88 research outputs found

    Nocturnal non-dipping pattern in untreated hypertensives at different cardiovascular risk according to the 2003 ESH/ESC guidelines.

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    To evaluate in a large population of untreated, uncomplicated essential hypertensives the relationship between alterations in nocturnal blood pressure (BP) profile, i.e. non-dipping pattern, and total cardiovascular risk.A total of 580 consecutive patients with grade 1 or 2 hypertension, referred to our outpatient clinic, underwent the following procedures: (i) clinical and routine laboratory examinations; (ii) 24-h ambulatory BP monitoring; (iii) 24-h collection for microalbuminuria; (iv) echocardiography; and (v) carotid ultrasonography. Cardiovascular risk was assessed according to the stratification scheme suggested by the 2003 ESH/ESC guidelines.According to this classification, 16.2% of the 580 patients were considered at low added risk, 42.4% at medium added risk and 41.4% at high added risk; 38.5% of the overall population was classified in the high-risk stratum because of at least one manifestation of target organ damage (TOD) and 6.3% for the presence of three or more risk factors. The prevalence rates of a non-dipping pattern (decrease in BP at nightor = 10% compared with the average daytime values) were 28.5% in low-risk, 32.6% in medium-risk and 42.2% in high-risk patients, respectively. CONCLUSIONS. Our findings show that the prevalence of a non-dipping profile is significantly greater in patients stratified at high compared with those at low and medium added risk

    Expression of chemokine receptors on circulating tumor cells in patients with solid tumors

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    <p>Abstract</p> <p>Background</p> <p>The study was performed to investigate the expression of chemokine receptors (CR) on circulating tumor cells (CTC), which may be of importance for organ-specific metastases and cancer treatment since CR are potential drug-targets.</p> <p>Methods</p> <p>Blood samples from patients with metastatic carcinoma (MC) or melanoma (MM) were enriched for CTC and expression of CR (CXCR4, CCR6, CCR7 and CCR9) was evaluated by flow cytometry.</p> <p>Results</p> <p>CTC were detected in 49 of 68 patients (72%) [28 MC; 21 MM] with a median number of 3 CTC (range: 1-94)/10 mL of blood. CXCR4 was expressed on CTC in 82% (40/49) of patients [median number 1 CTC/10 mL blood; range 1-14] and CCR6 in 29 patients (59%; median 1, range: 1-14). In MM patients, CCR7 was expressed on CTC in 6 (29%) samples and CCR9 in 12 (57%). A positive correlation between surface expression of CR and organ-specific metastatic pattern was not observed.</p> <p>Conclusions</p> <p>CR were expressed on CTC of patients with solid tumors. Along with our findings, the observation that CR could be involved in CTC proliferation and migration of tumor cells appoints CTC as potential CR-antagonist therapeutic target.</p

    The importance for immunoregulation for long-term cancer control.

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    Immune checkpoint blockades have recently emerged as a breakthrough treatment for solid tumors showing high response rates and long durability. In melanoma, the combination of ipilimumab with nivolumab showed high efficacy. However, still half the patients do not respond to this treatment. In order to increase the therapeutic ratio in melanoma and other cancers, different approaches are under evaluation. Three relevant questions are at the moment driving the research community: how to maximize benefit while minimizing toxicity; how to better identify patients who are more likely to benefit from immunotherapy; how to convert nonresponders into responders. In this review we summarize the most recent findings and we outline the most likely future challenges

    Negative enrichment by immunomagnetic nanobeads for unbiased characterization of circulating tumor cells from peripheral blood of cancer patients

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    BACKGROUND: A limitation of positive selection strategies to enrich for circulating tumor cells (CTCs) is that there might be CTCs with insufficient expression of the surface target marker which may be missed by the procedure. We optimized a method for enrichment, subsequent detection and characterization of CTCs based on depletion of the leukocyte fraction. METHODS: The 2-step protocol was developed for processing 20 mL blood and based on red blood cell lysis followed by leukocyte depletion. The remaining material was stained with the epithelial markers EpCAM and cytokeratin (CK) 7/8 or for the melanoma marker HMW-MAA/MCSP. CTCs were detected by flow cytometry. CTCs enriched from blood of patients with carcinoma were defined as EpCAM+CK+CD45-. CTCs enriched from blood of patients with melanoma were defined as MCSP+CD45-. One-hundred-sixteen consecutive blood samples from 70 patients with metastatic carcinomas (n = 48) or metastatic melanoma (n = 22) were analyzed. RESULTS: CTCs were detected in 47 of 84 blood samples (56%) drawn from carcinoma patients, and in 17 of 32 samples (53%) from melanoma patients. CD45-EpCAM-CK+ was detected in pleural effusion specimens, as well as in peripheral blood samples of patients with NSCLC. EpCAM-CK+ cells have been successfully cultured and passaged longer than six months suggesting their neoplastic origin. This was confirmed by CGH. By defining CTCs in carcinoma patients as CD45-CK+ and/or EpCAM+, the detection rate increased to 73% (61/84). CONCLUSION: Enriching CTCs using CD45 depletion allowed for detection of epithelial cancer cells not displaying the classical phenotype. This potentially leads to a more accurate estimation of the number of CTCs. If detection of CTCs without a classical epithelial phenotype has clinical relevance need to be determined

