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Sample records for potential clinical advantages

  1. Proton therapy of cancer: Potential clinical advantages and cost-effectiveness

    International Nuclear Information System (INIS)

    Lundkvist, Jonas; Ekman, Mattias; Rehn Ericsson, Suzanne; Glimelius, Bengt; Akademiska sjukhuset, Uppsala

    2005-01-01

    Proton therapy may offer potential clinical advantages compared with conventional radiation therapy for many cancer patients. Due to the large investment costs for building a proton therapy facility, however, the treatment cost with proton radiation is higher than with conventional radiation. It is therefore important to evaluate whether the medical benefits of proton therapy are large enough to motivate the higher costs. We assessed the cost-effectiveness of proton therapy in the treatment of four different cancers: left-sided breast cancer, prostate cancer, head and neck cancer, and childhood medulloblastoma. A Markov cohort simulation model was created for each cancer type and used to simulate the life of patients treated with radiation. Cost and quality adjusted life years (QALYs) were used as primary outcome measures. The results indicated that proton therapy was cost-effective if appropriate risk groups were chosen. The average cost per QALY gained for the four types of cancer assessed was about Euro 10,130. If the value of a QALY was set to Euro 55,000, the total yearly net benefit of treating 925 cancer patients with the four types of cancer was about Euro 20.8 million. Investment in a proton facility may thus be cost-effective. The results must be interpreted with caution, since there is a lack of data, and consequently large uncertainties in the assumptions used

  2. Submitted for your consideration: potential advantages of a novel clinical trial design and initial patient reaction

    Directory of Open Access Journals (Sweden)

    Matthew Shane Loop

    2012-08-01

    Full Text Available In many circumstances, individuals do not respond identically to the same treatment. This phenomenon, which is called treatment response heterogeneity (TRH, appears to be present in treatments for many conditions, including obesity. Estimating the total amount of TRH, predicting an individual’s response, and identifying the mediators of TRH are of interest to biomedical researchers. Clinical investigators and physicians commonly postulate that some of these mediators could be genetic. Current designs can estimate TRH as a function of specific, measurable observed factors; however, they cannot estimate the total amount of TRH, nor provide reliable estimates of individual persons’ responses. We propose a new repeated randomizations design (RRD, which can be conceived as a generalization of the Balaam design, that would allow estimates of that variability and facilitate estimation of the total amount of TRH, prediction of an individual’s response, and identification of the mediators of TRH. In a pilot study, we asked 118 subjects entering a weight loss trial for their opinion of the RRD, and they stated a preference for the RRD over the conventional 2-arm parallel groups design. Research is needed as to how the RRD will work in practice and its relative statistical properties, and we invite dialogue about it.

  3. Logistics potentials in business competitive advantage creation

    Directory of Open Access Journals (Sweden)

    Rafał Matwiejczuk

    2013-12-01

    Full Text Available Background: Companies constantly search for ways to achieve and sustain long-term competitive advantage. Among the factors influencing the competitive advantage creation there are so called logistics potentials, which constitute a component part of a business strategic potentials. Logistics resources, logistics capabilities and logistics competences are the main components of the logistics potentials structure and hierarchy. Methods: In order to recognize the logistics potentials which determine the competitive advantage creation one may use the assumptions and elements of contemporary management concepts, including strategic management. In particular the article deals with Resource-Based View (RBV, Dynamic Capabilities Concept (DCC and - first of all - Competence-Based Management (CBM. Results and conclusions: Several significant research projects have presented a wide scope and a large number of possibilities of logistics potentials (and logistics competences in particular influence on business competitive advantage creation. The article briefly presents the research results conducted by: (1 Michigan State University (USA, (2 European Logistics Association (ELA in cooperation with A.T. Kearney, (3 Computer Sciences Corporation and (4 Capgemini. The research results have pointed out to differentiated but at the same distinctive symptoms of logistics competences influence on competitive advantage creation. The article also refers to the results of the research carried out by the Chair of Logistics & Marketing at Opole University (Poland in companies operating in Poland. The research has been mainly dealing with the significance of logistics competences in competitive advantage creation.

  4. Clinical advantages of single port laparoscopic hepatectomy.

    Science.gov (United States)

    Han, Jae Hyun; You, Young Kyoung; Choi, Ho Joong; Hong, Tae Ho; Kim, Dong Goo

    2018-01-21

    To evaluate the clinical advantages of single-port laparoscopic hepatectomy (SPLH) compare to multi-port laparoscopic hepatectomy (MPLH). We retrospectively reviewed the medical records of 246 patients who underwent laparoscopic liver resection between January 2008 and December 2015 at our hospital. We divided the surgical technique into two groups; SPLH and MPLH. We performed laparoscopic liver resection for both benign and malignant disease. Major hepatectomy such as right and left hepatectomy was also done with sufficient disease-free margin. The operative time, the volume of blood loss, transfusion rate, and the conversion rate to MPLH or open surgery was evaluated. The post-operative parameters included the meal start date after operation, the number of postoperative days spent in the hospital, and surgical complications was also evaluated. Of the 246 patients, 155 patients underwent SPLH and 91 patients underwent MPLH. Conversion rate was 22.6% in SPLH and 19.8% in MPLH ( P = 0.358). We performed major hepatectomy, which was defined as resection of more than 2 sections, in 13.5% of patients in the SPLH group and in 13.3% of patients in the MPLH group ( P = 0.962). Mean operative time was 136.9 ± 89.2 min in the SPLH group and 231.2 ± 149.7 min in the MPLH group ( P started earlier in the SPLH group (1.06 ± 0.27 d after operation) than in the MPLH group (1.63 ± 1.27 d) ( P < 0.001). The mean hospital stay after operation was non-significantly shorter in the SPLH group than in the MPLH group (7.82 ± 2.79 d vs 7.97 ± 3.69 d, P = 0.744). The complication rate was not significantly different ( P = 0.397) and there was no major perioperative complication or mortality case in both groups. Single-port laparoscopic liver surgery seems to be a feasible approach for various kinds of liver diseases.

  5. Potential Advantages of Underground Nuclear Parks

    International Nuclear Information System (INIS)

    Myers, Carl W.; Elkins, Ned Z.; Kunze, Jay F.; Mahar, James M.

    2006-01-01

    In this paper we argue that an underground nuclear park (UNP) could potentially lead to lower capital and operating cost for the reactors installed in the UNP compared to the traditional approach, which would be to site the reactors at the earth's surface at distributed locations. The UNP approach could also lead to lower waste management cost. A secondary benefit would be the increased margins of safety and security that would be realized simply as a consequence of siting the reactors underground. Lowered capital and operating cost for a UNP relative to traditional reactor siting is possible through the aggregate effect of the elimination of containment structures, in-place decommissioning, reduced physical security costs, reduced weather-related costs, reduced cost of liability insurance and reduced unit-cost for the nth reactor made possible through the continuous construction of multiple reactors at the same underground location. Other cost reductions might be possible through the transfer of the capital cost for part of the underground construction from the reactor owners to the owners of the UNP. Lower waste management cost is possible by siting the UNP at a location where there are geological and hydrological conditions suitable for hosting both the reactors and the repository for the waste from those reactors. After adequate storage and cooling, and assuming direct disposal, this would enable the spent fuel from the reactors to be transported directly to the repository and remain entirely underground during the transport process. Community concerns and transportation costs would be significantly reduced relative to current situations where the reactors are separated from the repository by long distances and populated areas. The concept for a UNP in bedded salt is used to develop a rough order of magnitude cost estimate for excavation of the reactor array portion of a UNP. Excavation costs appear to be only a small fraction of the overall power plant costs

  6. Rhenium-188 - advantages and clinical potential for use of a readily available, cost effective therapeutic radioisotope for applications in nuclear medicine, oncology and interventional cardiology

    International Nuclear Information System (INIS)

    Knapp, F.F. jr.

    2002-01-01

    'conditioning' prior to stem cell rescue in leukemia patients. In addition to the development of the Re-188-P2045 peptide for the potential clinical treatment of lung tumors, a variety of other Re-188-labeled peptides and antibodies are being evaluated for tumor therapy, and Re-188-Lipiodol is being used for palliative therapy of hepatocellular carcinoma in IAEA-supported trials. Installation of the W-188/Re-188 generator in a centralized radiopharmacy would be expected to optimize the availability and costs of Re-188. This presentation will provide an overview of the current and expected broader role of Re-188 as an important therapeutic radioisotope. (author)

  7. [Overdenture supported by natural teeth: analysis of clinical advantages].

    Science.gov (United States)

    Scotti, R; Melilli, D; Pizzo, G

    2003-05-01

    Hybrid prosthesis supported by natural teeth (overdenture) is widely used in clinical practice and should be executed whenever the clinical conditions suggest it. Through a critical review of the literature, the anatomical, functional, psychological and clinical advantages are emphasized. Among the first ones, the prophylaxis of residual anatomical components, due to the limitation of bone resorption, and the preservation of sensorial proprioception are relevant. Important advantages are also represented by a better crown-root ratio of residual teeth supporting overdenture, with the consequent improvement of the longitudinal prognosis of such teeth. The greater retention and stability of overdenture in comparison with complete denture greatly improve the masticatory efficacy. The psychological advantages resulting from the dental anchorage, which allows the patient to be more confident in social life, are also relevant. Finally, when the dental support is lost, converting overdenture into complete denture is simple and quick, and makes easier the longitudinal clinical maintenance of the denture.

  8. Clinical applications of SPECT/CT: advantages and limitations

    International Nuclear Information System (INIS)

    Rigo, P.

    2006-01-01

    The application of hybrid SPECT cameras in Nuclear Medicine follows the revolutionary introduction of PET/CT. This review focuses on the advantages and limitations of SPECT/CT in its various clinical indications. It appears that SPECT/CT will be a clear factor of progress for Nuclear Medicine. (author)

  9. Platelet Function Tests: Preanalytical Variables, Clinical Utility, Advantages, and Disadvantages.

    Science.gov (United States)

    Hvas, Anne-Mette; Grove, Erik Lerkevang

    2017-01-01

    Platelet function tests are mainly used in the diagnostic work-up of platelet disorders. During the last decade, the additional use of platelet function tests to evaluate the effect of antiplatelet therapy has also emerged in an attempt to identify patients with an increased risk of arterial thrombosis. Furthermore, platelet function tests are increasingly used to measure residual effect of antiplatelet therapy prior to surgery with the aim of reducing the risk of bleeding. To a limited extend, platelet function tests are also used to evaluate hyperaggregability as a potential marker of a prothrombotic state outside the setting of antiplatelet therapy. This multifaceted use of platelet function tests and the development of simpler point-of-care tests with narrower application have increased the use of platelet function testing and also facilitated the use of platelet function tests outside the highly specialized laboratories. The present chapter describes the preanalytical variables, which should be taken into account when planning platelet function testing. Also, the most widely used platelet function tests are introduced, and their clinical utility and their relative advantages and disadvantages are discussed.

  10. Clinical advantages of 3.0 T MRI over 1.5 T

    Energy Technology Data Exchange (ETDEWEB)

    Willinek, Winfried A. [Department of Radiology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn (Germany)], E-mail: winfried.willinek@ukb.uni-bonn.de; Schild, Hans H. [Department of Radiology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn (Germany)

    2008-01-15

    Since approval by the FDA in 2000, human MR imaging (MRI) at 3.0 T has been increasingly used in clinical practice. In spite of the potential technical challenges, a number of clinical advantages of 3.0 T MRI over 1.5 T have been identified in the recent years. This article reviews the benefits and the current knowledge of 3.0 T whole-body MRI from an evidence-based perspective and summarizes its clinical applications.

  11. Clinical advantages of 3.0 T MRI over 1.5 T

    International Nuclear Information System (INIS)

    Willinek, Winfried A.; Schild, Hans H.

    2008-01-01

    Since approval by the FDA in 2000, human MR imaging (MRI) at 3.0 T has been increasingly used in clinical practice. In spite of the potential technical challenges, a number of clinical advantages of 3.0 T MRI over 1.5 T have been identified in the recent years. This article reviews the benefits and the current knowledge of 3.0 T whole-body MRI from an evidence-based perspective and summarizes its clinical applications

  12. Thermal plasma spraying for SOFCs: Applications, potential advantages, and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Hui, Rob; Wang, Zhenwei; Jankovic, Jasna; Yick, Sing; Maric, Radenka; Ghosh, Dave [National Research Council Institute for Fuel Cell Innovation, 4250 Wesbrook Mall, Vancouver, BC V6T 1W5 (Canada); Kesler, Olivera [National Research Council Institute for Fuel Cell Innovation, 4250 Wesbrook Mall, Vancouver, BC V6T 1W5 (Canada); Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC V6T 1Z4 (Canada); Rose, Lars [National Research Council Institute for Fuel Cell Innovation, 4250 Wesbrook Mall, Vancouver, BC V6T 1W5 (Canada); Department of Materials Engineering, University of British Columbia, 309-6350 Stores Road, Vancouver, BC V6T 1Z4 (Canada)

    2007-07-10

    In this article, the applications, potential advantages, and challenges of thermal plasma spray (PS) processing for nanopowder production and cell fabrication of solid oxide fuel cells (SOFCs) are reviewed. PS processing creates sufficiently high temperatures to melt all materials fed into the plasma. The heated material can either be quenched into oxide powders or deposited as coatings. This technique has been applied to directly deposit functional layers as well as nanopowder for SOFCs application. In particularly, low melting point and highly active electrodes can be directly fabricated on zirconia-based electrolytes. This is a simple processing technique that does not require the use of organic solvents, offering the opportunity for flexible adjustment of process parameters, and significant time saving in production of the cell and cost reduction compared with tape casting, screen printing and sintering processing steps. Most importantly, PS processing shows strong potential to enable the deposition of metal-supported SOFCs through the integrated fabrication of membrane-electrode assemblies (MEA) on porous metallic substrates with consecutive deposition steps. On the other hand, the application of PS processing to produce SOFCs faces some challenges, such as insufficient porosity of the electrodes, the difficulty of obtaining a thin (<10 {mu}m) and dense electrolyte layer. Fed with H{sub 2} as the fuel gas and oxygen as the oxidant gas, the plasma sprayed cell reached high power densities of 770 mW cm{sup -2} at 900 C and 430 mW cm{sup -2} at 800 C at a cell voltage of 0.7 V. (author)

  13. Clinical advantages of three dimensional cine cardiac images

    International Nuclear Information System (INIS)

    Kinosada, Yasutomi; Okuda, Yasuyuki; Nakagawa, Tsuyoshi; Itou, Takafumi; Hattori, Takao.

    1996-01-01

    We evaluated clinical advantages and the quantitativeness of computerized three-dimensional (3D) cinematic images of a human heart, which were produced with a set of magnetic resonance (MR) images by using the computer graphic technique. Many contiguous, multi-location and multi-phase short axis images were obtained with the ECG gated conventional and fast cardiac imaging sequences in normal volunteers and selected patients with myocardial infarction, hypertrophic cardiomyopathy, dilated cardiomyopathy and left ventricular dysfunction. Judging by visual impressions of the computerized 3D cinematic cardiac images, we could easily understand and evaluate the myocardial motions or the anatomic and volumetric changes of a heart according to the cardiac phases. These images were especially useful to compare the wall motion, the left ventricular ejection-fraction (LVEF), or other cardiac functions and conditions between before and after therapeutic procedures such as percutaneous transluminal coronary angioplasty for patients with myocardial infarction. A good correlation between the LVEF calculated from a set of computerized 3D cinematic images and the ultra sound examinations were found. The results of our study showed that computerized 3D cinematic cardiac images were clinically useful to understand the myocardial motions qualitatively and to evaluate cardiac functions such as the LVEF quantitatively. (author)

  14. [Laboratory unification: advantages and disadvantages for clinical microbiology].

    Science.gov (United States)

    Andreu, Antonia; Matas, Lurdes

    2010-10-01

    This article aims to reflect on which areas or tasks of microbiology laboratories could be unified with those of clinical biochemistry, hematology, immunology or pathology laboratories to benefit patients and the health system, as well as the areas that should remain independent since their amalgamation would not only fail to provide a benefit but could even jeopardize the quality of microbiological diagnosis, and consequently patient care. To do this, the distinct analytic phases of diagnosis are analyzed, and the advantages and disadvantages of amalgamation are evaluated in each phase. The pros and cons of the unification of certain areas such as the computer system, occupational risk units, customer service, purchasing logistics, and materials storage, etc, are also discussed. Lastly, the effect of unification on urgent microbiology diagnosis is analyzed. Microbiological diagnosis should be unique. The microbiologist should perform an overall evaluation of the distinct techniques used for a particular patient, both those that involve direct diagnosis (staining, culture, antigen detection techniques or molecular techniques) and indirect diagnosis (antibody detection). Moreover, the microbiology laboratory should be independent, with highly trained technicians and specialists in microbiology that provide added value as experts in infection and as key figures in the process of establishing a correct etiological diagnosis. Copyright © 2010 Elsevier España S.L. All rights reserved.

  15. Will the next generation of basal insulins offer clinical advantages?

    Science.gov (United States)

    Garber, A J

    2014-06-01

    The 21st century has seen the arrival of several insulin analogue products and the refinement of insulin regimens, with widespread advocacy of continuous titration algorithms and earlier initiation of supplementary insulin therapy (predominantly using basal insulins) in type 2 diabetes. Nevertheless, many insulin-treated diabetes patients remain in poor glycaemic control. This might reflect insufficient titration effort or lax adherence, but these issues could in some cases result from concerns about hypoglycaemia. Certainly there is scope for improving the pharmacokinetic/pharmacodynamic (PK/PD) profile of basal insulin, and three new products offer this prospect. Insulin degludec, now in clinical use, and PEGylated insulin lispro, in development, have greatly extended action profiles that result from two very different, but unique, mechanisms. With once-daily dosing, these insulins produce stable PK/PD profiles at steady state, associated with a low incidence of hypoglycaemia. The feasibility of varied daily dose timing has also been confirmed with insulin degludec. High strength formulations of insulin glargine and insulin degludec offer the prospect of a reduced injection number/volume in high dose users, and in the case of glargine, the PK/PD profile might also be favourably modified. This review considers critically the clinical evidence and expectations we should have for these new basal insulins. © 2013 John Wiley & Sons Ltd.

  16. INNOVATION POTENTIAL AS A DETERMINING FACTOR IN THE GROWTH OF COMPETITIVE ADVANTAGES BUILDING PRODUCTS

    OpenAIRE

    T. U. Levitsky; A. M. Esetova

    2014-01-01

    It is stipulated that the construction company, chosen the strategy of economic growth, should have some competitive advantages, determining opportunities for sustainable development and effective improving, and operational efficiency increase. One of the factors of the competitiveness increase of construction products is the innovative potential of construction industry. Methodical approaches to the evaluation of innovative capacity and its effect on the growth of competitive advantages have...

  17. INNOVATION POTENTIAL AS A DETERMINING FACTOR IN THE GROWTH OF COMPETITIVE ADVANTAGES BUILDING PRODUCTS

    Directory of Open Access Journals (Sweden)

    T. U. Levitsky

    2014-01-01

    Full Text Available It is stipulated that the construction company, chosen the strategy of economic growth, should have some competitive advantages, determining opportunities for sustainable development and effective improving, and operational efficiency increase. One of the factors of the competitiveness increase of construction products is the innovative potential of construction industry. Methodical approaches to the evaluation of innovative capacity and its effect on the growth of competitive advantages have been proposed. 

  18. Review of MammoSite brachytherapy: Advantages, disadvantages and clinical outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Bensaleh, Saleh; Bezak, Eva; Borg, Martin (Dept. of Radiation Oncology, Royal Adelaide Hospital, Adelaide (Australia))

    2009-05-15

    Background. The MammoSite radiotherapy system is an alternative treatment option for patients with early-stage breast cancer to overcome the longer schedules associated with external beam radiation therapy. The device is placed inside the breast surgical cavity and inflated with a combination of saline and radiographic contrast to completely fill the cavity. The treatment schedule for the MammoSite monotherapy is 34 Gy delivered in 10 fractions at 1.0 cm from the balloon surface with a minimum of 6 hours between fractions on the same day. Material and methods. This review article presents the advantages, disadvantages, uncertainties and clinical outcomes associated with the MammoSite brachytherapy (MSB). Results. Potential advantages of MSB are: high localised dose with rapid falloff for normal tissue sparing, minimum delay between surgery and RT, catheter moves with breast, improved local control, no exposure to staff, likely side-effects reduction and potential cost/time saving (e.g. for country patients). The optimal cosmetic results depend on the balloon-to-skin distance. Good-to-excellent cosmetic results are achieved for patients with balloon-skin spacing of =7 mm. There have been very few published data regarding the long term tumour control and cosmesis associated with the MSB. The available data on the local control achieved with the MSB were comparable with other accelerated partial breast irradiation techniques. The contrast medium inside the balloon causes dose reduction at the prescription point. Current brachytherapy treatment planning systems (BTPS) do not take into account the increased photon attenuation due to high Z of contrast. Some BTPS predicted up to 10% higher dose near the balloon surface compared with Monte Carlo calculations using various contrast concentrations (5-25%). Conclusion. Initial clinical results have shown that the MammoSite device could be used as a sole radiation treatment for selected patients with early stage breast cancer

  19. Review of MammoSite brachytherapy: Advantages, disadvantages and clinical outcomes

    International Nuclear Information System (INIS)

    Bensaleh, Saleh; Bezak, Eva; Borg, Martin

    2009-01-01

    Background. The MammoSite radiotherapy system is an alternative treatment option for patients with early-stage breast cancer to overcome the longer schedules associated with external beam radiation therapy. The device is placed inside the breast surgical cavity and inflated with a combination of saline and radiographic contrast to completely fill the cavity. The treatment schedule for the MammoSite monotherapy is 34 Gy delivered in 10 fractions at 1.0 cm from the balloon surface with a minimum of 6 hours between fractions on the same day. Material and methods. This review article presents the advantages, disadvantages, uncertainties and clinical outcomes associated with the MammoSite brachytherapy (MSB). Results. Potential advantages of MSB are: high localised dose with rapid falloff for normal tissue sparing, minimum delay between surgery and RT, catheter moves with breast, improved local control, no exposure to staff, likely side-effects reduction and potential cost/time saving (e.g. for country patients). The optimal cosmetic results depend on the balloon-to-skin distance. Good-to-excellent cosmetic results are achieved for patients with balloon-skin spacing of =7 mm. There have been very few published data regarding the long term tumour control and cosmesis associated with the MSB. The available data on the local control achieved with the MSB were comparable with other accelerated partial breast irradiation techniques. The contrast medium inside the balloon causes dose reduction at the prescription point. Current brachytherapy treatment planning systems (BTPS) do not take into account the increased photon attenuation due to high Z of contrast. Some BTPS predicted up to 10% higher dose near the balloon surface compared with Monte Carlo calculations using various contrast concentrations (5-25%). Conclusion. Initial clinical results have shown that the MammoSite device could be used as a sole radiation treatment for selected patients with early stage breast cancer

  20. THE RESOURCE POTENTIAL AND THE DEVELOPMENT STRATEGY OF COMPETITIVE ADVANTAGES IN BUSINESS STRUCTURE

    Directory of Open Access Journals (Sweden)

    Okolnishnikova Irina Yurievna

    2013-02-01

    Full Text Available The aim of the research is the development of theoretical approaches to the study of the essence and structure of the resource potential of entrepreneurship in the context of the development strategy of the competitive advantages in business structure. As the research methodology the complex of principles and tools of system and axiological approaches is used. According to the results of the conducted research, possessing the scientific novelty, the conceptual apparatus is clarified and the author's definition of the resource potential of the enterprise is given, a model of the resource potential structure in commercial organization is analyzed and the mechanism of strategy formation for sustainable competitive advantages provision of the organization on the basis of the effective use of its resource potential is identified. Area of application of the research results is the control of competitiveness in general and resource potential of entrepreneurial structures, in particular at all levels of the socio-economic system of society.

  1. Clinical and echocardiographic assessment of the Medtronic Advantage aortic valve prosthesis: the Scandinavian multicentre, prospective study

    DEFF Research Database (Denmark)

    Haaverstad, Rune; Vitale, Nicola; Karevold, Asbjørn

    2006-01-01

    OBJECTIVE: The aim of this report is the prospective, multicentre evaluation of clinical results and haemodynamic performance of the Medtronic Advantage aortic valve prosthesis. METHODS: From April 2001 to June 2003, 166 patients (male:female 125:41; mean (SD) age 61.8 (11.8) years) received...... an aortic advantage valve prosthesis. Complete cumulative follow-up was 242.7 patient-years (maximum 3.2; mean 1.6 years). Postoperatively, patients underwent early (within 30 days) and 1 year transthoracic echocardiography. RESULTS: 30 day mortality was 2.4% (n = 4). Kaplan-Meier estimates of freedom from...... echocardiography. CONCLUSIONS: Haemodynamic performance and early clinical results of Medtronic advantage in the aortic position were satisfactory and comparable with those of other bileaflet valves in current clinical use....

  2. Preclinical and clinical experience in vascular gene therapy: advantages over conservative/standard therapy.

    Science.gov (United States)

    Nikol, S; Huehns, T Y

    2001-04-01

    No systemic pharmacological treatment has been shown to convincingly reduce the incidence of restenosis after angioplasty or increase the formation of collaterals in ischemic tissue in patients. The lack of success of many pharmaceutical agents in reducing restenosis rates or in inducing angiogenesis post-angioplasty and following stent implantation has encouraged the development of new technological treatment approaches. Gene therapy is a novel strategy with the potential to prevent some of the sequelae after arterial injury, particularly cell proliferation, and to induce growth of new vessels or remodeling of pre-existing vessel branches, which may help patients with critical ischemia. Gene therapy strategies have the advantage of minimizing systemic side effects and may have a long-term effect as the encoded protein is released. Most clinical trials investigating gene therapy for vascular disease have been uncontrolled phase I and IIa trials. Gene therapy into vessels with the genes for growth factors has been demonstrated to be feasible and efficient. Local drug delivery devices have been used in combination with gene therapy in several trials to maximize safety and efficiency. Data from experimental animal work indicates that gene therapy may modify intimal hyperplasia after arterial injury, but there are few clinical trials on restenosis in patients. Preliminary clinical results show only limited success in altering restenosis rates. In vitro and experimental in vivo investigations into gene therapy for angiogenesis demonstrate increased formation of collaterals and functional improvement of limb ischemia. There is some evidence of increased collateral formation and clinical improvement in patients with critical limb ischemia. Results of placebo-controlled and double-blind trials of gene therapy for vascular disease are awaited.

  3. Adaptive Clinical Trials: Advantages and Disadvantages of Various Adaptive Design Elements.

    Science.gov (United States)

    Korn, Edward L; Freidlin, Boris

    2017-06-01

    There is a wide range of adaptive elements of clinical trial design (some old and some new), with differing advantages and disadvantages. Classical interim monitoring, which adapts the design based on early evidence of superiority or futility of a treatment arm, has long been known to be extremely useful. A more recent application of interim monitoring is in the use of phase II/III designs, which can be very effective (especially in the setting of multiple experimental treatments and a reliable intermediate end point) but do have the cost of having to commit earlier to the phase III question than if separate phase II and phase III trials were performed. Outcome-adaptive randomization is an older technique that has recently regained attention; it increases trial complexity and duration without offering substantial benefits to the patients in the trial. The use of adaptive trials with biomarkers is new and has great potential for efficiently identifying patients who will be helped most by specific treatments. Master protocols in which trial arms and treatment questions are added to an ongoing trial can be especially efficient in the biomarker setting, where patients are screened for entry into different subtrials based on evolving knowledge about targeted therapies. A discussion of three recent adaptive clinical trials (BATTLE-2, I-SPY 2, and FOCUS4) highlights the issues. Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.

  4. THE RESOURCE POTENTIAL AND THE DEVELOPMENT STRATEGY OF COMPETITIVE ADVANTAGES IN BUSINESS STRUCTURE

    Directory of Open Access Journals (Sweden)

    Ирина Юрьевна Окольнишникова

    2013-04-01

    Full Text Available The aim of the research is the development of theoretical approaches to the study of the essence and structure of the resource potential of entrepreneurship in the context of the development strategy of the competitive advantages in business structure.As the research methodology the complex of principles and tools of system and axiological approaches is used.According to the results of the conducted research, possessing the scientific novelty, the conceptual apparatus is clarified and the author's definition of the resource potential of the enterprise is given, a model of the resource potential structure in commercial organization is analyzed and the mechanism of strategy formation for sustainable competitive advantages provision of the organization on the basis of the effective use of its resource potential is identified.Area of application of the research results is the control of competitiveness in general and resource potential of entrepreneurial structures, in particular at all levels of the socio-economic system of society.DOI: http://dx.doi.org/10.12731/2218-7405-2013-2-39

  5. FCγ Chimeric Receptor-Engineered T Cells: Methodology, Advantages, Limitations, and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Giuseppe Sconocchia

    2017-04-01

    Full Text Available For many years, disappointing results have been generated by many investigations, which have utilized a variety of immunologic strategies to enhance the ability of a patient’s immune system to recognize and eliminate malignant cells. However, in recent years, immunotherapy has been used successfully for the treatment of hematologic and solid malignancies. The impressive clinical responses observed in many types of cancer have convinced even the most skeptical clinical oncologists that a patient’s immune system can recognize and reject his tumor if appropriate strategies are implemented. The success immunotherapy is due to the development of at least three therapeutic strategies. They include tumor-associated antigen (TAA-specific monoclonal antibodies (mAbs, T cell checkpoint blockade, and TAA-specific chimeric antigen receptors (CARs T cell-based immunotherapy. However, the full realization of the therapeutic potential of these approaches requires the development of strategies to counteract and overcome some limitations. They include off-target toxicity and mechanisms of cancer immune evasion, which obstacle the successful clinical application of mAbs and CAR T cell-based immunotherapies. Thus, we and others have developed the Fc gamma chimeric receptors (Fcγ-CRs-based strategy. Like CARs, Fcγ-CRs are composed of an intracellular tail resulting from the fusion of a co-stimulatory molecule with the T cell receptor ζ chain. In contrast, the extracellular CAR single-chain variable fragment (scFv, which recognizes the targeted TAA, has been replaced with the extracellular portion of the FcγRIIIA (CD16. Fcγ-CR T cells have a few intriguing features. First, given in combination with mAbs, Fcγ-CR T cells mediate anticancer activity in vitro and in vivo by an antibody-mediated cellular cytotoxicity mechanism. Second, CD16-CR T cells can target multiple cancer types provided that TAA-specific mAbs with the appropriate specificity are available

  6. Potential advantages and disadvantages of sequentially building small nuclear units instead of a large nuclear plant

    International Nuclear Information System (INIS)

    Feretic, D.; Cavlina, N.; Grgic, D.

    2008-01-01

    Renewal of nuclear power programs in countries with modest electricity consumptions and weak electrical grid interconnections has raised the question of optimal nuclear power plants sizes for such countries. The same question would be also valid for isolated or weakly connected regions within a large country. Building large size nuclear power plant could be prevented by technical or financial limits. Research programs have been initiated in the International Atomic Energy Agency and in the USA (within the framework of the Global Nuclear Energy Partnership (GNEP) program) with the aim to inspect under which circumstances small and medium reactors could be the preferred option compared to large nuclear plants. The economy of scale is a clear advantage of large plants. This paper compares, by using probabilistic methods, the net cash flow of large and medium size plants, taking as example a large nuclear plant (around 1200 MW) and four sequentially built smaller plants (300 MW). Potential advantages and disadvantageous of both options have been considered. Main advantages of the sequential construction of several identical small units could be the reduced investor risk and reduced investment costs due to the learning effect. This analysis is a part of studies for the Croatian power generating system development. (orig.)

  7. Co-development in the food industry: Status and potential advantages

    DEFF Research Database (Denmark)

    Olsen, Johanne R.; Harmsen, Hanne

    practice - co-development. Co-development gives the involved companies competitive advantages in the face of product imitation and globalization issues. An empirical study in the Danish food industry was performed to uncover tendencies in co-development activities and the potential for further development......The food industry is faced with new challenges. The need for fast solutions and convenience - and thus more complex products - is increasing as e.g. demographics and the every-day life of food consumers are changing. Companies have to break down traditional barriers to allow room for a new best...

  8. The Assessment of Patient Clinical Outcome: Advantages, Models, Features of an Ideal Model

    Directory of Open Access Journals (Sweden)

    Mou’ath Hourani

    2016-06-01

    Full Text Available Background: The assessment of patient clinical outcome focuses on measuring various aspects of the health status of a patient who is under healthcare intervention. Patient clinical outcome assessment is a very significant process in the clinical field as it allows health care professionals to better understand the effectiveness of their health care programs and thus for enhancing the health care quality in general. It is thus vital that a high quality, informative review of current issues regarding the assessment of patient clinical outcome should be conducted. Aims & Objectives: 1 Summarizes the advantages of the assessment of patient clinical outcome; 2 reviews some of the existing patient clinical outcome assessment models namely: Simulation, Markov, Bayesian belief networks, Bayesian statistics and Conventional statistics, and Kaplan-Meier analysis models; and 3 demonstrates the desired features that should be fulfilled by a well-established ideal patient clinical outcome assessment model. Material & Methods: An integrative review of the literature has been performed using the Google Scholar to explore the field of patient clinical outcome assessment. Conclusion: This paper will directly support researchers, clinicians and health care professionals in their understanding of developments in the domain of the assessment of patient clinical outcome, thus enabling them to propose ideal assessment models.

  9. The Assessment of Patient Clinical Outcome: Advantages, Models, Features of an Ideal Model

    Directory of Open Access Journals (Sweden)

    Mou’ath Hourani

    2016-06-01

    Full Text Available Background: The assessment of patient clinical outcome focuses on measuring various aspects of the health status of a patient who is under healthcare intervention. Patient clinical outcome assessment is a very significant process in the clinical field as it allows health care professionals to better understand the effectiveness of their health care programs and thus for enhancing the health care quality in general. It is thus vital that a high quality, informative review of current issues regarding the assessment of patient clinical outcome should be conducted. Aims & Objectives: 1 Summarizes the advantages of the assessment of patient clinical outcome; 2 reviews some of the existing patient clinical outcome assessment models namely: Simulation, Markov, Bayesian belief networks, Bayesian statistics and Conventional statistics, and Kaplan-Meier analysis models; and 3 demonstrates the desired features that should be fulfilled by a well-established ideal patient clinical outcome assessment model. Material & Methods: An integrative review of the literature has been performed using the Google Scholar to explore the field of patient clinical outcome assessment. Conclusion: This paper will directly support researchers, clinicians and health care professionals in their understanding of developments in the domain of the assessment of patient clinical outcome, thus enabling them to propose ideal assessment models.

  10. Surgery planning and navigation by laser lithography plastic replica. Features, clinical applications, and advantages

    International Nuclear Information System (INIS)

    Kihara, Tomohiko; Tanaka, Yuuko; Furuhata, Kentaro

    1995-01-01

    The use of three-dimensional replicas created using laserlithography has recently become popular for surgical planning and intraoperative navigation in plastic surgery and oral maxillofacial surgery. In this study, we investigated many clinical applications that we have been involved in regarding the production of three-dimensional replicas. We have also analyzed the features, application classes, and advantages of this method. As a result, clinical applications are categorized into three classes, which are 'three-dimensional shape recognition', 'simulated surgery', and 'template'. The distinct features of three-dimensional replicas are 'direct recognition', 'fast manipulation', and 'free availability'. Meeting the requirements of surgical planning and intraoperative navigation, they have produced satisfactory results in clinical applications. (author)

  11. The reactivation of the natural potentials of Belgrade: Biophilia and biomimicry as new competitive advantages?

    Directory of Open Access Journals (Sweden)

    Stupar Aleksandra

    2013-01-01

    Full Text Available Climate changes have influenced a new comprehension of living environment and instigated a number of trends noticeable in society, architecture and development strategies. The shaping of a purified, sustainable and 'low/no carbon' urban context, which has a higher environmental quality, has become an imperative which should be achieved by ecologically responsible behavior. Cities, as major nodes of global transmission and dissemination, act as experimental polygons. They simultaneously test the latest ecological and technological concepts, especially those based on the logic of natural systems - such as biophilia and biomimicry. Their application enables an intensive integration of nature into urban space, while the manifestation of nature - as a shape, function or a level of adaptability - becomes a new competitive advantage. The planning practice in Serbia has also started its gradual adjustment to the new imperatives but the pace of change is slow. Belgrade has recognized the importance of the latest ecoideas but they have not been materialized so far. The natural core of Belgrade, which consists of several river isles, river banks, forests and forelands, is nowadays emphasized as an important comparative advantage which could generate further changes in 'green' perception of urban environment. Therefore, the purpose of this article is to identify the potential of two natural areas within this core (Ada Ciganlija and Ada Medjica, critically evaluate their development possibilities based on biophilia and biomimicry, and to provide a set of recommendations which would support the activation and development of a similar natural area - Ada Čaplja.

  12. Complexity and availability for fusion power plants: The potential advantages of inertial fusion energy

    International Nuclear Information System (INIS)

    Perkins, L.J.

    1997-01-01

    Probably the single largest advantage of the inertial route to fusion energy (IFE) is the perception that its power plant embodiments could achieve acceptable capacity factors. This is a result of its relative simplicity, the decoupling of the driver and reactor chamber, and the potential to employ thick liquid walls. The author examines these issues in terms of the complexity, reliability, maintainability and, therefore, availability of both magnetic and inertial fusion power plants and compares these factors with corresponding scheduled and unscheduled outage data from present day fission experience. The author stresses that, given the simple nature of a fission core, the vast majority of unplanned outages in fission plants are due to failures outside the reactor vessel itself. Given one must be prepared for similar outages in the analogous plant external to a fusion power core, this puts severe demands on the reliability required of the fusion core itself. The author indicates that such requirements can probably be met for IFE plants. He recommends that this advantage be promoted by performing a quantitative reliability and availability study for a representative IFE power plant and suggests that databases are probably adequate for this task. 40 refs., 4 figs., 3 tabs

  13. Polarized phase shift mask: concept, design, and potential advantages to photolithography process and physical design

    Science.gov (United States)

    Wang, Ruoping; Grobman, Warren D.; Reich, Alfred J.; Thompson, Matthew A.

    2002-03-01

    In this paper we introduce the concept and design of a novel phase shift mask technology, Polarized Phase Shift Mask (P:PSM). The P:PSM technology utilizes non-interference between orthogonally polarized light sources to avoid undesired destructive interference seen in conventional two-phase shift mask technology. Hence P:PSM solves the well-known 'phase edge' or 'phase conflict' problem. By obviating the 2nd exposure and 2nd mask in current Complementary Phase Shift Mask (C:PSM) technology, this single mask/single exposure technology offers significant advantages towards photolithography process as well as pattern design. We use examples of typical design and process difficulties associated with the C:PSM technology to illustrate the advantages of the P:PSM technology. We present preliminary aerial image simulation results that support the potential of this new reticle technology for enhanced design flexibility. We also propose possible mask structures and manufacturing methods for building a P:PSM.

  14. Complexity versus availability for fusion: The potential advantages of inertial fusion energy

    International Nuclear Information System (INIS)

    Perkins, L.J.

    1996-01-01

    Probably the single largest advantage of the inertial route to fusion energy (IFE) is the perception that its power plant embodiments could achieve acceptable capacity factors. This is a result of its relative simplicity, the decoupling of the driver and reactor chamber, and the potential to employ thick liquid walls. We examine these issues in terms of the complexity, reliability, maintainability and, therefore, availability of both magnetic and inertial fusion power plants and compare these factors with corresponding scheduled and unscheduled outage data from present day fission experience. We stress that, given the simple nature of a fission core, the vast majority of unplanned outages in fission plants are due to failures outside the reactor vessel itself Given we must be prepared for similar outages in the analogous plant external to a fusion power core, this puts severe demands on the reliability required of the fusion core itself. We indicate that such requirements can probably be met for IFE plants. We recommend that this advantage be promoted by performing a quantitative reliability and availability study for a representative IFE power plant and suggest that databases are probably adequate for this task

  15. Adaptive Treatment Strategies in Youth Mental Health: A Commentary on Advantages, Challenges, and Potential Directions.

    Science.gov (United States)

    Sherrill, Joel T

    2016-01-01

    This commentary underscores the importance and potential of the research approaches and intervention strategies described in the JCCAP special issue on the Science of Adaptive Treatment Strategies in Child and Adolescent Mental Health for addressing the widely observed heterogeneity in response to even our most promising research-informed interventions. First, the commentary briefly summarizes the advantages of these approaches and highlights how these programs of research are responsive to widely agreed-upon calls for more personalized, prescriptive interventions. Next, the commentary briefly discusses key common challenges and gaps in our knowledge that might be addressed to advance the development, testing, and implementation of adaptive intervention strategies. For example, research to identify robust moderators that might serve as potential tailoring variables for initial assignment and sequencing of interventions, efforts to operationalize surrogate endpoints for early identification of individuals who are unlikely to respond to first-line interventions, and research that helps define what constitutes an adequate exposure (i.e., dose) or response threshold (e.g., response that suggests the need to intensify, switch, or augment interventions) would inform decision rules for adaptive algorithms. The commentary concludes with a discussion of potential strategies and current initiatives that might ultimately help facilitate research on more targeted, prescriptive approaches to intervening, including efforts to encourage investigators to use common data elements, to share and integrate data across trials, and to employ a more mechanism-based approach to intervention development and testing.

  16. Assessment of potential advantages of relevant ions for particle therapy: A model based study

    Energy Technology Data Exchange (ETDEWEB)

    Grün, Rebecca, E-mail: r.gruen@gsi.de [Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt 64291 (Germany); Institute of Medical Physics and Radiation Protection, University of Applied Sciences Gießen, Gießen 35390 (Germany); Medical Faculty of Philipps-University Marburg, Marburg 35032 (Germany); Friedrich, Thomas; Krämer, Michael; Scholz, Michael [Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt 64291 (Germany); Zink, Klemens [Institute of Medical Physics and Radiation Protection, University of Applied Sciences Gießen, Gießen 35390, Germany and Department of Radiotherapy and Radiation Oncology, University Medical Center Giessen and Marburg, Marburg 35043 (Germany); Durante, Marco [Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt 64291, Germany and Department of Condensed Matter Physics, Darmstadt University of Technology, Darmstadt 64289 (Germany); Engenhart-Cabillic, Rita [Medical Faculty of Philipps-University Marburg, Marburg 35032, Germany and Department of Radiotherapy and Radiation Oncology, University Medical Center Giessen and Marburg, Marburg 35043 (Germany)

    2015-02-15

    Purpose: Different ion types offer different physical and biological advantages for therapeutic applications. The purpose of this work is to assess the advantages of the most commonly used ions in particle therapy, i.e., carbon ({sup 12}C), helium ({sup 4}He), and protons ({sup 1}H) for different treatment scenarios. Methods: A treatment planning analysis based on idealized target geometries was performed using the treatment planning software TRiP98. For the prediction of the relative biological effectiveness (RBE) that is required for biological optimization in treatment planning the local effect model (LEM IV) was used. To compare the three ion types, the peak-to-entrance ratio (PER) was determined for the physical dose (PER{sub PHY} {sub S}), the RBE (PER{sub RBE}), and the RBE-weighted dose (PER{sub BIO}) resulting for different dose-levels, field configurations, and tissue types. Further, the dose contribution to artificial organs at risk (OAR) was assessed and a comparison of the dose distribution for the different ion types was performed for a patient with chordoma of the skull base. Results: The study showed that the advantages of the ions depend on the physical and biological properties and the interplay of both. In the case of protons, the consideration of a variable RBE instead of the clinically applied generic RBE of 1.1 indicates an advantage in terms of an increased PER{sub RBE} for the analyzed configurations. Due to the fact that protons show a somewhat better PER{sub PHY} {sub S} compared to helium and carbon ions whereas helium shows a higher PER{sub RBE} compared to protons, both protons and helium ions show a similar RBE-weighted dose distribution. Carbon ions show the largest variation of the PER{sub RBE} with tissue type and a benefit for radioresistant tumor types due to their higher LET. Furthermore, in the case of a two-field irradiation, an additional gain in terms of PER{sub BIO} is observed when using an orthogonal field configuration

  17. What are the potential advantages and disadvantages of volumetric CT scanning?

    Science.gov (United States)

    Voros, Szilard

    2009-01-01

    After the introduction and dissemination of 64-slice multislice computed tomography systems, cardiovascular CT has arrived at a crossroad, and different philosophies lead down different paths of technologic development. Increased number of detector rows in the z-axis led to the introduction of dynamic, volumetric scanning of the heart and allows for whole-organ imaging. Dynamic, volumetric "whole-organ" scanning significantly reduces image acquisition time; "single-beat whole-heart imaging" results in improved image quality and reduced radiation exposure and reduced contrast dose. It eliminates helical and pitch artifacts and allows for simultaneous imaging of the base and apex of the heart. Beyond coronary arterial luminal imaging, such innovations open up the opportunity for myocardial perfusion and viability imaging and coronary arterial plaque imaging. Dual-source technology with 2 x-ray tubes placed at 90-degree angles provides heart rate-independent temporal resolution and has the potential for tissue characterization on the basis of different attenuation values at different energy levels. Refined detector technology allows for improved low-contrast resolution and may be beneficial for more detailed evaluation of coronary arterial plaque composition. The clinical benefit of each of these technologies will have to be evaluated in carefully designed clinical trials and in everyday clinical practice. Such combined experience will probably show the relative benefit of each of these philosophies in different patient populations and in different clinical scenarios.

  18. The entry-level occupational therapy clinical doctorate: advantages, challenges, and international issues to consider.

    Science.gov (United States)

    Brown, Ted; Crabtree, Jeffrey L; Mu, Keli; Wells, Joe

    2015-04-01

    Internationally, occupational therapy education has gone through several paradigm shifts during the last few decades, moving from certificate to diploma to bachelors to masters and now in some instances to clinical doctorate as the entry-level professional credential to practice. In the United States there is a recommendation under consideration by the American Occupational Therapy Association (AOTA) that by 2025, all occupational therapy university programs will move to the clinical doctorate level. It should be noted, however, that the AOTA Board can only make recommendations and it is the Accreditation Council for Occupational Therapy Education (ACOTE) who has regulatory authority to approve such a change. What are the potential implications for the profession, our clients, and funders of occupational therapy services? What are the primary drivers for the move towards the clinical doctorate being the educational entry point? Is the next step in the evolution of occupational therapy education globally a shift to the entry-level clinical doctorate? This article reviews current literature and discusses issues about the occupational therapy entry-level clinical doctorate. The published evidence available about the occupational therapy entry-level clinical doctorate is summarized and the perceived or frequently cited pros and cons of moving to the clinical doctorate as the singular entry point to occupational therapy practice are considered. The potential impacts of the introduction of the clinical doctorate as the entry-to-practice qualification across the United States on the occupational therapy community internationally will be briefly discussed. If the United States moves toward the entry-level clinical doctorate as the only educational starting point for the profession, will other jurisdictions follow suit? Further discourse and investigation of this issue both inside and outside of the United States is needed so that informed decisions can be made.

  19. Advantages and limitations of potential methods for the analysis of bacteria in milk: a review.

    Science.gov (United States)

    Tabit, Frederick Tawi

    2016-01-01

    Contamination concerns in the dairy industry are motivated by outbreaks of disease in humans and the inability of thermal processes to eliminate bacteria completely in processed products. HACCP principles are an important tool used in the food industry to identify and control potential food safety hazards in order to meet customer demands and regulatory requirements. Milk testing is of importance to the milk industry regarding quality assurance and monitoring of processed products by researchers, manufacturers and regulatory agencies. Due to the availability of numerous methods used for analysing the microbial quality of milk in literature and differences in priorities of stakeholders, it is sometimes confusing to choose an appropriate method for a particular analysis. The objective of this paper is to review the advantages and disadvantages of selected techniques that can be used in the analysis of bacteria in milk. SSC, HRMA, REP, and RAPD are the top four techniques which are quick and cost-effective and possess adequate discriminatory power for the detection and profiling of bacteria. The following conclusions were arrived at during this review: HRMA, REP and RFLP are the techniques with the most reproducible results, and the techniques with the most discriminatory power are AFLP, PFGE and Raman Spectroscopy.

  20. Advantage of fan beam collimators for contrast recovery of hyperfixation in clinical SPECT

    International Nuclear Information System (INIS)

    Vera, P.

    1997-01-01

    The influence of the collimator on the contrast recovery of hyperfixation was studied using a dual-headed single photon emission computer tomography (SPECT) system with standard clinical acquisition parameters. Three parallel collimator sets and two fan beam collimator sets were tested with a Jaszczak phantom. The six spheres of the phantom were filled with 99m Tc, and four background levels were progressively obtained by adding radioactivity to the cylinder of the phantom, providing four hyperfixation levels. The effects of angular sampling and reconstruction filters have been tested. The statistical analysis was performed with analysis of variance (ANOVA). This study demonstrates the advantage of ultra-high resolution fan beam collimators for contrast recovery of hyperfixation with SPECT when using 64 projections over 360 degree, in particular when the contrast is low. The authors also demonstrate that fan beam collimators permit smaller size hyperfixation detection

  1. The Advantages, Potentials and Safety of VTOL Suborbital Space Tourism Operations

    Science.gov (United States)

    Ridzuan Zakaria, N.; Nasrun, N.; Abu, J.; Jusoh, A.; Azim, L.; Said, A.; Ishak, S.; Rafidi Zakaria, N.

    2012-01-01

    more risky for a suborbital vehicle to fly above such objects after taking off from a spaceport far away from the object, and later returning to the spaceport, the way to go is to have the operation of the suborbital vehicle near the exotic locations. Unfortunately, some exotic locations such as a tropical archipelago in the middle of a clear blue ocean or a permanent icecap on a mountain range with variety of vegetation around it due to differences in height may not have suitable runway to function as spaceport, and for such reason, VTOL (vertical take-off and landing) capability for suborbital tourism vehicle may be worth considered. VTOL suborbital space tourism vehicle may not operate from a remote uneconomical location even though the location is near an exotic viewing target, but such vehicle may operate from a luxury super yacht that can sail to exotic locations around the world, and during the journey, the passengers can be trained and prepared for the flight of their life. Such is an advantage and potential of VTOL suborbital space tourism vehicle, but VTOL operation can be more complex than a conventional operation and therefore will increase the risk of operation, and for this reason the safety issue for such operation is very significant. This paper explores and discusses some advantages and potentials of VTOL suborbital space tourism operations and safety issues related to them. It also describes a couple of proposed concepts of VTOL suborbital tourism vehicles and potential exotic locations on Earth to be viewed from such vehicles.

  2. Advantages and Limitations of BiRadstm System Application in Clinical Practice

    International Nuclear Information System (INIS)

    Torres Tabanera, M.; Acebal Blanco, M. M.

    2004-01-01

    The BiRads ' T m system (Breast-Imaging Report and Database System) was created by the American College of Radiology in 1992 with the participation of other American scientific societies. It is a quality assurance tool designed to standardize mammographic reports, reduce confusion in the interpretation of breast images and facilitate the monitoring of results. It consists of five sections: breast Imaging Lexicon, Reporting System, Follow-up and Outcome Monitoring, National Mammography Database and Appendices. It was designed in order to create a common lexicon, universally accepted by breast pathology specialists, which would standardize both content and format of mammographic reports, as well as constitute a tool for continuing quality improvement. However, these promising objectives give rise to some serious controversies when sufficient experience is gained in a daily clinical use of the system. In this study, the advantages and contributions of Bi-Rads TM system use is reviewed. Drawbacks are also cited, based on then years experience, with regard to lexicon, categories and recommendations. (Author)

  3. BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy

    Directory of Open Access Journals (Sweden)

    Chowdhary M

    2016-12-01

    Full Text Available Mudit Chowdhary,1,2 Kirtesh R Patel,1 Hasan H Danish,1 David H Lawson,3 Mohammad K Khan1 1Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 2Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, 3Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA Abstract: Melanoma is an aggressive malignancy that frequently spreads to the brain, resulting in rapid deterioration in both quality and quantity of life. Historically, treatment options for melanoma brain metastases (MBM have predominantly consisted of surgery and radiotherapy. While these options can help provide local control, the majority of patients still develop intracranial progression. Indeed, novel therapeutic options, including molecularly targeted agents and immunotherapy, have improved outcomes and are now changing the role of radiotherapy. Up to 50% of melanomas contain an activating BRAF mutation, resulting in hyperactive cellular proliferation and survival. Drugs that target BRAF have been introduced for the treatment of metastatic melanoma and offer hope in improving disease outcomes; however, many of these trials either excluded or had a limited amount of patients with MBM. Recent studies have revealed that melanoma cell lines become more radiosensitive following BRAF inhibition, thus providing a potential synergistic mechanism when combining BRAF inhibitor (BRAFi and radiotherapy. However, neurotoxicity concerns also exist with this combination. This article reviews the efficacy and limitations of BRAFi therapy for MBM, describes current evidence for combining BRAFis with radiation, discusses the rationale and evidence for combination modalities, and highlights emerging clinical trials specifically investigating this combination in MBM. Keywords: brain metastases, melanoma, radiation, BRAF inhibitors, vemurafenib, dabrafenib

  4. Spatially extended versus frontal cerebral near-infrared spectroscopy during cardiac surgery: a case series identifying potential advantages

    Science.gov (United States)

    Rummel, Christian; Basciani, Reto; Nirkko, Arto; Schroth, Gerhard; Stucki, Monika; Reineke, David; Eberle, Balthasar; Kaiser, Heiko A.

    2018-01-01

    Stroke due to hypoperfusion or emboli is a devastating adverse event of cardiac surgery, but early detection and treatment could protect patients from an unfavorable postoperative course. Hypoperfusion and emboli can be detected with transcranial Doppler of the middle cerebral artery (MCA). The measured blood flow velocity correlates with cerebral oxygenation determined clinically by near-infrared spectroscopy (NIRS) of the frontal cortex. We tested the potential advantage of a spatially extended NIRS in detecting critical events in three cardiac surgery patients with a whole-head fiber holder of the FOIRE-3000 continuous-wave NIRS system. Principle components analysis was performed to differentiate between global and localized hypoperfusion or ischemic territories of the middle and anterior cerebral arteries. In one patient, we detected a critical hypoperfusion of the right MCA, which was not apparent in the frontal channels but was accompanied by intra- and postoperative neurological correlates of ischemia. We conclude that spatially extended NIRS of temporal and parietal vascular territories could improve the detection of critically low cerebral perfusion. Even in severe hemispheric stroke, NIRS of the frontal lobe may remain normal because the anterior cerebral artery can be supplied by the contralateral side directly or via the anterior communicating artery.

  5. Potential advantages of a cesium fluoride scintillator for a time-of-flight positron camera

    International Nuclear Information System (INIS)

    Allemand, R.; Gresset, C.; Vacher, J.

    1980-01-01

    In order to improve the quality of positron tomographic imaging, a time-of-flight technique combined with a classical reconstruction method has been investigated. The decay time of NaI(Tl) and bismuth germanate (BGO) scintillators is too long for this application, and efficiency of the plastic scintillators is too low. Cesium fluoride appears to be a very promising detector material. This paper presents preliminary results obtained with a time-of-flight technique using CsF scintillators. The expected advantages were realized

  6. Next-Generation Sequencing in Clinical Molecular Diagnostics of Cancer: Advantages and Challenges

    Directory of Open Access Journals (Sweden)

    Rajyalakshmi Luthra

    2015-10-01

    Full Text Available The application of next-generation sequencing (NGS to characterize cancer genomes has resulted in the discovery of numerous genetic markers. Consequently, the number of markers that warrant routine screening in molecular diagnostic laboratories, often from limited tumor material, has increased. This increased demand has been difficult to manage by traditional low- and/or medium-throughput sequencing platforms. Massively parallel sequencing capabilities of NGS provide a much-needed alternative for mutation screening in multiple genes with a single low investment of DNA. However, implementation of NGS technologies, most of which are for research use only (RUO, in a diagnostic laboratory, needs extensive validation in order to establish Clinical Laboratory Improvement Amendments (CLIA and College of American Pathologists (CAP-compliant performance characteristics. Here, we have reviewed approaches for validation of NGS technology for routine screening of tumors. We discuss the criteria for selecting gene markers to include in the NGS panel and the deciding factors for selecting target capture approaches and sequencing platforms. We also discuss challenges in result reporting, storage and retrieval of the voluminous sequencing data and the future potential of clinical NGS.

  7. ERDA with an external helium ion micro-beam: Advantages and potential applications

    International Nuclear Information System (INIS)

    Calligaro, T.; Castaing, J.; Dran, J.-C.; Moignard, B.; Pivin, J.-C.; Prasad, G.V.R.; Salomon, J.; Walter, P.

    2001-01-01

    Preliminary ERDA experiments at atmospheric pressure have been performed with our external microprobe set-up currently used for the analysis of museum objects by PIXE, RBS and NRA. The objective was to check the feasibility of hydrogen (and deuterium) profiling with an external beam of 3-MeV helium ions. The standard scattering geometry (incident beam at 15 deg. with respect to sample surface and emerging protons or deuterons at 15 deg. in the forward direction) was kept, but the thin foil absorber was replaced by helium gas filling the space between the beam spot and the detector over a distance of about 84 mm. Several standards prepared by ion implantation, with well known H or D depth profiles, were first analysed, which indicated that the analytical capability was as good as under vacuum. A striking feature is the much lower surface peak than under vacuum, a fact that enhances the sensitivity for H analysis near the surface. The same type of measurement was then performed on different materials to show the usefulness of the technique. As a first example, we have checked that the incorporation of H or D into sapphire crystals during mechanical polishing is below the detection limit. Another example is the measurement of the H content in emeralds which can be used as an additional compositional criterion for determining the provenance of emeralds set in museum jewels. The advantages and limitations of our set-up are discussed and several possible applications in the field of cultural heritage are described

  8. Results, advantages, cost effectivity and installation potential of cooperation wind turbines

    International Nuclear Information System (INIS)

    Langenbach, J.; De Vries, J.

    1990-01-01

    September 1987 a cooperation of small electricity consumers installed the first cooperative wind turbine in Delft, Netherlands. At present there are 25 such cooperatives with more than 4000 members. In February 1990 14 cooperative wind turbines were in operation with a total capacity of 1,030 kWh. An extension to 23 wind turbines with a total capacity of circa 1.8 MW and a total investment of 3.8 million Dutch guilders is expected for 1990. In 1989 1.1 million kWh has been generated, and in 1990 a production of more than 2 million kWh is expected. The most important advantages of cooperative exploitation of wind turbines are the positive public opinion, extensive possibilities to install the wind turbines, the free choice of location, and cost effectivity. At the present level of investment subsidies and kWh compensations the installed capacity can increase to a maximum of 10 MW in 1995. If a national regulation for cooperative exploitation will be implemented, the kWh compensations increase to DFl 0.17-0.20 and the investment subsidies gradually decrease to zero, the total capacity can mount to 40 MW in 1995 and 125 MW in the year 2000. 1 fig., 3 tabs., 3 refs

  9. Assessment of potential advantages of high Tc-superconductors for technical application of superconductivity

    International Nuclear Information System (INIS)

    Schauer, F.; Juengst, K.P.; Komarek, P.; Maurer, W.

    1987-09-01

    A first assessment of the technical and economical consequences of liquid nitrogen cooling of new superconductors is given. For the investigation the applications of superconductivity are classified in two categories: First, systems where superconductors are practically indispensable for achieving the system's objectives; second, superconductor applications in competition with highly developed conventional technologies. Further development of those superconducting systems in the first category for which the cost of cryogenic equipment is a smaller fraction of the total system cost (e.g. fusion reactor or MHD generator) will hardly be affected. However, for systems like particle accelerators, research magnets, and NMR spectroscopy and imaging systems, the cryogenic equipment expenditures are significant and LN 2 cooling leads here to a reduction of investment and operating costs, to simplified handling and maintenance, to better reliability and availability, and will thereby improve the acceptance and further spread of these systems. In the second category each application of superconductivity has to be compared with its conventional counterpart, separately. Here, electonic components, power switches, resistive current limiters, and especially the power transmission cables are those applications which look most promising. For magnet applications the main advantageous arguments are less the cost saving aspect but more the higher reliability, simplicity, N 2 -availability, and ease of handling. (orig.) [de

  10. Insights into the Antimicrobial Properties of Hepcidins: Advantages and Drawbacks as Potential Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Lisa Lombardi

    2015-04-01

    Full Text Available The increasing frequency of multi-drug resistant microorganisms has driven research into alternative therapeutic strategies. In this respect, natural antimicrobial peptides (AMPs hold much promise as candidates for the development of novel antibiotics. However, AMPs have some intrinsic drawbacks, such as partial degradation by host proteases or inhibition by host body fluid composition, potential toxicity, and high production costs. This review focuses on the hepcidins, which are peptides produced by the human liver with a known role in iron homeostasis, as well by numerous other organisms (including fish, reptiles, other mammals, and their potential as antibacterial and antifungal agents. Interestingly, the antimicrobial properties of human hepcidins are enhanced at acidic pH, rendering these peptides appealing for the design of new drugs targeting infections that occur in body areas with acidic physiological pH. This review not only considers current research on the direct killing activity of these peptides, but evaluates the potential application of these molecules as coating agents preventing biofilm formation and critically assesses technical obstacles preventing their therapeutic application.

  11. [Instruments of management accounting in german hospitals - potentials for competitive advantage and status quo].

    Science.gov (United States)

    Berens, W; Lachmann, M; Wömpener, A

    2011-03-01

    The aim of this study is to provide an analysis of the status quo for the usage of instruments of management accounting in German hospitals. 600 managing directors of German hospitals were asked to answer a questionnaire about the usage of management accounting instruments in their hospitals. We obtained 121 usable datasets, which are evaluated in this study. A significant increase in the usage of management accounting instruments can be observed over time. The respondents have an overall positive perception of the usage of these instruments. Cost accounting and information systems are among the most widely used instruments, while widely discussed concepts like the balanced scorecard or clinical pathways show surprisingly low usage rates. © Georg Thieme Verlag KG Stuttgart · New York.

  12. The light-makeup advantage in facial processing: Evidence from event-related potentials

    OpenAIRE

    Tagai, Keiko; Shimakura, Hitomi; Isobe, Hiroko; Nittono, Hiroshi

    2017-01-01

    The effects of makeup on attractiveness have been evaluated using mainly subjective measures. In this study, event-related brain potentials (ERPs) were recorded from a total of 45 Japanese women (n = 23 and n = 22 for Experiment 1 and 2, respectively) to examine the neural processing of faces with no makeup, light makeup, and heavy makeup. To have the participants look at each face carefully, an identity judgement task was used: they were asked to judge whether the two faces presented in succ...

  13. The light-makeup advantage in facial processing: Evidence from event-related potentials.

    Science.gov (United States)

    Tagai, Keiko; Shimakura, Hitomi; Isobe, Hiroko; Nittono, Hiroshi

    2017-01-01

    The effects of makeup on attractiveness have been evaluated using mainly subjective measures. In this study, event-related brain potentials (ERPs) were recorded from a total of 45 Japanese women (n = 23 and n = 22 for Experiment 1 and 2, respectively) to examine the neural processing of faces with no makeup, light makeup, and heavy makeup. To have the participants look at each face carefully, an identity judgement task was used: they were asked to judge whether the two faces presented in succession were of the same person or not. The ERP waveforms in response to the first faces were analyzed. In two experiments with different stimulus probabilities, the amplitudes of N170 and vertex positive potential (VPP) were smaller for faces with light makeup than for faces with heavy makeup or no makeup. The P1 amplitude did not differ between facial types. In a subsequent rating phase, faces with light makeup were rated as more attractive than faces with heavy makeup and no makeup. The results suggest that the processing fluency of faces with light makeup is one of the reasons why light makeup is preferred to heavy makeup and no makeup in daily life.

  14. Constructing Tissue Microarrays: Protocols and Methods Considering Potential Advantages and Disadvantages for Downstream Use.

    Science.gov (United States)

    Bingle, Lynne; Fonseca, Felipe P; Farthing, Paula M

    2017-01-01

    Tissue microarrays were first constructed in the 1980s but were used by only a limited number of researchers for a considerable period of time. In the last 10 years there has been a dramatic increase in the number of publications describing the successful use of tissue microarrays in studies aimed at discovering and validating biomarkers. This, along with the increased availability of both manual and automated microarray builders on the market, has encouraged even greater use of this novel and powerful tool. This chapter describes the basic techniques required to build a tissue microarray using a manual method in order that the theory behind the practical steps can be fully explained. Guidance is given to ensure potential disadvantages of the technique are fully considered.

  15. Potential advantages and limitations of the Leo stent in endovascular treatment of complex cerebral aneurysms

    Energy Technology Data Exchange (ETDEWEB)

    Lv Xianli; Li Youxiang; Jiang Chuhan; Yang Xinjian [Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, 6, Tiantan Xili, 100050 Hebei, Beijing (China); Wu Zhongxue, E-mail: ttyyzjb@sina.com [Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, 6, Tiantan Xili, 100050 Hebei, Beijing (China)

    2011-08-15

    Objective: The Leo self-expandable stent is a new retractable stent that is delivered via a conventional catheter. The aim of this study was to evaluate the use of this stent for endovascular treatment of complex aneurysms. Methods: Twenty-eight complex cerebral aneurysms (27 saccular and 1 fusiform) in 28 patients were treated electively. They were located at the internal carotid artery (17), basilar trunk (3), anterior cerebral artery (1), anterior communicating artery (3), vertebral artery (2) and middle cerebral artery (2). One aneurysm exhibited recanalization after primary endovascular treatment without stent. Clinical outcome was assessed with the modified Glasgow Outcome Scale. Results: Deployment of Leo stent was successful in 26 lesions, and difficulties in stent positioning due to tortuous cerebral circulation in 2 cases, which were treated with Neuroform stent. Additional coil embolization was performed in 26 lesions. No permanent neurological deficits were encountered consequent to endovascular procedure. Complete or partial occlusion immediately after stent deployment was achieved in all aneurysms. There was no immediate coil embolization was chosen in 3 cases because of subsequent reduced filling of the aneurysms with contrast agent on angiograms. There were 3 asymptomatic parent artery occlusion related to the deployment of the Leo stent, one stent migration. Follow-up revealed patent stents in the remaining cases. No angiographic recurrences arose. Conclusion: The Leo stent is very useful for endovascular treatment of complex cerebral aneurysms because it is easy to navigate and place precisely. A drawback is that in-stent thrombosis caused by stent placement and stiffer delivery catheters to place larger stents.

  16. The potential advantages of microstructure modeling of titanium to the aerospace industry

    International Nuclear Information System (INIS)

    Boyer, R.R.; Furrer, D.U.

