Evolution of the Po–Alpine River System during the Last 45 Ky Inferred from Stratigraphic and Compositional Evidence (Ostiglia, Northern Italy)

The stratigraphic and compositional study of three sediment cores recovered close to the Po River near Ostiglia provides clues on changes in fluvial dynamics at the transition from the last glacial to the present interglacial. Upper Pleistocene units are dominated by sands with high content in volcanic lithics, denoting high sediment supply from the south-Alpine fluvio-glacial tributary system. The Early–Mid Holocene unit, peat-rich and barren in fluvial sands, results from low sediment supply and waterlogging, encompassing the maximum marine ingression. The Late Holocene unit, characterized by fluvial-channel sands with lower content in volcanics and relatively abundant metamorphic lithics, records the Po River sedimentation since the Late Bronze Age. Late Holocene sands show a lower content in siliciclastic lithic fragments (supplied mainly by Apennine tributaries) compared to modern Po River sands. This distinctive composition could reflect the diversion of Apennine sediments into a southern Po River branch during the Late Bronze Age and into an Apennine collector flowing south of Ostiglia during Roman times and the Middle Ages. The integrated stratigraphic-compositional methods used in this study permitted to reconstruct the major climate-related changes in sediment dispersal and may be potentially applied to other alluvial and coastal settings

Patient safety culture in Italian out-ofhours primary care service: a national cross-sectional survey study

Background: Out-of-hours (OOH) services in Italy provide >10 million consultations every year. To the authors' knowledge, no data on patient safety culture (PSC) have been reported. Aim: To assess PSC in the Italian OOH setting. Design & setting: National cross-sectional survey using the Safety Attitudes Questionnaire — Ambulatory Version (SAQ-AV). Method: The SAQ-AV was translated into Italian and distributed in a convenience sample of OOH doctors in 2015. Answers were collected anonymously by Qualtrics. Stata (version 14) was used to estimate Cronbach's alpha, perform exploratory and confirmatory factor analysis, correlate items to doctors' characteristics, and to do item descriptive analysis. Results: Overall, 692 OOH doctors were contacted, with a 71% response rate. In the exploratory factor analysis (EFA), four factors were identified: Communication and Safety Climate (14 items); Perceptions of Management (eight items); Workload and Clinical Risk (six items); and Burnout Risk (four items). These four factors accounted for 68% of the total variance (Kaiser-Meyer-Olkin [KMO] statistic = 0.843). Cronbach's alpha ranged from 0.710-0.917. OOH doctors were often dissatisfied with their job; there is insufficient staff to provide optimal care and there is no training or supervision for new personnel and family medicine trainees. Service managers are perceived as distant, with particular issues concerning the communication between managers and OOH doctors. A large proportion of OOH doctors (56.8%) state that they do not receive adequate support. Conclusion: These findings could be useful for informing policies on how to improve PSC in Italian OOH service

Nestin expression associates with poor prognosis and triple negative phenotype in locally advanced (T4) breast cancer

Nestin, an intermediate filament protein, has traditionally been noted for its importance as a neural stem cell marker. However, in recent years, expression of nestin has shown to be associated with general proliferation of progenitor cell populations within neoplasms. There is no reported study addressing nestin expression in T4 breast cancer patients. Thus, the aim of the present study was to investigate, through immunohistochemistry, the expression and distribution of nestin in T4 breast cancer, in order to determine its association with clinical and pathological parameters as well as with patients' outcome. Nestin was detectable in tumoral cells and in endothelial cells of blood microvessels, and it is significantly expressed in triple-negative and in inflammatory breast cancer (IBC) subgroups of T4 breast tumours. The Kaplan-Meier analysis showed that the presence of nestin in tumoral cells significantly predicted poor prognosis at 5-years survival (P=0.02) and with borderline significance at 10-years of survival (P=0.05) in T4 breast cancer patients. On the basis of these observations, we speculate that nestin expression may characterize tumours with an aggressive clinical behavior, suggesting that the presence of nestin in tumoral cells and vessels may be considered an important factor that leads to a poor prognosis. Further studies are awaited to define the biological role of nestin in the etiology of these subgroups of breast cancers

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

Pulmonary stretch and lung mechanotransduction: implications for progression in the fibrotic lung.

Lung fibrosis results from the synergic interplay between regenerative deficits of the alveolar epithelium and dysregulated mechanisms of repair in response to alveolar and vascular damage, followed by progressive fibroblast and myofibroblast proliferation and excessive deposition of extracellular matrix. The increased parenchymal stiffness of fibrotic lungs significantly affects respiratory mechanics, making the lung more fragile and prone to non-physiological stress during spontaneous breathing and mechanical ventilation. Given their parenchymal inhomogeneity, fibrotic lungs may display an anisotropic response to mechanical stresses with different regional deformations (micro-strain). This behavior is not described by the standard stress-strain curve but follows the mechano-elastic models of “squishy balls”, where the elastic limit can be reached due to the excessive deformation of parenchymal areas with normal elasticity, surrounded by inelastic fibrous tissue or collapsed induration areas, which tend to protrude outside the fibrous ring. Increasing evidence has shown that non-physiological mechanical forces applied to fibrotic lungs with as34 sociated abnormal mechanotransduction could favor the progression of pulmonary fibrosis. With this review we aim at summarizing the state of the art on the relation between mechanical forces acting on the lung and biological response in pulmonary fibrosis, with a focus on the progression of damage in the fibrotic lung during spontaneous breathing and assisted ventilatory support

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

n/

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