EPMA position paper in cancer:current overview and future perspectives

At present, a radical shift in cancer treatment is occurring in terms of predictive, preventive, and personalized medicine (PPPM). Individual patients will participate in more aspects of their healthcare. During the development of PPPM, many rapid, specific, and sensitive new methods for earlier detection of cancer will result in more efficient management of the patient and hence a better quality of life. Coordination of the various activities among different healthcare professionals in primary, secondary, and tertiary care requires well-defined competencies, implementation of training and educational programs, sharing of data, and harmonized guidelines. In this position paper, the current knowledge to understand cancer predisposition and risk factors, the cellular biology of cancer, predictive markers and treatment outcome, the improvement in technologies in screening and diagnosis, and provision of better drug development solutions are discussed in the context of a better implementation of personalized medicine. Recognition of the major risk factors for cancer initiation is the key for preventive strategies (EPMA J. 4(1):6, 2013). Of interest, cancer predisposing syndromes in particular the monogenic subtypes that lead to cancer progression are well defined and one should focus on implementation strategies to identify individuals at risk to allow preventive measures and early screening/diagnosis. Implementation of such measures is disturbed by improper use of the data, with breach of data protection as one of the risks to be heavily controlled. Population screening requires in depth cost-benefit analysis to justify healthcare costs, and the parameters screened should provide information that allow an actionable and deliverable solution, for better healthcare provision

Optimized sample-processing time and peptide recovery for the mass spectrometric analysis of protein digests

AbstractProteomics requires an optimized level of sample-processing, including a minimal sample-processing time and an optimal peptide recovery from protein digests, in order to maximize the percentage sequence coverage and to improve the accuracy of protein identification. The conventional methods of protein characterization from one-dimensional or two-dimensional gels include the destaining of an excised gel piece, followed by an overnight in-gel enzyme digestion. The aims of this study were to determine whether: (1) stained gels can be used without any destaining for trypsin digestion and mass spectrometry (MS); (2) tryptic peptides can be recovered from a matrix-assisted laser desorption/ionization (MALDI) target plate for a subsequent analysis with liquid chromatography (LC) coupled to an electrospray ionization (ESI) quadrupole ion trap MS; and (3) an overnight in-gel digestion is necessary for protein characterization with MS. These three strategies would significantly improve sample throughput. Cerebrospinal fluid (CSF) was the model biological fluid used to develop these methods. CSF was desalted by gel filtration, and CSF proteins were separated by two-dimensional gel electrophoresis (2DGE). Proteins were visualized with either silver, Coomassie, or Stains-All (counterstained with silver). None of the gels was destained. Protein spots were in-gel trypsin digested, the tryptic peptides were purified with ZipTip, and the peptides were analyzed with MALDI and ESI MS. Some of the samples that were spotted onto a wax-coated MALDI target plate were recovered and analyzed with ESI MS. All three types of stained gels were compatible with MALDI and ESI MS without any destaining. In-gel trypsin digestion can be performed in only 10–60 min for protein characterization with MS, the sample can be recovered from the MALDI target plate for use in ESI MS, and there was a 90% reduction in sample-processing time from overnight to ca. 3 h

Application of Energetic BEM to 2D Elastodynamic Soft Scattering Problems

Abstract Starting from a recently developed energetic space-time weak formulation of the Boundary Integral Equations related to scalar wave propagation problems, in this paper we focus for the first time on the 2D elastodynamic extension of the above wave propagation analysis. In particular, we consider elastodynamic scattering problems by open arcs, with vanishing initial and Dirichlet boundary conditions and we assess the efficiency and accuracy of the proposed method, on the basis of numerical results obtained for benchmark problems having available analytical solution

CVEM-BEM Coupling with Decoupled Orders for 2D Exterior Poisson Problems

For the solution of 2D exterior Dirichlet Poisson problems, we propose the coupling of a Curved Virtual Element Method (CVEM) with a Boundary Element Method (BEM), by using decoupled approximation orders. We provide optimal convergence error estimates, in the energy and in the weaker L-2-norm, in which the CVEM and BEM contributions to the error are separated. This allows for taking advantage of the high order flexibility of the CVEM to retrieve an accurate discrete solution by using a low order BEM. The numerical results confirm the a priori estimates and show the effectiveness of the proposed approach

A Robust Implicit Optimal Order Formula for Direct Integration of Second Order Orbital Problems

