Assessing worth of marine protected areas for the protection of threatened biodiversity using IUCN Red List and Red List Index. A pilot study in six mediterranean areas

Abstract The Mediterranean marine region is considered one of the world's biodiversity hotspots for conservation priorities due the high occurrence of rare and threatened species, endemism and high species richness. However, several pressure such as losses and alterations of habitats are ongoing and in order to increase conservation in this sea region, many marine protected areas were established, including Natura 2000 sites. The latter are areas designated under the Habitat and Bird Directives for the conservation of species in need of strict protection, so that they can reach a favourable conservation status. Species conservation status is also assessed through the IUCN (International Union for Conservation of Nature) Red List of Threatened Species. The aim of our study was to test whether IUCN Red List and the related Red List Index RLI (which aggregates in a single value all the information on conservation status of a particular set of species) can be used as a metrics to characterize MPAs, and orienting, consequently, local marine conservation policies. A pilot study was undertaken in the six Sicilian MPAs (Marine Protected Areas) and results highlighted that Egadi Island has a low RLI value (meaning that the MPA hosts many species with a threatened status) while the Capo Gallo MPA, at the opposite, as an high RLI value (i.e.less threatened species); the other four MPAs. Egadi, Pelagie, and Ustica showed similar distribution frequencies of Red List categories having similar RLI values. Biological resource use, natural system modifications, invasive species, and pollution all account for 90% of assessed threats. Outcomes of our study showed that IUCN indicators should be considered as a tool to: assess the conservation status of set of species in protected areas; drive prioritization in the decision process in order to support an effective management conservation plan; designate new MPAs

Long-term monitoring for the surveillance of the conservation status of Tursiops truncatus in an EU Natura2000 site in the Mediterranean Sea. A pilot study in the Tuscan Archipelago

A pilot study, using the dataset from the research network ‘FLT Med Net’, which regularly monitors transborder regions in the Mediterranean Sea using ferries as platform for systematic surveys, was undertaken to assess common bottlenose dolphin range and population trends within the Natura 2000 EU marine site “Tutela del Tursiops truncatus”. The site was recently designated by the Tuscany Region (Italy) within the requirement of the EU Habitats Directive. In order to evaluate the conservation status of bottlenose dolphin according to the surveillance scheme of the Directive, two six-year periods (2007-2012; 2013-2018) were compared to assess trends in distribution-occurrence (range); Sightings Per Unit of Effort and Density (population). In total, 18146 NM were surveyed along two fixed transects, recording 90 sightings of Tursiops truncatus and a total of 268 specimens. Between the two periods, slight but not statistically significant differences were assessed, with decreasing trend in range and population  of the species; no variation was detected in mean group sizes. Travelling was the most common behaviour, and juveniles were present in 20% of the sightings, concentrated during spring and summer. The consistent FLT Med Net dataset was found to be appropriate to evaluate important parameters for the assessment of trends in the conservation status of Tursiops truncatus at the Natura2000 site scale.

Feasibility and early clinical assessment of flattening filter free (FFF) based stereotactic body radiotherapy (SBRT) treatments

<p>Abstract</p> <p>Purpose</p> <p>To test feasibility and safety of clinical usage of Flattening Filter Free (FFF) beams for delivering ablative stereotactic body radiation therapy (SBRT) doses to various tumor sites, by means of Varian TrueBeam™ (Varian Medical Systems).</p> <p>Methods and Materials</p> <p>Seventy patients were treated with SBRT and FFF: 51 lesions were in the thorax (48 patients),10 in the liver, 9 in isolated abdominal lymph node, adrenal gland or pancreas. Doses ranged from 32 to 75 Gy, depending on the anatomical site and the volume of the lesion to irradiate. Lung lesions were treated with cumulative doses of 32 or 48 Gy, delivered in 4 consecutive fractions. The liver patients were treated in 3 fractions with total dose of 75 Gy. The isolated lymph nodes were irradiated in 6 fractions with doses of 45 Gy. The inclusion criteria were the presence of isolated node, or few lymph nodes in the same lymph node region, in absence of other active sites of cancer disease before the SBRT treatment.</p> <p>Results</p> <p>All 70 patients completed the treatment. The minimum follow-up was 3 months. Six cases of acute toxicities were recorded (2 Grade2 and 2 Grade3 in lung and 2 Grade2 in abdomen). No patient experienced acute toxicity greater than Grade3. No other types or grades of toxicities were observed at clinical evaluation visits.</p> <p>Conclusions</p> <p>This study showed that, with respect to acute toxicity, SBRT with FFF beams showed to be a feasible technique in 70 consecutive patients with various primary and metastatic lesions in the body.</p

Toward a common approach for assessing the conservation status of marine turtle species within the European marine strategy framework directive