    2004-01-01

    A multi-organization team across the entire titanium aerospace supply chain has been established to develop and implement modeling tools for the reduction of manufacturing lead-time and cost. This Air Force sponsored Metals Affordability Initiative (MAI) program is developing model tools capable of predicting the microstructure and mechanical properties of titanium alloys. The developed tools are intended to enable predicting the microstructure and texture evolution through wrought processing and heat treatment of ingot metallurgy titanium components, with a stronger emphasis on the latter stages of the processing. It will also take into account chemistry, including the composition of the individual phases during processing. Beta phase and primary alpha phase grain growth at temperature and during cooling along with morphological aspects will be taken into consideration.The success of this modeling effort could have a significant impact on the industry in terms of reducing cost and lead times of wrought products -- while this study is directed at forgings, there is no reason it would not be applicable to other product forms. Initial applications of these tools include the potential to reduce and in some cases eliminate certification testing presently done on forged or other components. There is also the potential for making a disposition on components with a metallurgical discrepancy without cutting up (sacrificing) a part(s), through the use of predictive tools. For parts where the property requirements are difficult to meet, these modeling tools could also enable one to determine the more critical parameters and concentrate efforts on controlling them, providing a more consistent product.In the longer term, titanium modeling tools could result in reduction of the lead time and cost of developing a new heat treatment or alloy to meet specific application requirements -- the models could be used to predict the proper aim chemistry, optimized chemistry limits, and

  17. Cognitive strategies take advantage of the cooperative potential of heterogeneous networks

    International Nuclear Information System (INIS)

    Vukov, Jeromos; Santos, Francisco C; Pacheco, Jorge M

    2012-01-01

    Understanding the emergence and maintenance of cooperation is one of the most challenging topics of our time. Evolutionary game theory offers a very flexible framework within which to address this challenge. Here we use the prisoner's dilemma game to investigate the performance of individuals who are capable of adopting reactive strategies in communities structurally organized by means of Barabási-Albert scale-free networks. We find that basic cognitive abilities, such as the capability to distinguish their partners and act according to their previous actions, enable cooperation to thrive. This result is particularly significant whenever fear is the leading social tension, as this fosters retaliation, thus enforcing and sustaining cooperation. Being able to simultaneously reward fellow cooperators and punish defectors proves instrumental in achieving cooperation and the welfare of the community. As a result, central individuals can successfully lead the community and turn defective players into cooperative ones. Finally, even when participation costs—known to be detrimental to cooperation in scale-free networks—are explicitly included, we find that basic cognitive abilities have enough potential to help cooperation to prevail. (paper)

  18. Potential advantages and disadvantages of an endgame strategy: a ‘sinking lid’ on tobacco supply

    Science.gov (United States)

    Wilson, Nick; Thomson, George W; Edwards, Richard; Blakely, Tony

    2013-01-01

    Background One possible supply-side strategy for the tobacco endgame is a government-mandated ‘sinking lid’ on tobacco supply (tradeable but decreasing quotas on sales or imports). Methods We considered literature on quota systems and from a tobacco endgame workshop at the University of Michigan. Findings Likely strengths of the sinking lid strategy include: (1) that it can provide a clear timetable and an unambiguous signal of a tobacco end-date; (2) that supply reduction is likely to increase product price levels, and there is very strong evidence that increasing price is a highly effective tobacco control intervention. Its feasibility is also supported by the growing international experience with, and political acceptability of, using quota and auction systems in other domains (eg, greenhouse gases, other air pollutants and for fisheries). However, the main disadvantages of this strategy are probably the need for strong political will and high public support (to pass a new law), potential legal challenges by industry (eg, under trade agreements), and vulnerability to problems from illegal supplies of tobacco and from corruption. Conclusions The sinking lid strategy is a plausible option that is worth considering when investigating possible tobacco endgame strategies, though it may be most applicable in well-organised jurisdictions with low (<15%) adult smoking prevalence. This idea could benefit from further research, such as studies in virtual worlds, and real-world testing on small island jurisdictions, or closed systems, such as military bases. PMID:23591499

  19. Potential advantages and disadvantages of an endgame strategy: a 'sinking lid' on tobacco supply.

    Science.gov (United States)

    Wilson, Nick; Thomson, George W; Edwards, Richard; Blakely, Tony

    2013-05-01

    One possible supply-side strategy for the tobacco endgame is a government-mandated 'sinking lid' on tobacco supply (tradeable but decreasing quotas on sales or imports). We considered literature on quota systems and from a tobacco endgame workshop at the University of Michigan. Likely strengths of the sinking lid strategy include: (1) that it can provide a clear timetable and an unambiguous signal of a tobacco end-date; (2) that supply reduction is likely to increase product price levels, and there is very strong evidence that increasing price is a highly effective tobacco control intervention. Its feasibility is also supported by the growing international experience with, and political acceptability of, using quota and auction systems in other domains (eg, greenhouse gases, other air pollutants and for fisheries). However, the main disadvantages of this strategy are probably the need for strong political will and high public support (to pass a new law), potential legal challenges by industry (eg, under trade agreements), and vulnerability to problems from illegal supplies of tobacco and from corruption. The sinking lid strategy is a plausible option that is worth considering when investigating possible tobacco endgame strategies, though it may be most applicable in well-organised jurisdictions with low (<15%) adult smoking prevalence. This idea could benefit from further research, such as studies in virtual worlds, and real-world testing on small island jurisdictions, or closed systems, such as military bases.

  20. Indications, advantages and limitations of perinatal postmortem imaging in clinical practice

    International Nuclear Information System (INIS)

    Arthurs, Owen J.; Taylor, Andrew M.; Sebire, Neil J.

    2015-01-01

    Just as there is a range of paediatric imaging techniques available during life, a similar repertoire is available as part of the foetal and perinatal postmortem examination. In this article, we review the literature regarding the diagnostic utility of postmortem radiography, US, CT and MRI in this clinical setting. There is limited direct evidence on the diagnostic utility of any of these techniques, apart from postmortem MRI, which when combined with other noninvasive investigations, has been shown to be highly sensitive and specific for many foetal postmortem diagnoses. The main disadvantages of postmortem MRI include the longer duration of imaging, the need for appropriate training in the interpretation of normal postmortem changes, and possible non-diagnostic imaging examinations in early gestation fetuses. As less-invasive autopsy becomes increasingly available, the true utility of these techniques will evolve, and clinical guidelines for maximal diagnostic yield can be developed. (orig.)

  1. Indications, advantages and limitations of perinatal postmortem imaging in clinical practice

    Energy Technology Data Exchange (ETDEWEB)

    Arthurs, Owen J. [Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Radiology, London (United Kingdom); University College London, Institute of Child Health, London (United Kingdom); Taylor, Andrew M. [Great Ormond Street Hospital for Children NHS Foundation Trust, Cardiorespiratory Division, London (United Kingdom); Centre for Cardiovascular Imaging, UCL Institute of Cardiovascular Science, London (United Kingdom); Sebire, Neil J. [University College London, Institute of Child Health, London (United Kingdom); Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Histopathology, London (United Kingdom)

    2015-04-01

    Just as there is a range of paediatric imaging techniques available during life, a similar repertoire is available as part of the foetal and perinatal postmortem examination. In this article, we review the literature regarding the diagnostic utility of postmortem radiography, US, CT and MRI in this clinical setting. There is limited direct evidence on the diagnostic utility of any of these techniques, apart from postmortem MRI, which when combined with other noninvasive investigations, has been shown to be highly sensitive and specific for many foetal postmortem diagnoses. The main disadvantages of postmortem MRI include the longer duration of imaging, the need for appropriate training in the interpretation of normal postmortem changes, and possible non-diagnostic imaging examinations in early gestation fetuses. As less-invasive autopsy becomes increasingly available, the true utility of these techniques will evolve, and clinical guidelines for maximal diagnostic yield can be developed. (orig.)

  2. Do Medicare Advantage Plans Select Enrollees in Higher Margin Clinical Categories?

    Science.gov (United States)

    Newhouse, Joseph P.; McWilliams, J. Michael; Price, Mary; Huang, Jie; Fireman, Bruce; Hsu, John

    2013-01-01

    The CMS-HCC risk adjustment system for Medicare Advantage (MA) plans calculates weights, which are effectively relative prices, for beneficiaries with different observable characteristics. To do so it uses the relative amounts spent per beneficiary with those characteristics in Traditional Medicare (TM). For multiple reasons one might expect relative amounts in MA to differ from TM, thereby making some beneficiaries more profitable to treat than others. Much of the difference comes from differences in how TM and MA treat different diseases or diagnoses. Using data on actual medical spending from two MA-HMO plans, we show that the weights calculated from MA costs do indeed differ from those calculated using TM spending. One of the two plans (Plan 1) is more typical of MA-HMO plans in that it contracts with independent community providers, while the other (Plan 2) is vertically integrated with care delivery. We calculate margins, or Average Revenue/Average Cost, for Medicare beneficiaries in the two plans who have one of 48 different combinations of medical conditions. The two plans’ margins for these 48 conditions are correlated (r=0.39, pincentive for selection by HCC. Nonetheless, we find no evidence of overrepresentation of beneficiaries in high margin HCC’s in either plan. Nor, using the margins from Plan 1, the more typical plan, do we find evidence of overrepresentation of high margin HCC’s in Medicare more generally. These results do not permit a conclusion on overall social efficiency, but we note that selection according to margin could be socially efficient. In addition, our findings suggest there are omitted interaction terms in the risk adjustment model that Medicare currently uses. PMID:24308879

  3. Traditional and innovative experimental and clinical trial designs and their advantages and pitfalls.

    Science.gov (United States)

    Weimer, Katja; Enck, Paul

    2014-01-01

    Many study designs and design variants have been developed in the past to either overcome or enhance drug-placebo differences in clinical trials or to identify and characterize placebo responders in experimental studies. They share many commonalities as well as differences that are discussed here: the role of deception and ethical restrictions, habituation effects and the control of the natural course of disease, assay sensitivity testing and effective blinding, acceptability and motivation of patients and volunteers, and the development of individualized medicine. These are fostered by two opposite strategies: utilizing the beneficial aspects of the placebo response-and avoiding its negative counterpart, the nocebo effect-in medical routine for the benefit of patients, and minimizing-by controlling-the negative aspects of the placebo effect during drug development.

  4. Clinical Trials With Large Numbers of Variables: Important Advantages of Canonical Analysis.

    Science.gov (United States)

    Cleophas, Ton J

    2016-01-01

    Canonical analysis assesses the combined effects of a set of predictor variables on a set of outcome variables, but it is little used in clinical trials despite the omnipresence of multiple variables. The aim of this study was to assess the performance of canonical analysis as compared with traditional multivariate methods using multivariate analysis of covariance (MANCOVA). As an example, a simulated data file with 12 gene expression levels and 4 drug efficacy scores was used. The correlation coefficient between the 12 predictor and 4 outcome variables was 0.87 (P = 0.0001) meaning that 76% of the variability in the outcome variables was explained by the 12 covariates. Repeated testing after the removal of 5 unimportant predictor and 1 outcome variable produced virtually the same overall result. The MANCOVA identified identical unimportant variables, but it was unable to provide overall statistics. (1) Canonical analysis is remarkable, because it can handle many more variables than traditional multivariate methods such as MANCOVA can. (2) At the same time, it accounts for the relative importance of the separate variables, their interactions and differences in units. (3) Canonical analysis provides overall statistics of the effects of sets of variables, whereas traditional multivariate methods only provide the statistics of the separate variables. (4) Unlike other methods for combining the effects of multiple variables such as factor analysis/partial least squares, canonical analysis is scientifically entirely rigorous. (5) Limitations include that it is less flexible than factor analysis/partial least squares, because only 2 sets of variables are used and because multiple solutions instead of one is offered. We do hope that this article will stimulate clinical investigators to start using this remarkable method.

  5. Customerizing the clinical laboratory. Repositioning for enhanced service and a competitive advantage.

    Science.gov (United States)

    Schuler, R S

    1989-01-01

    The call for excellence has never been louder, especially in the health-care industry. This call typically means increased service, i.e., faster, more accurate and, of course, friendlier service--all easier said than done, but qualities that make enhanced customer service so powerful. The excellent companies are learning that because it is so difficult to customerize, few competitors do so. Therefore, by devoting the time and effort necessary for customerization, they can move ahead of their competitors. But surpassing competitors by excellent service can be done inside of companies as well as outside. All units and departments have customers. The key to customerization inside is finding out what your customers want and behaving accordingly. The results go beyond enhanced customer satisfaction. They also include enhanced energy levels, reduced turnover, increased pride, and greater creativity for the newly customerized department. All it takes is an understanding of and dedication to customerization. Repositioning the existing department is critical to the success of any attempt to customerize. This article thoroughly describes customerization and the entire process of repositioning the clinical laboratory. One will not occur without the other.

  6. Comparing Integrated and Disciplinary Clinical Training Patterns for Dental Interns: Advantages, Disadvantages, and Effect on Students' Self-Confidence.

    Science.gov (United States)

    Wu, Junrong; Feng, Xiaoli; Chen, Aijie; Zhang, Yanli; Liu, Qi; Shao, Longquan

    2016-03-01

    In China, the five-year program of undergraduate education for stomatology consists of four years of lecture courses and one year of internship focused on clinical training. Dental schools provide this clinical training either in their own clinics (referred to as the one-stage pattern because all forms of practice are completed together) or by placing students in external clinics usually at non-affiliated hospitals (referred to as the three-stage program because the three primary areas are taught separately). The aims of this study were to investigate differences in teaching effect between the one-stage and the three-stage patterns and to evaluate advantages and disadvantages of the two patterns. A three-section, 31-item questionnaire was designed to assess basic and clinic information about the interns' training and their self-confidence in performing clinical procedures. The survey was administered to graduates who finished the fifth-year internship in 2012-14. Of the 356 individuals invited to participate, 303 graduates who spent their intern years in 43 academic dental institutions returned completed surveys (response rate of 85%). The one-stage group (n=121) reported longer independent operation time than the three-stage group (n=182) (p<0.01). No significant difference was found between the groups for assessment of clinic infrastructure (p=0.121). The interns were most confident in oral hygiene instruction and scale and polish (overall median=5), but showed low confidence in rubber dam placement and four other procedures (overall median=2). The one-stage group rated their confidence level higher than the three-stage group on comprehensive skills such as arranging appointments and managing patients and procedures needing long treatment periods such as molar endodontics. The three-stage group showed higher confidence on more specialized procedures such as surgical extractions and suturing. This study found that both of the two intern patterns had advantages and

  7. Medicare Advantage and Fee-for-Service Performance on Clinical Quality and Patient Experience Measures: Comparisons from Three Large States.

    Science.gov (United States)

    Timbie, Justin W; Bogart, Andy; Damberg, Cheryl L; Elliott, Marc N; Haas, Ann; Gaillot, Sarah J; Goldstein, Elizabeth H; Paddock, Susan M

    2017-12-01

    To compare performance between Medicare Advantage (MA) and Fee-for-Service (FFS) Medicare during a time of policy changes affecting both programs. Performance data for 16 clinical quality measures and 6 patient experience measures for 9.9 million beneficiaries living in California, New York, and Florida. We compared MA and FFS performance overall, by plan type, and within service areas associated with contracts between CMS and MA organizations. Case mix-adjusted analyses (for measures not typically adjusted) were used to explore the effect of case mix on MA/FFS differences. Performance measures were submitted by MA organizations, obtained from the nationwide fielding of the Medicare Consumer Assessment of Healthcare Providers and Systems (MCAHPS) Survey, or derived from claims. Overall, MA outperformed FFS on all 16 clinical quality measures. Differences were large for HEDIS measures and small for Part D measures and remained after case mix adjustment. MA enrollees reported better experiences overall, but FFS beneficiaries reported better access to care. Relative to FFS, performance gaps were much wider for HMOs than PPOs. Excluding HEDIS measures, MA/FFS differences were much smaller in contract-level comparisons. Medicare Advantage/Fee-for-Service differences are often large but vary in important ways across types of measures and contracts. © Health Research and Educational Trust.

  8. Institutional advantage

    NARCIS (Netherlands)

    Martin, Xavier

    Is there such a thing as institutional advantage—and what does it mean for the study of corporate competitive advantage? In this article, I develop the concept of institutional competitive advantage, as distinct from plain competitive advantage and from comparative institutional advantage. I first

  9. Potential advantages of coupling supercritical CO2 Brayton cycle to water cooled small and medium size reactor

    International Nuclear Information System (INIS)

    Yoon, Ho Joon; Ahn, Yoonhan; Lee, Jeong Ik; Addad, Yacine

    2012-01-01

    Highlights: ► S-CO 2 cycle as candidate for SMS. ► MATLAB code used for S-CO 2 cycle analysis. ► Pressure ratio and split ratio comparison analyzed. - Abstract: The supercritical carbon dioxide (S-CO 2 ) Brayton cycle is being considered as a favorable candidate for the next generation nuclear reactors power conversion systems. Major benefits of the S-CO 2 Brayton cycle compared to other Brayton cycles are: (1) high thermal efficiency in relatively low turbine inlet temperature, (2) compactness of the turbomachineries and heat exchangers and (3) simpler cycle layout at an equivalent or superior thermal efficiency. However, these benefits can be still utilized even in the water-cooled reactor technologies under special circumstances. A small and medium size water-cooled nuclear reactor (SMR) has been gaining interest due to its wide range of application such as electricity generation, seawater desalination, district heating and propulsion. Another key advantage of a SMR is that it can be transported from one place to another mostly by maritime transport due to its small size, and sometimes even through a railway system. Therefore, the combination of a S-CO 2 Brayton cycle with a SMR can reinforce any advantages coming from its small size if the S-CO 2 Brayton cycle has much smaller size components, and simpler cycle layout compared to the currently considered steam Rankine cycle. In this paper, SMART (System-integrated Modular Advanced ReacTor), a 330 MW th integral reactor developed by KAERI (Korea Atomic Energy Institute) for multipurpose utilization, is considered as a potential candidate for applying the S-CO 2 Brayton cycle and advantages and disadvantages of the proposed system will be discussed in detail. In consideration of SMART condition, the turbine inlet pressure and size of heat exchangers are analyzed by using in-house code developed by KAIST–Khalifa University joint research team. According to the cycle evaluation, the maximum cycle efficiency

  10. Potential benefits and risks of clinical xenotransplantation

    Directory of Open Access Journals (Sweden)

    Cooper DKC

    2012-07-01

    Full Text Available David KC Cooper,1 David Ayares21Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Revivicor, Blacksburg, VA, USAAbstract: The transplantation of organs and cells from pigs into humans could overcome the critical and continuing problem of the lack of availability of deceased human organs and cells for clinical transplantation. Developments in the genetic engineering of pigs have enabled considerable progress to be made in the experimental laboratory in overcoming the immune barriers to successful xenotransplantation. With regard to pig organ xenotransplantation, antibody- and cell-mediated rejection have largely been overcome, and the current major barrier is the development of coagulation dysregulation. This is believed to be due to a combination of immune activation of the vascular endothelial cells of the graft and molecular incompatibilities between the pig and primate coagulation–anticoagulation systems. Pigs with new genetic modifications specifically directed to this problem are now becoming available. With regard to less complex tissues, such as islets (for the treatment of diabetes, neuronal cells (for the treatment of Parkinson's disease, and corneas, the remaining barriers are less problematic, and graft survival in nonhuman primate models extends for >1 year in all three cases. In planning the initial clinical trials, consideration will be concentrated on the risk–benefit ratio, based to a large extent on the results of preclinical studies in nonhuman primates. If the benefit to the patient is anticipated to be high, eg, insulin-independent control of glycemia, and the potential risks low, eg, minimal risk of transfer of a porcine infectious agent, then a clinical trial would be justified.Keywords: infection, pigs, genetically-engineered, xenotransplantation, islets, xenotransplantation, organs

  11. China's energy saving potential from the perspective of energy efficiency advantages of foreign-invested enterprises

    International Nuclear Information System (INIS)

    Jiang, Xuemei; Zhu, Kunfu; Green, Christopher

    2015-01-01

    The paper investigates the energy saving potential associated with firm ownership-related differences in energy efficiency such as those between domestically and foreign-owned firms. Because of a gap in official statistics this topic has barely been touched upon in the scholarly literature. This paper employs a new energy input–output table that distinguishes firm ownership (Chinese owned enterprises, COEs; and foreign-invested enterprises, FIEs) and trade mode (export processing and normal goods production) to analyze the energy efficiency advantage of FIEs in China in 2007. The results show that the total energy intensities of COEs in the industrial sector are generally 5%–35% higher than that of FIEs across industry groups. At an aggregate level, China could save up to 20.3% of its energy use, if industrial COEs could duplicate the energy use efficiency and production technology of FIEs. This gain would require major technology upgrades among COEs. - Highlights: • A new input–output table distinguishing firm ownership and trade mode is employed. • The foreign-invested enterprises are 5%–35% energy efficient than Chinese enterprises in 2007. • China could save 20.3% of energy use if industrial COEs could duplicate the technologies of FIEs

  12. Mobile Device-Based Electronic Data Capture System Used in a Clinical Randomized Controlled Trial: Advantages and Challenges.

    Science.gov (United States)

    Zhang, Jing; Sun, Lei; Liu, Yu; Wang, Hongyi; Sun, Ningling; Zhang, Puhong

    2017-03-08

    Electronic data capture (EDC) systems have been widely used in clinical research, but mobile device-based electronic data capture (mEDC) system has not been well evaluated. The aim of our study was to evaluate the feasibility, advantages, and challenges of mEDC in data collection, project management, and telemonitoring in a randomized controlled trial (RCT). We developed an mEDC to support an RCT called "Telmisartan and Hydrochlorothiazide Antihypertensive Treatment (THAT)" study, which was a multicenter, double-blinded, RCT, with the purpose of comparing the efficacy of telmisartan and hydrochlorothiazide (HCTZ) monotherapy in high-sodium-intake patients with mild to moderate hypertension during a 60 days follow-up. Semistructured interviews were conducted during and after the trial to evaluate the feasibility, advantage, and challenge of mEDC. Nvivo version 9.0 (QSR International) was used to analyze records of interviews, and a thematic framework method was used to obtain outcomes. The mEDC was successfully used to support the data collection and project management in all the 14 study hospitals. A total of 1333 patients were recruited with support of mEDC, of whom 1037 successfully completed all 4 visits. Across all visits, the average time needed for 141 questions per patient was 53 min, which were acceptable to both doctors and patients. All the interviewees, including 24 doctors, 53 patients, 1 clinical research associate (CRA), 1 project manager (PM), and 1 data manager (DM), expressed their satisfaction to nearly all the functions of the innovative mEDC in randomization, data collection, project management, quality control, and remote monitoring in real time. The average satisfaction score was 9.2 (scale, 0-10). The biggest challenge came from the stability of the mobile or Wi-Fi signal although it was not a problem in THAT study. The innovative mEDC has many merits and is well acceptable in supporting data collection and project management in a timely

  13. Toxicology and clinical potential of nanoparticles

    Science.gov (United States)

    Yildirimer, Lara; Thanh, Nguyen T.K.; Loizidou, Marilena; Seifalian, Alexander M.

    2011-01-01

    Summary In recent years, nanoparticles (NPs) have increasingly found practical applications in technology, research and medicine. The small particle size coupled to their unique chemical and physical properties is thought to underlie their exploitable biomedical activities. Here, we review current toxicity studies of NPs with clinical potential. Mechanisms of cytotoxicity are discussed and the problem of extrapolating knowledge gained from cell-based studies into a human scenario is highlighted. The so-called ‘proof-of-principle’ approach, whereby ultra-high NP concentrations are used to ensure cytotoxicity, is evaluated on the basis of two considerations; firstly, from a scientific perspective, the concentrations used are in no way related to the actual doses required which, in many instances, discourages further vital investigations. Secondly, these inaccurate results cast doubt on the science of nanomedicine and thus, quite dangerously, encourage unnecessary alarm in the public. In this context, the discrepancies between in vitro and in vivo results are described along with the need for a unifying protocol for reliable and realistic toxicity reports. PMID:23293661

  14. Generic Advantages

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Generic Advantages. Scalability an incremental coverage. Standardization. Business Plan Flexibility. Lifecycle Flexibility. Reliability. Service Interoperability. Changed Industry dynamics.

  15. Absolute advantage

    NARCIS (Netherlands)

    J.G.M. van Marrewijk (Charles)

    2008-01-01

    textabstractA country is said to have an absolute advantage over another country in the production of a good or service if it can produce that good or service using fewer real resources. Equivalently, using the same inputs, the country can produce more output. The concept of absolute advantage can

  16. Clinical diagnostic potentials of thyroid ultrasonography and scintigraphy; An evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Torizuka, Tatsuo; Kasagi, Kanji; Hatabu, Hiroto; Misaki, Takashi; Iida, Yasuhiro; Konishi, Junji (Kyoto Univ. (Japan). Hospital); Endo, Keigo

    1993-06-01

    This prospective study was designed to evaluate the potential contributions of high resolution ultrasonography (US) and Tc-99m scintigraphy in the routine diagnosis of thyroid disease. The diagnostic impacts of US and Tc-99m scintigraphy results in 177 patients visiting our thyroid clinic were assessed and scored according to the following criteria: when the information provided by either test supported, confirmed or changed the initial clinical diagnosis, they received scores of 2, 3 and 4 respectively, while score 1 was given when the test itself was useless for the differential diagnosis. US identified focal lesions that both palpation and scintigraphy had failed to detect in 14 (12.1%) of 116 patients with diffuse thyroid diseases, suggesting the necessity of Hashimoto's thyroiditis, adenoma, adenocarcinoma and adenomatous goiter, and vice versa in the diagnosis of hyperthyroid and euthyroid Graves's diseases. Thus, the advantages of US over scintigraphy for morphological evaluation were confirmed. US was particularly useful for the differential diagnosis of adenomatous goiter from Hashimoto's thyroiditis or a single nodular disease. In contrast, scintigraphy gave functional images, being especially helpful for the differential diagnosis of thyrotoxicosis. (author).

  17. Clinical potentials of human pluripotent stem cells.

    Science.gov (United States)

    Mora, Cristina; Serzanti, Marialaura; Consiglio, Antonella; Memo, Maurizio; Dell'Era, Patrizia

    2017-08-01

    Aging, injuries, and diseases can be considered as the result of malfunctioning or damaged cells. Regenerative medicine aims to restore tissue homeostasis by repairing or replacing cells, tissues, or damaged organs, by linking and combining different disciplines including engineering, technology, biology, and medicine. To pursue these goals, the discipline is taking advantage of pluripotent stem cells (PSCs), a peculiar type of cell possessing the ability to differentiate into every cell type of the body. Human PSCs can be isolated from the blastocysts and maintained in culture indefinitely, giving rise to the so-called embryonic stem cells (ESCs). However, since 2006, it is possible to restore in an adult cell a pluripotent ESC-like condition by forcing the expression of four transcription factors with the rejuvenating reprogramming technology invented by Yamanaka. Then the two types of PSC can be differentiated, using standardized protocols, towards the cell type necessary for the regeneration. Although the use of these derivatives for therapeutic transplantation is still in the preliminary phase of safety and efficacy studies, a lot of efforts are presently taking place to discover the biological mechanisms underlying genetic pathologies, by differentiating induced PSCs derived from patients, and new therapies by challenging PSC-derived cells in drug screening.

  18. Seven-day human biological rhythms: An expedition in search of their origin, synchronization, functional advantage, adaptive value and clinical relevance.

    Science.gov (United States)

    Reinberg, Alain E; Dejardin, Laurence; Smolensky, Michael H; Touitou, Yvan

    2017-01-01

    This fact-finding expedition explores the perspectives and knowledge of the origin and functional relevance of the 7 d domain of the biological time structure, with special reference to human beings. These biological rhythms are displayed at various levels of organization in diverse species - from the unicellular sea algae of Acetabularia and Goniaulax to plants, insects, fish, birds and mammals, including man - under natural as well as artificial, i.e. constant, environmental conditions. Nonetheless, very little is known about their derivation, functional advantage, adaptive value, synchronization and potential clinical relevance. About 7 d cosmic cycles are seemingly too weak, and the 6 d work/1 d rest week commanded from G-d through the Laws of Mosses to the Hebrews is too recent an event to be the origin in humans. Moreover, human and insect studies conducted under controlled constant conditions devoid of environmental, social and other time cues report the persistence of 7 d rhythms, but with a slightly different (free-running) period (τ), indicating their source is endogenous. Yet, a series of human and laboratory rodent studies reveal certain mainly non-cyclic exogenous events can trigger 7 d rhythm-like phenomena. However, it is unknown whether such triggers unmask, amplify and/or synchronize previous non-overtly expressed oscillations. Circadian (~24 h), circa-monthly (~30 d) and circannual (~1 y) rhythms are viewed as genetically based features of life forms that during evolution conferred significant functional advantage to individual organisms and survival value to species. No such advantages are apparent for endogenous 7 d rhythms, raising several questions: What is the significance of the 7 d activity/rest cycle, i.e. week, storied in the Book of Genesis and adopted by the Hebrews and thereafter the residents of nearby Mediterranean countries and ultimately the world? Why do humans require 1 d off per 7 d span? Do 7 d rhythms bestow functional

  19. Multipotent Mesenchymal Stromal Stem Cell Expansion by Plating Whole Bone Marrow at a Low Cellular Density: A More Advantageous Method for Clinical Use

    Directory of Open Access Journals (Sweden)

    Katia Mareschi

    2012-01-01

    Full Text Available Mesenchymal stem cells (MSCs are a promising source for cell therapy due to their pluripotency and immunomodulant proprieties. As the identification of “optimal” conditions is important to identify a standard procedure for clinical use. Percoll, Ficoll and whole bone marrow directly plated were tested from the same sample as separation methods. The cells were seeded at the following densities: 100 000, 10 000, 1000, 100, 10 cells/cm2. After reaching confluence, the cells were detached, pooled and re-plated at 1000, 500, 100, and 10 cells/cm2. Statistical analyses were performed. Cumulative Population Doublings (PD did not show significant differences for the separation methods and seeding densities but only for the plating density. Some small quantity samples plated in T25 flasks at plating densities of 10 and 100 cells/cm2 did not produce any expansion. However, directly plated whole bone marrow resulted in a more advantageous method in terms of CFU-F number, cellular growth and minimal manipulation. No differences were observed in terms of gross morphology, differentiation potential or immunophenotype. These data suggest that plating whole bone marrow at a low cellular density may represent a good procedure for MSC expansion for clinical use.

  20. Multipotent Mesenchymal Stromal Stem Cell Expansion by Plating Whole Bone Marrow at a Low Cellular Density: A More Advantageous Method for Clinical Use

    Science.gov (United States)

    Mareschi, Katia; Rustichelli, Deborah; Calabrese, Roberto; Gunetti, Monica; Sanavio, Fiorella; Castiglia, Sara; Risso, Alessandra; Ferrero, Ivana; Tarella, Corrado; Fagioli, Franca

    2012-01-01

    Mesenchymal stem cells (MSCs) are a promising source for cell therapy due to their pluripotency and immunomodulant proprieties. As the identification of “optimal” conditions is important to identify a standard procedure for clinical use. Percoll, Ficoll and whole bone marrow directly plated were tested from the same sample as separation methods. The cells were seeded at the following densities: 100 000, 10 000, 1000, 100, 10 cells/cm2. After reaching confluence, the cells were detached, pooled and re-plated at 1000, 500, 100, and 10 cells/cm2. Statistical analyses were performed. Cumulative Population Doublings (PD) did not show significant differences for the separation methods and seeding densities but only for the plating density. Some small quantity samples plated in T25 flasks at plating densities of 10 and 100 cells/cm2 did not produce any expansion. However, directly plated whole bone marrow resulted in a more advantageous method in terms of CFU-F number, cellular growth and minimal manipulation. No differences were observed in terms of gross morphology, differentiation potential or immunophenotype. These data suggest that plating whole bone marrow at a low cellular density may represent a good procedure for MSC expansion for clinical use. PMID:23715383

  1. Comparative Advantage

    DEFF Research Database (Denmark)

    Zhang, Jie; Jensen, Camilla

    2007-01-01

    that are typically explained from the supply-side variables, the comparative advantage of the exporting countries. A simple model is proposed and tested. The results render strong support for the relevance of supply-side factors such as natural endowments, technology, and infrastructure in explaining international...

  2. Optical coherence tomography: potentialities in clinical practice

    Science.gov (United States)

    Zagaynova, Elena; Gladkova, Natalia D.; Shakhov, Andrey; Terentjeva, Anna; Snopova, Ludmila B.; Kuznetzova, Irina A.; Streltzova, Olga; Shakhova, Natalia M.; Kamensky, Vladislav A.; Gelikonov, Grigory V.; Gelikonov, Valentin M.; Kuranov, Roman V.; Myakov, Alex

    2004-08-01

    Clinical studies using OCT involved 2000 patients in various fields of medicine such as gastroenterology, urology, laryngology, gynecology, dermatology, stomatology, etc. Layered high-contrast images were typical for benign epithelial conditions. OCT distinguish in mucosae: epithelium, connective tissue layer, and smooth-muscle layer. Various benign processes occurring in mucosa manifest in OCT images as changes in the epithelial height, scattering properties and the course of the basement membrane. Lack of the layered structural pattern is the main criterion for dysplastic / malignant images. In clinic: OCT data may be critical for choosing a tissue site for excisional biopsy, OCT can detect tumor borders and their linear dimensions, OCT can be used to plan a resection line in operations and to control adequacy of resection, to monitor whether reparative processes are timely and adequate. OCT sensitivity of the uterine cervix, urinary bladder and larynx is 82, 98, 77%, respectively, specificity - 78, 71, 96%, diagnostic accuracy - 81, 85, 87% with significantly good agreement index of clinicians kappa - 0.65, 0.79, 0.83 (confidence intervals: 0.57-0.73; 0.71-0.88; 0.74-0.91). Error in detection of high grade dysplasia and microinvasive cancer is 21.4% in average. Additional modification of OCT (cross-polarisation OCT, OCM), development of the procedure (biotissue compression, application of chemical agents) can improve the specificity and sensitivity of traditional modality.

  3. Simulated Online Adaptive Magnetic Resonance–Guided Stereotactic Body Radiation Therapy for the Treatment of Oligometastatic Disease of the Abdomen and Central Thorax: Characterization of Potential Advantages

    Energy Technology Data Exchange (ETDEWEB)

    Henke, Lauren; Kashani, Rojano; Yang, Deshan; Zhao, Tianyu; Green, Olga; Olsen, Lindsey; Rodriguez, Vivian; Wooten, H. Omar; Li, H. Harold; Hu, Yanle; Bradley, Jeffrey; Robinson, Clifford; Parikh, Parag; Michalski, Jeff; Mutic, Sasa [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Olsen, Jeffrey R., E-mail: Jeffrey.R.Olsen@ucdenver.edu [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States)

    2016-12-01

    Purpose: To characterize potential advantages of online-adaptive magnetic resonance (MR)-guided stereotactic body radiation therapy (SBRT) to treat oligometastatic disease of the non-liver abdomen and central thorax. Methods and Materials: Ten patients treated with RT for unresectable primary or oligometastatic disease of the non-liver abdomen (n=5) or central thorax (n=5) underwent imaging throughout treatment on a clinical MR image guided RT system. The SBRT plans were created on the basis of tumor/organ at risk (OAR) anatomy at initial computed tomography simulation (P{sub I}), and simulated adaptive plans were created on the basis of observed MR image set tumor/OAR “anatomy of the day” (P{sub A}). Each P{sub A} was planned under workflow constraints to simulate online-adaptive RT. Prescribed dose was 50 Gy/5 fractions, with goal coverage of 95% planning target volume (PTV) by 95% of the prescription, subject to hard OAR constraints. The P{sub I} was applied to each MR dataset and compared with P{sub A} to evaluate changes in dose delivered to tumor/OARs, with dose escalation when possible. Results: Hard OAR constraints were met for all P{sub Is} based on anatomy from initial computed tomography simulation, and all P{sub As} based on anatomy from each daily MR image set. Application of the P{sub I} to anatomy of the day caused OAR constraint violation in 19 of 30 cases. Adaptive planning increased PTV coverage in 21 of 30 cases, including 14 cases in which hard OAR constraints were violated by the nonadaptive plan. For 9 P{sub A} cases, decreased PTV coverage was required to meet hard OAR constraints that would have been violated in a nonadaptive setting. Conclusions: Online-adaptive MRI-guided SBRT may allow PTV dose escalation and/or simultaneous OAR sparing compared with nonadaptive SBRT. A prospective clinical trial is underway at our institution to evaluate clinical outcomes of this technique.

  4. Exploration of the Super H-mode regime on DIII-D and potential advantages for burning plasma devices

    Energy Technology Data Exchange (ETDEWEB)

    Solomon, W. M., E-mail: solomon@fusion.gat.com; Bortolon, A.; Grierson, B. A.; Nazikian, R.; Poli, F. [Princeton Plasma Physics Laboratory, Princeton University, Princeton, New Jersey 08543 (United States); Snyder, P. B.; Burrell, K. H.; Garofalo, A. M.; Groebner, R. J.; Leonard, A. W.; Meneghini, O.; Osborne, T. H.; Petty, C. C. [General Atomics, P.O. Box 85608, San Diego, California 92186-5608 (United States); Loarte, A. [ITER Organization, Route de Vinon-sur-Verdon - CS 90 046, 13067 St Paul Lez Durance Cedex (France)

    2016-05-15

    A new high pedestal regime (“Super H-mode”) has been predicted and accessed on DIII-D. Super H-mode was first achieved on DIII-D using a quiescent H-mode edge, enabling a smooth trajectory through pedestal parameter space. By exploiting Super H-mode, it has been possible to access high pedestal pressures at high normalized densities. While elimination of Edge localized modes (ELMs) is beneficial for Super H-mode, it may not be a requirement, as recent experiments have maintained high pedestals with ELMs triggered by lithium granule injection. Simulations using TGLF for core transport and the EPED model for the pedestal find that ITER can benefit from the improved performance associated with Super H-mode, with increased values of fusion power and gain possible. Similar studies demonstrate that the Super H-mode pedestal can be advantageous for a steady-state power plant, by providing a path to increasing the bootstrap current while simultaneously reducing the demands on the core physics performance.

  5. Mammography - recent technical developments and their clinical potential

    Energy Technology Data Exchange (ETDEWEB)

    Hemdal, Bengt; Mattsson, Soeren [Malmoe Univ. Hospital (Sweden). Dept. of Radiation Physics; Andersson, Ingvar [Malmoe Univ. Hospital (Sweden). Dept. of Diagnostic Radiology; Thilander Klang, Anne [Sahlgrenska Univ. Hospital, Goeteborg (Sweden). Dept. of Medical Physics and Biomedical Engineering; Bengtsson, Gert; Jarlman, O. [Lund Univ. Hospital (Sweden). Dept. of Diagnostic Radiology; Leitz, Wolfram [Swedish Radiation Protection Authority, Stockholm (Sweden); Bjurstam, Nils [Univ. of North Norway, Troms (Norway). Dept. of Radiology

    2002-05-01

    The recent technical developments in digital as well as screen-film X-ray mammography have been reviewed in order to evaluate their clinical potential and to analyse possible lines for future development. Material and methods: The scientific literature has been reviewed, conferences covered and contacts with colleagues developed. Companies in the field have been inquired and invited for presentations. Own experience has been gathered from different screen-film and digital mammography systems. Results and conclusions: Although there are important complementary techniques such as ultrasound and magnetic resonance imaging (MRI), X-ray mammography is still the golden standard for breast imaging. It is relatively simple and cost-effective, and it is presently the only realistic technique for screening in a large scale. It is still largely the only technique that can detect breast cancer in a pre invasive stage. Equipment for digital mammography is commercially available both with small area and full field technique (FFDM). The development of FFDM systems is now intense, as well as the development of dedicated workstations and computer-aided detection (CAD). In spite of this, the introduction of digital mammography has been very slow compared to most other X-ray examinations due to high costs and technical challenges to meet the high demands on image quality and dose in mammography as well as the demands on specialised workflow support for screening mammography and suitable display techniques. Film reading of digital mammograms has been the most common display mode so far, but to take full advantage of the digital concept, diagnostic as well as logistic, monitor reading must be applied. There is a potential of FFDM systems for significantly higher image quality or significantly lower dose than screen-film mammography (SFM), or both. Further research is necessary to fully use this potential. The investment costs are much higher for digital than screen-film mammography

  6. Mammography - recent technical developments and their clinical potential

    International Nuclear Information System (INIS)

    Hemdal, Bengt; Mattsson, Soeren; Bjurstam, Nils

    2002-05-01

    The recent technical developments in digital as well as screen-film X-ray mammography have been reviewed in order to evaluate their clinical potential and to analyse possible lines for future development. Material and methods: The scientific literature has been reviewed, conferences covered and contacts with colleagues developed. Companies in the field have been inquired and invited for presentations. Own experience has been gathered from different screen-film and digital mammography systems. Results and conclusions: Although there are important complementary techniques such as ultrasound and magnetic resonance imaging (MRI), X-ray mammography is still the golden standard for breast imaging. It is relatively simple and cost-effective, and it is presently the only realistic technique for screening in a large scale. It is still largely the only technique that can detect breast cancer in a pre invasive stage. Equipment for digital mammography is commercially available both with small area and full field technique (FFDM). The development of FFDM systems is now intense, as well as the development of dedicated workstations and computer-aided detection (CAD). In spite of this, the introduction of digital mammography has been very slow compared to most other X-ray examinations due to high costs and technical challenges to meet the high demands on image quality and dose in mammography as well as the demands on specialised workflow support for screening mammography and suitable display techniques. Film reading of digital mammograms has been the most common display mode so far, but to take full advantage of the digital concept, diagnostic as well as logistic, monitor reading must be applied. There is a potential of FFDM systems for significantly higher image quality or significantly lower dose than screen-film mammography (SFM), or both. Further research is necessary to fully use this potential. The investment costs are much higher for digital than screen-film mammography

  7. Diagnostic potential of virtual bronchoscopy: advantages in comparison with axial CT slices, MPR and mIP?

    International Nuclear Information System (INIS)

    Rapp-Bernhardt, U.; Doehring, W.; Bernhardt, T.M.; Welte, T.; Kropf, S.

    2000-01-01

    The aim of this study was to evaluate the diagnostic potential of virtual endoscopy (VE) and to compare it with axial CT slices, multiplanar reconstructions (MPR), minimal intensity projections (mIP), and bronchoscopy in patients diagnosed with bronchogenic carcinoma. Thirty patients underwent a spiral CT. Axial CT images were transferred to an Onyx workstation (Silicon Graphics, Sun Microsystems, Mountain View, Calif.) for performing virtual endoscopy. Accuracy for this procedure was tested by three radiologists on a monitor in comparison with axial CT slices, MPR, mIP, and bronchoscopy concerning the localization and degree of stenoses. Endoluminal tumors were identified by virtual bronchoscopy with no statistically significant difference of localization or grading of stenosis in comparison with bronchoscopy, axial CT slices, MPR and mIP. Axial CT slices, MPR, and mIP showed poorer results with over- or underestimation of stenoses compared with VE and bronchoscopy. Passing of stenoses was only possible with VE in 5 patients. Virtual endoscopy is a non-invasive method for identification of endoluminal tumors and is comparable to real bronchoscopy. (orig.)

  8. Potential of Space-Borne Hyperspectral Data for Biomass Quantification in an Arid Environment: Advantages and Limitations

    Directory of Open Access Journals (Sweden)

    Harald Zandler

    2015-04-01

    Full Text Available In spite of considerable efforts to monitor global vegetation, biomass quantification in drylands is still a major challenge due to low spectral resolution and considerable background effects. Hence, this study examines the potential of the space-borne hyperspectral Hyperion sensor compared to the multispectral Landsat OLI sensor in predicting dwarf shrub biomass in an arid region characterized by challenging conditions for satellite-based analysis: The Eastern Pamirs of Tajikistan. We calculated vegetation indices for all available wavelengths of both sensors, correlated these indices with field-mapped biomass while considering the multiple comparison problem, and assessed the predictive performance of single-variable linear models constructed with data from each of the sensors. Results showed an increased performance of the hyperspectral sensor and the particular suitability of indices capturing the short-wave infrared spectral region in dwarf shrub biomass prediction. Performance was considerably poorer in the area with less vegetation cover. Furthermore, spatial transferability of vegetation indices was not feasible in this region, underlining the importance of repeated model building. This study indicates that upcoming space-borne hyperspectral sensors increase the performance of biomass prediction in the world’s arid environments.

  9. Diagnostic potential of virtual bronchoscopy: advantages in comparison with axial CT slices, MPR and mIP?

    Energy Technology Data Exchange (ETDEWEB)

    Rapp-Bernhardt, U.; Doehring, W.; Bernhardt, T.M. [Department of Diagnostic Radiology, Otto-von-Guericke University, Magdeburg (Germany); Welte, T. [Department of Cardiology, Angiology, and Pneumology, Otto-von-Guericke University, Magdeburg (Germany); Kropf, S. [Department of Biometrics and Medical Informatics, Otto-von-Guericke University, Magdeburg (Germany)

    2000-06-01

    The aim of this study was to evaluate the diagnostic potential of virtual endoscopy (VE) and to compare it with axial CT slices, multiplanar reconstructions (MPR), minimal intensity projections (mIP), and bronchoscopy in patients diagnosed with bronchogenic carcinoma. Thirty patients underwent a spiral CT. Axial CT images were transferred to an Onyx workstation (Silicon Graphics, Sun Microsystems, Mountain View, Calif.) for performing virtual endoscopy. Accuracy for this procedure was tested by three radiologists on a monitor in comparison with axial CT slices, MPR, mIP, and bronchoscopy concerning the localization and degree of stenoses. Endoluminal tumors were identified by virtual bronchoscopy with no statistically significant difference of localization or grading of stenosis in comparison with bronchoscopy, axial CT slices, MPR and mIP. Axial CT slices, MPR, and mIP showed poorer results with over- or underestimation of stenoses compared with VE and bronchoscopy. Passing of stenoses was only possible with VE in 5 patients. Virtual endoscopy is a non-invasive method for identification of endoluminal tumors and is comparable to real bronchoscopy. (orig.)

  10. Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges.

    Science.gov (United States)

    Kim, Dana; Kim, Young Sam; Shin, Dong Wun; Park, Chang Shin; Kang, Ju Hee

    2016-10-01

    No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.

  11. Computer-assisted technologies used in oral rehabilitation and the clinical documentation of alleged advantages - a systematic review.

    Science.gov (United States)

    Jokstad, A

    2017-04-01

    The objective of this systematic review is to identify current computer-assisted technologies used for managing patients with a need to re-establish craniofacial appearance, subjective discomfort and stomatognathic function, and the extent of their clinical documentation. Electronic search strategies were used for locating clinical studies in MEDLINE through PubMed and in the Cochrane library, and in the grey literature through searches on Google Scholar. The searches for commercial digital products for use in oral rehabilitation resulted in identifying 225 products per November 2016, used for patient diagnostics, communication and therapy purposes, and for other computer-assisted applications in context with oral rehabilitation. About one-third of these products were described in about 350 papers reporting from clinical human studies. The great majority of digital products for use in oral rehabilitation has no clinical documentation at all, while the products from a distinct minority of manufacturers have frequently appeared in more or less scientific reports. Moore's law apply also to digital dentistry, which predicts that the capacity of microprocessors will continue to become faster and with lower cost per performance unit, and innovative software programs will harness these improvements in performance. The net effect is the noticeable short product life cycle of digital products developed for use in oral rehabilitation and often lack of supportive clinical documentation. Nonetheless, clinicians must request clinically meaningful information about new digital products to assess net benefits for the patients or the dental professionals and not accept only technological verbiage as a basis for product purchases. © 2017 John Wiley & Sons Ltd.

  12. Clinical potential of implantable wireless sensors for orthopedic treatments.

    Science.gov (United States)

    Karipott, Salil Sidharthan; Nelson, Bradley D; Guldberg, Robert E; Ong, Keat Ghee

    2018-04-01

    Implantable wireless sensors have been used for real-time monitoring of chemicals and physical conditions of bones, tendons and muscles to diagnose and study orthopedic diseases and injuries. Due to the importance of these sensors in orthopedic care, a critical review, which not only analyzes the underlying technologies but also their clinical implementations and challenges, will provide a landscape view on their current state and their future clinical role. Areas covered: By conducting an extensive literature search and following the leaders of orthopedic implantable wireless sensors, this review covers the battery-powered and battery-free wireless implantable sensor technologies, and describes their implementation for hips, knees, spine, and shoulder stress/strain monitoring. Their advantages, limitations, and clinical challenges are also described. Expert commentary: Currently, implantable wireless sensors are mostly limited for scientific investigations and demonstrative experiments. Although rapid advancement in sensors and wireless technologies will push the reliability and practicality of these sensors for clinical realization, regulatory constraints and financial viability in medical device industry may curtail their continuous adoption for clinical orthopedic applications. In the next five years, these sensors are expected to gain increased interest from researchers, but wide clinical adoption is still unlikely.

  13. Surgical Treatment of Valvular Heart Disease: Overview of Mechanical and Tissue Prostheses, Advantages, Disadvantages, and Implications for Clinical Use.

    Science.gov (United States)

    Fiedler, Amy G; Tolis, George

    2018-02-05

    Valvular heart disease (VHD) affects a large number of patients annually. From a surgical standpoint, there are two primary options for valve replacement: mechanical or bioprosthetic. While there are clear advantages and disadvantages to either option, and recent literature does challenge some of the prior dictums of valve choice, a handful of absolutes remain true. Mechanical valves provide superior durability and freedom from re-operation when compared to their bioprosthetic counterparts, at the expense of bleeding or thrombotic complications associated with the need for lifelong oral anticoagulation. Unless a clear contraindication to oral anticoagulation exists, we recommend implanting mechanical valves for patients less than 60 years old and those who are older than 65 but maintained on anticoagulation for reasons other than their valvular disease. Bioprosthetic valves should be placed in patients who are greater than 65 years old or those patients who have a postoperative life expectancy of less than 10 years. Valve choice in patients between the ages of 60 to 70 is not dictated by guidelines and is less clear, with patient preference playing a larger role than their age range.

  14. Educational advantage.

    Science.gov (United States)

    2013-07-01

    This issue of JERHRE examines informed consent requirements as they arise in diverse countries and cultures, and in relation to level of risk of the research and vulnerability of the potential participants. It also examines issues of literacy as they affect informed consent. And it examines whether research participants want to be informed. Adequate informed consent is a statement that is meaningful and understandable by the particular research participant and that allows the participant free choice regarding participation. The way in which an adequate consent procedure is administered must, by definition, depend on the level of literacy of the potential research participants, and the nature and values of the culture of the potential participants. An implication of these requirements is that Western consent procedures are likely to violate ethical standards when employed in non-Western cultures. Educational activities presented below will enable readers to consolidate their knowledge and understanding of these issues. Written informed consent statements are not valid for use with research participants who lack literacy. The level of literacy required depends on the complexity of the research topic. In Clough et al., we find that cultural differences in self-concept, understanding of research methods, level of education, and deference to researchers challenge researchers to modify standard consent procedures to render them valid in some cultural contexts. In Abou Zeina et al., we find an even more complex problem of communicating patients' rights to illiterate patients in an Egyptian public hospital: not only can they not read, but they consider "patients' rights" as the least of their problems. In Iverson et al., we find still different issues concerning the scientific literacy of surrogate decision makers for critically ill patients. And in Ghandour et al., we find in Lebanon, within a very large sample of socioeconomically diverse students, a virtually total lack

  15. Exogenous stem cells pioneer a biobridge to the advantage of host brain cells following stroke: New insights for clinical applications

    Directory of Open Access Journals (Sweden)

    Marci G Crowley

    2017-01-01

    Full Text Available Stroke continues to maintain its status as one of the top causes of mortality within the United States. Currently, the only Food and Drug Administration (FDA-approved drug in place for stroke patients, tissue plasminogen activator (tPA, has a rigid therapeutic window, closing at approximately 4.5 h after stroke onset. Due to this short time frame and other restrictions, such as any condition that increases a patient's risk for hemorrhaging, it has been predicted that <5% of ischemic stroke patients benefit from tPA. Given that rehabilitation therapy remains the only other option for stroke victims, there is a clear unmet clinical need for treatment available for the remaining 95%. While still considered an experimental treatment, the utilization of stem cell therapies for stroke holds consistent promise. Copious preclinical studies report the capacity for transplanted stem cells to rescue the brain parenchyma surrounding the stroke-induced infarct core. At present, the exact mechanisms in which stem cells contribute a robust therapeutic benefit remains unclear. Following stem cell administration, researchers have observed cell replacement, an increase in growth factors, and a reduction in inflammation. With a deeper understanding of the precise mechanism of stem cells, these therapies can be optimized in the clinic to afford the greatest therapeutic benefit. Recent studies have depicted a unique method of endogenous stem cell activation as a result of stem cell therapy. In both traumatic brain injury and stroke models, transplanted mesenchymal stromal cells (MSCs facilitated a pathway between the neurogenic niches of the brain and the damaged area through extracellular matrix remodeling. The biobridge pioneered by the MSCs was utilized by the endogenous stem cells, and these cells were able to travel to the damaged areas distal to the neurogenic niches, a feat unachievable without prior remodeling. These studies broaden our understanding of stem

  16. Point-of-care testing (POCT) and evidence-based laboratory medicine (EBLM) - does it leverage any advantage in clinical decision making?

    Science.gov (United States)

    Florkowski, Christopher; Don-Wauchope, Andrew; Gimenez, Nuria; Rodriguez-Capote, Karina; Wils, Julien; Zemlin, Annalise

    Point-of-care testing (POCT) is the analysis of patient specimens outside the clinical laboratory, near or at the site of patient care, usually performed by clinical staff without laboratory training, although it also encompasses patient self-monitoring. It is able to provide a rapid result near the patient and which can be acted upon immediately. The key driver is the concept that clinical decision making may be delayed when samples are sent to the clinical laboratory. Balanced against this are considerations of increased costs for purchase and maintenance of equipment, staff training, connectivity to the laboratory information system (LIS), quality control (QC) and external quality assurance (EQA) procedures, all required for accreditation under ISO 22870. The justification for POCT depends upon being able to demonstrate that a more timely result (shorter turnaround times (TATs)) is able to leverage a clinically important advantage in decision making compared with the central laboratory (CL). In the four decades since POCT was adapted for the self-monitoring of blood glucose levels by subjects with diabetes, numerous new POCT methodologies have become available, enabling the clinician to receive results and initiate treatment more rapidly. However, these instruments are often operated by staff not trained in laboratory medicine and hence are prone to errors in the analytical phase (as opposed to laboratory testing where the analytical phase has the least errors). In some environments, particularly remote rural settings, the CL may be at a considerable distance and timely availability of cardiac troponins and other analytes can triage referrals to the main centers, thus avoiding expensive unnecessary patient transportation costs. However, in the Emergency Department, availability of more rapid results with POCT does not always translate into shorter stays due to other barriers to implementation of care. In this review, we apply the principles of evidence

  17. Potential clinical efficacy of intensity-modulated conformal therapy

    International Nuclear Information System (INIS)

    Meeks, Sanford L.; Buatti, John M.; Bova, Francis J.; Friedman, William A.; Mendenhall, William M.; Zlotecki, Robert A.

    1998-01-01

    Purpose: The purpose of this study was to examine the potential benefit of using intensity-modulated conformal therapy for a variety of lesions currently treated with stereotactic radiosurgery or conventional radiotherapy. Methods and Materials: Intensity-modulated conformal treatment plans were generated for small intracranial lesions, as well as head and neck, lung, breast, and prostate cases, using the Peacock Plan[reg] treatment-planning system (Nomos Corporation). For small intracranial lesions, intensity-modulated conformal treatment plans were compared with stereotactic radiosurgery treatment plans generated for patient treatment at the University of Florida Shands Cancer Center. For other sites (head and neck, lung, breast, and prostate), plans generated using the Peacock Plan[reg] were compared with conventional treatment plans, as well as beam's-eye-view conformal treatment plans. Plan comparisons were accomplished through conventional qualitative review of two-dimensional (2D) dose distributions in conjunction with quantitative techniques, such as dose-volume histograms, dosimetric statistics, normal tissue complication probabilities, tumor control probabilities, and objective numerical scoring. Results: For small intracranial lesions, there is little difference between intensity-modulated conformal treatment planning and radiosurgery treatment planning in the conformation of high isodose lines with the target volume. However, stereotactic treatment planning provides a steeper dose gradient outside the target volume and, hence, a lower normal tissue toxicity index. For extracranial sites, objective numerical scores for beam's-eye-view and intensity-modulated conformal planning techniques are superior to scores for conventional treatment plans. The beam's-eye-view planning technique prevents geographic target misses and better excludes healthy tissues from the treatment portal. Compared with scores for the beam's-eye-view planning technique, scores for

  18. 7T: Physics, safety, and potential clinical applications.

    Science.gov (United States)

    Kraff, Oliver; Quick, Harald H

    2017-12-01

    With more than 60 installed magnetic resonance imaging (MRI) systems worldwide operating at a magnetic field strength of 7T or higher, ultrahigh-field (UHF) MRI has been established as a platform for clinically oriented research in recent years. Profound technical and methodological developments have helped overcome the inherent physical challenges of UHF radiofrequency (RF) signal homogenization in the human body. The ongoing development of dedicated RF coil arrays was pivotal in realizing UHF body MRI, beyond mere brain imaging applications. Another precondition to clinical application of 7T MRI is the safety testing of implants and the establishment of safety concepts. Against this backdrop, 7T MRI and MR spectroscopy (MRS) recently have demonstrated capabilities and potentials for clinical diagnostics in a variety of studies. This article provides an overview of the immanent physical challenges of 7T UHF MRI and discusses recent technical solutions and safety concepts. Furthermore, recent clinically oriented studies are highlighted that span a broad application spectrum from 7T UHF brain to body MRI. 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1573-1589. © 2017 International Society for Magnetic Resonance in Medicine.

  19. Conducting qualitative research within Clinical Trials Units: avoiding potential pitfalls.

    Science.gov (United States)

    Cooper, Cindy; O'Cathain, Alicia; Hind, Danny; Adamson, Joy; Lawton, Julia; Baird, Wendy

    2014-07-01

    The value of using qualitative research within or alongside randomised controlled trials (RCTs) is becoming more widely accepted. Qualitative research may be conducted concurrently with pilot or full RCTs to understand the feasibility and acceptability of the interventions being tested, or to improve trial conduct. Clinical Trials Units (CTUs) in the United Kingdom (UK) manage large numbers of RCTs and, increasingly, manage the qualitative research or collaborate with qualitative researchers external to the CTU. CTUs are beginning to explicitly manage the process, for example, through the use of standard operating procedures for designing and implementing qualitative research with trials. We reviewed the experiences of two UK Clinical Research Collaboration (UKCRC) registered CTUs of conducting qualitative research concurrently with RCTs. Drawing on experiences gained from 15 studies, we identify the potential for the qualitative research to undermine the successful completion or scientific integrity of RCTs. We show that potential problems can arise from feedback of interim or final qualitative findings to members of the trial team or beyond, in particular reporting qualitative findings whilst the trial is on-going. The problems include: We make recommendations for improving the management of qualitative research within CTUs. Copyright © 2014. Published by Elsevier Inc.

  20. Identification and Pathogenic Potential of Clinical Bacillus and Paenibacillus Isolates.

    Directory of Open Access Journals (Sweden)

    Francesco Celandroni

    Full Text Available The soil-related Bacillus and Paenibacillus species have increasingly been implicated in various human diseases. Nevertheless, their identification still poses problems in the clinical microbiology laboratory and, with the exception of Bacillus anthracis and Bacillus cereus, little is known on their pathogenicity for humans. In this study, we evaluated the use of matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS in the identification of clinical isolates of these genera and conducted genotypic and phenotypic analyses to highlight specific virulence properties. Seventy-five clinical isolates were subjected to biochemical and MALDI-TOF MS identification. 16S rDNA sequencing and supplemental tests were used to solve any discrepancies or failures in the identification results. MALDI-TOF MS significantly outperformed classical biochemical testing for correct species identification and no misidentification was obtained. One third of the collected strains belonged to the B. cereus species, but also Bacillus pumilus and Bacillus subtilis were isolated at high rate. Antimicrobial susceptibility testing showed that all the B. cereus, B. licheniformis, B. simplex, B. mycoides, Paenibacillus glucanolyticus and Paenibacillus lautus isolates are resistant to penicillin. The evaluation of toxin/enzyme secretion, toxin-encoding genes, motility, and biofilm formation revealed that B. cereus displays the highest virulence potential. However, although generally considered nonpathogenic, most of the other species were shown to swim, swarm, produce biofilms, and secrete proteases that can have a role in bacterial virulence. In conclusion, MALDI-TOF MS appears useful for fast and accurate identification of Bacillus and Paenibacillus strains whose virulence properties make them of increasing clinical relevance.

  1. Use of the i2b2 research query tool to conduct a matched case-control clinical research study: advantages, disadvantages and methodological considerations.

    Science.gov (United States)

    Johnson, Emilie K; Broder-Fingert, Sarabeth; Tanpowpong, Pornthep; Bickel, Jonathan; Lightdale, Jenifer R; Nelson, Caleb P

    2014-01-30

    A major aim of the i2b2 (informatics for integrating biology and the bedside) clinical data informatics framework aims to create an efficient structure within which patients can be identified for clinical and translational research projects.Our objective was to describe the respective roles of the i2b2 research query tool and the electronic medical record (EMR) in conducting a case-controlled clinical study at our institution. We analyzed the process of using i2b2 and the EMR together to generate a complete research database for a case-control study that sought to examine risk factors for kidney stones among gastrostomy tube (G-tube) fed children. Our final case cohort consisted of 41/177 (23%) of potential cases initially identified by i2b2, who were matched with 80/486 (17%) of potential controls. Cases were 10 times more likely to be excluded for inaccurate coding regarding stones vs. inaccurate coding regarding G-tubes. A majority (67%) of cases were excluded due to not meeting clinical inclusion criteria, whereas a majority of control exclusions (72%) occurred due to inadequate clinical data necessary for study completion. Full dataset assembly required complementary information from i2b2 and the EMR. i2b2 was critical as a query analysis tool for patient identification in our case-control study. Patient identification via procedural coding appeared more accurate compared with diagnosis coding. Completion of our investigation required iterative interplay of i2b2 and the EMR to assemble the study cohort.

  2. Drivers of Collaborative Advantage

    DEFF Research Database (Denmark)

    Weihe, Gudrid

    processes and behavioural dimensions is practically non-existent. This article tries to remedy the current gap in the literature by reviewing research findings on interfirm collaboration (alliances). On that basis a conceptual framework for analyzing partnership processes is developed. Finally......, the antecedents of collaborative advantage are theoretically examined, and the organizational competences contributing to collaborative success are identified. The conclusion is that operational processes and social dynamics are vital drivers of collaborative advantage. Another significant conclusion...... is that public management research can benefit from drawing upon existing alliance research. Alliance scholars have during the past couple of decades accumulated an impressive amount of knowledge on different aspects of inter-firm cooperation, and therefore the learning potential for public management scholars...

  3. Mesenchymal stem cells: biological characteristics and potential clinical applications

    DEFF Research Database (Denmark)

    Kassem, Moustapha

    2004-01-01

    are among the first stem cell types to be introduced in the clinic. Several studies have demonstrated the possible use of MSC in systemic transplantation for systemic diseases, local implantation for local tissue defects, as a vehicle for genes in gene therapy protocols or to generate transplantable tissues...... and organs in tissue engineering protocols. Before their widespread use in therapy, methods allowing the generation of large number of cells without affecting their differentiation potential as well as technologies that overcome immunological rejection (in case allogenic transplantation) must be developed.......Mesenchymal stem cells (MSC) are clonogenic, non-hematpoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages, for example, osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages, for example, neuronal...

  4. Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanisms.

    Science.gov (United States)

    Sdrulla, Andrei D; Guan, Yun; Raja, Srinivasa N

    2018-03-11

    Spinal cord stimulation (SCS) is a minimally invasive therapy used for the treatment of chronic neuropathic pain. SCS is a safe and effective alternative to medications such as opioids, and multiple randomized controlled studies have demonstrated efficacy for difficult-to-treat neuropathic conditions such as failed back surgery syndrome. Conventional SCS is believed mediate pain relief via activation of dorsal column Aβ fibers, resulting in variable effects on sensory and pain thresholds, and measurable alterations in higher order cortical processing. Although potentiation of inhibition, as suggested by Wall and Melzack's gate control theory, continues to be the leading explanatory model, other segmental and supraspinal mechanisms have been described. Novel, non-standard, stimulation waveforms such as high-frequency and burst have been shown in some studies to be clinically superior to conventional SCS, however their mechanisms of action remain to be determined. Additional studies are needed, both mechanistic and clinical, to better understand optimal stimulation strategies for different neuropathic conditions, improve patient selection and optimize efficacy. © 2018 World Institute of Pain.

  5. Potential advantages of treatment of transplanted saphenous vein aorto-coronary artery bypass grafts with beta irradiation to prevent graft occlusion.

    Science.gov (United States)

    Smith, R G

    1997-01-01

    Intimal proliferation or Neointimal hyperplasia (NIH) is a vascular lesion that often arises in arteries after balloon angioplasty or other vessel wall injuries. FIH is a vascular lesion that develops in autologous saphenous vein grafts (SVG) after transplantation into the aorto-coronary circulation or the peripheral vascular circulation. FIH shares elements of smooth muscle migration, proliferation and fibrous tissue deposition in common with nibrointimal proliferation (NIH). Either NIH of a coronary artery or FIH of a SVG obstruct the vascular lumen and result in myocardial dysfunction. Local radiotherapy has been used for several decades to reduce the post-operative recurrence of the fibrovascular proliferations of pterygia and keloids. Similarly, in animal and human experiments, endovascular radiotherapy has been shown to reduce arterial smooth muscle proliferation. Consideration of the similarities of vascular smooth muscle cell proliferation in NIH and FIH leads one to suggest that endovascular beta irradiation can reduce FIH as well as it reduces NIH. The goal of such treatment is to achieve a clinically significant decrease in the morbidity and mortality resulting from SVG occlusions. The potential for large reduction of the consequences of SVG occlusion, the very large number of patients at risk, and the simplicity of the proposed intervention encourages prompt scientific evaluation of this technique.

  6. Pharmacogenetics: progress, pitfalls and clinical potential for coronary heart disease.

    Science.gov (United States)

    Humphries, Steve E; Hingorani, Aroon

    2006-02-01

    Much has been written about the potential of pharmacogenetic testing to inform therapy based on an individual's genetic makeup, and to decide the most effective choice of available drugs, or to avoid dangerous side effects. Currently, there is little hard data for either in the field of cardiovascular disease. The usual approach has been opportunistic use of drug trials in unrelated patients, and to look for differences in response or outcome by "candidate gene" genotype, for example genes coding for drug metabolising enzymes (activators and metabolisers), and enzymes and receptors involved in lipid metabolism, adrenergic response, etc. As with all association studies, initially promising results have often failed the test of replication in larger studies, and the relationship between the CETP Taq-I variant and response to statins has now been disproved. The strongest data to date is the report [Chasman, D.I., Posada, D., Subrahmanyan, L., Cook, N.R., Stanton Jr., V.P., Ridker, P.M., 2004. Pharmacogenetic study of statin therapy and cholesterol reduction. J. Am. Med. Assoc. 291, 2821-2827] of a poorer cholesterol-lowering response to Pravastatin in the 7% of patients carrying a certain haplotype of the HMG CoA reductase gene (14% fall versus 19%), but if this is overcome simply by a higher dose, it is of little clinical relevance. Currently, the best example of avoiding side effects is determining genotype at the CYP2C9 locus with respect of warfarin treatment, since carriers for functional variants (>20% of the population) require lower doses for optimal anticoagulation, and homozygotes, although rare, may well experience serious bleeding if given a usual dose. The full potential of this field will only be realised with much further work.

  7. Construction and Potential Applications of Biosensors for Proteins in Clinical Laboratory Diagnosis.

    Science.gov (United States)

    Liu, Xuan; Jiang, Hui

    2017-12-04

    Biosensors for proteins have shown attractive advantages compared to traditional techniques in clinical laboratory diagnosis. In virtue of modern fabrication modes and detection techniques, various immunosensing platforms have been reported on basis of the specific recognition between antigen-antibody pairs. In addition to profit from the development of nanotechnology and molecular biology, diverse fabrication and signal amplification strategies have been designed for detection of protein antigens, which has led to great achievements in fast quantitative and simultaneous testing with extremely high sensitivity and specificity. Besides antigens, determination of antibodies also possesses great significance for clinical laboratory diagnosis. In this review, we will categorize recent immunosensors for proteins by different detection techniques. The basic conception of detection techniques, sensing mechanisms, and the relevant signal amplification strategies are introduced. Since antibodies and antigens have an equal position to each other in immunosensing, all biosensing strategies for antigens can be extended to antibodies under appropriate optimizations. Biosensors for antibodies are summarized, focusing on potential applications in clinical laboratory diagnosis, such as a series of biomarkers for infectious diseases and autoimmune diseases, and an evaluation of vaccine immunity. The excellent performances of these biosensors provide a prospective space for future antibody-detection-based disease serodiagnosis.

  8. Clinical Potential of Hyperbaric Pressure-Treated Whey Protein

    Science.gov (United States)

    Piccolomini, André F.; Kubow, Stan; Lands, Larry C.

