MICROPLASTICS, ALIEN SPECIES AND AMPHIBIAN MALE-SPECIFIC PREDATION IN RIVER OTTER DIET (LUTRA LUTRA). A STUDY OF TWO POPULATIONS IN THE TICINO VALLEY (NORTH ITALY) AND SILA MASSIF (SOUTH ITALY).

Abstract Distribution and diet of Eurasian otter (Lutra lutra) was studied in two different Italian areas: in the North (Ticino River) and in the South (streams from Sila Massif). The Ticino population derives from a reintroduction project performed by the two Park Autorities in the 90\u2019, while the Sila Massif population are probably the descendent of relictus populations. The Ticino population is characterised by few founders coming from European reproduction centers. The release, in 1997, of a pair of otters Lutra lutra, from the breeding enclosure centre of Cameri \u201cBosco Vedro\u201d (Novara) and after the escape during a flood of two adult and a cub in 1993 from the breeding centre \u201cLa Fagiana\u201d (Magenta), create a little vital otter nucleous in the valley. The survey performed in 2010 provideed a small range of otter activity (7 km near the breeding centre of Cameri), in 2012 an otter sighting has been recorded and in 2013 an individual has been found dead in Southern stretch of the Ticino River near Pavia, about 30 km downstream the release site. Seven years after the last monitoring, a new survey was performed along all the Ticino River. Status and distribution of the Ticino\u2019s otters showed a surprising evolution of its distribution. 101 feces samples were recorded in 16 stations on the 32 survayed (50%). Positive stations covered near the whole watercourse from Lake Maggiore to Pavia for a length of 100 km of river. In otter diet, the allochtonous european catfish (S. glanis) has been recorded in Italy for the first time. The high incidence of this species in the otter diet reflects its demographic explosion in Ticino River and suggests river otter such potential natural predator to control the exponential diffusion of this alien fish. To quantify the presence of S. glanis in the otter diet, morphometric equations were developed basing on 28 S. glanis speciemens, coming from the same area. Regression equations relate the known fish mass to skeletrical element dimension. Two diagnostic elements were selected starting from those found in otter stools: vertebrae and a basicranial bone. A second unexpected result found in otter feces from Ticino River was that, unfortunality, for the first time, spectroscopy analysis performed on some unknown remains in otter stool showed theirs correlation with microplastics. Probably the mustelid ingested these particles not by directly ingestion but through fish preyed. Among the multiple human pressures on aquatic ecosystems, the accumulation of plastic debris is an increasing environmental problem in marine and freshwater system. The transfer of microplastic pollution across trophic levels has been proven in marine ecosystems such between mussels and crabs. The similarity between ecological niches and feeding strategies for species in marine and freshwater environments would suggest that trophic transfer should also occur in freshwater ecosystems. 5 Considering toxicological problems related to additives release and adsorbed pollutants, this result rises a new treat for otter conservation, and certainly requires further studies. South Italy represent for Italian otter population the main core. Although in 20th century the mustelid suffered an important constriction of its range also here, recent works showed an expansion in this zone as elsewhere. The south Mediterranean area is a delicate ecological environment characterized by extreme seasonal variations in water flow with dry and harsh period in summer and torrential floods usually occuring in autumn and spring. This conditions could make the trophic resources and the river accessibility for otters highly fluctuating. Strategies for facing fluctuations in habitat accessibility and food resources are essential for the lifestyle of otter which is metabolically costly and strictly linked to aquatic habitats. We analysed the southern Italian range on 8 streams flowing from the Sila massif, and we found a stable and positive trend of the otter presence. 357 otter stools were found from 2014 utill 2017 principally in Savuto, Amato, Lese and Neto rivers. Diet analysis confirmed an increase of trophic diversity from northern to southern Europe with a high proportion of amphibian consumption. Usually diet analyses focuses on fish preys, while amphibians are lees detailed with only one or few categories. Little number of studies classified amphibians to the species level. The high presence of amphibians in the present study induced us to perform an accurate species and genus analysis. Osteological identification of amphibian remains allowed to ascertain otter predation on seven out of the 11 species recorded for the study area. Particularly interesting was the discovery of newts in otters\u2019 feces for the presence of the powerful neurotoxin in skin secretion of these urodelans. Furthermore, osteological analysis provided a male-biased predation by otter on Anurans. Stool analysis provided further interesting insights on the feeding behavior of otter. By the analysis of unknown remains performed with Attenuated Total Reflectance (ATR-FT-IR) spectroscopy, the 61% of these materials showed peaks typical of protein and high correlations with amphibian eggs. According to other studies, results of this thesis showed that Italian otter populations are following a positive trend of expansion both in the North than in the South. The diet results highlighted the plastic feeding behavior of otter, through which otters feed on the most accessible prey: alien species in the North and amphibians, even newts, in the South, with a male specific predation. The presence of amphibian eggs in otter stools may derive from the ingestion of females before spawning