[EN] Environmental policies, including the European Marine Strategy Framework Directive (MSFD), generally rely on the measurement of indicators to assess the good environmental status (GES) and ensure the protection of marine ecosystems. However, depending on available scientific knowledge and monitoring programs in place, quantitative GES assessments are not always feasible. This is specifically the case for marine turtle species, which are listed under the Biodiversity Descriptor of the MSFD. Relying on an expert consultation, the goal of this study was to develop indicators and a common assessment approach to be employed by European Union Member States to evaluate the status of marine turtle populations in the frame of the MSFD. A dedicated international expert group was created to explore and test potential assessment approaches, in coherence with other environmental policies (i.e. Habitats Directive, OSPAR and Barcelona Conventions). Following a series of workshops, the group provided recommendations for the GES assessment of marine turtles. In particular, indicators and assessment methods were defined, setting a solid basis for future MSFD assessments. Although knowledge gaps remain, data requirements identified in this study will guide future data collection initiatives and inform monitoring programs implemented by EU Member States. Overall this study highlights the value of international collaboration for the conservation of vulnerable species, such as marine turtles.This study was funded by the French Ministry of Environment (MTES-MNHN Conventions n degrees 2102636187 (2019) and n degrees 2102994526 (2020)). DM acknowledges support from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement n degrees 794938. The work of ADM was supported by the Hellenic Foundation for Research and Innovation (H.F.R.I.) under the "First Call for H.F.R.I. Research Projects to support Faculty members and Researchers and the procurement of high-cost research equipment grant" (Project Number: 2340). FV was supported by the Investigator Programme of the Fundacao para a Ciencia e Tecnologia (FCT, CEECIND/03469/2017, CEECIND/03426/2020).Girard, F.; Girard, A.; Monsinjon, J.; Arcangeli, A.; Belda, E.; Cardona, L.; Casale, P.... (2022). Toward a common approach for assessing the conservation status of marine turtle species within the European marine strategy framework directive. Frontiers in Marine Science. 9:1-22. https://doi.org/10.3389/fmars.2022.790733122

The conformational state of hERG1 channels determines integrin association, downstream signaling, and cancer progression

Ion channels regulate cell proliferation, differentiation, and migration in normal and neoplastic cells through cell-cell and cell-extracellular matrix (ECM) transmembrane receptors called integrins. K+ flux through the human ether-\ue0-gogo- related gene 1 (hERG1) channel shapes action potential firing in excitable cells such as cardiomyocytes. Its abundance is often aberrantly high in tumors, where it modulates integrin-mediated signaling. We found that hERG1 interacted with the \u3b21 integrin subunit at the plasma membrane of human cancer cells. This interaction was not detected in cardiomyocytes because of the presence of the hERG1 auxiliary subunit KCNE1 (potassium voltage-gated channel subfamily E regulatory subunit 1), which blocked the \u3b21 integrin-hERG1 interaction. Although open hERG1 channels did not interact as strongly with \u3b21 integrins as did closed channels, current flow through hERG1 channelswas necessary to activate the integrin-dependent phosphorylation of Tyr397 in focal adhesion kinase (FAK) in both normal and cancer cells. In immunodeficient mice, proliferation was inhibited in breast cancer cells expressing forms of hERG1 with impaired K+ flow, whereas metastasis of breast cancer cells was reduced when the hERG1/\u3b21 integrin interaction was disrupted. We conclude that the interaction of \u3b21 integrins with hERG1 channels in cancer cells stimulated distinct signaling pathways that depended on the conformational state of hERG1 and affected different aspects of tumor progression

hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma

BACKGROUND: hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking. METHODS: hERG1 expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (α-hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre,LSL-Kras(G12D/+),LSL-Trp53(R175H/+) transgenic (KPC) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled α-hERG1-MoAb. RESULTS: (i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the α-hERG1-MoAb could detect PDAC in vivo. CONCLUSIONS: hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo

Stereotactic body radiation therapy for liver tumours using flattening filter free beam: dosimetric and technical considerations

Purpose: To report the initial institute experience in terms of dosimetric and technical aspects in stereotactic body radiation therapy (SBRT) delivered using flattening filter free (FFF) beam in patients with liver lesions.Methods and Materials: From October 2010 to September 2011, 55 consecutive patients with 73 primary or metastatic hepatic lesions were treated with SBRT on TrueBeam using FFF beam and RapidArc technique. Clinical target volume (CTV) was defined on multi-phase CT scans, PET/CT, MRI, and 4D-CT. Dose prescription was 75 Gy in 3 fractions to planning target volume (PTV). Constraints for organs at risk were: 700 cc of liver free from the 15 Gy isodose, D max < 21 Gy for stomach and duodenum, D max < 30 Gy for heart, D 0.1 cc < 18 Gy for spinal cord, V 15 Gy < 35% for kidneys. The dose was downscaled in cases of not full achievement of dose constraints. Daily cone beam CT (CBCT) was performed.Results: Forty-three patients with a single lesion, nine with two lesions and three with three lesions were treated with this protocol. Target and organs at risk objectives were met for all patients. Mean delivery time was 2.8 ± 1.0 min. Pre-treatment plan verification resulted in a Gamma Agreement Index of 98.6 ± 0.8%. Mean on-line co-registration shift of the daily CBCT to the simulation CT were: -0.08, 0.05 and -0.02 cm with standard deviations of 0.33, 0.39 and 0.55 cm in, vertical, longitudinal and lateral directions respectively.Conclusions: SBRT for liver targets delivered by means of FFF resulted to be feasible with short beam on time. © 2012 Mancosu et al; licensee BioMed Central Ltd

