State of the art, gaps and future perspectives on common kestrel ecotoxicology

Anthropogenic activities have caused a steady decline of common kestrel (Falco tinnunculus) since the 1980 s. Effects, especially sublethal effects of contaminants, need to be investigated to ensure the conservation of this species. Data about countries, biological material, contaminants classes, and methodological approaches were collected from scientific publications to highlight gaps on common kestrel toxicology and ecotoxicology. We found that most studies have been conducted in Europe and in the field, underlining a lack of in vitro studies. The studies investigated mainly contaminant levels, while sublethal effects, evaluation of emerging contaminants and use of non-invasive or low-invasive samples were scarce. This work shows important gaps on toxicological status of the common kestrel, highlighting the importance of developing a non-lethal approach that combines responses at different levels of biological organization, as well as data on chemical contamination and on the environment in which the different populations inhabit

Environmental management system implantation on a public university from Rio Grande do Sul, Brasil

Initiatives for environmental preservation have been taken since the 60s since the consequences of human negative impacts on the environment have been reported. Global conferences, discussions and publicity have made this issue gradually more relevant for the news and, more importantly, for the political agenda. Nowadays, in Brazil, for example, both government projects like A3P and regulatory instructions such as ABNT NBR ISO 14001: 2004 are crucial to reduce environmental damage caused by humans. Federal University of Rio Grande do Sul developed a tool called LAIA (an acronym, in Portuguese, for environmental aspect and impact analysis) to help implementing an environmental management system which includes concepts from ISO 14001: 2004 and adaptations of FMEA - a tool that is frequently used in automotive industry. Diagnosis were made on university buildings as to their environmental possible impacts and then action plans known as 5W2H were developed as part of the environmental management system. To represent the environmental performance analysis, 12 units were selected and 4 of them have gone through, at least, three LAIA cycles. By applying the Total Environmental Risk Index, we reported a decreasing trend in environmental risk for the studied units since there were, at least, three index measurements for each unit with a descending sequence over time. LAIA tool was efficient because it could suit to any diagnosed situation so far without losing analysis quality. Thus, the tool can be used in other institutions with different structures, procedures and products.Foi a partir dos anos sessenta que surgiram iniciativas claras a favor da preservação ambiental, decorrentes de uma série de fatores negativos resultantes da ação do homem no ambiente. Conferencias mundiais, debates e publicações fizeram com que o assunto gradativamente ganhasse espaço na mídia e mais importante, na lista de tarefas dos governantes. Hoje, a exemplo do Brasil, projetos governamentais como a A3P e instruções normativas como a ABNT NBR ISO 14001: 2004, são alicerces para a busca da minimização dos impactos gerados pelo homem no ambiente. A Universidade Federal do Rio Grande do Sul desenvolveu, então, uma ferramenta, chamada LAIA (Levantamento de Aspectos e Impactos Ambientais), com o intuito de auxiliar a implantação de seu sistema de gestão ambiental, a qual carrega conceitos da ISO 14001: 2004 e adaptações da ferramenta FMEA, amplamente utilizada pela indústria automobilística. Elaboram-se diagnósticos para os prédios da Universidade em relação aos seus potenciais impactos ambientais e, a partir destes, desenvolvem-se planos de ação, conhecidos como 5W2H, caracterizando a implementação da gestão ambiental. Como representantes para análise do desempenho ambiental, foram selecionadas 12 Unidades da Universidade, das quais, quatro já passaram por três ciclos da ferramenta. Através do acompanhamento do valor do Índice de Risco Ambiental Total, é possível afirmar que há uma tendência de diminuição do risco ambiental destas Unidades pelo fato de haver ao menos três medições do índice para cada uma em sequência decrescente ao longo do tempo. A ferramenta LAIA mostrouse competente por se adaptar a qualquer situação diagnosticada até agora sem perder qualidade de análise, podendo, então, ser utilizada por outros tipos de instituições com diferentes estruturas, processos e produtos.Comité de Medio Ambient

Environmental management system implantation on a public university from Rio Grande do Sul, Brasil