    2015-01-01

    Whey protein (WP) from cow’s milk is a rich source of essential and branched chain amino acids. Whey protein isolates (WPI) has been demonstrated to support muscle accretion, antioxidant activity, and immune modulation. However, whey is not readily digestible due to its tight conformational structure. Treatment of WPI with hyperbaric pressure results in protein unfolding. This enhances protein digestion, and results in an altered spectrum of released peptides, and greater release of essential and branched chain amino acids. Pressurized whey protein isolates (pWPI), through a series of cell culture, animal models and clinical studies, have been demonstrated to enhance muscle accretion, reduce inflammation, improve immunity, and decrease fatigue. It is also conceivable that pWPI would be more accessible to digestive enzymes, which would allow for a more rapid proteolysis of the proteins and an increased or altered release of small bioactive peptides. The altered profile of peptides released from WP digestion could thus play a role in the modulation of the immune response and tissue glutathione (GSH) concentrations. The research to date presents potentially interesting applications for the development of new functional foods based on hyperbaric treatment of WPI to produce products with more potent nutritional and nutraceutical properties. PMID:27417773

  9. Potentially harmful advantage to athletes: a putative connection between UGT2B17 gene deletion polymorphism and renal disorders with prolonged use of anabolic androgenic steroids

    Directory of Open Access Journals (Sweden)

    Barker James

    2010-04-01

    Full Text Available Abstract Background and objective With prolonged use of anabolic androgenic steroids (AAS, occasional incidents of renal disorders have been observed. Independently, it has also been established that there are considerable inter-individual and inter-ethnic differences, in particular with reference to the uridine diphosphate-glucuronosyltransferase 2B17 (UGT2B17 gene, in metabolising these compounds. This report postulates the association of deletion polymorphism in the UGT2B17 gene with the occurrence of renal disorders on chronic exposure to AAS. Presentation of the hypothesis The major deactivation and elimination pathway of AASs is through glucuronide conjugation, chiefly catalyzed by the UGT2B17 enzyme, followed by excretion in urine. Excretion of steroids is affected in individuals with a deletion mutation in the UGT2B17 gene. We hypothesize that UGT2B17 deficient individuals are more vulnerable to developing renal disorders with prolonged use of AAS owing to increases in body mass index and possible direct toxic effects of steroids on the kidneys. Elevated serum levels of biologically active steroids due to inadequate elimination can lead to prolonged muscle build up. An increase in body mass index may cause renal injuries due to sustained elevated glomerular pressure and flow rate. Testing the hypothesis In the absence of controlled clinical trials in humans, observational studies can be carried out. Real time PCR with allelic discrimination should be employed to examine the prevalence of different UGT2B17 genotypes in patients with impaired renal function and AAS abuse. In individuals with the UGT2B17 deletion polymorphism, blood tests, biofluid analyses, urinalysis, and hair analyses following the administration of an anabolic steroid can be used to determine the fate of the substance once in the body. Implications of the hypothesis If the hypothesis is upheld, anabolic steroid users with a deletion mutation in the UGT2B17 gene may be

  10. Competitive versus comparative advantage

    OpenAIRE

    Neary, J. Peter

    2002-01-01

    I explore the interactions between comparative, competitive and absolute advantage in a two-country model of oligopoly in general equilibrium. Comparative advantage always determines the direction of trade, but both competitive and absolute advantage affect resource allocation, trade patterns and trade volumes. Competitive advantage in the sense of more home firms drives foreign firms out of marginal sectors but also makes some marginal home sectors uncompetitive. Absolute advantage in the se...

  11. Dosimetric advantage and clinical implication of a micro-multileaf collimator in the treatment of prostate with intensity-modulated radiotherapy

    International Nuclear Information System (INIS)

    Wang Lu; Hoban, Peter; Paskalev, Kamen; Yang Jie; Li Jinsheng; Chen Lili; Xiong Weijun; Ma, Charlie

    2005-01-01

    This paper investigates the dosimetric benefits of a micro-multileaf (4-mm leaf width) collimator (mMLC) for intensity-modulated radiation therapy (IMRT) treatment planning of the prostate cancer and its potential application for dose escalation and hypofractionation. We compared treatment plans for IMRT delivery using 2 different multileaf collimator (MLC) leaf widths (4 vs. 10 mm) for 10 patients with prostate cancer. Treatment planning was performed on the XknifeRT2 treatment planning system. All beams and optimization parameters were identical for the mMLC and MLC plans. All of the plans were normalized to ensure that 95% of the planning target volume (PTV) received 100% of the prescribed dose (74 Gy). The differences in dose distribution between the 2 groups of plans using the mMLC and the MLC were assessed by dose-volume histogram (DVH) analysis of the target and critical organs. Significant reductions in the volume of rectum receiving medium to higher doses were achieved using the mMLC. The average decrease in the volume of the rectum receiving 40, 50, and 60 Gy using the mMLC plans was 40.2%, 33.4%, and 17.7%, respectively, with p-values less than 0.0001 for V 40 and V 50 and 0.012 for V 60 . The mean dose reductions for D 17 and D 35 for the rectum were 20.0% (p 0.78). Because of the reduction of rectal volume receiving medium to higher doses, dose to the prostate target can be escalated by about 20 Gy to over 74 Gy, while keeping the rectal dose (either denoted by D 17 or D 35 ) the same as those with the use of the MLC. The maximum achievable dose, derived when the rectum is allowed to reach the tolerance level, was found to be in the range of 113-172 Gy (using the tolerance value of D 17 ). We conclude that the use of the mMLC for IMRT of the prostate may facilitate dose hypofractionation due to its dosimetric advantage in significantly improving the DVH parameters of the prostate and critical organs. When used for conventional fractionation scheme, m

  12. Maximising the potential of part-time clinical teachers.

    Science.gov (United States)

    Patston, Philip; Holmes, David; Maalhagh-Fard, Ahmad; Ting, Kang; Ziccardi, Vincent B

    2010-12-01

    A problem faced by health professions education throughout the world is a lack of full-time clinical teachers. This is particularly serious in dentistry and nursing, but is increasingly also true in medicine. To make up for this shortfall there is a growing reliance on part-time clinical teachers. Part-time clinical teachers are essential for the education of students. However, compared with their full-time counterparts, the part-time teachers are often not adequately prepared for their roles as educators within the context of the clinical curriculum. They might not be trained in the latest educational practices, and may be unprepared for the time needed to excel as teachers and mentors. As part-time teachers take on more responsibility, it is important that they take part in orientation and training sessions to assist them in developing the skills they need to succeed. This will require a significant commitment from the institution as well as the part-time teacher, but is critical for maintaining the academic quality of the clinical training programmes. This also represents an untapped area for research into how to ensure the success of part-time clinical teachers. © Blackwell Publishing Ltd 2010.

  13. Potential use of recombinant human interleukin-6 in clinical oncology

    NARCIS (Netherlands)

    Veldhuis, GJ; Willemse, PHB; Mulder, NH; Limburg, PC; deVries, EGE

    Recombinant human IL-6 (rhIL-6) is a pleiotropic cytokine with stimulatory actions on the hematopoietic system, the immune system and hepatocytes. Clinical interest in the use of this cytokine was raised because of its thrombopoietic properties and also because of its anti-tumor activity, which was

  14. Immunomodulatory nutraceuticals with potential clinical use for dogs and cats

    Directory of Open Access Journals (Sweden)

    Leandro Zaine

    2014-09-01

    Full Text Available The use of nutraceuticals in veterinary medicine is growing and is assumed that they could aid in clinical treatment. This review aims to describe some nutraceuticals that act on the immunity of dogs and cats and show the possible benefits as an adjuvant treatment for some diseases. The action of some yeast derivates as immunomodulators, especially the beta-glucan fraction, was already proved to occur in dogs and cats, being beneficial as an adjuvant therapy in many clinical conditions. Omega-3 polyunsatured fatty acids, possibly the mostly used nutraceuticals, can improve the condition in some diseases, such as hypertension, renal, cardiac, gastrointestinal and autoimmune diseases, arthritis and cancer. Vitamin E has antioxidant and immunomodulatory action and can aid in the treatment of dermatologic and hepatobiliar conditions. The use of carotenoids, which have similar action to vitamin E, can be of interest for being potent antioxidants and might be helpful for enhancing immune response against microorganisms and also act preventing tumors. Despite it are still needed clinical trials to better understand the real benefits of nutraceuticals supplementation in each specific disease, the comprehension of the mechanisms by which they act indicates they are promising for clinical use.

  15. Potential biomarkers for the clinical prognosis of severe dengue

    Directory of Open Access Journals (Sweden)

    Mayara Marques Carneiro da Silva

    2013-09-01

    Full Text Available Currently, several assays can confirm acute dengue infection at the point-of-care. However, none of these assays can predict the severity of the disease symptoms. A prognosis test that predicts the likelihood of a dengue patient to develop a severe form of the disease could permit more efficient patient triage and treatment. We hypothesise that mRNA expression of apoptosis and innate immune response-related genes will be differentially regulated during the early stages of dengue and might predict the clinical outcome. Aiming to identify biomarkers for dengue prognosis, we extracted mRNA from the peripheral blood mononuclear cells of mild and severe dengue patients during the febrile stage of the disease to measure the expression levels of selected genes by quantitative polymerase chain reaction. The selected candidate biomarkers were previously identified by our group as differentially expressed in microarray studies. We verified that the mRNA coding for CFD, MAGED1, PSMB9, PRDX4 and FCGR3B were differentially expressed between patients who developed clinical symptoms associated with the mild type of dengue and patients who showed clinical symptoms associated with severe dengue. We suggest that this gene expression panel could putatively serve as biomarkers for the clinical prognosis of dengue haemorrhagic fever.

  16. Brokers and Competitive Advantage

    OpenAIRE

    Michael D. Ryall; Olav Sorenson

    2007-01-01

    The broker profits by intermediating between two (or more) parties. Using a biform game, we examine whether such a position can confer a competitive advantage, as well as whether any such advantage could persist if actors formed relations strategically. Our analysis reveals that, if one considers exogenous the relations between actors, brokers can enjoy an advantage but only if (1) they do not face substitutes either for the connections they offer or the value they can create, (2) they interm...

  17. Potential of adaptive clinical trial designs in pharmacogenetic research, A simulation based on the IPASS trial

    NARCIS (Netherlands)

    Van Der Baan, Frederieke H.; Knol, Mirjam J.|info:eu-repo/dai/nl/304820350; Klungel, Olaf H.|info:eu-repo/dai/nl/181447649; Egberts, Toine C.G.|info:eu-repo/dai/nl/162850050; Grobbee, Diederick E.; Roes, Kit C.B.

    2011-01-01

    Background: An adaptive clinical trial design that allows population enrichment after interim analysis can be advantageous in pharmacogenetic research if previous evidence is not strong enough to exclude part of the patient population beforehand.With this design, underpowered studies or unnecessary

  18. Human reporter genes: potential use in clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Serganova, Inna [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Ponomarev, Vladimir [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Blasberg, Ronald [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States)], E-mail: blasberg@neuro1.mskcc.org

    2007-10-15

    The clinical application of positron-emission-tomography-based reporter gene imaging will expand over the next several years. The translation of reporter gene imaging technology into clinical applications is the focus of this review, with emphasis on the development and use of human reporter genes. Human reporter genes will play an increasingly more important role in this development, and it is likely that one or more reporter systems (human gene and complimentary radiopharmaceutical) will take leading roles. Three classes of human reporter genes are discussed and compared: receptors, transporters and enzymes. Examples of highly expressed cell membrane receptors include specific membrane somatostatin receptors (hSSTrs). The transporter group includes the sodium iodide symporter (hNIS) and the norepinephrine transporter (hNET). The endogenous enzyme classification includes human mitochondrial thymidine kinase 2 (hTK2). In addition, we also discuss the nonhuman dopamine 2 receptor and two viral reporter genes, the wild-type herpes simplex virus 1 thymidine kinase (HSV1-tk) gene and the HSV1-tk mutant (HSV1-sr39tk). Initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: (a) gene therapy and (b) adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adenoviral-based, retroviral-based and lenteviral-based gene therapies, oncolytic bacterial and viral therapies, and adoptive cell-based therapies. Translational applications of noninvasive in vivo reporter gene imaging are likely to include: (a) quantitative monitoring of gene therapy vectors for targeting and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; (b) monitoring of cell trafficking, targeting, replication and activation in adoptive T-cell and stem/progenitor cell therapies

  19. Human reporter genes: potential use in clinical studies

    International Nuclear Information System (INIS)

    Serganova, Inna; Ponomarev, Vladimir; Blasberg, Ronald

    2007-01-01

    The clinical application of positron-emission-tomography-based reporter gene imaging will expand over the next several years. The translation of reporter gene imaging technology into clinical applications is the focus of this review, with emphasis on the development and use of human reporter genes. Human reporter genes will play an increasingly more important role in this development, and it is likely that one or more reporter systems (human gene and complimentary radiopharmaceutical) will take leading roles. Three classes of human reporter genes are discussed and compared: receptors, transporters and enzymes. Examples of highly expressed cell membrane receptors include specific membrane somatostatin receptors (hSSTrs). The transporter group includes the sodium iodide symporter (hNIS) and the norepinephrine transporter (hNET). The endogenous enzyme classification includes human mitochondrial thymidine kinase 2 (hTK2). In addition, we also discuss the nonhuman dopamine 2 receptor and two viral reporter genes, the wild-type herpes simplex virus 1 thymidine kinase (HSV1-tk) gene and the HSV1-tk mutant (HSV1-sr39tk). Initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: (a) gene therapy and (b) adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adenoviral-based, retroviral-based and lenteviral-based gene therapies, oncolytic bacterial and viral therapies, and adoptive cell-based therapies. Translational applications of noninvasive in vivo reporter gene imaging are likely to include: (a) quantitative monitoring of gene therapy vectors for targeting and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; (b) monitoring of cell trafficking, targeting, replication and activation in adoptive T-cell and stem/progenitor cell therapies

  20. Amyotrophic lateral sclerosis and the clinical potential of dexpramipexole

    Directory of Open Access Journals (Sweden)

    Corcia P

    2012-08-01

    Full Text Available Philippe Corcia,1 Paul H Gordon21Centre SLA, CHRU de Tours, Tours, France; UMR INSERM U930, Université François Rabelais de Tours (PC, Tours, France; 2AP-HP, Hôpital de la Pitié-Salpêtrière, Département des Maladies du Système Nerveux (PHG, Paris, FranceAbstract: Amyotrophic lateral sclerosis (ALS is a neurodegenerative disorder that leads to progressive weakness from loss of motor neurons and death on average in less than 3 years after symptom onset. No clear causes have been found and just one medication, riluzole, extends survival. Researchers have identified some of the cellular processes that occur after disease onset, including mitochondrial dysfunction, protein aggregation, oxidative stress, excitotoxicity, inflammation, and apoptosis. Mitochondrial disease may be a primary event in neurodegeneration or occur secondary to other cellular processes, and may itself contribute to oxidative stress, excitotoxicity, and apoptosis. Clinical trials currently aim to slow disease progression by testing drugs that impact one or more of these pathways. While every agent tested in the 18 years after the approval of riluzole has been ineffective, basic and clinical research methods in ALS have become dramatically more sophisticated. Dexpramipexole (RPPX, the R(+ enantiomer of pramiprexole, which is approved for symptomatic treatment of Parkinson disease, carries perhaps the currently largest body of pre- and early clinical data that support testing in ALS. The neuroprotective properties of RPPX in various models of neurodegeneration, including the ALS murine model, may be produced through protective actions on mitochondria. Early phase trials in human ALS suggest that the drug can be taken safely by patients in doses that provide neuroprotection in preclinical models. A Phase III trial to test the efficacy of RPPX in ALS is underway.Keywords: dexpramipexole, amyotrophic lateral sclerosis, survival, clinical trials, neurodegeneration

  1. Antimicrobial potentials of silver colloidal (nanorods) on clinical ...

    African Journals Online (AJOL)

    Antimicrobial resistance in developing countries has long been an issue of major concern. Nanotechnology has become an eye opener for the intervention on multiple drug resistance organisms. In this study we investigated the antimicrobial potentials of Silver Nitrate (nanorods) solution used in managing infectious ...

  2. Scandinavian Cooperative Advantage

    DEFF Research Database (Denmark)

    Strand, Robert; Freeman, R. Edward

    2015-01-01

    . We conclude by endorsing the expression “Scandinavian cooperative advantage” in an effort to draw attention to the Scandinavian context and encourage the field of strategic management to shift its focus from achieving a competitive advantage toward achieving a cooperative advantage....

  3. Accessing offshoring advantages

    DEFF Research Database (Denmark)

    Mykhaylenko, Alona; Motika, Agnes; Wæhrens, Brian Vejrum

    2015-01-01

    . Assuming that different levels of synergy may exist between particular offshoring strategic decisions (choosing offshore outsourcing or captive offshoring and the type of function) and different offshoring advantages, this work advocates that the actual fact of realization of certain offshoring advantages...

  4. What are the potential benefits of clinical beta-cell imaging in diabetes mellitus?

    Science.gov (United States)

    Göke, Burkhard

    2010-05-01

    Previously, studies of the endocrine pancreatic beta-cell were mainly performed ex vivo by morphological means. This data supported the analysis of pathophysiological changes in the pancreatic islet during insults such as diabetes mellitus. Metabolic testing of the pancreatic islet by assaying hormone parameters such als plasma insulin or C-peptide combined with more or less sophisticated calculations allowed conclusions about states of insulin resistance or secretory failure. It also allowed certain correlations of endocrine function with beta-cell mass. Today, with firmer pathophysiological concepts about beta-cell failure, modern protocols of islet transplantation, and drugs on the market coming with promises of preservation or even expansion of beta-cell mass in diabetes mellitus it has become very attractive to search for tools measuring beta-cell mass, if possible even repeatingly in the same organism in vivo. From a clinical point of view, the potential of pancreatic beta-cell mass imaging technologies is looked upon with high expectations. Methodologically, the decisive question is whether it is likely that future beta-cell imaging will provide significant advantages over the metabolic methods already in hand. With new in vivo tools, studies of beta-cell mass and function may offer even new approaches stratifying patients to anti-diabetic therapies.

  5. Competitive advantage of PET/MRI

    Energy Technology Data Exchange (ETDEWEB)

    Jadvar, Hossein, E-mail: jadvar@usc.edu; Colletti, Patrick M.

    2014-01-15

    Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved.

  6. Competitive advantage of PET/MRI.

    Science.gov (United States)

    Jadvar, Hossein; Colletti, Patrick M

    2014-01-01

    Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Competitive advantage of PET/MRI

    International Nuclear Information System (INIS)

    Jadvar, Hossein; Colletti, Patrick M.

    2014-01-01

    Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved

  8. Development of a portable blood irradiator for potential clinical uses

    Energy Technology Data Exchange (ETDEWEB)

    Hungate, F.P.

    1988-12-01

    This document provides an account of the development of a fully portable blood irradiator and the evaluation of its safety and efficacy when implanted in goats, sheep, a baboon and dogs. The program was initiated because the control of lymphocyte populations by irradiation is a potential method for improving success in organ or tissue transplantation and for treating a variety of blood diseases. 15 refs., 27 figs., 2 tabs.

  9. Advantages of semiconductor CZT for medical imaging

    Science.gov (United States)

    Wagenaar, Douglas J.; Parnham, Kevin; Sundal, Bjorn; Maehlum, Gunnar; Chowdhury, Samir; Meier, Dirk; Vandehei, Thor; Szawlowski, Marek; Patt, Bradley E.

    2007-09-01

    Cadmium zinc telluride (CdZnTe, or CZT) is a room-temperature semiconductor radiation detector that has been developed in recent years for a variety of applications. CZT has been investigated for many potential uses in medical imaging, especially in the field of single photon emission computed tomography (SPECT). CZT can also be used in positron emission tomography (PET) as well as photon-counting and integration-mode x-ray radiography and computed tomography (CT). The principal advantages of CZT are 1) direct conversion of x-ray or gamma-ray energy into electron-hole pairs; 2) energy resolution; 3) high spatial resolution and hence high space-bandwidth product; 4) room temperature operation, stable performance, high density, and small volume; 5) depth-of-interaction (DOI) available through signal processing. These advantages will be described in detail with examples from our own CZT systems. The ability to operate at room temperature, combined with DOI and very small pixels, make the use of multiple, stationary CZT "mini-gamma cameras" a realistic alternative to today's large Anger-type cameras that require motion to obtain tomographic sampling. The compatibility of CZT with Magnetic Resonance Imaging (MRI)-fields is demonstrated for a new type of multi-modality medical imaging, namely SPECT/MRI. For pre-clinical (i.e., laboratory animal) imaging, the advantages of CZT lie in spatial and energy resolution, small volume, automated quality control, and the potential for DOI for parallax removal in pinhole imaging. For clinical imaging, the imaging of radiographically dense breasts with CZT enables scatter rejection and hence improved contrast. Examples of clinical breast images with a dual-head CZT system are shown.

  10. Breath acetone as a potential marker in clinical practice.

    Science.gov (United States)

    Ruzsányi, Veronika; Péter Kalapos, Miklós

    2017-06-01

    In recent decades, two facts have changed the opinion of researchers about the function of acetone in humans. Firstly, it has turned out that acetone cannot be regarded as simply a waste product of metabolism, because there are several pathways in which acetone is produced or broken down. Secondly, methods have emerged making possible its detection in exhaled breath, thereby offering an attractive alternative to investigation of blood and urine samples. From a clinical point of view the measurement of breath acetone levels is important, but there are limitations to its wide application. These limitations can be divided into two classes, technical and biological limits. The technical limits include the storage of samples, detection threshold, standardization of clinical settings, and the price of instruments. When considering the biological ranges of acetone, personal factors such as race, age, gender, weight, food consumption, medication, illicit drugs, and even profession/class have to be taken into account to use concentration information for disorders. In some diseases such as diabetes mellitus and lung cancer, as well as in nutrition-related behavior such as starvation and ketogenic diet, breath acetone has been extensively examined. At the same time, there is a lack of investigations in other cases in which ketosis is also evident, such as in alcoholism or an inborn error of metabolism. In summary, the detection of acetone in exhaled breath is a useful and promising tool for diagnosis and it can be used as a marker to follow the effectiveness of treatments in some disorders. However, further endeavors are needed for clarification of the exact distribution of acetone in different body compartments and evaluation of its complex role in humans, especially in those cases in which a ketotic state also occurs.

  11. Intermittent Feeding Schedules—Behavioural Consequences and Potential Clinical Significance

    Directory of Open Access Journals (Sweden)

    Michelle Murphy

    2014-03-01

    Full Text Available Food availability and associated sensory cues such as olfaction are known to trigger a range of hormonal and behavioural responses. When food availability is predictable these physiological and behavioural responses can become entrained to set times and occur in anticipation of food rather than being dependent on the food-related cues. Here we summarise the range of physiological and behavioural responses to food when the time of its availability is unpredictable, and consider the potential to manipulate feeding patterns for benefit in metabolic and mental health.

  12. Gaining Relational Competitive Advantages

    DEFF Research Database (Denmark)

    Hu, Yimei; Zhang, Si; Li, Jizhen

    2015-01-01

    Establishing strategic technological partnerships (STPs) with foreign partners is an increasingly studied topic within the innovation management literature. Partnering firms can jointly create sources of relational competitive advantage. Chinese firms often lack research and development (R......&D) capabilities but are increasingly becoming preferred technological partners for transnational corporations. We investigate an STP between a Scandinavian and a Chinese firm and try to explore how to gain relational competitive advantage by focusing on its two essential stages: relational rent generation...... and appropriation. Based on an explorative case study, we develop a conceptual framework that consists of process, organizational alliance factors, and coordination modes that we propose lead to relational competitive advantage....

  13. Potential clinical impact of normal-tissue intrinsic radiosensitivity testing

    International Nuclear Information System (INIS)

    Bentzen, Soeren M.

    1997-01-01

    A critical appraisal is given of the possible benefit from a reliable pre-treatment knowledge of individual normal-tissue sensitivity to radiotherapy. The considerations are in part, but not exclusively, based on the recent experience with in vitro colony-forming assays of the surviving fraction at 2 Gy, the SF 2 . Three strategies are reviewed: (1) to screen for rare cases with extreme radiosensitivity, so-called over-reactors, and treat these with reduced total dose, (2) to identify the sensitive tail of the distribution of 'normal' radiosensitivities, refer these patients to other treatment, and to escalate the dose to the remaining patients, or (3) to individualize dose prescriptions based on individual radiosensitivity, i.e. treating to isoeffect rather than to a specific dose-fractionation schedule. It is shown that these strategies will have a small, if any, impact on routine radiotherapy. Screening for over-reactors is hampered by the low prevalence of these among otherwise un-selected patients that leads to a low positive predictive value of in vitro radiosensitivity assays. It is argued, that this problem may persist even if the noise on current assays could be reduced to (the unrealistic value of) zero, simply because of the large biological variation in SF 2 . Removing the sensitive tail of the patient population, will only have a minor effect on the dose that could be delivered to the remaining patients, because of the sigmoid shape of empirical dose-response relationships. Finally, individualizing dose prescriptions based exclusively on information from a normal-tissue radiosensitivity assay, leads to a nearly symmetrical distribution of dose-changes that would produce a very small gain, or even a loss, of tumor control probability if implemented in the clinic. From a theoretical point of view, other strategies could be devised and some of these are considered in this review. Right now the most promising clinical use of in vitro radiosensitivity

  14. Fructose use in clinical nutrition: metabolic effects and potential consequences.

    Science.gov (United States)

    Moulin, Sandra; Seematter, Gérald; Seyssel, Kevin

    2017-07-01

    The current article presents recent findings on the metabolic effects of fructose. Fructose has always been considered as a simple 'caloric' hexose only metabolized by splanchnic tissues. Nevertheless, there is growing evidence that fructose acts as a second messenger and induces effects throughout the human body. Recent discoveries made possible with the evolution of technology have highlighted that fructose induces pleiotropic effects on different tissues. The fact that all these tissues express the specific fructose carrier GLUT5 let us reconsider that fructose is not only a caloric hexose, but could also be a potential actor of some behaviors and metabolic pathways. The physiological relevance of fructose as a metabolic driver is pertinent regarding recent scientific literature.

  15. Targeted treatment for chronic lymphocytic leukemia: clinical potential of obinutuzumab

    Directory of Open Access Journals (Sweden)

    Smolej L

    2014-12-01

    Full Text Available Lukáš Smolej 4th Department of Internal Medicine – Hematology, University Hospital Hradec Králové and Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic Abstract: Introduction of targeted agents revolutionized the treatment of chronic lymphocytic leukemia (CLL in the past decade. Addition of chimeric monoclonal anti-CD20 antibody rituximab to chemotherapy significantly improved efficacy including overall survival (OS in untreated fit patients; humanized anti-CD52 antibody alemtuzumab and fully human anti-CD20 antibody ofatumumab lead to improvement in refractory disease. Novel small molecule inhibitors such as ibrutinib and idelalisib demonstrated excellent activity and were very recently licensed in relapsed/refractory CLL. Obinutuzumab (GA101 is the newest monoclonal antibody approved for the treatment of CLL. This novel, glycoengineered, type II humanized anti-CD20 antibody is characterized by enhanced antibody-dependent cellular cytotoxicity and direct induction of cell death compared to type I antibodies. Combination of obinutuzumab and chlorambucil yielded significantly better OS in comparison to chlorambucil monotherapy in untreated comorbid patients. These results led to approval of obinuzutumab for the treatment of CLL. Numerous clinical trials combining obinutuzumab with other cytotoxic drugs and novel small molecules are currently under way. This review focuses on the role of obinutuzumab in the treatment of CLL. Keywords: chronic lymphocytic leukemia, anti-CD20 antibodies, chlorambucil, rituximab, ofatumumab, obinutuzumab, overall survival

  16. Molecular biology of breast cancer stem cells: potential clinical applications.

    Science.gov (United States)

    Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

    2010-10-01

    Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy. 2010 Elsevier Ltd. All rights reserved.

  17. Potential and clinical utility of stem cells in cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Korff Krause

    2010-03-01

    Full Text Available Korff Krause, Carsten Schneider, Kai Jaquet, Karl-Heinz KuckHanseatic Heart Center Hamburg, Department of Cardiology, Asklepios Hospital St. Georg, Hamburg, GermanyAbstract: The recent identification of bone marrow-derived adult stem cells and other types of stem cells that could improve heart function after transplantation have raised high expectations. The basic mechanisms have been studied mostly in murine models. However, these experiments revealed controversial results on transdifferentiation vs transfusion of adult stem cells vs paracrine effects of these cells, which is still being debated. Moreover, the reproducibility of these results in precisely translated large animal models is still less well investigated. Despite these weaknesses results of several clinical trials including several hundreds of patients with ischemic heart disease have been published. However, there are no solid data showing that any of these approaches can regenerate human myocardium. Even the effectiveness of cell therapy in these approaches is doubtful. In future we need in this important field of regenerative medicine: i more experimental data in large animals that are closer to the anatomy and physiology of humans, including data on dose effects, comparison of different cell types and different delivery routes; ii a better understanding of the molecular mechanisms involved in the fate of transplanted cells; iii more intensive research on genuine regenerative medicine, applying genetic regulation and cell engineering.Keywords: stem cells, cardiovascular disease

  18. Clinical application of optical coherence tomography in combination with functional diagnostics: advantages and limitations for diagnosis and assessment of therapy outcome in central serous chorioretinopathy.

    Science.gov (United States)

    Schliesser, Joshua A; Gallimore, Gary; Kunjukunju, Nancy; Sabates, Nelson R; Koulen, Peter; Sabates, Felix N

    2014-01-01

    While identifying functional and structural parameters of the retina in central serous chorioretinopathy (CSCR) patients, this study investigated how an optical coherence tomography (OCT)-based diagnosis can be significantly supplemented with functional diagnostic tools and to what degree the determination of disease severity and therapy outcome can benefit from diagnostics complementary to OCT. CSCR patients were evaluated prospectively with microperimetry (MP) and spectral domain optical coherence tomography (SD-OCT) to determine retinal sensitivity function and retinal thickness as outcome measures along with measures of visual acuity (VA). Patients received clinical care that involved focal laser photocoagulation or pharmacotherapy targeting inflammation and neovascularization. Correlation of clinical parameters with a focus on functional parameters, VA, and mean retinal sensitivity, as well as on the structural parameter mean retinal thickness, showed that functional measures were similar in diagnostic power. A moderate correlation was found between OCT data and the standard functional assessment of VA; however, a strong correlation between OCT and MP data showed that diagnostic measures cannot always be used interchangeably, but that complementary use is of higher clinical value. The study indicates that integrating SD-OCT with MP provides a more complete diagnosis with high clinical relevance for complex, difficult to quantify diseases such as CSCR.

  19. COMPETITIVE PRODUCT ADVANTAGES

    Directory of Open Access Journals (Sweden)

    Adrian MICU

    2006-01-01

    Full Text Available Cost advantages may be either internal or external. Internal economics of scope, scale, or experience, and external economies of focus or logistical integration, enable a company to produce some products at a lower cost than the competition. The coordination of pricing with suppliers, although not actually economizing resources, can improve the efficiency of pricing by avoiding the incrementalization of a supplier's nonincremental fixed costs and profit. Any of these strategies can generate cost advantages that are, at least in the short run, sustainable. Even cost advantages that are not sustainable, however, can generate temporary savings that are often the key to building more sustainable cost or product advantages later.. Even when a product's physical attributes are not readily differentiable, opportunities to develop product advantages remain. The augmented product that customers buy is more than the particular product or service exchanged. It includes all sorts of ancillary services and intangible relationships that make buying thesame product from one company less difficult, less risky, or more pleasant than buying from a competitor. Superior augmentation of the same basic product can add substantial value in the eyes of consumers, leading them to pay willingly what are often considerable price premiums.

  20. Compositional Advantage and Strategy

    DEFF Research Database (Denmark)

    Li, Xin

    advantage is redefined as the attractiveness of the composition of the producer’s offering in terms of scope and perceived value/price ratio. I identify five ways or basic compositional strategies to improve the value/price ratio. A firm may have an overall compositional strategy that is composed of some......In this paper, I first critique the composition-based view of Yadong Luo and John Child for understanding how resource-poor firms survive and thrive. To remedy the deficiencies in their perspective, I then propose a dynamic theory of compositional advantage and strategy. Here, the compositional...... or all of the five basic compositional strategies. I argue there are three indispensable key success factors for a composition-based competition, i.e., aspiration (ambition-position asymmetry), attitude (being ALERT), and action (turning asymmetry into advantage). I also discuss the particular relevance...

  1. Competitive Advantage through Innovation

    DEFF Research Database (Denmark)

    Brem, Alexander; Maier, Maximilian; Wimschneider, Christine

    2016-01-01

    Purpose The purpose of this paper is to describe how Nespresso achieved competitive advantage through innovation by changing the rules of the game in its industry. Design/methodology/approach Nespresso was analyzed based on public available secondary data, in combination with related academic...... concepts on innovation and competitive advantage. Findings The company succeeded by the thorough application of a strategy that, through perfect alignment, allowed the company to reach a unique market position. However, as described in the case, it took a relatively long time and the company came close...... as a source for competitive advantage. Research limitations/implications Especially given the current market situation, the case offers different starting points for discussion about innovation and long-term company success. Practical implications Especially before the current market situation, the case...

  2. Comparison of neonatal MRI examinations with and without an MR-compatible incubator: advantages in examination feasibility and clinical decision-making.

    Science.gov (United States)

    Rona, Z; Klebermass, K; Cardona, F; Czaba, C D; Brugger, P C; Weninger, M; Pollak, A; Prayer, D

    2010-09-01

    To assess the utility of an MRI-compatible incubator (INC) by comparing. In a retrospective study, the clinical and radiological aspects of 129 neonatal MRI examinations during a 3 year period were analyzed. Routine protocols including fast spin-echo T2-weighted (w) sequences, axial T1w, Gradient-echo, diffusion sequences, and 3D T1 gradient-echo sequences were performed routinely, angiography and spectroscopy were added in some cases. Diffusion-tensor imaging was done in 50% of the babies examined in the INC and 26% without INC. Sequences, adapted from fetal MR-protocols were done in infants younger than 32 gestational weeks. Benefit from MR-information with respect to further management was evaluated. The number of the examinations increased (30-99), while the mean age (43-38, 8 weeks of gestational age) and weight (3308-2766 g) decreased significantly with the use of the MR-compatible incubator. The mean imaging time (34, 43-30, 29 min) decreased, with a mean of one additionally performed sequence in the INC group. All infants received sedatives according to our anaesthetic protocol preceding imaging, but a repeated dose was never necessary (10% without INC) using the INC. Regarding all cases, MR-based changes in clinical management were initiated in 58%, while in 57% of cases the initial ultrasound diagnosis was changed or further specified. The use of the INC enables the MR access of unstable infants with suspect CNS problems to the management, of whom is improved by MR information to significantly higher percentage, than without INC. Copyright (c) 2010 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  3. Anodal sensory nerve action potentials: From physiological understanding to potential clinical applicability.

    Science.gov (United States)

    Leote, Joao; Pereira, Pedro; Cabib, Christopher; Cipullo, Federica; Valls-Sole, Josep

    2016-06-01

    Low-intensity electrical stimuli of digital nerves may generate a double peak potential (DPp), composed of a cathodal (caAP) and an anodal (anAP) potential in orthodromic recordings. We studied the effects on caAP and anAP of stimuli of variable intensity, duration, and frequency. We also applied a conditioning stimulus to study potential differences in recovery time. The anAP was obtained in 33 of 40 healthy subjects (82.5%) and 4 of 20 patients with various types of sensory neuropathies (20%). Changes in stimulus duration and intensity had reciprocal effects on the amplitude of the anAP and the caAP. There were significant differences in recovery time between caAP and anAP after a conditioning stimulus. The caAP and anAP are 2 interdependent waveforms generated by different effects of the same stimulus over axons at the verge of depolarization. Muscle Nerve 53: 897-905, 2016. © 2015 Wiley Periodicals, Inc.

  4. Are research papers reporting results from nutrigenetics clinical research a potential source of biohype?

    Science.gov (United States)

    Stenne, R; Hurlimann, T; Godard, Béatrice

    2012-01-01

    Nutrigenetics is a promising field, but the achievability of expected benefits is challenged by the methodological limitations that are associated with clinical research in that field. The mere existence of these limitations suggests that promises about potential outcomes may be premature. Thus, benefits claimed in scientific journal articles in which these limitations are not acknowledged might stimulate biohype. This article aims to examine whether nutrigenetics clinical research articles are a potential source of biohype. Of the 173 articles identified, 16 contained claims in which clinical applications were extrapolated from study results. The methodological limitations being incompletely acknowledged, these articles could potentially be a source of biohype.

  5. Digital linear accelerator: The advantages for radiotherapy

    International Nuclear Information System (INIS)

    Andric, S.; Maksimovic, M.; Dekic, M.; Clark, T.

    1998-01-01

    Technical performances of Digital Linear Accelerator were presented to point out its advantages for clinical radiotherapy treatment. The accelerator installation is earned out at Military Medical Academy, Radiotherapy Department, by Medes and Elekta companies. The unit offers many technical advantages with possibility of introduction new conformal treatment techniques as stereotactic radiosurgery, total body and total skin irradiation. In the paper are underlined advantages in relation to running conventional accelerator units at Yugoslav radiotherapy departments, both from technical and medical point of view. (author)

  6. TRIENNIAL GROWTH AND DEVELOPMENT SYMPOSIUM: Dedifferentiated fat cells: Potential and perspectives for their use in clinical and animal science purpose.

    Science.gov (United States)

    Duarte, M S; Bueno, R; Silva, W; Campos, C F; Gionbelli, M P; Guimarães, S E F; Silva, F F; Lopes, P S; Hausman, G J; Dodson, M V

    2017-05-01

    An increasing body of evidences has demonstrated the ability of the mature adipocyte to dedifferentiate into a population of proliferative-competent cells known as dedifferentiated fat (DFAT) cells. As early as the 1970s, in vitro studies showed that DFAT cells may be obtained by ceiling culture, which takes advantage of the buoyancy property of lipid-filled cells. It was documented that DFAT cells may acquire a phenotype similar to mesenchymal stem cells and yet may differentiate into multiple cell lineages, such as skeletal and smooth muscle cells, cardiomyocytes, osteoblasts, and adipocytes. Additionally, recent studies showed the ability of isolated mature adipocytes to dedifferentiate in vivo and the capacity of the progeny cells to redifferentiate into mature adipocytes, contributing to the increase of body fatness. These findings shed light on the potential for use of DFAT cells, not only for clinical purposes but also within the animal science field, because increasing intramuscular fat without excessive increase in other fat depots is a challenge in livestock production. Knowledge of the mechanisms underlying the dedifferentiation and redifferentiation of DFAT cells will allow the development of strategies for their use for clinical and animal science purposes. In this review, we highlight several aspects of DFAT cells, their potential for clinical purposes, and their contribution to adipose tissue mass in livestock.

  7. Constructing Regional advantage

    DEFF Research Database (Denmark)

    Asheim, Bjørn T.; Boschma, Ron; Cooke, Phil

    2011-01-01

    This paper presents a regional innovation policy model based on the idea of constructing regional advantage. This policy model brings together concepts like related variety, knowledge bases and policy platforms. Related variety attaches importance to knowledge spillovers across complementary...... economic development within and between regions in action lines appropriate to incorporate the basic principles behind related variety and differentiated knowledge bases....

  8. Advantages of magnification radiography

    International Nuclear Information System (INIS)

    Doi, K.

    1976-01-01

    Geometric arrangements and exposure conditions used in different magnification techniques are described and the following advantages of radiographic magnification technique are discussed: sharpness effect; noise effect; air gap effect; and visual effect. The magnification technique can be used in various diagnostic procedures as a means of improving the image quality of radiographs

  9. Generation of dendritic cells from human bone marrow mononuclear cells: advantages for clinical application in comparison to peripheral blood monocyte derived cells.

    Science.gov (United States)

    Bai, L; Feuerer, M; Beckhove, P; Umansky, V; Schirrmacher, V

    2002-02-01

    Dendritic cells (DCs) currently used for vaccination in clinical studies to induce immunity against malignant cells are normally generated from peripheral blood-derived monocytes. Here we studied conditions for the generation of DCs from unseparated human bone marrow (BM) mononuclear cells and compared them functionally with DCs from blood. The two types of DCs, from bone marrow (BM-DC) and peripheral blood (BL-DC), were generated in parallel from the same normal healthy donors by culturing in serum-free X-VIVO 20 medium containing GM-CSF and IL-4, and then the phenotypes and functions were compared. BM-DC generation occurred in 14 days and involved proliferative expansion from CD34 stem cells and differentiation while BL-DC generation occurred in 7 days from CD14 monocytes and involved only differentiation. A 7- to 25-fold higher number of DCs could be obtained from BM than from blood. BM-DC had similar phenotypes as BL-DC. The capacity to stimulate MLR reactivity in allogeneic T lymphocytes was higher with BM-DC than that with BL-DC. Also, the capacity to stimulate autologous memory T cell responses to tetanus toxoid (TT) or tuberculin (PPD) was higher with BM-DC than with BL-DC. These results suggest that BM-DC as produced here may be a very economic and useful source of professional antigen-presenting cells for anti-tumor immunotherapeutic protocols.

  10. Clinically relevant potential drug-drug interactions among outpatients: A nationwide database study.

    Science.gov (United States)

    Jazbar, Janja; Locatelli, Igor; Horvat, Nejc; Kos, Mitja

    2018-06-01

    Adverse drug events due to drug-drug interactions (DDIs) represent a considerable public health burden, also in Slovenia. A better understanding of the most frequently occurring potential DDIs may enable safer pharmacotherapy and minimize drug-related problems. The aim of this study was to evaluate the prevalence and predictors of potential DDIs among outpatients in Slovenia. An analysis of potential DDIs was performed using health claims data on prescription drugs from a nationwide database. The Lexi-Interact Module was used as the reference source of interactions. The influence of patient-specific predictors on the risk of potential clinically relevant DDIs was evaluated using logistic regression model. The study population included 1,179,803 outpatients who received 15,811,979 prescriptions. The total number of potential DDI cases identified was 3,974,994, of which 15.6% were potentially clinically relevant. Altogether, 9.3% (N = 191,213) of the total population in Slovenia is exposed to clinically relevant potential DDIs, and the proportion is higher among women and the elderly. After adjustment for cofactors, higher number of medications and older age are associated with higher odds of clinically relevant potential DDIs. The burden of DDIs is highest with drug combinations that increase risk of bleeding, enhance CNS depression or anticholinergic effects or cause cardiovascular complications. The current study revealed that 1 in 10 individuals in the total Slovenian population is exposed to clinically relevant potential DDIs yearly. Taking into account the literature based conservative estimate that approximately 1% of potential DDIs result in negative health outcomes, roughly 1800 individuals in Slovenia experience an adverse health outcome each year as a result of clinically relevant potential interactions alone. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Compositional Advantage and Strategy

    DEFF Research Database (Denmark)

    Li, Xin

    In this paper, I first critique the composition-based view of Yadong Luo and John Child for understanding how resource-poor firms survive and thrive. To remedy the deficiencies in their perspective, I then propose a dynamic theory of compositional advantage and strategy. Here, the compositional...... advantage is redefined as the attractiveness of the composition of the producer’s offering in terms of scope and perceived value/price ratio. I identify five ways or basic compositional strategies to improve the value/price ratio. A firm may have an overall compositional strategy that is composed of some...... of the present theory to understanding Chinese firms. I conclude with managerial implications and suggestions for future research....

  12. Nitrogen-Based Diazeniumdiolates: Versatile Nitric Oxide-Releasing Compounds for Biomedical Research and Potential Clinical Applications

    Science.gov (United States)

    Saavedra, Joseph E.; Keefer, Larry K.

    2002-12-01

    Nitric oxide-generating ions of the nitrogen-diazeniumdiolate class with the general structure R1R2N-[N(O)NO]1 have been prepared by exposing primary, secondary, and polyamines to nitric oxide (NO). The resulting complexes regenerate bioactive NO at physiological pH with half-lives ranging from 2 seconds to 20 hours. An important goal in our research is to deliver NO to a specific organ or cell type where it is needed without affecting other NO-sensitive parts of the anatomy. By taking advantage of the remarkable chemical versatility of diazeniumdiolates, we have developed general strategies to prepare either tissue-selective NO donor drugs or materials containing NO delivery agents that can be physically placed near the target sites. Inhibition of blood coagulation, induction of penile erection, relief of pulmonary hypertension, and reversal of cerebral vasospasm are a few examples of their potential clinical applications. See Featured Molecules.

  13. Creating corporate advantage.

    Science.gov (United States)

    Collis, D J; Montgomery, C A

    1998-01-01

    What differentiates truly great corporate strategies from the merely adequate? How can executives at the corporate level create tangible advantage for their businesses that makes the whole more than the sum of the parts? This article presents a comprehensive framework for value creation in the multibusiness company. It addresses the most fundamental questions of corporate strategy: What businesses should a company be in? How should it coordinate activities across businesses? What role should the corporate office play? How should the corporation measure and control performance? Through detailed case studies of Tyco International, Sharp, the Newell Company, and Saatchi and Saatchi, the authors demonstrate that the answers to all those questions are driven largely by the nature of a company's special resources--its assets, skills, and capabilities. These range along a continuum from the highly specialized at one end to the very general at the other. A corporation's location on the continuum constrains the set of businesses it should compete in and limits its choices about the design of its organization. Applying the framework, the authors point out the common mistakes that result from misaligned corporate strategies. Companies mistakenly enter businesses based on similarities in products rather than the resources that contribute to competitive advantage in each business. Instead of tailoring organizational structures and systems to the needs of a particular strategy, they create plain-vanilla corporate offices and infrastructures. The company examples demonstrate that one size does not fit all. One can find great corporate strategies all along the continuum.

  14. Economic and environmental advantages for the utilization of the industrial potential of cogeneration in Mexico; Ventajas economicas y ambientales para el aprovechamiento del potencial industrial de cogeneracion en Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Leon de los Santos, G [Division de Estudios Posgrado, Facultad de ingenieria, Universidad Nacional Autonoma de Mexico, Mexico, D.F. (Mexico)

    2003-01-15

    Mexico has an industrial cogeneration potential very important, not evaluated or projected within its historical growth. The objective of the present work consist of studying the industrial cogeneration potential that exists in Mexico, as well as the economic and environmental savings that it would be achieved if one took advantage of this potential. As a result of the present work we can conclude that the cogeneration in Mexico offers a theoretical potential middle of 28,000 MWe to the 2007. It is estimated an economic saving potential in the construction of generation infrastructure electrical, for the high stage of its utilization of almost 7000 million dollars and a stage of emissions reduction of 2007- 21.4%, instead of 2007- 0.35%, for the industrial sector of the country. Provided that change the vision of the government of seeing to the cogeneration as a measure of energy saving and substitute it by that of political of complement to the development of the national electrical sector. [Spanish] Mexico tiene un importante potencial de cogeneracion industrial que no ha sido evaluado ni proyectado dentro de su crecimiento historico, por ello, el objetito de este trabajo consiste en estudiar y conocer los ahorros economicos y ambientales que se podrian lograr si se aprovechara dicho potencial. Como resultado, se muestra que la cogeneracion en Mexico ofrece un potencial teorico medio de 28,000 MW e al ano 2007. Se estima tambien un ahorro economico en la construccion de infraestructura de generacion electrica para el escenario alto de su aprovechamiento de casi 7000 mdd, y un escenario de reduccion de emisiones para el sector industrial del pais de un 0.35% a un 21.47% para el ano 2007. Estos pronosticos se pueden lograr, siempre y cunado el gobierno cambie la vision de manejar este tema como una medida de ahorro de energia, y la sustituya por la politica de complemento al desarrollo del sector electrico nacional.

  15. Economic and environmental advantages for the use of the industrial potential of cogeneration in Mexico City; Ventajas economicas y ambientales para el aprovechamiento del potencial industrial de cogeneracion en Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Leon de los Santos, G. [Division de Estudios de Posgrado, Facultad de Ingenieria, UNAM, Mexico, D.F. (Mexico)

    2003-03-01

    Mexico has an industrial cogeneration potential very important, not evaluated or projected within its historical growth. The objective of the present work consist of studying the industrial cogeneration potential that exists in Mexico, as well as the economic and environmental savings that it would be achieved if one took advantage of this potential. As a result of the present work we can conclude that the cogeneration in Mexico offers a theoretical potential middle of 28,000 MWe to the 2007. It is estimated an economic saving potential in the construction of generation infrastructure electrical, for the high stage of its utilization of almost 7000 million of dollars and a stage of emissions reduction of 2007- 21.37% instead of 2007- 0.35% for the industrial sector of the country. These prognoses can be obtained, as long as the government changes vision to handle this subject as a measure of energy saving, and substitute it by the policy of complement the development of the national electrical sector. [Spanish] Mexico tiene un importante potencial de cogeneracion industrial que no ha sido evaluado ni proyectado dentro de su crecimiento historico, por ello, el objetivo de este trabajo consiste en estudiar y conocer los ahorros economicos y ambientales que se podrian lograr si se aprovechara dicho potencial. Como resultado, se muestra que la cogeneracion en Mexico ofrece un potencial teorico medio de 28,000 MWe al ano 2007. Se estima tambien un ahorro economico en la construccion de infraestructura de generacion electrica para el escenario alto de su aprovechamiento de casi 7 000 mdd, y un escenario de reduccion de emisiones para el sector industrial del pais de un 0.35% a un 21.4% para el ano 2007. Estos pronosticos se pueden lograr, siempre y cuando el gobierno cambie la vision de manejar este tema como una medida de ahorro de energia, y la sustituya por la politica de complemento al desarrollo del sector electrico nacional.

  16. Evaluating sub-clinical cognitive dysfunction and event-related potentials (P300) in clinically isolated syndrome.

    Science.gov (United States)

    Kocer, Belgin; Unal, Tugba; Nazliel, Bijen; Biyikli, Zeynep; Yesilbudak, Zulal; Karakas, Sirel; Irkec, Ceyla

    2008-12-01

    This study investigated the presence of sub-clinical cognitive dysfunction in patients with clinically isolated syndrome (CIS) and the abnormalities of cognitive event-related potentials (ERPs). Subclinical cognitive dysfunction was assessed in 20 patients with CIS and in 20 healthy controls. Patients had impairments in verbal learning and long-term memory, evaluating attention, executive function and visuospatial skills, in decreasing order of frequency. SDLT and SIT were the most, and COWAT and BNT were the least affected tests. The N200 and P200 latencies were prolonged, and N100, N200 and P200 amplitudes were reduced in the patients relative to the controls, from the Fz, Cz and Pz electrode positions (p<0.05). Detailed cognitive testing is valuable in determining subclinical cognitive dysfunction in CIS patients. ERP abnormalities as well as abnormalities in detailed cognitivetesting in patients with CIS are helpful in the diagnosis of sub-clinical cognitive dysfunction.

  17. Advantages of robotics in benign gynecologic surgery.

    Science.gov (United States)

    Truong, Mireille; Kim, Jin Hee; Scheib, Stacey; Patzkowsky, Kristin

    2016-08-01

    The purpose of this article is to review the literature and discuss the advantages of robotics in benign gynecologic surgery. Minimally invasive surgery has become the preferred route over abdominal surgery. The laparoscopic or robotic approach is recommended when vaginal surgery is not feasible. Thus far, robotic gynecologic surgery data have demonstrated feasibility, safety, and equivalent clinical outcomes in comparison with laparoscopy and better clinical outcomes compared with laparotomy. Robotics was developed to overcome challenges of laparoscopy and has led to technological advantages such as improved ergonomics, visualization with three-dimensional capabilities, dexterity and range of motion with instrument articulation, and tremor filtration. To date, applications of robotics in benign gynecology include hysterectomy, myomectomy, endometriosis surgery, sacrocolpopexy, adnexal surgery, tubal reanastomosis, and cerclage. Though further data are needed, robotics may provide additional benefits over other approaches in the obese patient population and in higher complexity cases. Challenges that arose in the earlier adoption stage such as the steep learning curve, costs, and operative times are becoming more optimized with greater experience, with implementation of robotics in high-volume centers and with improved training of surgeons and robotic teams. Robotic laparoendoscopic single-site surgery, albeit still in its infancy where technical advantages compared with laparoscopic single-site surgery are still unclear, may provide a cost-reducing option compared with multiport robotics. The cost may even approach that of laparoscopy while still conferring similar perioperative outcomes. Advances in robotic technology such as the single-site platform and telesurgery, have the potential to revolutionize the field of minimally invasive gynecologic surgery. Higher quality evidence is needed to determine the advantages and disadvantages of robotic surgery in benign

  18. RECONSIDERING COMPETITIVE ADVANTAGES

    Directory of Open Access Journals (Sweden)

    Valentina Zaharia

    2011-12-01

    Full Text Available Development of the competitive advantage involves a considerable effort from any organization. In particular, those organizations involved in a strong competitive market require the development of strategies to allocate long-term strategic marketing resources, efficiently and with easily quantifiable results. Faced with a multitude of phenomena and processes sometimes contradictory on different markets of consumption, contemporarily marketing has the mission to develop as creative as possible the business strategy of the organizations, their capacity of interacting with customers and other categories of audience. Such concepts as strategic positioning, relational marketing, management of the relationship with the consumer, marketing integrated research, a.s.o. are only a few of the tools with the help of which the marketing managers will implement successful operational strategies. All these developments are creating a real new paradigm of Marketing aimed to better explain the new types of complex market relationship in which the 21st Century organization is .

  19. Canadian competitive advantage

    International Nuclear Information System (INIS)

    Wills, J.

    1997-01-01

    The evolution of the Canadian petrochemical industry was outlined, emphasizing the proximity to feedstocks as the principal advantage enjoyed by the industry over its international competitors. Annual sales statistics for 1995 were provided. Key players in the Canadian petrochemical industry (Nova, Dow, DuPont, Methanex, Esso, Union Carbide, Shell and Celanese), their share of the market and key products were noted. Manufacturing facilities are located primarily in Alberta, southern Ontario and Quebec. The feedstock supply infrastructure, historical and alternative ethane pricing in Canada and the US, the North American market for petrochemicals, the competitiveness of the industry, tax competitiveness among Canadian provinces and the US, the Canada - US unit labour cost ratio, ethylene facility construction costs in Canada relative to the US Gulf Coast, and projected 1997 financial requirements were reviewed. 19 figs

  20. A Conceptual Mapping Resource Advantage Theory, Competitive Advantage Theory, and Transient Competitive Advantage

    OpenAIRE

    Jasanta PERANGINANGIN

    2015-01-01

    Competitive advantage is the main purposed of the business entity focusing on market base view. Resource advantage theorists put their concern to empowering resources development with resources based view, in the other side needs to redefining competitive advantage. All the competitive advantage are transient, concluded the end of competitive advantage. Redefining competitive advantage by selling migration and shrewdness outward. This research to emphasize innovation capability rarely appears...

  1. Potential Impact on Clinical Decision Making via a Genome-Wide Expression Profiling: A Case Report

    Directory of Open Access Journals (Sweden)

    Hyun Kim

    2016-11-01

    Full Text Available Management of men with prostate cancer is fraught with uncertainty as physicians and patients balance efficacy with potential toxicity and diminished quality of life. Utilization of genomics as a prognostic biomarker has improved the informed decision-making process by enabling more rationale treatment choices. Recently investigations have begun to determine whether genomic information from tumor transcriptome data can be used to impact clinical decision-making beyond prognosis. Here we discuss the potential of genomics to alter management of a patient who presented with high-risk prostate adenocarcinoma. We suggest that this information help selecting patients for advanced imaging, chemotherapies, or clinical trial.

  2. Advantages of later motherhood.

    Science.gov (United States)

    Myrskylä, M; Barclay, K; Goisis, A

    2017-01-01

    In high-income countries childbearing has been increasingly postponed since the 1970s and it is crucial to understand the consequences of this demographic shift. The literature has tended to characterize later motherhood as a significant health threat for children and parents. We contribute to this debate by reviewing recent evidence suggesting that an older maternal age can also have positive effects. Literature linking the age at parenthood with the sociodemographic characteristics of the parents, with macrolevel interactions, and with subjective well-being. Comprehensive review of the existing literature. Recent studies show that there can also be advantages associated with later motherhood. First, whilst in past older mothers had low levels of education and large families, currently older mothers tend to have higher education and smaller families than their younger peers. Consequently, children born to older mothers in the past tended to have worse outcomes than children born to younger mothers, whilst the opposite is true in recent cohorts. Second, postponement of childbearing means that the child is born at a later date and in a later birth cohort, and may benefit from secular changes in the macroenvironment. Evidence shows that when the positive trends in the macroenvironment are strong they overweigh the negative effects of reproductive ageing. Third, existing studies show that happiness increases around and after childbirth among older mothers, whereas for younger mothers the effect does not exist or is short-lived. There are important sociodemographic pathways associated with postponement of childbearing which might compensate or even more than compensate for the biological disadvantages associated with reproductive ageing.

  3. Potential Immune Biomarkers in Diagnosis and Clinical Management for Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Zecevic Lamija

    2018-04-01

    Full Text Available Background: There is still no reliable, specific biomarker for precision diagnosis and clinical monitoring of systemic lupus erythematosus. The aim of this study was to investigate the importance of the determination of immunofenotypic profiles (T, B lymphocytes and NK cells and serum cytokine concentrations (IL-17 and IFN-alpha as potential biomarkers for this disease.

  4. Proton therapy for head and neck cancer: Rationale, potential indications, practical considerations, and current clinical evidence

    International Nuclear Information System (INIS)

    Mendenhall, Nancy P.; Malyapa, Robert S.; Su, Zhong; Yeung, Daniel; Mendenhall, William M.; Li, Zuofeng

    2011-01-01

    There is a strong rationale for potential benefits from proton therapy (PT) for selected cancers of the head and neck because of the opportunity to improve the therapeutic ratio by improving radiation dose distributions and because of the significant differences in radiation dose distribution achievable with x-ray-based radiation therapy (RT) and PT. Comparisons of dose distributions between x-ray-based and PT plans in selected cases show specific benefits in dose distribution likely to translate into improved clinical outcomes. However, the use of PT in head and neck cancers requires special considerations in the simulation and treatment planning process, and currently available PT technology may not permit realization of the maximum potential benefits of PT. To date, few clinical data are available, but early clinical experiences in sinonasal tumors in particular suggest significant improvements in both disease control and radiation-related toxicity

  5. Proton therapy for head and neck cancer: Rationale, potential indications, practical considerations, and current clinical evidence

    Energy Technology Data Exchange (ETDEWEB)

    Mendenhall, Nancy P.; Malyapa, Robert S.; Su, Zhong; Yeung, Daniel; Mendenhall, William M.; Li, Zuofeng (Univ. of Florida Proton Therapy Inst., Jacksonville, Florida (United States)), e-mail: menden@shands.ufl.edu

    2011-08-15

    There is a strong rationale for potential benefits from proton therapy (PT) for selected cancers of the head and neck because of the opportunity to improve the therapeutic ratio by improving radiation dose distributions and because of the significant differences in radiation dose distribution achievable with x-ray-based radiation therapy (RT) and PT. Comparisons of dose distributions between x-ray-based and PT plans in selected cases show specific benefits in dose distribution likely to translate into improved clinical outcomes. However, the use of PT in head and neck cancers requires special considerations in the simulation and treatment planning process, and currently available PT technology may not permit realization of the maximum potential benefits of PT. To date, few clinical data are available, but early clinical experiences in sinonasal tumors in particular suggest significant improvements in both disease control and radiation-related toxicity

  6. Nuclear energy. Risk or advantage

    International Nuclear Information System (INIS)

    Boettiger, Helmut

    2011-01-01

    Nuclear energy is controversial. But what's all about really in the controversy? It's about more than safty or electricity prices. Nuclear energy is not only a technical or political question, but also a moral, a human. The discussion enter various rational and irrational arguments, beside straightforward arguments various misleading and mendacious exist. The present publication is comprehensively dedicated to the thema of nuclear energy - its pro and contra - and considers its risks and advantages. Thereby the sources of energy, the processes in the nuclear reactor, and the risk potentials (Harrisburg, Chernobyl, Fukushima) are illustratively and reproducibly presented. Extensively the text explains the forms of the radiation, its doses, and the tolerance of it. Also to the theme waste and final disposal an explaining chapter is dedicated and the question for the exit from nuclear energy elucidated. Finally the author appoints with the question ''How considers mankind nuclear energy world-wide'' the international comparison.

  7. UFT and leucovorin: a review of its clinical development and therapeutic potential in the oral treatment of cancer.

    Science.gov (United States)

    Hoff, P M; Pazdur, R; Benner, S E; Canetta, R

    1998-07-01

    UFT is an oral antineoplastic drug combining uracil and tegafur in a 4:1 molar ratio. Tegafur acts as a prodrug of 5-fluorouracil (5-FU), being slowly metabolized by cytochrome P450 to 5-FU. Uracil competitively inhibits the metabolism of 5-FU, resulting in increased plasma and tumor 5-FU concentrations. At equimolar doses, higher peak plasma 5-FU concentrations are achieved with UFT plus oral leucovorin with similar systemic 5-FU exposure compared with low-dose continuous 5-FU infusions. The elimination half-life of 5-FU following UFT administration is approximately 7 h compared with 0.2 h with i.v. 5-FU. In phase II studies of UFT plus oral leucovorin for the treatment of advanced colorectal cancer, response rates ranged from 25 to 42%. UFT plus oral leucovorin is well tolerated, with manageable diarrhea being the only dose-limiting toxicity; the regimen is not associated with significant myelosuppression, mucositis, hand-foot syndrome or alopecia. UFT, with or without leucovorin, has also been evaluated alone or in combination with other cytotoxic agents for the treatment of advanced lung, breast and gastric cancers. UFT has also been evaluated as adjuvant therapy for colorectal, breast, gastric, head and neck, and superficial bladder cancers. UFT plus leucovorin offers patients an entirely oral cancer treatment, and appears to provide potential advantages over bolus 5-FU regimens with regard to toxicity and convenience of administration. These benefits should be advantageous in the adjuvant setting, as well as in advanced disease settings in which palliation is an important consideration. Ongoing clinical trials will further define the role of this promising oral treatment regimen.

  8. MOLDOVA: MISSED ADVANTAGES OF EURASIAN INTEGRATION

    Directory of Open Access Journals (Sweden)

    Ludmila Vasiljevna Fokina

    2015-01-01

    Full Text Available The article is devoted to potentially missed advantages of Eurasian integration (EAEU for Moldova. Special attention is given to the branches in which the country could get evident advantages including agriculture, power engineering, external trade ties with the EAEU countries. Possible positive effects of Eurasian integration in solution of the Transnistrian problem, in the sphere of labour migration and other fields are also shown.

  9. Prevalence of Potential and Clinically Relevant Statin-Drug Interactions in Frail and Robust Older Inpatients.

    Science.gov (United States)

    Thai, Michele; Hilmer, Sarah; Pearson, Sallie-Anne; Reeve, Emily; Gnjidic, Danijela

    2015-10-01

    A significant proportion of older people are prescribed statins and are also exposed to polypharmacy, placing them at increased risk of statin-drug interactions. To describe the prevalence rates of potential and clinically relevant statin-drug interactions in older inpatients according to frailty status. A cross-sectional study of patients aged ≥65 years who were prescribed a statin and were admitted to a teaching hospital between 30 July and 10 October 2014 in Sydney, Australia, was conducted. Data on socio-demographics, comorbidities and medications were collected using a standardized questionnaire. Potential statin-drug interactions were defined if listed in the Australian Medicines Handbook and three international drug information sources: the British National Formulary, Drug Interaction Facts and Drug-Reax(®). Clinically relevant statin-drug interactions were defined as interactions with the highest severity rating in at least two of the three international drug information sources. Frailty was assessed using the Reported Edmonton Frail Scale. A total of 180 participants were recruited (median age 78 years, interquartile range 14), 35.0% frail and 65.0% robust. Potential statin-drug interactions were identified in 10% of participants, 12.7% of frail participants and 8.5% of robust participants. Clinically relevant statin-drug interactions were identified in 7.8% of participants, 9.5% of frail participants and 6.8% of robust participants. Depending on the drug information source used, the prevalence rates of potential and clinically relevant statin-drug interactions ranged between 14.4 and 35.6% and between 14.4 and 20.6%, respectively. In our study of frail and robust older inpatients taking statins, the overall prevalence of potential statin-drug interactions was low and varied significantly according to the drug information source used.

  10. Immunosuppression by hypoxic cell radiosensitizers: a phenomenon of potential clinical importance

    International Nuclear Information System (INIS)

    Rockwell, S.; Kapp, D.S.

    1982-01-01

    The nitroimidazoles metronidazole, misonidazol, and desmethyl misonidazole are currently undergoing clinical trials as possible adjuncts to radiotherapy. Ongoing clinical trials are evaluating the effectiveness of these agents and also documenting the pharmacokinetics and toxicities of radiosensitizing doses of these drugs in man. A variety of toxic effects have been noted in man, including anorexia, nausea and vomiting, peripheral neuropathy, central nervous system symptoms, ototoxicity, allergy, and fear. Laboratory studies have also suggested that these agents have potential to be mutagenic, carcinogenic, and teratogenic. In the editorial presented, the author attempts to draw attention to an additional toxic effect of nitroimidazoles - the inhibition of cell-mediated immune responses

  11. Home advantage in professional tennis

    NARCIS (Netherlands)

    Koning, Ruud H.

    2011-01-01

    Home advantage is a pervasive phenomenon in sport. It has been established in team sports such as basketball, baseball, American football, and European soccer. Attention to home advantage in individual sports has so far been limited. The aim of this study was to examine home advantage in

  12. The potential of telehealth for 'business as usual' in outpatient clinics.

    Science.gov (United States)

    Day, Karen; Kerr, Patricia

    2012-04-01

    A six-month pilot study was conducted to ascertain the value of using high-definition videoconferencing equipment in an outpatients' setting. The videoconferencing equipment, which included digital biometric equipment, was installed in the outpatient clinics of a remote health service in New Zealand. Use of the equipment was evaluated using action research techniques. Clinicians were interviewed about their assessment of the equipment's usefulness. Patients and their carers completed questionnaires about their clinic experience. During the pilot trial, 109 patients were seen in 25 clinics of six different specialities. Questionnaire results showed that patients and their companions had a good user experience, similar to a face-to-face appointment. Clinicians found that the large screen, sense of proximity, video clarity and definition, and lack of sound/picture lag worked well for certain types of outpatients' clinics, e.g. methadone maintenance clinics. The need for process changes made it difficult to turn telehealth into business as usual in an environment built for face-to-face appointments. We conclude that videoconference equipment has potential to become integral to outpatients' clinics.

  13. The potential role for a pharmacist in a multidisciplinary general practitioner super clinic.

    Science.gov (United States)

    Bajorek, Beata; LeMay, Kate; Gunn, Kate; Armour, Carol

    2015-01-01

    The Australian government's General Practitioner (GP) super clinics programme aims to provide well-integrated, multidisciplinary, patient-centred care for people with chronic disease. However, there is no research into the current role of pharmacists in this setting. To explore the perspectives of GP super clinic staff on current and potential (future) pharmacist-led services provided in this setting. Individual interviews (facilitated using a semi-structured interview guide and thematically analysed) were conducted with purposively sampled staff of a GP super clinic in a semirural location in the state of New South Wales, until theme saturation. Participating staff included (n=9): three GPs, one pharmacist, one nurse, one business manager, and three reception staff. Three themes emerged conveying perspectives on: working relationships between staff; a pharmacist's current role; and potential future roles for a pharmacist. All clinic staff actively engaged the pharmacist in their "team approach". Currently established roles for home medicines reviews (HMRs) and drug information were well supported, but needed to be expanded, for example, with formalised case conferences between GPs, pharmacists, and other staff. New roles needed be explored in auditing medication use, optimising medication records, specialised drug information, dispensing, and prescribing. Although GPs had differing views about opportunities for pharmacists' prescribing in this setting, they saw several benefits to this service, such as reducing the time pressure on GPs to enable more effective consultations. Results suggest a pharmacist's services can potentially be better used within the multidisciplinary super clinic model of care to address current gaps within the semi-rural practice setting. Any future role for the pharmacist could be addressed as part of a formalised, strategic approach to creating an integrated healthcare team, with attention to funding and government legislation.

  14. [Clinical treatment adherence of health care workers and students exposed to potentially infectious biological material].

    Science.gov (United States)

    Almeida, Maria Cristina Mendes de; Canini, Silvia Rita Marin da Silva; Reis, Renata Karina; Toffano, Silmara Elaine Malaguti; Pereira, Fernanda Maria Vieira; Gir, Elucir

    2015-04-01

    To assess adherence to clinical appointments by health care workers (HCW) and students who suffered accidents with potentially infectious biological material. A retrospective cross-sectional study that assessed clinical records of accidents involving biological material between 2005 and 2010 in a specialized unit. A total of 461 individuals exposed to biological material were treated, of which 389 (84.4%) were HCWs and 72 (15.6%) students. Of the 461 exposed individuals, 307 (66.6%) attended a follow-up appointment. Individuals who had suffered an accident with a known source patient were 29 times more likely to show up to their scheduled follow-up appointments (OR: 29.98; CI95%: 16.09-55.83). The predictor in both univariate and multivariate analyses for adherence to clinical follow-up appointment was having a known source patient with nonreactive serology for the human immunodeficiency virus and/or hepatitis B and C.

  15. Opportunities for Cancer-relevant Innovative Technologies with Transformative Potential | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The National Cancer Institute (NCI) is seeking input from the community on identifying priorities with regards to supporting innovative technology development for cancer-relevant research. While the NCI provides support for technology development through a variety of mechanisms, it is important to understand whether or not these are sufficient for catalyzing and supporting the development of tools with significant potential for advancing important fields of cancer research or clinical care.

  16. Successful Teaching of Radiobiology Students in the Medical Management of Acute Radiation Effects From Real Case Histories Using Clinical Signs and Symptoms and Taking Advantage of Recently Developed Software Tools.