In this paper, a robust implicit formula of optimal order for direct integration of general second order orbital problems of ordinary differential equations (ODEs) is proposed. This method is considered capable avoiding the computational burden and wastage in computer time in connection with the method of reduction to first order systems. The integration algorithms and analysis of the basic properties are based on the adoption of Taylor’s expansion and Dahlquist stability model test. The resultant integration formula is of order ten and it is zero-stable, consistent, convergent and symmetric. The numerical implementation of the method to orbital and two-body problems demonstrates increased accuracy with the same computational effort on comparison with similar second order formulas. Keywords: Optimal-order, Zero-stability, Convergence, Consistent, IVPs, Predictor-corrector, Error constant, Symmetric

Nuclear and chloroplast microsatellite diversity in Phaseolus vulgaris L. from Sardinia (Italy).

Studies of the level and the structure of the genetic diversity of local varieties of Phaseolus vulgaris are of fundamental importance, both for the management of genetic resources and to improve our understanding of the pathways of dissemination and the evolution of this species in Europe. We have here characterized 73 local bean populations from Sardinia (Italy) using seed traits and molecular markers (phaseolins, nuSSRs and cpSSRs). American landraces and commercial varieties were also included for comparison. We see that: (a) the Sardinian material is distinct from the commercial varieties considered; (b) the variation in the seed traits is high and it mostly occurs among populations (95%); (c) compared to the American sample and the commercial varieties, the Sardinian collection has a low level of diversity; (d) the majority ([95%) of the Sardinian individuals belong to the Andean gene pool; (e) the Sardinian material shows a strong genetic structure, both for cpSSRs and nuSSRs; (f) the nuSSRs and cpSSRs concur in differentiating between gene pools, but a lack of congruence between nuclear and chloroplast has been observed within gene pools; and (g) there are three putative hybrids between the Andean and Mesoamerican gene pools. Despite the relatively low level of diversity, which is probably due to a strong founder effect, the Sardinian landraces are worth being conserved and studied further because of their distinctiveness and because hybridization within and between the gene pools could generate variation that will be useful for breeding

Efficacy of Percutaneous Transarterial Embolization in Patients with Spontaneous Abdominal Wall Hematoma and Comparison between Blind and Targeted Embolization Approaches

Background: Endovascular treatment of abdominal wall hematomas (AWHs) has been increasingly used when conservative treatments were not sufficiently effective, and it is often preferred to surgical interventions. The aim of our study was to evaluate the safety and technical and clinical success of percutaneous transarterial treatment of AWH and to evaluate the efficacy of blind embolization compared to targeted embolization. Materials and Methods: We retrospectively enrolled 43 patients (23 men and 20 females) with spontaneous AWH who underwent digital subtraction angiography (DSA) and embolization, focusing on the presence of signs of bleeding at pre-procedural CT-Angiography (CTA) and at DSA. Furthermore, we divided patients into two groups depending on blind or targeted embolization approaches. Results: The mean age of the study population was 71 \ub1 12 years. CTA revealed signs of active bleeding in 31 patients (72%). DSA showed signs of active bleeding in 34 patients (79%). In nine patients (21%), blind embolization was performed. The overall technical success rate was 100%. Clinical success was achieved in 33 patients (77%), while 10 patients (23%) rebled within 96 h, and all of them were re-treated. No major peri-procedural complication was reported. The comparison between blind and targeted embolization showed no statistically significant differences for characteristics of groups and for clinical success rates (78% and 77%, respectively, 12p = 0.71). The technical success was 100% in both groups. Conclusions: Our study confirms that transarterial embolization is a safe and effective option for the treatment of spontaneous AWHs, and it suggests that the efficacy and safety of blind embolization is comparable to non-blind

Saliva, a bodily fluid with recognized and potential diagnostic applications

Human whole saliva is a bodily fluid that can be obtained easily by noninvasive techniques. Specimens can be collected by the patient also at home in order to monitor health status and variations of several analytes of clinical interest. The contributions to whole saliva include secretions from salivary glands and, among others, from the gingival crevicular fluid that derives from the epithelial mucosa. Therefore, saliva is currently a relevant diagnostic fluid for many substances, including steroids, nonpeptide hormones, therapeutic drugs, and drugs of abuse. This review at first briefly describes the different contributions to whole saliva. A section illustrates the procedures for the collection, handling, and storage of salivary specimens. Another section describes the present use of whole saliva for diagnostic purposes and its specific utilization for the diagnosis of several local and systemic diseases. The final sections illustrate the future opportunities offered by various not conventional techniques with a focus on the most recent –omic investigations. It describes the various issues that have to be taken into account to avoid false positives and negatives, such as the strength of the experimental plan, the adequacy of the number of samples under study, and the proper choice of controls

