1,169 research outputs found

    The Cagliari Airport impact on Sardinia tourism: a Logit-based analysis

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    In the field of air transportation management, traditionally, airlines have been the main actors in the process for deciding which new flights open in a given airport, while airports acted only as the managers of the operations. The changes in the market due to the introduction of low cost companies, with consequent reduction of the airports' fares, as well as the increment of the density of regional airports in several European countries are modifying the mutual roles of airlines and airports. The final decision on new flight to be opened, in fact, is nowadays the result of a negotiation between airlines and airports. The airports must prove the sustainability on the new routes and forecast the economic impact on their catchment area. This paper contributes to advance the current state-of-the-art along two axes. From the pure transportation literature point of view, we introduce a Logit model able to predict the passengers flow in an airport when the management introduces a change in the flight schedule. The model is also able to predict the impact of this change on the airports in the surrounding areas. The second contribution is a case study on the tourist market of the Sardinia region, where we show how to use the results of the model to deduce the economic impact of the decisions of the management of the Cagliari airport on its catchment area in terms of tourists and economic growt

    In silico screening of mutational effects on enzyme-proteic inhibitor affinity: a docking-based approach

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    <p>Abstract</p> <p>Background</p> <p>Molecular recognition between enzymes and proteic inhibitors is crucial for normal functioning of many biological pathways. Mutations in either the enzyme or the inhibitor protein often lead to a modulation of the binding affinity with no major alterations in the 3D structure of the complex.</p> <p>Results</p> <p>In this study, a rigid body docking-based approach has been successfully probed in its ability to predict the effects of single and multiple point mutations on the binding energetics in three enzyme-proteic inhibitor systems. The only requirement of the approach is an accurate structural model of the complex between the wild type forms of the interacting proteins, with the assumption that the architecture of the mutated complexes is almost the same as that of the wild type and no major conformational changes occur upon binding. The method was applied to 23 variants of the ribonuclease inhibitor-angiogenin complex, to 15 variants of the barnase-barstar complex, and to 8 variants of the bovine pancreatic trypsin inhibitor-β Trypsin system, leading to thermodynamic and kinetic estimates consistent with in vitro data. Furthermore, simulations with and without explicit water molecules at the protein-protein interface suggested that they should be included in the simulations only when their positions are well defined both in the wild type and in the mutants and they result to be relevant for the modulation of mutational effects on the association process.</p> <p>Conclusion</p> <p>The correlative models built in this study allow for predictions of mutational effects on the thermodynamics and kinetics of association of three substantially different systems, and represent important extensions of our computational approach to cases in which it is not possible to estimate the absolute free energies. Moreover, this study is the first example in the literature of an extensive evaluation of the correlative weights of the single components of the ZDOCK score on the thermodynamics and kinetics of binding of protein mutants compared to the native state.</p> <p>Finally, the results of this study corroborate and extend a previously developed quantitative model for in silico predictions of absolute protein-protein binding affinities spanning a wide range of values, i.e. from -10 up to -21 kcal/mol.</p> <p>The computational approach is simple and fast and can be used for structure-based design of protein-protein complexes and for in silico screening of mutational effects on protein-protein recognition.</p

    Weekly versus three weeks chemotherapy for advanced ovarian cancer. A meta-analysis

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    Aim: Three weeks paclitaxel and carboplatin has been considered the standard of care for primary treatment of ovarian cancer (OC). Whether weekly therapy will further improve the clinical outcomes or not is still unclear. We conducted a meta-analysis to compare the two regimens. Method: Articles were selected with a systematic approach, using PubMed databases. Trials concerning comparison between carboplatin plus weekly paclitaxel (dose-dense regimen) and carboplatin plus paclitaxel every 3 weeks were considered. Outcomes included overall survival (OS), progression free survival (PFS) and severe acute toxicity. Results: Dose-dense regimen was associated with significant improvement of PFS compared with standard schedule, with HR of 0.73 (95% CI 0.61-0.88, p = 0.001). There was no difference in OS between treatment regimens (HR 0.95, 95% CI 0.77-1.16, p=0.06), as well as in term of severe acute toxicity. Conclusion: Dose-dense regimen is superior to standard schedule in terms of PFS. Further studies are necessary to firmly confirm this evidence in advanced OC treatment

    new efficiency opportunities arising from intelligent real time control tools applications the case of compressed air systems energy efficiency in production and use

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    Abstract Most of the production facilities in Europe make use of compressed air to drive equipment for manufacturing and Compressed Air Systems (CAS) account for about 10% of the total electrical energy consumption of European industries. Therefore, reducing CAS energy consumption is a crucial task to meet the European goals of improving energy efficiency and reducing environmental impact of the industrial sector. This work is part of a wider research activity aimed at developing a strategy to optimize the energy use in CAS. In particular, this paper shows the importance of monitoring energy consumption and control energy use in compressed air generation, to enable energy saving practices, enhance the outcomes of energy management projects, and to guide industries in energy management. We propose a novel procedure in which measured data are compared to a baseline obtained through mathematical modelling (i.e. regression functions) to enable faults detection and energy accounting, through the use of control charts (i.e. variations' control and the Cumulative Sums). The effectiveness of the proposed methodology is demonstrated in a case study, namely the compressed air system of a pharmaceutical manufacturing plant

    Efficacy and toxicity of bevacizumab in recurrent ovarian disease: an update meta-analysis on phase III trials