Initiatives for environmental preservation have been taken since the 60s since the consequences of human negative impacts on the environment have been reported. Global conferences, discussions and publicity have made this issue gradually more relevant for the news and, more importantly, for the political agenda. Nowadays, in Brazil, for example, both government projects like A3P and regulatory instructions such as ABNT NBR ISO 14001: 2004 are crucial to reduce environmental damage caused by humans. Federal University of Rio Grande do Sul developed a tool called LAIA (an acronym, in Portuguese, for environmental aspect and impact analysis) to help implementing an environmental management system which includes concepts from ISO 14001: 2004 and adaptations of FMEA - a tool that is frequently used in automotive industry. Diagnosis were made on university buildings as to their environmental possible impacts and then action plans known as 5W2H were developed as part of the environmental management system. To represent the environmental performance analysis, 12 units were selected and 4 of them have gone through, at least, three LAIA cycles. By applying the Total Environmental Risk Index, we reported a decreasing trend in environmental risk for the studied units since there were, at least, three index measurements for each unit with a descending sequence over time. LAIA tool was efficient because it could suit to any diagnosed situation so far without losing analysis quality. Thus, the tool can be used in other institutions with different structures, procedures and products.Foi a partir dos anos sessenta que surgiram iniciativas claras a favor da preservação ambiental, decorrentes de uma série de fatores negativos resultantes da ação do homem no ambiente. Conferencias mundiais, debates e publicações fizeram com que o assunto gradativamente ganhasse espaço na mídia e mais importante, na lista de tarefas dos governantes. Hoje, a exemplo do Brasil, projetos governamentais como a A3P e instruções normativas como a ABNT NBR ISO 14001: 2004, são alicerces para a busca da minimização dos impactos gerados pelo homem no ambiente. A Universidade Federal do Rio Grande do Sul desenvolveu, então, uma ferramenta, chamada LAIA (Levantamento de Aspectos e Impactos Ambientais), com o intuito de auxiliar a implantação de seu sistema de gestão ambiental, a qual carrega conceitos da ISO 14001: 2004 e adaptações da ferramenta FMEA, amplamente utilizada pela indústria automobilística. Elaboram-se diagnósticos para os prédios da Universidade em relação aos seus potenciais impactos ambientais e, a partir destes, desenvolvem-se planos de ação, conhecidos como 5W2H, caracterizando a implementação da gestão ambiental. Como representantes para análise do desempenho ambiental, foram selecionadas 12 Unidades da Universidade, das quais, quatro já passaram por três ciclos da ferramenta. Através do acompanhamento do valor do Índice de Risco Ambiental Total, é possível afirmar que há uma tendência de diminuição do risco ambiental destas Unidades pelo fato de haver ao menos três medições do índice para cada uma em sequência decrescente ao longo do tempo. A ferramenta LAIA mostrouse competente por se adaptar a qualquer situação diagnosticada até agora sem perder qualidade de análise, podendo, então, ser utilizada por outros tipos de instituições com diferentes estruturas, processos e produtos.Comité de Medio Ambient

Multi-biomarker approach and IBR index to evaluate the effects of different contaminants on the ecotoxicological status of Apis mellifera

The honeybee, Apis mellifera L. (Hymenoptera: Apidae), a keystone pollinator of wild plant species and agricultural crops, is disappearing globally due to parasites and diseases, habitat loss, genetic constraints, beekeeper management issues and to the widespread use of pesticides. Besides insecticides, widely studied in this species, honeybees are also exposed to herbicides and fungicides and heavy metals whose lethal and sublethal effects need to be investigated. In this context, our study aimed to evaluate the effects of fungicides and of heavy metals on honeybees and to develop and apply a multi-biomarker approach that include an Integrated Biological Index (IBRv2) to assess the toxicological status of this species. Biomarkers of neurotoxicity (AChE and CaE), metabolic alteration (ALP, and GST) and immune system (LYS, granulocytes) were measured, following honeybees’ exposure to cadmium or to a crop fungicide, using the genotoxic compound EMS as positive control. A biomarker of genotoxicity (NA assay) was developed and applied for the first time in honeybees. At the doses tested, all the contaminants showed sublethal toxicity to the bees, highlighting in particular genotoxic effects. The data collected were analyzed by an IBRv2 index, which integrated the seven biomarkers used in this study. IBRv2 index increased with increasing cadmium or fungicide concentrations. The IBRv2 represents a simple tool for a general description of honeybees ecotoxicological health status. Results highlight the need for more in-depth investigations on the effects of fungicides on non-target organisms, such as honeybees, using sensitive methods for the determination of sublethal effects. This study contributes to the development of a multi-biomarker approach to be used for a more accurate ecotoxicological environmental monitoring of these animals

