I2ECR: Integrated and Intelligent Environment for Clinical Research

Clinical trials are designed to produce new knowledge about a certain disease, drug or treatment. During these studies, a huge amount of data is collected about participants, therapies, clinical procedures, outcomes, adverse events and so on. A multicenter, randomized, phase III clinical trial in Hematology enrolls up to hundreds of subjects and evaluates post-treatment outcomes on stratified sub- groups of subjects for a period of many years. Therefore, data collection in clinical trials is becoming complex, with huge amount of clinical and biological variables. Outside the medical field, data warehouses (DWs) are widely employed. A Data Ware-house is a “collection of integrated, subject-oriented databases designed to support the decision-making process”. To verify whether DWs might be useful for data quality and association analysis, a team of biomedical engineers, clinicians, biologists and statisticians developed the “I2ECR” project. I2ECR is an Integrated and Intelligent Environment for Clinical Research where clinical and omics data stand together for clinical use (reporting) and for generation of new clinical knowledge. I2ECR has been built from the “MCL0208” phase III, prospective, clinical trial, sponsored by the Fondazione Italiana Linfomi (FIL); this is actually a translational study, accounting for many clinical data, along with several clinical prognostic indexes (e.g. MIPI - Mantle International Prognostic Index), pathological information, treatment and outcome data, biological assessments of disease (MRD - Minimal Residue Disease), as well as many biological, ancillary studies, such as Mutational Analysis, Gene Expression Profiling (GEP) and Pharmacogenomics. In this trial forty-eight Italian medical centers were actively involved, for a total of 300 enrolled subjects. Therefore, I2ECR main objectives are: • to propose an integration project on clinical and molecular data quality concepts. The application of a clear row-data analysis as well as clinical trial monitoring strategies to implement a digital platform where clinical, biological and “omics” data are imported from different sources and well-integrated in a data- ware-house • to be a dynamic repository of data congruency quality rules. I2ECR allows to monitor, in a semi-automatic manner, the quality of data, in relation to the clinical data imported from eCRFs (electronic Case Report Forms) and from biologic and mutational datasets internally edited by local laboratories. Therefore, I2ECR will be able to detect missing data and mistakes derived from non-conventional data- entry activities by centers. • to provide to clinical stake-holders a platform from where they can easily design statistical and data mining analysis. The term Data Mining (DM) identifies a set of tools to searching for hidden patterns of interest in large and multivariate datasets. The applications of DM techniques in the medical field range from outcome prediction and patient classification to genomic medicine and molecular biology. I2ECR allows to clinical stake-holders to propose innovative methods of supervised and unsupervised feature extraction, data classification and statistical analysis on heterogeneous datasets associated to the MCL0208 clinical trial. Although MCL0208 study is the first example of data-population of I2ECR, the environment will be able to import data from clinical studies designed for other onco-hematologic diseases, too

La faglia nascosta. Territori, decisioni e pratiche nel cratere sismico del 1980.

Il volume presenta i risultati di uno studio condotto sul terremoto del 1980 attraverso il contatto diretto con i territori colpiti, con gli attori di volta in volta entrati in scena,con documenti e dati conservati in archivi pubblici e privati

Effect of oxide nanoparticles on thermal and mechanical properties of electrospun separators for lithium-ion batteries

This study reports the fabrication and characterization of poly(ethylene oxide) (PEO) and poly(vinylidenefluoride-co-chlorotrifluoroethylene) (PVDF-CTFE) nanofibrous separators for lithium-ion batteries loaded with different amounts of fumed-silica and tin oxide nanoparticles. Membrane morphological characterization (SEM, TEM) showed the presence of good-quality nanofibres containing nanoparticles. Thermal degradation and membrane mechanical properties were also investigated, and a remarkable effect of nanoparticle addition on membrane mechanical properties was found. In particular, PEO membranes were strengthened by the addition of metal oxide, whereas PVDF-CTFE membranes acquired ductility