    Science.gov (United States)

    Majewski, Matthäus; Combs, Stephanie E; Trott, Klaus-Rüdiger; Abend, Michael; Port, Matthias

    2018-07-01

    In 2015, the Bundeswehr Institute of Radiobiology organized a North Atlantic Treaty Organization exercise to examine the significance of clinical signs and symptoms for the prediction of late-occurring acute radiation syndrome. Cases were generated using either the Medical Treatment Protocols for Radiation Accident Victims (METREPOL, n = 167) system or using real-case descriptions extracted from a database system for evaluation and archiving of radiation accidents based on case histories (SEARCH, n = 24). The cases ranged from unexposed [response category 0 (RC 0, n = 89)] to mild (RC 1, n = 45), moderate (RC 2, n = 19), severe (RC 3, n = 20), and lethal (RC 4, n = 18) acute radiation syndrome. During the previous exercise, expert teams successfully predicted hematological acute radiation syndrome severity, determined whether hospitalization was required, and gave treatment recommendations, taking advantage of different software tools developed by the North Atlantic Treaty Organization teams. The authors provided the same data set to radiobiology students who were introduced to the medical management of acute effects after radiation exposure and the software tools during a class lasting 15 h. Corresponding to the previous results, difficulties in the discrimination between RC 0/RC 1 and RC 3/RC 4, as well as a systematic underestimation of RC 1 and RC 2, were observed. Nevertheless, after merging reported response categories into clinically relevant groups (RC 0-1, RC 2-3, and RC 3-4), it was found that the majority of cases (95.2% ± 2.2 standard deviations) were correctly identified and that 94.7% (±2.6 standard deviations) developing acute radiation syndrome and z96.4% (±1.6 standard deviations) requiring hospitalization were identified correctly. Two out of three student teams also provided a dose estimate. These results are comparable to the best-performing team of the 2015 North Atlantic Treaty Organization exercise (response category: 92.5%; acute

  17. [Recommendations for the clinical use of motor evoked potentials in multiple sclerosis].

    Science.gov (United States)

    Fernández, V; Valls-Sole, J; Relova, J L; Raguer, N; Miralles, F; Dinca, L; Taramundi, S; Costa-Frossard, L; Ferrandiz, M; Ramió-Torrentà, Ll; Villoslada, P; Saiz, A; Calles, C; Antigüedad, A; Alvarez-Cermeño, J C; Prieto, J M; Izquierdo, G; Montalbán, X; Fernández, O

    2013-09-01

    To establish clinical guidelines for the clinical use and interpretation of motor evoked potentials (MEP) in diagnosing and monitoring patients with multiple sclerosis (MS). Recommendations for MEP use and interpretation will help us rationalise and optimise resources used in MS patient diagnosis and follow up. We completed an extensive literature review and pooled our own data to produce a consensus statement with recommendations for the clinical use of MEPs in the study of MS. MEPs, in addition to spinal and cranial magnetic resonance imaging (MRI), help us diagnose and assess MS patients whose disease initially presents as spinal cord syndrome and those with non-specific brain MRI findings, or a normal brain MRI and clinical signs of MS. Whenever possible, a multimodal evoked potential study should be performed on patients with suspected MS in order to demonstrate involvement of the motor pathway which supports a diagnosis of dissemination in space. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  18. Updates on ultrasound research in implant dentistry: a systematic review of potential clinical indications.

    Science.gov (United States)

    Bhaskar, Vaishnavi; Chan, Hsun-Liang; MacEachern, Mark; Kripfgans, Oliver D

    2018-05-23

    Ultrasonography has shown promising diagnostic value in dental implant imaging research; however, exactly how ultrasound was used and at what stage of implant therapy it can be applied has not been systematically evaluated. Therefore, the aim of this review is to investigate potential indications of ultrasound use in the three implant treatment phases, namely planning, intraoperative and postoperative phase. Eligible manuscripts were searched in major databases with a combination of key words related to the use of ultrasound imaging in implant therapy. An initial search yielded 414 articles, after further review, 28 articles were finally included for this systematic review. Ultrasound was found valuable, though at various development stages, for evaluating (1) soft tissues, (2) hard tissues (3) vital structures and (4) implant stability. B-mode, the main function to image anatomical structures of interest, has been evaluated in pre-clinical and clinical studies. Quantitative ultrasound parameters, e.g. sound speed and amplitude, are being developed to evaluate implant-bone stability, mainly in simulation and pre-clinical studies. Ultrasound could be potentially useful in all 3 treatment phases. In the planning phase, ultrasound could evaluate vital structures, tissue biotype, ridge width/density, and cortical bone thickness. During surgery, it can provide feedback by identifying vital structures and bone boundary. At follow-up visits, it could evaluate marginal bone level and implant stability. Understanding the current status of ultrasound imaging research for implant therapy would be extremely beneficial for accelerating translational research and its use in dental clinics.

  19. Advantages of Oscillatory Hydraulic Tomography

    Science.gov (United States)

    Kitanidis, P. K.; Bakhos, T.; Cardiff, M. A.; Barrash, W.

    2012-12-01

    Characterizing the subsurface is significant for most hydrogeologic studies, such as those involving site remediation and groundwater resource explo¬ration. A variety of hydraulic and geophysical methods have been developed to estimate hydraulic conductivity and specific storage. Hydraulic methods based on the analysis of conventional pumping tests allow the estimation of conductivity and storage without need for approximate petrophysical relations, which is an advantage over most geophysical methods that first estimate other properties and then infer values of hydraulic parameters. However, hydraulic methods have the disadvantage that the head-change signal decays with distance from the pumping well and thus becomes difficult to separate from noise except in close proximity to the source. Oscillatory hydraulic tomography (OHT) is an emerging technology to im¬age the subsurface. This method utilizes the idea of imposing sinusoidally varying pressure or discharge signals at several points, collecting head observations at several other points, and then processing these data in a tomographic fashion to estimate conductivity and storage coefficients. After an overview of the methodology, including a description of the most important potential advantages and challenges associated with this approach, two key promising features of the approach will be discussed. First, the signal at an observation point is orthogonal to and thus can be separated from nuisance inputs like head fluctuation from production wells, evapotranspiration, irrigation, and changes in the level of adjacent streams. Second, although the signal amplitude may be weak, one can extract the phase and amplitude of the os¬cillatory signal by collecting measurements over a longer time, thus compensating for the effect of large distance through longer sampling period.

  20. Microfluidic paper-based analytical devices for potential use in quantitative and direct detection of disease biomarkers in clinical analysis.

    Science.gov (United States)

    Lim, Wei Yin; Goh, Boon Tong; Khor, Sook Mei

    2017-08-15

    Clinicians, working in the health-care diagnostic systems of developing countries, currently face the challenges of rising costs, increased number of patient visits, and limited resources. A significant trend is using low-cost substrates to develop microfluidic devices for diagnostic purposes. Various fabrication techniques, materials, and detection methods have been explored to develop these devices. Microfluidic paper-based analytical devices (μPADs) have gained attention for sensing multiplex analytes, confirming diagnostic test results, rapid sample analysis, and reducing the volume of samples and analytical reagents. μPADs, which can provide accurate and reliable direct measurement without sample pretreatment, can reduce patient medical burden and yield rapid test results, aiding physicians in choosing appropriate treatment. The objectives of this review are to provide an overview of the strategies used for developing paper-based sensors with enhanced analytical performances and to discuss the current challenges, limitations, advantages, disadvantages, and future prospects of paper-based microfluidic platforms in clinical diagnostics. μPADs, with validated and justified analytical performances, can potentially improve the quality of life by providing inexpensive, rapid, portable, biodegradable, and reliable diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Clinical and Laboratory Potential Predictors of Blood Culture Positivity in Under Five Children with Clinically Severe Pneumonia - Khartoum -Sudan.

    Science.gov (United States)

    Salih, Karimeldin Mohamed Ali; El-Samani, El-Fatih; Bilal, Jalal Ali; Eldouch, Widad; Ibrahim, Salah Ahmed

    2015-08-01

    Blood culture is necessary for appropriate management of clinically severe pneumonia in children under five years of age. However, in limited resource countries it might be unduly costly and waste of valuable time because of the high negative culture rate. This study aims to identify clinical and laboratory parameters that potentially predict a positive blood culture in cases of severe pneumonia. A hospital based study, enrolled 189 cases satisfying the WHO definition of severe pneumonia. Age, gender, clinical history, physical examination, temperature, complete blood count, C-reactive protein, blood culture and Chest X Ray for all the patients were recorded. Forty one patients had positive blood culture giving a prevalence of 21.7%. All variables were used in a dichotomous manner. White Blood Count (WBC) more than 20 000, very high C-reactive protein (C-RP ≥8mg/L) and Temperature more than 40(o)C, had a positive predictive value of 46.1%, 44.3% and 40.0% respectively for a positive culture as well as a Negative Predictive Value of 91.1%, 91.6% and 91.7% respectively. The WBC more than 20 000 and temperature above 40(o)C had a significant association with a positive blood culture. Their adjusted Odds Ratios were 3.9 (95% CI: 1.4-10.90) and 3.1 (95% CI: 1.2-8.4) respectively. This was not the case for C-RP (Odds Ratio=2.2, 95% CI: 0.7-2.2) or positive Chest X Ray (Odds Ratio=1.5, 95% CI: 0.6-3.6). Temperature of more than 40(o)C, Very high C-RP and WBC of more than 20 000 are good indicators of a potential positive blood culture. It is therefore recommended that further research be undertaken to refine these predictors as screening tools before resorting to blood culture. It is also recommended that antibiotic treatment may be initiated on the basis of the high temperature and WBC, while waiting for the culture results.

  2. Potential of Mass Spectrometry in Developing Clinical Laboratory Biomarkers of Nonvolatiles in Exhaled Breath.

    Science.gov (United States)

    Beck, Olof; Olin, Anna-Carin; Mirgorodskaya, Ekaterina

    2016-01-01

    Exhaled breath contains nonvolatile substances that are part of aerosol particles of submicrometer size. These particles are formed and exhaled as a result of normal breathing and contain material from distal airways of the respiratory system. Exhaled breath can be used to monitor biomarkers of both endogenous and exogenous origin and constitutes an attractive specimen for medical investigations. This review summarizes the present status regarding potential biomarkers of nonvolatile compounds in exhaled breath. The field of exhaled breath condensate is briefly reviewed, together with more recent work on more selective collection procedures for exhaled particles. The relation of these particles to the surfactant in the terminal parts of the respiratory system is described. The literature on potential endogenous low molecular weight compounds as well as protein biomarkers is reviewed. The possibility to measure exposure to therapeutic and abused drugs is demonstrated. Finally, the potential future role and importance of mass spectrometry is discussed. Nonvolatile compounds exit the lung as aerosol particles that can be sampled easily and selectively. The clinical applications of potential biomarkers in exhaled breath comprise diagnosis of disease, monitoring of disease progress, monitoring of drug therapy, and toxicological investigations. © 2015 American Association for Clinical Chemistry.

  3. Potential consequences of clinical application of artificial gametes: a systematic review of stakeholder views.

    Science.gov (United States)

    Hendriks, Saskia; Dondorp, Wybo; de Wert, Guido; Hamer, Geert; Repping, Sjoerd; Dancet, Eline A F

    2015-01-01

    Recent progress in the formation of artificial gametes, i.e. gametes generated from progenitors or somatic cells, has led to scientific and societal discussion about their use in medically assisted reproduction. In animals, live births have already been achieved using artificial gametes of varying (cell type) sources and biological research seems to be progressing steadily toward clinical application in humans. Artificial gametes could potentially help not only infertile heterosexual couples of reproductive age of which one or both partners lacks functional gametes, but also post-menopausal women and same-sex couples, to conceive a child who will be genetically related to them. But as clinical application of these new technologies may have wider societal consequences, a proactive consideration of the possible impact seems timely and important. This review aims to contribute to this by providing a systematic overview of the potential consequences of clinical application of artificial gametes anticipated by different stakeholders. The electronic database 'Medline/Pubmed' was systematically searched with medical subject heading terms (MesH) for articles published in English between January 1970 and December 2013. Articles were selected based on eligibility and reference lists of eligible studies were hand searched. The reported potential consequences of clinical application of artificial gametes were extracted from the articles and were grouped into categories by content analysis. Per category, we noted which stakeholders referred to which potential consequences, based on author affiliations and, if applicable, study participants. The systematic search yielded 2424 articles, and 84 studies were included after screening. Nine positive consequences, 21 specific consequences requiring consideration and 22 recommendations referring to clinical application of artificial gametes were documented. All positive consequences, consequences requiring consideration and

  4. A diterpenoid taxodone from Metasequoia glyptostroboides with antimycotic potential against clinical isolates of Candida species.

    Science.gov (United States)

    Bajpai, V K; Park, Y-H; Kang, S C

    2015-03-01

    The increasing importance of clinical isolates of Candida species and emerging resistance of Candida species to current synthetic antifungal agents have stimulated the search for safer and more effective alternative drugs from natural sources. This study was directed towards exploring the antimycotic potential of a diterpenoid compound taxodone isolated from Metasequoia glyptostroboides against pathogenic isolates of Candida species. Antimycotic efficacy of taxodone was evaluated by disc diffusion assay, determination of minimum inhibitory (MIC) and minimum fungicidal (MFC) concentrations, and cell viability assay. To confirm a partial antimycotic mode of action of taxodone, the efficacy of taxodone was determined by measuring the release of 260 nm absorbing materials from the selected Candida species as compared to control. The taxodone at the concentration of 400 μg/disc displayed potential antimycotic effect against the tested clinical and pathogenic isolates of Candida species as diameters of zones of inhibitions, which were found in the range of 11 ± 0.0 to 12.6 ± 0.5mm. The MIC and MFC values of taxodone against the tested clinical isolates were found in the range of 250 to 1000 and 500 to 2000μ g/mL, respectively. On the other hand, the MIC and MFC values of positive control (amphotericin B) against the tested Candida isolates were found in the range of 62.5 to 250 and 500 to 2000 μg/mL. On the viable counts of the tested fungal isolates, the taxodone exerted significant antimycotic effect. Elaborative study of partial mode of action conducted onto the release of 260nm materials (DNA and RNA) revealed potential detrimental effect of taxodone on the membrane integrity of the tested pathogens at MIC concentration. With respect to the antimycotic effect of taxodone against pathogenic and clinical isolates of Candida species, it might be confirmed that bioactive compound taxodone present in M. glyptostroboides holds therapeutic value of medicinal

  5. Profiles in fibromyalgia: algometry, auditory evoked potentials and clinical characterization of different subtypes.

    Science.gov (United States)

    Triñanes, Yolanda; González-Villar, Alberto; Gómez-Perretta, Claudio; Carrillo-de-la-Peña, María T

    2014-11-01

    The heterogeneity found in fibromyalgia (FM) patients has led to the investigation of disease subgroups, mainly based on clinical features. The aim of this study was to test the hypothesis that clinical FM subgroups are associated with different underlying pathophysiological mechanisms. Sixty-three FM patients were classified in type I or type II, according to the Fibromyalgia Impact Questionnaire (FIQ), and in mild/moderate versus severe FM, according to the severity of three cardinal symptoms considered in the American College of Rheumatology (ACR) 2010 criteria (unrefreshed sleep, cognitive problems and fatigue). To validate the subgroups obtained by these two classifications, we calculated the area under the receiver operating characteristic curves for various clinical variables and for two potential biomarkers of FM: Response to experimental pressure pain (algometry) and the amplitude/intensity slopes of the auditory evoked potentials (AEPs) obtained to stimuli of increasing intensity. The variables that best discriminated type I versus type II were those related to depression, while the indices of clinical or experimental pain (threshold or tolerance) did not significantly differ between them. The variables that best discriminated the mild/moderate versus severe subgroups were those related to the algometry. The AEPs did not allow discrimination among the generated subsets. The FIQ-based classification allows the identification of subgroups that differ in psychological distress, while the index based on the ACR 2010 criteria seems to be useful to characterize the severity of FM mainly based on hyperalgesia. The incorporation of potential biomarkers to generate or validate classification criteria is crucial to advance in the knowledge of FM and in the understanding of pathophysiological pathways.

  6. Frozen blood products: clinically effective and potentially ideal for remote Australia.

    Science.gov (United States)

    Holley, A; Marks, D C; Johnson, L; Reade, M C; Badloe, J F; Noorman, F

    2013-01-01

    The development of effective cryopreservation techniques for both red blood cells and platelets, which maintain ex vivo biological activity, in combination with frozen plasma, provides for a unique blood banking strategy. This technology greatly enhances the storage life of these products. The rationale and potential advantages of using cryopreservation techniques for the provision of blood products to remote and military environments have been effectively demonstrated in several conflicts over the last decade. Current haemostatic resuscitation doctrine for the exsanguinating patient supports the use of red blood cells, platelets and frozen plasma early in the resuscitation. We believe an integrated fresh-frozen blood bank inventory could facilitate provision of blood products, not only in the military setting but also in regional Australia, by overcoming many logistic and geographical challenges. The processes involved in production and point of care thawing are sufficiently well developed and achievable to make this technology a viable option. The potential limitations of cryopreservation and subsequent product thawing need to be considered if such a strategy is to be developed. A substantial body of international experience using cryopreserved products in remote settings has already been accrued. This experience provides a template for the possible creation of an Australian integrated fresh-frozen blood bank inventory that could conceivably enhance the care of patients in both regional Australia and in the military setting.

  7. Linear Energy Transfer-Guided Optimization in Intensity Modulated Proton Therapy: Feasibility Study and Clinical Potential

    Energy Technology Data Exchange (ETDEWEB)

    Giantsoudi, Drosoula, E-mail: dgiantsoudi@partners.org [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Grassberger, Clemens; Craft, David; Niemierko, Andrzej; Trofimov, Alexei; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)

    2013-09-01

    Purpose: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in

  8. Linear Energy Transfer-Guided Optimization in Intensity Modulated Proton Therapy: Feasibility Study and Clinical Potential

    International Nuclear Information System (INIS)

    Giantsoudi, Drosoula; Grassberger, Clemens; Craft, David; Niemierko, Andrzej; Trofimov, Alexei; Paganetti, Harald

    2013-01-01

    Purpose: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in

  9. Competitive advantage and corporate communications

    Directory of Open Access Journals (Sweden)

    Mitić Sanja

    2013-01-01

    Full Text Available Strategic importance of corporate communications and its role in the development of competitive advantage has attracted interest of numerous researchers in the fields of organization, management, marketing and public relations. Recent studies particularly emphasise the growing importance of soft factors, such as reputation in the development of competitive advantage. Concept of reputation is strongly connected with stakeholder theory, which stresses the importance of corporate communications for competitive advantage of firms. The paper focuses on competitive advantage and the link among strategy, reputation and corporate communications.

  10. Systematic review of induced pluripotent stem cell technology as a potential clinical therapy for spinal cord injury.

    Science.gov (United States)

    Kramer, Anne S; Harvey, Alan R; Plant, Giles W; Hodgetts, Stuart I

    2013-01-01

    Transplantation therapies aimed at repairing neurodegenerative and neuropathological conditions of the central nervous system (CNS) have utilized and tested a variety of cell candidates, each with its own unique set of advantages and disadvantages. The use and popularity of each cell type is guided by a number of factors including the nature of the experimental model, neuroprotection capacity, the ability to promote plasticity and guided axonal growth, and the cells' myelination capability. The promise of stem cells, with their reported ability to give rise to neuronal lineages to replace lost endogenous cells and myelin, integrate into host tissue, restore functional connectivity, and provide trophic support to enhance and direct intrinsic regenerative ability, has been seen as a most encouraging step forward. The advent of the induced pluripotent stem cell (iPSC), which represents the ability to "reprogram" somatic cells into a pluripotent state, hails the arrival of a new cell transplantation candidate for potential clinical application in therapies designed to promote repair and/or regeneration of the CNS. Since the initial development of iPSC technology, these cells have been extensively characterized in vitro and in a number of pathological conditions and were originally reported to be equivalent to embryonic stem cells (ESCs). This review highlights emerging evidence that suggests iPSCs are not necessarily indistinguishable from ESCs and may occupy a different "state" of pluripotency with differences in gene expression, methylation patterns, and genomic aberrations, which may reflect incomplete reprogramming and may therefore impact on the regenerative potential of these donor cells in therapies. It also highlights the limitations of current technologies used to generate these cells. Moreover, we provide a systematic review of the state of play with regard to the use of iPSCs in the treatment of neurodegenerative and neuropathological conditions. The

  11. Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

    Science.gov (United States)

    Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

    2016-01-01

    MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

  12. Potentiating antibiotics in drug-resistant clinical isolates via stimuli-activated superoxide generation.

    Science.gov (United States)

    Courtney, Colleen M; Goodman, Samuel M; Nagy, Toni A; Levy, Max; Bhusal, Pallavi; Madinger, Nancy E; Detweiler, Corrella S; Nagpal, Prashant; Chatterjee, Anushree

    2017-10-01

    The rise of multidrug-resistant (MDR) bacteria is a growing concern to global health and is exacerbated by the lack of new antibiotics. To treat already pervasive MDR infections, new classes of antibiotics or antibiotic adjuvants are needed. Reactive oxygen species (ROS) have been shown to play a role during antibacterial action; however, it is not yet understood whether ROS contribute directly to or are an outcome of bacterial lethality caused by antibiotics. We show that a light-activated nanoparticle, designed to produce tunable flux of specific ROS, superoxide, potentiates the activity of antibiotics in clinical MDR isolates of Escherichia coli , Salmonella enterica , and Klebsiella pneumoniae . Despite the high degree of antibiotic resistance in these isolates, we observed a synergistic interaction between both bactericidal and bacteriostatic antibiotics with varied mechanisms of action and our superoxide-producing nanoparticles in more than 75% of combinations. As a result of this potentiation, the effective antibiotic concentration of the clinical isolates was reduced up to 1000-fold below their respective sensitive/resistant breakpoint. Further, superoxide-generating nanoparticles in combination with ciprofloxacin reduced bacterial load in epithelial cells infected with S. enterica serovar Typhimurium and increased Caenorhabditis elegans survival upon infection with S. enterica serovar Enteriditis, compared to antibiotic alone. This demonstration highlights the ability to engineer superoxide generation to potentiate antibiotic activity and combat highly drug-resistant bacterial pathogens.

  13. Clinical usefulness and feasibility of time-frequency analysis of chemosensory event-related potentials.

    Science.gov (United States)

    Huart, C; Rombaux, Ph; Hummel, T; Mouraux, A

    2013-09-01

    The clinical usefulness of olfactory event-related brain potentials (OERPs) to assess olfactory function is limited by the relatively low signal-to-noise ratio of the responses identified using conventional time-domain averaging. Recently, it was shown that time-frequency analysis of the obtained EEG signals can markedly improve the signal-to-noise ratio of OERPs in healthy controls, because it enhances both phase-locked and non phase-locked EEG responses. The aim of the present study was to investigate the clinical usefulness of this approach and evaluate its feasibility in a clinical setting. We retrospectively analysed EEG recordings obtained from 45 patients (15 anosmic, 15 hyposmic and 15 normos- mic). The responses to olfactory stimulation were analysed using conventional time-domain analysis and joint time-frequency analysis. The ability of the two methods to discriminate between anosmic, hyposmic and normosmic patients was assessed using a Receiver Operating Characteristic analysis. The discrimination performance of OERPs identified using conventional time-domain averaging was poor. In contrast, the discrimination performance of the EEG response identified in the time-frequency domain was relatively high. Furthermore, we found a significant correlation between the magnitude of this response and the psychophysical olfactory score. Time-frequency analysis of the EEG responses to olfactory stimulation could be used as an effective and reliable diagnostic tool for the objective clinical evaluation of olfactory function in patients.

  14. Post-use assay of vaginal rings (VRs) as a potential measure of clinical trial adherence.

    Science.gov (United States)

    Spence, Patrick; Nel, Annalene; van Niekerk, Neliëtte; Derrick, Tiffany; Wilder, Susan; Devlin, Bríd

    2016-06-05

    Adherence measurement for microbicide use within the clinical trial setting remains a challenge for the HIV prevention field. This paper describes an assay method used for determining residual dapivirine levels in post-use vaginal rings from clinical trials conducted with the Dapivirine Vaginal Matrix Ring-004 developed by the International Partnership for Microbicides to prevent male to female HIV transmission. Post-use assay results from three Ring-004 clinical trials showed that of the 25mg drug load, approximately 4mg of dapivirine is released from the matrix ring over a 28-day use period. Data obtained by both in vitro and in vivo studies indicate that dapivirine is released according to a diffusion mechanism, as determined by conformance of both data sets to the Higuchi equation. This, coupled with the low variability associated with batch production over two manufacturing sites and 20 batches of material, provides evidence that post-use ring analysis can contribute to the assessment of adherence to ring use. Limitations of this method include the potential of intra-participant and inter-participant variability and uncertainty associated with measuring the low amount of dapivirine actually released relative to the drug load. Therefore, residual drug levels should not serve as the only direct measurement for microbicide adherence in vaginal ring clinical trials but should preferably be used as part of a multi-pronged approach towards understanding and assessing adherence to vaginal ring use. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Immunoliposome-mediated delivery of neomycin phosphotransferase for the lineage-specific selection of differentiated/committed stem cell progenies: potential advantages over transfection with marker genes, fluorescence-activated and magnetic affinity cell-sorting.

    Science.gov (United States)

    Heng, Boon Chin; Cao, Tong

    2005-01-01

    A major challenge in the therapeutic application of stem cells in regenerative medicine is the lineage-specific selection of their committed/differentiated progenies for transplantation. This is necessary to avoid engraftment of undesired lineages at the transplantation site, i.e. fibroblastic scar tissue, as well as to enhance the efficacy of transplantation therapy. Commonly used techniques for lineage-specific selection of committed/differentiated stem cell progenies include marker gene transfection, fluorescence-activated (FACS) and magnetic-affinity (MACS) cell-sorting. Nevertheless, these have their disadvantages for therapeutic applications. Marker gene transfection invariably leads to permanent genetic modification of stem cells, which in turn limits their use in human clinical therapy due to overwhelming ethical and safety concerns. FACS requires expensive instrumentation and highly-skilled personnel, and is unsuited for handling bulk quantities of cells that would almost certainly be required for transplantation therapy. MACS is a cheaper alternative, but the level of purity attained is also reduced. A possible novel approach that has yet to be investigated is immunoliposome-mediated delivery of neomycin phosphotranferase (NPT) for lineage-specific selection of stem cell progenies. This would avoid permanent genetic modification to the cell, unlike recombinant NPT expression linked to activation of specific promoter sequences. Moreover, it could potentially provide a much more practical and cost-effective alternative for handling bulk quantities of cells that would be required for transplantation therapy, as compared to FACS or MACS. As such, this alternative approach needs to be rigorously investigated, in view of its potentially useful applications in stem cell therapeutics.

  16. Hypnosis in the Perioperative Management of Breast Cancer Surgery: Clinical Benefits and Potential Implications

    Science.gov (United States)

    Roelants, Fabienne; Pospiech, Audrey; Momeni, Mona; Watremez, Christine

    2016-01-01

    The aim of this review is to summarize data published on the use of perioperative hypnosis in patients undergoing breast cancer surgery (BCS). Indeed, the majority of BCS patients experience stress, anxiety, nausea, vomiting, and pain. Correct management of the perioperative period and surgical removal of the primary tumor are clearly essential but can affect patients on different levels and hence have a negative impact on oncological outcomes. This review examines the effect of clinical hypnosis performed during the perioperative period. Thanks to its specific properties and techniques allowing it to be used as complementary treatment preoperatively, hypnosis has an impact most notably on distress and postoperative pain. During surgery, hypnosis may be applied to limit immunosuppression, while, in the postoperative period, it can reduce pain, anxiety, and fatigue and improve wound healing. Moreover, hypnosis is inexpensive, an important consideration given current financial concerns in healthcare. Of course, large randomized prospective studies are now needed to confirm the observed advantages of hypnosis in the field of oncology. PMID:27635132

  17. The role of cannabinoids in prostate cancer: Basic science perspective and potential clinical applications

    Directory of Open Access Journals (Sweden)

    Juan A Ramos

    2012-01-01

    Full Text Available Prostate cancer is a global public health problem, and it is the most common cancer in American men and the second cause for cancer-related death. Experimental evidence shows that prostate tissue possesses cannabinoid receptors and their stimulation results in anti-androgenic effects. To review currently relevant findings related to effects of cannabinoid receptors in prostate cancer. PubMed search utilizing the terms "cannabis," "cannabinoids," "prostate cancer," and "cancer pain management," giving preference to most recent publications was done. Articles identified were screened for their relevance to the field of prostate cancer and interest to both urologist and pain specialists. Prostate cancer cells possess increased expression of both cannabinoid 1 and 2 receptors, and stimulation of these results in decrease in cell viability, increased apoptosis, and decreased androgen receptor expression and prostate-specific antigen excretion. It would be of interest to conduct clinical studies utilizing cannabinoids for patients with metastatic prostate cancer, taking advantage not only of its beneficial effects on prostate cancer but also of their analgesic properties for bone metastatic cancer pain.

  18. The Shift From Sentinel Lymph Node Biopsy Performed Either Before or After Neoadjuvant Systemic Therapy in the Clinical Negative Nodes of Breast Cancer Patients. Results, and the Advantages and Disadvantages of Both Procedures.

    Science.gov (United States)

    Fernandez-Gonzalez, Sergi; Falo, Catalina; Pla, Maria Jesus; Pernas, Sonia; Bajen, Maite; Soler, Teresa; Ortega, Raul; Quetglas, Cecilia; Perez-Martin, Xavier; Fernandez Montoli, Maria Eulalia; Campos, Miriam; Varela-Rodriguez, Mar; Ponce, Jordi; Garcia-Tejedor, Amparo

    2018-02-01

    In patients with breast cancer who are candidates for neoadjuvant therapy (NAT), the timing of when to perform sentinel lymph node biopsy (SLNB) remains under discussion. The aim of this study was to compare the advantages and disadvantages of SLNB performed before and after NAT. One hundred seventy-two patients, T1c to T3 and N0 (clinically and according to ultrasound) candidates for NAT were included. We compared the outcomes of 2 groups: (1) 122 patients of whom SLNB was performed before NAT (pre-NAT) from December 2006 to April 2014; and (2) 50 patients with SLNB performed after NAT (post-NAT) from May 2014 to July 2016. Both groups were homogeneous in baseline patient characteristics. The SLNB was positive in 50 patients [41.7%] (33 macrometastases [66%] and 17 micrometastases [34%]) versus 6 patients [12%] (5 macrometastases [83.3%] and 1 micrometastases [16.7%]) in pre- and post-NAT groups, respectively. The lymphadenectomy was performed in 34 patients [28.3%] versus 4 patients [8%], with an odds ratio of 3.48 (95% confidence interval, 1.3-9.3). The recurrences in the pre-NAT group after a median follow-up of 62 months were 12 systemic, 2 local and systemic, and none axillary. In the post-NAT group were no recurrences after a median follow-up of 16 months. Finally, SLNB after NAT reduces the delay in starting NAT from 24 to 14 days (medians; P < .001) and the identification of the SLNB was in 122 patients [100%] versus 49 patients [98%]. SLNB performed after NAT significantly reduces the rate of lymphadenectomies without any increase in recurrences at early follow-up. Furthermore, it allows systemic treatment to be started earlier without interfering in the SLNB identification rate. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke

    Directory of Open Access Journals (Sweden)

    Wentao Li

    2016-08-01

    Full Text Available Fingolimod (FTY720 is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720’s mechanisms of action in stroke

  20. PATIENTS WITH SUSPECTED METAL IMPLANT ALLERGY: POTENTIAL CLINICAL PICTURES AND ALLERGOLOGICAL DIAGNOSTIC APPROACH (REVIEW

    Directory of Open Access Journals (Sweden)

    P. Thomas

    2014-01-01

    Full Text Available The focus of this review are allergic complications following insertion of metallic orthopedic implants. Such potential allergic reactions encompass eczema, impaired wound and fracture healing, infection-mimicking reactions, effusions, pain and loosening. Nickel, cobalt and chromium seem to be the predominant eliciting allergens. Allergy might be considered prior to planned orthopaedic surgery or in patients with complications following arthroplasty We recommend, that differential diagnoses - in particular infection -should always be excluded in cooperation with surgery collegues. The clinical work up of a patient suspected of suffering from metal implant allergy should include a combined evaluation of medical history, clinical findings, patch testing and histology In vitro testing, namely the lymphocyte transformation test (LTT, can indicate metal sensitization, but needs careful interpretation.

  1. TH-B-BRC-01: How to Identify and Resolve Potential Clinical Errors

    Energy Technology Data Exchange (ETDEWEB)

    Das, I. [NYU Langone Medical Center, New York, NY (United States)

    2016-06-15

    Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803.

  2. TH-B-BRC-01: How to Identify and Resolve Potential Clinical Errors

    International Nuclear Information System (INIS)

    Das, I.

    2016-01-01

    Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803

  3. Diagnostic accuracy of clinical and blood examination for sepsis in potentially infected neonates

    Directory of Open Access Journals (Sweden)

    Ari Mulyani

    2006-10-01

    Full Text Available Background Neonatal sepsis remains a diagnostic challenge due to its nonspesific symptoms and signs. Blood culture as the gold standard is still a problem because it takes time, is expensive, and not every health facility is able to perionn. Objective To evaluate the diagnostic accuracy of clinical symptoms, hematologic findings, and C-reactive protein (CRP in neonatal sepsis. Methods Samples were taken from potentially infected neonates admitted to the Matemal-Perinatal Unit of Sardjito Hospital, between December 1st, 2000 and March 31st, 2001 using at least one of the criteria: prematurity, very low birth weight infants, matemal pyrexia during delivery, premature membrane rupture, or thick, cloudy amniotic fluid. Clinical symptoms, total leukocyte, neutrophil, platelet count, CRP, and blood culture as the gold standard were examined. Results Among 99 neonates enrolled, the sensitivity, specificity, positive and negative predictive value of clinical symptoms were 79.3%, 75.7%, 57.5%, and 89.9%, respectively; leukopenia/leukocytosis were 27.6%, 85.7%, 44.4%, and 74.1%; neutropenia! neutrophilia were 41.4%, 71.4%, 37.5%, and 74.6%; thrombocytopenia were 79.3%, 51.8%, 40.4%, and 85.7%; positive CRP were 58.6%,78.6%,53.1%, and 82.1%. Parallel tests increased the sensitivity up to 89.7%. Specificity, positive and negative predictive value, and likelihood ratio were 44.3%, 40%, 91.2%, and 1.6, respectively. Serial tests increased the specificity up to 88.6%. Sensitivity, positive and negative predictive value, and likelihood ratio were 58.6%, 68%, 83.8%, and 5.1, respectively. Conclusion Clinical sepsis, thrombocytopenia, and CRP are sufficiently accurate as diagnostic tests for sepsis in potentially infected neonates. Parallel tests will increase the sensitivity, while serial tests increase the specificity.

  4. Clinical potential of lixisenatide once daily treatment for type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Petersen, Andreas Brønden; Christensen, Mikkel

    2013-01-01

    The glucagon-like peptide (GLP)-1 receptor agonist lixisenatide (Lyxumia(®)) was approved for marketing by the European Medicines Agency in February 2013 and has been evaluated in a clinical study program called GetGoal. Lixisenatide activates the GLP-1 receptor and thereby exercises the range of...... of lixisenatide seems to be in combination with basal insulin. A large multicenter study will determine the future potential of lixisenatide in preventing cardiovascular events and mortality, in patients with type 2 diabetes and recent acute coronary syndrome....

  5. Radotinib and its clinical potential in chronic-phase chronic myeloid leukemia patients: an update.

    Science.gov (United States)

    Eskazan, Ahmet Emre; Keskin, Dilek

    2017-09-01

    Although imatinib has dramatically improved major outcomes in patients with chronic myeloid leukemia (CML), there are newer tyrosine kinase inhibitors (TKIs) approved worldwide for the treatment of resistant cases, and two second-generation TKIs (dasatinib, nilotinib) are approved in some nations for treating patients in the upfront setting. Radotinib (IY5511HCL, Supect® ) is a novel and selective second-generation BCR-ABL1 TKI, which is currently approved in Korea for the treatment of patients with CML both in the upfront and salvage settings. This review mainly focuses on the clinical potential of radotinib in patients with CML in chronic phase in terms of efficacy and safety.

  6. A scoping review of the potential for chart stimulated recall as a clinical research method.

    Science.gov (United States)

    Sinnott, Carol; Kelly, Martina A; Bradley, Colin P

    2017-08-22

    Chart-stimulated recall (CSR) is a case-based interviewing technique, which is used in the assessment of clinical decision-making in medical education and professional certification. Increasingly, clinical decision-making is a concern for clinical research in primary care. In this study, we review the prior application and utility of CSR as a technique for research interviews in primary care. Following Arksey & O'Malley's method for scoping reviews, we searched seven databases, grey literature, reference lists, and contacted experts in the field. We excluded studies on medical education or competence assessment. Retrieved citations were screened by one reviewer and full texts were ordered for all potentially relevant abstracts. Two researchers independently reviewed full texts and performed data extraction and quality appraisal if inclusion criteria were met. Data were collated and summarised using a published framework on the reporting of qualitative interview techniques, which was chosen a priori. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines informed the review report. From an initial list of 789 citations, eight studies using CSR in research interviews were included in the review: six from North America, one from the Netherlands, and one from Ireland. The most common purpose of included studies was to examine the influence of guidelines on physicians' decisions. The number of interviewees ranged from seven to twenty nine, while the number of charts discussed per interview ranged from one to twelve. CSR gave insights into physicians' reasoning for actions taken or not taken; the unrecorded social and clinical influences on decisions; and discrepancies between physicians' real and perceived practice. Ethical concerns and the training and influence of the researcher were poorly discussed in most of the studies. Potential pitfalls included the risk of recall, selection and observation biases. Despite the proven validity

  7. Prevention of hepatocellular carcinoma: potential targets, experimental models, and clinical challenges

    Science.gov (United States)

    Hoshida, Yujin; Fuchs, Bryan C.; Tanabe, Kenneth K.

    2013-01-01

    Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the goal. Studies have elucidated a wide variety of molecular mechanisms and signaling pathways involved in HCC development. Genetically-engineered or chemically-treated experimental models of cirrhosis and HCC have been developed and shown their potential value in investigating molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In this review, we overview potential targets of prevention and currently available experimental models, and discuss strategies to translate the findings into clinical practice. PMID:22873223

  8. [Potential antimicrobial drug interactions in clinical practice: consequences of polypharmacy and multidrug resistance].

    Science.gov (United States)

    Martínez-Múgica, Cristina

    2015-12-01

    Polypharmacy is a growing problem nowadays, which can increase the risk of potential drug interactions, and result in a loss of effectiveness. This is particularly relevant to the anti-infective therapy, especially when infection is produced by resistant bacteria, because therapeutic options are limited and interactions can cause treatment failure. All antimicrobial prescriptions were retrospectively reviewed during a week in the Pharmacy Department, in order to detect potential drug-interactions and analysing their clinical significance. A total of 314 antimicrobial prescriptions from 151 patients were checked. There was at least one potential interaction detected in 40% of patients, being more frequent and severe in those infected with multidrug-resistant microorganisms. Drugs most commonly involved were quinolones, azoles, linezolid and vancomycin. Potential drug interactions with antimicrobial agents are a frequent problem that can result in a loss of effectiveness. This is why they should be detected and avoided when possible, in order to optimize antimicrobial therapy, especially in case of multidrug resistant infections.

  9. Constructing a Local Potential Participant Registry to Improve Alzheimer's Disease Clinical Research Recruitment.

    Science.gov (United States)

    Grill, Joshua D; Hoang, Dan; Gillen, Daniel L; Cox, Chelsea G; Gombosev, Adrijana; Klein, Kirsten; O'Leary, Steve; Witbracht, Megan; Pierce, Aimee

    2018-01-01

    Potential participant registries are tools to address the challenge of slow recruitment to clinical research. In particular, registries may aid recruitment to secondary prevention clinical trials for Alzheimer's disease (AD), which enroll cognitively normal older individuals meeting specific genetic or biomarker criteria. Evidence of registry effectiveness is sparse, as is guidance on optimal designs or methods of conduct. We report our experiences of developing a novel local potential participant registry that implemented online enrollment and data collection. In the first year of operation, 957 individuals submitted email addresses to the registry, of whom 592 self-reported demographic, family history, and medical data. In addition, registrants provided information related to their interest and willingness to be contacted about studies. Local earned media and community education were the most effective methods of recruitment into the registry. Seventy-six (26%) of 298 registrants contacted about studies in the first year enrolled in those studies. One hundred twenty-nine registrants were invited to enroll in a preclinical AD trial, of whom 25 (18%) screened and 6 were randomized. These results indicate that registries can aid recruitment and provide needed guidance for investigators initiating new local registries.

  10. Human iPS Cell-Derived Germ Cells: Current Status and Clinical Potential

    Directory of Open Access Journals (Sweden)

    Tetsuya Ishii

    2014-10-01

    Full Text Available Recently, fertile spermatozoa and oocytes were generated from mouse induced pluripotent (iPS cells using a combined in vitro and in vivo induction system. With regard to germ cell induction from human iPS cells, progress has been made particularly in the male germline, demonstrating in vitro generation of haploid, round spermatids. Although iPS-derived germ cells are expected to be developed to yield a form of assisted reproductive technology (ART that can address unmet reproductive needs, genetic and/or epigenetic instabilities abound in iPS cell generation and germ cell induction. In addition, there is still room to improve the induction protocol in the female germline. However, rapid advances in stem cell research are likely to make such obstacles surmountable, potentially translating induced germ cells into the clinical setting in the immediate future. This review examines the current status of the induction of germ cells from human iPS cells and discusses the clinical potential, as well as future directions.

  11. Clinical potential of meningioma genomic insights: a practical review for neurosurgeons.

    Science.gov (United States)

    Karsy, Michael; Azab, Mohammed A; Abou-Al-Shaar, Hussam; Guan, Jian; Eli, Ilyas; Jensen, Randy L; Ormond, D Ryan

    2018-06-01

    Meningiomas are among the most common intracranial pathological conditions, accounting for 36% of intracranial lesions treated by neurosurgeons. Although the majority of these lesions are benign, the classical categorization of tumors by histological type or World Health Organization (WHO) grade has not fully captured the potential for meningioma progression and recurrence. Many targeted treatments have failed to generate a long-lasting effect on these tumors. Recently, several seminal studies evaluating the genomics of intracranial meningiomas have rapidly changed the understanding of the disease. The importance of NF2 (neurofibromin 2), TRAF7 (tumor necrosis factor [TNF] receptor-associated factor 7), KLF4 (Kruppel-like factor 4), AKT1, SMO (smoothened), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), and POLR2 (RNA polymerase II subunit A) demonstrates that there are at least 6 distinct mutational classes of meningiomas. In addition, 6 methylation classes of meningioma have been appreciated, enabling improved prediction of prognosis compared with traditional WHO grades. Genomic studies have shed light on the nature of recurrent meningioma, distinct intracranial locations and mutational patterns, and a potential embryonic cancer stem cell-like origin. However, despite these exciting findings, the clinical relevance of these findings remains elusive. The authors review the key findings from recent genomic studies in meningiomas, specifically focusing on how these findings relate to clinical insights for the practicing neurosurgeon.

  12. Human Induced Pluripotent Stem Cells from Basic Research to Potential Clinical Applications in Cancer

    Directory of Open Access Journals (Sweden)

    Teresa de Souza Fernandez

    2013-01-01

    Full Text Available The human induced pluripotent stem cells (hiPSCs are derived from a direct reprogramming of human somatic cells to a pluripotent stage through ectopic expression of specific transcription factors. These cells have two important properties, which are the self-renewal capacity and the ability to differentiate into any cell type of the human body. So, the discovery of hiPSCs opens new opportunities in biomedical sciences, since these cells may be useful for understanding the mechanisms of diseases in the production of new diseases models, in drug development/drug toxicity tests, gene therapies, and cell replacement therapies. However, the hiPSCs technology has limitations including the potential for the development of genetic and epigenetic abnormalities leading to tumorigenicity. Nowadays, basic research in the hiPSCs field has made progress in the application of new strategies with the aim to enable an efficient production of high-quality of hiPSCs for safety and efficacy, necessary to the future application for clinical practice. In this review, we show the recent advances in hiPSCs’ basic research and some potential clinical applications focusing on cancer. We also present the importance of the use of statistical methods to evaluate the possible validation for the hiPSCs for future therapeutic use toward personalized cell therapies.

  13. Recent Progress in Lab-on-a-Chip Technology and Its Potential Application to Clinical Diagnoses

    Directory of Open Access Journals (Sweden)

    Nae Yoon Lee

    2013-03-01

    Full Text Available We present the construction of the lab-on-a-chip (LOC system, a state-of-the-art technology that uses polymer materials (i.e., poly[dimethylsiloxane] for the miniaturization of conventional laboratory apparatuses, and show the potential use of these microfluidic devices in clinical applications. In particular, we introduce the independent unit components of the LOC system and demonstrate how each component can be functionally integrated into one monolithic system for the realization of a LOC system. In specific, we demonstrate microscale polymerase chain reaction with the use of a single heater, a microscale sample injection device with a disposable plastic syringe and a strategy for device assembly under environmentally mild conditions assisted by surface modification techniques. In this way, we endeavor to construct a totally integrated, disposable microfluidic system operated by a single mode, the pressure, which can be applied on-site with enhanced device portability and disposability and with simple and rapid operation for medical and clinical diagnoses, potentially extending its application to urodynamic studies in molecular level.

  14. Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 1: Regulatory Context and Risk Management.

    Science.gov (United States)

    Sellers, Edward M

    2018-02-01

    This article brings to the attention of drug developers the Food and Drug Administration's (FDA's) recent final Guidance to Industry on Assessment of Abuse Potential and provides practical suggestions about compliance with the Guidance. The Guidance areas are reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk. The Guidance provides substantial new detail on what needs to be done at all stages of drug development for central nervous system-active drugs. However, because many psychopharmacologic agents have unique preclinical and clinical features, the plan for each agent needs to be not only carefully prepared but also reviewed and approved by the FDA. Examples are provided where assumptions about interpretation of the Guidance can delay development. If the expertise and experience needed for assessing abuse potential during drug development do not exist within a company, external preclinical and clinical expert should be involved. Consultation with the FDA is encouraged and important because the specific requirements for each drug will vary.

  15. Profile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Keller-von Amsberg G

    2013-03-01

    Full Text Available Gunhild Keller-von Amsberg,1 Steffen Koschmieder21Department of Hematology and Oncology, University Cancer Center Hamburg, University Hospital Hamburg Eppendorf, 2Department of Medicine (Hematology, Oncology, and Stem Cell Transplantation, University Medical Center of Aachen and RWTH Aachen University, Aachen, GermanyAbstract: Bosutinib (SKI-606 is an orally available, once-daily, dual Src and Abl kinase inhibitor with promising clinical potential in first-, second-, and third-line treatment of chronic myeloid leukemia (CML. Bosutinib effectively inhibits wild-type BCR-ABL and most imatinib-resistant BCR-ABL mutations except for V299L and T315I. Low hematologic toxicity is a remarkable characteristic of this novel second-generation tyrosine kinase inhibitor, and this has been ascribed to its minimal activity against the platelet-derived growth factor receptor and KIT. Low-grade, typically self-limiting diarrhea, which usually appears within the first few weeks after treatment initiation, represents the predominant toxicity of bosutinib. Other treatment-associated adverse events are mostly mild to moderate. Bosutinib has been approved by the US Food and Drug Administration for the treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive CML in adult patients with resistance or intolerance to prior therapy. This review summarizes the main properties of bosutinib and the currently available data on its clinical potential in the treatment of CML.Keywords: bosutinib, chronic myeloid leukemia, BCR-ABL, Src/Abl kinase inhibitor, point mutation, imatinib resistance

  16. A clinically feasible method for the detection of potential collision in proton therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zou Wei; Lin Haibo; Plastaras, John P.; Wang Huanshu; Bui, Viet; Vapiwala, Neha; McDonough, James; Tochner, Zelig; Both, Stefan [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States) and Department of Mechanical Engineering, Drexel University, Philadelphia, Pennsylvania 19104 (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States)

    2012-11-15

    Purpose: Potential collision between the patient/couch and the gantry could delay the start of the treatment and reduce clinical efficiency. The ability to accurately detect possible collisions during the treatment planning phase is desired. Such collision detection should account for the specific proton gantry design, the treatment beam configuration, couch orientation, and the patient specific geometry. In this paper the authors developed an approach to detect possible patient-machine collisions using patient treatment plan data. Methods: The geometry of the machine and the patient was reconstructed relative to the isocenter of the proton treatment room. The surface contour of the gantry was first captured from the proton computer aided design and reconstructed to account for specific gantry rotation, snout position, collimator rotation, and range compensator dimensions based on the patient treatment plan data. The patient body and couch contours were captured from the patient's CT DICOM structure file. They were reconstructed relative to the isocenter taking into account treatment couch rotation. For potential collision that occurs at body portions where no CT images exist, scout images are used to construct the body contour. A software program was developed using a ray casting algorithm that was applied to detect collisions by determining if any of the patient and couch contour points fall into the spatial polygons formed by the proton gantry surfaces. Results: Twenty-four patient plans with or without potential collisions were retrospectively identified and analyzed using the collision detection software. In addition, five collision cases were artificially generated using an anthropomorphic phantom. The program successfully detected the collisions in all cases. The calculation time for each case was within 20 s. The software program was implemented in the authors' clinic to detect patient-gantry or gantry-couch collisions in the treatment planning

  17. Clinical treatment adherence of health care workers and students exposed to potentially infectious biological material

    Directory of Open Access Journals (Sweden)

    Maria Cristina Mendes de Almeida

    2015-04-01

    Full Text Available OBJECTIVE To assess adherence to clinical appointments by health care workers (HCW and students who suffered accidents with potentially infectious biological material. METHOD A retrospective cross-sectional study that assessed clinical records of accidents involving biological material between 2005 and 2010 in a specialized unit. RESULTS A total of 461 individuals exposed to biological material were treated, of which 389 (84.4% were HCWs and 72 (15.6% students. Of the 461 exposed individuals, 307 (66.6% attended a follow-up appointment. Individuals who had suffered an accident with a known source patient were 29 times more likely to show up to their scheduled follow-up appointments (OR: 29.98; CI95%: 16.09-55.83. CONCLUSION The predictor in both univariate and multivariate analyses for adherence to clinical follow-up appointment was having a known source patient with nonreactive serology for the human immunodeficiency virus and/or hepatitis B and C.

  18. Epicardial fat and atrial fibrillation: current evidence, potential mechanisms, clinical implications, and future directions.

    Science.gov (United States)

    Wong, Christopher X; Ganesan, Anand N; Selvanayagam, Joseph B

    2017-05-01

    Obesity is increasingly recognized as a major modifiable determinant of atrial fibrillation (AF). Although body mass index and other clinical measures are useful indications of general adiposity, much recent interest has focused on epicardial fat, a distinct adipose tissue depot that can be readily assessed using non-invasive imaging techniques. A growing body of data from epidemiological and clinical studies has demonstrated that epicardial fat is consistently associated with the presence, severity, and recurrence of AF across a range of clinical settings. Evidence from basic science and translational studies has also suggested that arrhythmogenic mechanisms may involve adipocyte infiltration, pro-fibrotic, and pro-inflammatory paracrine effects, oxidative stress, and other pathways. Despite these advances, however, significant uncertainty exists and many questions remain unanswered. In this article, we review our present understanding of epicardial fat, including its classification and quantification, existing evidence implicating its role in AF, potential mechanisms, implications for clinicians, and future directions for research. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  19. Application of the MALDI Biotyper to clinical microbiology: progress and potential.

    Science.gov (United States)

    Kostrzewa, Markus

    2018-03-01

    The introduction of the MALDI Biotyper in laboratories substantially changed microbiology practice, this has been called a revolution. The system accelerated diagnostic while costs were reduced and accuracy was increased. In just a few years MALDI-TOF MS became the first-line identification tool for microorganisms. Ten years after its introduction, more than 2000 MALDI Biotyper systems are installed in laboratories which are performing routine diagnostic, and the number is still increasing. Areas covered: This article summarises changes in clinical microbiology introduced by the MALDI Biotyper and its effects, as it has been published in peer reviewed articles found in PubMed. Further, the potential of novel developments to increase the value of the system is described. Expert commentary: The MALDI Biotyper has significantly improved clinical microbiology in the area of microorganism identification. Now new developments and applications, e.g. for typing and resistance testing, might further increase its value in clinical microbiology. The systems might get the central diagnostic analyser which is getting integrated into the widely automated microbiology laboratories of the future.

  20. Stem cell transplantation for amyotrophic lateral sclerosis: therapeutic potential and perspectives on clinical translation.

    Science.gov (United States)

    Faravelli, Irene; Riboldi, Giulietta; Nizzardo, Monica; Simone, Chiara; Zanetta, Chiara; Bresolin, Nereo; Comi, Giacomo P; Corti, Stefania

    2014-09-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by degeneration of upper and lower motor neurons. There are currently no clinically impactful treatments for this disorder. Death occurs 3-5 years after diagnosis, usually due to respiratory failure. ALS pathogenesis seems to involve several pathological mechanisms (i.e., oxidative stress, inflammation, and loss of the glial neurotrophic support, glutamate toxicity) with different contributions from environmental and genetic factors. This multifaceted combination highlights the concept that an effective therapeutic approach should counteract simultaneously different aspects: stem cell therapies are able to maintain or rescue motor neuron function and modulate toxicity in the central nervous system (CNS) at the same time, eventually representing the most comprehensive therapeutic approach for ALS. To achieve an effective cell-mediated therapy suitable for clinical applications, several issues must be addressed, including the identification of the most performing cell source, a feasible administration protocol, and the definition of therapeutic mechanisms. The method of cell delivery represents a major issue in developing cell-mediated approaches since the cells, to be effective, need to be spread across the CNS, targeting both lower and upper motor neurons. On the other hand, there is the need to define a strategy that could provide a whole distribution without being too invasive or burdened by side effects. Here, we review the recent advances regarding the therapeutic potential of stem cells for ALS with a focus on the minimally invasive strategies that could facilitate an extensive translation to their clinical application.

  1. Thoracoscopic versus robotic approaches: advantages and disadvantages.

    Science.gov (United States)

    Wei, Benjamin; D'Amico, Thomas A

    2014-05-01

    The overall advantages of thoracoscopy over thoracotomy in terms of patient recovery have been fairly well established. The use of robotics, however, is a newer and less proven modality in the realm of thoracic surgery. Robotics offers distinct advantages and disadvantages in comparison with video-assisted thoracoscopic surgery. Robotic technology is now used for a variety of complex cardiac, urologic, and gynecologic procedures including mitral valve repair and microsurgical treatment of male infertility. This article addresses the potential benefits and limitations of using the robotic platform for the performance of a variety of thoracic operations. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Advantaged Bidders in Franchise Auctions

    OpenAIRE

    van den Berg, V.A.C.

    2012-01-01

    Consider a government that auctions a franchise for, e.g., an airport, telecommunication network, or utility. Consider an 'incumbent bidder' that owns a complement or substitute. With an auction on the transfer (i.e. payment) to the government, the incumbent is advantaged.If the government regulates the market with an auction on the price asked to consumers, it depends who is advantaged. With complements, the incumbent is advantaged: it can set a lower price on the new franchise, as this inc...

  3. Potential Clinical and Economic Impact of Switching Branded Medications to Generics

    Science.gov (United States)

    Straka, Robert J.; Keohane, Denis J.; Liu, Larry Z.

    2017-01-01

    Switching branded to generic medications has become a common cost-containment measure. Although this is an important objective for health care systems worldwide, the impact of this practice on patient outcomes needs to be carefully considered. We reviewed the literature summarizing the potential clinical and economic consequences of switching from branded to generic medications on patient outcomes. A literature search of peer-reviewed articles published 2003–2013 using key words of “generic switching” or “substitution” was conducted using PubMed, OvidSP, and ScienceDirect. Of 30 articles identified and reviewed, most were related to the diseases of the central nervous system, especially epilepsy. Based on our review, potential impacts of switching fell into 3 broad categories: patient attitudes and adherence, clinical and safety outcomes, and cost and resource utilization. Although in many cases generics may represent an appropriate alternative to branded products, this may not always be the case. Specifically, several studies suggested that switching may negatively impact medication adherence, whereas other studies found that generic switching was associated with poorer clinical outcomes and more adverse events. In some instances, switching accomplished cost savings but did so at increased total cost of care because of increased physician visits or hospitalizations. Although in many cases generics may represent an appropriate alternative, mandatory generic switching may lead to unintended consequences, especially in certain therapeutic areas. Although further study is warranted, based on our review, it may be medically justifiable for physicians and patients to retain the right to request the branded product in certain cases. PMID:26099048

  4. Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer's disease.

    Science.gov (United States)

    Goozee, K G; Shah, T M; Sohrabi, H R; Rainey-Smith, S R; Brown, B; Verdile, G; Martins, R N

    2016-02-14

    Curcumin derived from turmeric is well documented for its anti-carcinogenic, antioxidant and anti-inflammatory properties. Recent studies show that curcumin also possesses neuroprotective and cognitive-enhancing properties that may help delay or prevent neurodegenerative diseases, including Alzheimer's disease (AD). Currently, clinical diagnosis of AD is onerous, and it is primarily based on the exclusion of other causes of dementia. In addition, phase III clinical trials of potential treatments have mostly failed, leaving disease-modifying interventions elusive. AD can be characterised neuropathologically by the deposition of extracellular β amyloid (Aβ) plaques and intracellular accumulation of tau-containing neurofibrillary tangles. Disruptions in Aβ metabolism/clearance contribute to AD pathogenesis. In vitro studies have shown that Aβ metabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and the development of dementia, because of its antioxidant and anti-inflammatory properties, as well as its ability to influence Aβ metabolism. However, clinical studies of curcumin have revealed limited effects to date, most likely because of curcumin's relatively low solubility and bioavailability, and because of selection of cohorts with diagnosed AD, in whom there is already major neuropathology. However, the fresh approach of targeting early AD pathology (by treating healthy, pre-clinical and mild cognitive impairment-stage cohorts) combined with new curcumin formulations that increase bioavailability is renewing optimism concerning curcumin-based therapy. The aim of this paper is to review the current evidence supporting an association between curcumin and modulation of AD pathology, including in vitro and in vivo studies. We also review the use of curcumin in emerging retinal imaging technology, as a fluorochrome for AD diagnostics.

  5. Does cultural integration explain a mental health advantage for adolescents?

    Science.gov (United States)

    Bhui, Kamaldeep S; Lenguerrand, Erik; Maynard, Maria J; Stansfeld, Stephen A; Harding, Seeromanie

    2012-06-01

    A mental health advantage has been observed among adolescents in urban areas. This prospective study tests whether cultural integration measured by cross-cultural friendships explains a mental health advantage for adolescents. A prospective cohort of adolescents was recruited from 51 secondary schools in 10 London boroughs. Cultural identity was assessed by friendship choices within and across ethnic groups. Cultural integration is one of four categories of cultural identity. Using gender-specific linear-mixed models we tested whether cultural integration explained a mental health advantage, and whether gender and age were influential. Demographic and other relevant factors, such as ethnic group, socio-economic status, family structure, parenting styles and perceived racism were also measured and entered into the models. Mental health was measured by the Strengths and Difficulties Questionnaire as a 'total difficulties score' and by classification as a 'probable clinical case'. A total of 6643 pupils in first and second years of secondary school (ages 11-13 years) took part in the baseline survey (2003/04) and 4785 took part in the follow-up survey in 2005-06. Overall mental health improved with age, more so in male rather than female students. Cultural integration (friendships with own and other ethnic groups) was associated with the lowest levels of mental health problems especially among male students. This effect was sustained irrespective of age, ethnicity and other potential explanatory variables. There was a mental health advantage among specific ethnic groups: Black Caribbean and Black African male students (Nigerian/Ghanaian origin) and female Indian students. This was not fully explained by cultural integration, although cultural integration was independently associated with better mental health. Cultural integration was associated with better mental health, independent of the mental health advantage found among specific ethnic groups: Black Caribbean and

  6. Does cultural integration explain a mental health advantage for adolescents?

    Science.gov (United States)

    Bhui, Kamaldeep S; Lenguerrand, Erik; Maynard, Maria J; Stansfeld, Stephen A; Harding, Seeromanie

    2012-01-01

    Background A mental health advantage has been observed among adolescents in urban areas. This prospective study tests whether cultural integration measured by cross-cultural friendships explains a mental health advantage for adolescents. Methods A prospective cohort of adolescents was recruited from 51 secondary schools in 10 London boroughs. Cultural identity was assessed by friendship choices within and across ethnic groups. Cultural integration is one of four categories of cultural identity. Using gender-specific linear-mixed models we tested whether cultural integration explained a mental health advantage, and whether gender and age were influential. Demographic and other relevant factors, such as ethnic group, socio-economic status, family structure, parenting styles and perceived racism were also measured and entered into the models. Mental health was measured by the Strengths and Difficulties Questionnaire as a ‘total difficulties score’ and by classification as a ‘probable clinical case’. Results A total of 6643 pupils in first and second years of secondary school (ages 11–13 years) took part in the baseline survey (2003/04) and 4785 took part in the follow-up survey in 2005–06. Overall mental health improved with age, more so in male rather than female students. Cultural integration (friendships with own and other ethnic groups) was associated with the lowest levels of mental health problems especially among male students. This effect was sustained irrespective of age, ethnicity and other potential explanatory variables. There was a mental health advantage among specific ethnic groups: Black Caribbean and Black African male students (Nigerian/Ghanaian origin) and female Indian students. This was not fully explained by cultural integration, although cultural integration was independently associated with better mental health. Conclusions Cultural integration was associated with better mental health, independent of the mental health advantage

  7. Innovation strategies and competitive advantage

    OpenAIRE

    Gërguri, Shqipe; Rexhepi, Gadaf; Ramadani, Veland

    2013-01-01

    Companies today operate in a very dynamic, uncertain and competitive environment. They compete in "nicety" that are so small but so important. Companies are trying to achieve competitive advantage in order to help them obtain a better and a stable position in the marketplace. The best way for companies to achieve a competitive advantage is through innovation. This paper addresses the meaning of innovation what does innovation present, types of innovation specifically discussing the right way ...

  8. Perceived versus Actual Competitive Advantage

    OpenAIRE

    Langemeier, Michael R.; Yeager, Elizabeth

    2014-01-01

    This paper examined the relationship between farm characteristics and perceived sources of competitive advantage, and cost-based and revenue-based efficiency indices. Gross farm income and the percentage of labor devoted to crop production were significant and positively correlated with cost and revenue efficiency while the perception of the cowherd being the most important part of the operation was negatively correlated with efficiency. In general, perceived sources of competitive advantage ...

  9. Practical advantages of evolutionary computation

    Science.gov (United States)

    Fogel, David B.

    1997-10-01

    Evolutionary computation is becoming a common technique for solving difficult, real-world problems in industry, medicine, and defense. This paper reviews some of the practical advantages to using evolutionary algorithms as compared with classic methods of optimization or artificial intelligence. Specific advantages include the flexibility of the procedures, as well as their ability to self-adapt the search for optimum solutions on the fly. As desktop computers increase in speed, the application of evolutionary algorithms will become routine.

  10. Competitive advantage and corporate communications

    OpenAIRE

    Mitić Sanja; Ognjanov Galjina

    2013-01-01

    Strategic importance of corporate communications and its role in the development of competitive advantage has attracted interest of numerous researchers in the fields of organization, management, marketing and public relations. Recent studies particularly emphasise the growing importance of soft factors, such as reputation in the development of competitive advantage. Concept of reputation is strongly connected with stakeholder theory, which stresses the importance of corporate communications ...

  11. STRATEGIES FOR ACHIEVING COMPETITIVE ADVANTAGE

    OpenAIRE

    Jusuf ZEKIRI; Alexandru NEDELEA

    2011-01-01

    This paper is organized in three parts. A brief overview of the importance of strategies within companies, as well as literature review is presented along with traditional approaches on strategies for achieving competitive advantage, and new approaches for gaining a competitive advantage. The main objective of the paper is to outline and discuss the relevant issues and challenges from a theoretical viewpoint related with the possible strategy formulation of companies in order to achieve a com...

  12. Corporate Finance and Comparative Advantage

    OpenAIRE

    Peter Egger; Christian Keuschnigg

    2009-01-01

    Since innovative firms are often financially constrained, access to external funds is important for the expansion of innovative industries. This paper reports four important results. First, comparative advantage is shaped by factor endowments as well as fundamental determinants of corporate finance. In particular, a larger equity ratio of firms and tough governance standards relax finance constraints and create a comparative advantage in innovative industries. Second, factor price equalizatio...

  13. Long-term potentiation and long-term depression: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Timothy V.P. Bliss

    2011-01-01

    Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

  14. Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications.

    Science.gov (United States)

    Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs

    2017-10-01

    Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.

  15. The treatment of Alzheimer's disease using Chinese medicinal plants: from disease models to potential clinical applications.

    Science.gov (United States)

    Su, Yang; Wang, Qiuhong; Wang, Changfu; Chan, Kelvin; Sun, Yanping; Kuang, Haixue

    2014-03-28

    Alzheimer's disease (AD) is characterized by the sustained higher nervous disorders of the activities and functions of the brain. Due to its heavy burden on society and the patients' families, it is urgent to review the treatments for AD to provide basic data for further research and new drug development. Among these treatments, Chinese Material Medica (CMM) has been traditionally clinical used in China to treat AD for a long time with obvious efficacy. With the further research reports of CMM, new therapeutic materials may be recovered from troves of CMM. However, So far, little or no review work has been reported to conclude anti-AD drugs from CMM in literature. Therefore, a systematic introduction of CMM anti-AD research progress is of great importance and necessity. This paper strives to systematically describe the progress of CMM in the treatment of AD, and lays a basis data for anti-AD drug development from CMM, and provides the essential theoretical support for the further development and utilization of CMM resources through a more comprehensive research of the variety of databases regarding CMM anti-AD effects reports. Literature survey was performed via electronic search (SciFinder®, Pubmed®, Google Scholar and Web of Science) on papers and patents and by systematic research in ethnopharmacological literature at various university libraries. This review mainly introduces the current research on the Chinese Material Medica (CMM) theoretical research on Alzheimer's disease (AD), anti-AD active constituent of CMM, anti-AD effects on AD models, anti-AD mechanism of CMM, and anti-AD effect of CMM formula. Scholars around the world have made studies on the anti-AD molecular mechanism of CMM from different pathways, and have made substantial progress. The progress not only enriched the anti-AD theory of CMM, but also provided clinical practical significance and development prospects in using CMM to treat AD. Western pure drugs cannot replace the advantages of

  16. Framing the research agenda for sickle cell trait: building on the current understanding of clinical events and their potential implications.

    Science.gov (United States)

    Goldsmith, Jonathan C; Bonham, Vence L; Joiner, Clinton H; Kato, Gregory J; Noonan, Allan S; Steinberg, Martin H

    2012-03-01

    Sickle Cell Trait (HbAS), the heterozygous state for the sickle hemoglobin beta globin gene is carried by as many as 100 million individuals including up to 25% of the population in some regions of the world (World Health Organization, Provisional agenda item 4.8, EB117/34 (22 December 2005) or World Health Organization, Provisional agenda item 11.4 (24 April 2006)). Persons with HbAS have some resistance to falciparum malaria infection in early childhood (Piel FB, Patil AP, Howes RE, et al., Nat Commun 2010;1104:1-7 and Aidoo M, Terlouw DJ, Kolczak M, et al., Lancet 2002;359:1311-1312) and as a result individuals with HbAS living in malarial endemic regions of Africa have a survival advantage over individuals with HbAA. Reports from the US emphasize possible health risks for individuals with HbAS including increased incidence of renal failure and malignancy, thromboembolic disorders, splenic infarction as a high altitude complication, and exercise-related sudden death. The National Heart, Lung, and Blood Institute, National Institutes of Health convened a workshop in Bethesda, Maryland on June 3-4, 2010, Framing the Research Agenda for Sickle Cell Trait, to review the clinical manifestations of HbAS, discuss the exercise-related sudden death reports in HbAS, and examine the public health, societal, and ethical implications of policies regarding HbAS. The goal of the workshop was to identify potential research questions to address knowledge gaps.

  17. Food irradiation: advantages and limitations

    International Nuclear Information System (INIS)

    Hernandes, N.K.; Vital, H. de C.; Sabaa-Srur, A.U.O.