Fragility curves for reinforced concrete frames characterised by different regularity

This paper presents a comparison between fragility curves developed for regular and non-regular reinforced frames. Three 3D reinforced concrete multi-story frames characterised by different regularity are analysed. These fragility curves are developed through the “Cloud Analysis“ procedure, which evaluates the structural response via Non-Linear Time History Analysis (NLTHA). Both maximum inter-story drift and maximum chord-rotation demand/capacity ratio are used as Engineering Demand Parameters, in which the chord-rotation capacity is calculated according to the Italian Code. To fully develop the fragility curves, both structure-independent and structure-dependent scalar intensity measures are selected among the most referred in practice and literature. This work shows the influence of regularity on the damage levels of the three buildings. Furthermore, it shows the uncertainties caused by the selection criteria for EDP thresholds, which are necessary for a correct representation of the Limit State

Distribution and diet of a recently-established population of Lutra lutra in the Valley of the River Ticino

During the 20th century, the European otter (Lutra lutra) has dramatically declined in central and southern Europe because of hunting, destruction of riparian habitat and chemical pollution. In Italy, few population have survived in the most remote areas of the southern Apennines, where recent studies have recorded an unexpected recovery. In the valley of the River Ticino, a pair of otters was reintroduced in 1997 from a breeding centre (Cameri) located in Piedmont. A further pair possibly escaped before the end of the century. Additionally, during floods in 1991 and 1993 respectively, a pair and a cub and a pair with two sub-adults escaped from their breeding enclosure \u201cLa Fagiana\u201d on the Lombardy side of the river. In spring 2016 an otter survey was carried out with the aim of drawing a picture of the current distribution of the species in the area. By surveying 600 m long transects, otter spraints were found in 8 different stations, between Cameri and Parasacco towns, corresponding to about a 35 km section of the river. Sprainting sites were mainly found inside the weave of meanders, on streams, canals and oxbow lakes, rather than on the main course of the river. All collected otter spraints were stored in silver paper, labelled and frozen until diet analysis. Each spraint was soaked for 12 hours in a solution of hydrogen peroxide and then placed into sieves with 0.5 mm wide meshes, and washed by a water jet. Fish remains were identified from their vertebrae, jawbones and scales, using personal collections and the keys of different authors. Amphibians were identified by the keys of Di Palma and Massa (1981), whilst the telson, chelae and thoracopods were the main diagnostic features for crustaceans. Results were expressed as percent frequency of occurrence F%, percent relative frequency of occurrence FR%, estimated per cent volume V% and per cent mean volume Vm%. In the area, fish - mainly trout (Vm%=21.4), redfin perch (Vm%=17.3), Eurasian minnow (Vm%=13.6) and South European nase (Vm% =9.4) -, formed the bulk of otter diet. Fresh faecal samples were preserved in 96% ethanol and frozen for genetic analyses with the aim of assessing the size and kinship for the otter population in the valley

Metformin and Everolimus: A Promising Combination for Neuroendocrine Tumors Treatment

Introduction: Treatment options for neuroendocrine tumors (NETs) are rarely curative, as NETs frequently show resistance to medical therapy. The use of everolimus, an mTOR inhibitor, is limited by the development of resistance, probably due to the activation of Akt signaling. In this context, the antidiabetic drug metformin is able to inhibit mTOR, providing a rationale for the use of metformin and everolimus in combination. Methods: We investigated the effects of the metformin and everolimus combination on NET cell proliferation, apoptosis, colony formation, cell viability, NET spheroids growth and the involvement of the Akt and mTOR pathways, and also developed everolimus-resistant NET cells to further study this combination. Results: Metformin and everolimus in combination are more effective than monotherapy in inhibiting pancreatic NET (PAN-NET) cell proliferation (-71% \ub1 13%, p < 0.0001 vs. basal), whereas no additive effects were observed on pulmonary neuroendocrine tumor (PNT) cell proliferation. The combinatorial treatment is more effective than monotherapy in inhibiting colony formation, cell viability, NET spheroids growth rate and mTOR phosphorylation in both NET cell lines. In a PAN-NET cell line, metformin did not affect Akt phosphorylation; conversely, it significantly decreased Akt phosphorylation in a PNT cell line. Using everolimus-resistant NET cells, we confirmed that metformin maintained its effects, acting by two different pathways: Akt-dependent or independent, depending on the cell type, with both leading to mTOR suppression. Conclusions: Considering the promising effects of the everolimus and metformin combination in NET cells, our results provide a rationale for its use in NET patients