Accelerated hypofractionated radiotherapy as adjuvant regimen after conserving surgery for early breast cancer: interim report of toxicity after a minimum follow up of 3 years

<p>Abstract</p> <p>Background</p> <p>Accelerated hypofractionation is an attractive approach for adjuvant whole breast radiotherapy. In this study we evaluated the adverse effects at least 3 years post an accelerated hypofractionated whole breast radiotherapy schedule.</p> <p>Methods</p> <p>From October 2004 to March 2006, 39 consecutive patients aged over 18 years with pTis, pT1-2, pN0-1 breast adenocarcinoma who underwent conservative surgery were treated with an adjuvant accelerated hypofractionated radiotherapy schedule consisting of 34 Gy in 10 daily fractions over 2 weeks to the whole breast, followed after 1 week by an electron boost dose of 8 Gy in a single fraction to the tumour bed. Skin and lung radiation toxicity was evaluated daily during therapy, once a week for one month after radiotherapy completion, every 3 months for the first year and from then on every six months. In particular lung toxicity was investigated in terms of CT density evaluation, pulmonary functional tests, and clinical and radiological scoring. Paired t-test, Chi-square test and non-parametric Wilcoxon test were performed.</p> <p>Results</p> <p>After a median follow-up of 43 months (range 36-52 months), all the patients are alive and disease-free. None of the patients showed any clinical signs of lung toxicity, no CT-lung toxicity was denoted by radiologist on CT lung images acquired about 1 year post-radiotherapy, no variation of pulmonary density evaluated in terms of normalised Hounsfield numbers was evident. Barely palpable increased density of the treated breast was noted in 9 out of 39 patients (in 2 patients this toxicity was limited to the boost area) and teleangectasia (<1/cm²) limited to the boost area was evident in 2 out of 39 patients. The compliance with the treatment was excellent (100%).</p> <p>Conclusion</p> <p>The radiotherapy schedule investigated in this study (i.e 34 Gy in 3.4 Gy/fr plus boost dose of 8 Gy in single fraction) is a feasible and safe treatment and does not lead to adjunctive acute and late toxicities. A longer follow up is necessary to confirm these favourable results.</p

Priorities for Mediterranean marine turtle conservation and management in the face of climate change

As climate-related impacts threaten marine biodiversity globally, it is important to adjust conservation efforts to mitigate the effects of climate change. Translating scientific knowledge into practical management, however, is often complicated due to resource, economic and policy constraints, generating a knowledge-action gap. To develop potential solutions for marine turtle conservation, we explored the perceptions of key actors across 18 countries in the Mediterranean. These actors evaluated their perceived relative importance of 19 adaptation and mitigation measures that could safeguard marine turtles from climate change. Of importance, despite differences in expertise, experience and focal country, the perceptions of researchers and management practitioners largely converged with respect to prioritizing adaptation and mitigation measures. Climate change was considered to have the greatest impacts on offspring sex ratios and suitable nesting sites. The most viable adaptation/mitigation measures were considered to be reducing other pressures that act in parallel to climate change. Ecological effectiveness represented a key determinant for implementing proposed measures, followed by practical applicability, financial cost, and societal cost. This convergence in opinions across actors likely reflects long-standing initiatives in the Mediterranean region towards supporting knowledge exchange in marine turtle conservation. Our results provide important guidance on how to prioritize measures that incorporate climate change in decision-making processes related to the current and future management and protection of marine turtles at the ocean-basin scale, and could be used to guide decisions in other regions globally. Importantly, this study demonstrates a successful example of how interactive processes can be used to fill the knowledge-action gap between research and management.This work was conducted under FutureMares EU project that received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 869300. The Mediterranean Marine Turtle Working Group was established in 2017 and is continuously supported by MedPAN and the National Marine Park of Zakynthos. The work of AC was supported by the Hellenic Foundation for Research and Innovation (H.F.R.I.) under the “First Call for H.F.R.I. Research Projects to support Faculty members and Researchers and the procurement of high-cost research equipment grant” (Project Number: 2340).Peer reviewe