199 research outputs found

    Operations and maintenance for multipurpose offshore platforms using statistical weather window analysis

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    With increasing offshore-related commerce, the choice of appropriate operations and maintenance activities must take into consideration safety, costs and performance targets. Stochastic weather conditions at each site of interest presents uncertain situations. We present an optimized decision making procedure that seeks to maximize monetary benefits while minimizing safety risks. Our proposed approach outlines and illustrates application of such a policy by incorporating traditional weather window analysis using a Markov Decision Process approach. In particular, the approach is applied in case study involving the operation of a multipurpose platform at an offshore Scotland site

    The FDR4ATMOS Project

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    The FDR4ATMOS project has two main tasks. The focus of task A is to update the SCIAMACHY processing chain for better Ozone total columns. After the full re-processing of the SCIAMACHY mission with processor versions 9 (Level 1) and version 7 (Level 2), the comparison with ground-based data showed that the total Ozone column showed a downward trend of nearly 2% from the beginning of the time series to its end. This trend is an artefact and is likely caused by changes made to the calibration algorithms in the Level 1 processor (the DOAS retrieval algorithm for Ozone was not changed). The most likely reason are changes in the degradation correction that lead to subtle changes in the spectral structures that in the retrieval are interpreted as an atmospheric signature. In task A we will update the Level 0-1 processor with the final aim of a mission re-processing. The second task in the FDR4ATMOS project is to develop a cross-instrument Level 1 product for GOME-1 and SCIAMACHY for the UV, VIS and NIR spectral range with a focus on the spectral windows used for O3, SO2, NO2 total column retrieval and the determination of cloud properties. Contrary to other projects, FDR4ATMOS does not aim to build a harmonised time series on Level 2 products but on Level 1 products, i.e. radiances and reflectances. The GOME-1 and SCIAMACHY instrument together span 17 years of spectrally highly resolved data. The goal of the FDR4ATMOS project is to generate harmonised data sets that allow the user to use it directly in long term trend analysis, independent of the instrument. Since this was never done for highly resolved spectrometers, new methods have to be developed that e.g. take into account the different observation geometries and observation times of the instrument without impacting the spectral structures that are used for the retrieval of the atmospheric species. The resulting algorithms and the processor should also be as generic as possible to be able to transfer the methodology easily to other instruments (e.g. GOME-2, Sentinel-5p) for a future extension of the time series. The FDR4ATMOS started in October 2019 and is currently in phase 1. We will present the goals of the project and first results

    Phase II study of single agent capecitabine in the treatment of metastatic non-pancreatic neuroendocrine tumours

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    BACKGROUND: This study sought to determine the safety of single agent capecitabine, a pro-drug of 5FU, in patients with metastatic non-pancreatic neuroendocrine tumours (NETs). METHODS: Multicentre phase II, first-line study design. Oral capecitabine was administered on days 1-14 of 3-week cycles. RESULTS: Treatment was safe and well tolerated. Common toxicities were diarrhoea and fatigue. CONCLUSION: The study provides evidence to support the use of capecitabine as a substitute for infusional 5FU in the management of NETs

    Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

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    <p>Abstract</p> <p>Background</p> <p>Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion plus long-acting release (LAR) octreotide in patients with neuroendocrine carcinoma.</p> <p>Methods</p> <p>Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m<sup>2 </sup>daily) plus LAR octreotide (20 mg monthly). Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival.</p> <p>Results</p> <p>Assessment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria showed partial response in 7 (24.1%), stable disease in 20 (69.0%), and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A) response was observed in 12/25 assessable patients (48.0%); symptom relief was obtained in 9/15 symptomatic patients (60.0%). There was non significant decrease in circulating vascular epithelial growth factor (VEGF) over time. Median time to progression was 22.6 months (range, 2.7-68.5); median overall survival was not reached yet. Toxicity was mild and manageable.</p> <p>Conclusion</p> <p>Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future.</p> <p>Trial registration</p> <p>NCT00953394</p

    Primary chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide in locally advanced thymomas: a single institution experience