    2003-01-01

    Food irradiation is a physical method of processing food (e.g. freezing, canning). It has been thoroughly researched over the last four decades and is recognized as a safe and wholesome method. It has the potential both of disinfesting dried food to reduce storage losses and disinfesting fruits and vegetables to meet quarantine requirements for export trade. Low doses of irradiation inhibit spoilage losses due to sprouting of root and tuber crops. Food- borne diseases due to contamination by pathogenic microorganisms and parasites of meat, poultry, fish, fishery products and spices are on the increase. Irradiation of these solid foods can decontaminate them of pathogenic organisms and thus provide safe food to the consumer. Irradiation can successfully replace the fumigation treatment of cocoa beans and coffee beans and disinfest dried fish, dates, dried fruits, etc. One of the most important advantages of food irradiation processing is that it is a coldprocess which does not significantly alter physico-chemical characters of the treated product. It can be applied to food after its final packaging. Similar to other physical processes of food processing, (e.g. canning, freezing), irradiation is a capital intensive process. Thus, adequate product volume must be made available in order to maximize the use of the facility and minimize the unit cost of treatment. Lack of harmonization of regulations among the countries which have approved irradiated foods hampers the introduction of this technique for international trade. Action at the international level has to be taken in order to remedy this situation. One of the important limitations of food irradiation processing is its slow acceptance by consumers, due inter alia to a perceived association with radioactivity. The food industry tends to be reluctant to use the technology in view of uncertainties regarding consumer acceptance of treated foods. Several market testing and consumer acceptance studies have been carried

  18. Using integration technology as a strategic advantage.

    Science.gov (United States)

    Fry, P A

    1993-08-01

    The underlying premise of the Managed Competition Act previously cited is that through managed competition providers will be forced to lower care costs while increasing the level of positive care outcomes. Because it may also be that tomorrow's hospitals will find a severe rationing of technology, what can they do to prepare? Most of the systems in place today already have built within them all the necessary potential to address this premise and technology requirement with no change, no conversion, no expense for new equipment and software, and no disruption in day-to-day operations, just a little re-engineering. Today, however, these systems are similar to a 20-mule team pulling in different directions: all the power is there, but the wagon remains motionless and totally unable to reach its objective. It takes a skilled wagonmaster to bring them together, to make the mules work as a cohesive unit, to make the power of 20 mules greater than the sum of 20 mules. So it is and will be for the hospital of tomorrow. System integration is no longer a question of whether but of when. Those hospitals that use it today as a strategic advantage will be in a better position tomorrow to use it as a competitive strategic advantage in an environment that will reward low cost and high positive care outcomes and will penalize those that cannot compete. The technology is already here and economically within reach of nearly every hospital, just waiting to be used. The question that must nag all of us who want to make the health care system of America better is, Why not make the when now? Rich Helppie, president of Superior Consultant Company, summarized the solution well: The old ways will not give way to the new overnight. The re-engineering process in healthcare must evolve. Compared to the last 20 years, however, such evolution may appear to be a massive, forthright, complete, comprehensive, drastic and rapid revolution. Survival is the name of the game, and for healthcare

  19. Potential role of a pharmacist to enhance medication-related aspects of clinical trials conducted in a dedicated clinical research unit

    Directory of Open Access Journals (Sweden)

    Kimberly A. Redic, PharmD

    2017-06-01

    Conclusions: This pilot study showed potential roles for pharmacy personnel involvement in medication reconciliation in the clinical research setting. Pharmacists have the opportunity to ensure that IDs are accurately included in patient medication lists and to identify the use of potential protocol prohibited concomitant medications.

  20. Miscellaneous conditions of the shoulder: Anatomical, clinical, and pictorial review emphasizing potential pitfalls in imaging diagnosis

    International Nuclear Information System (INIS)

    Farid, Nikdokht; Bruce, Dean; Chung, Christine B.

    2008-01-01

    The purpose of this article is to review the key imaging findings in major categories of pathology affecting the shoulder joint including hydroxyapatite deposition disease, rotator cuff interval pathology, acromioclavicular joint pathology, glenohumeral osteoarthrosis, and synovial inflammatory processes, with specific emphasis on findings that have associated pitfalls in imaging diagnosis. The pathophysiology and clinical manifestations of the above mentioned categories of pathology will be reviewed, followed in each section by a detailed pictorial review of the key imaging findings in each category including plain film, computed tomography, and magnetic resonance imaging findings as applicable. Imaging challenges that relate to both diagnosis and characterization will be addressed with each type of pathology. The goal is that after reading this article, the reader will be able to recognize the key imaging findings in major categories of pathology affecting the shoulder joint and will become familiar with the potential pitfalls in their imaging diagnosis

  1. Miscellaneous conditions of the shoulder: Anatomical, clinical, and pictorial review emphasizing potential pitfalls in imaging diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Farid, Nikdokht [University of California San Diego, Department of Radiology, 200 West Arbor Drive, San Diego, CA 92103 (United States); VA Healthcare System San Diego, Department of Radiology, 3350 La Jolla Village Drive, La Jolla, CA 92161 (United States); Bruce, Dean [University of California San Diego, Department of Radiology, 200 West Arbor Drive, San Diego, CA 92103 (United States); VA Healthcare System San Diego, Department of Radiology, 3350 La Jolla Village Drive, La Jolla, CA 92161 (United States); University of Alberta, Edmonton, Alberta (Canada); Chung, Christine B. [University of California San Diego, Department of Radiology, 200 West Arbor Drive, San Diego, CA 92103 (United States); VA Healthcare System San Diego, Department of Radiology, 3350 La Jolla Village Drive, La Jolla, CA 92161 (United States)], E-mail: cbchung@ucsd.edu

    2008-10-15

    The purpose of this article is to review the key imaging findings in major categories of pathology affecting the shoulder joint including hydroxyapatite deposition disease, rotator cuff interval pathology, acromioclavicular joint pathology, glenohumeral osteoarthrosis, and synovial inflammatory processes, with specific emphasis on findings that have associated pitfalls in imaging diagnosis. The pathophysiology and clinical manifestations of the above mentioned categories of pathology will be reviewed, followed in each section by a detailed pictorial review of the key imaging findings in each category including plain film, computed tomography, and magnetic resonance imaging findings as applicable. Imaging challenges that relate to both diagnosis and characterization will be addressed with each type of pathology. The goal is that after reading this article, the reader will be able to recognize the key imaging findings in major categories of pathology affecting the shoulder joint and will become familiar with the potential pitfalls in their imaging diagnosis.

  2. Diffusion and Perfusion MR Imaging in Acute Stroke: Clinical Utility and Potential Limitations for Treatment Selection

    DEFF Research Database (Denmark)

    Bateman, Mathew; Slater, Lee-Anne; Leslie-Mazwi, Thabele M

    2017-01-01

    Magnetic resonance (MR) diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) offer unique insight into acute ischemic stroke pathophysiology. These techniques may offer the ability to apply pathophysiology to accurately individualize acute stroke reperfusion treatment, including ...... to be investigated in ongoing randomized controlled trials, and continued research into these techniques will help achieve the goal of tissue-based decision making and individualized acute stroke treatment....... extending the opportunity of reperfusion treatment to well beyond the current time-based treatment windows. This review examines the use of DWI and PWI in the major stroke trials, their current clinical utility, and potential limitations for reperfusion treatment selection. DWI and PWI continue...

  3. Controversies surrounding the clinical potential of cinnamon for the management of diabetes.

    Science.gov (United States)

    Rafehi, H; Ververis, K; Karagiannis, T C

    2012-06-01

    Obesity levels have increased significantly in the past five decades and are predicted to continue rising, resulting in important health implications. In particular, this has translated to an increase in the occurrence of type II diabetes mellitus (T2D). To alleviate associated problems, certain nutraceuticals have been considered as potential adjuncts or alternatives to conventional prescription drugs. Cinnamon, a commonly consumed spice originating from South East Asia, is currently being investigated as a potential preventative supplement and treatment for insulin resistance, metabolic syndrome and T2D. Extensive in vitro evidence has shown that cinnamon may improve insulin resistance by preventing and reversing impairments in insulin signalling in skeletal muscle. In adipose tissue, it has been shown that cinnamon increases the expression of peroxisome proliferator-activated receptors including, PPARγ. This is comparable to the action of commonly used thiazolinediones, which are PPAR agonists. Studies have also shown that cinnamon has potent anti-inflammatory properties. However, numerous human clinical trials with cinnamon have been conducted with varying findings. While some studies have showed no beneficial effect, others have indicated improvements in cholesterol levels, systolic blood pressure, insulin sensitivity and postprandial glucose levels with cinnamon. However, the only measurement consistently improved by cinnamon consumption is fasting glucose levels. While it is still premature to suggest the use of cinnamon supplementation based on the evidence, further investigation into mechanisms of action is warranted. Apart from further characterization of genetic and epigenetic changes in model systems, systematic large-scale clinical trials are required. In this study, we discuss the mechanisms of action of cinnamon in the context of T2D and we highlight some of the associated controversies. © 2011 Blackwell Publishing Ltd.

  4. Transforming Experience: The Potential of Augmented Reality and Virtual Reality for Enhancing Personal and Clinical Change.

    Science.gov (United States)

    Riva, Giuseppe; Baños, Rosa M; Botella, Cristina; Mantovani, Fabrizia; Gaggioli, Andrea

    2016-01-01

    During life, many personal changes occur. These include changing house, school, work, and even friends and partners. However, the daily experience shows clearly that, in some situations, subjects are unable to change even if they want to. The recent advances in psychology and neuroscience are now providing a better view of personal change, the change affecting our assumptive world: (a) the focus of personal change is reducing the distance between self and reality (conflict); (b) this reduction is achieved through (1) an intense focus on the particular experience creating the conflict or (2) an internal or external reorganization of this experience; (c) personal change requires a progression through a series of different stages that however happen in discontinuous and non-linear ways; and (d) clinical psychology is often used to facilitate personal change when subjects are unable to move forward. Starting from these premises, the aim of this paper is to review the potential of virtuality for enhancing the processes of personal and clinical change. First, the paper focuses on the two leading virtual technologies - augmented reality (AR) and virtual reality (VR) - exploring their current uses in behavioral health and the outcomes of the 28 available systematic reviews and meta-analyses. Then the paper discusses the added value provided by VR and AR in transforming our external experience by focusing on the high level of personal efficacy and self-reflectiveness generated by their sense of presence and emotional engagement. Finally, it outlines the potential future use of virtuality for transforming our inner experience by structuring, altering, and/or replacing our bodily self-consciousness. The final outcome may be a new generation of transformative experiences that provide knowledge that is epistemically inaccessible to the individual until he or she has that experience, while at the same time transforming the individual's worldview.

  5. Transforming Experience: The Potential of Augmented Reality and Virtual Reality for Enhancing Personal and Clinical Change

    Directory of Open Access Journals (Sweden)

    Giuseppe Riva

    2016-09-01

    Full Text Available During our life we undergo many personal changes: we change our house, our school, our work and even our friends and partners. However, our daily experience shows clearly that in some situations subjects are unable to change even if they want to. The recent advances in psychology and neuroscience are now providing a better view of personal change, the change affecting our assumptive world: a the focus of personal change is reducing the distance between self and reality (conflict; b this reduction is achieved through (1 an intense focus on the particular experience creating the conflict or (2 an internal or external reorganization of this experience; c personal change requires a progression through a series of different stages; d clinical psychology is often used to facilitate personal change when subjects are unable to move forward. Starting from these premises, the aim of this paper is to review the potential of virtuality for enhancing the processes of personal and clinical change. First, the paper will focus on the two leading virtual technologies – Augmented Reality (AR and Virtual Reality (VR – exploring their current uses in behavioral health and the outcomes of the 28 available systematic reviews and meta-analyses. Then the paper discusses the added value provided by VR and AR in transforming our external experience, by focusing on the high level of self-reflectiveness and personal efficacy induced by their emotional engagement and sense of presence. Finally, it outlines the potential future use of virtuality for transforming our inner experience by structuring, altering and/or replacing our bodily self-consciousness. The final outcome may be a new generation of transformative experiences that provide knowledge that is epistemically inaccessible to the individual until he or she has that experience, while at the same time transforming the individual’s worldview.

  6. Clinical potential of regulatory T cell therapy in liver diseases: An overview and current perspectives

    Directory of Open Access Journals (Sweden)

    Hannah Claire Jeffery

    2016-09-01

    Full Text Available The increasing demand for liver transplantation and the decline in donor organs has highlighted the need for alternative novel therapies to prevent chronic active hepatitis, which eventually leads to liver cirrhosis and liver cancer. Liver histology of chronic hepatitis is composed of both effector and regulatory lymphocytes. The human liver contains different subsets of effector lymphocytes, that are kept in check by a subpopulation of T cells known as Regulatory T cells (Treg. The balance of effector and regulatory lymphocytes generally determines the outcome of hepatic inflammation: resolution, fulminant hepatitis or chronic active hepatitis. Thus, maintaining and adjusting this balance is crucial in immunological manipulation of liver diseases. One of the options to restore this balance is to enrich Treg in the liver disease patients.Advances in the knowledge of Treg biology and development of clinical grade isolation reagents, cell sorting equipment and Good Manufacturing Practice (GMP facilities have paved the way to apply Treg cells as a potential therapy to restore peripheral self-tolerance in autoimmune liver diseases, chronic rejection and post-transplantation. Past and on-going studies have applied Treg in type-1 diabetes mellitus, systemic lupus erythematosus, graft versus host diseases (GVHD and solid organ transplantations. There have not been any new therapies for the autoimmune liver diseases for more than three decades; thus the clinical potential for the application of autologous Treg cell therapy to treat autoimmune liver disease is an attractive and novel option. However, it is fundamental to understand the deep immunology, genetic profiles, biology, homing behavior and microenvironment of Treg before applying the cells to the patients.

  7. Hepatocellular carcinoma displays distinct DNA methylation signatures with potential as clinical predictors.

    Directory of Open Access Journals (Sweden)

    Hector Hernandez-Vargas

    Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is characterized by late detection and fast progression, and it is believed that epigenetic disruption may be the cause of its molecular and clinicopathological heterogeneity. A better understanding of the global deregulation of methylation states and how they correlate with disease progression will aid in the design of strategies for earlier detection and better therapeutic decisions. METHODS AND FINDINGS: We characterized the changes in promoter methylation in a series of 30 HCC tumors and their respective surrounding tissue and identified methylation signatures associated with major risk factors and clinical correlates. A wide panel of cancer-related gene promoters was analyzed using Illumina bead array technology, and CpG sites were then selected according to their ability to classify clinicopathological parameters. An independent series of HCC tumors and matched surrounding tissue was used for validation of the signatures. We were able to develop and validate a signature of methylation in HCC. This signature distinguished HCC from surrounding tissue and from other tumor types, and was independent of risk factors. However, aberrant methylation of an independent subset of promoters was associated with tumor progression and etiological risk factors (HBV or HCV infection and alcohol consumption. Interestingly, distinct methylation of an independent panel of gene promoters was strongly correlated with survival after cancer therapy. CONCLUSION: Our study shows that HCC tumors exhibit specific DNA methylation signatures associated with major risk factors and tumor progression stage, with potential clinical applications in diagnosis and prognosis.

  8. Potentially three distinct roles for hypoxic cell sensitizers in the clinic

    International Nuclear Information System (INIS)

    Chapman, J.D.; Raleigh, J.A.; Pedersen, J.E.; Ngan, J.; Shum, F.Y.

    1979-01-01

    Nitroaromatic drugs have been applied to radiation therapy on the basis of their effectiveness to enhance radiation damages selectively in hypoxic mammalian cells at nontoxic concentration. Such sensitizers could improve the rate of local tumor control by conventional radiotherapy in such cases that the resistance due to hypoxia in a limiting factor. The selective cytotoxicity of the drug to hypoxic cells is the second distinct action. A third potential role for nitroaromatic drugs could involve their use for the diagnosis of the number and location of hypoxic cells within tumors. The gain in therapeutic ratio by a factor from 5 to 10 is necessary before the full clinical impact of hypoxic cell radiosensitizers can be evaluated. The drugs selected for the use as clinical radiosensitizers were originally developed as the antibacterial agents with selective activity against anaerobes. The hypoxic cells in tumors are usually resistant to chemotherapy as well as resistant to radiation, and this specific drug action of sensitizers combined with that of an agent effective against oxygenated and cycling cells could possibly produce improved tumor cures. Electron-affinitive chemicals become selectively bound to the macromolecules of hypoxic mammalian cells by radiation-induced chemical reaction. This technique was used to identify by autoradiographic procedures the location of the radioactive nitrofurazone bound to hypoxic cells within multicellular spheroids. (Yamashita, S.)

  9. Automation of the consensus guidelines in diabetes care: potential impact on clinical inertia.

    Science.gov (United States)

    Albisser, A Michael; Inhaber, Francine

    2010-01-01

    To propose that automation of the consensus guidelines and mandated targets (CG&MT) in glycemia, hemoglobin A1c, and body weight will facilitate optimal clinical management of patients with diabetes. (1) A simplified method for capturing diabetes outcomes at home was devised, (2) relevant portions of the CG&MT were translated into computer code and automated, and (3) algorithms were applied to transform data from self-monitoring of blood glucose into circadian profiles and hemoglobin A1c levels. (4) The resulting procedures were integrated into a USB memory drive for use by health-care providers at the point of care. For input from patients, a simple form is used to capture data on diabetes outcomes, including blood glucose measurements before and after meals and at bedtime, medication, and lifestyle events in a structured fashion. At each encounter with a health-care provider, the patient's data are transferred into the device and become available to assist in identifying deviations from mandated targets, potential risks of hypoglycemia, and necessary prescription changes. Preliminary observations during a 2 1/2-year period from a community support group dedicated to glycemic control on 20 unselected patients (10 with and 10 without use of the device) are summarized. With use of the automated information, the health professional is supported at the point of care to achieve better, safer outcomes and practice evidence-based medicine entirely in lockstep with the CG&MT. This automation helps to overcome clinical inertia.

  10. Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges.

    Science.gov (United States)

    McKenna, Dennis J

    2004-05-01

    Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results from inhibition of monoamine oxidase (MAO) by beta-carboline alkaloids. MAO is the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it is used as a sacrament by several syncretic churches. Some of these organizations have incorporated in the United States. The recreational and religious use of ayahuasca in the United States, as well as "ayahuasca tourism" in the Amazon, is increasing. The current legal status of ayahuasca or its source plants in the United States is unclear, although DMT is a Schedule I controlled substance. One ayahuasca church has received favorable rulings in 2 federal courts in response to its petition to the Department of Justice for the right to use ayahuasca under the Religious Freedom Restoration Act. A biomedical study of one of the churches, the Uñiao do Vegetal (UDV), indicated that ayahuasca may have therapeutic applications for the treatment of alcoholism, substance abuse, and possibly other disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca can be used safely in normal healthy adults, but have done little to clarify its potential therapeutic uses. Because of ayahuasca's ill-defined legal status and variable botanical and chemical composition, clinical investigations in the United States, ideally under an approved Investigational New Drug (IND) protocol, are complicated by both regulatory and methodological issues. This article provides an overview of ayahuasca and discusses some of the challenges that must be overcome before it can be clinically investigated in the United States.

  11. Potential facilitators and barriers to adopting standard treatment guidelines in clinical practice.

    Science.gov (United States)

    Sharma, Sangeeta; Pandit, Ajay; Tabassum, Fauzia

    2017-04-18

    Purpose The purpose of this paper is to assess medicines information sources accessed by clinicians, if sources differed in theory and practice and to find out the barriers and facilitators to effective guideline adoption. Design/methodology/approach In all, 183 doctors were surveyed. Barriers and facilitators were classified as: communication; potential adopters; innovation; organization characteristics and environmental/social/economic context. Findings Most of the clinicians accessed multiple information sources including standard treatment guidelines, but also consulted seniors/colleagues in practice. The top three factors influencing clinical practice guideline adoption were innovation characteristics, environmental context and individual characteristics. The respondents differed in the following areas: concerns about flexibility offered by the guideline; denying patients' individuality; professional autonomy; insights into gaps in current practice and evidence-based practice; changing practices with little or no benefit. Barriers included negative staff attitudes/beliefs, guideline integration into organizational structures/processes, time/resource constraints. Fearing third parties (government and insurance companies) restricting medicines reimbursement and poor liability protection offered by the guidelines emerged as the barriers. Facilitators include aligning organizational structures/processes with the innovation; providing leadership support to guide diffusion; increasing awareness and enabling early innovation during pre/in-service training, with regular feedback on outcomes and use. Practical implications Guideline adoption in clinical practice is partly within doctors' control. There are other key prevailing factors in the local context such as environmental, social context, professional and organizational culture affecting its adoption. Organizational policy and accreditation standards necessitating adherence can serve as a driver. Originality

  12. Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Kim Y

    2012-08-01

    insulin, and as a monotherapy for metformin-intolerant patients. Clinical research also remains to be carried out on the long-term effects of glucosuria and other potential effects of SGLT2 inhibitors, especially in view of the observed increase in the incidence of bladder and breast cancer. SGLT2 inhibitors represent a promising approach for the treatment of diabetes, and could potentially be an addition to existing therapies.Keywords: sodium-glucose cotransporter type 2, SGLT2, inhibitors, kidney, glucosuria, oral diabetes agent, weight loss

  13. Potential clinical and economic effects of homocyst(e)ine lowering.

    Science.gov (United States)

    Nallamothu, B K; Fendrick, A M; Rubenfire, M; Saint, S; Bandekar, R R; Omenn, G S

    Elevated total homocyst(e)ine levels (>/=11 micromol/L) have been identified as a potential risk factor for coronary heart disease. However, the benefits expected from lowering homocyst(e)ine levels with folic acid and vitamin B(12) supplementation have yet to be demonstrated in clinical trials. We constructed a decision analytic model to estimate the clinical benefits and economic costs of 2 homocyst(e)ine-lowering strategies: (1) "treat all"-no screening, daily supplementation with folic acid (400 microg) and vitamin B(12) (cyanocobalamin; 500 microg) for all; (2) "screen and treat"-screening, followed by daily supplementation with folic acid and vitamin B(12) for individuals with elevated homocyst(e)ine levels. Simulated cohorts of 40-year-old men and 50-year-old women in the general population were evaluated. In the base-case analysis, we assumed that lowering elevated levels would reduce excess coronary heart disease risk by 40%; however, this assumption and others were evaluated across a broad range of potential values using sensitivity analysis. Primary outcomes were discounted costs per life-year saved. Although the treat-all strategy was slightly more effective overall, the screen and treat strategy resulted in a much lower cost per life-year saved ($13,600 in men and $27,500 in women) when compared with no intervention. Incremental cost-effectiveness ratios for the treat-all strategy compared with the screen and treat strategy were more than $500,000 per life-year saved in both cohorts. Sensitivity analysis showed that cost-effectiveness ratios for the screen and treat strategy remained less than $50,000 per life-year saved under several unfavorable scenarios, such as when effective homocyst(e)ine lowering was assumed to reduce the relative risk of coronary heart disease-related death by only 11% in men or 23% in women. Homocyst(e)ine lowering with folic acid and vitamin B(12) supplementation could result in substantial clinical benefits at reasonable

  14. A novel design for randomized immuno-oncology clinical trials with potentially delayed treatment effects

    Directory of Open Access Journals (Sweden)

    Pei He

    2015-10-01

    Full Text Available The semi-parametric proportional hazards model is widely adopted in randomized clinical trials with time-to-event outcomes, and the log-rank test is frequently used to detect a potential treatment effect. Immuno-oncology therapies pose unique challenges to the design of a trial as the treatment effect may be delayed, which violates the proportional hazards assumption, and the log-rank test has been shown to markedly lose power under the non-proportional hazards setting. A novel design and analysis approach for immuno-oncology trials is proposed through a piecewise treatment effect function, which is capable of detecting a potentially delayed treatment effect. The number of events required for the trial will be determined to ensure sufficient power for both the overall log-rank test without a delayed effect and the test beyond the delayed period when such a delay exists. The existence of a treatment delay is determined by a likelihood ratio test with resampling. Numerical results show that the proposed design adequately controls the Type I error rate, has a minimal loss in power under the proportional hazards setting and is markedly more powerful than the log-rank test with a delayed treatment effect.

  15. Clinically targeted screening for congenital CMV - potential for integration into the National Hearing Screening Programme.

    Science.gov (United States)

    Kadambari, S; Luck, S; Davis, A; Williams, Ej; Berrington, J; Griffiths, Pd; Sharland, M

    2013-10-01

    Screening for a condition should only be undertaken if certain strict criteria are met. Congenital CMV (cCMV) is a leading cause of sensorineuronal hearing loss (SNHL) and meets many of these criteria, but is not currently screened for in the UK. Ganciclovir reduces CMV-induced progressive SNHL if treatment is begun in the first month of life. The Newborn Hearing Screening Programme (NHSP) has been shown to identify SNHL at the earliest possible age. The potential of integrating screening for cCMV into the NHSP is discussed to consolidate the link between screening, early diagnosis and management. The early diagnosis and treatment of cCMV may prevent a small proportion of late SNHL. In the absence of any screening programme, we provide evidence that clinically targeted screening through the NHSP is a potential option in the UK, enhancing the diagnostic pathway and enabling appropriate early treatment to reduce long-term morbidity. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  16. Emerging treatments for advanced pancreatic cancer: clinical potential of albumin-bound paclitaxel

    Directory of Open Access Journals (Sweden)

    Fontana E

    2014-06-01

    Full Text Available Elisa Fontana, Francesco Sclafani, David Cunningham Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK Abstract: The management of pancreatic cancer has historically represented a major challenge for oncologists. The inherent aggressiveness of this tumor and the fibrotic features of the surrounding stromal tissue have significantly limited the impact of standard chemotherapy. Moreover, the paucity of available tumor tissue has hampered a better understanding of the biology of this disease as well as the development of new treatment strategies. Recently, the therapeutic landscape of metastatic pancreatic cancer has been enriched by two new combination regimens (FOLFIRINOX and gemcitabine-nab-paclitaxel which have been demonstrated to improve the outcome in patients with good performance status. Moreover, the peritumoral stroma has been increasingly recognized as a potential therapeutic target for this disease, and several new agents targeting stromal components are currently under investigation. In this paper, we review the current treatment options for advanced pancreatic cancer, highlight the role of the peritumoral stroma, and discuss the clinical potential of nab-paclitaxel and antistromal treatment strategies. Keywords: pancreatic cancer, nab-paclitaxel, stroma, SPARC

  17. Antimicrobial Potential of Momordica charantia L. against Multiresistant Standard Species and Clinical Isolates.

    Science.gov (United States)

    Lucena Filho, José Hardman Sátiro de; Lima, Rennaly de Freitas; Medeiros, Ana Claudia Dantas de; Pereira, Jozinete Vieira; Granville-Garcia, Ana Flávia; Costa, Edja Maria Melo de Brito

    2015-11-01

    The aim of the present study was to evaluate the antibacterial and antifungal potential in vitro of Momordica charantia L. against the microorganisms of clinical interest (standard strains and multiresistant isolates) in order to aggregate scientific information in relation to its use as a therapeutic product. M. charantia L. plant material was acquired in municipality of Malta, Paraiba, Brazil. The extract was obtained through maceration, filtration and then concentrated under reduced pressure in a rotary evaporator, resulting in a dough, and was then dried in an oven for 72 hours at 40°C. Antimicrobial action of ethanolic extract of seed M. charantia L. was evaluated based on the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC) against standard strains of bacteria, isolates multiresistant bacteria and Candida species, by microdilution in broth method. All organisms were sensitive to the extract, being considered strong antimicrobial activity (MIC and MBC/MFC charantia L. showed strong antimicrobial potential, with bactericidal and fungicidal profile, there is the prospect to constitute a new therapeutic strategy for the control of infections, particularly in multiresistant strains. The use of medicinal plants in treatment of infectious processes have an important function nowadays, due to the limitations of the use of synthetic antibiotics available, related specifically to the microbial resistance emergence.

  18. Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 2: Optimizing the Design of Human Abuse Potential Studies.

    Science.gov (United States)

    Sellers, Edward M

    2018-04-01

    This article discusses the conduct of a human abuse potential study as outlined in the Food and Drug Administration Final Guidance to Industry on Assessment of Abuse Potential. In addition, areas where alternative approaches should be considered are proposed. The design, end points, conduct, and interpretation of the human abuse potential study were reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk and expedite drug development. The guidance is based on regulatory needs and current scientific practices. However, the reliability and utility of such studies can be improved with better subject selection, data collection, standardization of data collection and staff training, and a better understanding of the measurement properties of the dependent measures. The guidance provides a useful framework for conduct of human abuse potential studies. However, design assumptions, poor choice of end points, failure to consider alternate approaches, and limited experience with interpretation can result in an inadequate study or one that does not fairly represent the abuse potential of a new chemical entity. Methodologic development is needed to strengthen the regulatory framework. The Food and Drug Administration or the National Institutes on Drug Abuse could take a targeted initiative to encourage this work.

  19. Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

    Directory of Open Access Journals (Sweden)

    Monica Marzagalli

    2016-10-01

    Full Text Available Cutaneous melanoma is an aggressive tumor with its incidence increasing faster than any other cancer in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies.Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ER and ERβ that exert opposite effects on cancer growth: ER is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant estrogen receptor in melanoma and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation. However, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention

  20. Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

    Science.gov (United States)

    Marzagalli, Monica; Montagnani Marelli, Marina; Casati, Lavinia; Fontana, Fabrizio; Moretti, Roberta Manuela; Limonta, Patrizia

    2016-01-01

    Cutaneous melanoma is an aggressive tumor; its incidence has been reported to increase fast in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies. Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females, and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ERα and ERβ) that affect cancer growth in an opposite way: ERα is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant ER in melanoma, and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation; however, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF) mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention. Natural compounds that specifically bind to

  1. How to Achieve a Competitive Advantage

    OpenAIRE

    Adina Musetescu

    2013-01-01

    In order to succeed in any market a company has to decide which strategy is more appropriate to use, which means identifying the sources of a potential competitive advantage such as skills or resources. Superior skills in creating a special product can represent the element that is setting the company apart from its competitors. That is easily translated into a very good quality of the products. The resources of the company refer to the great number of retailers (a good distribution chain tha...

  2. Transnasal endoscopy: Technical considerations, advantages and limitations.

    Science.gov (United States)

    Atar, Mustafa; Kadayifci, Abdurrahman

    2014-02-16

    Transnasal endoscopy (TNE) is an upper endoscopy method which is performed by the nasal route using a thin endoscope less than 6 mm in diameter. The primary goal of this method is to improve patient tolerance and convenience of the procedure. TNE can be performed without sedation and thus eliminates the risks associated with general anesthesia. In this way, TNE decreases the cost and total duration of endoscopic procedures, while maintaining the image quality of standard caliber endoscopes, providing good results for diagnostic purposes. However, the small working channel of the ultra-thin endoscope used for TNE makes it difficult to use for therapeutic procedures except in certain conditions which require a thinner endoscope. Biopsy is possible with special forceps less than 2 mm in diameter. Recently, TNE has been used for screening endoscopy in Far East Asia, including Japan. In most controlled studies, TNE was found to have better patient tolerance when compared to unsedated endoscopy. Nasal pain is the most significant symptom associated with endoscopic procedures but can be reduced with nasal pretreatment. Despite the potential advantage of TNE, it is not common in Western countries, usually due to a lack of training in the technique and a lack of awareness of its potential advantages. This paper briefly reviews the technical considerations as well as the potential advantages and limitations of TNE with ultra-thin scopes.

  3. Transnasal endoscopy: Technical considerations, advantages and limitations

    Science.gov (United States)

    Atar, Mustafa; Kadayifci, Abdurrahman

    2014-01-01

    Transnasal endoscopy (TNE) is an upper endoscopy method which is performed by the nasal route using a thin endoscope less than 6 mm in diameter. The primary goal of this method is to improve patient tolerance and convenience of the procedure. TNE can be performed without sedation and thus eliminates the risks associated with general anesthesia. In this way, TNE decreases the cost and total duration of endoscopic procedures, while maintaining the image quality of standard caliber endoscopes, providing good results for diagnostic purposes. However, the small working channel of the ultra-thin endoscope used for TNE makes it difficult to use for therapeutic procedures except in certain conditions which require a thinner endoscope. Biopsy is possible with special forceps less than 2 mm in diameter. Recently, TNE has been used for screening endoscopy in Far East Asia, including Japan. In most controlled studies, TNE was found to have better patient tolerance when compared to unsedated endoscopy. Nasal pain is the most significant symptom associated with endoscopic procedures but can be reduced with nasal pretreatment. Despite the potential advantage of TNE, it is not common in Western countries, usually due to a lack of training in the technique and a lack of awareness of its potential advantages. This paper briefly reviews the technical considerations as well as the potential advantages and limitations of TNE with ultra-thin scopes. PMID:24567791

  4. Energy Advantages for Green Schools

    Science.gov (United States)

    Griffin, J. Tim

    2012-01-01

    Because of many advantages associated with central utility systems, school campuses, from large universities to elementary schools, have used district energy for decades. District energy facilities enable thermal and electric utilities to be generated with greater efficiency and higher system reliability, while requiring fewer maintenance and…

  5. Competitive Intelligence and Social Advantage.

    Science.gov (United States)

    Davenport, Elisabeth; Cronin, Blaise

    1994-01-01

    Presents an overview of issues concerning civilian competitive intelligence (CI). Topics discussed include competitive advantage in academic and research environments; public domain information and libraries; covert and overt competitive intelligence; data diversity; use of the Internet; cooperative intelligence; and implications for library and…

  6. Clinical assessment of the effect of digital filtering on the detection of ventricular late potentials

    Directory of Open Access Journals (Sweden)

    P.R. Benchimol-Barbosa

    2002-11-01

    Full Text Available Ventricular late potentials are low-amplitude signals originating from damaged myocardium and detected on the body surface by ECG filtering and averaging. Digital filters present in commercial equipment may interfere with the ability of arrhythmia stratification. We compared 40-Hz BiSpec (BI and classical 40- to 250-Hz band-pass Butterworth bidirectional (BD filters in terms of impact on time domain variables and diagnostic properties. In a transverse retrospective age-adjusted case-control study, 221 subjects with sinus rhythm without bundle branch block were divided into three groups after signal-averaged ECG acquisition: GI (N = 40, clinically normal controls, GII (N = 158, subjects with coronary heart disease without sustained monomorphic ventricular tachycardia (SMVT, and GIII (N = 23, subjects with heart disease and documented SMVT. Conventional variables analyzed from vector magnitude data after averaging to 0.3 µV final noise were obtained by application of each filter to the averaged signal, and evaluated in pairs by numerical comparison and by diagnostic agreement assessment, using conventional and optimized thresholds of normality. Significant differences were found between BI and BD variables in all groups, with diagnostic results showing significant disagreement between both filters [kappa value of 0.61 (P<0.05 for GII and 0.31 for GIII (P = NS]. Sensitivity for SMVT was lower with BI than with BD (65.2 vs 91.3%, respectively, P<0.05. Filters provided significantly different numerical and diagnostic results and the BI filter showed only limited clinical application to risk stratification of ventricular arrhythmia.

  7. Alterations in neuropeptides in aging and disease. Pathophysiology and potential for clinical intervention.

    Science.gov (United States)

    Leake, A; Ferrier, I N

    1993-01-01

    Marked specific and selective changes in the levels of some neuropeptides in age-related diseases, such as senile dementia of the Alzheimer (SDAT) or Lewy body (SDLT) types, Parkinson's disease, Huntington's disease and major depressive disorder, versus normal aging have been noted. However, the levels of most neuropeptides are normal. The only 2 peptides consistently altered in SDAT are somatostatin and corticotrophin-releasing hormone both of which are reduced. In Huntington's disease, the level of substance P in the basal ganglia is reduced suggesting a preferential vulnerability of spiny neurones in this disease. In Parkinson's disease, substance P is attenuated in the basal ganglia while somatostatin is reduced in the neocortex. These and other results suggest that substance P deficits are related to movement disorders while somatostatin deficits are related to cognitive impairment. SDLT is a type of dementia with features common to both SDAT and Parkinson's disease, although the changes in neuropeptides suggest that neurochemically the disease is more closely related to SDAT. In major depressive disorder, the level of corticotrophin-releasing hormone is reduced while there is a reciprocal increase in corticotrophin-releasing hormone receptors suggesting that the neurones remain functional. Potential clinical intervention has been limited by problems such as poor penetration of agents into the brain and the short half-lives of neuropeptide agonists and antagonists. However, some currently available agents may act, at least in part, through modulation of neuropeptide pathways, e.g. carbamazepine and alprazolam both modulate the corticotrophin-releasing hormone system in animals, and both have clinically proven antidepressant activity.

  8. Clinical definition of respiratory viral infections in young children and potential bronchiolitis misclassification.

    Science.gov (United States)

    Megalaa, Rosemary; Perez, Geovanny F; Kilaikode-Cheruveettara, Sasikumar; Kotwal, Nidhi; Rodriguez-Martinez, Carlos E; Nino, Gustavo

    2018-01-01

    Viral respiratory infections are often grouped as a single respiratory syndrome named 'viral bronchiolitis', independently of the viral etiology or individual risk factors. Clinical trials and guidelines have used a more stringent definition of viral bronchiolitis, including only the first episode of wheezing in children less than 12 months of age without concomitant respiratory comorbidities. There is increasing evidence suggesting that this definition is not being followed by pediatric care providers, but it is unclear to what extent viral respiratory infections are currently misclassified as viral bronchiolitis using standard definitions. We conducted a retrospective analysis of hospitalized young children (≤3 years) due to viral respiratory infections. Bronchiolitis was defined as the first wheezing episode less than 12 months of age. Demographic variables and comorbidities were obtained by electronic medical record review. The study comprised a total of 513 hospitalizations (n=453). Viral bronchiolitis was diagnosed in 144 admissions (28.1%). Notably, we identified that the majority of children diagnosed with bronchiolitis (63%) were misclassified as they had prior episodes of wheezing. Many children with bronchiolitis misclassification had significant comorbidities, including prematurity (51%), neuromuscular conditions (9.8%), and congenital heart disease (9.8%). Misclassification of bronchiolitis is a common problem that may lead to inappropriate management of viral respiratory infections in young children. A comprehensive approach that takes into consideration viral etiology and individual risk factors may lead to a more accurate clinical assessment of this condition and would potentially prevent bronchiolitis misclassification. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Clinical realism: a new literary genre and a potential tool for encouraging empathy in medical students.

    Science.gov (United States)

    McDonald, Paula; Ashton, Katy; Barratt, Rachel; Doyle, Simon; Imeson, Dorrie; Meir, Amos; Risser, Gregoire

    2015-07-03

    Empathy has been re-discovered as a desirable quality in doctors. A number of approaches using the medical humanities have been advocated to teach empathy to medical students. This paper describes a new approach using the medium of creative writing and a new narrative genre: clinical realism. Third year students were offered a four week long Student Selected Component (SSC) in Narrative Medicine and Creative Writing. The creative writing element included researching and creating a character with a life-changing physical disorder without making the disorder the focus of the writing. The age, gender, social circumstances and physical disorder of a character were randomly allocated to each student. The students wrote repeated assignments in the first person, writing as their character and including details of living with the disorder in all of their narratives. This article is based on the work produced by the 2013 cohort of students taking the course, and on their reflections on the process of creating their characters. Their output was analysed thematically using a constructivist approach to meaning making. This preliminary analysis suggests that the students created convincing and detailed narratives which included rich information about living with a chronic disorder. Although the writing assignments were generic, they introduced a number of themes relating to illness, including stigma, personal identity and narrative wreckage. Some students reported that they found it difficult to relate to "their" character initially, but their empathy for the character increased as the SSC progressed. Clinical realism combined with repeated writing exercises about the same character is a potential tool for helping to develop empathy in medical students and merits further investigation.

  10. A rat retinal damage model predicts for potential clinical visual disturbances induced by Hsp90 inhibitors

    International Nuclear Information System (INIS)

    Zhou, Dan; Liu, Yuan; Ye, Josephine; Ying, Weiwen; Ogawa, Luisa Shin; Inoue, Takayo; Tatsuta, Noriaki; Wada, Yumiko; Koya, Keizo; Huang, Qin; Bates, Richard C.; Sonderfan, Andrew J.

    2013-01-01

    In human trials certain heat shock protein 90 (Hsp90) inhibitors, including 17-DMAG and NVP-AUY922, have caused visual disorders indicative of retinal dysfunction; others such as 17-AAG and ganetespib have not. To understand these safety profile differences we evaluated histopathological changes and exposure profiles of four Hsp90 inhibitors, with or without clinical reports of adverse ocular effects, using a rat retinal model. Retinal morphology, Hsp70 expression (a surrogate marker of Hsp90 inhibition), apoptotic induction and pharmacokinetic drug exposure analysis were examined in rats treated with the ansamycins 17-DMAG and 17-AAG, or with the second-generation compounds NVP-AUY922 and ganetespib. Both 17-DMAG and NVP-AUY922 induced strong yet restricted retinal Hsp70 up-regulation and promoted marked photoreceptor cell death 24 h after the final dose. In contrast, neither 17-AAG nor ganetespib elicited photoreceptor injury. When the relationship between drug distribution and photoreceptor degeneration was examined, 17-DMAG and NVP-AUY922 showed substantial retinal accumulation, with high retina/plasma (R/P) ratios and slow elimination rates, such that 51% of 17-DMAG and 65% of NVP-AUY922 present at 30 min post-injection were retained in the retina 6 h post-dose. For 17-AAG and ganetespib, retinal elimination was rapid (90% and 70% of drugs eliminated from the retina at 6 h, respectively) which correlated with lower R/P ratios. These findings indicate that prolonged inhibition of Hsp90 activity in the eye results in photoreceptor cell death. Moreover, the results suggest that the retina/plasma exposure ratio and retinal elimination rate profiles of Hsp90 inhibitors, irrespective of their chemical class, may predict for ocular toxicity potential. - Highlights: • In human trials some Hsp90 inhibitors cause visual disorders, others do not. • Prolonged inhibition of Hsp90 in the rat eye results in photoreceptor cell death. • Retina/plasma ratio and retinal

  11. Potential clinical impact of laser-accelerated beams in cancer ion therapy

    Energy Technology Data Exchange (ETDEWEB)

    Obcemea, Ceferino

    2016-09-01

    In this article, I present three advantages of plasma-accelerated ion beams for cancer therapy. I discuss how: 1. low-emittance and well-collimated beams are advantageous in proximal normal tissue-sparing; 2. highly-peaked quasi-monoenergetic beams are ideal for fast energy selection and switching in Pencil Beam Scanning (PBS) as a treatment delivery; 3. high fluence and ultra-short pulse delivery produce collective excitations in the medium and enhance the stopping power. This in turn produces denser ionization track signatures (spurs, blobs, etc.) in target tumors, higher linear energy transfer, higher Bragg peak, and higher radiobiological effectiveness at the micro-level.

  12. Major adverse cardiovascular event reduction with GLP-1 and SGLT2 agents: evidence and clinical potential

    Science.gov (United States)

    Røder, Michael E.

    2017-01-01

    Treatment of patients with type 2 diabetes is directed against treating symptoms of hyperglycemia, minimizing the risk of hypoglycemia, and the risk of microvascular and macrovascular complications. The majority of patients with type 2 diabetes die from cardiovascular or cerebrovascular disease. Future therapies should therefore focus on reducing cardiovascular morbidity in this high-risk population. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are two drug classes with proven antihyperglycemic effect in type 2 diabetes. However, these drugs seem to have other effects such as weight reduction, low risk of hypoglycemia, and blood pressure reduction. Emerging evidence suggests pleiotropic effects, which potentially could be important in reducing cardiovascular risk. Prompted by regulatory authorities demanding cardiovascular outcome trials (CVOTs) assessing the cardiovascular safety of new antihyperglycemic drug candidates, many CVOTs are ongoing and a few of these are finalized. Somewhat surprising recent CVOTs in both drug classes have shown promising data on cardiovascular morbidity and mortality in patients with a very high risk of cardiovascular events. It is uncertain whether this is a class effect of the two drug classes, and it is yet unproven whether long-term cardiovascular benefits of these drugs can be extrapolated to populations at lower risk of cardiovascular disease. The aim of the present review is to give an overview of our current knowledge of the GLP-1RA and SGLT2-i classes, with specific focus on mechanisms of action, effects on cardiovascular risk factors and cardiovascular morbidity and mortality from the CVOTs presently available. The clinical potential of these data is discussed. PMID:29344329

  13. Proven and potential clinical benefits of washing red blood cells before transfusion: current perspectives

    Directory of Open Access Journals (Sweden)

    Schmidt AE

    2016-08-01

    Full Text Available Amy E Schmidt, Majed A Refaai, Scott A Kirkley, Neil Blumberg Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA Abstract: Red blood cells (RBCs are washed for a variety of reasons such as to remove excess potassium, cytokines, and other allergen proteins from the supernatant and/or to mitigate the effects of the storage lesion. The storage lesion is a product of RBC aging and include leakage of potassium and chloride from the RBCs, depletion of 2,3-diphosphoglycerate and adenosine triphosphate, loss of phospholipids and cholesterol, exposure of phosphatidylserine, elaboration of lipid mediators, loss of glutathione, autoxidation of hemoglobin to methemoglobin contributing to decreased blood flow viscosity and adherence to endothelial cells, increased microparticle formation, and disruption of NO-mediated vasodilation. A storage lesion is thought to be caused in part by oxidative stress, which is characterized by functional and structural changes to the RBCs. The effects of the RBC storage lesion on patient morbidity and mortality have been studied intensively with mixed results. Here, we will summarize the potential benefits of RBC washing. Notably, all patient-based studies on washed RBCs are single-center, small randomized studies or observational data, which await replication and tests of generalizability. Some of the most promising preliminary data suggest that washed transfusions of red cells and platelets reduce mortality in low risk, younger patients with acute myeloid leukemia, mitigate lung injury, and substantially reduce mortality in cardiac surgery. Larger randomized trials to replicate or refute these findings are urgently needed and, most importantly, have the potential to strikingly improve clinical outcomes following transfusion. Keywords: washed blood, transfusion, immunomodulation, red blood cell

  14. Mesenchymal stem cells: Properties and clinical potential for cell based therapies in reconstructive surgery with a focus on peripheral nerve surgery

    Directory of Open Access Journals (Sweden)

    Kuhbier, Jörn W.

    2015-08-01

    Full Text Available The isolation and expansion of multipotent mesenchymal stem cells (MSCs could be demonstrated from bone marrow, peripheral blood, skin, umbilical cord blood and adipose issue. They can be differentiated to different mesodermal cell lines like bone, cartilage, muscle or adipose tissue cells as well as . Thus MSCs represent an attractive cell population for the substitution of mesenchymal tissues via tissue engineering due to their potential of differentiation and their favourable expansion properties. In contrast to embryonic stem cells (ESCs they have the advantage that they can be autologously harvested in high numbers. Besides, there are fewer ethical issues in the use of MSCs. Another advantage of MSCs is the highly regenerative secretion profile of cytokines and growth factors, in particular supporting angiogenesis. A plethora of studies describe the morphological and phenotypical characterization of this cell type as well as regulatory mechanisms lying the differentiation into specific tissues aiming to optimize conditions for differentiation and thus clinical application. This review describes the definition of a mesenchymal stem cell, methods for isolation and phenotypical characterization, possibilities of differentiation and possible therapeutical applications of MSCs.

  15. The potential of SGLT2 inhibitors in phase II clinical development for treating type 2 diabetes.

    Science.gov (United States)

    Pafili, K; Maltezos, E; Papanas, N

    2016-10-01

    There is now an abundance of anti-diabetic agents. However, only few patients achieve glycemic targets. Moreover, current glucose-lowering agents mainly depend upon insulin secretion or function. Sodium glucose co-transporter type 2 (SGLT2) inhibitors present a novel glucose-lowering therapy, inducing glycosuria in an insulin-independent fashion. In this review, the authors discuss the key efficacy and safety data from phase II clinical trials in type 2 diabetes mellitus (T2DM) of the main SGLT2 inhibitors approved or currently in development, and provide a rationale for their use in T2DM. Despite the very promising characteristics of this new therapeutic class, a number of issues await consideration. One important question is what to expect from head-to-head comparison data. We also need to know if dual inhibition of SGLT1/SGLT2 is more efficacious in reducing HbA1c and how this therapy affects metabolic and cardiovascular parameters. Additionally, several SGLT2 agents that have not yet come to market have hitherto been evaluated in Asian populations, whereas approved SGLT2 inhibitors have been frequently studied in other populations, including Caucasian subjects. Thus, we need more information on the potential role of ethnicity on their efficacy and safety.

  16. Clinical investigation of TROP-2 as an independent biomarker and potential therapeutic target in colon cancer.

    Science.gov (United States)

    Zhao, Peng; Yu, Hai-Zheng; Cai, Jian-Hui

    2015-09-01

    Colon cancer is associated with a severe demographic and economic burden worldwide. The pathogenesis of colon cancer is highly complex and involves sequential genetic and epigenetic mechanisms. Despite extensive investigation, the pathogenesis of colon cancer remains to be elucidated. As the third most common type of cancer worldwide, the treatment options for colon cancer are currently limited. Human trophoblast cell‑surface marker (TROP‑2), is a cell‑surface transmembrane glycoprotein overexpressed by several types of epithelial carcinoma. In addition, TROP‑2 has been demonstrated to be associated with tumorigenesis and invasiveness in solid types of tumor. The aim of the present study was to investigate the protein expression of TROP‑2 in colon cancer tissues, and further explore the association between the expression of TROP‑2 and clinicopathological features of patients with colon cancer. The expression and localization of the TROP‑2 protein was examined using western blot analysis and immunofluorescence staining. Finally, the expression of TROP‑2 expression was correlated to conventional clinicopathological features of colon cancer using a χ2 test. The results revealed that TROP‑2 protein was expressed at high levels in the colon cancer tissues, which was associated with the development and pathological process of colon cancer. Therefore, TROP‑2 may be used as a biomarker to determine the clinical prognosis, and as a potential therapeutic target in colon cancer.

  17. ATF1 and RAS in exosomes are potential clinical diagnostic markers for cervical cancer.

    Science.gov (United States)

    Shi, Yanhua; Wang, Wei; Yang, Baozhi; Tian, Hongge

    2017-10-01

    Cervical cancer is one of the most common cancers among women worldwide. It is highly lethal yet can be treated when found in early stage. Thus, early detection is of significant important for early diagnosis of cervical cancer. Exosomes have been used as biomarkers in clinical diagnosis. It is unknown that whether blood exosomes associated with cervical cancer can be detected and if these exosomes can accurately represent the developmental stage of cervical cancer. Mouse models were made out of a relapsed cervical cancer patient's tumour sample for original and recurrent cervical cancer, and gene analysis in both tumours and exosomes in these mouse models were performed. We found that activating transcription factor 1 (ATF1) and RAS genes were significantly up-regulated in tumours of both primary and recurrent cervical cancer mouse model, and they can also be detected in the blood exosomes of the mouse model. Our results indicated that ATF1 and RAS could be potential candidate biomarkers for cervical cancer in early diagnosis. ATF1 and RAS genes were found significantly elevated in tumours of primary and recurrent cervical cancer mouse model, and they were also detected in the blood exosomes. Therefore, ATF1 and RAS could be used as a diagnostic marker for cervical cancer in the future. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Methodology optimization and diversification for the investigation of virulence potential in Haemophilus influenzae clinical strains.

    Science.gov (United States)

    Giucă, Mihaela Cristina; Străuţ, Monica; Surdeanu, Maria; Nica, Maria; Ungureanu, Vasilica; Mihăescu, Grigore

    2011-01-01

    Ten Haemophilus influenzae strains were isolated from patients aged between 1.6 - 24 years, with various diagnoses (acute meningitis, acute upper respiratory infection, otitis media and acute sinusitis). Identification was based on phenotypic and molecular characteristics; antibiotic susceptibility testing was performed by diffusion method according to CLSI standards 2011 for seven antibiotics. The results of molecular testing showed that all the studied strains produced an amplicon of 1000 bp with ompP2 primers indicating that all strains were H. influenzae. For six strains, the PCR amplicon obtained with bexA specific primers, proving that the strains were capsulated. The results of phenotypic testing showed that four strains were ampicillin nonsusceptible and (beta-lactamase-positive. The virulence potential of H. influenzae clinical strains was investigated by phenotypic methods, including the assessment of the soluble virulence factors on specific media containing the biochemical substratum for the investigated enzymatic factor, as well as the adherence and invasion capacity to HeLa cells monolayer using Cravioto modified method. The studied strains exhibited mainly a diffuse adherence pattern and different adherence indexes. Interestingly, two strains isolated from the same pacient (blood and CSF) showed a different degree of invasiveness, the strain isolated from blood being 20 times more invasive than the one isolated from CSF.

  19. High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.

    Science.gov (United States)

    Ocak, S; Sos, M L; Thomas, R K; Massion, P P

    2009-08-01

    During the last decade, high-throughput technologies including genomic, epigenomic, transcriptomic and proteomic have been applied to further our understanding of the molecular pathogenesis of this heterogeneous disease, and to develop strategies that aim to improve the management of patients with lung cancer. Ultimately, these approaches should lead to sensitive, specific and noninvasive methods for early diagnosis, and facilitate the prediction of response to therapy and outcome, as well as the identification of potential novel therapeutic targets. Genomic studies were the first to move this field forward by providing novel insights into the molecular biology of lung cancer and by generating candidate biomarkers of disease progression. Lung carcinogenesis is driven by genetic and epigenetic alterations that cause aberrant gene function; however, the challenge remains to pinpoint the key regulatory control mechanisms and to distinguish driver from passenger alterations that may have a small but additive effect on cancer development. Epigenetic regulation by DNA methylation and histone modifications modulate chromatin structure and, in turn, either activate or silence gene expression. Proteomic approaches critically complement these molecular studies, as the phenotype of a cancer cell is determined by proteins and cannot be predicted by genomics or transcriptomics alone. The present article focuses on the technological platforms available and some proposed clinical applications. We illustrate herein how the "-omics" have revolutionised our approach to lung cancer biology and hold promise for personalised management of lung cancer.

  20. Advertising Dynamics and Competitive Advantage

    OpenAIRE

    Ulrich Doraszelski; Sarit Markovich

    2004-01-01

    Can advertising lead to a sustainable competitive advantage? To answer this question, we propose a dynamic model of advertising competition where firms repeatedly advertise, compete in the product market, and make entry as well as exit decisions. Within this dynamic framework, we study two different models of advertising: In the first model, advertising influences the goodwill consumers extend towards a firm ("goodwill advertising"), whereas in the second model it influences the share of cons...

  1. Interest alignment and competitive advantage

    OpenAIRE

    Gottschalg, Oliver; Zollo, Mauricio

    2006-01-01

    This paper articulates a theory of the conditions under which the alignment between individual and collective interests generates sustainable competitive advantage. The theory is based on the influence of tacitness, context-specificity and casual ambiguity in the determinants of different types of motivation (extrinsic, normative intrinsic and hedonic intrinsic), under varying conditions of environmental dynamism. The analysis indicates the need to consider mitivational processes as a complem...

  2. [Radiation-induced bystander effect: the important part of ionizing radiation response. Potential clinical implications].

    Science.gov (United States)

    Wideł, Maria; Przybyszewski, Waldemar; Rzeszowska-Wolny, Joanna

    2009-08-18

    It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the "bystander effect" or "radiation-induced bystander effect" (RIBE). This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy), but also after conventional irradiation (X-rays, gamma rays) at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not definitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effect may have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation field and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The bystander effect may be a

  3. Radiation-induced bystander effect: The important part of ionizing radiation response. Potential clinical implications

    Directory of Open Access Journals (Sweden)

    Maria Wideł

    2009-08-01

    Full Text Available It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the “bystander effect” or “radiation-induced bystander effect” (RIBE. This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy, but also after conventional irradiation (X-rays, gamma rays at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not defi nitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effectmay have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation fi eld and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The

  4. Quality attributes of LED lighting. Current state-of-the-art , advantages, problem areas and potential for development - Final report; Qualitaetsmerkmale der LED-Beleuchtung. Aktueller Stand der Technik, Vorteile, Problempunkte und Entwicklungspotential - Schlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Gasser, S.

    2009-09-15

    The present report describes the state-of-the-art of LED technology for room lighting in June 2009, based on internet research, expert interviews as well as a workshop with experts. Of the 20 attributes determined, three key quality characteristics crucial for the breakthrough of LED technology were identified: (i) Energy efficiency: with values of 50 - 70 lumen/watt when in usage, current LED lamps on the market are comparable to energy saving lamps. Experts expect the luminous efficiency to double within the next five years. Declaration is often poor: instead of efficiency in real-life usage many producers declare unrealistic lab measurement results; sometimes even fantasy values are declared. (ii) Light quality: Today's good LEDs reach colour rendering attributes which are comparable to those of halogen lamps and usually better than the CFL's (colour rendering index 80 to 90, with a continuous light spectrum). (iii) Lamp life: A lamp life of up to 50,000 hours can only be reached if the heat dissipation is secured and if the Control gears quality keeps up with the LED's life time. According to the experts, many of today's LED products on the market don't meet these two requirements. Strong uncertainty is caused by inconsistent declaration and partly missing standardisation. With the ANSI standard, the US is ahead of Europe in this matter. Today LED lighting is attractive and economic where its unique advantages can be applied: directional light, very long life-span, no heat in the luminous flux, UV-free light, colour modulation, dimming with little losses. Interesting applications today include: (i) Professional field: operating time > 3,000 hours per year, e.g. shop illumination or downlights in a hall (hotel, administration, etc.). Further spotlights in museums, working place table light fixtures, hybrid solutions (e.g. indirect fluorescent lamp, direct LED). (ii) Domestic field: working place and reading lamps (low luminance, no heat

  5. Antimicrobial potential of Dialium guineense (Wild.) stem bark on some clinical isolates in Nigeria.

    Science.gov (United States)

    Olajubu, Fa; Akpan, I; Ojo, DA; Oluwalana, Sa

    2012-01-01

    The persistent increase in the number of antibiotic-resistant strains of microorganisms has led to the development of more potent but also more expensive antibiotics. In most developing countries of the world these antibiotics are not readily affordable, thus making compliance difficult. This calls for research into alternative sources of antimicrobials. Dialium guineense is a shrub of the family Leguminosae. Its stem bark is used for the treatment of cough, toothache, and bronchitis. Despite the acclaimed efficacy of D guineense, there is no scientific evidence in its support. This work was carried out to assess the antimicrobial activity of D guineense in vitro against some clinical isolates. D guineense stem bark was collected and 50 gm of air-dried and powdered stem bark of the plant was soaked for 72 hours in 1 l of each of the six solvents used in this study. Each mixture was refluxed, agitated at 200 rpm for 1 hour, filtered using Whatman No. 1 filter paper and, finally, freeze dried. The extracts were then tested for antimicrobial activity using the agar diffusion method. The highest percentage yield of 23.2% was obtained with ethanol. Phytochemical screening showed that D guineense contains anthraquinone, alkaloids, flavonoids, tannins, and saponins. The antimicrobial activity of the extracts revealed a broad spectrum of activity, with Salmonella typhi and Staphylococcus aureusa showing the greatest zones of inhibition (18.0 mm). Only Candida albicans among the fungi tested was inhibited by the extract. The greatest zone of inhibition among the fractions was 16.0 mm. D guineense exhibited bactericidal activity at the 7th and 9th hours against Streptococcus pneumoniae and S. aureus 25923 while the 10th hour against S. typhi and C. albicans. The greatest activity was noted against S pneumoniae, where there was reduced viable cell count after 6 hours of exposure. Stem bark extract of D guineense (Wild.) has the potential to be developed into an antimicrobial

  6. Can the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) be used to accurately report clinic total reproductive potential (TRP)?

    Science.gov (United States)

    Stern, Judy E; Hickman, Timothy N; Kinzer, Donna; Penzias, Alan S; Ball, G David; Gibbons, William E

    2012-04-01

    To assess whether total reproductive potential (TRP), the chance of a live birth from each fresh cycle (fresh cycle plus frozen transfers), could be calculated from the national Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database and whether information not available in SART CORS resulted in significant changes to the TRP calculation. Retrospective study using SART CORS and clinic data. Three assisted reproductive technology clinics. Women undergoing ART. None. Two- and three-year TRPs for 2005 and 2006 were calculated according to patient age at cycle start by linking fresh to frozen cycles up to first live birth. Clinic records were used to adjust for (remove) frozen cycles that used more than one fresh cycle as a source of embryos and for any embryos donated to other patients or research or shipped to another facility before a live birth. TRP was higher than fresh per-cycle rates for most ages at all clinics, although accuracy was compromised when there were fewer than 20 cycles per category. Two- and 3-year TRPs differed in only 2 of 24 calculations. Adjusted TRPs differed less than three percentage points from unadjusted TRPs when volume was sufficient. Clinic TRP can be calculated from SART CORS. Data suggest that calculations of clinic TRP from the national dataset would be meaningful. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  7. BUSINESS COMPETITORS AND COMPETITIVE ADVANTAGE

    Directory of Open Access Journals (Sweden)

    SUCIU TITUS

    2013-08-01

    Full Text Available The paper presents the concept of competition, both from the perspective of the economic sector –where it is characteristic for pure monopole, oligopoly, monopole competition and pure competition, as well asfrom the market’s point of view – where it determines the strategies, objectives, advantages and weaknesses of acompany. The main point of the paper is the criticism of the pure and perfect competition theory. Concluding,the author insists on innovation, especially on the model of open innovation.

  8. Ecology. The advantages of togetherness.

    Science.gov (United States)

    Cox, E; Bonner, J

    2001-04-20

    What would be the advantage of unicellular organisms becoming multicellular? For organisms that feed on organic food (heterotrophs), the most efficient way to produce energy is to metabolize the food by aerobic respiration, but the fastest way is to metabolize it by fermentation. In their Perspective, Cox and Bonner discuss a mathematical model (Pfeiffer et al.), which shows that when these two kinds of organisms (respirators and fermenters) compete for a limited food source, the respirators manage best when they are grouped in clusters rather than remaining as separate cells. In this way, multicellularity could have originated.

  9. Advantages of computed tomographic guidance

    International Nuclear Information System (INIS)

    Casola, G.; Vansonnenberg, E.

    1987-01-01

    Both ultrasound and CT are successfully used to guide interventional procedures throughout the body. There are advantages and disadvantages to each modality and choosing one over the other will vary from case to case. Major factors influencing choice are discussed in this paper. As a general rule CT guidance is usually required for lesions in the thorax, the adrenals, the pancreas, lymph nodes, and for percutaneous abscess drainage. The authors feel that a complimentary use of ultrasound and CT is essential to optimize success and cost-effectiveness; therefore, the interventional radiologist should be familiar with both imaging modalities

  10. CpG Methylation Analysis—Current Status of Clinical Assays and Potential Applications in Molecular Diagnostics

    Science.gov (United States)

    Sepulveda, Antonia R.; Jones, Dan; Ogino, Shuji; Samowitz, Wade; Gulley, Margaret L.; Edwards, Robin; Levenson, Victor; Pratt, Victoria M.; Yang, Bin; Nafa, Khedoudja; Yan, Liying; Vitazka, Patrick

    2009-01-01

    Methylation of CpG islands in gene promoter regions is a major molecular mechanism of gene silencing and underlies both cancer development and progression. In molecular oncology, testing for the CpG methylation of tissue DNA has emerged as a clinically useful tool for tumor detection, outcome prediction, and treatment selection, as well as for assessing the efficacy of treatment with the use of demethylating agents and monitoring for tumor recurrence. In addition, because CpG methylation occurs early in pre-neoplastic tissues, methylation tests may be useful as markers of cancer risk in patients with either infectious or inflammatory conditions. The Methylation Working Group of the Clinical Practice Committee of the Association of Molecular Pathology has reviewed the current state of clinical testing in this area. We report here our summary of both the advantages and disadvantages of various methods, as well as the needs for standardization and reporting. We then conclude by summarizing the most promising areas for future clinical testing in cancer molecular diagnostics. PMID:19541921

  11. Contextual Advantage for State Discrimination

    Science.gov (United States)

    Schmid, David; Spekkens, Robert W.

    2018-02-01

    Finding quantitative aspects of quantum phenomena which cannot be explained by any classical model has foundational importance for understanding the boundary between classical and quantum theory. It also has practical significance for identifying information processing tasks for which those phenomena provide a quantum advantage. Using the framework of generalized noncontextuality as our notion of classicality, we find one such nonclassical feature within the phenomenology of quantum minimum-error state discrimination. Namely, we identify quantitative limits on the success probability for minimum-error state discrimination in any experiment described by a noncontextual ontological model. These constraints constitute noncontextuality inequalities that are violated by quantum theory, and this violation implies a quantum advantage for state discrimination relative to noncontextual models. Furthermore, our noncontextuality inequalities are robust to noise and are operationally formulated, so that any experimental violation of the inequalities is a witness of contextuality, independently of the validity of quantum theory. Along the way, we introduce new methods for analyzing noncontextuality scenarios and demonstrate a tight connection between our minimum-error state discrimination scenario and a Bell scenario.

  12. Contextual Advantage for State Discrimination

    Directory of Open Access Journals (Sweden)

    David Schmid

    2018-02-01

    Full Text Available Finding quantitative aspects of quantum phenomena which cannot be explained by any classical model has foundational importance for understanding the boundary between classical and quantum theory. It also has practical significance for identifying information processing tasks for which those phenomena provide a quantum advantage. Using the framework of generalized noncontextuality as our notion of classicality, we find one such nonclassical feature within the phenomenology of quantum minimum-error state discrimination. Namely, we identify quantitative limits on the success probability for minimum-error state discrimination in any experiment described by a noncontextual ontological model. These constraints constitute noncontextuality inequalities that are violated by quantum theory, and this violation implies a quantum advantage for state discrimination relative to noncontextual models. Furthermore, our noncontextuality inequalities are robust to noise and are operationally formulated, so that any experimental violation of the inequalities is a witness of contextuality, independently of the validity of quantum theory. Along the way, we introduce new methods for analyzing noncontextuality scenarios and demonstrate a tight connection between our minimum-error state discrimination scenario and a Bell scenario.

  13. Explaining Asian Americans’ academic advantage over whites

    Science.gov (United States)

    Hsin, Amy; Xie, Yu

    2014-01-01

    The superior academic achievement of Asian Americans is a well-documented phenomenon that lacks a widely accepted explanation. Asian Americans’ advantage in this respect has been attributed to three groups of factors: (i) socio-demographic characteristics, (ii) cognitive ability, and (iii) academic effort as measured by characteristics such as attentiveness and work ethic. We combine data from two nationally representative cohort longitudinal surveys to compare Asian-American and white students in their educational trajectories from kindergarten through high school. We find that the Asian-American educational advantage is attributable mainly to Asian students exerting greater academic effort and not to advantages in tested cognitive abilities or socio-demographics. We test explanations for the Asian–white gap in academic effort and find that the gap can be further attributed to (i) cultural differences in beliefs regarding the connection between effort and achievement and (ii) immigration status. Finally, we highlight the potential psychological and social costs associated with Asian-American achievement success. PMID:24799702

  14. Explaining Asian Americans' academic advantage over whites.

    Science.gov (United States)

    Hsin, Amy; Xie, Yu

    2014-06-10

    The superior academic achievement of Asian Americans is a well-documented phenomenon that lacks a widely accepted explanation. Asian Americans' advantage in this respect has been attributed to three groups of factors: (i) socio-demographic characteristics, (ii) cognitive ability, and (iii) academic effort as measured by characteristics such as attentiveness and work ethic. We combine data from two nationally representative cohort longitudinal surveys to compare Asian-American and white students in their educational trajectories from kindergarten through high school. We find that the Asian-American educational advantage is attributable mainly to Asian students exerting greater academic effort and not to advantages in tested cognitive abilities or socio-demographics. We test explanations for the Asian-white gap in academic effort and find that the gap can be further attributed to (i) cultural differences in beliefs regarding the connection between effort and achievement and (ii) immigration status. Finally, we highlight the potential psychological and social costs associated with Asian-American achievement success.

  15. Preclinical Evaluation of Raman Nanoparticle Biodistribution for their Potential Use in Clinical Endoscopy Imaging

    DEFF Research Database (Denmark)

    Zavaleta, Cristina L; Hartman, Keith B; Miao, Zheng

    2011-01-01

    Raman imaging offers unsurpassed sensitivity and multiplexing capabilities. However, its limited depth of light penetration makes direct clinical translation challenging. Therefore, a more suitable way to harness its attributes in a clinical setting would be to couple Raman spectroscopy with endo...