The otter population of the River Ticino (N Italy) 20 years after its reintroduction

On the River Ticino (Piedmont and Lombardy regions, N Italy), the Eurasian otter Lutra lutra became extinct in the 1980s and was reintroduced in 1997. Since then, the status of the reintroduced population has been assessed only occasionally, in 2008 and 2010. Between 2016 and 2018, we conducted an extensive survey for otter signs along the whole Italian stretch of the River Ticino, following the \u2018Standard Method\u2019 for otter surveys. In 2016\u20132017, we found 101 spraints (mean marking intensity: 0.40 spraints/100 m), spread over a 97-km long stretch of the river. In 2018 only five spraints were collected, the two furthermost marking sites being 32 km apart. Genotyping of nDNA extracted from 21 faecal samples enabled the identification of six different individuals. The surveys led to drawing a reliable picture of otter distribution and population size, with evidence of otter occurrence on a longer than previously recorded stretch of the river. The results of the 2018 survey suggest that stochastic factors may still threaten the survival of reintroduced otters and would suggest a reinforcement of the population is required to increase its genetic diversity

o 016first line folfox plus panitumumab followed by 5 fu lv plus panitumumab or single agent panitumumab as maintenance therapy in patients with ras wild type metastatic colorectal cancer mcrc the valentino study

n/

Tremelimumab and durvalumab combination for the non-operative management (Nom) of microsatellite instability (msi)-high resectable gastric or gastroesophageal junction cancer: The multicentre, single-arm, multi-cohort, phase ii infinity study

SIMPLE SUMMARY: The status of microsatellite instability (MSI-H) in gastric or gastroesophageal junction cancer (GC/GEJC) patients eligible for radical surgery proved to be prognostic for an improved survival outcome and predictive for poor/no benefit from the combination of adjuvant/peri-operative chemotherapy. MSI-H tumors display a high sensitivity to immunotherapy and exploratory studies showed that a pre-operative treatment with immune-checkpoint inhibitors may achieve elevated rates of pathological complete responses. The ongoing proof-of-concept INFINITY study is aimed at investigating the role of the combo-immunotherapy durvalumab plus tremelimumab as a neoadjuvant or potentially definitive treatment (avoiding surgery in case of complete clinical response) for MSI-H resectable GC/GEJC patients. ABSTRACT: In resectable gastric or gastroesophageal junction cancer (GC/GEJC), the powerful positive prognostic effect and the potential predictive value for a lack of benefit from the combination of adjuvant/peri-operative chemotherapy for the MSI-high status was demonstrated. Given the high sensitivity of MSI-high tumors for immunotherapy, exploratory trials showed that combination immunotherapy induces a high rate of complete pathological response (pCR), potentially achieving cancer cure without surgery. INFINITY is an ongoing phase II, multicentre, single-arm, multi-cohort trial investigating the activity and safety of tremelimumab and durvalumab as neoadjuvant (Cohort 1) or potentially definitive (Cohort 2) treatment for MSI-high/dMMR/EBV-negative, resectable GC/GEJC. About 310 patients will be pre-screened, to enroll a total of 31 patients, 18 and 13 in Cohort 1 and 2, at 25 Italian Centres. The primary endpoint of Cohort 1 is rate of pCR (ypT0N0) and negative ctDNA after neoadjuvant immunotherapy, of Cohort 2 is 2-year complete response rate, defined as absence of macroscopic or microscopic residual disease (locally/regionally/distantly) at radiological examinations, tissue and liquid biopsy, during non-operative management without salvage gastrectomy. The ongoing INFINITY proof-of-concept study may provide evidence on immunotherapy and the potential omission of surgery in localized/locally advanced GC/GEJC patients selected for dMMR/MSI-high status eligible for radical resection

Maintenance Therapy with Panitumumab Alone vs Panitumumab Plus Fluorouracil-Leucovorin in Patients with RAS Wild-Type Metastatic Colorectal Cancer: A Phase 2 Randomized Clinical Trial

