Structural control on the directional amplification of seismic noise (Campo Imperatore, central Italy)

Abstract Seismic signals propagating across a fault may yield information on the internal structure of the fault zone. Here we have assessed the amplification of seismic noise (i.e., ambient vibrations generated by natural or anthropogenic disturbances) across the Vado di Corno Fault (Campo Imperatore, central Italy). The fault zone is considered as an exhumed analogue of the normal faults activated during the L'Aquila 2009 earthquake sequence. Detailed structural geological survey of the footwall block revealed that the fault zone is highly anisotropic and is affected by a complex network of faults and fractures with dominant WNW–ESE strike. We measured seismic noise with portable seismometers along a ∼500 m long transect perpendicular to the average fault strike. Seismic signals were processed calculating the horizontal-to-vertical spectral ratios and performing wavefield polarization analyses. We found a predominant NE–SW to NNE–SSW (i.e., ca. perpendicular to the average strike of the fault-fracture network) amplification of the horizontal component of the seismic waves. Numerical simulations of earthquake-induced ground motions ruled out the role of topography in controlling the polarization and the amplitude of the waves. Therefore, the higher seismic noise amplitude observed in the fault-perpendicular direction was related to the measured fracture network and the resulting stiffness anisotropy of the rock mass. These observations open new perspectives in using measures of ambient seismic noise, which are fast and inexpensive, to estimate the dominant orientation of fracture networks within fault zones

Submarine Geomorphology of the Southwestern Sardinian Continental Shelf (Mediterranean Sea): Insights into the Last Glacial Maximum Sea-Level Changes and Related Environments

During the lowstand sea-level phase of the Last Glacial Maximum (LGM), a large part of the current Mediterranean continental shelf emerged. Erosional and depositional processes shaped the coastal strips, while inland areas were affected by aeolian and fluvial processes. Evidence of both the lowstand phase and the subsequent phases of eustatic sea level rise can be observed on the continental shelf of Sardinia (Italy), including submerged palaeo-shorelines and landforms, and indicators of relict coastal palaeo-environments. This paper shows the results of a high-resolution survey on the continental shelf off San Pietro Island (southwestern Sardinia). Multisensor and multiscale data\u2014obtained by means of seismic sparker, sub-bottom profiler chirp, multibeam, side scan sonar, diving, and uncrewed aerial vehicles\u2014made it possible to reconstruct the morphological features shaped during the LGM at depths between 125 and 135 m. In particular, tectonic controlled palaeo-cliffs affected by landslides, the mouth of a deep palaeo-valley fossilized by marine sediments and a palaeo-lagoon containing a peri-littoral thanatocenosis (18,983 \ub1 268 cal BP) were detected. The Younger Dryas palaeo-shorelines were reconstructed, highlighted by a very well preserved beachrock. The coastal paleo-landscape with lagoon-barrier systems and retro-littoral dunes frequented by the Mesolithic populations was reconstructed

Identification and characterization of ERV-W-like sequences in Platyrrhini species provides new insights into the evolutionary history of ERV-W in primates

Background: Endogenous Retroviruses (ERVs) constitute approximately 8% of every human genome and are relics of ancestral infections that affected the germ line cells. The ERV-W group contributed to primate physiology by providing an envelope protein (Syncytin-1) that has been adopted for placenta development in hominoids. Expression of Human ERV-W (HERV-W) sequences is investigated for a pathological role in various human diseases. Results: We previously characterized ERV-W group genomic sequences in human and non-human Catarrhini species. We now investigated ERV-W-like sequences in the parvorder Platyrrhini, especially regarding two species with complete genome assemblies, namely marmoset (Callithrix jacchus) and squirrel monkey (Saimiri boliviensis). We identified in both species proviral sequences, annotated as ERV1-1 in respective genome assemblies, sharing high sequence similarities with Catarrhini ERV-W. A total of 130 relatively intact proviruses from the genomes of marmoset and squirrel monkey were characterized regarding their structural and evolutionarily relationships with Catarrhini ERV-W elements. Platyrrhini ERV-W sequences share several structural features with Catarrhini ERV-W elements and are closely related phylogenetically with the latter as well as with other ERV-W-related gammaretrovirus-like ERVs. The ERV-W group colonized Platyrrhini primates of both Callitrichidae and Atelidae lineages, with provirus formations having occurred mostly between 25 and 15 mya. Two LTR subgroups were associated with monophyletic proviral bodies. A pre-gag region appears to be a sequence feature common to the ERV-W group: it harbors a putative intron sequence that is missing in some ERV-W loci, holding a putative ORF as well. The presence of a long pre-gag portion was confirmed among all gammaretroviral ERV analyzed, suggesting a role in the latter biology. It is noteworthy that, contrary to Catarrhini ERV-W, there was no evidence of L1-mediated mobilization for Platyrrhini ERV-W sequences. Conclusions: Our data establish that ERV-W is not exclusive to Catarrhini primates but colonized both parvorders of Simiiformes, providing further insight into the evolution of ERV-W and the colonization of primate genomes