    IUE observations of blue horizontal branch stars in the globular clusters M 3 and NGC 6752

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    IUE observations of 3 blue horizontal branch (BHB) stars in M 3 and 4 stars in NGC 6752 are presented. In addition, unpublished IUE archive data have been used for 5 more BHB stars in NGC 6752. Using the most recent model atmospheres (Kurucz 1992) the physical parameters of these stars have been derived, and compared with the ZAHB evolutionary tracks by Dorman et al. (1993). All the stars, including those that appear to be evolved off the ZAHB, are consistent with the theoretical predictions. The present results are compared with those obtained in previous similar analyses: the possible presence of some low-gravity stars is confirmed in M 3, while no clear indication is found of multiple stellar populations on the HB of NGC 6752. However different populations, if any, would be difficult to identify in the logg-logT_e_ plane because of the simultaneous effect of various parameters and the poor accuracy of the gravity estimates from IUE data

    Comparison of T-cell receptor repertoire restriction in blood and tumor tissue of colorectal cancer patients

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    Several immunotherapeutic approaches rely on antigen-specific T-cells. Restrictions in the T-cell receptor (TCR) repertoire were reported as indicator of anti-tumor cytotoxic T-lymphocyte (CTL) response in various tumor entities. It is unclear yet whether a TCR restriction in peripheral blood mirrors the tumor compartment. We compared the expression of TCR Vβ-families for the quantification of TCR repertoire alterations in blood and tissue samples from patients with colorectal carcinoma. Blood samples from patients with colorectal carcinoma and healthy volunteers and tissue samples of normal colonic mucosa and colorectal carcinoma were analyzed. Relative Vβ-family quantification was performed based on quantitative reverse transcribed PCR. Standard deviation and average mean of the single families were determined. Two variables describing the degree of Vβ-repertoire restriction were defined. Forty-eight blood samples and 37 tissue samples were analyzed. TCR repertoire restriction was higher in blood of tumor patients than in blood of healthy controls (p < 0.05). No difference in the degree of TCR repertoire restriction was found between carcinoma and unaffected colon tissue. We found no corresponding elevated TCR families among the different compartments blood, normal colon, and carcinoma tissue of the same patient. In conclusion, we observed a repertoire restriction in peripheral blood as well as in tumor tissue of cancer patients. However, in tumor tissue, repertoire alterations were comparable to normal mucosa, suggesting compartment-specific TCR distribution rather than alterations due to tumor-T-cell interaction questioning the presence of highly restricted clonal T-cell expansions in colorectal cancer as they have been described in other, assumingly more immunogenic tumor entities