  16. Clinical potential of naloxegol in the management of opioid-induced bowel dysfunction

    Directory of Open Access Journals (Sweden)

    Poulsen JL

    2014-09-01

    Full Text Available Jakob Lykke Poulsen,1 Christina Brock,1,2 Anne Estrup Olesen,1,2 Matias Nilsson,1 Asbjørn Mohr Drewes1,3 1Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; 2Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark; 3Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkAbstract: Opioid-induced bowel dysfunction (OIBD is a burdensome condition which limits the therapeutic benefit of analgesia. It affects the entire gastrointestinal tract, predominantly by activating opioid receptors in the enteric nervous system, resulting in a wide range of symptoms, such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation. The majority of studies evaluating OIBD focus on constipation experienced in approximately 60% of patients. Nevertheless, other presentations of OIBD seem to be equally frequent. Furthermore, laxative treatment is often insufficient, which in many patients results in decreased quality of life and discontinuation of opioid treatment. Novel mechanism-based pharmacological approaches targeting the gastrointestinal opioid receptors have been marketed recently and even more are in the pipeline. One strategy is prolonged release formulation of the opioid antagonist naloxone (which has limited systemic absorption and oxycodone in a combined tablet. Another approach is peripherally acting, µ-opioid receptor antagonists (PAMORAs that selectively target µ-opioid receptors in the gastrointestinal tract. However, in Europe the only PAMORA approved for OIBD is the subcutaneously administered methylnaltrexone. Alvimopan is an oral PAMORA, but only approved in the US for postoperative ileus in hospitalized patients. Finally, naloxegol is a novel, oral PAMORA expected to be approved soon. In this review, the prevalence and pathophysiology of OIBD is presented. As PAMORAs seem to be a promising approach, their potential

  17. Clinical potential of eliglustat tartrate in the treatment of type 1 Gaucher disease

    Directory of Open Access Journals (Sweden)

    Kaplan P

    2014-05-01

    counts, and bone density, as well as decreases in biomarkers of Gaucher disease activity. Few adverse events, none of which was serious, have been reported. Eliglustat tartrate has the clinical potential to enable a larger number of patients with type 1 Gaucher disease to be treated successfully.Keywords: type 1 Gaucher disease, substrate reduction therapy, eliglustat tartrate

  18. Advantages and Applications of CAR-Expressing Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Wolfgang eGlienke

    2015-02-01

    Full Text Available In contrast to donor T cells, natural killer (NK cells are known to mediate anti-cancer effects without the risk of inducing graft-versus-host disease (GvHD. In order to improve cytotoxicity against resistant cancer cells, auspicious efforts have been made with chimeric antigen receptor (CAR expressing T- and NK cells. These CAR-modified cells express antigen receptors against tumor-associated surface antigens, thus redirecting the effector cells and enhancing tumor-specific immunosurveillance. However, many cancer antigens are also expressed on healthy tissues, potentially leading to off tumor/ on target toxicity by CAR-engineered cells. In order to control such potentially severe side effects, the insertion of suicide genes into CAR-modified effectors can provide a means for efficient depletion of these cells. While CAR-expressing T cells have entered successfully clinical trials, experience with CAR-engineered NK cells is mainly restricted to pre-clinical investigations and predominantly to NK cell lines. In this review we summarize the data on CAR expressing NK cells focusing on the possible advantage using these short-lived effector cells and discuss the necessity of suicide switches. Furthermore, we address the compliance of such modified NK cells with regulatory requirements as a new field in cellular immunotherapy.

  19. Parenting Advantage in the MNC

    DEFF Research Database (Denmark)

    Nell, Phillip C.; Ambos, Björn

    2013-01-01

    subsidiaries located in Europe. Our results indicate that the external embeddedness of the MNC is an antecedent to headquarters' value creation. We find that headquarters' investments into their own relationships with the subsidiaries' contexts are positively related to the value added by headquarters....... Furthermore, this relationship is stronger when the subsidiary itself is strongly embedded. We discuss implications for the MNC literature, embeddedness research, and the literature on parenting and headquarters' roles......What determines the value an MNC's headquarters adds to its own affiliates? In this paper, we shed light on this question by linking the embeddedness view of the multinational corporation to the literature on parenting advantage. We test our hypotheses on an original dataset of 124 manufacturing...

  20. Marketing channels and competitive advantage

    Directory of Open Access Journals (Sweden)

    Jovičić Dragoljub

    2005-01-01

    Full Text Available Issue that can already be seen and will be very clear in the future is that the central problem in the market of tube caps will not be the product or the price or promotion, but marketing channels. Therefore, the competitive advantage will most probably be built on marketing channels and not the production - as it has been so far, so, the questions of choice functioning and modification of marketing channels, as well as selection of the most appropriate members of channels will become more and more important. Accordingly, it may freely be said that the choice, i.e. the movement of marketing channels represents one of the strategic decisions which has to be made by a company management and which will subsequently very significantly influence the functioning and efficacy of not only the system of distribution, but also the entire business transactions.

  1. Innovating information-delivery for potential clinical trials participants. What do patients want from multi-media resources?

    Science.gov (United States)

    Shneerson, Catherine; Windle, Richard; Cox, Karen

    2013-01-01

    To discover whether the provision of clinical trials information via a multi-media platform could better meet the needs, preferences and practices of potential cancer trial participants. A mixed qualitative and quantitative questionnaire was delivered to 72 participants from cancer support groups to elicit views on the provision and design features of multimedia resources in delivering clinical trials information. Perceived lack of information is an expressed barrier to clinical trials participation. Multimedia resources were viewed positively as a way to address this barrier by most potential clinical trials participants; in particular by helping to align information to individual needs, promote active engagement with information, and by allowing more control of the learning experience. Whilst text remained the most valued attribute of any resource, other highly rated attributes included the resource being simple to use, easily accessible, having a clear focus, incorporating examples and visual aids, and being interactive. Provision of support for the learning resource was also rated highly. As in other areas, such as education, multimedia resources may enhance the delivery and acceptance of information regarding clinical trials. Better alignment of information may have a positive impact on recruitment and retention into clinical trials. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Quality of clinical supervision and counselor emotional exhaustion: the potential mediating roles of organizational and occupational commitment.

    Science.gov (United States)

    Knudsen, Hannah K; Roman, Paul M; Abraham, Amanda J

    2013-01-01

    Counselor emotional exhaustion has negative implications for treatment organizations as well as the health of counselors. Quality clinical supervision is protective against emotional exhaustion, but research on the mediating mechanisms between supervision and exhaustion is limited. Drawing upon data from 934 counselors affiliated with treatment programs in the National Institute on Drug Abuse's Clinical Trials Network (CTN), this study examined commitment to the treatment organization and commitment to the counseling occupation as potential mediators of the relationship between quality clinical supervision and emotional exhaustion. The final ordinary least squares (OLS) regression model, which accounted for the nesting of counselors within treatment organizations, indicated that these two types of commitment were plausible mediators of the association between clinical supervision and exhaustion. Higher quality clinical supervision was strongly correlated with commitment to the treatment organization as well as commitment to the occupation of SUD counseling. These findings suggest that quality clinical supervision has the potential to yield important benefits for counselor well-being by strengthening ties to both their employing organization as well the larger treatment field, but longitudinal research is needed to establish these causal relationships. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Renal Transplants from Older Deceased Donors: Use of Preimplantation Biopsy and Differential Allocation to Dual or Single Kidney Transplant according to Histological Score Has No Advantages over Allocation to Single Kidney Transplant by Simple Clinical Indication

    Directory of Open Access Journals (Sweden)

    Costanza Casati

    2018-01-01

    Full Text Available Background. Grafts from elderly donors (ECD are increasingly allocated to single (SKT or dual (DKT kidney transplantation according to biopsy score. Indications and benefits of either procedure lack universal agreement. Methods. A total of 302 ECD-transplants in period from Jan 1, 2000, to Dec 31, 2015, were allocated to SKT (SKTpre on clinical grounds alone (before Dec 2010, pre-DKT era, n=170 or according to a clinical-histological protocol (after Dec 2010, DKT era, n=132 to DKT (n=48, SKT biopsy-based protocol (“high-risk”, SKThr, n=51, or SKT clinically based protocol (“low-risk”, SKTlr, n=33. Graft and patient survival were compared between the two periods and between different transplant categories. Results. Graft and overall survival in recipients from ECD in pre-DKT and DKT era did not differ (5-year graft survival 87.7% and 84.2%, resp.; equal survival in the 2 ECD periods was shown in both donor age ranges of 60–69 and >70-years, and in low-risk or high-risk ECD categories. Within the DKT protocol SKThr showed worst graft and overall survival in the 60–69 donor age range; DKT did not result in significantly better outcome than SKT from ECD in either era. One-year posttransplant creatinine clearance in recipients did not differ between any ECD transplant category. At 3 and 5 years after transplantation there were significantly higher total dialysis-free recipient life years from an equal donor number in the pre-DKT era than in the DKT protocol. Conclusions. Use of a biopsy-based protocol to allocate grafts from aged donors to SKT or DKT did not result in better short term graft survival than a clinically based protocol with allocation only to SKT and reduced overall recipient dialysis-free life years in time.

  4. Renal Transplants from Older Deceased Donors: Use of Preimplantation Biopsy and Differential Allocation to Dual or Single Kidney Transplant according to Histological Score Has No Advantages over Allocation to Single Kidney Transplant by Simple Clinical Indication.

    Science.gov (United States)

    Casati, Costanza; Colombo, Valeriana Giuseppina; Perrino, Marialuisa; Rossetti, Ornella Marina; Querques, Marialuisa; Giacomoni, Alessandro; Binaggia, Agnese; Colussi, Giacomo

    2018-01-01

    Grafts from elderly donors (ECD) are increasingly allocated to single (SKT) or dual (DKT) kidney transplantation according to biopsy score. Indications and benefits of either procedure lack universal agreement. A total of 302 ECD-transplants in period from Jan 1, 2000, to Dec 31, 2015, were allocated to SKT (SKT pre ) on clinical grounds alone (before Dec 2010, pre-DKT era, n = 170) or according to a clinical-histological protocol (after Dec 2010, DKT era, n = 132) to DKT ( n = 48), SKT biopsy-based protocol ("high-risk", SKT hr , n = 51), or SKT clinically based protocol ("low-risk", SKT lr , n = 33). Graft and patient survival were compared between the two periods and between different transplant categories. Graft and overall survival in recipients from ECD in pre-DKT and DKT era did not differ (5-year graft survival 87.7% and 84.2%, resp.); equal survival in the 2 ECD periods was shown in both donor age ranges of 60-69 and >70-years, and in low-risk or high-risk ECD categories. Within the DKT protocol SKT hr showed worst graft and overall survival in the 60-69 donor age range; DKT did not result in significantly better outcome than SKT from ECD in either era. One-year posttransplant creatinine clearance in recipients did not differ between any ECD transplant category. At 3 and 5 years after transplantation there were significantly higher total dialysis-free recipient life years from an equal donor number in the pre-DKT era than in the DKT protocol. Use of a biopsy-based protocol to allocate grafts from aged donors to SKT or DKT did not result in better short term graft survival than a clinically based protocol with allocation only to SKT and reduced overall recipient dialysis-free life years in time.

  5. Evolutionary advantages of adaptive rewarding

    International Nuclear Information System (INIS)

    Szolnoki, Attila; Perc, Matjaž

    2012-01-01

    Our well-being depends on both our personal success and the success of our society. The realization of this fact makes cooperation an essential trait. Experiments have shown that rewards can elevate our readiness to cooperate, but since giving a reward inevitably entails paying a cost for it, the emergence and stability of such behavior remains elusive. Here we show that allowing for the act of rewarding to self-organize in dependence on the success of cooperation creates several evolutionary advantages that instill new ways through which collaborative efforts are promoted. Ranging from indirect territorial battle to the spontaneous emergence and destruction of coexistence, phase diagrams and the underlying spatial patterns reveal fascinatingly rich social dynamics that explain why this costly behavior has evolved and persevered. Comparisons with adaptive punishment, however, uncover an Achilles heel of adaptive rewarding, coming from over-aggression, which in turn hinders optimal utilization of network reciprocity. This may explain why, despite its success, rewarding is not as firmly embedded into our societal organization as punishment. (paper)

  6. Analysis of Potential Drug-Drug Interactions and Its Clinical Manifestation of Pediatric Prescription on 2 Pharmacies in Bandung

    Directory of Open Access Journals (Sweden)

    Melisa I. Barliana

    2013-09-01

    Full Text Available The potential of Drug-Drug Interactions (DDI in prescription have high incidence around the world, including Indonesia. However, scientific evidence regarding DDI in Indonesia is not available. Therefore, in this study we have conducted survey in 2 pharmacies in Bandung against pediatric prescription given by pediatrician. These prescriptions then analyzed the potential for DDI contained in the prescription and clinical manifestation. The analysis showed that in pharmacy A, there are 33 prescriptions (from a total of 155 prescriptions that have potential DDI, or approximately 21.19% (2 prescriptions have the potential DDI major categories, 23 prescriptions categorized as moderate, and 8 prescriptions as minor. In Pharmacy B, there are 6 prescriptions (from a total of 40 prescriptions or 15% of potential DDI (4 prescriptions categorized as moderate and 2 prescriptions as minor. This result showed that potential DDI happened less than 50% in pediatric prescription from both pharmacies. However, this should get attention because DDI should not happen in a prescription considering its clinical manifestations caused by DDI. Moreover, current pharmaceutical care refers to patient oriented than product oriented. In addition, further study for the pediatric prescription on DDI incidence in large scale need to be investigated.

  7. Clinical potential for imaging in patients with asthma and other lung disorders.

    Science.gov (United States)

    DeBoer, Emily M; Spielberg, David R; Brody, Alan S

    2017-01-01

    The ability of lung imaging to phenotype patients, determine prognosis, and predict response to treatment is expanding in clinical and translational research. The purpose of this perspective is to describe current imaging modalities that might be useful clinical tools in patients with asthma and other lung disorders and to explore some of the new developments in imaging modalities of the lung. These imaging modalities include chest radiography, computed tomography, lung magnetic resonance imaging, electrical impedance tomography, bronchoscopy, and others. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. Potential clinical usefulness of new glandular and circulating parathyroid peptides illuminated by sequence specific radioimmunoassay

    International Nuclear Information System (INIS)

    Lindall, A.W.; Cecchettin, M.

    1981-01-01

    It is now well known that human PTH peptides constitute a heterogeneous population of fragments of the eighty-four amino acid molecules. Over the years, considerable confusion has resulted from measurements made in both clinical and experimental settings with radioimmunoassays of either undefined or partially-defined specificity for a particular region of the intact molecule. The approach of the authors has been to make use of modern technology to synthesize peptide fragments that mimic portions of native molecules, and to use these fragments in RIA. A more detailed description of a portion of this work will appear in the Journal of Clinical Endocrinology and Metabolism. (Auth.)

  9. Advantages of digital imaging for radiological diagnostic

    International Nuclear Information System (INIS)

    Trapero, M. A.; Gonzalez, S.; Albillos, J. C.; Martel, J.; Rebollo, M.

    2006-01-01

    The advantages and limitations of radiological digital images in comparison with analogic ones are analyzed. We discuss three main topics: acquisition, post-procedure manipulation, and visualization, archive and communication. Digital acquisition with computed radiology systems present a global sensitivity very close to conventional film for diagnostic purposes. However, flat panel digital systems seems to achieve some advantages in particular clinical situations. A critical issue is the radiation dose-reduction that can be accomplished without reducing image quality nor diagnostic exactitude. The post-procedure manipulation allows, particularly in multiplanar modalities like CT or MR, to extract all implicit diagnostic information in the images: Main procedures are multiplanar and three-dimensional reformations, dynamic acquisitions, functional studies and image fusion. The use of PACS for visualization, archive and communication of images, improves the effectiveness and the efficiency of the workflow, allows a more comfortable diagnosis for the radiologist and gives way to improvements in the communication of images, allowing tele consulting and the tele radiology. (Author) 6 refs

  10. Assessment by human research ethics committees of potential conflicts of interest arising from pharmaceutical sponsorship of clinical research.

    Science.gov (United States)

    Newcombe, J P; Kerridge, I H

    2007-01-01

    Conflicts of interest arising from pharmaceutical industry sponsorship of clinical research have the potential to bias research outcomes and ultimately prejudice patient care. It is unknown how Australian Human Research Ethics Committees (HREC) assess and manage such conflicts of interest. We aimed to gain an understanding of how HREC approach the problem of potential conflicts of interest arising from pharmaceutical sponsorship of clinical research. We conducted a survey of HREC chairpersons in New South Wales. HREC vary widely in their approaches to conflicts of interest, including in their use of National Health and Medical Research Council guidelines, which were often misinterpreted or overlooked. Many committees rely primarily on researchers disclosing potential conflicts of interest, whereas a majority of HREC use disclosure to research participants as the primary tool for preventing and managing conflicts of interest. Almost no HREC place limitations on researcher relationships with pharmaceutical companies. These findings suggest reluctance on the part of HREC to regulate many potential conflicts of interest between researchers and pharmaceutical sponsors, which may arise from uncertainty regarding the meaning or significance of conflicts of interest in research, from ambiguity surrounding the role of HREC in assessing and managing conflicts of interest in research or from misinterpretation or ignorance of current National Health and Medical Research Council guidelines. Further review of policies and practices in this important area may prove beneficial in safeguarding clinical research and patient care while promoting continuing constructive engagement with the pharmaceutical industry.

  11. Potential Strategies to Address the Major Clinical Barriers Facing Stem Cell Regenerative Therapy for Cardiovascular Disease: A Review.

    Science.gov (United States)

    Nguyen, Patricia K; Neofytou, Evgenios; Rhee, June-Wha; Wu, Joseph C

    2016-11-01

    Although progress continues to be made in the field of stem cell regenerative medicine for the treatment of cardiovascular disease, significant barriers to clinical implementation still exist. To summarize the current barriers to the clinical implementation of stem cell therapy in patients with cardiovascular disease and to discuss potential strategies to overcome them. Information for this review was obtained through a search of PubMed and the Cochrane database for English-language studies published between January 1, 2000, and July 25, 2016. Ten randomized clinical trials and 8 systematic reviews were included. One of the major clinical barriers facing the routine implementation of stem cell therapy in patients with cardiovascular disease is the limited and inconsistent benefit observed thus far. Reasons for this finding are unclear but may be owing to poor cell retention and survival, as suggested by numerous preclinical studies and a small number of human studies incorporating imaging to determine cell fate. Additional studies in humans using imaging to determine cell fate are needed to understand how these factors contribute to the limited efficacy of stem cell therapy. Treatment strategies to address poor cell retention and survival are under investigation and include the following: coadministration of immunosuppressive and prosurvival agents, delivery of cardioprotective factors packaged in exosomes rather than the cells themselves, and use of tissue-engineering strategies to provide structural support for cells. If larger grafts are achieved using these strategies, it will be imperative to carefully monitor for the potential risks of tumorigenicity, immunogenicity, and arrhythmogenicity. Despite important achievements to date, stem cell therapy is not yet ready for routine clinical implementation. Significant research is still needed to address the clinical barriers outlined herein before the next wave of large clinical trials is under way.

  12. Cell-mediated immune response: a clinical review of the therapeutic potential of human papillomavirus vaccination.

    Science.gov (United States)

    Meyer, Sonja Izquierdo; Fuglsang, Katrine; Blaakaer, Jan

    2014-12-01

    This clinical review aims to assess the efficacy of human papillomavirus 16/18 (HPV16/18) vaccination on the cell-mediated immune response in women with existing cervical intraepithelial neoplasia or cervical cancer induced by HPV16 or HPV18. A focused and thorough literature search conducted in five different databases found 996 publications. Six relevant articles were chosen for further review. In total, 154 patients (>18 years of age) were enrolled in prospective study trials with 3-15 months of follow up. The vaccine applications were administered two to four times. The vaccines contained different combinations of HPV16 and HPV18 and early proteins, E6 and E7. The primary outcome was the cell-mediated immune response. Correlation to clinical outcome (histopathology) and human leukocyte antigen genes were secondary endpoints. All vaccines triggered a detectable cell-mediated immune response, some of which were statistically significant. Correlations between immunological response and clinical outcome (histopathology) were not significant, so neoplasms may not be susceptible to vaccine-generated cytotoxic T cells (CD8(+)). Prophylactic HPV vaccines have been introduced to reduce the incidence of cervical cancer in young women. Women already infected with HPV could benefit from a therapeutic HPV vaccination. Hence, it is important to continue the development of therapeutic HPV vaccines to lower the rate of HPV-associated malignancies and crucial to evaluate vaccine efficacy clinically. This clinical review represents an attempt to elucidate the theories supporting the development of an HPV vaccine with a therapeutic effect on human papillomavirus-induced malignancies of the cervix. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  13. How Successful Is Medicare Advantage?

    Science.gov (United States)

    Newhouse, Joseph P; McGuire, Thomas G

    2014-01-01

    Context Medicare Part C, or Medicare Advantage (MA), now almost 30 years old, has generally been viewed as a policy disappointment. Enrollment has vacillated but has never come close to the penetration of managed care plans in the commercial insurance market or in Medicaid, and because of payment policy decisions and selection, the MA program is viewed as having added to cost rather than saving funds for the Medicare program. Recent changes in Medicare policy, including improved risk adjustment, however, may have changed this picture. Methods This article summarizes findings from our group's work evaluating MA's recent performance and investigating payment options for improving its performance even more. We studied the behavior of both beneficiaries and plans, as well as the effects of Medicare policy. Findings Beneficiaries make “mistakes” in their choice of MA plan options that can be explained by behavioral economics. Few beneficiaries make an active choice after they enroll in Medicare. The high prevalence of “zero-premium” plans signals inefficiency in plan design and in the market's functioning. That is, Medicare premium policies interfere with economically efficient choices. The adverse selection problem, in which healthier, lower-cost beneficiaries tend to join MA, appears much diminished. The available measures, while limited, suggest that, on average, MA plans offer care of equal or higher quality and for less cost than traditional Medicare (TM). In counties, greater MA penetration appears to improve TM's performance. Conclusions Medicare policies regarding lock-in provisions and risk adjustment that were adopted in the mid-2000s have mitigated the adverse selection problem previously plaguing MA. On average, MA plans appear to offer higher value than TM, and positive spillovers from MA into TM imply that reimbursement should not necessarily be neutral. Policy changes in Medicare that reform the way that beneficiaries are charged for MA plan

  14. Reaching their potential: Perceived impact of a collaborative academic-clinical partnership programme for early career nurses in New Zealand.

    Science.gov (United States)

    McKillop, Ann; Doughty, Lesley; Atherfold, Cheryl; Shaw, Kathy

    2016-01-01

    The dynamic nature of healthcare ensures that early career nurses enter an uncertain and complex world of practice and consequently require support to develop their practice, build confidence and reach their potential. The New Zealand Nurse Entry to Practice programme for registered nurses in their first year of practice has been operating since 2005 to enable safe and confident practice, improve the quality of care, and positively impact on recruitment and retention. This academic and clinical programme was offered as a partnership between a university and a clinical provider with postgraduate academic credits gained. The aim of this study was to explore the perceived impact of postgraduate university education for early career nurses in one regional health area of New Zealand. Participants were registered nurses who had completed the early career nurse programme and their clinical preceptors. The research was conducted via an online survey of 248 nurses and three focus groups to explore how the programme was experienced and its impact on knowledge and practice. Early career nurses and their preceptors found that the programme enables improved knowledge and skills of patient assessment, application of critical thinking to clinical practice, perceived improvement in patient care delivery and outcomes, enhanced interprofessional communication and knowledge sharing, and had a positive impact on professional awareness and career planning. This clinical-academic partnership positively impacted on the clinical practice and transition experience of early career nurses and was closely aligned to an organization's strategic plan for nursing workforce development. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Evaluating tactile feedback in robotic surgery for potential clinical application using an animal model.

    Science.gov (United States)

    Wottawa, Christopher R; Genovese, Bradley; Nowroozi, Bryan N; Hart, Steven D; Bisley, James W; Grundfest, Warren S; Dutson, Erik P

    2016-08-01

    The aims of this study were to evaluate (1) grasping forces with the application of a tactile feedback system in vivo and (2) the incidence of tissue damage incurred during robotic tissue manipulation. Robotic-assisted minimally invasive surgery has been shown to be beneficial in a variety of surgical specialties, particularly radical prostatectomy. This innovative surgical tool offers advantages over traditional laparoscopic techniques, such as improved wrist-like maneuverability, stereoscopic video displays, and scaling of surgical gestures to increase precision. A widely cited disadvantage associated with robotic systems is the absence of tactile feedback. Nineteen subjects were categorized into two groups: 5 experts (six or more robotic cases) and 14 novices (five cases or less). The subjects used the da Vinci with integrated tactile feedback to run porcine bowel in the following conditions: (T1: deactivated tactile feedback; T2: activated tactile feedback; and T3: deactivated tactile feedback). The grasping force, incidence of tissue damage, and the correlation of grasping force and tissue damage were analyzed. Tissue damage was evaluated both grossly and histologically by a pathologist blinded to the sample. Tactile feedback resulted in significantly decreased grasping forces for both experts and novices (P system was deactivated (P > 0.05 in all subjects). The in vivo application of integrated tactile feedback in the robotic system demonstrates significantly reduced grasping forces, resulting in significantly less tissue damage. This tactile feedback system may improve surgical outcomes and broaden the use of robotic-assisted minimally invasive surgery.

  16. High-resolution proton NMR spectroscopy of cerebrospinal fluid: methodological issues and potential clinical applications

    International Nuclear Information System (INIS)

    Kriat, M.; Nicoli, F.; Vion-Dury, J.; Confort-Gouny, S.; Cozzone, P.J.; Nicoli, F.; Gastaut, J.L.; Dano, P.; Grisoli, F.

    1991-01-01

    High resolution proton nuclear magnetic resonance (NMR) spectroscopy is a new analytical technique which allows to readily identify and quantitate a variety of key metabolites in cerebrospinal fluid (CSF) in relation to normal and pathological brain activity. Proton NMR spectroscopy can be performed on native CSF, with or without addition of exchange reagent (NH 4 Cl). The analysis of native CSF provides qualitative information (identification) of metabolites or xenobiotics present in the fluid. Alternately, CSF can be lyophilized and dissolved in deuterated water. This concentration offers 2 advantages: additional compounds are detected and a precise quantification of all CSF metabolites can be obtained. Both protocols require a very small volume of CFS (1-2 ml). The high informational content available on the NMR spectra of CSF, the ease-of-use of NMR spectroscopy and its cost effectiveness concur to predict that this analytical approach will keep developing to completement the array of existing tests which are already routinely performed on CSF. 6 figs [fr

  17. Exploring the potential duty of care in clinical genomics under UK law.

    Science.gov (United States)

    Mitchell, Colin; Ploem, Corrette; Chico, Victoria; Ormondroyd, Elizabeth; Hall, Alison; Wallace, Susan; Fay, Michael; Goodwin, Deirdre; Bell, Jessica; Phillips, Simon; Taylor, Jenny C; Hennekam, Raoul; Kaye, Jane

    2017-09-01

    Genome-wide sequencing technologies are beginning to be used in projects that have both clinical diagnostic and research components. The clinical application of this technology, which generates a huge amount of information of varying diagnostic certainty, involves addressing a number of challenges to establish appropriate standards. In this article, we explore the way that UK law may respond to three of these key challenges and could establish new legal duties in relation to feedback of findings that are unrelated to the presenting condition (secondary, additional or incidental findings); duties towards genetic relatives as well as the patient and duties on the part of researchers and professionals who do not have direct contact with patients. When considering these issues, the courts will take account of European and international comparisons, developing guidance and relevant ethical, social and policy factors. The UK courts will also be strongly influenced by precedent set in case law.

  18. Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges

    OpenAIRE

    Kim, Dana; Kim, Young-Sam; Shin, Dong Wun; Park, Chang-Shin; Kang, Ju-Hee

    2016-01-01

    No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested bio...

  19. Prehospital Ultrasound in Trauma: A Review of Current and Potential Future Clinical Applications

    Directory of Open Access Journals (Sweden)

    Tharwat El Zahran

    2018-01-01

    Full Text Available Ultrasound (US is an essential tool for evaluating trauma patients in the hospital setting. Many previous in-hospital studies have been extrapolated to out of hospital setting to improve diagnostic accuracy in prehospital and austere environments. This review article presents the role of prehospital US in blunt and penetrating trauma management with emphasis on its current clinical applications, challenges, and future implications of such use.

  20. Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans.

    Science.gov (United States)

    Verloop, Herman; Dekkers, Olaf M; Peeters, Robin P; Schoones, Jan W; Smit, Johannes W A

    2014-09-01

    Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation. © 2014 European Society of Endocrinology.

  1. Theileriosis in six dogs in South Africa and its potential clinical significance

    Directory of Open Access Journals (Sweden)

    Chantal T. Rosa

    2014-08-01

    Full Text Available Theileriosis is a tick-borne disease caused by a piroplasma of the genus Theileria that can causeanaemia and thrombocytopenia. Its clinical importance for dogs’ remains poorly understood,as only some develop clinical signs. In this study, physical and laboratory findings, treatment and outcomes of six client-owned diseased dogs presented at the Onderstepoort Veterinary Academic Hospital are described retrospectively. In the dogs, Theileria species (n = 4and Theileria equi (n = 2 were detected by a polymerase chain reaction (PCR-reverse blothybridisation assay in blood samples, whilst PCR for Babesia, Anaplasma and Ehrlichia were negative. The most common physical findings were pale mucous membranes (five out of six dogs, bleeding tendencies (five out of six dogs and lethargy (three out of six dogs. All dogs were thrombocytopenic [median 59.5 x 109/L (range 13–199] and five out of six dogs were anaemic [median haematocrit 18% (range 5–32]. Bone marrow core biopsies performed in two dogs showed myelofibrosis. Theileriosis was treated with imidocarb dipropionate and the suspected secondary immune-mediated haematological disorders with prednisolone and azathioprine. Five dogs achieved clinical cure and post-treatment PCR performed in three out of five dogs confirmed absence of circulating parasitaemia. An immune-mediated response to Theileria species is thought to result in anaemia and/or thrombocytopenia in diseased dogs with theileriosis. A bleeding tendency, most likely secondary to thrombocytopenia and/or thrombocytopathy, was the most significant clinical finding in these cases. The link between thrombocytopenia, anaemia and myelofibrosis in theileriosis requires further investigation and theileriosis should be considered a differential diagnosis for dogs presenting with anaemia and/or thrombocytopenia in endemic tick-borne disease areas.

  2. The potential of predictive analytics to provide clinical decision support in depression treatment planning.

    Science.gov (United States)

    Kessler, Ronald C

    2018-01-01

    To review progress developing clinical decision support tools for personalized treatment of major depressive disorder (MDD). Over the years, a variety of individual indicators ranging from biomarkers to clinical observations and self-report scales have been used to predict various aspects of differential MDD treatment response. Most of this work focused on predicting remission either with antidepressant medications versus psychotherapy, some antidepressant medications versus others, some psychotherapies versus others, and combination therapies versus monotherapies. However, to date, none of the individual predictors in these studies has been strong enough to guide optimal treatment selection for most patients. Interest consequently turned to decision support tools made up of multiple predictors, but the development of such tools has been hampered by small study sample sizes. Design recommendations are made here for future studies to address this problem. Recommendations include using large prospective observational studies followed by pragmatic trials rather than smaller, expensive controlled treatment trials for preliminary development of decision support tools; basing these tools on comprehensive batteries of inexpensive self-report and clinical predictors (e.g., self-administered performance-based neurocognitive tests) versus expensive biomarkers; and reserving biomarker assessments for targeted studies of patients not well classified by inexpensive predictor batteries.

  3. Reflective THz and MR imaging of burn wounds: a potential clinical validation of THz contrast mechanisms

    Science.gov (United States)

    Bajwa, Neha; Nowroozi, Bryan; Sung, Shijun; Garritano, James; Maccabi, Ashkan; Tewari, Priyamvada; Culjat, Martin; Singh, Rahul; Alger, Jeffry; Grundfest, Warren; Taylor, Zachary

    2012-10-01

    Terahertz (THz) imaging is an expanding area of research in the field of medical imaging due to its high sensitivity to changes in tissue water content. Previously reported in vivo rat studies demonstrate that spatially resolved hydration mapping with THz illumination can be used to rapidly and accurately detect fluid shifts following induction of burns and provide highly resolved spatial and temporal characterization of edematous tissue. THz imagery of partial and full thickness burn wounds acquired by our group correlate well with burn severity and suggest that hydration gradients are responsible for the observed contrast. This research aims to confirm the dominant contrast mechanism of THz burn imaging using a clinically accepted diagnostic method that relies on tissue water content for contrast generation to support the translation of this technology to clinical application. The hydration contrast sensing capabilities of magnetic resonance imaging (MRI), specifically T2 relaxation times and proton density values N(H), are well established and provide measures of mobile water content, lending MRI as a suitable method to validate hydration states of skin burns. This paper presents correlational studies performed with MR imaging of ex vivo porcine skin that confirm tissue hydration as the principal sensing mechanism in THz burn imaging. Insights from this preliminary research will be used to lay the groundwork for future, parallel MRI and THz imaging of in vivo rat models to further substantiate the clinical efficacy of reflective THz imaging in burn wound care.

  4. Hsp90 as a Gatekeeper of Tumor Angiogenesis: Clinical Promise and Potential Pitfalls

    Directory of Open Access Journals (Sweden)

    J. E. Bohonowych

    2010-01-01

    Full Text Available Tumor vascularization is an essential modulator of early tumor growth, progression, and therapeutic outcome. Although antiangiogenic treatments appear promising, intrinsic and acquired tumor resistance contributes to treatment failure. Clinical inhibition of the molecular chaperone heat shock protein 90 (Hsp90 provides an opportunity to target multiple aspects of this signaling resiliency, which may elicit more robust and enduring tumor repression relative to effects elicited by specifically targeted agents. This review highlights several primary effectors of angiogenesis modulated by Hsp90 and describes the clinical challenges posed by the redundant circuitry of these pathways. The four main topics addressed include (1 Hsp90-mediated regulation of HIF/VEGF signaling, (2 chaperone-dependent regulation of HIF-independent VEGF-mediated angiogenesis, (3 Hsp90-dependent targeting of key proangiogenic receptor tyrosine kinases and modulation of drug resistance, and (4 consideration of factors such as tumor microenvironment that pose several challenges for the clinical efficacy of anti-angiogenic therapy and Hsp90-targeted strategies.

  5. In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions.

    Science.gov (United States)

    Flanagan, S; Bartizal, K; Minassian, S L; Fang, E; Prokocimer, P

    2013-07-01

    Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions. In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥ 30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥ 2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-B in vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered at www.clinicaltrials.gov as NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459

  6. Advantages and Limitations of Direct PCR Amplification of Bacterial 16S-rDNA from Resected Heart Tissue or Swabs Followed by Direct Sequencing for Diagnosing Infective Endocarditis: A Retrospective Analysis in the Routine Clinical Setting

    Directory of Open Access Journals (Sweden)

    Daniela Maneg

    2016-01-01

    Full Text Available Infective endocarditis (IE is a life-threatening disease that is associated with high morbidity and mortality. Its long-term prognosis strongly depends on a timely and optimized antibiotic treatment. Therefore, identification of the causative pathogen is crucial and currently based on blood cultures followed by characterization and susceptibility testing of the isolate. However, antibiotic treatment starting prior to blood sampling or IE caused by fastidious or intracellular microorganisms may cause negative culture results. Here we investigate the additional diagnostic value of broad-range PCR in combination with direct sequencing on resected heart tissue or swabs in patients with tissue or swab culture-negative IE in a routine clinical setting. Sensitivity, specificity, and positive and negative predictive values of broad-range PCR from diagnostic material in our patients were 33.3%, 76.9%, 90.9%, and 14.3%, respectively. We identified a total of 20 patients (21.5% with tissue or culture-negative IE who profited by the additional application of broad-range PCR. We conclude that broad-range PCR on resected heart tissue or swabs is an important complementary diagnostic approach. It should be seen as an indispensable new tool for both the therapeutic and diagnostic management of culture-negative IE and we thus propose its possible inclusion in Duke’s diagnostic classification scheme.

  7. Advantages and Limitations of Direct PCR Amplification of Bacterial 16S-rDNA from Resected Heart Tissue or Swabs Followed by Direct Sequencing for Diagnosing Infective Endocarditis: A Retrospective Analysis in the Routine Clinical Setting.

    Science.gov (United States)

    Maneg, Daniela; Sponsel, Janina; Müller, Iris; Lohr, Benedikt; Penders, John; Madlener, Katharina; Hunfeld, Klaus-Peter

    2016-01-01

    Infective endocarditis (IE) is a life-threatening disease that is associated with high morbidity and mortality. Its long-term prognosis strongly depends on a timely and optimized antibiotic treatment. Therefore, identification of the causative pathogen is crucial and currently based on blood cultures followed by characterization and susceptibility testing of the isolate. However, antibiotic treatment starting prior to blood sampling or IE caused by fastidious or intracellular microorganisms may cause negative culture results. Here we investigate the additional diagnostic value of broad-range PCR in combination with direct sequencing on resected heart tissue or swabs in patients with tissue or swab culture-negative IE in a routine clinical setting. Sensitivity, specificity, and positive and negative predictive values of broad-range PCR from diagnostic material in our patients were 33.3%, 76.9%, 90.9%, and 14.3%, respectively. We identified a total of 20 patients (21.5%) with tissue or culture-negative IE who profited by the additional application of broad-range PCR. We conclude that broad-range PCR on resected heart tissue or swabs is an important complementary diagnostic approach. It should be seen as an indispensable new tool for both the therapeutic and diagnostic management of culture-negative IE and we thus propose its possible inclusion in Duke's diagnostic classification scheme.

  8. Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma

    International Nuclear Information System (INIS)

    Hantson, Philippe; Grandin, Cecile; Duprez, Thierry; Nassogne, Marie-Cecile; Guerit, Jean-Michel

    2005-01-01

    Magnetic resonance (MR) multimodality evoked potentials (MEPs) and clinical findings were correlated in a 47-year-old epileptic man in whom parenteral valproic acid (VPA) therapy induced severe comatose hyperammonemic encephalopathy without biological signs of hepatotoxicity (or hepatocytic dysfunction). Although the plasma VPA level remained within a normal therapeutic range, the ammoniemia increased to a toxic peak level at 411 μmol/l 24 h after symptom onset, requiring VPA therapy discontinuation. Brain MR monitoring demonstrated early cytotoxic edema evolving into delayed vasogenic edema and final brain atrophy. Concomitantly to abnormalities within the brainstem on MR images, an increase in brainstem conduction at MEPs and clinical disturbance of brainstem reflexes were observed at the initial phase of the disease course. Later, the resolution of the MR and MEPs abnormalities paralleled the clinical recovery of the reflexes. (orig.)

  9. Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma

    Energy Technology Data Exchange (ETDEWEB)

    Hantson, Philippe [Universite Catholique de Louvain, Department of Intensive Care, Cliniques Saint-Luc, Brussels (Belgium); Grandin, Cecile; Duprez, Thierry [Universite Catholique de Louvain, Department of Neuroradiology, Cliniques Saint-Luc, Brussels (Belgium); Nassogne, Marie-Cecile [Universite Catholique de Louvain, Department of Pediatric Neurology, Cliniques Saint-Luc, Brussels (Belgium); Guerit, Jean-Michel [Universite Catholique de Louvain, Laboratory of Neurophysiology, Cliniques Saint-Luc, Brussels (Belgium)

    2005-01-01

    Magnetic resonance (MR) multimodality evoked potentials (MEPs) and clinical findings were correlated in a 47-year-old epileptic man in whom parenteral valproic acid (VPA) therapy induced severe comatose hyperammonemic encephalopathy without biological signs of hepatotoxicity (or hepatocytic dysfunction). Although the plasma VPA level remained within a normal therapeutic range, the ammoniemia increased to a toxic peak level at 411 {mu}mol/l 24 h after symptom onset, requiring VPA therapy discontinuation. Brain MR monitoring demonstrated early cytotoxic edema evolving into delayed vasogenic edema and final brain atrophy. Concomitantly to abnormalities within the brainstem on MR images, an increase in brainstem conduction at MEPs and clinical disturbance of brainstem reflexes were observed at the initial phase of the disease course. Later, the resolution of the MR and MEPs abnormalities paralleled the clinical recovery of the reflexes. (orig.)

  10. Advantages and disadvantages of biodegradable platforms in drug eluting stents.

    Science.gov (United States)

    Rodriguez-Granillo, Agustina; Rubilar, Bibiana; Rodriguez-Granillo, Gaston; Rodriguez, Alfredo E

    2011-03-26

    Coronary angioplasty with drug-eluting stent (DES) implantation is currently the most common stent procedure worldwide. Since the introduction of DES, coronary restenosis as well as the incidence of target vessel and target lesion revascularization have been significantly reduced. However, the incidence of very late stent thrombosis beyond the first year after stent deployment has more commonly been linked to DES than to bare-metal stent (BMS) implantation. Several factors have been associated with very late stent thrombosis after DES implantation, such as delayed healing, inflammation, stent mal-apposition and endothelial dysfunction. Some of these adverse events were associated with the presence of durable polymers, which were essential to allow the elution of the immunosuppressive drug in the first DES designs. The introduction of erodable polymers in DES technology has provided the potential to complete the degradation of the polymer simultaneously or immediately after the release of the immunosuppressive drug, after which a BMS remains in place. Several DES designs with biodegradable (BIO) polymers have been introduced in preclinical and clinical studies, including randomized trials. In this review, we analyze the clinical results from 6 observational and randomized studies with BIO polymers and discuss advantages and disadvantages of this new technology.

  11. Prevalence and clinical outcomes of patients with multiple potential causes of syncope

    NARCIS (Netherlands)

    Chen, Lin Y.; Gersh, Bernard J.; Hodge, David O.; Wieling, Wouter; Hammill, Stephen C.; Shen, Win-Kuang

    2003-01-01

    Objective: To determine the prevalence, predictors, and prognosis of patients with multiple potential causes of syncope. Patients and Methods: This is a retrospective cohort study with prospective follow-up of consecutive patients with syncope of uncertain cause who were referred to the

  12. High throughput static and dynamic small animal imaging using clinical PET/CT: potential preclinical applications

    International Nuclear Information System (INIS)

    Aide, Nicolas; Desmonts, Cedric; Agostini, Denis; Bardet, Stephane; Bouvard, Gerard; Beauregard, Jean-Mathieu; Roselt, Peter; Neels, Oliver; Beyer, Thomas; Kinross, Kathryn; Hicks, Rodney J.

    2010-01-01

    The objective of the study was to evaluate state-of-the-art clinical PET/CT technology in performing static and dynamic imaging of several mice simultaneously. A mouse-sized phantom was imaged mimicking simultaneous imaging of three mice with computation of recovery coefficients (RCs) and spillover ratios (SORs). Fifteen mice harbouring abdominal or subcutaneous tumours were imaged on clinical PET/CT with point spread function (PSF) reconstruction after injection of [18F]fluorodeoxyglucose or [18F]fluorothymidine. Three of these mice were imaged alone and simultaneously at radial positions -5, 0 and 5 cm. The remaining 12 tumour-bearing mice were imaged in groups of 3 to establish the quantitative accuracy of PET data using ex vivo gamma counting as the reference. Finally, a dynamic scan was performed in three mice simultaneously after the injection of 68 Ga-ethylenediaminetetraacetic acid (EDTA). For typical lesion sizes of 7-8 mm phantom experiments indicated RCs of 0.42 and 0.76 for ordered subsets expectation maximization (OSEM) and PSF reconstruction, respectively. For PSF reconstruction, SOR air and SOR water were 5.3 and 7.5%, respectively. A strong correlation (r 2 = 0.97, p 2 = 0.98; slope = 0.89, p 2 = 0.96; slope = 0.62, p 68 Ga-EDTA dynamic acquisition. New generation clinical PET/CT can be used for simultaneous imaging of multiple small animals in experiments requiring high throughput and where a dedicated small animal PET system is not available. (orig.)

  13. Proteomic profiling in multiple sclerosis clinical courses reveals potential biomarkers of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Maria Liguori

    Full Text Available The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF proteomic profiles of Multiple Sclerosis (MS patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS, 16 Relapsing Remitting (RR MS, 11 Progressive (Pr MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000-25000 Da. Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ≥ 1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05, whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04. Additionally, the intensity of the Tymosin β4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p = 0.013. Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS.

  14. Harnessing the potential clinical use of medicinal plants as anti-diabetic agents

    Directory of Open Access Journals (Sweden)

    Campbell-Tofte JI

    2012-08-01

    Full Text Available Joan IA Campbell-Tofte,1 Per Mølgaard,2 Kaj Winther11Department of Clinical Biochemistry, Frederiksberg University Hospital, Frederiksberg, Denmark; 2Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, DenmarkAbstract: Diabetes is a metabolic disorder arising from complex interactions between multiple genetic and/or environmental factors. The characteristic high blood sugar levels result from either lack of the hormone insulin (type 1 diabetes, T1D, or because body tissues do not respond to the hormone (type 2 diabetes, T2D. T1D patients currently need exogenous insulin for life, while for T2D patients who do not respond to diet and exercise regimes, oral anti-diabetic drugs (OADs and sometimes insulin are administered to help keep their blood glucose as normal as possible. As neither the administration of insulin nor OADs is curative, many patients develop tissue degenerative processes that result in life-threatening diabetes comorbidities. Several surveys of medicinal plants used as anti-diabetic agents amongst different peoples have been published. Some of this interest is driven by the ongoing diabetes pandemic coupled with the inadequacies associated with the current state of-the-art care and management of the syndrome. However, there is a huge cleft between traditional medicine and modern (Western medicine, with the latter understandably demanding meaningful and scientific validation of anecdotal evidence for acceptance of the former. The main problems for clinical evaluation of medicinal plants with promising anti-diabetic properties reside both with the complexity of components of the plant materials and with the lack of full understanding of the diabetes disease etiology. This review is therefore focused on why research activities involving an integration of Systems Biology-based technologies of pharmacogenomics, metabolomics, and bioinformatics with standard clinical data

  15. Clinical evidence of the efficacy of everolimus and its potential in the treatment of breast cancer

    Directory of Open Access Journals (Sweden)

    Saksena R

    2013-05-01

    Full Text Available Rujuta Saksena, Serena T WongThe Cancer Institute of New Jersey, New Brunswick, NJ, USAAbstract: The PI3K/Akt/mTOR (phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway regulates several key cellular functions and its dysregulation creates an environment that promotes tumorigenesis as well as resistance to therapy. The mTOR inhibitor everolimus has emerged as a promising agent in the treatment of breast cancer and was recently approved in combination with exemestane for advanced hormone receptor–positive disease after progression on a nonsteroidal aromatase inhibitor. Everolimus may also be effective in combination with cytotoxic and human epidermal growth factor receptor-2-directed therapies for the treatment of other subtypes of breast cancer. This paper highlights preclinical and clinical data that have emerged on the role of mTOR inhibition in breast cancer. Although generally well tolerated, everolimus carries a unique side effect profile of which both patients and providers should be made aware. Recommendations related to the administration of everolimus in the clinical setting are also discussed.Keywords: everolimus, breast cancer, mTOR inhibition

  16. Diffusion weighted imaging demystified. The technique and potential clinical applications for soft tissue imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ahlawat, Shivani [The Johns Hopkins Medical Institutions, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Fayad, Laura M. [The Johns Hopkins Medical Institutions, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); The Johns Hopkins Medical Institutions, Department of Oncology, Baltimore, MD (United States); The Johns Hopkins Medical Institutions, Department of Orthopaedic Surgery, Baltimore, MD (United States)

    2018-03-15

    Diffusion-weighted imaging (DWI) is a fast, non-contrast technique that is readily available and easy to integrate into an existing imaging protocol. DWI with apparent diffusion coefficient (ADC) mapping offers a quantitative metric for soft tissue evaluation and provides information regarding the cellularity of a region of interest. There are several available methods of performing DWI, and artifacts and pitfalls must be considered when interpreting DWI studies. This review article will review the various techniques of DWI acquisition and utility of qualitative as well as quantitative methods of image interpretation, with emphasis on optimal methods for ADC measurement. The current clinical applications for DWI are primarily related to oncologic evaluation: For the assessment of de novo soft tissue masses, ADC mapping can serve as a useful adjunct technique to routine anatomic sequences for lesion characterization as cyst or solid and, if solid, benign or malignant. For treated soft tissue masses, the role of DWI/ADC mapping in the assessment of treatment response as well as recurrent or residual neoplasm in the setting of operative management is discussed, especially when intravenous contrast medium cannot be given. Emerging DWI applications for non-neoplastic clinical indications are also reviewed. (orig.)

  17. Diffusion weighted imaging demystified. The technique and potential clinical applications for soft tissue imaging

    International Nuclear Information System (INIS)

    Ahlawat, Shivani; Fayad, Laura M.

    2018-01-01

    Diffusion-weighted imaging (DWI) is a fast, non-contrast technique that is readily available and easy to integrate into an existing imaging protocol. DWI with apparent diffusion coefficient (ADC) mapping offers a quantitative metric for soft tissue evaluation and provides information regarding the cellularity of a region of interest. There are several available methods of performing DWI, and artifacts and pitfalls must be considered when interpreting DWI studies. This review article will review the various techniques of DWI acquisition and utility of qualitative as well as quantitative methods of image interpretation, with emphasis on optimal methods for ADC measurement. The current clinical applications for DWI are primarily related to oncologic evaluation: For the assessment of de novo soft tissue masses, ADC mapping can serve as a useful adjunct technique to routine anatomic sequences for lesion characterization as cyst or solid and, if solid, benign or malignant. For treated soft tissue masses, the role of DWI/ADC mapping in the assessment of treatment response as well as recurrent or residual neoplasm in the setting of operative management is discussed, especially when intravenous contrast medium cannot be given. Emerging DWI applications for non-neoplastic clinical indications are also reviewed. (orig.)

  18. Bicuspid aortic valve syndrome and fibrillinopathies: potential impact on clinical approach

    Directory of Open Access Journals (Sweden)

    Rosina De Cario

    2014-01-01

    Full Text Available Bicuspid aortic valve (BAV is a common heterogeneous disorder whose natural history is determined by hemodynamic valvular impairment and/or increased prevalence of aortic abnormalities ranging from dilatation to aneurysm and dissection. BAV-related aortopathy is frequently associated with relevant aortic pathologic changes leading to structural alterations, characteristic degenerative lesions and histological changes of the aorta very similar to those identified and described in patients with Marfan syndrome (MFS, an inherited connective tissue disorder associated with mutations in fibrillin 1 (FBN1 gene in more than 90% of patients. Recently, a 4-fold increase in the prevalence of BAV in MFS patients has been reported. Subsequently, pathogenetic FBN1 mutations in patients with BAV and aortic dilatation/aneurysm in whom MFS and other more severe type 1 fibrillinopathies were clinically excluded have been identified. In this review we discuss how this evidence, together with that of the wide heterogeneity in pathogenetic mechanisms of BAV-related aortopathy, may impact the clinical management of BAV.

  19. Microscope use in clinical veterinary practice and potential implications for veterinary school curricula.

    Science.gov (United States)

    Stewart, Sherry M; Dowers, Kristy L; Cerda, Jacey R; Schoenfeld-Tacher, Regina M; Kogan, Lori R

    2014-01-01

    Microscopy (skill of using a microscope) and the concepts of cytology (study of cells) and histology (study of tissues) are most often taught in professional veterinary medicine programs through the traditional method of glass slides and light microscopes. Several limiting factors in veterinary training programs are encouraging educators to explore innovative options for teaching microscopy skills and the concepts of cytology and histology. An anonymous online survey was administered through the Colorado Veterinary Medical Association to Colorado veterinarians working in private practice. It was designed to assess their current usage of microscopes for cytological and histological evaluation of specimens and their perceptions of microscope use in their veterinary education. The first part of the survey was answered by 183 veterinarians, with 104 indicating they had an onsite diagnostic lab. Analysis pertaining to the use of the microscope in practice and in veterinary programs was conducted on this subset. Most respondents felt the amount of time spent in the curriculum using a microscope was just right for basic microscope use and using the microscope for viewing and learning about normal and abnormal histological sections and clinical cytology. Participants felt more emphasis could be placed on clinical and diagnostic cytology. Study results suggest that practicing veterinarians frequently use microscopes for a wide variety of cytological diagnostics. However, only two respondents indicated they prepared samples for histological evaluation. Veterinary schools should consider these results against the backdrop of pressure to implement innovative teaching techniques to meet the changing needs of the profession.

  20. Therapeutic Potential of Tolerogenic Dendritic Cells in IBD: From Animal Models to Clinical Application

    Directory of Open Access Journals (Sweden)

    Raquel Cabezón

    2013-01-01

    Full Text Available The gut mucosa undergoes continuous antigenic exposure from food antigens, commensal flora derived ligands, and pathogens. This constant stimulation results in controlled inflammatory responses that are effectively suppressed by multiple factors. This tight regulation, necessary to maintain intestinal homeostasis, is affected during inflammatory bowel diseases (IBD resulting in altered immune responses to harmless microorganisms. Dendritic cells (DCs are sentinels of immunity, located in peripheral and lymphoid tissues, which are essential for homeostasis of T cell-dependent immune responses. The expression of a particular set of pathogen recognition receptors allows DCs to initiate immune responses. However, in the absence of danger signals, different DC subsets can induce active tolerance by inducing regulatory T cells (Treg, inhibiting inflammatory T helper cell responses, or both. Interestingly, several protocols to generate clinical grade tolerogenic DC (tol-DCs in vitro have been described, opening the possibility to restore the intestinal homeostasis to bacterial flora by cellular therapy. In this review, we discuss different DC subsets and their role in IBD. Additionally, we will review preclinical studies performed in animal models while describing recent characterization of tol-DCs from Crohn’s disease patients for clinical application.

  1. Amniotic membrane-derived stem cells: immunomodulatory properties and potential clinical application

    Directory of Open Access Journals (Sweden)

    Insausti CL

    2014-03-01

    Full Text Available Carmen L Insausti,1 Miguel Blanquer,1 Ana M García-Hernández,1 Gregorio Castellanos,2 José M Moraleda11Unidad de Trasplante Hematopoyético y Terapia Celular, 2Servicio de Cirugía, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB, Campus Mare Nostrum, Universidad de Murcia, El Palmar, Murcia, SpainAbstract: Epithelial and mesenchymal cells isolated from the amniotic membrane (AM possess stem cell characteristics, differentiation potential toward lineages of different germ layers, and immunomodulatory properties. While their expansion and differentiation potential have been well studied and characterized, knowledge about their immunomodulatory properties and the mechanisms involved is still incomplete. These mechanisms have been evaluated on various target cells of the innate and the adaptive system and in animal models of different inflammatory diseases. Some results have evidenced that the immunomodulatory effect of AM-derived cells is dependent on cell-cell contact, but many of them have demonstrated that these properties are mediated through the secretion of suppressive molecules. In this review, we present an update on the described immunomodulatory properties of the derived amniotic cells and some of the proposed involved mechanisms. Furthermore, we describe some assays in animal models of different inflammatory diseases which reveal the potential use of these cells to treat such diseases.Keywords: epithelial cells, mesenchymal cells, cell therapy, immunomodulation

  2. Nurses' creativity: advantage or disadvantage.

    Science.gov (United States)

    Shahsavari Isfahani, Sara; Hosseini, Mohammad Ali; Fallahi Khoshknab, Masood; Peyrovi, Hamid; Khanke, Hamid Reza

    2015-02-01

    Recently, global nursing experts have been aggressively encouraging nurses to pursue creativity and innovation in nursing to improve nursing outcomes. Nurses' creativity plays a significant role in health and well-being. In most health systems across the world, nurses provide up to 80% of the primary health care; therefore, they are critically positioned to provide creative solutions for current and future global health challenges. The purpose of this study was to explore Iranian nurses' perceptions and experiences toward the expression of creativity in clinical settings and the outcomes of their creativity for health care organizations. A qualitative approach using content analysis was adopted. Data were collected through in-depth semistructured interviews with 14 nurses who were involved in the creative process in educational hospitals affiliated to Jahrom and Tehran Universities of Medical Sciences in Iran. Four themes emerged from the data analysis, including a) Improvement in quality of patient care, b) Improvement in nurses' quality of work, personal and social life, c) Promotion of organization, and d) Unpleasant outcomes. The findings indicated that nurses' creativity in health care organizations can lead to major changes of nursing practice, improvement of care and organizational performance. Therefore, policymakers, nurse educators, nursing and hospital managers should provide a nurturing environment that is conducive to creative thinking, giving the nurses opportunity for flexibility, creativity, support for change, and risk taking.

  3. NEW METABOLIC INDEX USE POTENTIALITIES IN EVALUATION OF INSULIN RESISTANCE IN CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    G. E. Roytberg

    2015-09-01

    Full Text Available Early diagnostics of insulin resistance (IR is one of the methods of primary prevention of cardio-vascular diseases and type 2 diabetes mellitus. The HOMA-IR index and ratio of plasma triglyceride to high-density lipoprotein cholesterol concentration are the most frequently used indices in clinical and epidemiological scientific research. Prognostic value and efficacy of these tests as a screening method are not high. What method of IR detection should be used in clinical practice and how to interpret received values of the indices is still a matter of dispute.Aim. To evaluate informative value, sensitivity and specificity of a new metabolic index (MI for IR estimation in comparison with the calculated HOMA-IR index.Material and methods. A total of 845 patients (298 men, 547 women were enrolled into the further study after an outpatient regular medical check-up of 2,615 persons. Mean age of the patients was 45.77±12.18 years, body mass index – 28.95±1.44 kg/m2. To evaluate lipid and carbohydrate metabolism blood chemistry parameters were assessed. IR was determined by the Homeostasis Model Assessment (HOMA-IR and an oblique calculated index based on lipid metabolism parameters. In accordance with the developed screening method of IR detection (invention patent № 2493566 MI considering carbohydrate and lipid changes was proposed.Results. Calculation of MI and its threshold level was performed by analysis of a characteristic curve. Graphical dependence between sensitivity and specificity of the proposed index was demonstrated: sensitivity of the test was 75.7%, specificity – 89.1%. Probability of IR at MI value >7.0 was 63.5% (positive predictive value, probability of IR absence at the index value ≤7.0 was 93.6% (negative predictive value. The general accuracy of the test, which is characterized by the area under the characteristic curve, was 0.881 with 95%-confidence interval within 0.854-0.905.Conclusion. The importance of negative

  4. NEW METABOLIC INDEX USE POTENTIALITIES IN EVALUATION OF INSULIN RESISTANCE IN CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    G. E. Roytberg

    2014-01-01

    Full Text Available Early diagnostics of insulin resistance (IR is one of the methods of primary prevention of cardio-vascular diseases and type 2 diabetes mellitus. The HOMA-IR index and ratio of plasma triglyceride to high-density lipoprotein cholesterol concentration are the most frequently used indices in clinical and epidemiological scientific research. Prognostic value and efficacy of these tests as a screening method are not high. What method of IR detection should be used in clinical practice and how to interpret received values of the indices is still a matter of dispute.Aim. To evaluate informative value, sensitivity and specificity of a new metabolic index (MI for IR estimation in comparison with the calculated HOMA-IR index.Material and methods. A total of 845 patients (298 men, 547 women were enrolled into the further study after an outpatient regular medical check-up of 2,615 persons. Mean age of the patients was 45.77±12.18 years, body mass index – 28.95±1.44 kg/m2. To evaluate lipid and carbohydrate metabolism blood chemistry parameters were assessed. IR was determined by the Homeostasis Model Assessment (HOMA-IR and an oblique calculated index based on lipid metabolism parameters. In accordance with the developed screening method of IR detection (invention patent № 2493566 MI considering carbohydrate and lipid changes was proposed.Results. Calculation of MI and its threshold level was performed by analysis of a characteristic curve. Graphical dependence between sensitivity and specificity of the proposed index was demonstrated: sensitivity of the test was 75.7%, specificity – 89.1%. Probability of IR at MI value >7.0 was 63.5% (positive predictive value, probability of IR absence at the index value ≤7.0 was 93.6% (negative predictive value. The general accuracy of the test, which is characterized by the area under the characteristic curve, was 0.881 with 95%-confidence interval within 0.854-0.905.Conclusion. The importance of negative

  5. Predicting PTSD using the New York Risk Score with genotype data: potential clinical and research opportunities

    Directory of Open Access Journals (Sweden)

    Boscarino JA

    2013-04-01

    Full Text Available Joseph A Boscarino,1,2 H Lester Kirchner,3,4 Stuart N Hoffman,5 Porat M Erlich1,4 1Center for Health Research, Geisinger Clinic, Danville, 2Department of Psychiatry, Temple University School of Medicine, Philadelphia, 3Division of Medicine, Geisinger Clinic, Danville, 4Department of Medicine, Temple University School of Medicine, Philadelphia, 5Department of Neurology, Geisinger Clinic, Danville, PA, USA Background: We previously developed a post-traumatic stress disorder (PTSD screening instrument, ie, the New York PTSD Risk Score (NYPRS, that was effective in predicting PTSD. In the present study, we assessed a version of this risk score that also included genetic information. Methods: Utilizing diagnostic testing methods, we hierarchically examined different prediction variables identified in previous NYPRS research, including genetic risk-allele information, to assess lifetime and current PTSD status among a population of trauma-exposed adults. Results: We found that, in predicting lifetime PTSD, the area under the receiver operating characteristic curve (AUC for the Primary Care PTSD Screen alone was 0.865. When we added psychosocial predictors from the original NYPRS to the model, including depression, sleep disturbance, and a measure of health care access, the AUC increased to 0.902, which was a significant improvement (P = 0.0021. When genetic information was added in the form of a count of PTSD risk alleles located within FKBP, COMT, CHRNA5, and CRHR1 genetic loci (coded 0–6, the AUC increased to 0.920, which was also a significant improvement (P = 0.0178. The results for current PTSD were similar. In the final model for current PTSD with the psychosocial risk factors included, genotype resulted in a prediction weight of 17 for each risk allele present, indicating that a person with six risk alleles or more would receive a PTSD risk score of 17 × 6 = 102, the highest risk score for any of the predictors studied. Conclusion: Genetic

  6. Complexities and potential pitfalls of clinical study design and data analysis in assisted reproduction.

    Science.gov (United States)

    Patounakis, George; Hill, Micah J

    2018-06-01

    The purpose of the current review is to describe the common pitfalls in design and statistical analysis of reproductive medicine studies. It serves to guide both authors and reviewers toward reducing the incidence of spurious statistical results and erroneous conclusions. The large amount of data gathered in IVF cycles leads to problems with multiplicity, multicollinearity, and over fitting of regression models. Furthermore, the use of the word 'trend' to describe nonsignificant results has increased in recent years. Finally, methods to accurately account for female age in infertility research models are becoming more common and necessary. The pitfalls of study design and analysis reviewed provide a framework for authors and reviewers to approach clinical research in the field of reproductive medicine. By providing a more rigorous approach to study design and analysis, the literature in reproductive medicine will have more reliable conclusions that can stand the test of time.

  7. Biology and potential clinical implications of tissue inhibitor of metalloproteinases-1 in colorectal cancer treatment

    DEFF Research Database (Denmark)

    Sørensen, Nanna Møller; Sørensen, irene Vejgaard; Würtz, Sidse Ørnbjerg

    2008-01-01

    Colorectal cancer (CRC) is the second leading cause of cancer-related death in the industrialized world. About half of "curatively" resected patients develop recurrent disease within the next 3-5 years despite the lack of clinical, histological and biochemical evidence of remaining overt disease...... after resection of the primary tumour. Availability of validated biological markers for early detection, selection for adjuvant therapy, prediction of treatment efficacy and monitoring of treatment efficacy would most probably increase survival. Tissue inhibitor of metalloproteinases-1 (TIMP-1) may...... patients, suggesting that TIMP-1 could have a tumour-promoting function. Furthermore, measurement of plasma TIMP-1 has been shown to be useful for disease detection, with a high sensitivity and high specificity for early-stage colon cancer. This review describes some basic information on the current...

  8. Towards Achieving the Full Clinical Potential of Proton Therapy by Inclusion of LET and RBE Models

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Bleddyn [Gray Laboratory, CRUK/MRC Oxford Oncology Institute, The University of Oxford, ORCRB-Roosevelt Drive, Oxford OX3 7DQ (United Kingdom)

    2015-03-17

    Despite increasing use of proton therapy (PBT), several systematic literature reviews show limited gains in clinical outcomes, with publications mostly devoted to recent technical developments. The lack of randomised control studies has also hampered progress in the acceptance of PBT by many oncologists and policy makers. There remain two important uncertainties associated with PBT, namely: (1) accuracy and reproducibility of Bragg peak position (BPP); and (2) imprecise knowledge of the relative biological effect (RBE) for different tissues and tumours, and at different doses. Incorrect BPP will change dose, linear energy transfer (LET) and RBE, with risks of reduced tumour control and enhanced toxicity. These interrelationships are discussed qualitatively with respect to the ICRU target volume definitions. The internationally accepted proton RBE of 1.1 was based on assays and dose ranges unlikely to reveal the complete range of RBE in the human body. RBE values are not known for human (or animal) brain, spine, kidney, liver, intestine, etc. A simple efficiency model for estimating proton RBE values is described, based on data of Belli et al. and other authors, which allows linear increases in α and β with LET, with a gradient estimated using a saturation model from the low LET α and β radiosensitivity parameter input values, and decreasing RBE with increasing dose. To improve outcomes, 3-D dose-LET-RBE and bio-effectiveness maps are required. Validation experiments are indicated in relevant tissues. Randomised clinical studies that test the invariant 1.1 RBE allocation against higher values in late reacting tissues, and lower tumour RBE values in the case of radiosensitive tumours, are also indicated.

  9. Clinical potentials of methylator phenotype in stage 4 high-risk neuroblastoma: an open challenge.

    Directory of Open Access Journals (Sweden)

    Barbara Banelli

    Full Text Available Approximately 20% of stage 4 high-risk neuroblastoma patients are alive and disease-free 5 years after disease onset while the remaining experience rapid and fatal progression. Numerous findings underline the prognostic role of methylation of defined target genes in neuroblastoma without taking into account the clinical and biological heterogeneity of this disease. In this report we have investigated the methylation of the PCDHB cluster, the most informative member of the "Methylator Phenotype" in neuroblastoma, hypothesizing that if this epigenetic mark can predict overall and progression free survival in high-risk stage 4 neuroblastoma, it could be utilized to improve the risk stratification of the patients, alone or in conjunction with the previously identified methylation of the SFN gene (14.3.3sigma that can accurately predict outcome in these patients. We have utilized univariate and multivariate models to compare the prognostic power of PCDHB methylation in terms of overall and progression free survival, quantitatively determined by pyrosequencing, with that of other markers utilized for the patients' stratification utilizing methylation thresholds calculated on neuroblastoma at stage 1-4 and only on stage 4, high-risk patients. Our results indicate that PCDHB accurately distinguishes between high- and intermediate/low risk stage 4 neuroblastoma in agreement with the established risk stratification criteria. However PCDHB cannot predict outcome in the subgroup of stage 4 patients at high-risk whereas methylation levels of SFN are suggestive of a "methylation gradient" associated with tumor aggressiveness as suggested by the finding of a higher threshold that defines a subset of patients with an extremely severe disease (OS <24 months. Because of the heterogeneity of neuroblastoma we believe that clinically relevant methylation markers should be selected and tested on homogeneous groups of patients rather than on patients at all stages.

  10. The human immune response to streptococcal extracellular antigens: clinical, diagnostic, and potential pathogenetic implications.

    Science.gov (United States)

    Johnson, Dwight R; Kurlan, Roger; Leckman, James; Kaplan, Edward L

    2010-02-15

    Determination of an immune response to group A Streptococcus (GAS) antigens, frequently anti-streptolysin O and anti-DNase B, is crucial for documentation of bona fide GAS infection. Although the importance of immunologic confirmation of infection is widely accepted, the immediate and long-term immunokinetics of the human antibody response are incompletely documented and poorly understood. Pediatric study participants (n = 160) were followed during a 2-year study with monthly throat cultures (n = 3491) and blood samples (n = 1679) obtained every 13 weeks. Recovered GAS were characterized; serum anti-streptolysin O and anti-DNase B antibody titers were determined. Antibody titers and GAS culture results were temporally correlated and analyzed. The analyses clearly document, in some instances for the first time, that an increase in antibody titer more accurately defines infection than does an absolute titer (eg, "upper limit of normal"), that antibody titers can remain elevated for many months even without GAS, and that some individuals may harbor GAS continuously for months or years without symptoms of infection and without an associated immune response. Measuring 2 different antibodies is more accurate in defining infection. Single time-point cultures and single antibody titers are often misleading. Sequential samples more accurately define infection, allowing correlation of titer increases with temporal confirmation of GAS acquisition. Understanding kinetics of the immune response(s) to GAS infection is necessary in formulating accurate clinical diagnostic conclusions, to appropriate design of clinical and epidemiological studies examining the association of GAS with subsequent sequelae, and to providing insight into pathogenetic mechanisms associated with this important human pathogen.