Increased facial asymmetry in focal epilepsies associated with unilateral lesions

The epilepsies are now conceptualized as network disruptions: focal epilepsies are considered to have network alterations in the hemisphere of seizure onset, whilst generalized epilepsies are considered to have bi-hemispheric network changes. Increasingly, many epilepsies are also considered to be neurodevelopmental disorders, with early changes in the brain underpinning seizure biology. The development of the structure of the face is influenced by complex molecular interactions between surface ectoderm and underlying developing forebrain and neural crest cells. This influence is likely to continue postnatally, given the evidence of facial growth changes over time in humans until at least 18 years of age. In this case–control study, we hypothesized that people with lateralized focal epilepsies (i.e. unilateral network changes) have an increased degree of facial asymmetry, compared with people with generalized epilepsies or controls without epilepsy. We applied three-dimensional stereophotogrammetry and dense surface models to evaluate facial asymmetry in people with epilepsy, aiming to generate new tools to explore pathophysiological mechanisms in epilepsy. We analysed neuroimaging data to explore the correlation between face and brain asymmetry. We consecutively recruited 859 people with epilepsy attending the epilepsy clinics at a tertiary referral centre. We used dense surface modelling of the full face and signature analyses of three-dimensional facial photographs to analyse facial differences between 378 cases and 205 healthy controls. Neuroimaging around the time of the facial photograph was available for 234 cases. We computed the brain asymmetry index between contralateral regions. Cases with focal symptomatic epilepsy associated with unilateral lesions showed greater facial asymmetry compared to controls (P = 0.0001, two-sample t-test). This finding was confirmed by linear regression analysis after controlling for age and gender. We also found a significant correlation between duration of illness and the brain asymmetry index of total average cortical thickness (r = −0.19, P = 0.0075) but not for total average surface area (r = 0.06, P = 0.3968). There was no significant correlation between facial asymmetry and asymmetry of regional cortical thickness or surface area. We propose that the greater facial asymmetry in cases with focal epilepsy caused by unilateral abnormality might be explained by early unilateral network disruption, and that this is independent of underlying brain asymmetry. Three-dimensional stereophotogrammetry and dense surface modelling are a novel powerful phenotyping tool in epilepsy that may permit greater understanding of pathophysiology in epilepsy, and generate further insights into the development of cerebral networks underlying epilepsy, and the genetics of facial and neural development

Hormone Receptor-Positive/HER2-Positive Breast Cancer: Hormone Therapy and Anti-HER2 Treatment: An Update on Treatment Strategies

Hormone receptor (HR)-positive/HER2-positive breast cancer represents a distinct subtype expressing estrogen and progesterone receptors with an overexpression of HER2. Approximately 14% of female breast cancer cases are HER2-positive, with the majority being HR-positive. These tumors show a cross-talk between the hormonal and HER2 pathways; the interaction has implications for the treatment options for the disease. In this review, we analyze the biology of HR-positive/HER2-positive breast cancer and summarize the evidence concerning the standard of care options both in neoadjuvant/adjuvant settings and in advanced disease. Additionally, we focus on new trials and drugs for HR-positive/HER2-positive breast cancer and the new entity: HER2-low breast cancer

The Role of p53 Expression in Patients with RAS/BRAF Wild-Type Metastatic Colorectal Cancer Receiving Irinotecan and Cetuximab as Later Line Treatment