Results from the CUORE experiment

Neutrinoless double beta decay (0νββ) is a rare, second-order nuclear transition that occurs only if neutrinos are massive Majorana particles or through new physics beyond Standard Model. This process explicitly violates the lepton number (L) by two units and, therefore, the observation of 0νββ would demonstrate that L is not a symmetry of nature. Combined with flavour mixing and cosmological measurements, it can provide unique contraints on neutrino mass scale and establish whether neutrinos are Dirac or Majorana particles. The Cryogenic Underground Observatory for Rare Events (CUORE) is an experiment located at the LNGS searching for 0νββ decay of 130Te. CUORE exploits the bolometric technique to reach high resolution around the Q-value (2527.5 keV). It consists of an array of 988 natural TeO2 cubic crystals grouped into 19 towers. With a total active mass of 742 kg (∼206 kg of 130Te), CUORE is operated at very low temperature with a new 3He/4He refrigerator. Data taking started at the beginning of 2017. After a brief introduction on the detector and the way data analysis is performed, I describe CUORE first results for the search of the 0νββ decay that were published in March 2018

Toward a quantitative approach to migrants integration

Migration phenomena and all the related issues, like integration of different social groups, are intrinsically complex problems since they strongly depend on several competitive mechanisms as economic factors, cultural differences and many others. By identifying a few essential assumptions, and using the statistical mechanics of complex systems, we propose a novel quantitative approach that provides a minimal theory for those phenomena. We show that the competitive interactions in decision making among a population of $N$ host citizens and $P$ immigrants, a bi-partite spin-glass, give rise to a "social consciousness" inside the host community in the sense of the associative memory of neural networks. The theory leads to a natural quantitative definition of migrant's "integration" inside the community. From the technical point of view this minimal picture assumes, as control parameters, only general notions like strength of the random interactions, the ratio among the two party sizes and the cultural influence. Few steps forward, toward more refined models, which include some structure on the random interaction topology (as dilution to avoid the plain mean field approach) and correlations of experiences felt among the two parties (biasing the distribution of the coupling) are discussed at the end, where we show the robustness of our approach

Real-Life Clinical Data of Cabozantinib for Unresectable Hepatocellular Carcinoma

Introduction: Cabozantinib has been approved by the European Medicine Agency (EMA) for hepatocellular carcinoma (HCC) previously treated with sorafenib. Cabozantinib is also being tested in combination with immune checkpoint inhibitors in the frontline setting. Real-life clinical data of cabozantinib for HCC are still lacking. Moreover, the prognostic factors for HCC treated with cabozantinib have not been investigated. Methods: We evaluated clinical data and outcome of HCC patients who received cabozantinib in the legal context of named patient use in Italy. Results: Ninety-six patients from 15 centres received cabozantinib. All patients had preserved liver function (Child-Pugh A), mostly with an advanced HCC (77.1%) in a third-line setting (75.0%). The prevalence of performance status (PS) > 0, macrovascular invasion (MVI), extrahepatic spread, and alpha-fetoprotein (AFP) >400 ng/mL was 50.0, 30.2, 67.7, and 44.8%, respectively. Median overall survival (OS) and progression-free survival were 12.1 (95% confidence interval 9.4-14.8) and 5.1 (3.3-6.9) months, respectively. Most common treatment-related adverse events (AEs) were fatigue (67.7%), diarrhoea (54.2%), anorexia (45.8%), HFSR (43.8%), weight loss (24.0%), and hypertension (24.0%). Most common treatment-related Grade 3-4 AEs were fatigue (6.3%), HFSR (6.3%), and increased aminotransferases (6.3%). MVI, ECOG-PS > 0, and AFP >400 ng/mL predicted a worse OS. Discontinuation for intolerance and no new extrahepatic lesions at the progression were associated with better outcomes. Conclusions: In a real-life Western scenario (mostly in a third-line setting), cabozantinib efficacy and safety data were comparable with those reported in its registration trial. Data regarding the prognostic factors might help in patient selection and design of clinical trials

