80 research outputs found

    Identification of plasma lipid biomarkers for prostate cancer by lipidomics and bioinformatics

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    Background: Lipids have critical functions in cellular energy storage, structure and signaling. Many individual lipid molecules have been associated with the evolution of prostate cancer; however, none of them has been approved to be used as a biomarker. The aim of this study is to identify lipid molecules from hundreds plasma apparent lipid species as biomarkers for diagnosis of prostate cancer. Methodology/Principal Findings: Using lipidomics, lipid profiling of 390 individual apparent lipid species was performed on 141 plasma samples from 105 patients with prostate cancer and 36 male controls. High throughput data generated from lipidomics were analyzed using bioinformatic and statistical methods. From 390 apparent lipid species, 35 species were demonstrated to have potential in differentiation of prostate cancer. Within the 35 species, 12 were identified as individual plasma lipid biomarkers for diagnosis of prostate cancer with a sensitivity above 80%, specificity above 50% and accuracy above 80%. Using top 15 of 35 potential biomarkers together increased predictive power dramatically in diagnosis of prostate cancer with a sensitivity of 93.6%, specificity of 90.1% and accuracy of 97.3%. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) demonstrated that patient and control populations were visually separated by identified lipid biomarkers. RandomForest and 10-fold cross validation analyses demonstrated that the identified lipid biomarkers were able to predict unknown populations accurately, and this was not influenced by patient's age and race. Three out of 13 lipid classes, phosphatidylethanolamine (PE), ether-linked phosphatidylethanolamine (ePE) and ether-linked phosphatidylcholine (ePC) could be considered as biomarkers in diagnosis of prostate cancer. Conclusions/Significance: Using lipidomics and bioinformatic and statistical methods, we have identified a few out of hundreds plasma apparent lipid molecular species as biomarkers for diagnosis of prostate cancer with a high sensitivity, specificity and accuracy

    CO2 gasification of chars prepared from wood and forest residue

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    The CO2 gasification of chars prepared from Norway spruce and its forest residue was investigated in a thermogravimetric analyzer (TGA) at slow heating rates. The volatile content of the samples was negligible; hence the gasification reaction step could be studied alone, without the disturbance of the devolatilization reactions. Six TGA experiments were carried out for each sample with three different temperature programs in 60 and 100% CO2. Linear, modulated, and constant-reaction rate (CRR) temperature programs were employed to increase the information content available for the modeling. The temperatures at half of the mass loss were lower in the CRR experiments than in the other experiments by around 120 degrees C. A relatively simple, well-known reaction kinetic equation described the experiments. The dependence on the reacted fraction as well as the dependence on the CO2, concentration were described by power functions (n-order reactions). The evaluations were also carried out by assuming a function of the reacted fraction that can mimic the various random pore/random capillary models. These attempts, however, did not result in an improved fit quality. Nearly identical activation energy values were obtained for the chars made from wood and forest residues (221 and 218 kJ/mol, respectively). Nevertheless, the forest residue char was more reactive; the temperatures at half of the mass loss showed 20-34 degrees C differences between the two chars at 10 degrees C/min heating rates. The assumption of a common activation energy, E, and a common reaction order, v, on the CO2, concentration for the two chars had only a negligible effect on the fit quality

    New Lipidomic Approaches in Cystic Fibrosis

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    Lipid analysis has been a crucial source of information in cystic fibrosis (CF). New methodologies for qualitative and quantitative lipidomics allow evaluation of a large number of samples, of special interest in patient screening for diagnostic and prognostic biological markers, as well as in cell physiology. In this chapter, two new complementary approaches are described: matrix-assisted laser desorption coupled to time of flight (MALDI-TOF-ClinProTools™) and liquid chromatography coupled to ion trap mass spectrometry (LC-MS( n )). MALDI-TOF-ClinProTools™ offers a large unbiased screening for the discovery of potential lipid alterations in diseased patients. LC-MS( n ) represents a state-of-the-art lipidomic tool for the identification and quantification of such alterations. The combination of both may open new perspectives in the quest for lipids participating in CF pathogenesis, therapy targets, and biomarkers

    River Restoration in Spain: Theoretical and Practical Approach in the Context of the European Water Framework Directive.

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    River restoration is becoming a priority in many countries because of increasing the awareness of environmental degradation. In Europe, the EU Water Framework Directive (WFD) has significantly reinforced river restoration, encouraging the improvement of ecological status for water bodies. To fulfill the WFD requirements, the Spanish Ministry of the Environment developed in 2006 a National Strategy for River Restoration whose design and implementation are described in this paper. At the same time many restoration projects have been conducted, and sixty of them have been evaluated in terms of stated objectives and pressures and implemented restoration measures. Riparian vegetation enhancement, weir removal and fish passes were the most frequently implemented restoration measures, although the greatest pressures came from hydrologic alteration caused by flow regulation for irrigation purposes. Water deficits in quantity and quality associated with uncontrolled water demands seriously affect Mediterranean rivers and represent the main constraint to achieving good ecological status of Spanish rivers, most of them intensively regulated. Proper environmental allocation of in-stream flows would need deep restrictions in agricultural water use which seem to be of very difficult social acceptance. This situation highlights the need to integrate land-use and rural development policies with water resources and river management, and identifies additional difficulties in achieving the WFD objectives and good ecological status of rivers in Mediterranean countries

    Indicators of river system hydromorphological character and dynamics: understanding current conditions and guiding sustainable river management

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    The work leading to this paper received funding from the EU’s FP7 programme under Grant Agreement No. 282656 (REFORM). The Indicators were developed within the context of REFORM deliverable D2.1, therefore all partners involved in this deliverable contributed to some extent to their discussion and development

    A framework to move forward on the path to eco-innovation in the construction industry: implications to improve firms´ sustainable orientation

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    This paper examines key aspects in the innovative behavior of the construction firms that determine their environmental orientation while innovating. Structural equation modeling was used and data of 222 firms retrieved from the Spanish Technological Innovation Panel (PITEC) for 2010 to analyse the drivers of environmental orientation of the construction firms during the innovation process. The results show that the environmental orientation is positively affected by the product and process orientation of construction firms during the innovation process. Furthermore, the positive relation between the importance of market information sources and environmental orientation, mediated by process and product orientation, is discussed. Finally, a model that explains these relations is proposed and validated. 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    Spermatozoal sensitive biomarkers to defective protaminosis and fragmented DNA

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    Human sperm DNA damage may have adverse effects on reproductive outcome. Infertile men possess substantially more spermatozoa with damaged DNA compared to fertile donors. Although the extent of this abnormality is closely related to sperm function, the underlying etiology of ensuing male infertility is still largely controversial. Both intra-testicular and post-testicular events have been postulated and different mechanisms have been proposed to explain the presence of damaged DNA in human spermatozoa. Three among them, i.e. abnormal chromatin packaging, oxidative stress and apoptosis, are the most studied and discussed in the present review. Furthermore, results from numerous investigations are presented, including our own findings on these pathological conditions, as well as the techniques applied for their evaluation. The crucial points of each methodology on the successful detection of DNA damage and their validity on the appraisal of infertile patients are also discussed. Along with the conventional parameters examined in the standard semen analysis, evaluation of damaged sperm DNA seems to complement the investigation of factors affecting male fertility and may prove an efficient diagnostic tool in the prediction of pregnancy outcome

    Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

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    Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1
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