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    From 1990 to 1997, 16 consecutive patients with stage III and IVa invasive thymoma were treated in a single institution with primary chemotherapy consisting in adriamycin (40 mg m–2), cisplatin (50 mg m–2) administered intravenously on day 1, vincristine (0.6 mg m–2) on day 2 and cyclophosphamide (700 mg m–2) on day 4 (ADOC). The courses were repeated every 3 weeks. The aim was to evaluate the impact of this cytotoxic regimen with respect to response rate, per cent of patients radically resected, time to progression and overall survival. Two complete responses (one clinical and one pathological) and 11 partial responses were observed (overall response rate 81.2%); two patients had stable disease and one progressed. Toxicity was mild as only two patients developed grade III/IV neutropenia and one patient grade III nausea/vomiting. Nine patients were radically resected (five out of ten with stage III, and four out of six with stage IVa). Median time to progression and overall survival was 33.2 and 47.5 months respectively. Three patients were alive and disease free after more than 5 years. The ADOC scheme is highly active and manageable in the treatment of locally advanced thymoma. As a preoperative approach it should be offered to patients not amenable to surgery or to those surgically resectable but with a great deal of morbidity. © 1999 Cancer Research Campaig

    A classification prognostic score to predict OS in stage IV well-differentiated neuroendocrine tumors

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    No validated prognostic tool is available for predicting overall survival (OS) of patients with well-differentiated neuroendocrine tumors (WDNETs). This study, conducted in three independent cohorts of patients from five different European countries, aimed to develop and validate a classification prognostic score for OS in patients with stage IV WDNETs. We retrospectively collected data on 1387 patients: (i) patients treated at the Istituto Nazionale Tumori (Milan, Italy; n = 515); (ii) European cohort of rare NET patients included in the European RARECAREnet database (n = 457); (iii) Italian multicentric cohort of pancreatic NET (pNETs) patients treated at 24 Italian institutions (n = 415). The score was developed using data from patients included in cohort (i) (training set); external validation was performed by applying the score to the data of the two independent cohorts (ii) and (iii) evaluating both calibration and discriminative ability (Harrell C statistic). We used data on age, primary tumor site, metastasis (synchronous vs metachronous), Ki-67, functional status and primary surgery to build the score, which was developed for classifying patients into three groups with differential 10-year OS: (I) favorable risk group: 10-year OS &gt;= 70%; (II) intermediate risk group: 30% &lt;= 10-year OS &lt; 70%; (III) poor risk group: 10-year OS &lt; 30%. The Harrell C statistic was 0.661 in the training set, and 0.626 and 0.601 in the RARECAREnet and Italian multicentric validation sets, respectively. In conclusion, based on the analysis of three 'field-practice' cohorts collected in different settings, we defined and validated a prognostic score to classify patients into three groups with different long-term prognoses

    The prolyl hydroxylase enzymes are positively associated with hypoxia-inducible factor-1α and vascular endothelial growth factor in human breast cancer and alter in response to primary systemic treatment with epirubicin and tamoxifen

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    Introduction: The purpose of the present study was to investigate the relationship of expression of hypoxia inducible factor (HIF)-1α-modifying enzymes prolyl hydroxylase (PHD)1, PHD2 and PHD3 to response of tumours and survival in breast cancer patients enrolled in a phase II trial of neoadjuvant anthracycline and tamoxifen therapy.Methods: The expression of PHD1, PHD2 and PHD3 together with HIF-1α and the HIF-inducible genes vascular endothelial cell growth factor (VEGF) and carbonic anhydrase IX were assessed by immunohistochemistry using a tissue microarray approach in 211 patients with T2-4 N0-1 breast cancer enrolled in a randomised trial comparing single-agent epirubicin versus epirubicin and tamoxifen as the primary systemic treatment.Results: PHD1, PHD2 and PHD3 were detected in 47/179 (26.7%), 85/163 (52.2%) and 69/177 (39%) of tumours at baseline. PHD2 and PHD3 expression was moderate/strong whereas PHD1 expression was generally weak. There was a significant positive correlation between HIF-1α and PHD1 (P = 0.002) and PHD3 (P &lt; 0.05) but not PHD2 (P = 0.41). There was a significant positive relationship between VEGF and PHD1 (P &lt; 0.008) and PHD3 (P = 0.001) but not PHD2 (P = 0.09). PHD1, PHD2 and PHD3 expression was significantly increased after epirubicin therapy (all P &lt; 0.000) with no significant difference in PHD changes between the treatment arms. There was no significant difference in response in tumours that expressed PHDs and PHD expression was not associated with survival.Conclusions: Although expression of the PHDs was not related to response or survival in patients receiving neoadjuvant epirubicin, our data provide the first evidence that these enzymes are upregulated on therapy in breast cancer and that the biological effects independent of HIF make them therapeutic targets. © 2011 Fox et al.; licensee BioMed Central Ltd