Randomized phase II study with two gemcitabine- and docetaxel-based combinations as first-line chemotherapy for metastatic non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Docetaxel and gemcitabine combinations have proven active for the treatment of non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate and compare two treatment schedules, one based on our own preclinical data and the other selected from the literature.</p> <p>Methods</p> <p>Patients with stage IV NSCLC and at least one bidimensionally-measurable lesion were eligible. Adequate bone marrow reserve, normal hepatic and renal function, and an ECOG performance status of 0 to 2 were required. No prior chemotherapy was permitted. Patients were randomized to arm A (docetaxel 70 mg/m²on day 1 and gemcitabine 900 mg/m²on days 3–8, every 3 weeks) or B (gemcitabine 900 mg/m2 on days 1 and 8, and docetaxel 70 mg/m2 on day 8, every 3 weeks).</p> <p>Results</p> <p>The objective response rate was 20% (95% CI:10.0–35.9) and 18% (95% CI:8.6–33.9) in arms A and B, respectively. Disease control rates were very similar (54% in arm A and 53% in arm B). No differences were noted in median survival (32 vs. 33 weeks) or 1-year survival (33% vs. 35%). Toxicity was mild in both treatment arms.</p> <p>Conclusion</p> <p>Our results highlighted acceptable activity and survival outcomes for both experimental and empirical schedules as first-line treatment of NSCLC, suggesting the potential usefulness of drug sequencing based on preclinical models.</p> <p>Trial registration number</p> <p>IOR 162 02</p

Identification of lenvatinib prognostic index via recursive partitioning analysis in advanced hepatocellular carcinoma

Background: After the advent of new treatment options for advanced hepatocellular carcinoma (HCC), the identification of prognostic factors is crucial for the selection of the most appropriate therapy for each patient. Patients and methods: With the aim to fill this gap, we applied recursive partitioning analysis (RPA) to a cohort of 404 patients treated with lenvatinib. Results: The application of RPA resulted in a classification based on five variables that originated a new prognostic score, the lenvatinib prognostic index (LEP) index, identifying three groups: low risk [patients with prognostic nutritional index (PNI) &gt;43.3 and previous trans-arterial chemoembolization (TACE)]; medium risk [patients with PNI &gt;43.3 but without previous TACE and patients with PNI &lt;43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage B (BCLC-B)]; high risk [patients with PNI &lt;43.3 and ALBI grade 2 and patients with PNI &lt;43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage C (BCLC-C)]. Median overall survival was 29.8 months [95% confidence interval (CI) 22.8-29.8 months] in low risk patients (n = 128), 17.0 months (95% CI 15.0-24.0 months) in medium risk (n = 162) and 8.9 months (95% CI 8.0-10.7 months) in high risk (n = 114); low risk hazard ratio (HR) 1 (reference group), medium risk HR 1.95 (95% CI 1.38-2.74), high risk HR 4.84 (95% CI 3.16-7.43); P &lt; 0.0001. The LEP index was validated in a cohort of 127 Italian patients treated with lenvatinib. While the same classification did not show a prognostic value in a cohort of 311 patients treated with sorafenib, we also show a possible predictive role in favor of lenvatinib in the low risk group. Conclusions: LEP index is a promising, easy-to-use tool that may be used to stratify patients undergoing systemic treatment of advanced HCC