Key PointsQuestionIs maintenance therapy with single-agent panitumumab noninferior to panitumumab plus fluorouracil and leucovorin after a 4-month induction treatment with panitumumab plus FOLFOX-4 in patients with previously untreated RAS wild-type metastatic colorectal cancer? FindingsIn this open-label, phase 2 randomized clinical trial of 229 patients, maintenance therapy with single-agent panitumumab alone was inferior to panitumumab plus fluorouracil-leucovorin in terms of 10-month progression-free survival (49.0% vs 59.9%). MeaningThe continuation of single-agent anti-epidermal growth factor receptor treatment in the maintenance setting will likely achieve inferior progression-free survival compared with the continuation of chemotherapy plus an anti-epidermal growth factor receptor agent in a phase 3 confirmation trial. This open-label, phase 2 randomized clinical trial assesses whether maintenance therapy with single-agent panitumumab was noninferior to panitumumab plus combined fluorouracil and leucovorin calcium among patients with RAS wild-type metastatic colorectal cancer. ImportanceFew studies are available on the role of maintenance strategies after induction treatment regimens based on anti-epidermal growth factor receptors, and the optimal regimen for an anti-epidermal growth factor receptors-based maintenance treatment in patients with RAS wild-type metastatic colorectal cancer is still to be defined. ObjectiveTo determine whether maintenance therapy with single-agent panitumumab was noninferior to panitumumab plus fluorouracil and leucovorin after a 4-month induction treatment regimen. Design, Setting, and ParticipantsThis open-label, randomized phase 2 noninferiority trial was conducted from July 7, 2015, through October 27, 2017, at multiple Italian centers. Patients with RAS wild-type, unresectable metastatic colorectal adenocarcinoma who had not received previous treatment for metastatic disease were eligible. Induction therapy consisted of panitumumab plus FOLFOX-4 (panitumumab, 6 mg/kg, oxaliplatin, 85 mg/m(2) at day 1, leucovorin calcium, 200 mg/m(2), and fluorouracil, 400-mg/m(2) bolus, followed by 600-mg/m(2) continuous 24-hour infusion at days 1 and 2, every 2 weeks). Cutoff date for analyses was July 30, 2018. InterventionsPatients were randomized (1:1) to first-line panitumumab plus FOLFOX-4 for 8 cycles followed by maintenance therapy with panitumumab plus fluorouracil-leucovorin (arm A) or panitumumab (arm B) until progressive disease, unacceptable toxic effects, or consent withdrawal. The minimization method was used to stratify randomization by previous adjuvant treatment and number of metastatic sites. Main Outcomes and MeasuresThe prespecified primary end point was 10-month progression-free survival (PFS) analyzed on an intention-to-treat basis with a noninferiority margin of 1.515 for the upper limit of the 1-sided 90% CI of the hazard ratio (HR) of arm B vs A. ResultsOverall, 229 patients (153 male [66.8%]; median age, 64 years [interquartile range (IQR), 56-70 years]) were randomly assigned to arm A (n=117) or arm B (n=112). At a median follow-up of 18.0 months (IQR, 13.1-23.3 months]), a total of 169 disease progression or death events occurred. Arm B was inferior (upper limit of 1-sided 90% CI of the HR,1.857). Ten-month PFS was 59.9% (95% CI, 51.5%-69.8%) in arm A vs 49.0% (95% CI, 40.5%-59.4%) in arm B (HR,1.51; 95% CI, 1.11-2.07; P=.01). During maintenance, arm A had a higher incidence of grade 3 or greater treatment-related adverse events (36 [42.4%] vs 16 [20.3%]) and panitumumab-related adverse events (27 [31.8%] vs 13 [16.4%]), compared with arm B. Conclusions and RelevanceIn patients with RAS wild-type metastatic colorectal cancer, maintenance therapy with single-agent panitumumab was inferior in terms of PFS compared with panitumumab plus fluorouracil-leucovorin, which slightly increased the treatment toxic effects. Trial RegistrationClinicalTrials.gov identifier: NCT0247604

Management of Asymptomatic Sporadic Nonfunctioning Pancreatic Neuroendocrine Neoplasms (ASPEN) ≤2 cm: Study Protocol for a Prospective Observational Study

Introduction: The optimal treatment for small, asymptomatic, nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNEN) is still controversial. European Neuroendocrine Tumor Society (ENETS) guidelines recommend a watchful strategy for asymptomatic NF-PanNEN 18 years, the presence of asymptomatic sporadic NF-PanNEN ≤2 cm proven by a positive fine-needle aspiration (FNA) or by the presence of a measurable nodule on high-quality imaging techniques that is positive at 68Gallium DOTATOC-PET scan. Conclusion: The ASPEN study is designed to investigate if an active surveillance of asymptomatic NF-PanNEN ≤2 cm is safe as compared to surgical approach.info:eu-repo/semantics/publishedVersio