Non-invasive tool to assess heart rhythm in Zebrafish embryos

In the last years the zebrafish (Danio rerio) has emerged as model organism for cardiac research, in spite of the morphological differences with the human heart. In consequence of the similarity to humans in the early function, the zebrafish embryo has been suggested as an ideal model i) to study the molecular mechanism of cardiac development, and ii) to identify genes related to congenital cardiac defects in human [1]. The overall similarity of zebrafish embryos and human, in responses to human cardiotoxic drugs, was demonstrated, for example, in drug-induced cardiac arrhythmia [2]. For this reason, several methods have been developed to assess cardiac functions in zebrafish embryos [3,4]. Unfortunately, all these techniques suffer from drawbacks (time consuming, skillful operator are ended to perform the experiments) which limit their applications for large scale studies. The development in digital imaging has recently made analysis of cardiac functions in genetically modified transparent zebrafish embryos easier. This allowed to assess non-invasively heart rate variability in zebrafish embryos from videos of beating heart, but without measuring heartbeat rhythm, an important indicator of the cardiac function (heartbeat regularity is associated with cardiotoxicity in humans [1]), from power spectrum of heart signal. In the present study, we present a simple, non-invasive method that, by video-recording embryo images using confocal microscopy, and integrating image processing and power spectral analysis, allows to measure the heartbeat rhythm in zebrafish embryos heart chambers (atrium, ventricle, bulb) (Figure 1). The reliability of the herein proposed method was verified. Some embryos undergone treatment by tricaine, a cardiac anaesthetizing drug, in consequence of which a decrease of the heart rate is expected: the heartbeat regularity in tricaine- treated embryos determined from power spectral analysis decreased as compared to no-treated embryos. The results demonstrated that our method is able to assess the cardiac physiology, in term of heart rhythm, in zebrafish embryos

Micronutrient Deficiencies and Nutritional Pattens as Possible Risk Factors in the Onset of Retinopathy in Type 2 Diabetic Patients

Diabetic retinopathy (DR) is a common complication in diabetes. Many studies have demonstrated a strong correlation between diet and the onset and progression of diabetes, but only few focused on possible link between nutritional patterns, micronutrient deficiency and DR. In this observational study, by using 10-day food diary recordings, we analyzed the eating habits of 34 patients affected by DR, 35 controls with a long history of type 2 diabetes mellitus (T2DM) but no retinopathy and 35 matched healthy subjects. Macro- and micronutrient intakes were calculated based on the Italian food composition database of the Center of Research for Food and Nutrition (CREA) by using a validated nutritional software. Moreover, the adherence to the Mediterranean diet (MD) was evaluated by using a widely adopted questionnaire. Respect to the type 2 diabetic group the average daily intake of vitamin A (total retinol activity equivalents) was strongly reduced in DR group (524 vs 1072 mg/d, P<0.01); those of vitamin C was also reduced in DR group (48.0 vs 85.2 mg/d, P<0.01) as well as vitamin D (3.73 vs 5.40 mg/d, P<0.01). Copper average daily intake was lower in DR group (0,50 vs 0,82 mg/d, P<0.01) and similarly potassium intake was lower in this group respect to the type 2 non retinopathic diabetic one (1271 vs 2180 mg/d, P<0.01). DR patients also showed a significatively lower adherence to the MD respect to the T2DM patients and to the healthy subjects. This study confirmed a possible role of unhealthy nutritional patterns and micronutrient deficiency in the development and progression of the diabetic retinopathy

Reduced long-term overall mortality in heart failure patients with prolonged QRS treated with CRT combined with ICD vs. heart failure patients with narrow QRS treated with ICD only

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Lamprophyre as the Source of Zircon in the Veneto Region, Italy

Discrete zircons, up to 9 mm in length, occur in alluvial deposits from the Veneto area. They are likely derived from the disaggregation of lamprophyric rocks belonging to a regional, pervasive dyke-swarm. Zircon and REE phases occur in both alkaline lamprophyres and connate calcite-bearing felsic lithics and their debris in lamprophyre breccia. We present 36 new complete U–Pb and trace element analyses of zircons and associated inclusions. We used a statistical approach on a larger dataset using new and literature data to evaluate the confidence figure to give an estimation of age of zircons. Inclusions suggest a genetic link with an S–CO2–ZrO–BaO–SrO–CaO-rich fluid/melt possibly associated with carbonate-rich alkaline parental magma and a metasomatised mantle source. This paper confirms the importance of calcite–syenite and lamprophyre genetic link and zircon magmatic origin, in contrast with hydrothermal and metamorphic zircons. U–Pb dating by LA-ICP-MS provides time constrains (40.5–48.4 Ma, Lutetian), consistent with the age of the alkaline magmatic event. Trace element data indicate a link to anorogenic magmatism associated with mantle upwelling. Complex zoning is highlighted by cathodoluminescence images. The Veneto zircons are helpful for regional geological information and may have commercial potential as a critical resource for green technologies