  11. Towards Achieving the Full Clinical Potential of Proton Therapy by Inclusion of LET and RBE Models

    International Nuclear Information System (INIS)

    Jones, Bleddyn

    2015-01-01

    Despite increasing use of proton therapy (PBT), several systematic literature reviews show limited gains in clinical outcomes, with publications mostly devoted to recent technical developments. The lack of randomised control studies has also hampered progress in the acceptance of PBT by many oncologists and policy makers. There remain two important uncertainties associated with PBT, namely: (1) accuracy and reproducibility of Bragg peak position (BPP); and (2) imprecise knowledge of the relative biological effect (RBE) for different tissues and tumours, and at different doses. Incorrect BPP will change dose, linear energy transfer (LET) and RBE, with risks of reduced tumour control and enhanced toxicity. These interrelationships are discussed qualitatively with respect to the ICRU target volume definitions. The internationally accepted proton RBE of 1.1 was based on assays and dose ranges unlikely to reveal the complete range of RBE in the human body. RBE values are not known for human (or animal) brain, spine, kidney, liver, intestine, etc. A simple efficiency model for estimating proton RBE values is described, based on data of Belli et al. and other authors, which allows linear increases in α and β with LET, with a gradient estimated using a saturation model from the low LET α and β radiosensitivity parameter input values, and decreasing RBE with increasing dose. To improve outcomes, 3-D dose-LET-RBE and bio-effectiveness maps are required. Validation experiments are indicated in relevant tissues. Randomised clinical studies that test the invariant 1.1 RBE allocation against higher values in late reacting tissues, and lower tumour RBE values in the case of radiosensitive tumours, are also indicated

  12. Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs: Review and Perspectives.

    Science.gov (United States)

    Sulochana, Suresh P; Syed, Muzeeb; Chandrasekar, Devaraj V; Mullangi, Ramesh; Srinivas, Nuggehally R

    2016-10-01

    Sucralfate, a complex of aluminium hydroxide with sulfated sucrose, forms a strong gastrointestinal tract (GIT) mucosal barrier with excellent anti-ulcer property. Because sucralfate does not undergo any significant oral absorption, sucralfate resides in the GIT for a considerable length of time. The unabsorbed sucralfate may alter the pharmacokinetics of the oral drugs by impeding its absorption and reducing the oral bioavailability. Because of the increased use of sucralfate, it was important to provide a reappraisal of the published clinical drug-drug interaction studies of sucralfate with scores of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along with study design, objectives and key remarks. While the loss of oral bioavailability was significant for the fluoroquinolone class, it generally varied for other classes of drugs, suggesting that impact of the co-administration of sucralfate is manageable in clinical situations. Given the technology advancement in formulation development, it may be in order feasible to develop appropriate formulation strategies to either avoid or minimize the absorption-related issues when co-administered with sucralfate. It is recommended that consideration of both in vitro and preclinical studies may be in order to gauge the level of interaction of a drug with sucralfate. Such data may aid in the development of appropriate strategies to navigate the co-administration of sucralfate with other drugs in this age of polypharmacy.

  13. Antifungal potential of eugenyl acetate against clinical isolates of Candida species.

    Science.gov (United States)

    Musthafa, Khadar Syed; Hmoteh, Jutharat; Thamjarungwong, Benjamas; Voravuthikunchai, Supayang Piyawan

    2016-10-01

    The study evaluated the efficiency of eugenyl acetate (EA), a phytochemical in clove essential oil, against clinical isolates of Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida glabrata. Minimum inhibitory concentrations (MIC) of EA against Candida isolates were in the range between 0.1% and 0.4% (v/v). Spot assay further confirmed the susceptibility of Candida isolates to the compound upon treatment with respective 1 × MIC. Growth profile measured in time kill study evidence that the compound at 1 × MIC and 1/2 × MIC retarded the growth of Candida cells, divulging the fungicidal activity. Light microscopic observation demonstrated that upon treated with EA, rough cell morphology, cell damage, and fragmented patterns were observed in C. albicans, C. parapsilosis, C. tropicalis, and C. glabrata. Furthermore, unusual morphological changes of the organism were observed in scanning electron microscopic study. Therefore, it is validated that the compound could cause cell damage resulting in the cell death of Candida clinical isolates. Eventually, the compound at sub-MIC (0.0125% v/v) significantly inhibited serum-induced germ tube formation by C. albicans. Eugenyl acetate inhibited biofilm forming ability of the organisms as well as reduced the adherence of Candida cells to HaCaT keratinocytes cells. In addition, upon treatment with EA, the phagocytic activity of macrophages was increased significantly against C. albicans (P Candida infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Structuring the competitive advantage of printing company

    OpenAIRE

    Kukharuk A. D.

    2013-01-01

    The nature of the concept of "competitive advantage of the company" if analyzed. The concept of "structuring a competitive advantage" is suggested. The model of structuring of printing company’s competitive advantage based on fundamentals of stakeholder theory is developed.

  15. 76 FR 56262 - Community Advantage Pilot Program

    Science.gov (United States)

    2011-09-12

    ... SMALL BUSINESS ADMINISTRATION [Docket No. SBA 2011-0003] Community Advantage Pilot Program AGENCY: U.S. Small Business Administration (SBA). ACTION: Notice of change to Community Advantage Pilot... Community Advantage Pilot Program. In that notice, SBA modified or waived as appropriate certain regulations...

  16. Otolithic disease: clinical features and the role of vestibular evoked myogenic potentials.

    Science.gov (United States)

    Curthoys, Ian S; Manzari, Leonardo

    2013-07-01

    Through selective tests of the function of the canal and otolith sense organs, it is possible to assert that patient conditions are purely otolithic and that the canals are not involved. The video head impulse test selectively tests each semicircular canal; the ocular vestibular-evoked myogenic potential to 500 Hz Fz (Fz is the location on the forehead in the midline at the hairline) bone-conducted vibration (BCV) selectively tests the utricular macula and the cervical vestibular-evoked myogenic potential to 500 Hz Fz BCV selectively tests the saccular macula. The development of new specific tests of otolith function has shown that some patients may have specific deficits of just otolithic function. In the authors' experience, patients who complain strongly of postural unsteadiness should be suspected to have otolithic deficits. They may also have vertigo and in some cases have spontaneous nystagmus of peripheral origin, even though their semicircular canal function is normal. The prognosis for such patients is good. They usually appear to regain their postural stability spontaneously over weeks (or longer), even though they still have an otolithic deficit as shown by objective tests when they are free of symptoms. It is not known what procedures may accelerate the recovery of otolith function. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Magnetic resonance imaging of the lumbar spine: determining clinical impact and potential harm from overuse.

    Science.gov (United States)

    Wnuk, Nathan M; Alkasab, Tarik K; Rosenthal, Daniel I

    2018-04-18

    Lumbar spine MRI is frequently said to be "overused" in the evaluation of low-back pain, yet data concerning the extent of overuse and on potential harmful effects are lacking. To determine the proportion of examinations with a detectable impact on patient care (actionable outcomes). Retrospective cohort study PATIENT SAMPLE: 5,365 outpatient lumbar spine MR examinations OUTCOME MEASURES: Actionable outcomes included: 1) findings leading to an intervention making use of anatomical information such as surgery; 2) new diagnoses of cancer, infection, or fracture; or 3) following known lumbar spine pathology. Potential harm was assessed by identifying examinations where suspicion of cancer or infection was raised but no positive diagnosis made. A medical record aggregation/search system was used to identify lumbar spine MR examinations with positive outcome measures. Patient notes were examined to verify outcomes. A random sample was manually inspected to identify missed positive outcomes. The proportion of actionable lumbar spine MRIs was 13%, although 93% were appropriate according to American College of Radiology guidelines. Of 36 suspected cases of cancer/infection 81% were false positives. Further investigations were ordered on 59% of suspicious exams, 86% of which were false positives. The proportion of lumbar spine MR examinations that inform management is small. The false positive rate and proportion of false positives involving further investigation is high. Further study to improve the efficiency of imaging is warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Comparison of the Developmental Potential and Clinical Results of In Vivo Matured Oocytes Cryopreserved with Different Vitrification Media

    Directory of Open Access Journals (Sweden)

    Mei Li

    2015-01-01

    Full Text Available Background: Oocyte vitrification is widely used throughout the world, but its clinical efficacy is inconsistent and depends on the vitrification media. This study compared the developmental potential and clinical results of in vivo matured oocytes cryopreserved with different vitrification media. Methods: This retrospective study involved vitrified-warmed oocytes at one in vitro fertilization laboratory. Vitrification media kits comprised the MC kit (ethylene glycol [EG] plus 1,2-propanediol [PROH], the KT kit (EG plus dimethyl sulphoxide [DMSO], and the Modified kit (EG plus DMSO and PROH kit. Rates of oocyte survival and subsequent developmental potential were recorded and analyzed. The t-test and the Chi-square test were used to evaluate each method′s efficacy. Results: Oocyte survival rate was significantly higher for the Modified kit (92.0% than for the MC kit (88.2% (P 0.05. The high-quality embryo rate per warmed oocyte was significantly higher (23.4% in the Modified kit group than in the other groups (P 0.05. Conclusions: Modified vitrification media are efficient for oocyte vitrification and, with further verification, may be able to replace commercially available media in future clinical applications.

  19. Optimization and scale up of microfluidic nanolipomer production method for preclinical and potential clinical trials.

    Science.gov (United States)

    Gdowski, Andrew; Johnson, Kaitlyn; Shah, Sunil; Gryczynski, Ignacy; Vishwanatha, Jamboor; Ranjan, Amalendu

    2018-02-12

    The process of optimization and fabrication of nanoparticle synthesis for preclinical studies can be challenging and time consuming. Traditional small scale laboratory synthesis techniques suffer from batch to batch variability. Additionally, the parameters used in the original formulation must be re-optimized due to differences in fabrication techniques for clinical production. Several low flow microfluidic synthesis processes have been reported in recent years for developing nanoparticles that are a hybrid between polymeric nanoparticles and liposomes. However, use of high flow microfluidic synthetic techniques has not been described for this type of nanoparticle system, which we will term as nanolipomer. In this manuscript, we describe the successful optimization and functional assessment of nanolipomers fabricated using a microfluidic synthesis method under high flow parameters. The optimal total flow rate for synthesis of these nanolipomers was found to be 12 ml/min and flow rate ratio 1:1 (organic phase: aqueous phase). The PLGA polymer concentration of 10 mg/ml and a DSPE-PEG lipid concentration of 10% w/v provided optimal size, PDI and stability. Drug loading and encapsulation of a representative hydrophobic small molecule drug, curcumin, was optimized and found that high encapsulation efficiency of 58.8% and drug loading of 4.4% was achieved at 7.5% w/w initial concentration of curcumin/PLGA polymer. The final size and polydispersity index of the optimized nanolipomer was 102.11 nm and 0.126, respectively. Functional assessment of uptake of the nanolipomers in C4-2B prostate cancer cells showed uptake at 1 h and increased uptake at 24 h. The nanolipomer was more effective in the cell viability assay compared to free drug. Finally, assessment of in vivo retention in mice of these nanolipomers revealed retention for up to 2 h and were completely cleared at 24 h. In this study, we have demonstrated that a nanolipomer formulation can be successfully

  20. Potential Relationship between Season of Birth and Clinical Characteristics in Major Depressive Disorder in Koreans: Results from the CRESCEND Study.

    Science.gov (United States)

    Park, Seon-Cheol; Sakong, Jeong-Kyu; Koo, Bon Hoon; Kim, Jae-Min; Jun, Tae-Youn; Lee, Min-Soo; Kim, Jung-Bum; Yim, Hyeon-Woo; Park, Yong Chon

    2016-05-01

    We aimed to examine the potential relationship between season of birth (SOB) and clinical characteristics in Korean patients with unipolar non-psychotic major depressive disorder (MDD). Using data from the Clinical Research Center for Depression (CRESCEND) study in South Korea, 891 MDD patients were divided into two groups, those born in spring/summer (n=457) and those born in autumn/winter (n=434). Measurement tools comprising the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Brief Psychiatric Rating Scale, Scale for Suicidal Ideation, Clinical Global Impression of severity, Social and Occupation Functional Assessment Scale, WHO Quality of Life assessment instrument-abbreviated version, Alcohol Use Disorder Identification Test, and Temperament and Character Inventory were used to evaluate depression, anxiety, overall symptoms, suicidal ideation, global severity, social function, quality of life, drinking, and temperament and character, respectively. Using independent t-tests for continuous variables and χ² tests for discrete variables, the clinical characteristics of the two groups were compared. MDD patients born in spring/summer were on average younger at onset of first depressive episode (t=2.084, p=0.038), had greater loss of concentration (χ²=4.589, p=0.032), and were more self-directed (t=2.256, p=0.025) than those born in autumn/winter. Clinically, there was a trend for the MDD patients born in spring/summer to display the contradictory characteristics of more severe clinical course and less illness burden; this may have been partly due to a paradoxical effect of the 5-HT system.

  1. LASIK vs LASEK vs PRK: advantages and indications.

    Science.gov (United States)

    Ambrósio, Renato; Wilson, Steven

    2003-03-01

    The advent of the excimer laser as an instrument for use in reshaping the corneal stroma was a great step forward in refractive surgery. Laser energy can be delivered on the stromal surface in the photorefractive keratectomy (PRK) procedure or deeper on the corneal stroma by the means of a lamellar surgery in which a flap is created with the microkeratome in the laser in situ keratomileusis (LASIK) procedure. LASIK is currently the dominant procedure in refractive surgery. The main advantage of LASIK over PRK is related to maintaining the central corneal epithelium. This increases comfort during the early post-operative period, allows for rapid visual recovery, and reduces the wound healing response. Reduced wound healing correlates with less regression for high corrections and a lower rate of complications such as significant stromal opacity (haze). PRK, however, remains as an excellent option for mild to moderate corrections, particularly for cases associated with thin corneas, recurrent erosions, or a predisposition for trauma (Martial arts, military, etc.). Recently, a modification of PRK, laser subepithelial keratomileusis (LASEK), was introduced. In the LASEK procedure, an epithelial flap is created and replaced after the ablation. The benefits, if any, of the creation of an epithelial flap compared to traditional PRK are not fully appreciated. Advocates of LASEK suggest that there is less discomfort in the early postoperative period, faster visual recovery, and less haze compared to standard PRK for correction of similar levels of refractive error. Additional long-term clinical studies, along with laboratory research, will be crucial to validate these potential advantages of LASEK procedure.

  2. Corticotropin-releasing factor peptide antagonists: design, characterization and potential clinical relevance.

    Science.gov (United States)

    Rivier, Jean E; Rivier, Catherine L

    2014-04-01

    Elusive for more than half a century, corticotropin-releasing factor (CRF) was finally isolated and characterized in 1981 from ovine hypothalami and shortly thereafter, from rat brains. Thirty years later, much has been learned about the function and localization of CRF and related family members (Urocortins 1, 2 and 3) and their 2 receptors, CRF receptor type 1 (CRFR1) and CRF receptor type 2 (CRFR2). Here, we report the stepwise development of peptide CRF agonists and antagonists, which led to the CRFR1 agonist Stressin1; the long-acting antagonists Astressin2-B which is specific for CRFR2; and Astressin B, which binds to both CRFR1 and CRFR2.This analog has potential for the treatment of CRF-dependent diseases in the periphery, such as irritable bowel syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Maximum recovery potential of human tumor cells may predict clinical outcome in radiotherapy

    International Nuclear Information System (INIS)

    Weichselbaum, R.R.; Beckett, M.

    1987-01-01

    We studied inherent radiosensitivity/resistance (D0), ability to accumulate sublethal damage (n) and repair of potentially lethal damage (PLDR) in established human tumor cell lines as well as early passage human tumor cell lines derived from patients with known outcome following radiotherapy. Survival 24 hrs after treatment of human tumor cells with X rays in plateau phase cultures is a function of initial damage (D0, n), as well as recovery over 24 hrs (PLDR). A surviving fraction greater than .1 24 hrs following treatment with 7 Gy in plateau phase cultures is associated with tumor cell types (melanoma, osteosarcoma) with a high probability of radiotherapy failure or tumor cells derived from patients who actually failed radiotherapy. Therefore, total cellular recovery following radiation may be an important determinant of radiocurability. Accurate assays of radiotherapy outcome may need to account for all these radiobiological parameters

  4. Sensory action potentials of the maxillary nerve: a methodologic study with clinical implications

    DEFF Research Database (Denmark)

    Thygesen, Torben; Baad-Hansen, Lene; Svensson, Peter

    2009-01-01

    PURPOSE: Recently, recording of sensory nerve action potentials (SNAPs) of the inferior alveolar nerve (IAN) was described and is used as a diagnostic test of traumatic neuropathic trigeminal disorders. The technique is limited to IAN damage; therefore, we adapted the technique to the maxillary...... nerve, which is also frequently injured by either trauma or orthognathic surgery. PATIENTS AND METHODS: Fourteen healthy volunteers participated in this methodologic study in which the infraorbital nerve (ION) was stimulated with 2 needle electrodes. The SNAPs were recorded from the maxillary nerve...... difference. Repeated tests within a session test demonstrated no significant differences in the latency data (ANOVA: P= .225) or amplitude data (ANOVA: P= .44). Stimulus-response curves indicated that the SNAPs saturated at 5.1+/-4.4 mA stimulus intensity. In 1 subject, stimulation of the mental nerve...

  5. Deciphering spreading mechanisms in amyotrophic lateral sclerosis: clinical evidence and potential molecular processes.

    Science.gov (United States)

    Pradat, Pierre-François; Kabashi, Edor; Desnuelle, Claude

    2015-10-01

    The aim of this review is to refer to recent arguments supporting the existence of specific propagation mechanisms associated with spreading of neuron injury in amyotrophic lateral sclerosis (ALS). Misfolded ALS-linked protein accumulation can induce aggregation of their native equivalent isoforms through a mechanism analogous to the infectious prion proteins initiation and its propagation. Although ALS is clinically heterogeneous, a shared characteristic is the focal onset and the progressive extension to all body regions. Being viewed until now as just summation of the increased number of affected neurons, dispersion is now rather considered as the result of a seeded self-propagating process. A sequential regional spreading pattern is supported by the distribution of TDP-43 aggregates in ALS autopsy cases. Electrophysiology and advanced neuroimaging methods also recently provided some evidence for propagation of lesions both in the brain and spinal cord, more longitudinal studies being still needed. Lesions are supposed to spread cell-to-cell regionally or through connected neuronal pathway. At the molecular level, the prion-like spreading is an emerging mechanism hypothesis, but other machineries such as those that are in charge of dealing with misfolded proteins and secretion of deleterious peptides may be involved in the propagation of neuron loss. Deciphering the mechanisms underlying spreading of ALS symptoms is of crucial importance to better understand this neurodegenerative disease, build new and appropriate animal models and to define novel therapeutic targets.

  6. Psychological variables potentially implicated in opioid-related mortality as observed in clinical practice.

    Science.gov (United States)

    Passik, Steven D; Lowery, Amy

    2011-06-01

    Opioid-related deaths in the United States have become a public health problem, with accidental and unintended overdoses being especially troubling. Screening for psychological risk factors is an important first step in safeguarding against nonadherence practices and identifying patients who may be vulnerable to the risks associated with opioid therapy. Validated screening instruments can aid in this attempt as a complementary tool to clinicians' assessments. A structured screening is imperative as part of an assessment, as clinician judgment is not the most reliable method of identifying nonadherence. As a complement to formal screening, we present for discussion and possible future study certain psychological variables observed during years of clinical practice that may be linked to medication nonadherence and accidental overdose. These variables include catastrophizing, fear, impulsivity, attention deficit disorders, existential distress, and certain personality disorders. In our experience, chronic pain patients with dual diagnoses may become "chemical copers" as a way of coping with their negative emotion. For these patients, times of stress could lead to accidental overdose. Behavioral, cognitive-behavioral (acceptance and commitment, dialectical behavior), existential (meaning-centered, dignity), and psychotropic therapies have been effective in treating these high-risk comorbidities, while managing expectations of pain relief appears key to preventing accidental overdose. Wiley Periodicals, Inc.

  7. The capsular group B meningococcal vaccine, 4CMenB : clinical experience and potential efficacy.

    Science.gov (United States)

    Rollier, Christine S; Dold, Christina; Marsay, Leanne; Sadarangani, Manish; Pollard, Andrew J

    2015-01-01

    Capsular group B meningococcal disease is a leading cause of childhood meningitis and septicaemia. Up to 10% of sufferers die, and sequelae remain in > 30% of survivors. A vaccine, four component meningococcal group B ( 4CMenB ), designed with the aim to induce broad coverage against this highly variable bacterium, has been licensed in countries including in the European Union, Canada and Australia. Immunogenicity and safety data, published in peer-reviewed literature between 2004 and 2014, are presented in the context of the recent recommendation for the use of the vaccine in infants in the UK. 4CMenB induces significant reactogenicity when administered with routine infant vaccines, in particular with respect to fever rates. Fevers can be somewhat reduced using paracetamol. The efficacy of the vaccine is unknown but has been extrapolated from effectiveness data obtained from use of one of its components in New Zealand, immunogenicity data from clinical trials and estimation of coverage from in vitro studies. These data suggest that the vaccine will prevent a proportion of invasive meningococcal disease cases in infants and young children. Implementation and well-planned post-marketing surveillance will address uncertainties over field effectiveness.

  8. Nonword repetition in children with cochlear implants: a potential clinical marker of poor language acquisition.

    Science.gov (United States)

    Nittrouer, Susan; Caldwell-Tarr, Amanda; Sansom, Emily; Twersky, Jill; Lowenstein, Joanna H

    2014-11-01

    Cochlear implants (CIs) can facilitate the acquisition of spoken language for deaf children, but challenges remain. Language skills dependent on phonological sensitivity are most at risk for these children, so having an effective way to diagnose problems at this level would be of value for school speech-language pathologists. The goal of this study was to assess whether a nonword repetition (NWR) task could serve that purpose. Participants were 104 second graders: 49 with normal hearing (NH) and 55 with CIs. In addition to NWR, children were tested on 10 measures involving phonological awareness and processing, serial recall of words, vocabulary, reading, and grammar. Children with CIs performed more poorly than children with NH on NWR, and sensitivity to phonological structure alone explained that performance for children in both groups. For children with CIs, 2 audiological factors positively influenced outcomes on NWR: being identified with hearing loss at a younger age and having experience with wearing a hearing aid on the unimplanted ear at the time of receiving a 1st CI. NWR scores were better able to rule out than to rule in such language deficits. Well-designed NWR tasks could have clinical utility in assessments of language acquisition for school-age children with CIs.

  9. An evaluation of the infection control potential of a UV clinical podiatry unit.

    Science.gov (United States)

    Humphreys, Paul N; Davies, Chris S; Rout, Simon

    2014-02-28

    Infection control is a key issue in podiatry as it is in all forms of clinical practice. Airborne contamination may be particularly important in podiatry due to the generation of particulates during treatment. Consequently, technologies that prevent contamination in podiatry settings may have a useful role. The aims of this investigation were twofold, firstly to determine the ability of a UV cabinet to protect instruments from airborne contamination and secondly to determine its ability to remove microbes from contaminated surfaces and instruments. A UV instrument cabinet was installed in a University podiatry suite. Impact samplers and standard microbiological techniques were used to determine the nature and extent of microbial airborne contamination. Sterile filters were used to determine the ability of the UV cabinet to protect exposed surfaces. Artificially contaminated instruments were used to determine the ability of the cabinet to remove microbial contamination. Airborne bacterial contamination was dominated by Gram positive cocci including Staphylococcus aureus. Airborne fungal levels were much lower than those observed for bacteria. The UV cabinet significantly reduced (p podiatry settings due to the presence of S. aureus. The use of a UV instrument cabinet can reduce the risk of contamination by airborne microbes. The UV cabinet tested was unable to decontaminate instruments and as such could pose an infection risk if misused.

  10. Passing through the renal clearance barrier: toward ultrasmall sizes with stable ligands for potential clinical applications

    Directory of Open Access Journals (Sweden)

    Zhang XD

    2014-04-01

    Full Text Available Xiao-Dong Zhang,1 Jiang Yang,2 Sha-Sha Song,1 Wei Long,1 Jie Chen,1 Xiu Shen,1 Hao Wang,1 Yuan-Ming Sun,1 Pei-Xun Liu,1 Saijun Fan11Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China; 2Department of Biological Systems Engineering, University of Wisconsin-Madison, Madison, WI, USAAbstract: The use of nanoparticles holds promise for medical applications, such as X-ray imaging, photothermal therapy and radiotherapy. However, the in vivo toxicity of inorganic nanoparticles raises some concern regarding undesirable side effects which prevent their further medical application. Ultrasmall sub-5.5 nm particles can pass through the barrier for renal clearance, minimizing their toxicity. In this letter we address some recent interesting work regarding in vivo toxicity and renal clearance, and discuss the possible strategy of utilizing ultrasmall nanomaterials. We propose that small hydrodynamic sized nanoclusters can achieve both nontoxic and therapeutic clinical features.Keywords: in vivo clearance, gold nanoparticles, small size

  11. The pharmacokinetics and clinical efficacy of AVP-825: a potential advancement for acute treatment of migraine.

    Science.gov (United States)

    Cady, Roger

    2015-01-01

    Oral triptans have dominated the prescription market for acute treatment of migraine for nearly 25 years. Today, patients often express dissatisfaction with prescribed acute treatment in part because they do not have confidence that the therapy will provide consistent efficacy over time. Major limitations to sustained successful use of oral triptans are their relatively slow onset of meaningful clinical benefit and variable absorption/efficacy due to impaired gastrointestinal function during migraine. AVP-825, a new intranasal delivery system for sumatriptan , may be an effective alternative to oral triptans. This article reviews AVP-825, which deposits low-dose sumatriptan powder deep into the vascular mucosa of the posterior nose, allowing rapid absorption of drug into the systemic circulation. Studies suggest that AVP-825 is a highly effective, well-tolerated acute treatment for episodic migraine. Oral triptans are limited in providing effective patient-centered outcomes to migraine patients. Failed or suboptimal abortive treatment of migraine is a major driver of migraine chronification and increases in healthcare costs. AVP-825 is an easy to use, novel, breath-powered intranasal delivery system that provides early onset of efficacy with low systemic drug exposure and few triptan-associated adverse events. AVP-825 will be a welcomed therapeutic tool for the acute treatment of migraine.

  12. Potential clinical impact of radionuclide imaging technologies: highlights of the ITBS 2003 meeting

    Energy Technology Data Exchange (ETDEWEB)

    Itti, Roland E-mail: roland.itti@univ-lyon1.fr

    2004-07-11

    Radiopharmaceuticals are major determinants of progress in Nuclear Medicine. Besides {sup 18}FDG, the most common PET tracer, several other molecules are under evaluation, such as {sup 18}F-fluoride for bone studies, numerous ligands for neurotransmission, {sup 18}F-DOPA for neuro-endocrine tumors or generator produced {sup 68}Ga-peptides for various cancers. Nuclear medicine gradually changes for 'molecular imaging' and medical imaging, which was at the beginning mainly anatomic, has progressed in the direction of functional and metabolic imaging. The present challenge is to achieve some degree of 'in vivo' biochemistry or even histology or genetics. The importance of anatomic/functional image fusion justifies the development of combined PET-CT instrumentation, whose objectives have to be discussed in terms of anatomical landmarks and/or additional clinical information. The question of 'hard' or 'soft' image co-registration remains open, involving not only CT, but also SPECT or MRI. Development of dedicated imaging devices, whether single photon or positron, is of major interest for breast imaging, allowing optimal imaging conditions, with results definitely superior to classical gamma-cameras or PET. The patient population concerned with scintimammography is still controversial, as well as the imaging modalities: FDG or sestaMIBI, planar or tomographic, scintillators or semi-conductors, and the research field remains open. This is also valid for external or per-operative probe systems for tumor or lymph nodes localization.

  13. Clinical Characterization of Gastric Antral Vascular Ectasia: A Potential Manifestation of the Metabolic Syndrome.

    Science.gov (United States)

    Smith, Elliot; Tekola, Bezawit; Patrie, James; Cornella, Scott; Caldwell, Stephen

    2016-12-01

    Gastric antral vascular ectasia is a relatively common endoscopic finding. Past studies have shown an association of gastric antral vascular ectasia with cirrhosis and autoimmune disorders. We aimed to re-examine these associations and to investigate a possible association of gastric antral vascular ectasia with features of the metabolic syndrome. There were 135 patients with a diagnosis of gastric antral vascular ectasia from years 1995-2013 seen at the University of Virginia who were identified from a clinical data repository and age and sex matched to a cohort of patients without gastric antral vascular ectasia undergoing endoscopy within the same time frame as the index cases. The groups were compared for comorbidities including autoimmune disease, cirrhosis, vascular disease, body mass index (BMI), diabetes mellitus, and cirrhosis due to nonalcoholic steatohepatitis. Sixty-four percent of gastric antral vascular ectasia patients were cirrhotic, compared with 14% of controls (P correlation of gastric antral vascular ectasia with features of metabolic syndrome such as diabetes, BMI, vascular disease, and nonalcoholic steatohepatitis cirrhosis. The pathophysiology of gastric antral vascular ectasia remains uncertain, but we speculate that it may be a manifestation of the metabolic syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Potential of robots as next-generation technology for clinical assessment of neurological disorders and upper-limb therapy.

    Science.gov (United States)

    Scott, Stephen H; Dukelow, Sean P

    2011-01-01

    Robotic technologies have profoundly affected the identification of fundamental properties of brain function. This success is attributable to robots being able to control the position of or forces applied to limbs, and their inherent ability to easily, objectively, and reliably quantify sensorimotor behavior. Our general hypothesis is that these same attributes make robotic technologies ideal for clinically assessing sensory, motor, and cognitive impairments in stroke and other neurological disorders. Further, they provide opportunities for novel therapeutic strategies. The present opinionated review describes how robotic technologies combined with virtual/augmented reality systems can support a broad range of behavioral tasks to objectively quantify brain function. This information could potentially be used to provide more accurate diagnostic and prognostic information than is available from current clinical assessment techniques. The review also highlights the potential benefits of robots to provide upper-limb therapy. Although the capital cost of these technologies is substantial, it pales in comparison with the potential cost reductions to the overall healthcare system that improved assessment and therapeutic interventions offer.

  15. Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system.

    Science.gov (United States)

    McPartland, John M; Guy, Geoffrey W; Di Marzo, Vincenzo

    2014-01-01

    The "classic" endocannabinoid (eCB) system includes the cannabinoid receptors CB1 and CB2, the eCB ligands anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their metabolic enzymes. An emerging literature documents the "eCB deficiency syndrome" as an etiology in migraine, fibromyalgia, irritable bowel syndrome, psychological disorders, and other conditions. We performed a systematic review of clinical interventions that enhance the eCB system--ways to upregulate cannabinoid receptors, increase ligand synthesis, or inhibit ligand degradation. We searched PubMed for clinical trials, observational studies, and preclinical research. Data synthesis was qualitative. Exclusion criteria limited the results to 184 in vitro studies, 102 in vivo animal studies, and 36 human studies. Evidence indicates that several classes of pharmaceuticals upregulate the eCB system, including analgesics (acetaminophen, non-steroidal anti-inflammatory drugs, opioids, glucocorticoids), antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Clinical interventions characterized as "complementary and alternative medicine" also upregulate the eCB system: massage and manipulation, acupuncture, dietary supplements, and herbal medicines. Lifestyle modification (diet, weight control, exercise, and the use of psychoactive substances--alcohol, tobacco, coffee, cannabis) also modulate the eCB system. Few clinical trials have assessed interventions that upregulate the eCB system. Many preclinical studies point to other potential approaches; human trials are needed to explore these promising interventions.

  16. Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system.

    Directory of Open Access Journals (Sweden)

    John M McPartland

    Full Text Available The "classic" endocannabinoid (eCB system includes the cannabinoid receptors CB1 and CB2, the eCB ligands anandamide (AEA and 2-arachidonoylglycerol (2-AG, and their metabolic enzymes. An emerging literature documents the "eCB deficiency syndrome" as an etiology in migraine, fibromyalgia, irritable bowel syndrome, psychological disorders, and other conditions. We performed a systematic review of clinical interventions that enhance the eCB system--ways to upregulate cannabinoid receptors, increase ligand synthesis, or inhibit ligand degradation.We searched PubMed for clinical trials, observational studies, and preclinical research. Data synthesis was qualitative. Exclusion criteria limited the results to 184 in vitro studies, 102 in vivo animal studies, and 36 human studies. Evidence indicates that several classes of pharmaceuticals upregulate the eCB system, including analgesics (acetaminophen, non-steroidal anti-inflammatory drugs, opioids, glucocorticoids, antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Clinical interventions characterized as "complementary and alternative medicine" also upregulate the eCB system: massage and manipulation, acupuncture, dietary supplements, and herbal medicines. Lifestyle modification (diet, weight control, exercise, and the use of psychoactive substances--alcohol, tobacco, coffee, cannabis also modulate the eCB system.Few clinical trials have assessed interventions that upregulate the eCB system. Many preclinical studies point to other potential approaches; human trials are needed to explore these promising interventions.

  17. Potential clinical applications of halichondrins in breast cancer and other neoplasms

    Directory of Open Access Journals (Sweden)

    Ortega V

    2012-02-01

    Full Text Available Vanesa Ortega1, Javier Cortés1,21Department of Oncology, Vall d’Hebrón University Hospital, Barcelona, Spain; 2Vall d’Hebron Institute of Oncology (VHIO, Barcelona, SpainAbstract: Halichondrin B is a large polyether macrolide found in a rare Japanese sponge, Halichondria okadai and has been shown to have anticancer activity. Eribulin mesylate is a completely synthetic analog of halichondrin B with a unique mechanism of action relative to other antimicrotubule agents. This new agent has demonstrated activity in preclinical studies, and it is being developed for the treatment of different tumor types. Eribulin has been approved by the United States Food and Drug Administration and the European Medicines Agency as late-line therapy for metastatic breast cancer patients previously treated with an anthracycline and a taxane. It has demonstrated superiority over other treatments in overall survival (OS (hazard ratio: 0.81, P = 0.041, leading to its regulatory approbation for clinical practice use. Median OS for the eribulin-treated group was 13.1 months versus 10.6 months in the physician’s treatment-of-choice group. Eribulin demonstrated a manageable toxicity profile. Most common adverse events associated with treatment were mild neutropenia and fatigue, mainly of grade 1 or 2. In contrast to other antimicrotubule agents, eribulin has a relatively low incidence of peripheral neuropathy and alopecia. Eribulin has been extensively studied in breast cancer and is currently being developed for treatment of other cancer types. Eribulin has demonstrated activity in Phase II trials in non-small cell lung cancer, pancreatic cancer, urothelial tract cancer, and sarcomas. Further studies in these cancers are ongoing. This article reviews pharmacology, mechanism of action, pharmacokinetics and efficacy of eribulin in breast cancer and other neoplasms.Keywords: halichondrin B, eribulin, antimicrotubule, metastatic breast cancer

  18. Developmental neurotoxicity of the organophosphorus insecticide chlorpyrifos: from clinical findings to preclinical models and potential mechanisms.

    Science.gov (United States)

    Burke, Richard D; Todd, Spencer W; Lumsden, Eric; Mullins, Roger J; Mamczarz, Jacek; Fawcett, William P; Gullapalli, Rao P; Randall, William R; Pereira, Edna F R; Albuquerque, Edson X

    2017-08-01

    Organophosphorus (OP) insecticides are pest-control agents heavily used worldwide. Unfortunately, they are also well known for the toxic effects that they can trigger in humans. Clinical manifestations of an acute exposure of humans to OP insecticides include a well-defined cholinergic crisis that develops as a result of the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that hydrolyzes the neurotransmitter acetylcholine (ACh). Prolonged exposures to levels of OP insecticides that are insufficient to trigger signs of acute intoxication, which are hereafter referred to as subacute exposures, have also been associated with neurological deficits. In particular, epidemiological studies have reported statistically significant correlations between prenatal subacute exposures to OP insecticides, including chlorpyrifos, and neurological deficits that range from cognitive impairments to tremors in childhood. The primary objectives of this article are: (i) to address the short- and long-term neurological issues that have been associated with acute and subacute exposures of humans to OP insecticides, especially early in life (ii) to discuss the translational relevance of animal models of developmental exposure to OP insecticides, and (iii) to review mechanisms that are likely to contribute to the developmental neurotoxicity of OP insecticides. Most of the discussion will be focused on chlorpyrifos, the top-selling OP insecticide in the United States and throughout the world. These points are critical for the identification and development of safe and effective interventions to counter and/or prevent the neurotoxic effects of these chemicals in the developing brain. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

  19. TH-B-BRC-00: How to Identify and Resolve Potential Clinical Errors Before They Impact Patients Treatment: Lessons Learned

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2016-06-15

    Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803.

  20. TH-B-BRC-00: How to Identify and Resolve Potential Clinical Errors Before They Impact Patients Treatment: Lessons Learned

    International Nuclear Information System (INIS)

    2016-01-01

    Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803

  1. The potential carcinogenic risk of tanning beds: clinical guidelines and patient safety advice

    Directory of Open Access Journals (Sweden)

    Mette Mogensen

    2010-10-01

    Full Text Available Mette Mogensen1, Gregor BE Jemec21Department of Dermatology, Gentofte Hospital, Hellerup, Denmark; 2Department of Dermatology, Roskilde Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, DenmarkIntroduction: In 2009, the WHO listed ultraviolet (UV radiation as a group 1 carcinogen. In spite of this, each year, millions of people tan indoor in Western countries. The aim of this review is to summarize evidence of tanning bed carcinogenesis and to present guidelines for use of tanning beds and patient safety advice.Methods: A narrative review of the literature was conducted based on both PubMed and Medline searches and on literature review of the retrieved papers.Results: Use of indoor tanning beds represents a significant and avoidable risk factor for the development of both melanoma and nonmelanoma skin cancers. Frequent tanners are more often adolescent females. Tanning beds have additional potential adverse effects such as burns, solar skin damage, infection, and possibly also addictive behavior.Discussion: The effort in preventing UV light-induced carcinogenesis should currently be aimed at developing new strategies for public health information. Tanning beds are one preventable source of UV radiation. In the majority of people solar UV radiation continues to be the major factor and therefore anti-tanning campaigns must always include sunbathers.Keywords: tanning beds, skin cancers, melanoma, nonmelanoma

  2. The potential carcinogenic risk of tanning beds: clinical guidelines and patient safety advice

    International Nuclear Information System (INIS)

    Mogensen, Mette; Jemec, Gregor BE

    2010-01-01

    In 2009, the WHO listed ultraviolet (UV) radiation as a group 1 carcinogen. In spite of this, each year, millions of people tan indoor in Western countries. The aim of this review is to summarize evidence of tanning bed carcinogenesis and to present guidelines for use of tanning beds and patient safety advice. A narrative review of the literature was conducted based on both PubMed and Medline searches and on literature review of the retrieved papers. Use of indoor tanning beds represents a significant and avoidable risk factor for the development of both melanoma and nonmelanoma skin cancers. Frequent tanners are more often adolescent females. Tanning beds have additional potential adverse effects such as burns, solar skin damage, infection, and possibly also addictive behavior. The effort in preventing UV light-induced carcinogenesis should currently be aimed at developing new strategies for public health information. Tanning beds are one preventable source of UV radiation. In the majority of people solar UV radiation continues to be the major factor and therefore anti-tanning campaigns must always include sunbathers

  3. Clinical application of multifocal visual evoked potentials in children with epilepsy caused by intracranial disease

    International Nuclear Information System (INIS)

    Yukawa, Eiichi; Kim, Yeong-Jin; Kawasaki, Kensuke; Yoshii, Toshiaki; Hara, Yoshiaki

    2006-01-01

    We investigated whether visual field defects could be objectively evaluated using multifocal visual evoked potential (m-VEP) in two children with epilepsy caused by intracranial disease in whom it was difficult to measure the visual field. To determine normal waves in m-VEP, recording was performed using a visual evoked response imaging system (VERIS) Junior Science program (Mayo, Aichi, Japan) in 20 healthy children (20 eyes) peak latency and amplitude were used for assessment. In the two children with epilepsy, m-VEPs were recorded, and compared with the results of static perimetry or the lesions observed by Magnetic Resonance Imaging (MRI). In the 20 healthy children, there was no significant difference in the peak latency or amplitude among 4 quadrants by one-way analysis of variance. m-VEP in the children with epilepsy showed abnormal waves, corresponding to the visual field defects in the static perimetry or the lesions observed by MRI. Objective evaluation of visual field defects using m-VEP may be useful in children with epilepsy caused by intracranial disease in whom kinetic/static perimetry as a subjective examination is difficult. (author)

  4. Potential of cancer cell-derived exosomes in clinical application: a review of recent research advances.

    Science.gov (United States)

    Sun, Yu; Liu, Jing

    2014-06-01

    Exosomes are 30- to 100-nm, membrane-bound vesicles that are released by most types of cells, including tumor cells. Exosomes contain a great variety of bioactive molecules, including signal peptides, microRNA, lipids, and DNA. In cancer, tumor cells aberrantly secrete large quantities of exosomes to transport paracrine signals or to contribute to tumor-environment interaction at a distance. The goal of this review was to discuss the recent advances on the mechanism of cancer-derived exosomes in tumor regulation. Pertinent articles and abstracts were identified through searches of PubMed for literature published from 1983 to December 2013. Search terms included exosome, tumor, cancer, diagnosis, and therapy. All of the exposed evidence points to communication between cancer cells and their surroundings, either mediated by cancer cell-derived exosomes or by stromal cell-derived exosomes. This communication probably supports tumor proliferation, motility, invasion, angiogenesis, and premetastatic niche preparation. In addition, recent research implies that cancer cell-derived exosomes play a suppressive role in cancer-directed immune response. The biomarkers detected in bodily fluid-derived exosomes imply a potential for exosomes in cancer diagnosis. Also, exosomes could be used as a vehicle to selectively deliver therapeutic nucleic-acid drugs or conventional drugs for tumor therapy. The tolerability and feasibility of cancer exosomes in diagnosis and therapy need to be further evaluated. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

  5. Nanoparticles as potential clinical therapeutic agents in Alzheimer's disease: focus on selenium nanoparticles.

    Science.gov (United States)

    Nazıroğlu, Mustafa; Muhamad, Salina; Pecze, Laszlo

    2017-07-01

    In etiology of Alzheimer's disease (AD), involvement of amyloid β (Aβ) plaque accumulation and oxidative stress in the brain have important roles. Several nanoparticles such as titanium dioxide, silica dioxide, silver and zinc oxide have been experimentally using for treatment of neurological disease. In the last decade, there has been a great interest on combination of antioxidant bioactive compounds such as selenium (Se) and flavonoids with the oxidant nanoparticles in AD. We evaluated the most current data available on the physiological effects of oxidant and antioxidant nanoparticles. Areas covered: Oxidative nanoparticles decreased the activities of reactive oxygen species (ROS) scavenging enzymes such as glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase in the brain of rats and mice. However, Se-rich nanoparticles in small size (5-15 nm) depleted Aβ formation through decreasing ROS production. Reports on low levels of Se in blood and tissue samples and the low activities of GSH-Px, catalase and SOD enzymes in AD patients and animal models support the proposed crucial role of oxidative stress in the pathogenesis of AD. Expert commentary: In conclusion, present literature suggests that Se-rich nanoparticles appeared to be a potential therapeutic compound for the treatment of AD.

  6. Clinical impact of Positron Emission Tomography (PET) on oncological patients and their potentially application context

    International Nuclear Information System (INIS)

    Alonso, O.

    2006-01-01

    (PET) Positron Emission Tomography is a technique of nuclear medicine that has ability of detecting cancer through mechanisms based on molecular alterations of neoplastic processes. This review describes the PET Oncology applications and discusses the potential application of this technology in the sanitary and national academic framework . The most widely used in Oncology plotter is an analogue of laglucosa labelled with fluo: 18F-2-fluoro-2-Deoxy-D-glucose (FDG). In this way, the PET detects tumour retention of FDG, due to the highest glycolytic of cancer cells. In addition, the PET allow the study of the entire body at the same exploratory and some teams are coupled to systems of axial tomography (PET-CT). By ET-FDG, it is possible to diagnose, staging and restaged the majority of cancers, with diagnostic accuracy close to 90 per cent higher than the values provided by the conventional imaging techniques such. It is also possible to know early response to cancer treatments and obtain relevant medical prognosis information. (author) [es

  7. Volatile substance misuse : clinical considerations, neuropsychopharmacology and potential role of pharmacotherapy in management.

    Science.gov (United States)

    Garland, Eric L; Howard, Matthew O

    2012-11-01

    Volatile substance misuse is among the most prevalent and toxic forms of psychoactive drug use, and often results in highly deleterious social, psychological and medical consequences. The prevalence of this pernicious form of substance misuse owes in part to the fact that volatile substances of misuse are ubiquitous in the natural environment. Commonly misused commercial products include glue, shoe polish, nail polish remover, butane lighter fluid, gasoline and computer duster spray. National samples of volatile substance misusers tend to exhibit high rates of psychiatric problems and antisocial behaviour. In addition, cognitive impairments and affective dysregulation are often observed among these individuals. Volatile substances exert their complex neuropharmacological effects on dopaminergic, glutamatergic, GABAergic and serotoninergic receptor systems, as well as on cell membranes and ion channels. Concomitantly, pharmacotherapies for volatile substance abuse might profitably target a number of mechanisms, including reward circuitry in the brain, symptoms of craving and withdrawal, neuropsychiatric and emotional impairments that promote volatile substance abuse, and cognitive enhancement to rectify deficits in executive function. This review details the modes of use, subjective effects, epidemiology, adverse consequences, neuropsychopharmacology and drug treatment of volatile substance misuse, and discusses the potential role of novel forms of pharmacological intervention for this oft-overlooked public health threat of epidemic proportions.

  8. Angiotensin receptor-neprilysin inhibitors: clinical potential in heart failure and beyond

    Directory of Open Access Journals (Sweden)

    Singh JSS

    2015-06-01

    Full Text Available Jagdeep SS Singh, Chim C Lang Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK Abstract: Heart failure remains a major concern across the globe as life expectancies and delivery of health care continue to improve. There has been a dearth of new developments in heart failure therapies in the last decade until last year, with the release of the results from the PARADIGM-HF Trial heralding the arrival of a promising new class of drug, ie, the angiotensin receptor-neprilysin inhibitor. In this review, we discuss the evolution of our incremental understanding of the neurohormonal mechanisms involved in the pathophysiology of heart failure, which has led to our success in modulating its various pathways. We start by examining the renin-angiotensin-aldosterone system, followed by the challenges of modulating the natriuretic peptide system. We then delve deeper into the pharmacology and mechanisms by which angiotensin receptor-neprilysin inhibitors achieve their significant cardiovascular benefits. Finally, we also consider the potential application of this new class of drug in other areas, such as heart failure with preserved ejection fraction, hypertension, patients with renal impairment, and following myocardial infarction. Keywords: heart failure, angiotensin receptor-neprilysin inhibitor, heart failure with preserved ejection fraction, nesiritide, candoxatril, omapatrilat, hypertension, renal impairment, myocardial infarction

  9. Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.

    Science.gov (United States)

    Logan, Randall; Funk, Ryan S; Axcell, Erick; Krise, Jeffrey P

    2012-08-01

    Many commercially available, weakly basic drugs have been shown to be lysosomotropic, meaning they are subject to extensive sequestration in lysosomes through an ion trapping-type mechanism. The extent of lysosomal trapping of a drug is an important therapeutic consideration because it can influence both activity and pharmacokinetic disposition. The administration of certain drugs can alter lysosomes such that their accumulation capacity for co-administered and/or secondarily administered drugs is altered. In this review the authors explore what is known regarding the mechanistic basis for drug-drug interactions involving lysosomes. Specifically, the authors address the influence of drugs on lysosomal pH, volume and lipid processing. Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.

  10. Calcium sensing receptor as a novel mediator of adipose tissue dysfunction: mechanisms and potential clinical implications

    Directory of Open Access Journals (Sweden)

    Roberto Bravo

    2016-09-01

    Full Text Available Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For decades, dietary and behavioral approaches have failed to prevent this disease from expanding, and health authorities are challenged by the elevated prevalence of co-morbid conditions. Understanding how obesity-associated diseases develop from a basic science approach is recognized as an urgent task to face this growing problem. White adipose tissue is an active endocrine organ, with a crucial influence on whole-body homeostasis. White adipose tissue dysfunction plays a key role linking obesity with its associated diseases such as type 2 diabetes mellitus, cardiovascular disease and some cancers. Among the regulators of white adipose tissue physiology, the calcium-sensing receptor has arisen as a potential mediator of white adipose tissue dysfunction. Expression of the receptor has been described in human preadipocytes, adipocytes, and the human adipose cell lines LS14 and SW872. The evidence suggests that calcium-sensing receptor activation in the visceral (i.e. unhealthy white adipose tissue is associated with an increased proliferation of adipose progenitor cells and elevated adipocyte differentiation. In addition, exposure of adipose cells to calcium-sensing receptor activators in vitro elevates proinflammatory cytokine expression and secretion. An increased proinflammatory environment in white adipose tissue plays a key role in the development of white adipose tissue dysfunction that leads to peripheral organ fat deposition and insulin resistance, among other consequences. We propose that calcium-sensing receptor may be one relevant therapeutic target in the struggle to confront the health consequences of the current worldwide obesity pandemic.

  11. Clinical potential of necitumumab in non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Genova C

    2016-08-01

    Full Text Available Carlo Genova,1–3 Fred R Hirsch1 1Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, Aurora, CO, USA; 2Lung Cancer Unit, IRCCS AOU San Martino IST, 3Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, Italy Abstract: Despite significant progress, new therapeutic approaches for advanced non-small cell lung cancer (NSCLC are highly needed, particularly for the treatment of patients with squamous cell carcinoma. The epidermal growth factor receptor (EGFR is often overexpressed in NSCLC and represents a relevant target for specific treatments. Although EGFR mutations are more frequent in non-squamous histology, the receptor itself is more often overexpressed in squamous NSCLC. Necitumumab is a human monoclonal antibody that is able to inhibit the EGFR pathway and cause antibody-dependent cell cytotoxicity. This drug has been studied in combination with first-line chemotherapy for advanced NSCLC in two Phase III trials, and a significant survival benefit was reported in squamous NSCLC (SQUIRE trial; by contrast, necitumumab did not prove itself beneficial in non-squamous histotype (INSPIRE trial. On the basis of the SQUIRE results, necitumumab was approved in combination with cisplatin and gemcitabine as a first-line treatment for advanced squamous NSCLC, both in the US and Europe, where its availability is limited to patients with EGFR-expressing tumors. The aim of this review is to describe the tolerability and the efficacy of necitumumab by searching the available published data and define its potential role in the current landscape of NSCLC treatment. Keywords: necitumumab, EGFR, non-small cell lung cancer, monoclonal antibody, H-score

  12. Strong ion and weak acid analysis in severe preeclampsia: potential clinical significance.

    Science.gov (United States)

    Ortner, C M; Combrinck, B; Allie, S; Story, D; Landau, R; Cain, K; Dyer, R A

    2015-08-01

    The influence of common disturbances seen in preeclampsia, such as changes in strong ions and weak acids (particularly albumin) on acid-base status, has not been fully elucidated. The aims of this study were to provide a comprehensive acid-base analysis in severe preeclampsia and to identify potential new biological predictors of disease severity. Fifty women with severe preeclampsia, 25 healthy non-pregnant- and 46 healthy pregnant controls (26-40 weeks' gestation), were enrolled in this prospective case-control study. Acid-base analysis was performed by applying the physicochemical approach of Stewart and Gilfix. Mean [sd] base excess was similar in preeclamptic- and healthy pregnant women (-3.3 [2.3], and -2.8 [1.5] mEq/L respectively). In preeclampsia, there were greater offsetting contributions to the base excess, in the form of hyperchloraemia (BE(Cl) -2 [2.3] vs -0.4 [2.3] mEq/L, Palkalosis was associated with a non-reassuring/abnormal fetal heart tracing (Prespiratory and hypoalbuminaemic alkalosis that was metabolically offset by acidosis, secondary to unmeasured anions and dilution. While the overall base excess in severe preeclampsia is similar to that in healthy pregnancy, preeclampsia is associated with a greater imbalance offsetting hypoalbuminaemic alkalosis and hyperchloraemic acidosis. Rather than the absolute value of base excess, the magnitude of these opposing contributors may be a better indicator of the severity of this disease. Hypoalbuminaemic alkalosis may also be a predictor of fetal compromise. clinicaltrials.gov: NCT 02164370. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. ALTERNATIVE ROUTES OF DRUG ADMINISTRATION: ADVANTAGES AND DISADVANTAGES (SUBJECT REVIEW OF AMERICAN ACADEMY OF PEDIATRICS

    Directory of Open Access Journals (Sweden)

    article editorial

    2006-01-01

    Full Text Available During the past 20 years advances in drug formulations and innovative routes of administration have been made. Our understanding of drug transport across tissues has increased. These changes have often resulted in improved patient adherence to the therapeutic regiment and pharmacologic response. The administration of drugs by transdermal or transmucosal routes offers the advantage of being relatively painless. Also, the potential for greater flexibility in a variety of clinical situations exists, often precluding the need to establish intravinus access which is a particular benefit for children. This statement focuses on the advantages and disadvantages of alternative routes of drug administration. Issues of particular importance in the care of pediatric patients especially factors that could lead to drug-relaxed toxicity or adverse responses are emphasized.Key words: drug formulation, pharmacoKINETICS, pharmacodynamics, drug, children.

  14. DNM3, p65 and p53 from exosomes represent potential clinical diagnosis markers for glioblastoma multiforme

    Science.gov (United States)

    Yang, Jian-kai; Song, Jian; Huo, Hao-ran; Zhao, Yin-long; Zhang, Guang-yu; Zhao, Zong-mao; Sun, Guo-zhu; Jiao, Bao-hua

    2017-01-01

    Background: Glioblastoma multiforme (GBM) is the most aggressive and deadly primary brain cancer that arises from astrocytes and classified as grade IV. Recently, exosomes have been reported as an essential mediator in diverse cancer carcinogenesis and metastasis. However, their role in GBM is still unclear. In this study, we aimed to investigate whether blood exosomes can be potential clinical diagnostic markers for GBM. Methods: We used a xenograft orthotopic mouse model to detect the differentially expressed genes in the brain and blood exosomes of original/recurrent GBM. Results: We found that recurrent GBM had stronger growth capacity and lethality than original GBM in the mouse model. A gene microarray of original tumors and blood exosomes from GBM orthotopic xenografts results showed that DNM3, p65 and CD117 expressions increased, whereas PTEN and p53 expressions decreased in both original tumors and blood exosomes. In the recurrent GBM tumor model, DNM3 and p65 showed increased expressions, whereas ST14 and p53 showed decreased expressions in tumor and blood exosomes of the recurrent GBM mouse model. Conclusion: In summary, we found that DNM3, p65 and p53 had a similar trend in brain and blood exosomes both for original and recurrent GBM, and could serve as potential clinical diagnostic markers for GBM. PMID:29449895

  15. Does being female provide a neuroprotective advantage following spinal cord injury?

    Directory of Open Access Journals (Sweden)

    Jeffrey P Datto

    2015-01-01

    Full Text Available It has been controversial whether gender has any effect on recovery following spinal cord injury (SCI. Past experimental and clinical research aimed at addressing this subject has led to constrasting findings on whether females hold any advantage in locomotor recovery. Additionally, for studies supporting the notion of a female gender related advantage, a definite cause has not been explained. In a recent study, using large sample sizes for comparative male and female spinal cord injury cohorts, we reported that a significant gender advantage favoring females existed in both tissue preservation and functional recovery after taking into consideration discrepancies in age and weight of the animals across sexes. Prior animal research frequently used sample sizes that were too small to determine significance with certainty and also did not account for two other factors that influence locomotor performance: age and weight. Our finding is important in light of controversy surrounding the effect of gender on outcome and the fact that SCI affects more than ten thousand new individuals annually, a population that is disproportionately male. By deepening our understanding of why a gender advantage exists, potential new therapeutics can be designed to improve recovery for the male population following the initial trauma or putatively augment the neuroprotective privilege in females for enhanced outcomes.

  16. Dosimetric Comparison and Potential for Improved Clinical Outcomes of Paediatric CNS Patients Treated with Protons or IMRT

    Energy Technology Data Exchange (ETDEWEB)

    Armoogum, Kris S., E-mail: kris.armoogum@nhs.net [Department of Radiotherapy Physics, Royal Derby Hospital, Derby Hospitals NHS Foundation Trust, Uttoxeter Road, Derby DE22 3NE (United Kingdom); Thorp, Nicola [The Clatterbridge Cancer Centre NHS Foundation Trust, Clatterbridge Road, Bebington, Wirral CH63 4JY (United Kingdom)

    2015-04-28

    Background: We compare clinical outcomes of paediatric patients with CNS tumours treated with protons or IMRT. CNS tumours form the second most common group of cancers in children. Radiotherapy plays a major role in the treatment of many of these patients but also contributes to late side effects in long term survivors. Radiation dose inevitably deposited in healthy tissues outside the clinical target has been linked to detrimental late effects such as neurocognitive, behavioural and vascular effects in addition to endocrine abnormalities and second tumours. Methods: A literature search was performed using keywords: protons, IMRT, CNS and paediatric. Of 189 papers retrieved, 10 were deemed relevant based on title and abstract screening. All papers directly compared outcomes from protons with photons, five papers included medulloblastoma, four papers each included craniopharyngioma and low grade gliomas and three papers included ependymoma. Results: This review found that while proton beam therapy offered similar clinical target coverage, there was a demonstrable reduction in integral dose to normal structures. Conclusions: This in turn suggests the potential for superior long term outcomes for paediatric patients with CNS tumours both in terms of radiogenic second cancers and out-of-field adverse effects.

  17. Dosimetric Comparison and Potential for Improved Clinical Outcomes of Paediatric CNS Patients Treated with Protons or IMRT

    Directory of Open Access Journals (Sweden)

    Kris S. Armoogum

    2015-04-01

    Full Text Available Background: We compare clinical outcomes of paediatric patients with CNS tumours treated with protons or IMRT. CNS tumours form the second most common group of cancers in children. Radiotherapy plays a major role in the treatment of many of these patients but also contributes to late side effects in long term survivors. Radiation dose inevitably deposited in healthy tissues outside the clinical target has been linked to detrimental late effects such as neurocognitive, behavioural and vascular effects in addition to endocrine abnormalities and second tumours. Methods: A literature search was performed using keywords: protons, IMRT, CNS and paediatric. Of 189 papers retrieved, 10 were deemed relevant based on title and abstract screening. All papers directly compared outcomes from protons with photons, five papers included medulloblastoma, four papers each included craniopharyngioma and low grade gliomas and three papers included ependymoma. Results: This review found that while proton beam therapy offered similar clinical target coverage, there was a demonstrable reduction in integral dose to normal structures. Conclusions: This in turn suggests the potential for superior long term outcomes for paediatric patients with CNS tumours both in terms of radiogenic second cancers and out-of-field adverse effects.

  18. TH-C-BRF-01: The Promise and Potential Pitfalls of Deformable Image Registration in Clinical Practice

    International Nuclear Information System (INIS)

    Brock, K; Oldham, M; Cai, J; Pouliot, J

    2014-01-01

    Accurate and robust deformable image registration (DIR) is a key enabling technique in the clinical realization of two approaches for advancing radiation therapy treatment efficacy: adaptive radiation therapy and treatment response assessment. Currently there are a wide variety of DIR methods including the categories of splines, optical/diffusion, free-form, and biomechanical algorithms. All methods aim to translate information between image sets (including multi-modal data) in the presence of spatial deformation of tissues. However, recent research has shown that different DIR algorithms can yield substantially different results for the same reference deformation, and that DIR performance can be site and application dependent. As a result, errors can occur, and subsequent patient treatment can be compromised. There is a clear need for greater understanding of appropriate use of DIR techniques, as well as effective methods of validation, evaluation, and improvement. In this session, we will review the state-of-the-art concerning DIR development, clinical application, and performance evaluation. Novel DIR methods and evaluating technologies will be reviewed. Learning Objectives: To understand the underlying principles and physics of current DIR techniques To explore potential clinical applications and areas of high impact for DIR To investigate sources of uncertainty, appropriate usage, and methods for validating and evaluating DIR performance

  19. A protocol for a randomized clinical trial of interactive video dance: potential for effects on cognitive function.

    Science.gov (United States)

    Jovancevic, Jelena; Rosano, Caterina; Perera, Subashan; Erickson, Kirk I; Studenski, Stephanie

    2012-06-06

    Physical exercise has the potential to affect cognitive function, but most evidence to date focuses on cognitive effects of fitness training. Cognitive exercise also may influence cognitive function, but many cognitive training paradigms have failed to provide carry-over to daily cognitive function. Video games provide a broader, more contextual approach to cognitive training that may induce cognitive gains and have carry over to daily function. Most video games do not involve physical exercise, but some novel forms of interactive video games combine physical activity and cognitive challenge. This paper describes a randomized clinical trial in 168 postmenopausal sedentary overweight women that compares an interactive video dance game with brisk walking and delayed entry controls. The primary endpoint is adherence to activity at six months. Additional endpoints include aspects of physical and mental health. We focus this report primarily on the rationale and plans for assessment of multiple cognitive functions. This randomized clinical trial may provide new information about the cognitive effects of interactive videodance. It is also the first trial to examine physical and cognitive effects in older women. Interactive video games may offer novel strategies to promote physical activity and health across the life span.The study is IRB approved and the number is: PRO08080012ClinicalTrials.gov Identifier: NCT01443455.

  20. A protocol for a randomized clinical trial of interactive video dance: potential for effects on cognitive function

    Directory of Open Access Journals (Sweden)

    Jovancevic Jelena

    2012-06-01

    Full Text Available Abstract Background Physical exercise has the potential to affect cognitive function, but most evidence to date focuses on cognitive effects of fitness training. Cognitive exercise also may influence cognitive function, but many cognitive training paradigms have failed to provide carry-over to daily cognitive function. Video games provide a broader, more contextual approach to cognitive training that may induce cognitive gains and have carry over to daily function. Most video games do not involve physical exercise, but some novel forms of interactive video games combine physical activity and cognitive challenge. Methods/Design This paper describes a randomized clinical trial in 168 postmenopausal sedentary overweight women that compares an interactive video dance game with brisk walking and delayed entry controls. The primary endpoint is adherence to activity at six months. Additional endpoints include aspects of physical and mental health. We focus this report primarily on the rationale and plans for assessment of multiple cognitive functions. Discussion This randomized clinical trial may provide new information about the cognitive effects of interactive videodance. It is also the first trial to examine physical and cognitive effects in older women. Interactive video games may offer novel strategies to promote physical activity and health across the life span. The study is IRB approved and the number is: PRO08080012 ClinicalTrials.gov Identifier: NCT01443455

  1. The Potential Role of Lycopene for the Prevention and Therapy of Prostate Cancer: From Molecular Mechanisms to Clinical Evidence

    Science.gov (United States)

    Holzapfel, Nina Pauline; Holzapfel, Boris Michael; Champ, Simon; Feldthusen, Jesper; Clements, Judith; Hutmacher, Dietmar Werner

    2013-01-01

    Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red, lipophilic and naturally occurring in many fruits and vegetables, with tomatoes and tomato-based products containing the highest concentrations of bioavailable lycopene. Several epidemiological studies have linked increased lycopene consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that lycopene not only enhances the antioxidant response of prostate cells, but that it is even able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, there is still no clearly proven clinical evidence supporting the use of lycopene in the prevention or treatment of prostate cancer, due to the only limited number of published randomized clinical trials and the varying quality of existing studies. The scope of this article is to discuss the potential impact of lycopene on prostate cancer by giving an overview about its molecular mechanisms and clinical effects. PMID:23857058

  2. Virtual online consultations: advantages and limitations (VOCAL) study.

    Science.gov (United States)

    Greenhalgh, Trisha; Vijayaraghavan, Shanti; Wherton, Joe; Shaw, Sara; Byrne, Emma; Campbell-Richards, Desirée; Bhattacharya, Satya; Hanson, Philippa; Ramoutar, Seendy; Gutteridge, Charles; Hodkinson, Isabel; Collard, Anna; Morris, Joanne

    2016-01-29

    Remote video consultations between clinician and patient are technically possible and increasingly acceptable. They are being introduced in some settings alongside (and occasionally replacing) face-to-face or telephone consultations. To explore the advantages and limitations of video consultations, we will conduct in-depth qualitative studies of real consultations (microlevel) embedded in an organisational case study (mesolevel), taking account of national context (macrolevel). The study is based in 2 contrasting clinical settings (diabetes and cancer) in a National Health Service (NHS) acute trust in London, UK. Main data sources are: microlevel--audio, video and screen capture to produce rich multimodal data on 45 remote consultations; mesolevel--interviews, ethnographic observations and analysis of documents within the trust; macrolevel--key informant interviews of national-level stakeholders and document analysis. Data will be analysed and synthesised using a sociotechnical framework developed from structuration theory. City Road and Hampstead NHS Research Ethics Committee, 9 December 2014, reference 14/LO/1883. We plan outputs for 5 main audiences: (1) academics: research publications and conference presentations; (2) service providers: standard operating procedures, provisional operational guidance and key safety issues; (3) professional bodies and defence societies: summary of relevant findings to inform guidance to members; (4) policymakers: summary of key findings; (5) patients and carers: 'what to expect in your virtual consultation'. The research literature on video consultations is sparse. Such consultations offer potential advantages to patients (who are spared the cost and inconvenience of travel) and the healthcare system (eg, they may be more cost-effective), but fears have been expressed that they may be clinically risky and/or less acceptable to patients or staff, and they bring significant technical, logistical and regulatory challenges. We

  3. Human Amniotic Membrane-Derived Products in Sports Medicine: Basic Science, Early Results, and Potential Clinical Applications.

    Science.gov (United States)

    Riboh, Jonathan C; Saltzman, Bryan M; Yanke, Adam B; Cole, Brian J

    2016-09-01

    Amniotic membrane (AM)-derived products have been successfully used in ophthalmology, plastic surgery, and wound care, but little is known about their potential applications in orthopaedic sports medicine. To provide an updated review of the basic science and preclinical and clinical data supporting the use of AM-derived products and to review their current applications in sports medicine. Systematic review. A systematic search of the literature was conducted using the Medline, EMBASE, and Cochrane databases. The search term amniotic membrane was used alone and in conjunction with stem cell, orthopaedic, tissue engineering, scaffold, and sports medicine. The search identified 6870 articles, 80 of which, after screening of the titles and abstracts, were considered relevant to this study. Fifty-five articles described the anatomy, basic science, and nonorthopaedic applications of AM-derived products. Twenty-five articles described preclinical and clinical trials of AM-derived products for orthopaedic sports medicine. Because the level of evidence obtained from this search was not adequate for systematic review or meta-analysis, a current concepts review on the anatomy, physiology, and clinical uses of AM-derived products is presented. Amniotic membranes have many promising applications in sports medicine. They are a source of pluripotent cells, highly organized collagen, antifibrotic and anti-inflammatory cytokines, immunomodulators, and matrix proteins. These properties may make it beneficial when applied as tissue engineering scaffolds, improving tissue organization in healing, and treatment of the arthritic joint. The current body of evidence in sports medicine is heavily biased toward in vitro and animal studies, with little to no human clinical data. Nonetheless, 14 companies or distributors offer commercial AM products. The preparation and formulation of these products alter their biological and mechanical properties, and a thorough understanding of these

  4. Clinical utility of fixed-dose combinations in hypertension: evidence for the potential of nebivolol/valsartan

    Directory of Open Access Journals (Sweden)

    Varagic J

    2014-11-01

    Full Text Available Jasmina Varagic,1–3 Henry Punzi,4,5 Carlos M Ferrario2,3,61Hypertension and Vascular Research Center, 2Division of Surgical Sciences, 3Department of Physiology and Pharmacology, Wake Forest University, Winston-Salem, NC USA; 4Trinity Hypertension and Diagnostic Research Center, Carrollton, TX, USA; 5Department of Family and Community Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA; 6Department of Internal Medicine and Nephrology, Wake Forest University, Winston-Salem, NC, USAAbstract: Despite significant advances in pharmacologic approaches to treat hypertension during the last decades, hypertension- and hypertension-related organ damage are still a high health and economic burden because a large proportion of patients with hypertension do not achieve optimal blood pressure control. There is now general agreement that combination therapy with two or more antihypertensive drugs is required for targeted blood pressure accomplishment and reduction of global cardiovascular risk. The goals of combination therapies are to reduce long-term cardiovascular events by targeting different mechanism underlying hypertension and target organ disease, to block the counterregulatory pathways activated by monotherapies, to improve tolerability and decrease the adverse effects of up-titrated single agents, and to increase persistence and adherence with antihypertensive therapy. Multiple clinical trials provide evidence that fixed-dose combinations in a single pill offer several advantages when compared with loose-dose combinations. This review discusses the advances in hypertension control and associated cardiovascular disease as they relate to the prospect of combination therapy targeting a third-generation beta (β 1-adrenergic receptor (nebivolol and an angiotensin II receptor blocker (valsartan in fixed-dose single-pill formulations.Keywords: blood pressure control, hypertension, β1-adrenergic receptor, renin angiotensin system

  5. Towards single embryo transfer? Modelling clinical outcomes of potential treatment choices using multiple data sources: predictive models and patient perspectives.