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    Background: To analyze the efficacy and toxicity of bevacizumab on survival outcomes in recurrent ovarian cancer. Results: Bevacizumab was associated with significant improvement of PFS and OS compared with standard treatment with HRs of 0.53 (95% CI 0.44 - 0.63; p &lt; 0.00001) and 0.87 (95% CI, 0.77 to 0.99; p = 0.03), respectively. Bevacizumab increased the incidence of G3/G4 hypertension (RR 19.01, 95% CI 7.77 - 46.55; p &lt; 0.00001), proteinuria (RR 17.31, 95% CI 5.42 - 55.25; p &lt; 0.00001), arterial thromboembolic events (ATE) (RR 4.99, 95% CI 1.29 - 19.27; p = 0.02) and bleeding (RR 3.14, 95% CI 1.35 - 7.32; p = 0.008). Materials and Methods: Three randomized phase III trials representing 1502 patients were identified. Pooled hazard ratio (HR), odd ratio (OR), risk ratio (RR) with 95% confidence interval (CI) were calculated using fixed or random effects model. Conclusions: Adding bevacizumab to standard chemotherapy improved ORR, PFS and OS, and it had a higher, but manageable, incidence of toxicities graded 3 to 4

    Fertility preservation in gynaecologic cancers

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    Due to substantial improvement in the diagnosis and treatment of gynaecologic cancers, a better understanding of patient care needs to be revised. We reviewed the literature related to fertility preservation strategies in gynaecological cancer and discussed current general management approaches. New technical modalities and patients’ own desire for motherhood should be integral and paramount in the clinical evaluation to significantly contribute to preserving fertility in those women diagnosed with gynaecologic cancers during the reproductive years

    Comparison of anogenital distance and correlation with vulvo-vaginal atrophy: a pilot study on premenopausal and postmenopausal women

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    OBJECTIVES: Anogenital distance (AGD) represents the space between labia posterior commissure and anus. This was pilot study to investigate how menopause and so lack of oestrogens affects AGD. METHODS: A total of 109 patients were enrolled. AGD was measured in lithotomy position using sterile paper ruler. Anogenital index (AGI) was used to control 2 variables of height and weight (body mass index, kg/m2). Vaginal health index (VHI) was used to evaluate vaginal wellness. Female sexual function index (FSFI) questionnaire was administered to all women to evaluate the impact of menopause on their sexual function. RESULTS: AGD (30.87 ± 2.98 vs. 17.57 ± 2.18; P = 0.0001) and AGI (1.40 ± 0.21 vs. 0.70 ± 0.15; P = 0.0001) were both significantly lower in the postmenopausal group. Postmenopausal women were affected by vulvovaginal atrophy (VVA) significantly. Thus, VHI scores were dramatically worse in postmenopausal group (23.95 ± 1.28 vs. 10.75 ± 3.41; P = 0.0001) as well as FSFI results (32.68 ± 2.25 vs. 19.78 ± 5.46; P = 0.0001). CONCLUSIONS: This study confirms that AGD in post-menopausal women was significantly shorter than AGD in premenopausal women, correlating with an increase of VVA and sexual impairment. Changes of AGD and AGI demonstrated to predict hormonal changes that may occur after menopause

    assessing and improving compressed air systems energy efficiency in production and use findings from an explorative study in large and energy intensive industrial firms

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    Compressed Air Systems (CAS) are one of the most common and energy intensive utilities in industry, representing up to 10% of the industrial energy needs. Nevertheless, benchmarks currently available are usually based on nominal data and referred to the quality of the design, while there are still no available benchmarks based on measured industrial data, taking into consideration actual operating conditions, and referred to compressed air production and, most of all, use. In accordance with the Italian transposition of the European Directive 2012/27/EU (i.e. Legislative Decree 102/2014) large and energy-intensive enterprises have been asked to perform mandatory energy audits in 2015. In this context, a data collection focused on CAS has been carried out by means of a semi-structured questionnaire in the form of a spreadsheet. First data analyses performed and relative findings are here illustrated, together with the next steps for the creation of reliable sectorial and cross-sectorial benchmarks

    Analysis of gene expression levels and their impact on survival in 31 cancer-types patients identifies novel prognostic markers and suggests unexplored immunotherapy treatment options in a wide range of malignancies

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    Background Immunotherapy has dramatically improved cancer treatment by inhibiting or activating specific cell receptors, thus unleashing the host anti-tumor response. However, the engagement of the three main immune checkpoints so far identified, CTLA4, PD-1 and PD-L1, is effective in a fraction of patients, therefore novel targets must be identified and tested. Methods We focused our attention on the following nine highly relevant immune checkpoint (ICR) receptors: CTLA4, PD1, PD-L1, LAG3, TIM3, OX40, GITR, 4-1BB and TIGIT. All of them are targets of existing drugs currently under clinical scrutiny in several malignancies. Their expression levels were evaluated in patient tissues of 31 different cancer types vs. proper controls, in a total of 15,038 individuals. This analysis was carried out by interrogating public databases available on GEPIA2 portal and UALCAN portal. By the Principal Component Analysis (PCA) their ability to effectively discriminate patients form controls was then investigated. Expression of the nine ICRs was also related to overall survival in 31 cancer types and expressed as Hazard Ratio, on the GEPIA2 portal and validated, for melanoma patients, in patients-datasets available on PROGgene V2 portal. Results Significant differential expression was observed for each ICR molecule in many cancer types. A 7-molecules profile was found to specifically discriminate melanoma patients from controls, while two different 6-molecules profiles discriminate pancreatic cancer patients and Testicular Germ Cell Tumors from matched controls. Highly significant survival improvement was found to be related to the expression levels of all nine ICRs in a wide spectrum of malignancies. For melanoma analysis, the relation with survival observed in TCGA datasets was validated in independent GSE melanoma datasets. Conclusion Analysis the nine ICR molecules demonstrates that their expression patterns may be considered as markers of disease and strong survival predictors in a variety of malignancies frequently associated to poor prognosis. Thus, the present findings are strongly advocating that exploratory clinical trials are worth to be performed, using available drugs, targeting these molecules
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