Background: Preclinical and clinical data indicate that p53 expression might modulate the activity of the epidermal growth factor receptor (EGFR), influencing response/resistance to anti-EGFR monoclonal antibodies. However, the association between p53 status and clinical outcome has not been clarified yet. Objective: In our study, we evaluated the role of p53 expression in patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC) receiving irinotecan/cetuximab in an exploratory and a validation cohort. Patients and Methods: p53 expression was analysed in patients with RAS/BRAF wild-type mCRC receiving second-line or third-line irinotecan/cetuximab. Survival distribution was assessed by the Kaplan–Meier method, while the log-rank test was used for survival comparison. Results: Among 120 patients with RAS/BRAF wild-type mCRC included in our analysis, 52 (59%) and 19 (59%) patients showed p53 overexpression in the exploratory and validation cohort, respectively. In the exploratory cohort, low p53 expression was correlated with better median progression-free survival (hazard ratio 0.39; p < 0.0001), median overall survival (hazard ratio: 0.23; p < 0.0001) and response rate (p < 0.0001). These results were confirmed by data of the validation cohort where we observed better median progression-free survival (hazard ratio: 0.48; p = 0.0399), median overall survival (hazard ratio: 0.26; p = 0.0027) and response rate (p =0.0007) in patients with p53 normal expression mCRC. Conclusions: In our study, p53 overexpression was associated with anti-EGFR treatment resistance in patients with RAS/BRAF WT mCRC, as confirmed in a validation cohort. Larger studies are needed to validate the role of p53 and investigate EGFR cross-talk in these patients

Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients

Regorafenib monotherapy is a potential option for metastatic colorectal cancer patients. However, the lack of predictive factors and the severe toxicities related to treatment have made its use in clinical practice challenging. Polymorphisms of VEGF and its receptor (VEGFR) genes might regulate angiogenesis and thus potentially influence outcome during anti-angiogenesis treatment such as regorafenib. Aim of our study was to evaluate the role of VEGF and VEGFR genotyping in determining clinical outcome for colorectal cancer patients receiving regorafenib. We retrospectively collected clinical data and samples (tumour or blood) of 138 metastatic colorectal cancer patients treated with regorafenib. We analysed the correlation of different VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs) with patients' progression-free survival (PFS) and overall survival (OS). Results from angiogenesis genotyping showed that only VEGF-A rs2010963 maintained an independent correlation with PFS and OS. Among clinical factors only ECOG PS was independently correlated with OS, whereas no correlation with PFS was evident. Grouping together those results allowed further patients stratification into 3 prognostic groups: favourable, intermediate and unfavourable. VEGF-A rs2010963 genotyping may represent an important tool for a more accurate selection of optimal candidates for regorafenib therap

From central to sentral (Serum angiogenesis central): Circulating predictive biomarkers to anti-VEGFR therapy

Background: In the last decade, a series of analyses failed to identify predictive biomarkers of resistance/susceptibility for anti-angiogenic drugs in metastatic colorectal cancer (mCRC). We conducted an exploratory preplanned analysis of serum pro-angiogenic factors (SErum aNgiogenesis-cenTRAL) in 72 mCRC patients enrolled in the phase II CENTRAL (ColorEctalavastiNTRiAlLdh) trial, with the aim to identify potential predictive factors for sensitivity/resistance to first line folinic acid-fluorouracil-irinotecan regimen (FOLFIRI) plus bevacizumab. Methods: First-line FOLFIRI/bevacizumab patients were prospectively assessed for the following circulating pro-angiogenic factors, evaluated with ELISA (enzyme-linked immunosorbent assay)-based technique at baseline and at every cycle: Vascular endothelial growth factor A (VEGF-A), hepatocyte growth factor (HGF), stromal derived factor-1 (SDF-1), placental derived growth factor (PlGF), fibroblast growth factor-2 (FGF-2), monocyte chemotactic protein-3 (MCP-3), interleukin-8 (IL-8). Results: Changes in circulating FGF-2 levels among different blood samples seemed to correlate with clinical outcome. Patients who experienced an increase in FGF-2 levels at the second cycle of chemotherapy compared to baseline, had a median Progression Free Survival (mPFS) of 12.85 vs. 7.57 months (Hazard Ratio—HR: 0.73, 95% Confidence Interval—CI: 0.43-1.27, p = 0.23). Similar results were seen when comparing FGF-2 concentrations between baseline and eight-week time point (mPFS 12.98 vs. 8.00 months, HR: 0.78, 95% CI: 0.46–1.33, p = 0.35). Conclusions: Our pre-planned, prospective analysis suggests that circulating FGF-2 levels’ early increase could be used as a marker to identify patients who are more likely to gain benefit from FOLFIRI/bevacizumab first-line therapy

p 291the distinctive study a biologically enriched phase ii study of second line folfiri aflibercept in prospectively stratified anti egfr resistant metastatic colorectal cancer patients with ras validated wild type status trial in progress

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