    Pretreatment haemoglobin levels significantly predict the tumour response to primary chemotherapy in human breast cancer

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    The purpose of this study was to evaluate whether tumour response to primary chemotherapy in human breast cancer is influenced by baseline haemoglobin (Hb) status. A total of 157 patients with T2-4, N0-1 M0 breast cancer were treated with chemotherapy consisting of either the CMF regimen + tamoxifen (the first 76 cases) or the single-agent epirubicin (the subsequent 81) before definitive surgery. In total, 144 patients were fully assessable. Ki67, p53, bcl-2, c-erbB2, steroid hormone receptor, and microvessel density were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage >50% occurred in 72.1% of patients. Responding patients had higher baseline Hb levels and red blood cell counts than nonresponders (P<0.01 and <0.003, respectively). The distribution of disease response according to increasing cutoffs of baseline Hb status showed that from 12.5 mg l(-1) onwards, patients with Hb levels above the cutoff obtained a greater response rate than those with lower Hb values. The difference attained the statistical significance at 12.5 (76.1 vs 59.5%, P<0.05) and 13.0 g/dl(-1) (81.0 vs 57.6%, P<0.002) cutoffs, respectively. The predictive role of Hb levels was maintained in multivariate analysis after adjustment for clinical and biological characteristics and treatment regimen. Patients with baseline Hb levels </=13 g dl(-1) showed a lower treatment-induced reduction in Ki67 expression (P<0.04) and a higher Ki67 expression at postoperative evaluation (P<0.02) than their counterparts. In conclusion, low Hb levels may negatively influence the response rate of chemotherapy in breast cancer patients. Inhibition of antiproliferative activity could be a possible mechanism

    Caspase-dependent proteolytic cleavage of STAT3alpha in ES cells, in mammary glands undergoing forced involution and in breast cancer cell lines.

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    BACKGROUND: The STAT (Signal Transducers and Activators of Transcription) transcription factor family mediates cellular responses to a wide range of cytokines. Activated STATs (particularly STAT3) are found in a range of cancers. Further, STAT3 has anti-apoptotic functions in a range of tumour cell lines. After observing a proteolytic cleavage in STAT3alpha close to a potential apoptotic caspase protease cleavage site we investigated whether STAT3alpha might be a caspase substrate. METHODS: STAT3alpha status was investigated in vitro in several cell systems:- HM-1 murine embryonic stem (ES) cells following various interventions; IOUD2 murine ES cells following induction to differentiate along neural or adipocyte lineages; and in a number of breast cancer cell lines. STAT3alpha status was also analysed in vivo in wild type murine mammary glands undergoing controlled, forced involution. RESULTS: Immunoblotting for STAT3alpha in HM-1 ES cell extracts detected amino and carboxy terminal species of approximately 48 kDa and 43 kDa respectively--which could be diminished dose-dependently by cell treatment with the nitric oxide (NO) donor drug sodium nitroprusside (SNP). UV irradiation of HM-1 ES cells triggered the STAT3alpha cleavage (close to a potential caspase protease cleavage site). Interestingly, the pan-caspase inhibitor z-Val-Ala-DL-Asp-fluoromethylketone (z-VAD-FMK) and the JAK2 tyrosine kinase inhibitor AG490 both inhibited cleavage dose-dependently, and cleavage was significantly lower in a heterozygous JAK2 knockout ES cell clone. STAT3alpha cleavage also occurred in vivo in normal murine mammary glands undergoing forced involution, coinciding with a pulse of phosphorylation of residue Y705 on full-length STAT3alpha. Cleavage also occurred during IOUD2 ES cell differentiation (most strikingly along the neural lineage) and in several human breast cancer cell lines, correlating strongly with Y705 phosphorylation. CONCLUSION: This study documents a proteolytic cleavage of STAT3alpha into 48 kDa amino and 43 kDa carboxyl terminal fragments in a range of cell types. STAT3alpha cleavage occurs close to a potential caspase site, and can be inhibited dose-dependently by SNP, AG490 and z-VAD-FMK. The cleavage seems to be caspase-dependent and requires the phosphorylation of STAT3alpha at the Y705 residue. This highly regulated STAT3alpha cleavage may play an important role in modulating STAT3 transcriptional activity.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    Channel sounding and indoor radio channel characteristics in the W-band

