Applications to cancer research of "lab-on-a-chip" devices based on dielectrophoresis (DEP).

The recent development of advanced analytical and bioseparation methodologies based on microarrays and biosensors is one of the strategic objectives of the so-called post-genomic. In this field, the development of microfabricated devices could bring new opportunities in several application fields, such as predictive oncology, diagnostics and anti-tumor drug research. The so called "Laboratory-on-a-chip technology", involving miniaturisation of analytical procedures, is expected to enable highly complex laboratory testing to move from the central laboratory into non-laboratory settings. The main advantages of Lab-on-a-chip devices are integration of multiple steps of different analytical procedures, large variety of applications, sub-microliter consumption of reagents and samples, and portability. One of the requirement for new generation Lab-on-a-chip devices is the possibility to be independent from additional preparative/analytical instruments. Ideally, Lab-on-a-chip devices should be able to perform with high efficiency and reproducibility both actuating and sensing procedures. In this review, we discuss applications of dielectrophoretic(DEP)-based Lab-on-a-chip devices to cancer research. The theory of dielectrophoresis as well as the description of several devices, based on spiral-shaped, parallel and arrayed electrodes are here presented. In addition, in this review we describe manipulation of cancer cells using advanced DEP-based Lab-on-a-chip devices in the absence of fluid flow and with the integration of both actuating and sensing procedures

The First Vega Ride-Share Mission Flight

The first European ride-share mission will be carried out by the Vega launch system in September 2019. The VEGA PoC (Proof of Concept) flight using the SSMS (Small Satellite Mission Service) hardware was conceived in the context of ESA LLL Initiative. This paper reports on the highlights of the preparation of the first European rideshare mission with Vega launcher and on the development of the related launch system. Based on Vega flights accumulated experience, the development of multi-Payload mission concept started from analysis of the activities currently foreseen to fly a single payload mission adapted to the needs of multi payload rideshare missions. After evaluation of impacts in terms of technical feasibility, missioning schedule and related programmatic and cost elements for the missioning of the Light Sats launch service, the implementation phase was initiated and description of its major tasks is the focus of this paper. The described hardware development and processes to reach SSMS PoC flight using the Vega launch system, are the first step towards the ultimate goal of a finally optimized process for Light Sats ride-share missions applicable to all European launchers

Real-life comparison of Pirfenidone and Nintedanib in patients with Idiopathic Pulmonary Fibrosis: a 24-month assessment.

Background: Real-life data on the use of pirfenidone and nintedanib to treat patients with idiopathic pulmonary fibrosis (IPF) are still scarce. Methods: We compared the efficacy of either pirfenidone (n=78) or nintedanib (n=28) delivered over a 24-month period in patients with IPF, followed at two regional clinic centers in Italy, with a group of patients who refused the treatment (n=36), and who were considered to be controls. All patients completed regular visits at 1- to 3-month intervals, where primary [forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)] and secondary outcomes (side effects, treatment compliance, and mortality) were recorded. Results: Over time, the decline in FVC and DLCO was significantly higher (p=0.0053 and p=0.037, respectively) in controls when compared with the combined treated group, with no significant difference between the two treated groups. Compared to patients with less advanced disease (GAP (Gender, Age, Physiology) stage I), those in GAP stages II and III showed a significantly higher decline in both FVC and DLCO irrespective of the drug taken. Side effects were similarly reported in patients receiving pirfenidone and nintedanib (5% and 7%, respectively), whereas mortality did not differ among the three groups. Conclusion: This real-life study demonstrated that both pirfenidone and nintedanib were equally effective in reducing the decline of FVC and DLCO versus non-treated patients after 24 months of treatment; however, patients with more advanced disease were likely to show a more rapid decline in respiratory function

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe

Pulmonary involvement in adult Still's disease: Case report and brief review of literature

Background: Adult onset Still disease (AOSD) is a rare condition characterized by elevated fever along with arthritic symptoms, elevated polymorphonuclear neutrophil count, evanescent rash, and hyperferritinemia. Diagnosis can be made only after have ruled out more frequent conditions, and Yamagouchi or Fautrel criteria should be applied. Parenchimal lung involvement (PLI) is present in less than 5% of AOSD cases and ranges from aspecific reticular interstitial opacities to life threatening conditions, such as acute respiratory distress syndrome (ARDS). Case: We report the case of a 59 years old man who was referred to our ward because of high fever treated as a pneumonia with antibiotic but not responding to medical treatment, and findings suggestive of interstitial lung disease prevalent in the lower zone on high resolution computed tomography (HRCT). AOSD was diagnosed when the diagnostic Yamaguchi criteria were fulfilled and our suspect was confirmed by the rheumatologist; the patient was then successfully treated with corticosteroids. Conclusions: PLI in AOSD is very rare but must be considered among differential diagnosis in patients with high fever and aspecific interstial parenchimal lung involvement

Effects of Extracorporeal CO2 Removal on Inspiratory Effort and Respiratory Pattern in Patients Who Fail Weaning from Mechanical Ventilation

In patients with acute respiratory failure, severe respiratory acidosis is managed by either invasive or noninvasive ventilation (NIV). Recent data suggest that mechanical ventilation may be supported by extracorporeal CO2 removal (ECCO2R) to manage the severe respiratory acidosis consequent to super protective ventilatory strategies in patients with acute respiratory distress syndrome or failure of NIV in patients with acute hypercapnic respiratory failure.This pilot physiological report demonstrates that in patients with chronic obstructive pulmonary disease who are not yet ready to be weaned, the addition of ECCO2R during unsupported breathing avoids the increase in PaCO2 and inspiratory effort and the occurrence of a rapid shallow breathing pattern.We hope these results encourage future investigations on the use ECCO2R to facilitate the weaning process

The Atlas of breeding birds of Lazio (PAUNIL 2006-2008)

10 years after the previous regional atlas (PAL) (Boano et alii, 1995) the Ornithological Societies of Lazio (SROPU, GPRO, GAROL, GOC e Parus ) with the support of Regional Parks Agency (ARP) decided to update the inventory and distribution of breeding species in the Region. The project follows the European standard proposed by EOAC (European Ornithological Atlas Committee) for collecting qualitative data on atlas and by the Italian Breeding Bird Monitoring Program called MITO2000 (Italian Ornithological Monitoring) for collecting quantitative data. The Atlas project provides for the collection of data from 2000, utilizing the records collected during the MITO2000 program and those from to 2006-2008 in specific samplings. As of 2007 the data archive of PAUNIL contained 51.343 records relating to 183 breeding species. The average species for each RU (recording units of 10x10 km) is 54.4 (± 14.5 DS). All the 10 species with more sightings belong to Passerines (Sylvia atricapilla, Turdus merula, Corvus corone cornix, Passer italiae, Fringilla coelebs, Carduelis carduelis, Parus major, Serinus serinus, Luscinia megarhynchos, Hirundo rustica)