability to resolve conflicts and generate explanations for its results. We also discuss its advantages over and relation to Multiple-criteria Decision-making (MCDM) in this particular setting.- (undefined

Mediterranean ocean colour Level 3 operational multi-sensor processing

The Mediterranean near-real-time multi-sensor processing chain has been set up and is operational in the framework of the Copernicus Marine Environment Monitoring Service (CMEMS). This work describes the main steps operationally performed to enable single ocean colour sensors to enter the multi-sensor processing applied to the Mediterranean Sea by the Ocean Colour Thematic Assembly Centre within CMEMS. Here, the multi-sensor chain takes care of reducing the inter-sensor bias before data from different sensors are merged together. A basin-scale in situ bio-optical dataset is used both to fine tune the algorithms for the retrieval of phytoplankton chlorophyll and the attenuation coefficient of light, Kd, and to assess the uncertainty associated with them. The satellite multi-sensor remote sensing reflectance spectra agree better with the in situ observations than those of the single sensors. Here, we demonstrate that the operational multi-sensor processing chain compares sufficiently well with the historical in situ datasets to also confidently be used for reprocessing the full data time series.</p

Goldstones in Diphotons

We study the conditions for a new scalar resonance to be observed first in diphotons at the LHC Run-2. We focus on scenarios where the scalar arises either from an internal or spacetime symmetry broken spontaneously, for which the mass is naturally below the cutoff and the low-energy interactions are fixed by the couplings to the broken currents, UV anomalies, and selection rules. We discuss the recent excess in diphoton resonance searches observed by ATLAS and CMS at 750 GeV, and explore its compatibility with other searches at Run-1 and its interpretation as Goldstone bosons in supersymmetry and composite Higgs models. We show that two candidates naturally emerge: a Goldstone boson from an internal symmetry with electromagnetic anomalies, and the scalar partner of the Goldstone of supersymmetry breaking: the sgoldstino. The dilaton from conformal symmetry breaking is instead disfavoured by present data, in its minimal natural realization.Comment: 18 pages + refs, 2 figures. v2: typos corrected, references added, discussions extended and three new plots. Conclusion unchanged. v3: published versio

Not all KIT 557/558 codons mutations have the same prognostic influence on recurrence-free survival: breaking the exon 11 mutations in gastrointestinal stromal tumors (GISTs)

Background: Although the gastrointestinal stromal tumor (GIST) genotype is not currently included in risk-stratification systems, a growing body of evidence shows that the pathogenic variant (PV) type and codon location hold a strong prognostic influence on recurrence-free survival (RFS). This information has particular relevance in the adjuvant setting, where an accurate prognostication could help to better identify high-risk tumors and guide clinical decision-making. Materials and Methods: Between January 2005 and December 2020, 96 patients with completely resected GISTs harboring a KIT proto-oncogene receptor tyrosine kinase (KIT) exon 11 PV were included in the study. We analyzed the type and codon location of the PV according to clinicopathological characteristics and clinical outcome; the metastatic sites in relapsed patients were also investigated. Results: Tumors harboring a KIT exon 11 deletion or deletion/insertion involving the 557 and/or 558 codons, showed a more aggressive clinical behavior compared with tumors carrying deletion/deletion/insertion in other codons, or tumors with duplication/insertion/single-nucleotide variant (SNV) (7-year RFS: 50% versus 73.1% versus 88.2%, respectively; p &lt; 0.001). Notably, among 18 relapsed patients with 557 and/or 558 deletion or deletion/insertion, 14 patients (77.8%) harbored deletions simultaneously involving 557 and 558 codons, while only 4 patients (22.2%) harbored deletions involving only 1 of the 557/558 codons. Thus, when 557 or 558 deletions occurred separately, the tumor showed a prognostic behavior similar to the GIST carrying deletions outside the 557/558 position. Remarkably, patients with GISTs stratified as intermediate risk, but carrying the 557/558 deletion, showed a similar outcome to the high-risk patients with tumors harboring deletions in codons other than 557/558, or duplication/insertion/SNV. Conclusion: Our data support the inclusion of the PV type and codon location in routine risk prediction models, and suggest that intermediate-risk patients whose GISTs harbor 557/558 deletions may also need to be treated with adjuvant imatinib like the high-risk patients