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    This work presents directional radio channel measurements in the W-band using a commercial versatile channel sounder based on a vector network analyzer (VNA), capable of measuring scattering parameters from 75 to 500 GHz with frequency converters. The commercial setup has been modified by increasing the distance for one of the converters using precision coaxial cables and avoiding the use of amplifiers. Firstly, initial distance-dependent single-input single-output (SISO) measurements of indoor radio channels are presented to assess the validity of the setup in the 75 110 GHz frequency band with highly directive horn antennas. Then, single-input multiple-output (SIMO) radio channels were measured at 94 GHz using one directional and one omnidirectional antenna mounted on two positioners. Initial channel characterization is presented comprising root mean square (rms) delay spread, rms angular spread, K-factor, and path loss in an indoor environment at 94 GHz.This work was supported by MINECO, Spain (TEC2013-47360-C3-2-P TEC2013-47360-C3-3-P) and by European FEDER funds.Martínez Inglés, M.; Gaillot, D.; Pascual-García, J.; Molina-García-Pardo, JM.; Rodriguez Rodriguez, JV.; Rubio Arjona, L.; Juan Llacer, L. (2016). Channel sounding and indoor radio channel characteristics in the W-band. EURASIP Journal on Wireless Communications and Networking. 30:1-8. doi:10.1186/s13638-016-0530-7S1830D Zico, Ultra-wideband and 60 GHz communications for biomedical applications. Springer. http://link.springer.com/book/10.1007%2F978-1-4614-8896-5 .L Jofre, J Romeu, S Capdevila, J Abril, E Nova, M Alonso, The “challenging” world of Terahertz radiation and imaging. Proceedings of the 5th European Conference on Antennas and Propagation (EUCAP), 2011, pp. 3470–3475M Kawase, “Non-destructive evaluation method of pharmaceutical tablet by terahertz-time-domain spectroscopy: application to sound-alike medicines”, J. Infrared Millimeter Terahertz Waves, 34(9), 566–571KD Anderson, 94 GHz propagation in the evaporation duct. IEEE Trans. Antennas Propag. 38(5), 746–753 (1990)K Aydin, Y-M Lure, Millimeter wave scattering and propagation in rain: a computational study at 94 and 140 GHz for oblate spheroidal and spherical raindrops. IEEE Trans. Geosci. Remote Sens. 29(1), 593–601 (1991)C Gloaguen, An experiment for propagation studies at 94 GHz. Eighth Int. Conf. Antennas Propagation 1, 406–409 (1993)A Kajiwara, “Indoor propagation measurements at 94 GHz,” personal, indoor and mobile radio communications, 1995. Sixth IEEE Int. Symp PIMRC’95. Wireless Merging Inf. Superhighway 3, 1026 (1995)J Helminger, J Detlefsen, H Groll, Propagation properties of an indoor-channel at 94 GHz. Int. Conf. Microw Millimeter Wave Technol.Proc 98, 9–14 (1998)R Piesiewicz, R Geise, M Jacob, J Jemai, T Kurner, “Indoor channel measurements of point-to-point ultra broadband short range links between 75 GHz and 110 GHz”, in International Symposium Antennas and Propagation Society, 2008, pp. 1–4A Brizzi, A Pellegrini, Y Hao, “Experimental characterization of the propagation on the human torso at W band”, in Radio Science Meeting (Joint with AP-S Symposium), USNC-URSI, 2013, p. 39K Haneda, J Järveläinen, A Karttunen, M Kyro, J Putkonen, Indoor short-range radio propagation measurements At 60 and 70 GHz, in EuCAP 2014, The Hague, The Netherlands, 2014, pp. 1–4S Promwong, J Takada, Free space link budget estimation scheme for ultra wideband impulse radio with imperfect antennas. IEICE Electronics Express 1(7), 188–192 (2004)NL Johnson, S Kotz, N Balakrishnan, Continuous univariate distributions, vol. 1 (Wiley-Interscience, Hoboken, 1993)A Richter, Estimation of radio channel parameters: models and algorithms (Dr.-Ing. dissertation, TU Ilmenau, Ilmenau, Germany, 2005
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