Data collection protocol

This document shows the data collection protocol to perform the sustainability assessment of different 4CE-MED cropping systems by applying life cycle thinking methodologies. Within 4CE-MED project, WP4 will select 3 countries and trials will be selected to compare the sustainability performance of current situations with the introduction of 4CE-MED cropping systems. The cases will belong to three major camelina cropping models presented in the project: Model A introduces Camelina to replace fallow in winter cereal sole-cropping systems, in marginal areas with very dry climate; Model B considers Camelina as a double-cropping cultivation in autumn, to precede typical Mediterranean summer crops; and Model C uses Camelina as a double-cropping in late spring/early summer in colder areas to follow winter pulses (e.g. pea) or cereals harvested as fodder. The selected cases would have followed the experimental protocol presented in WP2. This protocol is based on the Methodological framework to develop life cycle thinking assessment on 4CE-MED systems (D4.1). A literature review was also conducted for this deliverable, which allowed to observe there is limited LCA, E-LCC and S-LCA studies of the Camelina crop in Mediterranean regions. Most of the information found is referred to the application of Camelina as biofuel, while some articles even highlighted that camelina is not used as food. The definition of a goal and scope, expressed in the methodological framework for the assessment, expects to conduct a cradle-to-farm gate assessment with functionality based mostly on yield, and a perspective based on the crop succession. Functional unit is expected to be mass based, with derivations towards the environmental, economic and social impact categories of interest. The environmental dimension will refer to midpoint categories, with a consistent use as in most of the studies of Global Warming Potential, Eutrophication Potential and Terrestrial Acidification Potential. Regarding the economic dimension, cost categories, income and net margin will be observed, and the social dimension will include impact categories that range from endpoint to midpoint categories, where human rights, working conditions and community are to be addressed

Vascular and Metabolic Response to Statin in the Mildly Hypertensive Hypercholesterolemic Elderly

INTRODUCTION: Much evidence indicates the importance of the endothelium and hypercholesterolemia in atherosclerosis, as well as the decline in endothelial function with aging. However, it is unclear if treating dyslipidemia in elderly patients improves endothelial function and reduces C-reactive protein levels. OBJECTIVES: To evaluate vasomotor function, lipids and C-reactive protein in mildly hypertensive and hypercholesterolemic elderly patients treated with atorvastatin. METHODS: Forty-seven elderly Brazilian subjects (> 65 years old) with LDL cholesterol (LDL-c) > 130 mg/dL were randomly assigned, in a double-blinded manner, to receive either placebo (n = 23) or 20 mg/day of atorvastatin (n = 24) for 4 weeks. Exclusion criteria included diabetes, serious hypertension, obesity, steroid use, hormone replacement, and statin use within the previous six months. All patients underwent clinical examinations, laboratory tests (glucose, lipids, liver enzymes, creatine phosphokinase and high sensitivity C-reactive protein) and assessment of vasomotor function by high-resolution ultrasound examination of the brachial artery (flow-mediated dilation and sublingual nitrate), both before and after treatment. RESULTS: The patients were 65 to 91 years old; there was no significant difference between basal flow-mediated dilation of placebo (7.3 ± 6.1%) and atorvastatin (4.5 ± 5.1%; p = 0.20). The same was observed after treatment (6.6 ± 6.2 vs. 5.0 ± 5.6; p = 0.55). The initial nitrate dilatation (8.1 ± 5.4% vs. 10.8 ± 7.5%; p = 0.24) and that after 4 week treatment (7.1 ± 4.7% vs. 8.6 ± 5.0%; p = 0.37) were similar. Atorvastatin produced a reduction of 20% of the C-reactive protein and 42% in the LDL-c; however, there were no changes in the flow-mediated dilation. CONCLUSIONS: Atorvastatin produced a significant change of lipids and C-reactive protein; however, there were no changes in vasomotor function, suggesting the existence of intrinsic age-related vessel alterations