    Science.gov (United States)

    Roberts, Sa; McGowan, L; Hirst, Wm; Brison, Dr; Vail, A; Lieberman, Ba

    2010-07-01

    In vitro fertilisation (IVF) treatments involve an egg retrieval process, fertilisation and culture of the resultant embryos in the laboratory, and the transfer of embryos back to the mother over one or more transfer cycles. The first transfer is usually of fresh embryos and the remainder may be cryopreserved for future frozen cycles. Most commonly in UK practice two embryos are transferred (double embryo transfer, DET). IVF techniques have led to an increase in the number of multiple births, carrying an increased risk of maternal and infant morbidity. The UK Human Fertilisation and Embryology Authority (HFEA) has adopted a multiple birth minimisation strategy. One way of achieving this would be by increased use of single embryo transfer (SET). To collate cohort data from treatment centres and the HFEA; to develop predictive models for live birth and twinning probabilities from fresh and frozen embryo transfers and predict outcomes from treatment scenarios; to understand patients' perspectives and use the modelling results to investigate the acceptability of twin reduction policies. A multidisciplinary approach was adopted, combining statistical modelling with qualitative exploration of patients' perspectives: interviews were conducted with 27 couples at various stages of IVF treatment at both UK NHS and private clinics; datasets were collated of over 90,000 patients from the HFEA registry and nearly 9000 patients from five clinics, both over the period 2000-5; models were developed to determine live birth and twin outcomes and predict the outcomes of policies for selecting patients for SET or DET in the fresh cycle following egg retrieval and fertilisation, and the predictions were used in simulations of treatments; two focus groups were convened, one NHS and one web based on a patient organisation's website, to present the results of the statistical analyses and explore potential treatment policies. The statistical analysis revealed no characteristics that

  6. Analysis of yield advantage in mixed cropping

    NARCIS (Netherlands)

    Ranganathan, R.

    1993-01-01

    It has long been recognized that mixed cropping can give yield advantages over sole cropping, but methods that can identify such yield benefits are still being developed. This thesis presents a method that combines physiological and economic principles in the evaluation of yield advantage.

  7. Competitive advantage, what does it really mean?

    NARCIS (Netherlands)

    dr. Haijing de Haan; Hongjue Yan

    2013-01-01

    Competitive advantage is probably the most popular business concept today (Mooney, 2007). This article aims to investigate critically the discourse on competitive advantage, as expressed by business literature, by locating its meanings in the public higher education sector. This research reveals

  8. Strategic Positioning for Sustainable Competitive Advantage: An ...

    African Journals Online (AJOL)

    Organizational learning is increasingly being considered as one of the fundamental sources of competitive advantage within the context of strategic management. However, most literature has not clearly linked organizational learning with sustainable competitive advantage. This paper, therefore, explores and discusses the ...

  9. Analisis Dampak Servant Leadership Terhadap Competitive Advantage

    OpenAIRE

    Oktavia, Pek Nike

    2014-01-01

    Penelitian ini bertujuan untuk mengetahui apakah terdapat dampak antara Servant Leadership terhadap Competitve Advantage, Employee Empowerment dan Organizational Learning. Variabel Servant Leadership diukur dari lima indikator, yaitu altruistic calling, emotional healing, wisdom, persuasive mapping, dan organizational stewardship. Variabel Competitive Advantage diukur dari lima indikator, yaitu price/cost, quality, delivery dependability, time to market, dan product innovation. Variabel Emplo...

  10. Mechanistic Basis of Cocrystal Dissolution Advantage.

    Science.gov (United States)

    Cao, Fengjuan; Amidon, Gordon L; Rodríguez-Hornedo, Naír; Amidon, Gregory E

    2018-01-01

    Current interest in cocrystal development resides in the advantages that the cocrystal may have in solubility and dissolution compared with the parent drug. This work provides a mechanistic analysis and comparison of the dissolution behavior of carbamazepine (CBZ) and its 2 cocrystals, carbamazepine-saccharin (CBZ-SAC) and carbamazepine-salicylic acid (CBZ-SLC) under the influence of pH and micellar solubilization. A simple mathematical equation is derived based on the mass transport analyses to describe the dissolution advantage of cocrystals. The dissolution advantage is the ratio of the cocrystal flux to drug flux and is defined as the solubility advantage (cocrystal to drug solubility ratio) times the diffusivity advantage (cocrystal to drug diffusivity ratio). In this work, the effective diffusivity of CBZ in the presence of surfactant was determined to be different and less than those of the cocrystals. The higher effective diffusivity of drug from the dissolved cocrystals, the diffusivity advantage, can impart a dissolution advantage to cocrystals with lower solubility than the parent drug while still maintaining thermodynamic stability. Dissolution conditions where cocrystals can display both thermodynamic stability and a dissolution advantage can be obtained from the mass transport models, and this information is useful for both cocrystal selection and formulation development. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  11. Potential clinical applications of {sup 18}F-fluorodeoxyglucose position emission tomography/magnetic resonance mammography in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Ihn Ho; Kong, Eun Jung [Dept. of Nuclear Medicine, Yeugnam University Hospital, Daegu (Korea, Republic of)

    2017-09-15

    The whole-body positron emission tomography (PET)/magnetic resonance (MR) scan is a cutting edge technology providing comprehensive structural information from MR imaging and functional features from PET in a single session. Recent research findings and clinical experience have shown that 18F-fluorodeoxyglucose (FDG) whole-body PET/MR imaging has a diagnostic performance comparable with or superior to that of PET/CT in the field of oncology, including for breast cancer. In particular, FDG PET/MR mammography in the prone position with the breast hanging in a pendant manner can provide more comprehensive information about the metabolism, anatomy, and functional features of a breast lesion than a whole-body PET/MR scan. This article reports on current state-of-the-art PET/MR mammography in patients with breast cancer and the prospects for potential application in the future.

  12. COMPETITIVE ADVANTAGE IN THE ENTERPRISE PERFORMANCE

    Directory of Open Access Journals (Sweden)

    PRUNEA Ana Daniela

    2014-07-01

    Full Text Available Rapid changes in market characteristics and the technological innovations are common and faster challenges, resulting in products, processes and technologies. The competitive advantage is volatile, difficult to obtain and more difficult to maintain and strengthened with consumers who through their individual choices polarization confirms the recognition performance and award competitive advantages, thus causing the competitive ranking of companies present in a particular market. The competitive advantage lies in the focus of the performance of companies in competitive markets and innovation is a source for obtaining and consolidating it. Companies will need to demonstrate the capacity to adapt to changes in the business environment so as to maintain the helded positions. This paper treats this aspect behavior that companies should adopt to get on the account of innovation a sustainable competitive advantage. I started of the work in the elaboration from the theory of developed by Michael Porter in his book "Competitive Advantage: Creating and Sustaining Superior Performance" we applied methods listed thus trying to point out possible ways of creating competitive advantage by companies. We have presented the sources of competitive advantage and the factors on which depends its creation. Walking theoretical research revealed how lack of competitive advantage leads to a lack of competitiveness of companies and the benefits that arise with the creation of this type of asset. Among the most important benefits is to increase performances. Once the competitive advantage is achieved, it must be maintained and updated market conditions and the methods that can be created a sustainable competitive advantage represent the answers to many of the companies questions are fighting for survival in an environment of fierce competition. The implementation of methods for obtaining competitive advantages, but also exist dangers, that every company should know them

  13. Chemoradiation Therapy for Potentially Resectable Gastric Cancer: Clinical Outcomes Among Patients Who Do Not Undergo Planned Surgery

    International Nuclear Information System (INIS)

    Kim, Michelle M.; Mansfield, Paul F.; Das, Prajnan; Janjan, Nora A.; Badgwell, Brian D.; Phan, Alexandria T.; Delclos, Marc E.; Maru, Dipen; Ajani, Jaffer A.; Crane, Christopher H.; Krishnan, Sunil

    2008-01-01

    Purpose: We retrospectively analyzed treatment outcomes among resectable gastric cancer patients treated preoperatively with chemoradiation therapy (CRT) but rendered ineligible for planned surgery because of clinical deterioration or development of overt metastatic disease. Methods and Materials: Between 1996 and 2004, 39 patients with potentially resectable gastric cancer received preoperative CRT but failed to undergo surgery. At baseline clinical staging, 33 (85%) patients had T3-T4 disease, and 27 (69%) patients had nodal involvement. Most patients received 45 Gy of radiotherapy with concurrent 5-fluorouracil-based chemotherapy. Twenty-one patients underwent induction chemotherapy before CRT. Actuarial times to local control (LC), distant control (DC), and overall survival (OS) were calculated by the Kaplan-Meier method. Results: The cause for surgical ineligibility was development of metastatic disease (28 patients, 72%; predominantly peritoneal, 18 patients), poor performance status (5 patients, 13%), patient/physician preference (4 patients, 10%), and treatment-related death (2 patients, 5%). With a median follow-up of 8 months (range, 1-95 months), actuarial 1-year LC, DC, and OS were 46%, 12%, and 36%, respectively. Median LC and OS were 11.0 and 10.1 months, respectively. Conclusions: Patients with potentially resectable gastric cancer treated with preoperative CRT are found to be ineligible for surgery principally because of peritoneal progression. Patients who are unable to undergo planned surgery have outcomes comparable to that of patients with advanced gastric cancer treated with chemotherapy alone. CRT provides durable LC for the majority of the remaining life of these patients

  14. Assessing emotional status following acquired brain injury: the clinical potential of the depression, anxiety and stress scales.

    Science.gov (United States)

    Ownsworth, Tamara; Little, Trudi; Turner, Ben; Hawkes, Anna; Shum, David

    2008-10-01

    To investigate the clinical potential of the Depression, Anxiety and Stress Scales (DASS 42) and its shorter version (DASS 21) for assessing emotional status following acquired brain injury. Participants included 23 individuals with traumatic brain injury (TBI), 25 individuals with brain tumour and 29 non-clinical controls. Investigations of internal consistency, test-re-test reliability, theory-consistent differences, sensitivity to change and concurrent validity were conducted. Internal consistency of the DASS was generally acceptable (r > 0.70), with the exception of the anxiety scale for the TBI sample. Test-re-test reliability (1-3 weeks) was sound for the depression scale (r > 0.75) and significant but comparatively lower for other scales (r = 0.60-0.73, p scale (p DASS in the context of hospital discharge was demonstrated for depression and stress (p 0.05). Concurrent validity with the Hospital Anxiety and Depression Scale was significant for all scales of the DASS (p DASS following ABI, further research examining the factor structure of existing and modified versions of the DASS is recommended.

  15. Intra-oral orthosis vs amitriptyline in chronic tension-type headache: a clinical and laser evoked potentials study

    Directory of Open Access Journals (Sweden)

    Sardaro Michele

    2006-05-01

    Full Text Available Abstract Background In the present study, we examined clinical and laser-evoked potentials (LEP features in two groups of chronic tension-type headache (CTTH patients treated with two different approaches: intra-oral appliance of prosthesis, aiming to reduce muscular tenderness, and 10 mg daily amitriptyline. Methods Eighteen patients with diagnosed CTTH participated in this open label, controlled study. A baseline evaluation was performed for clinical features, Total Tenderness Score (TTS and a topographic analysis of LEPs obtained manually and the pericranial points stimulation in all patients vs. healthy subjects. Thereafter, patients were randomly assigned to a two-month treatment by either amitriptyline or intra-oral appliance. Results and discussion Both the intra-oral appliance and amitriptyline significantly reduced headache frequency. The TTS was significantly reduced in the group treated with the appliance. The amplitude of P2 response elicited by stimulation of pericranial zones showed a reduction after amitriptyline treatment. Both therapies were effective in reducing headache severity, the appliance with a prevalent action on the pericranial muscular tenderness, amitriptyline reducing the activity of the central cortical structures subtending pain elaboration Conclusion The results of this study may suggest that in CTTH both the interventions at the peripheral and central levels improve the outcome of headache.

  16. In vitro and clinical evaluation of OATP-mediated drug interaction potential of sacubitril/valsartan (LCZ696).

    Science.gov (United States)

    Ayalasomayajula, S; Han, Y; Langenickel, T; Malcolm, K; Zhou, W; Hanna, I; Alexander, N; Natrillo, A; Goswami, B; Hinder, M; Sunkara, G

    2016-08-01

    Sacubitril/valsartan (LCZ696) has been recently approved for the treatment of heart failure (HF) patients with reduced ejection fraction. Several HF patients receive statins as co-medication. Because clearance of statins is meditated via OATP1B1/1B3, the inhibition potential of these transporters by LCZ696 analytes was evaluated in vitro. Furthermore, an open-label, fixed-sequence clinical study was conducted to determine the effect of LCZ696 on the exposure of simvastatin and its active metabolite simvastatin acid. In this clinical study, 26 healthy subjects received simvastatin 40 mg alone or in combination with LCZ696 or after 1 or 2 h of LCZ696 dosing. Although no significant inhibition by LBQ657 (an active metabolite of sacubitril) and valsartan was observed, sacubitril inhibited OATP1B1 and OATP1B3 in vitro, with IC50 of 1·91 and 3·81 μm, respectively. Upon co-administration of simvastatin with LCZ696, the Cmax of simvastatin and simvastatin acid decreased by 7% and 13%, respectively. When administered 1 h after LCZ696 dosing, the corresponding Cmax of simvastatin and simvastatin acid decreased by 16% and 4%, respectively. When administered 2 h after LCZ696 dosing, the Cmax of simvastatin decreased by 33% and that of simvastatin acid increased by 16%. However, no notable changes were observed in the AUCs of simvastatin or simvastatin acid upon co-administration or time-separated administration with LCZ696. No notable impact of simvastatin co-administration was observed on the pharmacokinetics of LCZ696 analytes. LCZ696 and simvastatin were generally well tolerated when administered alone or in combination. Overall, the results of this study suggest that although sacubitril inhibited OATP1B1 and OATP1B3 in vitro, it does not translate into any clinically relevant in vivo effect. © 2016 John Wiley & Sons Ltd.

  17. The greenhouse advantage of natural gas appliances

    International Nuclear Information System (INIS)

    Coombe, N.

    2000-01-01

    The life cycle report prepared recently by Energetics for the AGA, Assessment of Greenhouse Gas Emissions from Natural Gas, demonstrates clearly the greenhouse advantage natural gas has over coal in generating electricity. This study also goes one step further in applying this life cycle approach to the use of space and water heating within the home. The study shows the significant green-house advantage that natural gas appliances have over electric appliances. Findings from other studies also support this claim. The natural gas suppliers are encouraged to take advantage of the marketing opportunity that these studies provide, offering the householders the fuel that will significantly reduce their contribution to greenhouse emission

  18. Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis

    Science.gov (United States)

    Tupone, Domenico; Madden, Christopher J.; Morrison, Shaun F.

    2014-01-01

    From mouse to man, brown adipose tissue (BAT) is a significant source of thermogenesis contributing to the maintenance of the body temperature homeostasis during the challenge of low environmental temperature. In rodents, BAT thermogenesis also contributes to the febrile increase in core temperature during the immune response. BAT sympathetic nerve activity controlling BAT thermogenesis is regulated by CNS neural networks which respond reflexively to thermal afferent signals from cutaneous and body core thermoreceptors, as well as to alterations in the discharge of central neurons with intrinsic thermosensitivity. Superimposed on the core thermoregulatory circuit for the activation of BAT thermogenesis, is the permissive, modulatory influence of central neural networks controlling metabolic aspects of energy homeostasis. The recent confirmation of the presence of BAT in human and its function as an energy consuming organ have stimulated interest in the potential for the pharmacological activation of BAT to reduce adiposity in the obese. In contrast, the inhibition of BAT thermogenesis could facilitate the induction of therapeutic hypothermia for fever reduction or to improve outcomes in stroke or cardiac ischemia by reducing infarct size through a lowering of metabolic oxygen demand. This review summarizes the central circuits for the autonomic control of BAT thermogenesis and highlights the potential clinical relevance of the pharmacological inhibition or activation of BAT thermogenesis. PMID:24570653

  19. Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis.

    Science.gov (United States)

    Tupone, Domenico; Madden, Christopher J; Morrison, Shaun F

    2014-01-01

    From mouse to man, brown adipose tissue (BAT) is a significant source of thermogenesis contributing to the maintenance of the body temperature homeostasis during the challenge of low environmental temperature. In rodents, BAT thermogenesis also contributes to the febrile increase in core temperature during the immune response. BAT sympathetic nerve activity controlling BAT thermogenesis is regulated by CNS neural networks which respond reflexively to thermal afferent signals from cutaneous and body core thermoreceptors, as well as to alterations in the discharge of central neurons with intrinsic thermosensitivity. Superimposed on the core thermoregulatory circuit for the activation of BAT thermogenesis, is the permissive, modulatory influence of central neural networks controlling metabolic aspects of energy homeostasis. The recent confirmation of the presence of BAT in human and its function as an energy consuming organ have stimulated interest in the potential for the pharmacological activation of BAT to reduce adiposity in the obese. In contrast, the inhibition of BAT thermogenesis could facilitate the induction of therapeutic hypothermia for fever reduction or to improve outcomes in stroke or cardiac ischemia by reducing infarct size through a lowering of metabolic oxygen demand. This review summarizes the central circuits for the autonomic control of BAT thermogenesis and highlights the potential clinical relevance of the pharmacological inhibition or activation of BAT thermogenesis.

  20. Clinical relevancy and determinants of potential drug–drug interactions in chronic kidney disease patients: results from a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Saleem A

    2017-02-01

    Full Text Available Ahsan Saleem,1,2 Imran Masood,1 Tahir Mehmood Khan3 1Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2Pharmacy Services Department, Integrated Medical Center, The Aga Khan University Hospital, Lahore, Pakistan; 3School of Pharmacy, Monash University, Sunway Campus, Selangor, Malaysia Background: Chronic kidney disease (CKD alters the pharmacokinetic and pharmacodynamic responses of various renally excreted drugs and increases the risk of drug-related problems, such as drug–drug interactions.Objectives: To assess the pattern, determinants, and clinical relevancy of potential drug–drug interactions (pDDIs in CKD patients.Materials and methods: This study retrospectively reviewed medical charts of all CKD patients admitted in the nephrology unit of a tertiary care hospital in Pakistan from January 2013 to December 2014. The Micromedex Drug-Reax® system was used to screen patient profiles for pDDIs, and IBM SPSS version 20 was used to carry out statistical analysis.Results: We evaluated 209 medical charts and found pDDIs in nearly 78.5% CKD patients. Overall, 541 pDDIs were observed, of which, nearly 60.8% patients had moderate, 41.1% had minor, 27.8% had major, and 13.4% had contraindicated interactions. Among those interactions, 49.4% had good evidence, 44.0% had fair, 6.3% had excellent evidence, and 35.5% interactions had delayed onset of action. The potential adverse outcomes of pDDIs included postural hypotension, QT prolongation, ceftriaxone–calcium precipitation, cardiac arrhythmias, and reduction in therapeutic effectiveness. The occurrence of pDDIs was found strongly associated with the age of <60 years, number of prescribed medicines ≥5, hypertension, and the lengthy hospitalization of patients.Conclusion: The occurrence of pDDIs was high in CKD patients. It was observed that CKD patients with an older age, higher number of prescribed medicines, lengthy hospitalization, and hypertension were at

  1. Competitive advantage on a warming planet.

    Science.gov (United States)

    Lash, Jonathan; Wellington, Fred

    2007-03-01

    Whether you're in a traditional smokestack industry or a "clean" business like investment banking, your company will increasingly feel the effects of climate change. Even people skeptical about global warming's dangers are recognizing that, simply because so many others are concerned, the phenomenon has wide-ranging implications. Investors already are discounting share prices of companies poorly positioned to compete in a warming world. Many businesses face higher raw material and energy costs as more and more governments enact policies placing a cost on emissions. Consumers are taking into account a company's environmental record when making purchasing decisions. There's also a burgeoning market in greenhouse gas emission allowances (the carbon market), with annual trading in these assets valued at tens of billions of dollars. Companies that manage and mitigate their exposure to the risks associated with climate change while seeking new opportunities for profit will generate a competitive advantage over rivals in a carbon-constrained future. This article offers a systematic approach to mapping and responding to climate change risks. According to Jonathan Lash and Fred Wellington of the World Resources Institute, an environmental think tank, the risks can be divided into six categories: regulatory (policies such as new emissions standards), products and technology (the development and marketing of climate-friendly products and services), litigation (lawsuits alleging environmental harm), reputational (how a company's environmental policies affect its brand), supply chain (potentially higher raw material and energy costs), and physical (such as an increase in the incidence of hurricanes). The authors propose a four-step process for responding to climate change risk: Quantify your company's carbon footprint; identify the risks and opportunities you face; adapt your business in response; and do it better than your competitors.

  2. National and International Library Collaboration: Necessity, Advantages

    Directory of Open Access Journals (Sweden)

    Timothy Mark

    2007-11-01

    Full Text Available The advantages of cooperation between research library associations can be demonstrated quite clearly. Where cooperation becomes essential is where there is a common cause to champion or an initiative to pursue for the common good. Thanks in part to the power of information communications technology, research is becoming increasingly international in scope. The members of interdisciplinary and multidisciplinary research teams are frequently drawn from across the world. Correspondingly, scholarly publishing (especially in medicine and the sciences is dominated by a few multinational publishers. In this context, issues that play a vital role in global scholarly communication - such as copyright, journal pricing, the managing of datasets, digital preservation and open access - are issues for the research library community everywhere in the world. Certainly there are many challenges at the local or regional level. However there are definite roles that research library associations can play most effectively at the national or international level. It is clear that by sharing expertise, building partnerships and alliances, it is possible to address common issues much more effectively than when working alone. What is special is that potentially the most powerful form of cooperation is advocacy at the national and international levels. It is essential for research library associations to work together at the political level to move their agenda forward. Examples are lobbying about copyright legislation (nationally, or within the EC or at WIPO; or promoting the cause of Open Access. The unique value of LIBER is to provide a forum and a platform for European research library associations to explore and benefit from cooperation and their shared strength.

  3. Information needs for making clinical recommendations about potential drug-drug interactions: a synthesis of literature review and interviews.

    Science.gov (United States)

    Romagnoli, Katrina M; Nelson, Scott D; Hines, Lisa; Empey, Philip; Boyce, Richard D; Hochheiser, Harry

    2017-02-22

    Drug information compendia and drug-drug interaction information databases are critical resources for clinicians and pharmacists working to avoid adverse events due to exposure to potential drug-drug interactions (PDDIs). Our goal is to develop information models, annotated data, and search tools that will facilitate the interpretation of PDDI information. To better understand the information needs and work practices of specialists who search and synthesize PDDI evidence for drug information resources, we conducted an inquiry that combined a thematic analysis of published literature with unstructured interviews. Starting from an initial set of relevant articles, we developed search terms and conducted a literature search. Two reviewers conducted a thematic analysis of included articles. Unstructured interviews with drug information experts were conducted and similarly coded. Information needs, work processes, and indicators of potential strengths and weaknesses of information systems were identified. Review of 92 papers and 10 interviews identified 56 categories of information needs related to the interpretation of PDDI information including drug and interaction information; study design; evidence including clinical details, quality and content of reports, and consequences; and potential recommendations. We also identified strengths/weaknesses of PDDI information systems. We identified the kinds of information that might be most effective for summarizing PDDIs. The drug information experts we interviewed had differing goals, suggesting a need for detailed information models and flexible presentations. Several information needs not discussed in previous work were identified, including temporal overlaps in drug administration, biological plausibility of interactions, and assessment of the quality and content of reports. Richly structured depictions of PDDI information may help drug information experts more effectively interpret data and develop recommendations

  4. Exploring the sequential lineup advantage using WITNESS.

    Science.gov (United States)

    Goodsell, Charles A; Gronlund, Scott D; Carlson, Curt A

    2010-12-01

    Advocates claim that the sequential lineup is an improvement over simultaneous lineup procedures, but no formal (quantitatively specified) explanation exists for why it is better. The computational model WITNESS (Clark, Appl Cogn Psychol 17:629-654, 2003) was used to develop theoretical explanations for the sequential lineup advantage. In its current form, WITNESS produced a sequential advantage only by pairing conservative sequential choosing with liberal simultaneous choosing. However, this combination failed to approximate four extant experiments that exhibited large sequential advantages. Two of these experiments became the focus of our efforts because the data were uncontaminated by likely suspect position effects. Decision-based and memory-based modifications to WITNESS approximated the data and produced a sequential advantage. The next step is to evaluate the proposed explanations and modify public policy recommendations accordingly.

  5. Measuring Coding Intensity in Medicare Advantage - SUPP.

    Data.gov (United States)

    U.S. Department of Health & Human Services — In 2004, Medicare implemented a risk-adjustment system that pays Medicare Advantage (MA) plans based on diagnoses reported for their enrollees, giving the plans an...

  6. AquAdvantage Salmon Genetically modified organism

    OpenAIRE

    Núñez Saurí, Ester; Universitat Autònoma de Barcelona. Facultat de Veterinària

    2014-01-01

    Póster AquAdvantage Salmon is a genetically modified organism developed by AquBounty Technologies. The objective of this transgenic organism is to increase the growth rate to obtain the same of conventional salmon faster.

  7. Tanzania's Revealed Comparative Advantage and Structural ...

    African Journals Online (AJOL)

    example, the contribution from vegetable products fell by 7%, and that from textiles .... 43 -‐ Furskins and artificial fur, manufactures thereof ... example, while Tanzania has comparative advantage in raw hides and skins (see Figure 6), it.

  8. Abnormal uterine bleeding: advantages of formal classification to patients, clinicians and researchers.

    Science.gov (United States)

    Madhra, Mayank; Fraser, Ian S; Munro, Malcolm G; Critchley, Hilary O D

    2014-07-01

    To highlight the advantages of formal classification of causes of abnormal uterine bleeding from a clinical and scientific perspective. Review and recommendations for local implementation. In the past, research in the field of menstrual disorders has not been funded adequately with respect to the impact of symptoms on individuals, healthcare systems and society. This was confounded by a diverse terminology, which lead to confusion between clinical and scientific groups, ultimately harming the underlying evidence base. To address this, a formal classification system (PALM-COEIN) for the causes of abnormal uterine bleeding has been published for worldwide use by FIGO (International Federation of Gynecology and Obstetrics). This commentary explains problems created by the prior absence of such a system, the potential advantages stemming from its use, and practical suggestions for local implementation. The PALM-COEIN classification is applicable globally and, as momentum gathers, will ameliorate recurrence of historic problems, and harmonise reporting of clinical and scientific research to facilitate future progress in women's health. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  9. The Temporal Limits of Technological Advantage

    Science.gov (United States)

    2017-06-01

    technologically advanced capabilities. “ Technology , in fact, is one of the keys to understanding relations between Hitler’s regime and the German business ...strategy sought to “leverage US advantages in technologies 2 like big data, stealth, advanced manufacturing (e.g. 3-D printing), robotics, and... history has had different parameters and different results, examining historical situations in which a technological advantage has been achieved

  10. COMPETITIVE ADVANTAGE IN THE ENTERPRISE PERFORMANCE

    OpenAIRE

    PRUNEA Ana Daniela

    2014-01-01

    Rapid changes in market characteristics and the technological innovations are common and faster challenges, resulting in products, processes and technologies. The competitive advantage is volatile, difficult to obtain and more difficult to maintain and strengthened with consumers who through their individual choices polarization confirms the recognition performance and award competitive advantages, thus causing the competitive ranking of companies present in a particular market. The competiti...

  11. ENTERPRISE IRELAND: Design for Competitive Advantage Conference

    OpenAIRE

    Dee, Peter

    2003-01-01

    A stimulating conference bringing together world leading experts on design to address the importance of brand development strategies to achieve competitive advantage. Peter Dee - Strategic Design and Marketing Consultant, specialised in the creation of brand development strategies for Enterprise Ireland’s Design Unit. Peter was responsible for the design and development of the the brand identity for the Enterprise Ireland Design for Competitive Advantage Conference in Dublin.

  12. Advantages and risks in service standardization

    Directory of Open Access Journals (Sweden)

    Veres Zoltán

    2004-01-01

    Full Text Available Comparing the advantages and risks in standardizing services, there can be no clear-cut answer concerning the strategy to be followed. Exploiting advantages in the long run is only worth it for a provider of a service that is able to build up a powerful brand image. However, the more successful a service concept, the stronger the temptation to imitation. The success of imitators will sooner or later bring about multibrand loyalty.

  13. Theoretical aspects of competitive advantage and competition

    OpenAIRE

    Hudakova, Ivana

    2009-01-01

    The concept of competitive advantage is well-known for many of us and a number of literary resources focused on entrepreneurship and functioning of economies deal with it, either directly or indirectly. The understanding of the term competitive advantage though sometimes varies. One can only perceive it when looking at it as a whole, a live organism that is constantly developing in a complex dynamic entrepreneurial environment, the individual parts of which do not function when separated from...

  14. Safety and environmental advantages of breeding blanketless fusion reactors

    International Nuclear Information System (INIS)

    Zucchetti, M.; Merola, M.; Matera, R.

    1994-01-01

    Next-step reactors will use DT cycle. However, environmental advantage will be the main chance for fusion to compete with other energy sources. The environmental problems of DT cycle due to tritium and neutron activation, are examined. Fusion commercial reactors could be based on alternative fuel cycles like D-He3. Advantages and disadvantages of this fuel cycle are outlined. All the technologies related with the self-breeding of tritium and the concept of breeding blanket itself may be not reactor relevant. In the frame of the Next-step studies, the potential advantages of intermediate DT devices without breeding blanket are discussed. Simplified design, lower cost, higher safety are the main ones. The problem of the source of tritium is examined. (author)

  15. Places and faces: Geographic environment influences the ingroup memory advantage.

    Science.gov (United States)

    Rule, Nicholas O; Garrett, James V; Ambady, Nalini

    2010-03-01

    The preferential allocation of attention and memory to the ingroup (the ingroup memory advantage) is one of the most replicated effects in the psychological literature. But little is known about what factors may influence such effects. Here the authors investigated a potential influence: category salience as determined by the perceiver's geographic environment. They did so by studying the ingroup memory advantage in perceptually ambiguous groups for whom perceptual cues do not make group membership immediately salient. Individuals in an environment in which a particular group membership was salient (Mormon and non-Mormon men and women living in Salt Lake City, Utah) showed better memory for faces belonging to their ingroup in an incidental encoding paradigm. Majority group participants in an environment where this group membership was not salient (non-Mormon men and women in the northeastern United States), however, showed no ingroup memory advantage whereas minority group participants (Mormons) in the same environment did. But in the same environment, when differences in group membership were made accessible via an unobtrusive priming task, non-Mormons did show an ingroup memory advantage and Mormons' memory for ingroup members increased. Environmental context cues therefore influence the ingroup memory advantage for categories that are not intrinsically salient.

  16. Polyploidy in haloarchaea: advantages for growth and survival

    Directory of Open Access Journals (Sweden)

    Karolin eZerulla

    2014-06-01

    Full Text Available The investigated haloarchaeal species, Halobacterium salinarum, Haloferax mediterranii, and H. volcanii, have all been shown to be polyploid. They contain several replicons that have independent copy number regulation, and most have a higher copy number during exponential growth phase than stationary phase. The possible evolutionary advantages of polyploidy for haloarchaea, most of which have experimental support for at least one species, are discussed. These advantages include a low mutation rate and high resistance towards X-ray irradiation and desiccation, which depend on homologous recombination. For H. volcanii, it has been shown that gene conversion operates in the absence of selection, which leads to the equalization of genome copies. On the other hand, selective forces might lead to heterozygous cells, which have been verified in the laboratory. Additional advantages of polyploidy are survival over geological times in halite deposits as well as at extreme conditions on earth and at simulated Mars conditions. Recently, it was found that H. volcanii uses genomic DNA as genetic material and as a storage polymer for phosphate. In the absence of phosphate, H. volcanii dramatically decreases its genome copy number, thereby enabling cell multiplication, but diminishing the genetic advantages of polyploidy. Stable storage of phosphate is proposed as an alternative driving force for the emergence of DNA in early evolution. Several additional potential advantages of polyploidy are discussed that have not been addressed experimentally for haloarchaea. An outlook summarizes selected current trends and possible future developments.

  17. Identification of potential new protein vaccine candidates through pan-surfomic analysis of pneumococcal clinical isolates from adults.

    Directory of Open Access Journals (Sweden)

    Alfonso Olaya-Abril

    Full Text Available Purified polysaccharide and conjugate vaccines are widely used for preventing infections in adults and in children against the Gram-positive bacterium Streptococcus pneumoniae, a pathogen responsible for high morbidity and mortality rates, especially in developing countries. However, these polysaccharide-based vaccines have some important limitations, such as being serotype-dependent, being subjected to losing efficacy because of serotype replacement and high manufacturing complexity and cost. It is expected that protein-based vaccines will overcome these issues by conferring a broad coverage independent of serotype and lowering production costs. In this study, we have applied the "shaving" proteomic approach, consisting of the LC/MS/MS analysis of peptides generated by protease treatment of live cells, to a collection of 16 pneumococcal clinical isolates from adults, representing the most prevalent strains circulating in Spain during the last years. The set of unique proteins identified in all the isolates, called "pan-surfome", consisted of 254 proteins, which included most of the protective protein antigens reported so far. In search of new candidates with vaccine potential, we identified 32 that were present in at least 50% of the clinical isolates analyzed. We selected four of them (Spr0012, Spr0328, Spr0561 and SP670_2141, whose protection capacity has not yet been tested, for assaying immunogenicity in human sera. All of them induced the production of IgM antibodies in infected patients, thus indicating that they could enter the pipeline for vaccine studies. The pan-surfomic approach shows its utility in the discovery of new proteins that can elicit protection against infectious microorganisms.

  18. Longitudinal split of the posterior cruciate ligament: description of a new MR finding and evaluation of its potential clinical significance

    Energy Technology Data Exchange (ETDEWEB)

    Cha, J.H. [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Chung, H.W., E-mail: chung@amc.seoul.k [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Kwon, J.W. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of); Choi, B.K.; Lee, S.H.; Shin, M.J. [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2011-03-15

    Aim: To evaluate the clinical significance of the intra-substance longitudinal split of the posterior cruciate ligament (LS-PCL) and to evaluate its potential clinical significance on MRI. Materials and methods: The databases of two centres were searched for LS-PCL, 6917 knee magnetic resonance imaging (MRI) examinations undertaken were retrospectively reviewed. LS-PCL was defined as increased signal intensity in a PCL in the longitudinal direction, but with an intact ligament outer surface on MRI. Twelve patients were enrolled in this study. Available arthroscopic results, degree of posterior knee instability, and changes in MRI findings, or the degree of instability during follow-up (FU), were reviewed from the patients medical records and via their MRI images. MRI images were reviewed by two musculoskeletal radiologists in consensus for presence and location of LS-PCL and any combined injuries: menisci lesions, ligament injuries, and bone marrow changes. Results: Seven of 12 patients (58.3%) had morphological or functional evidence of PCL injury or insufficiency according to the change of posterior instability on FU stress testing (n = 3), insufficiency during arthroscopy (n = 2), or decreased extent and altered shape of the PCL split on the FU MRI (n = 3). One patient revealed both change of posterior instability on FU stress testing and insufficiency during arthroscopy. Combined injuries were revealed in seven patients. Five patients had isolated LS-PCL: two patients underwent arthroscopic PCL reconstructions; and another three patients revealed knee instability on stress testing. Conclusion: Although LS-PCL has not been described before, it can be a type of partial tear of the PCL, which causes PCL insufficiency.

  19. Growth Potential of Subdural Hematomas Under Clinical Observation: Which Subdural Hematomas Tend to Grow and Why They Do.

    Science.gov (United States)

    Asan, Ziya

    2018-05-01

    To study the prognoses of patients with subdural hematoma (SDH) who were not operated on at the time of the first diagnosis and the causes of enlarged hematomas in some patients during the follow-up period. The records, service files, and radiologic examination results of the patients with diagnoses of SDH were reviewed. The SDH patients were recorded under 5 different categories: acute SDH (ASDH), subacute SDH (SSDH), chronic SDH (CSDH), acute component with chronic SDH (A-CSDH), and subacute component with chronic SDH (S-CSDH). The symptoms, clinical findings, and progression in the patients were correlated with radiologic examinations. A total of 291 patients received diagnoses of SDHs: 80 patients with acute, 29 patients with subacute, and 163 patients with chronic hematoma. Thirty-five patients had diagnoses of SDH with a combination of different components. It was determined that in the follow-up period, patients with A-CSDH showed the greatest increase in hematoma size over time and required surgical intervention the most often. SDHs reveal different prognoses in different age groups. Multicomponent SDHs are within the group that shows the greatest increase in size in the follow-up period. SDHs and CSDHs cause recurrent hemorrhages by sustaining the tension on the bridging veins. The greater the hematoma volume, the greater the growth potential of the hematoma tends to be. CSDHs that do not manifest changes in volume for a long time can be monitored without surgical intervention as long as the clinical picture remains stable. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. BADERI: an online database to coordinate handsearching activities of controlled clinical trials for their potential inclusion in systematic reviews.

    Science.gov (United States)

    Pardo-Hernandez, Hector; Urrútia, Gerard; Barajas-Nava, Leticia A; Buitrago-Garcia, Diana; Garzón, Julieth Vanessa; Martínez-Zapata, María José; Bonfill, Xavier

    2017-06-13

    Systematic reviews provide the best evidence on the effect of health care interventions. They rely on comprehensive access to the available scientific literature. Electronic search strategies alone may not suffice, requiring the implementation of a handsearching approach. We have developed a database to provide an Internet-based platform from which handsearching activities can be coordinated, including a procedure to streamline the submission of these references into CENTRAL, the Cochrane Collaboration Central Register of Controlled Trials. We developed a database and a descriptive analysis. Through brainstorming and discussion among stakeholders involved in handsearching projects, we designed a database that met identified needs that had to be addressed in order to ensure the viability of handsearching activities. Three handsearching teams pilot tested the proposed database. Once the final version of the database was approved, we proceeded to train the staff involved in handsearching. The proposed database is called BADERI (Database of Iberoamerican Clinical Trials and Journals, by its initials in Spanish). BADERI was officially launched in October 2015, and it can be accessed at www.baderi.com/login.php free of cost. BADERI has an administration subsection, from which the roles of users are managed; a references subsection, where information associated to identified controlled clinical trials (CCTs) can be entered; a reports subsection, from which reports can be generated to track and analyse the results of handsearching activities; and a built-in free text search engine. BADERI allows all references to be exported in ProCite files that can be directly uploaded into CENTRAL. To date, 6284 references to CCTs have been uploaded to BADERI and sent to CENTRAL. The identified CCTs were published in a total of 420 journals related to 46 medical specialties. The year of publication ranged between 1957 and 2016. BADERI allows the efficient management of handsearching

  1. Multimodal assessment of SERS nanoparticle biodistribution post ingestion reveals new potential for clinical translation of Raman imaging.

    Science.gov (United States)

    Campbell, Jos L; SoRelle, Elliott D; Ilovich, Ohad; Liba, Orly; James, Michelle L; Qiu, Zhen; Perez, Valerie; Chan, Carmel T; de la Zerda, Adam; Zavaleta, Cristina

    2017-08-01

    Despite extensive research and development, new nano-based diagnostic contrast agents have faced major barriers in gaining regulatory approval due to their potential systemic toxicity and prolonged retention in vital organs. Here we use five independent biodistribution techniques to demonstrate that oral ingestion of one such agent, gold-silica Raman nanoparticles, results in complete clearance with no systemic toxicity in living mice. The oral delivery mimics topical administration to the oral cavity and gastrointestinal (GI) tract as an alternative to intravenous injection. Biodistribution and clearance profiles of orally (OR) vs. intravenously (IV) administered Raman nanoparticles were assayed over the course of 48 h. Mice given either an IV or oral dose of Raman nanoparticles radiolabeled with approximately 100 μCi (3.7MBq) of 64 Cu were imaged with dynamic microPET immediately post nanoparticle administration. Static microPET images were also acquired at 2 h, 5 h, 24 h and 48 h. Mice were sacrificed post imaging and various analyses were performed on the excised organs to determine nanoparticle localization. The results from microPET imaging, gamma counting, Raman imaging, ICP-MS, and hyperspectral imaging of tissue sections all correlated to reveal no evidence of systemic distribution of Raman nanoparticles after oral administration and complete clearance from the GI tract within 24 h. Paired with the unique signals and multiplexing potential of Raman nanoparticles, this approach holds great promise for realizing targeted imaging of tumors and dysplastic tissues within the oral cavity and GI-tract. Moreover, these results suggest a viable path for the first translation of high-sensitivity Raman contrast imaging into clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The Effect of Gluten-free Diet on Clinical Symptoms and the Intestinal Mucosa of Patients With Potential Celiac Disease.

    Science.gov (United States)

    Mandile, Roberta; Discepolo, Valentina; Scapaticci, Serena; Del Vecchio, Maria Rosaria; Maglio, Maria Antonia; Greco, Luigi; Troncone, Riccardo; Auricchio, Renata

    2018-04-01

    In this prospective study, we evaluated the effect of gluten-free diet (GFD) in a cohort of 65 children with potential celiac disease. Patients received GFD for signs/symptoms (N = 47) or parents' choice (N = 18). Most frequent signs/symptoms were low body mass index (36%), recurrent abdominal pain (34%), and diarrhea (19%). Of the 35/47 patients followed-up on GFD, only 54% (19/35) showed a complete clinical response. In 9 of 65 patients an intestinal biopsy was also performed after at least 1 year of GFD. No significant differences were observed in terms of Marsh grade (P = 0.33), lamina propria CD25+ cells (P = 0.80), CD3+ (P = 0.9), and γδ+ (P = 0.59) intraepithelial lymphocytes density and intestinal anti-TG2 deposits (P = 0.60). In conclusion, caution is necessary before attributing all symptoms to gluten in this condition.

  3. Antibiotic Resistance Genetic Markers and Integrons in White Soft Cheese: Aspects of Clinical Resistome and Potentiality of Horizontal Gene Transfer.

    Science.gov (United States)

    de Paula, Ana Caroline L; Medeiros, Julliane D; de Azevedo, Analice C; de Assis Chagas, Jéssica M; da Silva, Vânia L; Diniz, Cláudio G

    2018-02-19

    Antibiotic resistance poses an important threat to global public health and has become a challenge to modern medicine. The occurrence of antibiotic-resistant bacteria in a broad range of foods has led to a growing concern about the impact that food may have as a reservoir of antibiotic resistance genes. Considering Minas Frescal Cheese (MFC)-a typical Brazilian white soft cheese-and its economic and cultural values, in this study, medically relevant antimicrobial-resistance genetic markers (AR genes) were screened, and the occurrence of integrons were evaluated in manufactured MFC using culture-independent approaches. Through a fingerprinting analysis, the tested MFCs were brand-clustered, indicating reproducibility along the production chain. A common core of resistance markers in all brands evaluated and related antimicrobials such as β-lactams, tetracyclines, quinolones, and sulfonamide was detected. Several other markers, including efflux pumps and aminoglycosides-resistance were distributed among brands. Class 1 and 2 integrons were observed, respectively, in 77% and 97% of the samples. The presence of AR genes is of special interest due to their clinical relevance. Taken together, the data may suggest that the production chain of MFC might contribute to the spread of putative drug-resistant bacteria, which could greatly impact human health. Furthermore, detection of class 1 and class 2 integrons in MFC has led to discussions about resistance gene spread in this traditional cheese, providing evidence of potential horizontal transfer of AR genes to human gut microbiota.

  4. Antibiotic Resistance Genetic Markers and Integrons in White Soft Cheese: Aspects of Clinical Resistome and Potentiality of Horizontal Gene Transfer

    Directory of Open Access Journals (Sweden)

    Ana Caroline L. de Paula

    2018-02-01

    Full Text Available Antibiotic resistance poses an important threat to global public health and has become a challenge to modern medicine. The occurrence of antibiotic-resistant bacteria in a broad range of foods has led to a growing concern about the impact that food may have as a reservoir of antibiotic resistance genes. Considering Minas Frescal Cheese (MFC—a typical Brazilian white soft cheese—and its economic and cultural values, in this study, medically relevant antimicrobial-resistance genetic markers (AR genes were screened, and the occurrence of integrons were evaluated in manufactured MFC using culture-independent approaches. Through a fingerprinting analysis, the tested MFCs were brand-clustered, indicating reproducibility along the production chain. A common core of resistance markers in all brands evaluated and related antimicrobials such as β-lactams, tetracyclines, quinolones, and sulfonamide was detected. Several other markers, including efflux pumps and aminoglycosides-resistance were distributed among brands. Class 1 and 2 integrons were observed, respectively, in 77% and 97% of the samples. The presence of AR genes is of special interest due to their clinical relevance. Taken together, the data may suggest that the production chain of MFC might contribute to the spread of putative drug-resistant bacteria, which could greatly impact human health. Furthermore, detection of class 1 and class 2 integrons in MFC has led to discussions about resistance gene spread in this traditional cheese, providing evidence of potential horizontal transfer of AR genes to human gut microbiota.

  5. Ocular vestibular evoked myogenic potential elicited from binaural air-conducted stimulations: clinical feasibility in patients with peripheral vestibular dysfunction.

    Science.gov (United States)

    Iwasaki, Shinichi; Egami, Naoya; Inoue, Aki; Kinoshita, Makoto; Fujimoto, Chisato; Murofushi, Toshihisa; Yamasoba, Tatsuya

    2013-07-01

    Ocular vestibular evoked myogenic potentials (oVEMPs) to binaural air-conducted stimulation (ACS) may provide a convenient way of assessing the crossed vestibulo-ocular reflex in patients with vestibular dysfunction as well as in healthy subjects. To investigate the clinical feasibility of using oVEMPs in response to binaural ACS to assess normal subjects and patients with vestibular dysfunction. The study investigated 24 normal subjects (14 men and 10 women, aged from 23 to 60 years) and 14 patients with unilateral peripheral vestibular dysfunction. Each subject underwent oVEMP testing in response to monaural ACS and binaural ACS (500 Hz tone burst, 135 dBSPL). In normal subjects, bilateral oVEMPs were elicited in 75% of subjects in response to monaural ACS and in 91% in response to binaural ACS. Asymmetry ratios (ARs) of the responses to binaural ACS were significantly smaller than those of the responses to monaural ACS (p binaural ACS. Approximately 30% of patients showed reduced ARs to binaural ACS relative to monaural ACS, primarily due to contamination by uncrossed responses elicited in healthy ears.

  6. A clinical case study of a Wolfram syndrome-affected family: pattern-reversal visual evoked potentials and electroretinography analysis.

    Science.gov (United States)

    Langwińska-Wośko, Ewa; Broniek-Kowalik, Karina; Szulborski, Kamil

    2012-04-01

    Wolfram syndrome (WFS), or DIDMOAD, is a rare (1/100 000 to 1/770 000), progressive neurodegenerative disorder. In its early stages, it is characterized by insulin-dependent diabetes mellitus, optic atrophy and loss of sensorineural hearing-this is followed by diabetes insipidus, progressive neurological abnormalities and other endocrine abnormalities, which occur in later years. The aim of this study was to report on the clinical and electrophysiological findings from a family with the WFS1 mutation. The five family members were subjected to a complete ophthalmic examination, which included a flash full-field electroretinogram and pattern-reversal visual evoked potentials (PVEPs) performed according to ISCEV standards. Optic atrophy was confirmed in two homozygotic patients, where P100 latencies were significantly delayed-up to 146 ms in PVEP. P100 latencies were normal in the three heterozygotic patients we examined. Curve morphology abnormalities were observed in all five patients we examined. No literature describing the morphology of PVEP in Wolfram syndrome patients was found. In flash electroretinography, scotopic and photopic responses appeared in normal morphology and value. Diabetic retinopathy was not observed in the diabetes mellitus patients.

  7. The Relational View of Interorganizational Competitive Advantage

    DEFF Research Database (Denmark)

    Hu, Yimei; Zhang, Si; Li, Jizhen

    Collaborating with external partners on R&D and forming strategic partnership for R&D have been popular phenomena for long, which leads new development in existing theories. Though the relational view of competitive advantage has been proposed for more than a decade, few in-depth empirical...... they generate relational rents (interorganizational competitive advantage) from this alliance? Based on this case study, we will propose some implications for the R&D collaboration between Chinese and Scandinavian countries. Also, the case will help us to test and enrich the existing theories...... on interorganizational competitive advantage. At the end of the paper, based on existing theories and the case study result, we will propose our conceptual framework on researching R&D strategic alliance between Scandinavian and Chinese firms....

  8. ELECTRONIC BANKING ADVANTAGES FOR FINANCIAL SERVICES DELIVERY

    Directory of Open Access Journals (Sweden)

    Paun Dragos

    2010-12-01

    Full Text Available E-banking is a fully automatic service for traditionally banking customers products based on information technology platforms. E-banking services provide customer access to accounts, the ability to move their money between different accounts or making payments via e-channels. The advantages generated by this services have determined an accelerate developing of this industry over the entire world. This paper examines some of the advantages of electronic banking products together with the characteristic management issues generated by the implementation of this new channel for financial services delivery.

  9. THE TAX ADVANTAGES OF INCOME TAX PAYERS

    Directory of Open Access Journals (Sweden)

    SUCIU GHEORGHE

    2015-04-01

    Full Text Available The paper analyzes the cost of financing through financial and operational leasing due to the deductibility of depreciation and interest. The shareholders of any company aim to obtain profit and to increase their ownership equity. In order for this to happen, the company must have profit, for which a corporate tax must be paid. A good management translates into choosing the most advantageous means of financing, which will lead to paying a lower corporate tax. Leasing and the non-taxation of reinvested profits are two means through which companies can obtain significant fiscal advantages, by increasing the deductible expenses, or by paying lower taxes.

  10. Motor Third Party Liability Insurance in Russia: Gaining Competitive Advantage

    OpenAIRE

    Rogozin, Konstantin

    2006-01-01

    The report identifies which factors of service-based offerings are of utmost importance for customers, considers the areas of MTPL insurance that may contain a potential sources for differentiation, and stresses importance of knowing customer needs and requirements. This report should assist the insurance company to categorise and systematise relevant information so as to develop a product position, which may give a competitive advantage.

  11. Advantages of polarization experiments at RHIC

    International Nuclear Information System (INIS)

    Underwood, D.G.

    1991-01-01

    We point out various spin experiments that could be done if the polarized beam option is pursued at RHIC. The advantages of RHIC for investigating several current and future physics problems are discussed. In particular, the gluon spin dependent structure function of the nucleon could be measured cleanly and systematically. Relevant experience developed in conjunction with the Fermilab Polarized Beam program is also presented

  12. Advantages of the production contractor concept

    Energy Technology Data Exchange (ETDEWEB)

    Gisvold, K.M. [Golar-Nor Offshore, Trondheim (Norway)

    1994-12-31

    This paper presents some thoughts on the Production Contractor concept. It starts with an attempt to define the prerequisites for such contractorship to exist and develop, going on to examine the considerations that the oil company and the contractor respectively have to go through, and finally trying to summarize what emerges as the advantages of production contracting. Examples are given to emphasize particular points

  13. Distance learning: its advantages and disadvantages

    OpenAIRE

    KEGEYAN SVETLANA ERIHOVNA

    2016-01-01

    Distance learning has become popular in higher institutions because of its flexibility and availability to learners and teachers at anytime, regardless of geographic location. With so many definitions and phases of distance education, this paper only focuses on the delivery mode of distance education (the use of information technology), background, and its disadvantages and advantages for today’s learners.

  14. On the measurement of comparative advantage

    NARCIS (Netherlands)

    Hoen, A.R.; Oosterhaven, J.

    This paper shows-that the standard measure of revealed comparative advantage (RCA), ranging from 0 to infinity, has problematic properties. Due to its multiplicative specification, it has a moving mean larger than its expected value of 1, while its distribution strongly depends on the number of

  15. On the measurement of comparative advantage

    NARCIS (Netherlands)

    Hoen, Alex R.

    2001-01-01

    This article shows that the distribution of the standard measure of revealed comparative advantage (RCA), which runs from 0 to 8, has problematic properties. Due to its multiplicative specification, it has a moving mean without a useful interpretation, while its distribution depends on the number of

  16. Overview of research in the ADVANTAGE project

    DEFF Research Database (Denmark)

    Angjelichinoski, Marko; Cosovic, Mirsad; Kalalas, Charalampos

    2016-01-01

    The European Marie Curie Project ADVANTAGE (Advanced Communications and Information processing in smart grid systems) was launched in 2014. It represents a major inter-disciplinary research project into the topic of Smart Grid technology. A key aspect of the project is to bring together and train...

  17. Advantages and disadvantages by using safety culture

    DEFF Research Database (Denmark)

    Dyhrberg, Mette Bang

    2003-01-01

    Safety culture is a major issue in accident research. A recently finished ph.d.-study has evaluated the symbolic safety culture approach and found four advantages and two disadvantages. These are presented and discussed in this contribution. It is concluded that the approach can be useful...

  18. Online Shopping: Advantages over the Offline Alternative

    OpenAIRE

    Dr Joshua Chang

    2003-01-01

    The advent of the Internet as a shopping medium has enabled shoppers to gain shopping benefits such as convenience and time-saving, better information, and price savings. This paper aims to provide a better understanding of the benefits of Internet shopping by identifying and discussing the advantages of Internet shopping over traditional storefront shopping.

  19. Advantages and disadvantages of developing nuclear power

    International Nuclear Information System (INIS)

    Wang Zhixin

    1987-01-01

    To solve the problem of the shortage of electricity in China, an objective assessment of the advantages and disadvantages of generating electricity from different energy sources is necessary. Nuclear power is evaluated against hydro-, oil-, gas- and coal-power. It is proposed to develop nuclear power in a planned way as a sensible long term strategy

  20. Creating Competitive Advantage through Effective Management Education.

    Science.gov (United States)

    Longenecker, Clinton O.; Ariss, Sonny S.

    2002-01-01

    Managers trained in executive education programs (n=203) identified ways in which management education can increase an organization's competitive advantage: exposure to new ideas and practices, skill development, and motivation. Characteristics of effective management education included experience-based learning orientation, credible instructors,…

  1. home advantage in the commonwealth games

    African Journals Online (AJOL)

    The occurrence of home advantage in sport is generally well doc- umented and has been shown to exist in a ... there are 53 Commonwealth nations, there are at present 71. Commonwealth Games Associations ... market share values for each host nation were analysed relative to the distance travelled by them (in terms of ...

  2. Robustness of the Sequential Lineup Advantage

    Science.gov (United States)

    Gronlund, Scott D.; Carlson, Curt A.; Dailey, Sarah B.; Goodsell, Charles A.

    2009-01-01

    A growing movement in the United States and around the world involves promoting the advantages of conducting an eyewitness lineup in a sequential manner. We conducted a large study (N = 2,529) that included 24 comparisons of sequential versus simultaneous lineups. A liberal statistical criterion revealed only 2 significant sequential lineup…

  3. Business Intelligence Solutions for Gaining Competitive Advantage

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available Business Intelligence is the process for increasing the competitive advantage of a company by intelligent use of available data in decision-making. Only a revolutionary Business Intelligence solution, like the proposed portal-based, can solve the complex issues faced when evaluating decision support applications and ensures the availability of any business-critical information.

  4. [The advantage of multidisciplinary treatment of presbycusis].

    Science.gov (United States)

    Bouccara, Didier; Madjlessi, Arach; Mosnier, Isabelle

    2010-01-01

    Attributable to the ageing of the hearing system, presbycusis presents a wide variability in the general population. Early detection is necessary in order to be able to provide the patient with a suitable hearing aid. Collaboration between otolaryngologists and geriatricians proves to be advantageous as a consultation for a memory complaint may be the opportunity to detect presbycusis and vice versa.

  5. Advantages of the production contractor concept

    International Nuclear Information System (INIS)

    Gisvold, K.M.

    1994-01-01

    This paper presents some thoughts on the Production Contractor concept. It starts with an attempt to define the prerequisites for such contractorship to exist and develop, going on to examine the considerations that the oil company and the contractor respectively have to go through, and finally trying to summarize what emerges as the advantages of production contracting. Examples are given to emphasize particular points

  6. Advantages of Intelligent SDH/SONET Networks

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Advantages of Intelligent SDH/SONET Networks. GMPLS simplifies network management, thus reducing operating expenses (“staff”) and minimizing errors. Same benefits as computerization of banking, accounts, etc. Auto-discovery simplifies equipment installation ...

  7. Project safety as a sustainable competitive advantage.

    Science.gov (United States)

    Rechenthin, David

    2004-01-01

    To be consistently profitable, a construction company must complete projects in scope, on schedule, and on budget. At the same time, the nature of the often high-risk work performed by construction companies can result in high accident rates. Clients and other stakeholders are placing increasing pressure on companies to decrease those accident rates. Clients routinely demand copies of safety plans and evidence of past results at the "pre-qualification" or "request for proposal" stages of the procurement process. Are high accident rates and the associated costs just a part of business? Companies that deliver on scope, schedule, and budget have a competitive advantage. Is it possible for projects with low accident rates to use it as a competitive advantage? Is the value added by safety just a temporary or parity issue, or does a successful safety program offer significant advantage to the company and the client? This article concludes that in the case of a high-risk industry, such as the construction industry, an organization with a successful safety program can promote safety performance as a sustainable competitive advantage. It is a choice the company can make.

  8. Achieving a competitive advantage in managed care.

    Science.gov (United States)

    Stahl, D A

    1998-02-01

    When building a competitive advantage to thrive in the managed care arena, subacute care providers are urged to be revolutionary rather than reactionary, proactive rather than passive, optimistic rather than pessimistic and growth-oriented rather than cost-reduction oriented. Weaknesses must be addressed aggressively. To achieve a competitive edge, assess the facility's strengths, understand the marketplace and comprehend key payment methods.

  9. 77 FR 67433 - Community Advantage Pilot Program

    Science.gov (United States)

    2012-11-09

    ... comments. SUMMARY: The Community Advantage (``CA'') Pilot Program is a pilot program to increase SBA... small businesses and entrepreneurs in underserved markets, SBA is issuing this Notice to extend the term... Pilot Program was introduced to increase the number of SBA-guaranteed loans made to small businesses in...

  10. Dual mobility cups provide biomechanical advantages in situations at risk for dislocation: a finite element analysis.

    Science.gov (United States)

    Terrier, Alexandre; Latypova, Adeliya; Guillemin, Maika; Parvex, Valérie; Guyen, Olivier

    2017-03-01

    Constrained devices, standard implants with large heads, and dual mobility systems have become popular options to manage instability after total hip arthroplasty (THA). Clinical results with these options have shown variable success rates and significant higher rates of aseptic loosening and mechanical failures with constrained implants. Literature suggests potential advantages of dual mobility, however little is known about its biomechanics. We present a comparative biomechanical study of a standard implant, a constrained implant, and a dual mobility system. A finite element analysis was developed to assess and compare these acetabular options with regard to the range of motion (ROM) to impingement, the angle of dislocation, the resistive torque, the volume of polyethylene (PE) with a stress above 80% of the elastic limit, and the interfacial cup/bone stress. Dual mobility implants provided the greatest ROM to impingement and allowed delaying subluxation and dislocation when compared to standard and constrained implants. Dual mobility also demonstrated the lowest resistive torque at subluxation while the constrained implant provided the greatest one. The lowest critical PE volume was observed with the dual mobility implant, and the highest stress at the interfaces was observed with the constrained implant. This study highlights the biomechanical advantages of dual mobility systems over constrained and standard implants, and is supported by the clinical results reported. Therefore, the use of dual mobility systems in situations at risk for instability should be advocated and constrained implants should be restricted to salvage situations.

  11. Site selection in global clinical trials in patients hospitalized for heart failure: perceived problems and potential solutions.

    Science.gov (United States)

    Gheorghiade, Mihai; Vaduganathan, Muthiah; Greene, Stephen J; Mentz, Robert J; Adams, Kirkwood F; Anker, Stefan D; Arnold, Malcolm; Baschiera, Fabio; Cleland, John G F; Cotter, Gadi; Fonarow, Gregg C; Giordano, Christopher; Metra, Marco; Misselwitz, Frank; Mühlhofer, Eva; Nodari, Savina; Frank Peacock, W; Pieske, Burkert M; Sabbah, Hani N; Sato, Naoki; Shah, Monica R; Stockbridge, Norman L; Teerlink, John R; van Veldhuisen, Dirk J; Zalewski, Andrew; Zannad, Faiez; Butler, Javed

    2014-03-01

    There are over 1 million hospitalizations for heart failure (HF) annually in the United States alone, and a similar number has been reported in Europe. Recent clinical trials investigating novel therapies in patients with hospitalized HF (HHF) have been negative, and the post-discharge event rate remains unacceptably high. The lack of success with HHF trials stem from problems with understanding the study drug, matching the drug to the appropriate HF subgroup, and study execution. Related to the concept of study execution is the importance of including appropriate study sites in HHF trials. Often overlooked issues include consideration of the geographic region and the number of patients enrolled at each study center. Marked differences in baseline patient co-morbidities, serum biomarkers, treatment utilization and outcomes have been demonstrated across geographic regions. Furthermore, patients from sites with low recruitment may have worse outcomes compared to sites with higher enrollment patterns. Consequently, sites with poor trial enrollment may influence key patient end points and likely do not justify the costs of site training and maintenance. Accordingly, there is an unmet need to develop strategies to identify the right study sites that have acceptable patient quantity and quality. Potential approaches include, but are not limited to, establishing a pre-trial registry, developing site performance metrics, identifying a local regionally involved leader and bolstering recruitment incentives. This manuscript summarizes the roundtable discussion hosted by the Food and Drug Administration between members of academia, the National Institutes of Health, industry partners, contract research organizations and academic research organizations on the importance of selecting optimal sites for successful trials in HHF.

  12. Evaluation of the Potential Risk of Drugs to Induce Hepatotoxicity in Human?Relationships between Hepatic Steatosis Observed in Non-Clinical Toxicity Study and Hepatotoxicity in Humans-

    OpenAIRE

    Goda, Keisuke; Kobayashi, Akio; Takahashi, Akemi; Takahashi, Tadakazu; Saito, Kosuke; Maekawa, Keiko; Saito, Yoshiro; Sugai, Shoichiro

    2017-01-01

    In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies of compound X, a candidate compound in drug development, and mitochondrial dysfunction in order to estimate the potential risk of the compound to induce drug-induced liver injury...

  13. The Survival Advantage: Underlying Mechanisms and Extant Limitations

    Directory of Open Access Journals (Sweden)

    Stephanie A. Kazanas

    2015-04-01

    Full Text Available Recently, researchers have begun to investigate the function of memory in our evolutionary history. According to Nairne and colleagues (e.g., Nairne, Pandeirada, and Thompson, 2008; Nairne, Thompson, and Pandeirada, 2007, the best mnemonic strategy for learning lists of unrelated words may be one that addresses the same problems that our Pleistocene ancestors faced: fitness-relevant problems including securing food and water, as well as protecting themselves from predators. Survival processing has been shown to promote better recall and recognition memory than many well-known mnemonic strategies (e.g., pleasantness ratings, imagery, generation, etc.. However, the survival advantage does not extend to all types of stimuli and tasks. The current review presents research that has replicated Nairne et al.'s (2007 original findings, in addition to the research designs that fail to replicate the survival advantage. In other words, there are specific manipulations in which survival processing does not appear to benefit memory any more than other strategies. Potential mechanisms for the survival advantage are described, with an emphasis on those that are the most plausible. These proximate mechanisms outline the memory processes that may contribute to the advantage, although the ultimate mechanism may be the congruity between the survival scenario and Pleistocene problem-solving.

  14. [Internet research methods: advantages and challenges].

    Science.gov (United States)

    Liu, Yi; Tien, Yueh-Hsuan

    2009-12-01

    Compared to traditional research methods, using the Internet to conduct research offers a number of advantages to the researcher, which include increased access to sensitive issues and vulnerable / hidden populations; decreased data entry time requirements; and enhanced data accuracy. However, Internet research also presents certain challenges to the researcher. In this article, the advantages and challenges of Internet research methods are discussed in four principle issue areas: (a) recruitment, (b) data quality, (c) practicality, and (d) ethics. Nursing researchers can overcome problems related to sampling bias and data truthfulness using creative methods; resolve technical problems through collaboration with other disciplines; and protect participant's privacy, confidentiality and data security by maintaining a high level of vigilance. Once such issues have been satisfactorily addressed, the Internet should open a new window for Taiwan nursing research.

  15. COMPETITIVE ADVANTAGES ENTERPRISES IN KOOPERATION RELATIONS

    Directory of Open Access Journals (Sweden)

    O. Mikitiuk

    2013-09-01

    Full Text Available Formation of new approaches to the definition of competitive advantage requires different ways to implement them according to market conditions. These paths can be cooperative relations entities that are implemented in the competitive advantage of enterprises in the new stage of development of a competitive society. The result of the interaction of small businesses with industrial and economic structures is the formation and development of such forms of cooperation entities as subcontracting, franchising, leasing, venture finance. The content of these forms is to integrate (interlacing of the functional areas of business including production of functional form is subcontracting relationships, forms of supply – franchising, industrial and financial shape – leasing as a form of innovative functional integration relations is venture financing.

  16. Sustainable competitive advantage for accountable care organizations.

    Science.gov (United States)

    Macfarlane, Michael Alex

    2014-01-01

    In the current period of health industry reform, accountable care organizations (ACOs) have emerged as a new model for the delivery of high-quality and cost-effective healthcare. However, few ACOs operate in direct competition with one another, and the accountable care business model has yet to present a means of continually developing new marginal value for patients and network partners. With value-based purchasing and patient consumerism strengthening as market forces, ACOs must build organizational sustainability and competitive advantage to meet the value demands set by customers and competitors. This essay proposes a strategy, adapted from the disciplines of agile software development and Lean product development, through which ACOs can engage internal and external customers in the development of new products that will provide sustainability and competitive advantage to the organization by decreasing waste in development, promoting specialized knowledge, and closely targeting customer value.

  17. The potential value on medication safety of a clinical decision support system in intensive care patients with renal insufficiency.

    NARCIS (Netherlands)

    Helmons, P.J.; Grouls, R.J.E.; Roos, A.N.; Bindels, A.J.G.H.; Clercq, de P.A.; Wessels-Basten, S.J.W.; Ackerman, E.W.; Korsten, H.H.M.

    2007-01-01

    Clinical decision support systems (CDSS) are defined as electronic or non-electronic systems designed to aid in clinical decision making, using characteristics of individual patients to generate patient-specific assessments or recommendations that are then presented to clinicians for consideration

  18. [Post-marketing reevaluation for potential quality risk and quality control in clinical application of traditional Chinese medicines].

    Science.gov (United States)

    Li, Hong-jiao; He, Li-yun; Liu, Bao-yan

    2015-06-01

    The effective quality control in clinical practices is an effective guarantee for the authenticity and scientificity of the findings. The post-marketing reevaluation for traditional Chinese medicines (TCM) focuses on the efficacy, adverse reaction, combined medication and effective dose of drugs in the market by expanded clinical trials, and requires a larger sample size and a wider range of patients. Therefore, this increases the difficulty of quality control in clinical practices. With the experience in quality control in clinical practices for the post-marketing reevaluation for Kangbingdu oral for cold, researchers in this study reviewed the study purpose, project, scheme design and clinical practice process from an overall point of view, analyzed the study characteristics of the post-marketing reevaluation for TCMs and the quality control risks, designed the quality control contents with quality impacting factors, defined key review contents and summarized the precautions in clinical practices, with the aim to improve the efficiency of quality control of clinical practices. This study can provide reference to clinical units and quality control-related personnel in the post-marketing reevaluation for TCMs.

  19. Advantages of polarization experiments at RHIC