    Pankkialan operatiiviset riskit tulevaisuudessa

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    Opinnäytetyön tarkoitus oli kartoittaa operatiivisten riskien tulevaisuuden näkymiä pankkitoiminnassa Suomessa. Opinnäytetyön tutkimuksellisena tavoitteena oli asiantuntijoiden avustuksella selvittää tulevaisuuden näkymiä riskimaailmassa. Kehittämistavoitteena oli tuottaa konkreettisia suuntaviivoja tulevaisuuden riskien näkökulmaan ja niiden hallinnointiin. Tietoperustassa tarkasteltiin finanssialaa pankkialan näkökulmasta. Riskin, riskienhallinnan ja operatiivisen riskin määritelmiä sekä tulevaisuuden ennakointia. Tutkimuksellisessa osiossa tarkoituksena oli tuottaa tutkittavasta aiheesta sellaista tietoa ja ymmärrystä, jota voidaan hyödyntää tulevaisuudessa operatiivisten riskien tunnistamisessa ja hallinnassa. Pääaineiston keruu toteutettiin Delfoi-menetelmällä antamalla viisi tulevaisuuden väittämää panelistien arvioitavaksi. Tutkimustulokset osoittivat, että tulevaisuuden ennakoinnin ja riskienhallinnan yhdistäminen on edelleen haastavaa. Digitalisaatio tuo omat haasteet riskienhallinnalle, henkilöstön erikoisosaaminen nousee kilpailuvaltiksi, vastuullisuuteen kiinnitetään entistä enemmän huomiota asiakkaiden näkökulmasta sekä pankkitoiminta koetaan edelleen ihmisten väliseksi luottamuskaupaksi eikä sitä suhdetta voi digitalisoida. Johtopäätöksenä todetaan, että esille nousee selkeästi neljä teemaa, joihin tulee riskienhallinnan tulevaisuuden näkökulmasta reagoida. Nämä ovat digitalisaatio ja palveluiden siirtyminen verkkoon tuo haasteita verkkoturvallisuuden kannalta, yhteistyön vahvistaminen eri toimijoiden välillä noussee kilpailuvaltiksi, riskienhallinnan fokusointi vaatii robotiikan ja osaavan henkilöstön yhdistelmää sekä vastuullinen yritystoiminta vahvistuu. Opinnäytetyön tuotoksena tunnistettiin neljä mahdollista tulevaisuuden riskiä ja niiden hallintakeinot. Tutkimus antaa kokonaiskuvan tulevaisuuden näkökulmista operatiivisten riskien tunnistamisessa ja hallinnoinnissa. Opinnäytetyö on hyödynnettävissä yleisesti organisaatioissa riskienhallinnan kehittämisen tukena.The purpose of this study is to examine the future of the banking industry in Finland from the perspective of operational risks. The aim of this research is to examine with the help of experts the future views in the risk industry and to create a better insight of how the future looks and how operational risks can be managed. The theory section focuses on the financial industry from the perspective of banking, future forecasts and the definition of risk, risk management and operational risk. In the research section the aim was to produce information about the topic that can be used for identification and manage-ment of operational risks in the future. The main research data acquisition was conducted using the Delfoi-method by providing five future propositions to be evaluated by chosen panelists. The results of the study showed that combining the future perspective and risk management is still challenging. Digitalization brings its own challenges to risk management, special expertise of the employees will become a competitive asset, customers will pay increasing attention to sustainability and banking will still be considered as a confidential relationship between people, which therefore cannot be digitalized. The conclusion was that there are four clear themes that must be responded from the future perspective of risk management. These themes are digitalization and services moving online, which brings challenges from the perspective of online security, open cooperation and sharing of information will become a competitive asset, focusing of risk management will require a combination of robotics and humans, and sustainable entrepreneurship will become stronger. As an outcome of this study, a concept of possible future operational risks was gained, as well as risk management methods. The study provides an overview into the perspectives of the future of operational risk identification and management, and is also publicly available to give support to be utilized in the development of risk management in organizations

    High-Resolution 3D FEM Stability Analysis of the Sabereebi Cave Monastery, Georgia

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    This study assesses the static stability of the artificial Sabereebi Cave Monastery southeast of Georgia's capital, Tbilisi. The cliff into which these Georgian-Orthodox caverns, chapels, and churches were carved consists of a five-layered sequence of weak sedimentary rock—all of which bear a considerable failure potential and, consequently, pose the challenge of preservation to geologists, engineers, and archaeologists. In the first part of this study, we present a strategy to process point cloud data from drone photogrammetry as well as from laser scanners acquired in- and outside the caves into high-resolution CAD objects that can be used for numerical modeling ranging from macro- to micro-scale. In the second part, we explore four distinct series of static elasto-plastic finite element stability models featuring different levels of detail, each of which focuses on specific geomechanical scenarios such as classic landsliding due to overburden, deformation of architectural features as a result of stress concentration, material response to weathering, and pillar failure due to vertical load. With this bipartite approach, the study serves as a comprehensive 3D stability assessment of the Sabereebi Cave Monastery on the one hand; on the other hand, the established procedure should serve as a pilot scheme, which could be adapted to different sites in the future combining non-invasive and relatively cost-efficient assessment methods, data processing and hazard estimation

    IUE observations of UB-bright stars in M 3

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    IUE UV observations of three "UV-bright" stars in M3 are presented. The brightest object - vZ1128 - is confirmed to be a bright Post-AGB star with logL/Lsun=3.09 and Te=30,000 K, which contributes about 25% of the integrated UV light from the cluster at λ=1500Å. The nature of the two other stars, i.e. 524 (logL/Lsun=2.06, Te=33,000 K) and 7561 (iogL/Lsun=2.04, Te=35,000 K), is still controversial. They might be respectively AGB-manque' stars of the sort suggested by Greggio & Renzini (1990), or the result of mergers of binary systems according to Iben (1990), but other possibilities are considered and discussed
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